Unique regioselectivity in the C(sp3)-H α-alkylation of amines: the benzoxazole moiety as a removable directing group.

The benzoxazol-2-yl- substituent was found to act as a removable activating and directing group in the Ir-catalyzed alkylation of C(sp(3))-H bonds adjacent to nitrogen in secondary amines. It can be easily introduced by oxidative coupling or by an SNAr reaction, and it can be removed by hydroxide or by hydride reduction. For 1,2,3,4-tetrahydroisoquinolines, activation exclusively takes place in the 3-position. A variety of activated as well as unactivated terminal olefins are suitable reaction partners.

Anodic Oxidation as an Enabling Tool for the Synthesis of Natural Products

Electrochemistry provides a valuable toolbox for organic synthesis and offers an appealing, environmentally benign alternative to the use of stoichiometric quantities of chemical oxidants or reductants. Its potential to control current efficiency along with providing alternative reaction conditions in a classical sense makes electrochemistry a suitable method for large-scale industrial transformations as well as for laboratory applications in the synthesis of complex molecular architectures. Even though research in this field has intensified over the recent decades, many synthetic chemists still hesitate to add electroorganic reactions to their standard repertoire, and hence, the full poten…

Left, Right, or Both? On the Configuration of the Phenanthroindolizidine Alkaloid Tylophorine from Tylophora indica

The alkaloid (-)-tylophorine was isolated from a sample of Tylophora indica, and the crude extract was analyzed by HPLC/MS(n) and chiral HPLC/MS. While the literature states that the naturally occurring form of this alkaloid is the R-enantiomer and that its S-antipode is usually not found in nature, we confirmed the hypothesis of Govindachari and Nagarajan that natural levorotatory tylophorine is indeed a nearly racemic mixture with a slight excess of the R-enantiomer.

One-Pot Oxidative C–H Activation/Aza-Prins-Type Reaction of Tertiary Alkynylamines: A Counter Ion-Induced Iminium Ion–Alkyne Cyclization

Herein, the design and development of a new one-pot and metal-free oxidative C-H activation/aza-Prins type cyclization of alkynylamines is reported. The scope of this method was demonstrated by the preparation of ten new pyrido[2,1-a]isoquinolines in moderate to high yields (38-92%). Furthermore, a mechanistic proposal for the alkyne aza-Prins cyclization is described based on DFT calculations.

Cover Picture: Photo-Chromium: Sensitizer for Visible-Light-Induced Oxidative C−H Bond Functionalization-Electron or Energy Transfer? (ChemPhotoChem 8/2017)

Microwave-Assisted Synthesis of Polysubstituted 4-Quinolones from Deprotonated α-Aminonitriles

The α-alkylation of deprotonated N-aryl-α-aminonitriles with α-bromoesters furnishes intermediates that can be cyclized to 4-quinolones upon microwave irradiation. Alternatively, base-induced dehydrocyanation of the alkylation products furnishes enaminoesters, which can, for example, be converted into quinoline-3-carboxylates.

ChemInform Abstract: A Short Synthesis of Pyridines from Deprotonated α-Aminonitriles by an Alkylation/RCM Sequence.

Saponin with antibacterial activity from the roots of Albizia adianthifolia

AbstractAn unprecedented saponin is being reported herein together with five known compounds from the methanol extract of the roots of Albizia adianthifolia. The metabolites were obtained over repe...

A Highly Active System for the Metal-Free Aerobic Photocyanation of Tertiary Amines with Visible Light: Application to the Synthesis of Tetraponerines and Crispine A

A highly efficient metal-free catalytic system for the aerobic photocyanation of tertiary amines with visible light is reported. The use of air as terminal oxidant offers an improved safety profile compared with pure oxygen, the used compact fluorescent lamp (CFL) light sources are highly economical, and no halogenated solvents are required. This system not only proves to be effective for a wide variety of trialkylamines, pharmaceuticals, and alkaloids but remarkably also allows the lowest catalyst loading (0.00001 mol% or 0.1 ppm) ever reported for an organic dye. Bruylants reactions and C-alkylation/decyanations were performed on the obtained α-aminonitriles to demonstrate the postfunctio…

Isolation, structure elucidation, and biological evaluation of the unusual heterodimer chrysoxanthone from the ascomycete IBWF11-95A

Chrysoxanthone, an unusual heterodimer of blennolide A and 2-hydroxychrysophanol linked through a diaryl ether bridge, was isolated from mycelia of the ascomycete IBWF11-95A grown in submerged culture. Its structure was elucidated by two-dimensional NMR spectroscopy. The metabolite shows antibacterial activity against different species with MIC values between 2.5 and 20 μg/mL while also inhibiting the growth of several fungi.

Marine Pyrrole Alkaloids

Nitrogen heterocycles are essential parts of the chemical machinery of life and often reveal intriguing structures. They are not only widespread in terrestrial habitats but can also frequently be found as natural products in the marine environment. This review highlights the important class of marine pyrrole alkaloids, well-known for their diverse biological activities. A broad overview of the marine pyrrole alkaloids with a focus on their isolation, biological activities, chemical synthesis, and derivatization covering the decade from 2010 to 2020 is provided. With relevant structural subclasses categorized, this review shall provide a clear and timely synopsis of this area.

Constituents of Peperomia vulcanica Baker & C. H. Wright (Piperaceae) with antiparasitic activity

Abstract The investigation of the CH2Cl2-MeOH (1:1) extract of Peperomia vulcanica which showed antileishmanial activity during preliminary screening led to the isolation of two previously unknown compounds named peperolignan (1) and peperotannin (2) along with 13 known compounds. Their structures were determined on the basis of their spectroscopic data. The isolated compounds were assessed in vitro for their antileishmanial and antiplasmodial activities against Leishmania donovani 1S (MHOM/SD/62/1S) promastigotes and the Plasmodium falciparum chloroquine-sensitive 3D7 strain (Pf3D7), respectively. They were also assessed for their cytotoxicity on Raw 264.7 macrophage cells. The mixture of …

Modular one-pot synthesis of tetrasubstituted pyrroles from alpha-(alkylideneamino)nitriles.

2,3,4,5-Tetrasubstituted pyrroles have been prepared with high regioselectivity by a formal cycloaddition of alpha-(alkylideneamino)nitriles and nitroolefins followed by elimination of HCN and HNO2. The reaction allows the convergent construction of the pyrrole ring in four steps from a nitroalkane and three aldehydes.

Cyclocondensation of alpha-aminonitriles and enones: a short access to 3,4-dihydro-2H-pyrrole 2-carbonitriles and 2,3,5-trisubstituted pyrroles.

The reaction of alpha,beta-unsaturated carbonyl compounds with aminoacetonitrile hydrochloride furnishes 3,5-disubstituted 3,4-dihydro-2H-pyrrole-2-carbonitriles in a one-pot reaction sequence. While these products can serve as starting materials for the preparation of polysubstituted pyrrolizidines, they are kinetically stable against the base-induced elimination of HCN. In contrast, their 2-substituted analogues obtained from alpha-substituted alpha-aminonitriles can be readily converted to the corresponding 2,3,5-trisubstituted pyrroles under microwave irradiation. The key step presumably involves the thermal electrocyclization of a stabilized 2-azapentadienyl anion formed by condensatio…

Silver Oxide Mediated Monotosylation of Poly(ethylene glycol) (PEG): Heterobifunctional PEG via Polymer Desymmetrization

Heterobifunctional poly(ethylene glycol)s (PEGs) are key structures for bioconjugation in the context of the “PEGylation” strategy to enhance blood circulation times of, for example, peptide drugs or “stealth” liposomes. The formation of heterobifunctional PEGs from symmetric PEG diols is challenging because of limited yields of the targeted monofunctional product and difficulties associated with separation steps. On the basis of a detailed comparison of reaction conditions, we have investigated a “polymer desymmetrization” strategy to maximize the yields of monofunctional PEG tosylate. The tosylation reaction in the presence of the heterogeneous catalyst silver oxide and potassium iodide i…

Omphalotins E-I, Five Oxidatively Modified Nematicidal Cyclopeptides fromOmphalotus olearius

Omphalotins E–I, oxidatively modified cyclic dodecapeptides, were isolated from mycelial extracts of the basidiomycete Omphalotus olearius, and their structures were determined by NMR spectroscopic and MS methods. Four of the five omphalotins contained an unprecedented N-hydroxylated tricyclic tryptophan derivative. All compounds exhibited strong and selective nematicidal activity against the plant pathogen Meloidogyne incognita with LD90 values between 2 and 5 μg mL–1. Cytotoxic activities were not detected up to 50 μg mL–1. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

4-Dechloro-14-deoxy-oxacyclododecindione and 14-deoxy-oxacylododecindione, two inhibitors of inducible connective tissue growth factor expression from the imperfect fungus Exserohilum rostratum

Connective tissue growth factor (CTGF/CCN2), a member of the CCN superfamily of secreted cysteine-rich glycoproteins, is a central mediator of tissue remodeling and fibrosis. CTGF is suggested to be an important down-stream effector of transforming growth factor-beta (TGF-β) signaling and has therefore reached considerable pathophysiological relevance because of its involvement in the pathogenesis of fibrotic diseases, atherosclerosis, skin scarring, and other conditions with excess production of connective tissue. In a search for inhibitors of inducible CTGF expression from fungi, two new macrocyclic lactones, namely 4-dechloro-14-deoxy-oxacyclododecindione (1) and 14-deoxy-oxacylododecind…

Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes

Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these unicellular eukaryotic parasites differs from the human host and their enzymes thus constitute promising drug targets. Tryparedoxin (Tpx) from Trypanosoma brucei is the essential oxidoreductase in the parasite's hydroperoxide-clearance cascade. In vitro and in vivo functional assays show that a small, selective inhibitor efficiently inhibits Tpx. With X-ray crystallography, SAXS, analytical SEC, SEC-MALS, MD simulations, ITC, and NMR spectroscopy, we show how covalent binding of this monofunctional inhibitor leads to Tpx dimerization. Intra- and intermolecular inhibitor-inhibitor, pro…

A Modular Access to (±)-Tubocurine and (±)-Curine - Formal Total Synthesis of Tubocurarine.

Two consecutive Cu-catalyzed Ullmann-type C–O couplings permitted the first successful entry toward the curare alkaloids (±)-tubocurine and (±)-curine. Starting from vanillin, the synthetic sequence comprises 15 linear steps and includes a total of 24 transformations. In addition, the total synthesis of tubocurine represents a formal total synthesis of the famous arrow poison alkaloid tubocurarine.

Resolving Binding Events on the Multifunctional Human Serum Albumin

Abstract Physiological processes rely on initial recognition events between cellular components and other molecules or modalities. Biomolecules can have multiple sites or mode of interaction with other molecular entities, so that a resolution of the individual binding events in terms of spatial localization as well as association and dissociation kinetics is required for a meaningful description. Here we describe a trichromatic fluorescent binding‐ and displacement assay for simultaneous monitoring of three individual binding sites in the important transporter and binding protein human serum albumin. Independent investigations of binding events by X‐ray crystallography and time‐resolved dyn…

Erysacleuxins C and D, new isoflavones from the twigs of Erythrina sacleuxii Hua and their cytotoxic activity

Two previously undescribed isoflavones, erysacleuxin C (1) and erysacleuxin D (2), together with seven known compounds (3–9), were isolated and identified from the EtOAc extract of the twigs of Erythrina sacleuxii Hua (Leguminosae). The structures of the isolated compounds were determined on the basis of their spectroscopic and spectrometric data. Evaluation of their cytotoxicity against the human cancer HeLa-S3 cell lines indicated IC50 values of 130.4, 54.9 and 73.9 µM for erysacleuxin C (1), erysacleuxin D (2) and butin (9), respectively. Keywords: Erythrina sacleuxii, Leguminosae, Isoflavone, Erysacleuxin C, Erysacleuxin D, Cytotoxicity

Recent Advances in the Synthesis of Piperidines: Functionalization of Preexisting Ring Systems

Abstract The present review focuses on strategies for the construction of piperidines which have appeared in the literature since 2003 through mid-2017. In a preceding chapter ( 2017AHC191 ), we summarized synthetic methods involving the construction of the piperidine ring from essentially acyclic starting materials in an intra- or intermolecular manner. The present chapter aims at giving a general overview of decoration or modification of previously generated pyridines or piperidines. The hydrogenation of preformed pyridine or pyridinium rings and introduction of substituents into fully saturated piperidines as well as ring expansion of pyrrolidines to piperidines are the most prevalent me…

Six-Step Gram-Scale Synthesis of the Human Immunodeficiency Virus Integrase Inhibitor Dolutegravir Sodium

This is the accepted manuscript version of the work published in its final form as Dietz, Jule-Philipp; Lucas, Tobias; Groß, Jonathan; Seitel, Sebastian; Brauer, Jan; Ferenc, Dorota; Gupton, B. Frank; Opatz, Till. Organic Process Research & Development; Volume: 25; Issue: 11; Pages: 1898-1910; https://doi.org/10.1021/acs.oprd.1c00139. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.

GKK1032A2, a secondary metabolite from Penicillium sp. IBWF-029-96, inhibits conidial germination in the rice blast fungus Magnaporthe oryzae

GKK1032A 2 , a secondary metabolite from Penicillium sp. IBWF-029-96, inhibits conidial germination in the rice blast fungus Magnaporthe oryzae

Crystal structure analysis of a star-shaped triazine compound: a combination of single-crystal three-dimensional electron diffraction and powder X-ray diffraction.

The solid-state structure of star-shaped 2,4,6-tris{(E)-2-[4-(dimethylamino)-phenyl]ethenyl}-1,3,5-triazine is determined from a powder sample by exploiting the respective strengths of single-crystal three-dimensional electron diffraction and powder X-ray diffraction data. The unit-cell parameters were determined from single crystal electron diffraction data. Using this information, the powder X-ray diffraction data were indexed, and the crystal structure was determined from the powder diffraction profile. The compound crystallizes in a noncentrosymmetric space group,P212121. The molecular conformation in the crystal structure was used to calculate the molecular dipole moment of 3.22 Debye,…

Synthesis of (-)-Cryptopleurine by Combining Gold(I) Catalysis with a Free Radical Cyclization (Eur. J. Org. Chem. 10/2015)

Enantioselective Synthesis of (−)-Dihydrocodeine and Formal Synthesis of (−)-Thebaine, (−)-Codeine, and (−)-Morphine from a Deprotonated α-Aminonitrile

The α-benzylation of a deprotonated bicyclic α-aminonitrile, followed by Noyori's asymmetric transfer hydrogenation combined with the Grewe cyclization onto a symmetrical A-ring precursor, are the key steps of a short and high-yielding enantioselective synthesis of the morphinan (-)-dihydrocodeine. This compound can be converted to (-)-thebaine in high yield by known transformations, while (-)-codeine and (-)-morphine are available from an advanced intermediate.

Predicting 19F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex

Abstract The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable 19F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the 19F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleepi…

Chemical recycling of polyenaminones by transamination reaction via amino–enaminone polymerisation/depolymerisation

Abstract Novel oligo- and polyenaminones with Mw ∼ 3000 Da were prepared in excellent yields by amino–enaminone ‘click’ polymerisation of 1,3- and 1,4-bis[3-(dimethylamino)acryloyl]arenes with 1,3- and 1,4-phenylenediamine. The obtained oligomers and polymers were depolymerised quantitatively to the starting bis-enaminones and diamines by treatment with excess dimethylamine in ethanol at 50 °C. This simple polymerisation/depolymerisation method allows for a closed-loop recycling of polyenaminone-based materials. UV light absorbance at wavelengths below 470 nm indicates promising optical properties of these polymers.

ChemInform Abstract: A Modular Synthesis of Polysubstituted Indolizines.

Title compounds are synthesized by [3 + 2] cycloaddition of nitroalkenes (IV) with pyridinium salts.

ChemInform Abstract: Selective C-H Activation of Methoxy Groups in a Three-Component Photoreaction.

Surprisingly, the photocatalytic activation of ethers by H-abstraction and addition of the generated radicals to iminium ions formed in situ from aldehydes and anilines predominantly yielded the products of methoxy activation for dimethoxymethane and 1,2-dimethoxyethane. Various anilines and aromatic as well as aliphatic aldehydes are suitable reaction partners for this three-component photoreaction (Porta-type process) which also provides a simple access to 1,2-aminoalcohols.

A concise route to MK-4482 (EIDD-2801) from cytidine.

A two-step route to MK-4482 (EIDD-2801, 1) was developed consisting of an esterification and hydroxamination of cytidine. The selective acylation and direct amination eliminate the need for protecting and activating groups and proceed in overall yield of 75%, a significant advancement over the reported yield of 17%. The step count is reduced from five transformations to two, and expensive uridine is replaced with the more available cytidine.

Total Synthesis of the Antifungal Natural Product Mollisin

Mollisin, a bioactive polyketide secondary metabolite of the fungus Mollisia caesia, was synthesized in nine linear steps from commercially available 2,6-dimethyl-γ-pyrone. A key transformation in this first total synthesis of mollisin was the ipso substitution of an arylstannane, which permitted the otherwise cumbersome introduction of the characteristic dichloroacetyl moiety. The fungal fungicide was obtained in an overall yield of 9 %.

Synthesis of Optically Active Hydroxyalkyl Cycloheptatrienes: A Key Step in the Total Synthesis of 6,11-Methylene-LXB4

AbstractStarting from methyl cycloheptatrienyl-1-carboxylate, 6-acylation was successfully achieved employing glutaryl chloride in the presence of AlCl3 under controlled reaction conditions to furnish keto carboxylic acid product. After protection of this keto carboxylic acid as tert-butyl ester, reagent-controlled enantioselective reductions delivered configuration-defined methyl-6-hydroxylalkyl cycloheptatriene-1-carboxylates with up to 80% ee. Whereas simple NaBH4 reduction of the keto carboxylic acid and subsequent lactonization afforded a methyl-6-tetrahydropyranonyl cycloheptatriene-1-carboxylate. Resolution using chiral HPLC delivered the product enantiomers with up to >99% ee Fin…

Xylochemical Synthesis of Cytotoxic 2-Aminophenoxazinone-Type Natural Products Through Oxidative Cross Coupling

Today, the total synthesis of natural products mostly relies on the use of petroleum-based starting materials. The commercial availability of building blocks of this type often deflects attention away from lengthy synthetic routes required for the reintroduction of heteroatom substitution patterns lost in the geological process of kerogenesis. Herein, the use of wood-based starting materials, the so-called xylochemicals, for the synthesis of 2-aminophenoxazinone natural products is presented. The inherent heteroatom substitution patterns as well as chemical functionalities were employed and permitted a short and straightforward synthetic strategy. Moreover, a novel and “green” method for co…

Gold(II) Porphyrins in Photoinduced Electron Transfer Reactions

Chemistry - a European journal 25(23), 5940 - 5949 (2019). doi:10.1002/chem.201900050

Nickel‐Mediated Photoreductive Cross Coupling of Carboxylic Acid Derivatives for Ketone Synthesis**

A simple photochemical, nickel-catalyzed synthesis of ketones starting from carboxylic acids is presented. Hantzsch-ester (HE) functions as a cheap, green and strong photoreductant upon visible-light excitation to facilitate radical generation and also engages in the Ni-catalytic cycle to restore the reactive species. With this dual role, HE allows for the coupling of a large variety of radicals (1°,2°, benzylic, α-oxy & α-amino) with aroyl and alkanoyl moieties, a new feature in the synthesis of ketones through dual nickel photoredox catalysis. With both precursors deriving from abundant carboxylic acids, this protocol is a welcome addition to the organic chemistry toolbox. The reactio…

ChemInform Abstract: Assignment of the Absolute Configuration and Total Synthesis of (+)-Caripyrin.

The antifungal secondary metabolite (+)-caripyrin was studied by vibrational circular dichroism spectroscopy. Analysis of the recorded data, with the Boltzmann weighted-average of the spectra calculated at the B3LYP/6-311G(d,p) level of theory for all relevant conformers, unequivocally proved the (R,R)-configuration for the dextrorotatory natural product. Based on this finding, a short enantioselective synthesis of (+)-caripyrin was developed.

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

Two hitherto unknown fusaricidins were obtained from fermentation broths of three Paenibacillus strains. After structure elucidation based on tandem mass spectrometry and NMR spectroscopy, fusaricidin E was synthesized to confirm the structure and the suggested stereochemistry. The synthesis was based on a new strategy which includes an efficient access to the 15-guanidino-3-hydroxypentadecanoyl (GHPD) side chain from erucamide.

Making natural products from renewable feedstocks: back to the roots?

Covering: up to mid-2019 This review highlights the utilization of biomass-derived building blocks in the total synthesis of natural products. An overview over several renewable feedstock classes, namely wood/lignin, cellulose, chitin and chitosan, fats and oils, as well as terpenes, is given, covering the time span from the initial beginning of natural product synthesis until today. The focus is put on the origin of the employed carbon atoms and on the nature of the complex structures that were assembled therefrom. The emerging trend of turning away from petrochemically derived starting materials back to bio-based resources, just as seen in the early days of total synthesis, shall be demon…

ChemInform Abstract: α-Cyanation of Aromatic Tertiary Amines Using Ferricyanide as a Non-Toxic Cyanide Source.

Aromatic tertiary amines, mostly isoquinoline derivatives and analogous N-heterocycles, are treated with the non-toxic agent (II) under conditions A) or B) to produce the desired N-aminonitrile compounds as amino acid precursors and as building blocks of complex nitrogen heterocycles.

A Light-Induced Vinylogous Nazarov-Type Cyclization

The first examples of a photochemically induced vinylogous Nazarov-type cyclization forming a cycloheptadienone core are described. The reaction can be included in a three-step cascade consisting of a photochemical isoxazole-azirine ring contraction, cobalt(II)-catalyzed ring expansion, and the photochemical cyclization. Furthermore, the first representative of the hitherto unknown 1-azatricyclo[2.2.0.0(2,6)]hexanes has been identified as a side product of the azirine formation.

Photoredox-catalyzed synthesis of N-unsubstituted enaminosulfones from vinyl azides and sulfinates

Abstract A metal-free visible light photoredox-catalyzed synthesis of N-unsubstituted enaminosulfones from vinyl azides and sodium sulfinates in moderate to high yields is described. The reaction proceeds in ethanol and uses eosin Y as a readily available photocatalyst in combination with nitrobenzene as an electron shuttle. Taking into account the number of steps involved (generation of the sulfonyl radical, its addition to the double bond, elimination of molecular nitrogen with formation of an iminyl radical, followed by its reduction and protonation) as well as the number of redox-active reaction partners involved, the selectivity of the process is quite impressive.

Coumarin derivatives from Pedilanthus tithymaloides as inhibitors of conidial germination in Magnaporthe oryzae

In a screening for inhibitors of infection-related morphogenesis in the rice blast fungus Magnaporthe oryzae, a series of 10 coumarin derivatives were isolated from Pedilanthus tithymaloides (Euphorbiaceae). Seven of these compounds turned out to be known while three represent previously unreported natural products. Their structures were established on the basis of spectroscopic data and X-ray crystallography. Nine out of 10 coumarin derivatives were found to inhibit conidial germination in the phytopathogenic fungus at low concentrations.

Absolute Configuration Determination of 2,3-Dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles Using Chiroptical Methods at Different Wavelengths

A correlation between the absolute configuration and chiroptical properties of nonracemic 1,6,7-trisubstituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles was studied. A series of 16 novel representatives were prepared by Cu-catalyzed [3 + 2] cycloadditions of racemic (Z)-2-benzylidene-5-oxopyrazolidin-2-ium-1-ides to tert-butyl (S)-(3-oxopent-4-yn-2-yl)carbamate, and their structures were determined by NMR, VCD, ECD, and X-ray diffraction. A clear correlation between the sign of specific rotation and configuration at position C(1) allows for easy determination of the absolute configuration of 1,6,7-trisubstituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles by ECD and NMR. While VCD, requirin…

Xylochemicals and where to find them

This article surveys a range of important platform and high value chemicals that may be considered primary and secondary 'xylochemicals'. A summary of identified xylochemical substances and their natural sources is provided in tabular form. In detail, this review is meant to provide useful assistance for the consideration of potential synthetic strategies using xylochemicals, new methodologies and the development of potentially sustainable, xylochemistry-based processes. It should support the transition from petroleum-based approaches and help to move towards more sustainability within the synthetic community. This feasible paradigm shift is demonstrated with the total synthesis of natural …

Tanzawaic acids I-L: Four new polyketides from Penicillium sp. IBWF104-06.

Four new polyketides have been identified in culture filtrates of the fungal strain Penicillium sp. IBWF104-06 isolated from a soil sample. They are structurally based on the same trans-decalinpentanoic acid skeleton as tanzawaic acids A–H. One of the new compounds was found to inhibit the conidial germination in the rice blast fungus Magnaporthe oryzae at concentrations of 25 μg/mL.

ChemInform Abstract: Microwave-Assisted Synthesis of Polysubstituted 4-Quinolones from Deprotonated α-Aminonitriles.

The α-alkylations of deprotonated Strecker products such as (I) or (V) give a series of intermediates such as (III), (VI), or (X), which undergo microwave-assisted HCN and EtOH eliminations leading to the title quinolones (IV), (VII)/(VIII), or (XI).

ChemInform Abstract: Sterelactones: New Isolactarane Type Sesquiterpenoids with Antifungal Activity from Stereum sp. IBWF 01060.

Four members of a new family of tetracyclic sesquiterenoids possessing the isolactarane skeleton have been isolated from mycelial cultures of Stereum sp. IBWF 01060. Their structure elucidation and their antifungal activity against several plant pathogens as well as other microorganisms are reported.

A New Flavonol Glycoside from Tristemma hirtum (Melastomataceae)

ChemInform Abstract: 3,4-Dihydro-2H-pyrrole-2-carbonitriles: Useful Intermediates in the Synthesis of Fused Pyrroles and 2,2′-Bipyrroles.

Various heterocyclic structures containing the pyrrole moiety have been synthesized from easily accessible 3,4-dihydro-2H-pyrrole-2-carbonitriles in one-pot procedures. 5,6,7,8-Tetrahydroindolizines, 2,3-dihydro-1H-pyrrolizines as well as 6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepines were obtained from these precursors in high yields in an alkylation/annulation sequence. The same conditions were applied in the synthesis of a 5,8-dihydroindolizine, which could easily be transformed to the corresponding indolizine by dehydrogenation. Furthermore, oxidative couplings of 3,4-dihydro-2H-pyrrole-2-carbonitriles with copper(II)-salts furnished 2,2′-bipyrroles as well as 5,5′-bis(5-cyano-1-pyrroline…

Photochemical Approaches to the Bilobalide Core

Bilobalide is a tetracyclic sesquiterpene containing three contiguous γ-lactone rings and an unusual tert-butyl group, which is found in the leaves of the ginkgo tree (Ginkgo biloba). Three different photochemical approaches towards bilobalide's unique skeleton are presented. A meta photocycloaddition, a [2 + 2] photocycloaddition, and a Paterno–Buchi-reaction were chosen as the respective key steps.

Anti-inflammatory dihydroxanthones from a Diaporthe species

Abstract In a search for anti-inflammatory compounds from fungi inhibiting the promoter activity of the small chemokine CXCL10 (Interferon-inducible protein 10, IP-10) as a pro-inflammatory marker gene, the new dihydroxanthone methyl (1R, 2R)-1,2,8-trihydroxy-6-(hydroxymethyl)-9-oxo-2,9-dihydro-1H-xanthene-1-carboxylate (2) and the previously described dihydroxanthone AGI-B4 (1) were isolated from fermentations of a Diaporthe species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy, mass spectrometry, and calculations using density functional theory (DFT). Compounds 1 and 2 inhibited the LPS/IFNγ induced CXCL10 promoter activity …

Thoughts on What Chemists Can Contribute to Fighting SARS-CoV-2 - A Short Note on Hand Sanitizers, Drug Candidates and Outreach.

Abstract The SARS‐CoV‐2 outbreak causing the respiratory disease COVID‐19 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three‐pronged approach is proposed.

ChemInform Abstract: Total Synthesis of the Antifungal Natural Product Mollisin.

The title compound is synthesized in nine steps from commercially available 2,6-dimethyl-γ-pyrone in an overall yield of 9%.

Carbohydrate-Based Nanocarriers Exhibiting Specific Cell Targeting with Minimum Influence from the Protein Corona.

Whenever nanoparticles encounter biological fluids like blood, proteins adsorb on their surface and form a so-called protein corona. Although its importance is widely accepted, information on the influence of surface functionalization of nanocarriers on the protein corona is still sparse, especially concerning how the functionalization of PEGylated nanocarriers with targeting agents will affect protein corona formation and how the protein corona may in turn influence the targeting effect. Herein, hydroxyethyl starch nanocarriers (HES-NCs) were prepared, PEGylated, and modified on the outer PEG layer with mannose to target dendritic cells (DCs). Their interaction with human plasma was then s…

An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines

Abstract: Herein, we report further improvements to the synthesis of tenofovir 1, the precursor to tenofovir disoproxil fumarate and tenofovir alafenamide fumarate. Starting from acyclic precursor diaminomalononitrile 12, a four-step protocol to tenofovir 1 will allow for vertical integration for more manufacturers. The key transformation is a more convergent one step procedure from 6 as compared to the current commercial process, with an improved yield from 59% (two steps) to 70%. Further improvements include eliminating the need for problematic magnesium tert-butoxide (MTB) and significant solvent reduction by eliminating the need for an intermediate workup. With the costs of HIV/AIDS tre…

Rearrangements of Nitrile-Stabilized Ammonium Ylides

Rearrangements of nitrile-stabilized ammonium ylides are useful reactions for the construction of alkylamines, nitrogen heterocycles, or carbonyl compounds. In spite of their attractive synthetic potential, they are much less frequently used than rearrangements of ammonium ylides either carrying charge-stabilizing carbonyl groups or being devoid of additional stabilization of the negative charge. This review focuses on different classes of rearrangements of nitrile-stabilized ammonium ylides as well as their application in synthetic organic chemistry. 1 Introduction 2 [1,2]-Stevens Rearrangements 3 [2,3]-Sommelet–Hauser Rearrangement 4 [2,3]-Stevens Rearrangements 5 Competitive [1,2]-, [2,3…

ChemInform Abstract: Ring Expansion of 1,2,3,4-Tetrahydroisoquinolines to Dibenzo[c,f]azonines. An Unexpected [1,4]-Sigmatropic Rearrangement of Nitrile-Stabilized Ammonium Ylides.

When the products of a Strecker reaction of 1,2,3,4-tetrahydroisoquinolines with aromatic aldehydes are quaternized with alkyl triflates and subsequently treated with base, a ring expansion to 6,7,8,13-tetrahydro-5H-dibenzo[c,f]azonine-5-carbonitriles takes place. The nine-membered cyclic products can be obtained in good yields (78–89%) in a process involving the [1,4]-sigmatropic rearrangement of a nitrile-stabilized ammonium ylide. The reaction sequence provides a new, simple, and efficient method for the synthesis of these unusual N-heterocycles.

Drimane Sesquiterpenoids from Marasmius sp. Inhibiting the Conidial Germination of Plant-Pathogenic Fungi

From the basidiomycete Marasmius sp., strain IBWF 96046, three new sesquiterpenoids based on the drimane skeleton were isolated and named marasmene B and marasmals B and C. In this study, their isolation, structure elucidation, and biological evaluation are described. The compounds have a pronounced inhibitory effect on the conidial germination of several plant-pathogenic fungi.

Secondary brown carbon formation via the dicarbonyl imine pathway: nitrogen heterocycle formation and synergistic effects.

Dicarbonyls are known to be important precursors of so-called atmospheric brown carbon, significantly affecting aerosol optical properties and radiative forcing. In this systematic study we report the formation of light-absorbing nitrogen containing compounds from simple 1,2-, 1,3-, 1,4-, and 1,5-dicarbonyl + amine reactions. A combination of spectrophotometric and mass spectrometric techniques was used to characterize reaction products in solutions mimicking atmospheric particulates. Experiments with individual dicarbonyls and dicarbonyl mixtures in ammonium sulfate and glycine solutions demonstrate that nitrogen heterocycles are common structural motifs of brown carbon chromophores formed…

Bioconjugation of Small Molecules to RNA Impedes Its Recognition by Toll-Like Receptor 7

A fundamental mechanism of the innate immune system is the recognition, via extra- and intracellular pattern recognition receptors, of pathogen-associated molecular patterns. A prominent example is represented by foreign nucleic acids, triggering the activation of several signaling pathways. Among these, the endosomal toll-like receptor 7 (TLR7) is known to be activated by single stranded RNA (ssRNA), which can be specifically influenced through elements of sequence structure and posttranscriptional modifications. Furthermore, small molecules TLR7 agonists (smTLRa) are applied as boosting adjuvants in vaccination processes. In this context, covalent conjugations between adjuvant and vaccine…

Combinatorial solid-phase synthesis using D-galactose as a chiral five-dimension-deversity scaffold

Abstract All five hydroxy groups of galactose as the scaffold are used for selective coupling of side chains in a combinatorial methodology by application of a set of orthogonally stable protecting groups in combination with a thioglycoside anchor.

A short synthesis of pyridines from deprotonated α-aminonitriles by an alkylation/RCM sequence

Abstract α-Aminonitriles can serve as versatile key precursors for the synthesis of nitrogen containing heterocycles. After unsuccessful trials involving the [1,2]-Stevens rearrangement of nitrile-stabilized ammonium ylides, we herein report a simple three-step synthesis of substituted pyridines based on an alkylation/ring-closing metathesis/aromatization sequence.

One-Pot Synthesis of Pyrrole-2-carboxylates and -carboxamides via an Electrocyclization/Oxidation Sequence

An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.

The Di-Tert-Butyl Oxymethylphosphonate Route to the Antiviral Drug Tenofovir

<div>The present manuscript describes a simple, two step synthesis of tenofovir from HPA through phosphonomethalation with a novel doubly protected oxymethylphosphonate electrophile. The crystalline electrophile can be prepared in a simple reaction sequence and can be deblocked more easily than its ditehyl analogue involved in the current commercial process for making the drug.</div><div>The approach is general and can also be used for the preparation of related antivirals and the synthesis of adefovir is described as well.<br></div>

3,4-Dihydro-2H-pyrrole-2-carbonitriles: Useful Intermediates in the Synthesis of Fused Pyrroles and 2,2′-Bipyrroles

Various heterocyclic structures containing the pyrrole moiety have been synthesized from easily accessible 3,4-dihydro-2H-pyrrole-2-carbonitriles in one-pot procedures. 5,6,7,8-Tetrahydroindolizines, 2,3-dihydro-1H-pyrrolizines as well as 6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepines were obtained from these precursors in high yields in an alkylation/annulation sequence. The same conditions were applied in the synthesis of a 5,8-dihydroindolizine, which could easily be transformed to the corresponding indolizine by dehydrogenation. Furthermore, oxidative couplings of 3,4-dihydro-2H-pyrrole-2-carbonitriles with copper(II)-salts furnished 2,2'-bipyrroles as well as 5,5'-bis(5-cyano-1-pyrroline…

ChemInform Abstract: Synthetic Approaches to Antiinflammatory Macrolactones of the Oxacyclododecindione Type.

A variety of attempts to synthesize oxacyclododecindione macrolactones through carbonylative ring-closure, intramolecular alkyne hydroacyalation, and Ru-catalyzed double bond isomerization fails.

A facile cleavage of allyl ethers on solid phase

Abstract A simple and efficient protocol for the cleavage of allyl ethers on solid phase using a palladium(0)-catalyzed allyl transfer reaction is reported.

A new ceramide from the leaves of Lannea schimperi (Hochst. ex A.Rich.) Engl.

A new ceramide is being reported herein together with six known compounds from the methanol extract of the leaves of Lannea schimperi (Hochst. ex A.Rich.) Engl. The metabolites were obtained through repeated open column chromatography and were characterized by spectroscopic and spectrometric techniques. The radical-scavenging activity of the crude extract and isolated compounds was evaluated using the DPPH radical. The obtained results suggest the studied species as prominent candidate to fight reactive oxygen species (ROS).

ChemInform Abstract: Synthesis and Isolation of Enantiomerically Enriched Cyclopenta[b]benzofurans Based on Products from Anodic Oxidation of 2,4-Dimethylphenol.

Tetramer (I) is obtained by anodic oxidation of 2,4-dimethylphenol as reported in a previous paper.

1,3-Benzyl Migration in Iminium Ions: Evidence for a Fast Free-Radical Chain Reaction

The “exocyclic” 1,3-benzyl shift observed in iminium salts derived from 1-benzyl-1,2,3,4-tetrahydroisoquinolines is related to the “endocyclic” Knabe rearrangement. A crossover experiment, isotopic labelling, the study of initiators and inhibitors as well as DFT calculations of gas-phase model structures provide evidence for a free-radical pathway under kinetic entropy control that is not affected by “slow” radical traps.

Targeting of immune cells with trimannosylated liposomes

Di-tert-butyl Phosphonate Route to the Antiviral Drug Tenofovir

Di-tert-butyl oxymethyl phosphonates were investigated regarding their suitability for preparing the active pharmaceutical ingredient tenofovir (PMPA). First, an efficient and simple access to the crystalline di-tert-butyl(hydroxymethyl)phosphonate was developed. O-Mesylation gave high yields of the active phosphonomethylation reagent. For the synthesis of tenofovir, a two-step sequence was developed using Mg(OtBu)2 as the base for the alkylation of (R)-9-(2-hydroxypropyl)adenine. Subsequent deprotection could be achieved with aqueous acids. (Di-tert-butoxyphosphoryl)methyl methanesulfonate showed to be the most efficient electrophile tested, affording PMPA in 72% yield on a 5 g scale. The …

The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC50 values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol was the most effe…

Total Synthesis of (-)-Oxycodone via Anodic Aryl-Aryl Coupling.

A fully regio- and diastereoselective electrochemical 4a–2′-coupling of a 3′,4′,5′-trioxygenated laudanosine derivative enables the synthesis of the corresponding morphinandienone. This key intermediate is further transformed into (−)-oxycodone through conjugate nucleophilic substitution for E-ring closure and [4 + 2] cycloaddition with photogenerated singlet oxygen to accomplish diastereoselective hydroxylation at C-14. The anodic transformation provides high yields and can be performed under constant current conditions both in a simple undivided cell or in continuous flow.

ChemInform Abstract: Radical Addition to Iminium Ions and Cationic Heterocycles

Carbon-centered radicals represent highly useful reactive intermediates in organic synthesis. Their nucleophilic character is reflected by fast additions to electron deficient C=X double bonds as present in iminium ions or cationic heterocycles. This review covers diverse reactions of preformed or in situ-generated cationic substrates with various types of C-radicals, including alkyl, alkoxyalkyl, trifluoromethyl, aryl, acyl, carbamoyl, and alkoxycarbonyl species. Despite its high reactivity, the strong interaction of the radical’s SOMO with the LUMO of the cation frequently results in a high regioselectivity. Intra- and intermolecular processes such as the Minisci reaction, the Porta react…

Two-Step Synthesis of 2-Aminoindolizines from 2-Alkylpyridines

An efficient method for the synthesis of 2-aminoindolizines by the 5-exo-dig cyclization of 2-alkyl-1-(1-cyanoalkyl)pyridinium salts has been developed. These substrates were prepared by N-alkylation of 2-alkylpyridines with readily available cyanohydrin triflates. The method allows the introduction of various substituents at the 1-, 3-, 6-, 7-, and 8-positions and leaves no undesired acceptor groups in the products.

Total synthesis of two potent anti-inflammatory macrolactones of the oxacyclododecindione type

An esterification/Friedel-Crafts-cyclization approach permitted the first successful synthetic entry into the oxacyclododecindione subclass of the dihydroxyphenylacetic acid lactone-type natural products. This route allowed the preparation of two highly active anti-inflammatory fungal secondary metabolites 14-deoxyoxacyclododecindione and 14-deoxy-4-dechlorooxacyclododecindione as well as their 14-desmethyl analogues.

Synthesis of Lamellarin D Trimethyl Ether and Lamellarin H via 6π-Electrocyclization.

An electrocyclic ring closure of a 2-azapentadienyl anion generated in situ from a chalcone and glycine ester is the key step of an efficient synthesis of the pyrrole core of the lamellarin alkaloids. A recently developed scalable one-pot procedure provides multigram quantities of a 3,5-diaryl-4-iodopyrrole-2-carboxylate intermediate which is transformed in four further high-yielding operations including a one-pot Pomeranz–Fritsch alkylation/cyclization and an Ullmann-type lactone ring closure into the pentacyclic lamellarin skeleton.

ChemInform Abstract: Sweet (Hetero)aromatics: Glycosylated Templated for the Construction of Saccharide Mimetics.

Several general strategies for the construction of mono- and diglycosylated (hetero)aromatics as potential metabolically stable oligosaccharides are described.

Synthesis of Morphinans through Anodic Aryl‐Aryl Coupling

The morphinans are an important class of structurally fascinating and physiologically important natural products as exemplified by the famous opium alkaloids of the morphine family. Although this class of secondary metabolites from the juice of the opium poppy capsule was already used for medicinal purposes thousands of years ago, chemical modifications are still being applied to the core structure today in order to achieve the most specific effect on the various receptor subtypes possible with the fewest possible side effects. The unusual architecture of the morphinan core has also proven to be a highly challenging target for total synthesis. This review highlights electrosynthetic approac…

Bürgenstock: Stereochemie ohne Grenzen

Auch in diesem Fruhjahr war der Burgenstock oberhalb von Luzern Schauplatz der ESF/-EUCHEM Conference on Stereochemistry. State-of-the-Art-Synthesemethoden und Entwicklungen an den Schnittstellen der Chemie zu den Bio- und Materialwissenschaften bildeten die thematischen Schwerpunkte der Tagung.

One-Pot Synthesis of (.+-.)-Crispine A and Its C-Ring-Substituted Analogues.

d-Glucose as a multivalent chiral scaffold for combinatorial chemistry

Due to their high density of functional groups and their availability in a variety of diastereomeric forms, monosaccharides are considered attractive scaffolds for combinatorial chemistry that allow the attachment and defined spatial alignment of up to five different pharmacophoric groups. For their application in combinatorial syntheses on solid phase, a set of selectively removable hydroxy protecting groups in combination with a cleavable anchor is required. Herein, we report on the construction and use of a versatile multivalent glucose building block for parallel synthesis on the solid phase.

Synthesis of alkaloids by Stevens rearrangement of nitrile-stabilized ammonium ylides: (±)-laudanosine, (±)-laudanidine, (±)-armepavine, (±)-7-methoxycryptopleurine, and (±)-xylopinine.

The Stevens rearrangement of nitrile-stabilized ammonium ylides in conjunction with the reductive removal of the nitrile function permits the facile construction of α-branched amines from α-aminonitriles. We employed this reaction sequence for the preparation of (±)-laudanosine, (±)-laudanidine and (±)-armepavine, (±)-7-methoxycryptopleurine, and (±)-xylopinine from two closely related and readily accessible bicyclic α-aminonitriles. The final products were obtained in high to almost quantitative yields (71–98%) from the quaternary ammonium salts obtained by N-alkylation of these starting materials.

Xylochemie – Naturstoffsynthese aus Holz

Combinatorial synthesis of amino acid- and peptide-carbohydrate conjugates on solid phase

Carbohydrates are useful polyfunctional scaffold molecules which allow the selective attachment of a number of different side chains. The combinatorial solid phase synthesis of diverse amino acid or peptide conjugates of a polyfunctional glucose scaffold based on a set of selectively removable and orthogonally stable protecting groups is described. The resulting carbohydrate-peptide hybrids constitute potential turn mimetics.

ChemInform Abstract: Two-Step Synthesis of 2-Aminoindolizines from 2-Alkylpyridines.

5-Exo-dig cyclization of 2-alkyl-1-(1-cyanoalkyl)pyridinium triflates offers a convenient method for the synthesis of 2-aminoindolizines.

Marine Isonitriles and Their Related Compounds.

Marine isonitriles represent the largest group of natural products carrying the remarkable isocyanide moiety. Together with marine isothiocyanates and formamides, which originate from the same biosynthetic pathways, they offer diverse biological activities and in spite of their exotic nature they may constitute potential lead structures for pharmaceutical development. Among other biological activities, several marine isonitriles show antimalarial, antitubercular, antifouling and antiplasmodial effects. In contrast to terrestrial isonitriles, which are mostly derived from α-amino acids, the vast majority of marine representatives are of terpenoid origin. An overview of all known marine isoni…

Caffeate and piperidine-3-ol derivatives from the stem bark of Cassia sieberiana

A new caffeate derivative from the ethanol extract of the stem bark of Cassia sieberiana DC. is described herein along with the known secondary metabolites spectaline (2), iso-6-cassine (3), 3-O-methyl-chiro-inositol (4), monobehenin (5), octyl nonadecyloate (6), β-sitosterol (7), stigmasterol (8) and sitosterol 3-O-β-D-glucopyranoside (9). The chemical structures were elucidated by means of various spectroscopic and spectrometric techniques. Extract and isolated compounds were devoid of inhibitory action against the herein selected bacterial strains (MICs > 256 μg/mL) but showed capacities to reduce 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (EC50 50 6.47 ± 0.48 μg/mL).

Sunflow: Sunlight Drives Fast and Green Photochemical Flow Reactions in Simple Microcapillary Reactors - Application to Photoredox and H-Atom-Transfer Chemistry

“Sunflow“ – The combination of a microcapillary reactor in continuous flow mode with sunlight as the most sustainable energy source imaginable was applied to a range of photoredox and H-atom-transfer reactions making them both fast and green.

Cover Feature: Flow Photochemistry of Azosulfones: Application of “Sunflow” Reactors (ChemPhotoChem 10/2018)

ChemInform Abstract: Unique Regioselectivity in the C(sp3)-H α-Alkylation of Amines: The Benzoxazole Moiety as a Removable Directing Group.

The benzoxazol-2-yl substituent is easily introduced by oxidative coupling or nucleophilic substitution and can be removed by hydroxide or by hydride reduction.

Prenylated isoflavones from the stem bark of Erythrina sacleuxii

Abstract Two new prenylated isoflavones, named erysacleuxin A (1) and B (2), along with eight known compounds, biochanin A (3), 5′-(3-methylbut-2-enyl)pratensein (4), 7-demethylrobustigenin (5), 3′-(3-methylbut-2-enyl)biochanin A (6) abyssinone V-4′-methyl ether (7), sigmoidin E (8), erythrinasinate (9), and burtinone (10) were isolated from the stem bark of Erythrina sacleuxii Hua (Leguminosae). The structures were determined based on spectroscopic and spectrometric data. All isolated compounds were evaluated for antifungal activity against Botrytis cinerea, Candida albicans, Eremothecium coryli, Penicillium notatum, Pyricularia oryzae, and Rhizomucor miehei with compounds 3, 4 and 6 showi…

Kohlenhydrat-basierte Nanocarrier mit spezifischem Zell-Targeting und minimalem Einfluss durch die Proteinkorona

Sobald Nanopartikel mit biologischen Flussigkeiten wie Blut in Kontakt kommen, adsorbieren Proteine auf ihrer Oberflache, welche die sogenannte Proteinkorona ausbilden. Die Wichtigkeit dieser Proteinhulle ist weitgehend anerkannt, jedoch untersuchen nur wenige Studien den Einfluss von Oberflachenfunktionalisierung der Nanocarrier auf die Proteinkorona. Vor allem die Variation der Proteinkorona von PEGylierten und zusatzlich mit Targeting-Molekulen versehenen Nanotragern und der Einfluss auf das Targeting sind nicht bekannt. Hydroxyethylstarke-Nanocarrier (HES-NCs) wurden synthetisiert, anschliesend PEGyliert und zusatzlich (“on top”) mit Mannose funktionalisiert, um dendritische Zellen (DCs…

Noncovalent Targeting of Nanocarriers to Immune Cells with Polyphosphoester‐Based Surfactants in Human Blood Plasma

Abstract Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T‐cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to nanocarriers requires new chemistry for each nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the nanoca…

Synthesis of 5‐Fluorocytosine Using 2‐Cyano‐2‐fluoroethenolate as a Key Intermediate

Synthesis of 1,3- and 2,3-Diglycosylated Indoles as Potential Trisaccharide Mimetics

Diglycosylated heteroaromatics may serve as metabolically stable mimetics of trisaccharides. Herein, the preparation of several 1,3- and 2,3-diglycosylindoles by direct C-glycosylation of monoglycosylated precursors is described.

Synthesis of (-)-Cryptopleurine by Combining Gold(I) Catalysis with a Free Radical Cyclization

(R)-(–)-Cryptopleurine, a highly cytotoxic alkaloid found in Cryptocarya and Boehmeria species, was synthesized in high optical purity using a gold(I)-NHC catalyzed cyclization of an unsymmetrical phenanthrene precursor combined with a free radical cyclization to achieve closure of the C-ring.

Glucose as an Eco‐Friendly Reductant in a One‐Pot Synthesis of 2,3‐Dihydroquinazolin‐4(1 H )‐ones

Back Cover: A Regio- and Diastereoselective Anodic Aryl-Aryl Coupling in the Biomimetic Total Synthesis of (−)-Thebaine (Angew. Chem. Int. Ed. 34/2018)

Assignment of the Absolute Configuration and Total Synthesis of (+)-Caripyrin

The antifungal secondary metabolite (+)-caripyrin was studied by vibrational circular dichroism spectroscopy. Analysis of the recorded data, with the Boltzmann weighted-average of the spectra calculated at the B3LYP/6-311G(d,p) level of theory for all relevant conformers, unequivocally proved the (R,R)-configuration for the dextrorotatory natural product. Based on this finding, a short enantioselective synthesis of (+)-caripyrin was developed.

An Unexpected Three-Component Condensation Leading to Amino(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)acetonitriles.

The reaction of 2-carboxybenzaldehyde with primary amines in the presence of cyanide leads to the formation of 2-substituted amino(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)acetonitriles. These compounds originate from the condensation of 2-carboxybenzaldehyde with the amine and two molecules of hydrogen cyanide and represent a novel class of isoindolinones.

Synthesis of 2,3‐Dihydro‐4‐pyridones, 4‐Quinolones, and 2,3‐Dihydro‐4‐azocinones by Visible‐Light Photocatalytic Aerobic Dehydrogenation

ChemInform Abstract: A Photochemical One-Pot Three-Component Synthesis of Tetrasubstituted Imidazoles.

α-(alkylideneamino)nitriles generated in situ from α-aminonitriles and aldehydes react with acylaziridines formed in situ by photochemical ring transformation of isoxazoles.

Sweet (hetero)aromatics: glycosylated templates for the construction of saccharide mimetics

Mono- and diglycosylated aromatics and heteroaromatics may serve as building blocks for the construction of metabolically stable mimetics of oligosaccharides. Methods for their preparation from monosaccharidic precursors by direct C-glycosylation, dipolar cycloaddition or Larock cyclization are described.

Anti-inflammatory drimane sesquiterpene lactones from an Aspergillus species

Abstract IFN-γ inducible protein 10 (IP-10, CXCL10) is a 10 kDa chemokine, which is secreted from various cell types after exposure to pro-inflammatory stimuli. This chemokine is a ligand for the CXCR3 receptor and regulates immune responses by activating and recruiting leukocytes such as T cells, eosinophils, monocytes, and NK cells to sites of inflammation. Altered expression of CXCL10 has been associated with chronic inflammatory and infectious diseases and therefore CXCL10 represents a promising target for the development of new anti-inflammatory drugs. In a search for inhibitors of CXCL10 promoter activity, three structurally related drimane sesquiterpene lactones (compounds 1–3) were …

Titelbild: Xylochemie – Naturstoffsynthese aus Holz (Angew. Chem. 47/2015)

Insight into the synthesis of N-methylated polypeptides

The ring-opening polymerization (ROP) of N-carboxy anhydrides (NCAs) is mostly divided into two classes: NCAs of α-substituted amino acids and N-methylated NCAs of α-unsubstituted glycine derivatives (NNCAs). The use of both monomer types offers different mechanistic features and results in a multitude of functional materials. To combine these properties, the synthesis and ROP of α-substituted and N-methylated NCAs (αNNCAs) of several amino acids were investigated. The current study provides insight into the influence of polymerization conditions and the limitations caused by the enhanced steric demand of the amino acid NCA monomers and their N-methylated derivatives. Namely, the effects of…

Photo-Chromium: Sensitizer for Visible-Light-Induced Oxidative C−H Bond Functionalization-Electron or Energy Transfer?

The chromium(III) sensitizer [Cr(ddpd)2]3+ - based on an earth-abundant metal center - possesses a unique excited state potential energy landscape (ddpd = N,N'-dimethyl-N,N'-dipyridine-2-ylpyridine-2,6-diamine). The very large energy gap between the redox active and substitutionally labile 4T2 state and the long-lived low-energy 2E spin-flip state enables a selective, efficient sensitization of triplet dioxygen to give singlet dioxygen. Ultrafast intersystem crossing after the Franck Condon point from the 4T2 to the 2E excited state within 3.5 ps precludes intermolecular electron transfer pathways from the ultrashort-lived excited 4T2 state. This specific excited state reactivity enables a …

Isolactarane and Sterpurane Sesquiterpenoids from the Basidiomycete Phlebia uda

Three new sesquiterpenoids, named udasterpurenol A, udalactarane A, and udalactarane B, as well as the known compounds hyphodontal and sterpuric acid have been isolated from the basidiomycete Phlebia uda. These compounds represent the first natural products described from this species. The structures were elucidated by NMR spectroscopy and mass spectrometry. Udalactaranes A and B were isolated as mixtures with their respective epimeric acetals. These mixtures inhibited the spore germination of the plant pathogenic fungus Fusarium graminearum at 10 and 5 μg/mL, respectively, and were active against Jurkat cells with IC(50) values of 101 and 42 μM, respectively.

An Unexpected Three-Component Condensation Leading to Amino- (3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)- acetonitriles

The reaction of 2-carboxybenzaldehyde with primary amines in the presence of cyanide leads to the formation of 2-substituted amino(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)acetonitriles. These compounds originate from the condensation of 2-carboxybenzaldehyde with the amine and two molecules of hydrogen cyanide and represent a novel class of isoindolinones.

Synthesis of Highly Substituted Unsymmetrical 1,2-Diamines, 1,2-Diimines, Imidazolium Salts and Imidazolylidenes by Aldimine Cross-Coupling

α-Aminonitriles derived from aromatic aldehydes and primary amines can be deprotonated quantitatively without the use of protecting groups. The 1,2-addition of the resulting stabilized α-aminocarbanions to imines yields α-aminoimines and the tautomeric enediamines. These unstable compounds can directly be oxidized to 1,2-diimines or reduced to 1,2-diamines in a one-pot reaction. 1,2-Diamines can be obtained in high diastereoselectivity by reduction of the 1,2-diimines. In this case, the relative configuration of the products can be chosen depending on the reduction conditions. Cyclization of the unsymmetrical diimines with halomethyl ethers or esters leads to 1,3,4,5-tetrasubstituted imidaz…

Vinylcyclopropane [3+2] Cycloaddition with Acetylenic Sulfones Based on Visible Light Photocatalysis

We describe the first intermolecular visible light [3+2] cycloaddition reaction being performed on a meta photocycloadduct employing acetylenic sulfones. The developed methodology exploits the advantages of combining UV and Visible light in a two-step sequence that provides a photogenerated cyclopropane which, through a strain-release process, generates a new cyclopentane ring while increasing significally the molecular complexity. This strategy could be extended to simpler vinylcyclopropanes.

A Photoredox-Catalyzed Four Component Reaction for the Atom-Efficient Synthesis of Complex Secondary Amines

The one-pot sulfonylation/aminoalkylation of styrene derivatives furnishing highly substituted gamma-sulfonylamines was accomplished through a photoredox-catalyzed four-component reaction. Apart from one molecule of water and the sodium counterion of the sulfinate, all atoms of the starting materials are transferred to the final product, rendering this process highly atom-efficient. The operationally simple protocol allows for the simultaneous formation of three new single bonds (C–S, C–N, and C–C) and therefore grants rapid access to structurally diverse products. The reaction proceeds under mild conditions in aqueous acetonitrile and shows a broad scope, including natural products and dru…

Synthesis of two Conformationally Restricted Piperazine Scaffolds for Combinatorial Chemistry

Piperazines are widely used as central elements in the construction of bioactive molecules. Herein, the short synthesis of two chiral 2,6-bridged piperazines possessing orthogonally stable protecting groups from readily available starting materials is described. It is suggested that these molecules may be used as conformationally restricted scaffolds for the combinatorial synthesis of drug-like compounds. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

ChemInform Abstract: Heterocycles from α-Aminonitriles

Owing to their various modes of reactivity, α-aminonitriles represent versatile building blocks for the construction of a wide range of nitrogen heterocycles. The present Concept article focuses on synthetic methodologies using their bifunctional nature which is the basis of their reactivity as α-amino carbanions and as iminium ions. Reactions exclusively taking place on either the amine or on the nitrile moiety will not be considered.

A Modular Formal Total Synthesis of (±)-Cycloclavine

Cycloclavine is a clavine-type Ergot alkaloid noteworthy for its unique pentacyclic skeleton featuring a 3-azabicyclo[3.1.0]hexane substructure. A short convergent route to the racemic alkaloid is described which comprises only eight linear steps and requires only four chromatographic purifications. The two key building blocks can be prepared in high yield from commercially available starting materials. Two consecutive coupling reactions, namely a selective alkylation of a dienolate and a Heck reaction, are the key steps of the reaction sequence.

Flavans and other chemical constituents of Crinum biflorum (Amaryllidaceae)

Abstract The ethyl acetate extract from the whole plant of Crinum biflorum Rottb. Showed a moderate activity against Enterococcus faecalis. Its phytochemical investigation led to the isolation of a new flavan-3-ol derivative namely (2R,3R)-3-hydroxy-7-methoxy-3′,4′-methylenedioxyflavan, together with (2S)-7-hydroxy-3′,4′-methylenedioxyflavan, (2R,3R)-7-methoxy-flavan-3-ol, (2S)-7-hydroxy-3′,4′-dimethoxyflavan, 3′,7-dihydroxy-4′-methoxyflavan, 4′,7-dimethoxy-3′-hydroxyflavan, farrerol, β-sitosterol, β-sitosterol-3-O-β-D-glucopyranoside, oleanolic acid, kaempferol, pancratistatin, lupeol, aurantiamide acetate, Narciprimine and 2,3-dihydroxypropyl palmitate. Their structures were elucidated ma…

Elucidation of the biosynthesis and degradation of allantofuranone by isotopic labelling and fermentation of modified precursors.

Feeding experiments with the ascomycete Allantophomopsis lycopodina indicated that the potent fungistatic allantofuranone is biosynthesized from phenylalanine. Further experiments with synthetic precursors gave evidence that the naturally occurring polyporic acid serves as a key intermediate in the biosynthesis. In addition to the formation of allantofuranone, its abiotic and metabolic degradation were investigated.

ChemInform Abstract: Synthetic Approaches Towards Huperzine A and B

Huperzine A and B are potent acetylcholinesterase inhibitors and promising against Alzheimer's disease. Completed and formal total syntheses of these medically relevant alkaloids are presented and discussed.

Non-toxic cyanide sources and cyanating agents

The present review gives an overview over non-toxic cyanation agents and cyanide sources used in the synthesis of structurally diverse products containing the nitrile function. Nucleophilic as well as electrophilic agents/systems that transfer the entire CN-group were taken in consideration. Reactions in which a preexisting carbon functionality is transformed into a nitrile function by addition of nitrogen are however not covered here.

Chemical constituents of the root wood of Erythrina sacleuxii and determination of the absolute configuration of suberectin

Phytochemical investigation on the root wood of Erythrina sacleuxii (Leguminosae) led to the isolation of nine secondary metabolites (1-9). Compound 1 was isolated from the genus Erythrina for the first time. The pure compounds were identified on the basis of comprehensive spectroscopic and spectrometric analyses, while their absolute configurations were determined based on chiroptical measurements. Compounds 5 and 6 showed weak antifungal activity against Pyricularia oryzae with MIC values of 20 µg/mL.
  
 Bull. Chem. Soc. Ethiop. 2020, 34(1), 135-140.
 DOI: https://dx.doi.org/10.4314/bcse.v34i1.12

HPMA-Based Nanocarriers for Effective Immune System Stimulation.

The selective activation of the immune system using nanoparticles as a drug delivery system is a promising field in cancer therapy. Block copolymers from HPMA and laurylmethacrylate-co-hymecromone-methacrylate allow the preparation of multifunctionalized core-crosslinked micelles of variable size. To activate dendritic cells (DCs) as antigen presenting cells, the carbohydrates mannose and trimannose are introduced into the hydrophilic corona as DC targeting units. To activate DCs, a lipophilic adjuvant (L18-MDP) is incorporated into the core of the micelles. To elicit an immune response, a model antigen peptide (SIINFEKL) is attached to the polymeric nanoparticle-in addition-via a click rea…

N-[(1S,2S)-2-Amino-1,2-diphenyl­eth­yl]-4-methyl­benzene­sulfonamide [(S,S)-TsDPEN]

The crystal structure of the title compound, C21H22N2O2S, shows a network of N—H...N and N—H...O hydrogen bonds. The tolyl and 1-phenyl rings are almost mutually coplanar [7.89 (9)°], while the 2-phenyl ring makes a dihedral angle of 50.8 (1) ° with the 1-phenyl ring. An intramolecular N—H...N hydrogen bond stabilizes the molecular conformation.

Synthesis of γ-Amino Acid Esters by 1,4-Addition of Deprotonated α-Aminonitriles and α-(Alkylideneamino)nitriles to α,β-Unsaturated Esters.

α-Aminonitriles and α-(alkylideneamino)nitriles can serve as readily available α-aminocarbanion equivalents. Their conjugate addition to α,β-unsaturated esters followed by reduction furnishes polysubstituted γ-amino acid esters in moderate to high yield.

Applications of xylochemistry from laboratory to industrial scale

Xylochemicals and their utilisation in total synthesis and industrial applications are highlighted in this review. This class of chemicals consists of bio-based molecules or building blocks derived from renewable feedstocks like plant-biomass, lignocellulose as well as waste-streams. The advantages over petroleum-based chemicals are presented with the aid of specific examples ranging from the total synthesis of natural products, relevant industrial applications to the exploitation of CO2 as a C1 feedstock. This review contributes to the trend of a “greener” and a more sustainable chemistry.

Chromatographically separable rotamers of an unhindered amide

Surprisingly stable formamide rotamers were encountered in the tetrahydroisoquinoline and morphinan series of alkaloids. We investigated the hindered rotation around the amide bond by dynamic high-performance liquid chromatography (DHPLC) and kinetic measurements of the interconversion of the rotamers which can readily be separated by HPLC as well as TLC. The experimental results of the different methods were compared to each other as well as to results obtained by DFT calculations.

Chemical constituents from Anthocleista liebrechtsiana De Wild & T. Durand (Loganiaceae)

Abstract A new steroid derivative, (24S)-3β-hydroxy-7β-methoxyergost-5-ene (1), was isolated along with eleven known compounds: 7α-hydroxysterol (2), β-sitosterol (3), oleanolic acid (4), betulinic acid (5), lupeol (6), swertiaperennin (7), decussatin (8), tetracosanoic acid (9) β-sitosterol-3-O-β- d -glucopyranoside (10), (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran (11) and acacetin 6-C-β- d -glucopyranoside (12) from the tree bark and leaves of Anthocleista liebrechtsiana De Wild & T. Durand. Their structures were elucidated on the basis of spectroscopic (1D and 2D NMR) and mass spectrometric data. Compounds 2 and 7–10 have already bee…

A new ursane-type triterpene oxoglucopyranoside from Crossopteryx febrifuga.

Abstract A new saponin, 3-O-β-d-3-oxo-glucopyranosyl-ursa-12,20(30)-diene-27,28-dioic acid (1), was isolated from the methanol extract of stem bark of Crossopteryx febrifuga together with the known 3β-d-glucopyranosyl-ursa-12,20(30)-diene-27,28-dioic acid (2), shanzhiside methyl ester (3), shanzhiside (4), β-sitosterol (5), β-sitosterol-3-O-β-d-glucopyranoside (6), ursa-12,20(30)-diene-27,28-dioic acid (7), hederagenin (8), and oleanolic acid (9). The structures were established by comprehensive interpretation of their spectral data 1D- (1H and 13C), 2D-NMR (1H-1H COSY, HMQC, HMBC), spectroscopic, and electrospray ionisation time-of-flight mass spectrometry analysis. The isolated compounds …

Separation, isolation and stereochemical assignment of imazalil enantiomers and their quantitation in an in vitro toxicity test

A simple method for the separation of the enantiomers of the fungicide imazalil was developed. Racemic imazalil was separated into its enantiomers with an enantiomeric purity of 99% using HPLC-UV with an enantioselective column (permethylated cyclodextrin) operated in reversed phase mode (water with 0.2% trimethylamine and 0.08% acetic acid and methanol). The absolute configuration of the separated enantiomers was assigned and unequivocally confirmed by optical rotation as well as by vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) combined with ab-initio calculations. The same enantioselective column was also used to develop an HPLC-MS/MS method for the quantifi…

Chemical profiling of the synthetic cannabinoid MDMB-CHMICA: Identification, assessment, and stability study of synthesis-related impurities in seized and synthesized samples.

In this work, the most discriminating synthesis-related impurities found in samples from seizures and controlled synthesis of the synthetic cannabinoid MDMB-CHMICA (methyl (S)-2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate) were characterized. Based on 61 available powder samples of MDMB-CHMICA, 15 key-impurities were assessed, isolated in larger quantities via flash chromatography and structurally elucidated and characterized via high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Apart from verifying the relation of the impurities to the major component, the interpretation of their chemical structures with distinct structural elements pro…

Donellanic acids A–C: new cyclopropanic oleanane derivatives from Donella ubanguiensis (Sapotaceae)

Abstract Three new cyclopropanic oleanane triterpenoids and ten known compounds were obtained from Donella ubanguiensis using chromatographic methods. The structures were established on the basis of mass spectrometric and NMR data and by comparison with values reported in the literature. The structures of the new compounds were confirmed by X-ray crystallography. A part of the isolated compounds was evaluated for cytotoxic and antimicrobial activities.

A Photochemical One-Pot Three-Component Synthesis of Tetrasubstituted Imidazoles

Tetrasubstituted imidazoles can be formed in a photochemical one-pot synthesis from aldehydes, α-aminonitriles, and isoxazoles. Condensation of the first two components produces α-(alkylideneamino)nitriles which react under basic conditions with the acylazirines formed in situ by photochemical ring transformation of the isoxazole component. This process includes an unusual cleavage of the C(2)-C(3) bond of the acylazirine. The reaction mechanism was studied by DFT calculations.

ChemInform Abstract: Pyrroles and Indolizidines from Deprotonated α-(Alkylideneamino)nitriles.

Caffeate and piperidine-3-ol derivatives from the stem bark of Cassia sieberiana

A new caffeate derivative from the ethanol extract of the stem bark of Cassia sieberiana DC. is described herein along with the known secondary metabolites spectaline (2), iso-6-cassine (3), 3-O-methyl-chiro-inositol (4), monobehenin (5), octyl nonadecyloate (6), β-sitosterol (7), stigmasterol (8) and sitosterol 3-O-β-D-glucopyranoside (9). The chemical structures were elucidated by means of various spectroscopic and spectrometric techniques. Extract and isolated compounds were devoid of inhibitory action against the herein selected bacterial strains (MICs > 256 μg/mL) but showed capacities to reduce 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (EC50 < 3 μg/mL) considerably better than the …

Eine regio- und diastereoselektive anodische Aryl-Aryl-Kupplung in der biomimetischen Totalsynthese von (−)-Thebain

Omphalocarpoidone, a new lanostane-type furano-spiro-γ-lactone from the wood of Tridesmostemon omphalocarpoides Engl. (Sapotaceae)

Abstract Phytochemical studies of the wood and the stem bark of Tridesmostemon omphalocarpoides Engl. (Sapotaceae) led to the isolation of omphalocarpoidone (1), a new lanostane-type furano-spiro-γ-lactone together with β-amyrin acetate (2), taraxerol (3), spinasterol (4), lichexanthone (5), epi-catechin (6), spinasterol 3-O-β- d -glucopyranoside (7), tormentic acid (8), and 1,2,3,4-tetrahydronorharman-1-one (9). Their structures were established on the basis of extensive NMR studies, mass spectrometry, and by comparison of the data with those previously reported in the literature. The structure of the new secondary metabolite was later confirmed by X-ray crystallography. Except for spinast…

Oxidation of Trialkylamines by BrCCl3 : Scope, Applications and Mechanistic Aspects

Hirsutane-Type Sesquiterpenes with Uncommon Modifications from Three Basidiomycetes

From three basidiomycetes, Xeromphalina sp., Stereum sp., and Pleurocybella porrigens, six triquinane sesquiterpenes with unprecendented modifications and a rearranged sesquiterpene related to coriolin C have been isolated. Their isolation, structure elucidation, and biological evaluation are described.

Carbohydrate nanocarriers in biomedical applications: functionalization and construction

The specific targeting of either tumor cells or immune cells in vivo by carefully designed and appropriately surface-functionalized nanocarriers may become an effective therapeutic treatment for a variety of diseases. Carbohydrates, which are prominent biomolecules, have shown their outstanding ability in balancing the biocompatibility, stability, biodegradability, and functionality of nanocarriers. The recent applications of sugar (mono/oligosaccharides and/or polysaccharides) for the development of nanomedicines are summarized in this review, including the application of carbohydrates for the surface-functionalization of various nanocarriers and for the construction of the nanocarrier its…

Visible Light Enables Aerobic Iodine Catalyzed Glycosylation

Acute and Repeated Treatment with 5-PAHSA or 9-PAHSA Isomers Does Not Improve Glucose Control in Mice

Summary Fatty acid esters of hydroxylated fatty acids (FAHFAs) were discovered as a novel class of endogenous mammalian lipids whose profound effects on metabolism have been shown. In the current study, in vitro and in vivo the metabolic effects of two of these FAHFAs, namely palmitic acid-5- (or -9) -hydroxy-stearic acid (5- or 9-PAHSA, respectively) were profiled. In DIO mice fed with differentially composed low- or high-fat diets, acute and subchronic treatment with 5-PAHSA and 9-PAHSA alone, or in combination, did not significantly improve the deranged metabolic status. Neither racemic 5- or 9-PAHSA, nor the enantiomers were able to: (1) increase basal or insulin-stimulated glucose upta…

D-Glucose as a Pentavalent Chiral Scaffold

A novel carbohydrate-based scaffold for combinatorial chemistry has been developed. This scaffold allows the selective attachment of five different side chains, giving rise to products of enormous structural diversity. As a demonstration of its usefulness, a series of model compounds has been prepared in high purity and yield by multistep parallel synthesis on a solid phase. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

ChemInform Abstract: Iodocyclization of o-Alkynylbenzamides Revisited: Formation of Isobenzofuran-1(3H)-imines and 1H-Isochromen-1-imines Instead of Lactams.

Remarkably, isobenzofuran and benzopyran derivatives are obtained by the title reaction and not as described in earlier publications five- or six-membered lactams.

Light-Induced Alkylation of (Hetero)aromatic Nitriles in a Transition-Metal-Free C–C-Bond Metathesis

A light-induced C–C-σ-bond metathesis was achieved through transition-metal-free activation of an unstrained C(sp3)–C(sp3)-σ-bond in 1-benzyl-1,2,3,4-tetrahydroisoquinolines. A photoredox-mediated single-electron oxidation of these precursor amines yield radical cations which undergo a homolytic cleavage of a C(sp3)–C(sp3)-σ-bond rather than the well-known α-C–H-scission. The resulting carbon-centered radicals are used in the ipso-substitution of (hetero)aromatic nitriles proceeding through another single-electron transfer-mediated C–C-bond cleavage and formation.

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

The cyclocondensation of enones with aminoacetonitrile furnishes 3,4-dihydro-2H-pyrrole-2-carbonitriles which can be readily converted to 2,4-disubstituted pyrroles by microwave-induced dehydrocyanation. Alternatively, oxidation of the intermediates produces 3,5-disubstituted pyrrole-2-carbonitriles.

Total Synthesis of (±)-Oxalicumone C and Chiral Resolution and Elucidation of Its Absolute Configuration

The racemic total synthesis, the chiral resolution, and the elucidation of the absolute configuration of the natural product oxalicumone C were investigated. The goal was achieved by a synthetic strategy beginning with the synthesis of a 5-hydroxy-7-methylchromone precursor. Further modification possibilities were achieved by introduction of a vinyl moiety into the chromone, which was based on a selective iodination step in the 3-position. Further transformations furnished the racemic natural product. To determinate the absolute configuration of naturally occurring oxalicumone C, both enantiomers were separated by chiral HPLC. Comparison of the calculated and experimental vibrational circul…

Synthesis and Unusual NMR-Spectroscopic Behavior of a Strained Bicyclic Ammonium Salt

A new polyketide from the bark of Hypericum roeperianum Schimp. (Hypericaceae)

The isolation and spectroscopic data of a hitherto undescribed polyketide (1) from Hypericum roeperianum Schimp. (Hypericaceae) together with six known compounds (2–7) is herein reported. The structure elucidation is based on extensive 1D- and 2D-NMR, infrared, UV and MS experiments. The structures of the known compounds were confirmed by comparison of their spectroscopic data with those of similar reported compounds in the literature. Some of the isolated compounds had a significant activity against a panel of multidrug-resistant bacterial strains.

Front Cover: Glucose as an Eco‐Friendly Reductant in a One‐Pot Synthesis of 2,3‐Dihydroquinazolin‐4(1 H )‐ones (Eur. J. Org. Chem. 41/2020)

Neo-clerodane diterpenoids from Conyza pyrrhopappa Sch.Bip. ex A.Rich

Two hitherto unknown neo-clerodane-type diterpenoids along with twelve known compounds have been isolated from Conyza pyrrhopappa Sch.Bip. ex A.Rich, a medicinal plant traditionally used across tropical Africa to relieve fever. The structures of isolates have been elucidated by a combination of spectroscopic techniques. The crude extract and the isolated compounds were evaluated in the Hela-S3 cell line and in a panel of microorganisms (bacteria and fungi) at concentrations up to 50 ��g/mL. The new compounds were inactive while the pentamethylated flavonoids showed low to significant activity against the cancer cell line used. However, none of the samples showed any activity against the tes…

Assignment of Configuration in a Series of Dioxolanone-Type Secondary Metabolites fromGuignardia bidwellii- A Comparison of VCD and ECD Spectroscopy

The absolute configurations of a series of phytotoxic dioxolanone-type secondary metabolites isolated from culture filtrates of the grape black rot fungus Guignardia bidwellii were determined by vibrational circular dichroism (VCD) spectroscopy in the mid-IR frequency range. Comparison of the recorded data with DFT calculations showed good agreement between experiment and theory for VCD, whereas electronic circular dichroism (ECD) data for the compounds matched poorly with the predicted spectra obtained by time-dependent DFT (TDDFT) calculations at the same level of theory.

Visible Light-Induced Sulfonylation/Arylation of Styrenes in a Double Radical Three-Component Photoredox Reaction

Simultaneous sulfonylation/arylation of styrene derivatives is achieved in a photoredox-catalyzed three-component reaction using visible light. A broad variety of difunctionalized products is accessible in mostly excellent yields and high diastereoselectivity. The developed reaction is scalable and suitable for the modification of styrene-functionalized biomolecules. Mechanistic investigations suggest the transformation to be operating through a designed sequence of radical formation and radical combination.

Mechanism and cis/trans Selectivity of Vinylogous Nazarov-type [6π] Photocyclizations

Vinylogous Nazarov-type cyclizations yield seven-membered rings from butadienyl vinyl ketones via a photochemical [6π] photocyclization followed by subsequent isomerization steps. The mechanism of this recently developed method was investigated using unrestricted DFT, SF-TDDFT, and CASSCF/NEVPT2 calculations, suggesting three different pathways that lead either to pure trans, pure cis, or mixed cis/trans configured products. Singlet biradicals or zwitterions occur as intermediates. The computational results are supported by deuterium-labeling experiments.

Enantioselective Synthesis of α-Quaternary Amino Acids by Alkylation of Deprotonated α-Aminonitriles.

A series of α-quaternary arylglycines were prepared in high optical purity (up to 98% ee) by α-alkylation of deprotonated α-aminonitriles derived by the Strecker reaction from (4S,5S)-5-amino-2,2-dimethyl-4-phenyl-1,3-dioxane. The procedure includes only chromatographic purification of the final products and is devoid of chromatography or crystallization operations on intermediates to raise the optical purity.

Enantioselective Synthesis of Tetrahydroprotoberberines and Bisbenzylisoquinoline Alkaloids from a Deprotonated α-Aminonitrile

Under controlled conditions, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile can be quantitatively deprotonated in the α-position. Its alkylation directly furnishes 3,4-dihydroisoquinolines which can serve as starting materials for the preparation of various alkaloids. Here, the preparation of the benzylisoquinolines (+)-laudanidine, (+)-armepavine, and (+)-laudanosine as well as the tetrahydroprotoberberines (-)-corytenchine and (-)-tetrahydropseudoepiberberine using Noyori's asymmetric transfer hydrogenation are described. The dimeric alkaloids (+)-O-methylthalibrine and (+)-tetramethylmagnolamine were obtained from nonracemic precursors in Ullmann diaryl ether syntheses.

Selective C-H Activation of Methoxy Groups in a Three-Component Photoreaction.

Surprisingly, the photocatalytic activation of ethers by H-abstraction and addition of the generated radicals to iminium ions formed in situ from aldehydes and anilines predominantly yielded the products of methoxy activation for dimethoxymethane and 1,2-dimethoxyethane. Various anilines and aromatic as well as aliphatic aldehydes are suitable reaction partners for this three-component photoreaction (Porta-type process) which also provides a simple access to 1,2-aminoalcohols.

Frontispiece: Strain Release Chemistry of Photogenerated Small‐Ring Intermediates

Six-Step Gram Scale Synthesis of the HIV Integrase Inhibitor Dolutegravir Sodium

A short and practical synthesis for preparing the active pharmaceutical ingredient dolutegravir sodium was investigated. The convergent strategy developed herein starts from 3-(R)-amino-1- butanol and builds up the BC ring system in 76% isolated yield over four steps. Ring A was constructed by a one-pot 1,4-addition to diethyl-(2E/Z)-2-(ethoxymethylidene)-3-oxobutandioate and subsequent MgBr2·OEt2-mediated regioselective cyclization. Amide formation with 2,4- difluorobenzylamine was either performed from the carboxylic acid or through aminolysis of the corresponding ester precursor. Final salt formation afforded dolutegravir sodium in 48–51% isolated yield (HPLC-purity: 99.7–99.9%) over six…

Total Synthesis of epi-Trichosetin.

The natural 3-decalinoyltetramic acid epi-trichosetin was synthesized in ten steps starting from ( R)-(+)-citronellal using an intramolecular Diels-Alder reaction and a Lacey-Dieckmann cyclization as the key steps. The use of a 2-nitrobenzyl protecting group resulted in an efficient synthetic endgame. The natural product was obtained in 4.1% overall yield.

Synthesis of (–)-(S)-Norlaudanosine, (+)-(R)-O,O-Dimethylcoclaurine, and (+)-(R)-Salsolidine by Alkylation of an α-Aminonitrile

A short asymmetric synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinoline alkaloids by deprotonation of an unprotected α-aminonitrile and alkylation of the resulting carbanion followed by spontaneous elimination of HCN and asymmetric reduction is described. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Marine Indole Alkaloids.

Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed.

Asymmetric One-Pot Synthesis of (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol: A Key Component of Current HIV Protease Inhibitors

A concise and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol, a key building block for several clinical and experimental HIV protease inhibitors including the highly important drug darunavir, was achieved via a one-pot procedure using furan and Cbz-protected glycol aldehyde as starting materials. A [2+2]-photocycloaddition between both reactants which can be prepared from wood-based starting materials according to the principles of xylochemistry, followed by hydrogenation and lipase-catalyzed kinetic resolution afforded the target compound in high yield and up to 99% ee.

Unravelling the biosynthesis of pyriculol in the rice blast fungus Magnaporthe oryzae

Pyriculol was isolated from the rice blast fungus Magnaporthe oryzae and found to induce lesion formation on rice leaves. These findings suggest that it could be involved in virulence. The gene MoPKS19 was identified to encode a polyketide synthase essential for the production of the polyketide pyriculol in the rice blast fungus M. oryzae. The transcript abundance of MoPKS19 correlates with the biosynthesis rate of pyriculol in a time-dependent manner. Furthermore, gene inactivation of MoPKS19 resulted in a mutant unable to produce pyriculol, pyriculariol and their dihydro derivatives. Inactivation of a putative oxidase-encoding gene MoC19OXR1, which was found to be located in the genome cl…

Antimicrobial secondary metabolites from the medicinal plant Crinum glaucum A. Chev. (Amaryllidaceae)

Abstract Medicinal plants are known as sources of potential antibacterial compounds including alkaloids. The aim of the present study was to evaluate the antibacterial activities of the extract, fractions, and some secondary metabolites isolated from the leaves of Crinum glaucum A. Chev. (Amaryllidaceae). The antibacterial activities were performed with the ethanol (EtOH) extract, as well as with ethyl acetate (EtOAc) and n-butanol (n-BuOH) fractions. Repeated column chromatography of the fractions led to the isolation of several compounds and their structures were elucidated mainly by means of extensive spectroscopic analysis [(one-dimensional (1D) and two-dimensional (2D) nuclear magnetic…

Chemical constituents, total phenolic content, antioxidant activity and bactericidal effect of Dicliptera verticillate (Acanthaceae)

Abstract This study investigated the phytochemical constituents and evaluated the total phenolic content, it also determined the antioxidant and antibacterial activities of the ethanol (EtOH) extract of the whole plant of Dicliptera verticillata. The phytochemical study was carried out using repeated silica gel column chromatography followed by Sephadex LH-20 to purify the extract which afforded three known compounds: lutein (1), shikimic acid (2) and guaiacylglycerol (3). The structures of these compounds were identified after analyses of their NMR and MS data and comparison of these data with those reported in the literature. The antioxidant and antibacterial activities were evaluated by …

A one-pot cascade to protoberberine alkaloids via Stevens rearrangement of nitrile-stabilized ammonium ylides.

A facile one-pot synthesis of protoberberines from readily accessible 1,2,3,4-tetrahydroisoquinoline-1-carbonitriles and 1,2-bis(bromomethyl)arenes is described. The reaction cascade comprises four consecutive transformations, all of which can be effected under a single set of conditions. Ten protoberberines, including the alkaloids pseudopalmatine and pseudoepiberberine, were prepared in yields up to 86% according to this strategy. No chromatographic purification of the products is required, and the route is devoid of any protecting group manipulations.

ChemInform Abstract: A High-Yielding Modular Access to the Lamellarins: Synthesis of Lamellarin G Trimethyl Ether (Ia), Lamellarin η (II) and Dihydrolamellarin η (Ib).

Front Cover: Visible‐Light‐Induced Cleavage of C−S Bonds in Thioacetals and Thioketals with Iodine as a Photocatalyst (ChemPhotoChem 2/2020)

Neo-clerodane diterpenoids from Conyza pyrrhopappa Sch.Bip. ex A.Rich

Two hitherto unknown neo-clerodane-type diterpenoids along with twelve known compounds have been isolated from Conyza pyrrhopappa Sch.Bip. ex A.Rich, a medicinal plant traditionally used across tropical Africa to relieve fever. The structures of isolates have been elucidated by a combination of spectroscopic techniques. The crude extract and the isolated compounds were evaluated in the Hela-S3 cell line and in a panel of microorganisms (bacteria and fungi) at concentrations up to 50 µg/mL. The new compounds were inactive while the pentamethylated flavonoids showed low to significant activity against the cancer cell line used. However, none of the samples showed any activity against the test…

Modular synthesis of tetrasubstituted imidazoles and trisubstituted oxazoles by aldimine cross-coupling.

A surprising switch in absolute configuration of anti-inflammatory macrolactones.

Oxacyclododecindione-type macrolactones exhibit highly potent anti-inflammatory activities even at nanomolar concentration. After the determination of the relative configuration of the stereocenters at C14 and C15 by total synthesis of 4-dechloro-14-deoxyoxacyclododecindione and 14-deoxyoxacyclododecindione, the absolute configuration has now been assigned by X-ray crystallography. Surprisingly, the absolute configuration is (14S,15R) which differs for C15 from that of the well-known derivatives of (S)-curvularin. The biological activities of both enantiomers of 14-deoxyoxacyclododecindione, obtained by racemic synthesis and optical resolution, were investigated and the ring conformation of…

Structure determination and preliminary cytotoxicity researches of the compounds isolated from Rumex acetosella L. on leukemia cells

Ring Contracting Rearrangements of 3-Amino-4-(arylamino)-1H-isochromen-1-ones

Two new ring contracting rearrangements of 3-amino-4-(arylamino)-1H-isochromen-1-ones, leading to 1-(arylamino)-3-oxo-1,3-dihydroisobenzofuran-1-carboxamides and2-aryl-3-oxo-2,3-dihydro-1H-isoindole-1-carboxamides, are described. Both conversions proceed in high yield and no further purification of the products is necessary. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

New tracer compounds for secondary organic aerosol formation from β-caryophyllene oxidation

Abstract Five products from β-caryophyllene oxidation (β-caryophyllonic acid (I), 3,3-dimethyl-2-(3-oxobutyl)cyclobutanecarboxylic acid (βCA198) (II), β-nocaryophyllonic acid (III), β-caryophyllinic acid (IV), and 2-(2-carboxyethyl)-3,3-dimethylcyclobutanecarboxylic acid (βCA200) (V)) were synthesized and their structures confirmed by nuclear magnetic resonance spectroscopy. Reaction chamber experiments with β-caryophyllene at two different ozone mixing ratios were performed and the carboxylic acid oxidation products in the particle phase were characterized by APCI–MS and HPLC–ESI–MS. All five synthesized acids were found as β-caryophyllene oxidation products in the reaction chamber aerosol…

An Aldimine Cross-Coupling for the Diastereoselective Synthesis of Unsymmetrical 1,2-Diamines

Transition-Metal-Free Decarboxylative Photoredox Coupling of Carboxylic Acids and Alcohols with Aromatic Nitriles.

A transition-metal-free protocol for the redox-neutral light-induced decarboxylative coupling of carboxylic acids with (hetero)aromatic nitriles at ambient temperature is presented. A broad scope of acids and nitriles is accepted, and alcohols can be coupled in a similar fashion through their oxalate half esters. Various inexpensive sources of UV light and even sunlight can be used to achieve this C–C bond formation proceeding through a free radical mechanism.

ChemInform Abstract: Synthesis of 1,2-Disubstituted Indoles from α-Aminonitriles and 2-Halobenzyl Halides.

The α-alkylation of deprotonated Strecker products derived from primary amines and aromatic aldehydes with 2-halobenzyl halides furnishes intermediates that can be cyclized to 1,2-disubstituted indoles in moderate to high yields (up to 94% over two steps) by microwave-assisted copper- or palladium-catalyzed intramolecular cross-coupling.

Facile access to foldable redox-active flavin-peptide conjugates

A convenient approach for the synthesis of foldable redox-active flavin peptide conjugates was established. A model β-hairpin oligopeptide motif was utilized to demonstrate that azidolysine side-chains are readily functionalised with an alkyne-bearing flavine derivative. The folding equilibrium of the peptide backbone as well as the redox behaviour of the flavin moieties remains intact after the conjugation.

ChemInform Abstract: Carbohydrate Nanocarriers in Biomedical Applications: Functionalization and Construction

The specific targeting of either tumor cells or immune cells in vivo by carefully designed and appropriately surface-functionalized nanocarriers may become an effective therapeutic treatment for a variety of diseases. Carbohydrates, which are prominent biomolecules, have shown their outstanding ability in balancing the biocompatibility, stability, biodegradability, and functionality of nanocarriers. The recent applications of sugar (mono/oligosaccharides and/or polysaccharides) for the development of nanomedicines are summarized in this review, including the application of carbohydrates for the surface-functionalization of various nanocarriers and for the construction of the nanocarrier its…

ChemInform Abstract: Light Induced C-C Coupling of 2-Chlorobenzazoles with Carbamates, Alcohols, and Ethers.

A light induced, transition-metal-free C-C coupling reaction of 2-chlorobenzazoles with aliphatic carbamates, alcohols, and ethers is presented. Inexpensive reagents, namely sodium acetate, benzophenone, water, and acetonitrile, are employed in a simple reaction protocol using a cheap and widely available 25 W energy saving UV-A lamp at ambient temperature.

ChemInform Abstract: Modular One-Pot Synthesis of Tetrasubstituted Pyrroles from α-(Alkylideneamino)nitriles.

2,3,4,5-Tetrasubstituted pyrroles have been prepared with high regioselectivity by a formal cycloaddition of α-(alkylideneamino)nitriles and nitroolefins followed by elimination of HCN and HNO2. The reaction allows the convergent construction of the pyrrole ring in four steps from a nitroalkane and three aldehydes.

ESI-MS2and Anti-inflammatory Studies of Cyclopropanic Triterpenes. UPLC-ESI-MS and MS2Search of Related Metabolites fromDonella ubanguiensis

Introduction Triterpenes are one of the largest secondary metabolites groups spread in the plant kingdom with various skeletons. These metabolites have showed various bioactivities including anti-inflammatory activity. Objective The study aims to explore the mass spectrometry fragmentation of donellanic acids A-C (DA A–C), three compounds identified from Donella ubanguiensis; in addition, the fragmentation behaviour of these metabolites will serve as a fingerprint to search and characterise triterpenes congeners in fruits, bark and wood crude extracts of D. ubanguiensis. This work was prompted by the anti-inflammatory activity on leukocyte migration, exudate concentrations and myeloperoxida…

Synthetic Approaches to Anti-Inflammatory Macrolactones of the Oxacyclododecindione Type

Various synthetic approaches to the oxacyclododecindione-type macrolactones, known for their potent anti-inflammatory activity, are presented. These include an attempted carbonylative ring closure, a hydroacylation route, and an approach by ring-closing metathesis and double bond isomerization, as well as a strategy including ring-closing metathesis/unsaturation. The last route allowed the preparation of a bioactive analogue of the recently described 14-deoxyoxacyclododecindione.

Preparation of Indoles from α-Aminonitriles:  A Short Synthesis of FGIN-1-27

α-Aminonitriles derived from 2-aminocinnamic acid esters and amides can be cyclized under basic conditions to furnish substituted indole-3-acetic acid derivatives in quantitative yield. The reaction provides a simple access to a class of biologically active compounds.

Hantzsch Ester-Mediated Photochemical Transformations in the Ketone Series: Remote C(sp3)–H Arylation and Cyclopentene Synthesis through Strain Release

A metal-free Hantzsch ester-mediated synthesis of cyclopentenylketones as well as γ-hetarylketones starting from ketocyclopropanes under eco-friendly conditions was developed. The versatility of the developed conditions is shown by reacting ketocyclopropanes in both a formal [3 + 2] cycloaddition with terminal alkynes (further investigated using theoretical calculations) and a radical C-C-coupling with cyanopyridines. The newly developed methodologies were later on utilized as a downstream reaction for photogenerated cyclopropanes combining UV and visible light photochemistry. Following this procedure, a UV-driven Norrish-Yang-type reaction induces the ring strain of the intermediates, whic…

ChemInform Abstract: Total Synthesis of (-)-Hymenosetin.

Hymenosetin (I) and its N-methyl analogue are prepared in 11 and 8 steps, respectively, from citronellal employing an intramolecular Diels-Alder reaction as the key step.

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

Survivin, a member of the IAP (inhibitor of apoptosis) gene family, is overexpressed in virtually all human cancers and is functionally involved in the inhibition of apoptosis, regulation of cell proliferation, metastasis and resistance to therapy. Because of its upregulation in malignancy, survivin has currently attracting considerable interest as a new target for anticancer therapy. In a screening of approximately 200 strains of imperfect fungi for the production of inhibitors of survivin promoter activity, a new drimane sesquiterpene lactone, SF002-96-1, was isolated from fermentations of an Aspergillus species. The compound inhibited survivin promoter activity in transiently transfected…

Preparation of Indoles from α-Aminonitriles: A Short Synthesis of FGIN-1-27 (VIc).

Ganodermycin, a novel inhibitor of CXCL10 expression from Ganoderma applanatum

CXCL10 (inducible protein-10) is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells, such as macrophages and T-lymphocytes, and thereby has important roles in chronic inflammatory conditions. In a search for new inhibitors of CXCL10 expression in MonoMac6 cells, a novel compound, designated as Ganodermycin, was isolated from fermentations of the basidiomycete Ganoderma applanatum. The structure was determined by a combination of spectroscopic techniques. Ganodermycin inhibited the lipopolysaccharide (LPS)/interferon (IFN)-γ-induced CXCL10 promoter activity in transiently transfected MonoMac6 cells in a dose-dependent manner with IC(50) values of 1…

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.

Total Synthesis of (-)-Hymenosetin.

The 3-decalinoyltetramic acid (−)-hymenosetin and its N-methyl analogue were prepared in 11 and 8 steps, respectively, from (+)-citronellal using an intramolecular Diels–Alder reaction as the key step. This method represents the first example for the synthesis of a 3-decalinoyltetramic acid with a free NH moiety. The stereochemistry of the title compound, an unnatural diastereomer, and of a decalin building block was studied in detail using circular dichroism spectroscopy in the IR and UV/VIS freqeuncy range. This allowed to determine the absolute configuration of the natural product and to plan the synthetic route.

Saponin with antibacterial activity from the roots of Albizia adianthifolia

An unprecedented saponin is being reported herein together with five known compounds from the methanol extract of the roots of Albizia adianthifolia. The metabolites were obtained over repeated open column chromatography methods and spectroscopic followed by spectrometric techniques. The isolated compounds were tested against eleven Gram-negative bacteria including multidrug resistant strains. The results revealed considerable inhibition of the new saponin against the studied bacteria with MIC values ranging from 16 to 128 μg/mL.

Synthesis of Lamellarin U and Lamellarin G Trimethyl Ether by Alkylation of a Deprotonated α-Aminonitrile

1,2,3,4-Tetrahydroisoquinoline-1-carbonitriles can serve as starting materials for the one-pot synthesis of 5,6-dihydropyrrolo[2,1 a]isoquinolines and 1-benzyl-3,4-dihydroisoquinolines. The latter compounds were transformed to lamellarin G trimethyl ether and lamellarin U in short reaction sequences. This method allows the introduction of acid-sensitive protecting groups for the phenolic hydroxy functions which would be cleaved under the harsh conditions of the classical Bischler-Napieralski reaction.

Synthesis of Lamellarin G Trimethyl Ether by von Miller-Plöchl-Type Cyclocondensation

Addition of α-Aminonitriles to α,β-Unsaturated Carbonyl Compounds: A One-Pot Synthesis of Polysubstituted Pyrrolidines.

The vinylogous addition of deprotonated N-alkyl-α-aminonitriles to α,β-unsaturated carbonyl compounds yields cyclic intermediates which can be reduced to form polysubstituted pyrrolidines in a one-pot reaction sequence. Since the cyano substituent is lost in the reduction step, the aminonitriles serve as easily accessible (N-alkylamino)-substituted carbanion equivalents.

Cover Picture: Xylochemistry-Making Natural Products Entirely from Wood (Angew. Chem. Int. Ed. 47/2015)

Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D

A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.

Photoredox-Catalyzed Four-Component Reaction for the Synthesis of Complex Secondary Amines.

The one-pot sulfonylation/aminoalkylation of styrene derivatives furnishing substituted γ-sulfonylamines was accomplished through a photoredox-catalyzed four-component reaction. Besides one molecule of water and the sodium counterion of the sulfinate, all atoms of the starting materials are transferred to the final product, rendering this process highly atom-efficient. The operationally simple protocol allows for the simultaneous formation of three new single bonds (C-S, C-N, and C-C) and therefore grants rapid access to structurally diverse products.

Identification of NF-κB as Determinant of Posttraumatic Stress Disorder and Its Inhibition by the Chinese Herbal Remedy Free and Easy Wanderer

Posttraumatic stress disorder (PTSD) is a mental disorder developing after exposure to traumatic events. Although psychotherapy reveals some therapeutic effectiveness, clinically sustainable cure is still uncertain. Some Chinese herbal formulae are reported to work well clinically against mental diseases in Asian countries, but the safety and their mode of action are still unclear. In this study, we investigated the mechanisms of Chinese remedy free and easy wanderer (FAEW) on PTSD. We used a reverse pharmacology approach combining clinical data to search for mechanisms of PTSD with subsequent in vitro verification and bioinformatics techniques as follows: (1) by analyzing microarray-based …

ChemInform Abstract: Omphalotins E-I, Five Oxidatively Modified Nematicidal Cyclopeptides from Omphalotus olearius.

Omphalotins E–I, oxidatively modified cyclic dodecapeptides, were isolated from mycelial extracts of the basidiomycete Omphalotus olearius, and their structures were determined by NMR spectroscopic and MS methods. Four of the five omphalotins contained an unprecedented N-hydroxylated tricyclic tryptophan derivative. All compounds exhibited strong and selective nematicidal activity against the plant pathogen Meloidogyne incognita with LD90 values between 2 and 5 μg mL–1. Cytotoxic activities were not detected up to 50 μg mL–1. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthetic Approaches to the Lamellarins—A Comprehensive Review

The present review discusses the known synthetic routes to the lamellarin alkaloids published until 2014. It begins with syntheses of the structurally simpler type-II lamellarins and then focuses on the larger class of the 5,6-saturated and -unsaturated type-I lamellarins. The syntheses are grouped by the strategy employed for the assembly of the central pyrrole ring.

A Xylochemically Inspired Synthesis of Lamellarin G Trimethyl Ether via an Enaminone Intermediate.

A concise high yielding synthesis of lamellarin G trimethyl ether has been achieved from precursors and solvents that can in principle be derived from xylochemical (woody biomass) sources. The route is comparatively green in that some reactions are performed without solvent or with relatively benign solvents. In addition, chromatographic purification of products is avoided, and only a single aqueous workup is performed. The novelty of the synthesis lies in the intermediacy of an enaminone for the construction of the central pyrrole ring. The overall yield of the product is among the highest reported to date.

New Alkenylresorcinols with Cytotoxic and Antimicrobial Activities from the Leaves of Embelia schimperi.

AbstractA phytochemical study of the methanol extract of the leaves of Embelia schimperi resulted in the isolation of three new alkenylresorcinols, 1 – 3, together with the known analogs 4 – 7. Their structures were established by a combination of spectroscopic techniques. Compounds 1 – 7 exhibited moderate cytotoxic activity against human cervical cancer cells HeLa-S3 and more pronounced antimicrobial properties towards bacteria and filamentous fungi. The present study falls into an ongoing research project on the characterization of bioactive phenolic lipids from plants of the family Primulaceae.

ChemInform Abstract: A Light-Induced Vinylogous Nazarov-Type Cyclization.

The title reaction is incorporated in a three-step cascade transformation providing novel tetracyclic ring structures containing a seven-membered ring.

ChemInform Abstract: Transition-Metal-Free Decarboxylative Photoredox Coupling of Carboxylic Acids and Alcohols with Aromatic Nitriles.

A transition-metal-free protocol for the redox-neutral light-induced decarboxylative coupling of carboxylic acids with (hetero)aromatic nitriles at ambient temperature is presented. A broad scope of acids and nitriles is accepted, and alcohols can be coupled in a similar fashion through their oxalate half esters. Various inexpensive sources of UV light and even sunlight can be used to achieve this C–C bond formation proceeding through a free radical mechanism.

A Modular Synthesis of Polysubstituted Indolizines

The N-alkylation of pyridines with cyanohydrin triflates or α-halonitriles furnishes 1-(1-cyanoalkyl)pyridinium salts that can react with nitroolefins under basic conditions to furnish polysubstituted indolizines. Overall, the indolizine core can be constructed from a pyridine, two aldehydes, and a nitroalkane, and no undesired functional groups remain in the products. When bromoacetonitrile was used for the N-alkylation, indolizine-3-carbonitriles were obtained instead. The pyridine component may be replaced by other azines, giving rise to related heterocyclic systems.

A short and modular approach towards 3,5-disubstituted indolizidine alkaloids.

3,5-Dialkyl indolizidines have been prepared in four linear steps from commercially available starting materials. The sequence involves two direct α-functionalization steps and a subsequent reductive amination and provides diastereoselective access to both C-3 epimers of the 5,9-trans-substituted indolizines. The naturally occurring indolizidines 195B and 223AB have been synthesized using this methodology.

Synthesis of α-aminonitriles using aliphatic nitriles, α-amino acids, and hexacyanoferrate as universally applicable non-toxic cyanide sources

In cyanation reactions, the cyanide source is often directly added to the reaction mixture, which restricts the choice of conditions. The spatial separation of cyanide release and consumption offers higher flexibility instead. Such a setting was used for the cyanation of iminium ions with a variety of different easy-to-handle HCN sources such as hexacyanoferrate, acetonitrile or α-amino acids. The latter substrates were first converted to their corresponding nitriles through oxidative decarboxylation. While glycine directly furnishes HCN in the oxidation step, the aliphatic nitriles derived from α-substituted amino acids can be further converted into the corresponding cyanohydrins in an oxi…

Synthesis of Piperidines and Dehydropiperidines

Abstract The present review focuses on strategies for the construction of piperidines and dehydropiperidines, which have appeared in the literature since 2003/2004 through mid-2016. Synthetic methods involving the construction of the six-membered ring from essentially acyclic starting materials in intra- or intermolecular will be highlighted and discussed. In contrast, methods using only the decoration or modification of previously generated pyridines or piperidines will not be part of this review. The published syntheses will be categorized based on the topology of the bond forming events generating the piperidine core.

Synthesis of 1,2-Disubstituted Indoles from α-Aminonitriles and 2-Halobenzyl Halides

The α-alkylation of deprotonated Strecker products derived from primary amines and aromatic aldehydes with 2-halobenzyl halides furnishes intermediates that can be cyclized to 1,2-disubstituted indoles in moderate to high yields (up to 94% over two steps) by microwave-assisted copper- or palladium-catalyzed intramolecular cross-coupling.

Iodocyclization of o-Alkynylbenzamides Revisited: Formation of Isobenzofuran-1(3H)-imines and 1H-Isochromen-1-imines Instead of Lactams

The iodocyclization of o-alkynylbenzamides with various electrophiles has been reported to yield five- or six-membered lactams by nucleophilic attack of the amide nitrogen onto the triple bond. While the formation of an isobenzofuran-1(3H)-imine with two bulky substituents under Larock conditions was initially attributed to steric hindrance, we found out that cyclization via the amide oxygen is the rule rather than the exception. Thus, the structures of the products reported in the literature need to be revised.

Unexpected Formation of a 1,2-Dichloroacenaphthylene in a Friedel-Crafts Reaction with Chloral Hydrate

An unprecedented rearrangement was encountered during an attempted alkylation of an electron-rich naphthalene with chloral hydrate. The reaction produced a dichlorinated acenaphthylene and presumably involves the intermediate formation of a chloronium ion which is opened to produce the five-membered ring of the final product.

Total synthesis and biological evaluation of the natural product (−)-cyclonerodiol, a new inhibitor of IL-4 signaling

In a screening program of natural compounds from fungi, the known cyclopentanoid sesquiterpene (-)-cyclonerodiol was identified as a specific inhibitor of the IL-4 induced STAT6 signaling pathway (IC50 = 9.7 μM) which is required for the differentiation of naive CD4 T cells to T helper type 2 (Th2) lymphocytes. As many allergic conditions, including allergic asthma and atopic diseases, are driven by an excessive Th2 response, STAT6 is a promising target for the development of new therapeutics. The compound was synthesized in six steps from (-)-linalool using an epoxide radical cyclization as the key step.

Synthetic approaches towards huperzine A and B

Huperzine A and B are potent acetylcholinesterase inhibitors and promising against Alzheimer's disease. Completed and formal total syntheses of these medically relevant alkaloids are presented and discussed.

Chemoenzymatic Synthesis of Functional Sialyl LewisX Mimetics with a Heteroaromatic Core

Functional mimetics of the sialyl Lewis(X) tetrasaccharide were prepared by the enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl-Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide.

ChemInform Abstract: Cyclocondensation of α-Aminonitriles and Enones: A Short Access to 3,4-Dihydro-2H-pyrrole 2-Carbonitriles and 2,3,5-Trisubstituted Pyrroles.

The reaction of α,β-unsaturated carbonyl compounds with aminoacetonitrile hydrochloride furnishes 3,5-disubstituted 3,4-dihydro-2H-pyrrole-2-carbonitriles in a one-pot reaction sequence. While these products can serve as starting materials for the preparation of polysubstituted pyrrolizidines, they are kinetically stable against the base-induced elimination of HCN. In contrast, their 2-substituted analogues obtained from α-substituted α-aminonitriles can be readily converted to the corresponding 2,3,5-trisubstituted pyrroles under microwave irradiation. The key step presumably involves the thermal electrocyclization of a stabilized 2-azapentadienyl anion formed by condensation of the reacta…

Modular De novo Synthesis of Unsymmetrical BODIPY Dyes Possessing Four Different Aryl Substituents

A modular synthesis of unsymmetrical BODIPY dyes based on a [6π]-electrocyclization to construct the two pyrrole rings is presented. The products carry four aryl moieties in positions 1, 3, 5, and 7 which can be freely selected as well as optional substitution in positions 2 and 8. The method employs acetophenones, benzaldehydes as well as glycine nitrile or glycine ethyl ester as the key building blocks.

ChemInform Abstract: Enantioselective Synthesis of α-Quaternary Amino Acids by Alkylation of Deprotonated α-Aminonitriles.

An α-alkylation of deprotonated α-amino nitriles, prepared from chiral phenyldioxanamine (I) by Strecker reaction, leads to α-quaternary arylglycines with high optical purity after hydrolysis and oxidative cleavage of the chiral auxiliary.

Smooth Metal‐Free Photoinduced Preparation of Valuable 8‐Arylxanthines

Programmed Formation of HCN Oligomers through Organosulfur Catalysis

An efficient, inexpensive, and reliable synthesis of diaminomaleonitrile (DAMN, 1) is described starting from readily available acetone cyanohydrin as the source of hydrogen cyanide (HCN). Diaminomaleonitrile (DAMN) is known to be an important intermediate in heterocyclic and medicinal chemistry as well as being a possible precursor for the origin of life's hypothesis within prebiotic chemistry. The mechanism of its formation through organosulfur catalysis has been investigated by electrospray ionization mass spectrometry (ESI-MS) using two newly synthesized cationic "marker" molecules as a tool that allows for sensitive detection. As a result, the proposed mechanism of a thiocyanate-mediat…

A Photoinduced Cobalt-Catalyzed Synthesis of Pyrroles through in Situ-Generated Acylazirines

Tetrasubstituted pyrroles can be synthesized in a one-pot procedure from isoxazoles. The process includes the photoinduced in situ formation of acylazirines combined with a subsequent cobalt(II)-catalyzed ring expansion with 1,3-diketones.

TiO2 Nanoparticles Functionalized with Non-innocent Ligands Allow Oxidative Photocyanation of Amines with Visible/Near-Infrared Photons

Photosynthesis is an efficient mechanism for converting solar light energy into chemical energy. We report on a strategy for the aerobic photocyanation of tertiary amines with visible and near-infrared (NIR) light. Panchromatic sensitization was achieved by functionalizing TiO2 with a 2-methylisoquinolinium chromophore, which captures essential features of the extended π-system of 2,7-diazapyrenium (DAP2+) dications or graphitic carbon nitride. Two phenolic hydroxy groups make this ligand highly redox-active and allow for efficient surface binding and enhanced electron transfer to the TiO2 surface. Non-innocent ligands have energetically accessible levels that allow redox reactions to chang…

Polyethylene bio-degradation by caterpillars?

In their recent paper on the degradation of polyethylene by caterpillars of the wax moth Galleria melonella, Bombelli et al.[1] report various experiments, including microscopic and spectroscopic data which the authors believe support the chemical digestion of the polymers by these insects. While the biodegradation of mostly inert artificial polymers is definitely a very interesting research field, we must respectfully disagree with the methodology and conclusions from this paper.

Valorisation of Cashew Nut Shell Liquid Phenolics in the Synthesis of UV Absorbers

ChemInform Abstract: Unexpected Formation of a 1,2-Dichloroacenaphthylene in a Friedel-Crafts Reaction with Chloral Hydrate.

Inhibitor-induzierte Dimerisierung einer essentiellen Oxidoreduktase aus afrikanischen Trypanosomen

Correction: Total synthesis of two potent anti-inflammatory macrolactones of the oxacyclododecindione type

Correction for ‘Total synthesis of two potent anti-inflammatory macrolactones of the oxacyclododecindione type’ by Johannes Tauber et al., Org. Biomol. Chem., 2015, 13, 7813–7821.

Synthesis of Bioactive 2-Aza-Analogues of Ipecac and Alangium Alkaloids

3′-Demethyldihydromaldoxin and dihydromaldoxin, two anti-inflammtory diaryl ethers from a Steganospora species

CXCL10 (IP-10) is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells such as macrophages and T-lymphocytes and thereby has important roles in chronic inflammatory conditions. In a search for new inhibitors of CXCL10 expression in MonoMac6 (MM6) cells, the new diaryl ether 3'-demethyldihydromaldoxin (1) along with the known compound dihydromaldoxin (2), were isolated from fermentations of a Steganospora species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds (1) and (2) inhibited lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced CXCL10 promoter activ…

Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure–Activity Relationship, Inhibition Mechanism, Metabolism, and In Vivo Studies

Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorabl…

Front Cover: Valorisation of Cashew Nut Shell Liquid Phenolics in the Synthesis of UV Absorbers (Eur. J. Org. Chem. 30/2019)

C-28/C-30 oxidized cycloartanes from the leaves and twigs of Caloncoba dusenii Gilg

Abstract Four hitherto unreported cycloartane-type triterpenes (1-4) with C-28/C-30 oxidized methyl groups together with two known compounds (5-6) have been obtained from the leaves and twigs of Caloncoba dusenii Gilg. The compounds were isolated through extraction and silica gel column chromatography. Their structures and relative stereochemistry were determined by extensive use of spectroscopic techniques including IR, 1D and 2D-NMR as well as mass spectrometry. This is the first report of C-28/C-30 oxidized positions in cycloartanes from nature.

‐Aminonitriles: From Sustainable Preparation to Applications in Natural Product Synthesis

Due to their numerous reactivity modes, α-aminonitriles represent versatile and valuable building blocks in organic total synthesis. Since their discovery by Adolph Strecker in 1850, this compound class has seen a wide dissemination in synthetic applications from laboratory to million-ton industrial scale and was extensively used in the syntheses of various classes of natural products. As these compounds provide a multitude of reactivity options, we feel that a broad overview of their multiple reaction modes may reveal less familiar opportunities for successful total synthesis planning. This personal account article will thus focus on α-aminonitriles used as key intermediates in selected na…

Phytotoxic dioxolanone-type secondary metabolites from Guignardia bidwellii.

Phenguignardic acid was recently described as a phytotoxic secondary metabolite from submerged cultures of the grape black rot fungus Guignardia bidwellii. Since the production rate of this natural product in submerged culture is very low, fermentation optimisation was carried out. The optimisation of cultivation conditions led to the identification of seven secondary metabolites, structurally related to guignardic acid, a known secondary metabolite from Guignardia species containing a dioxolanone moiety. All metabolites presented here have not been described to date and are presumably biosynthesised via deamination products of amino acids, such as phenylalanine, valine, tyrosine, and alani…

J. Christoffers, A. Baro: Quaternary Stereocenters – Challenges and Solutions for Organic Synthesis.

Strain Release Chemistry of Photogenerated Small‐Ring Intermediates

Abstract Photochemical processes, such as isomerizations and cycloadditions, have proven to be very useful in the construction of highly strained molecular frameworks. Photoinduced ring strain enables subsequent exergonic reactions which do not require the input of additional chemical energy and provides a variety of attractive synthetic options leading to complex structures. This review covers the progress achieved in the application of sequences combining excitation by ultraviolet light to form strained intermediates, which are further transformed to lower energy products in strain‐release reactions. As ring strain is considerable in small ring systems, photogenerated three‐ and four‐memb…

Terphenyl Derivatives from Allantophomopsis lycopodina.

Three secondary fungal metabolites 1–3 with a benzo[b]naphtho[2,1-d]furan skeleton were isolated from submerged cultures of the ascomycete Allantophomopsis lycopodina. The NMR-based structure elucidation was challenging due to a low H/C ratio of only 0.64 and 0.68, respectively. NMR measurements in two different solvents and the use of NMR experiments such as HSQC-TOCSY and LR-HSQMBC proved to be helpful in this respect. The proposed structures obtained from the comprehensive analysis of the NMR data were verified by comparison of recorded and computed NMR chemical shifts from quantum chemical calculations of several constitutional isomers and were further analyzed with the aid of the DP4 a…

Total Synthesis of (±)-Scopolamine: Challenges of the Tropane Ring

Scopolamine was synthesized using 6,7-dehydrotropine as a key intermediate. Rhodium-catalyzed [4 + 3] cycloaddition chemistry and a modified Robinson–Schopf reaction were each independently evaluated for their utility in constructing the tropane core. Both synthetic approaches gave comparable overall yields.

Front Cover: Visible Light Enables Aerobic Iodine Catalyzed Glycosylation (Eur. J. Org. Chem. 28/2019)

Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention

Abstract Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy‐protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy‐protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins. Therefore, a pentasaccharide partial structure was selected for total synthesis and subse…

ChemInform Abstract: Modular Synthesis of Tetrasubstituted Imidazoles and Trisubstituted Oxazoles by Aldimine Cross-Coupling.

Facile Preparation of 3-Amino-4-(arylamino)-1H-isochromen-1-ones by a New Multicomponent Reaction

Reactions between 2-formylbenzoic acid, various anilines and HCN result in the formation of 3-amino-4-(arylamino)-1H-isochromen-1-ones in high yield. The mechanism of this three-component condensation involves the intermediate formation of an α-aminonitrile and subsequent cyclization through nucleophilic attack of the ortho-carboxylate at the nitrile carbon. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

ChemInform Abstract: Total Synthesis of (.+-.)-Scopolamine: Challenges of the Tropane Ring.

Scopolamine was synthesized using 6,7-dehydrotropine as a key intermediate. Rhodium-catalyzed [4 + 3] cycloaddition chemistry and a modified Robinson–Schopf reaction were each independently evaluated for their utility in constructing the tropane core. Both synthetic approaches gave comparable overall yields.

ChemInform Abstract: Ganodermycin, a Novel Inhibitor of CXCL10 Expression from Ganoderma applanatum.

Ganodermycin (I), a novel inhibitor of CXCL10 expression, is isolated from Ganoderma applanatum.

ChemInform Abstract: A Photoinduced Cobalt-Catalyzed Synthesis of Pyrroles Through in situ-Generated Acylazirines.

Tetrasubstituted pyrroles can be synthesized in a one-pot procedure from isoxazoles. The process includes the photoinduced in situ formation of acylazirines combined with a subsequent cobalt(II)-catalyzed ring expansion with 1,3-diketones.

Hepatoprotective effects of extracts, fractions and compounds from the stem bark of Pentaclethra macrophylla Benth: Evidence from in vitro and in vivo studies

Abstract Aim To identify the bioactive hepatoprotective components of the ethanol extract of Pentaclethra macrophylla stem bark using in vitro and in vivo approaches. Methods The bioguided-fractionation of the ethanol extract was based on the substances’ capacity to prevent in vitro, the lipid peroxidation of hepatocytes’ membranes induced by hydrogen peroxide. For the in vivo hepatoprotective test, mice were treated orally with the ethyl acetate (EtOAc) fraction of the ethanol extract at doses of 50 and 75 mg/kg/day for one week and subjected to d -galactosamine/lipopolysaccharide (GaIN/LPS)-induced hepatotoxicity. Blood samples were collected for alanine aminotransferase (ALAT), aspartate…

Characterization of the synthetic cannabinoid MDMB-CHMCZCA

The synthetic cannabinoid MDMB-CHMCZCA was characterized by various spectroscopic techniques including NMR spectroscopy and tandem mass spectrometry. The synthetic sample was found to be of S-configuration by VCD spectroscopy and comparison of the data with DFT calculations, while ECD spectroscopy was found to be inconclusive in this case. The enantiomeric purity of samples from test purchases and police seizures was assessed by a self-developed chiral HPLC method.

Multivalency Beats Complexity: A Study on the Cell Uptake of Carbohydrate Functionalized Nanocarriers to Dendritic Cells.

Herein, we report the synthesis of carbohydrate and glycodendron structures for dendritic cell targeting, which were subsequently bound to hydroxyethyl starch (HES) nanocapsules prepared by the inverse miniemulsion technique. The uptake of the carbohydrate-functionalized HES nanocapsules into immature human dendritic cells (hDCs) revealed a strong dependence on the used carbohydrate. A multivalent mannose-terminated dendron was found to be far superior in uptake compared to the structurally more complex oligosaccharides used.

Examples of xylochemistry: colorants and polymers

Against the backdrop of modern sustainable chemistry and valorization of biomass for chemical raw materials, the syntheses of indigo dyes and polyamides as representatives of two classes of everyday chemical products based on xylochemicals are described. Wood-derived starting materials were transformed into functional materials using the principles of green chemistry to expand the scope of products gained from renewable resources. The indigo dyes were synthesized in a short, straightforward sequence starting from vanillin. Two polyamides, representatives of an important class of polymers, were obtained from 4-propylcyclohexanol, which is one of the longest known (and most abundant) hydrogen…

Buchbesprechung: Glycoscience Chemistry and Chemical Biology. Band I–III. Herausgegeben von Betram Fraser-Reid, Kuniaki Tatsuta und Joachim Thiem

The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation

Levetiracetam is an active pharmaceutical ingredient widely used to treat epilepsy. We describe a new synthesis of levetiracetam by a dynamic kinetic resolution and a ruthenium-catalysed ex-cell anodic oxidation. For the enzymatic resolution, we tailored a high throughput screening method to identify Comamonas testosteroni nitrile hydratase variants with high (S)-selectivity and activity. Racemic nitrile was applied in a fed-batch reaction and was hydrated to (S)-(pyrrolidine-1-yl)butaneamide. For the subsequent oxidation to levetiracetam, we developed a ligand-free ruthenium-catalysed method at a low catalyst loading. The oxidant was electrochemically generated in 86% yield. This route pro…

Ring Expansion of 1,2,3,4-Tetrahydroisoquinolines to Dibenzo[c,f]azonines. An Unexpected [1,4]-Sigmatropic Rearrangement of Nitrile-Stabilized Ammonium Ylides

When the products of a Strecker reaction of 1,2,3,4-tetrahydroisoquinolines with aromatic aldehydes are quaternized with alkyl triflates and subsequently treated with base, a ring expansion to 6,7,8,13-tetrahydro-5H-dibenzo[c,f]azonine-5-carbonitriles takes place. The nine-membered cyclic products can be obtained in good yields (78-89%) in a process involving the [1,4]-sigmatropic rearrangement of a nitrile-stabilized ammonium ylide. The reaction sequence provides a new, simple, and efficient method for the synthesis of these unusual N-heterocycles.

Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin.

A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using an NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C12 fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with the known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X-ray crystal structure …

A Short Synthesis of Polysubstituted Pyrrolidines via α-(Alkylidene­amino)nitriles

α-(Alkylideneamino)nitriles can be deprotonated under mild conditions. Their conjugated anions react with enones in a 1,4-addition to yield δ-keto-α-(alkylideneamino)nitriles which in turn can be reduced to form pyrrolidines in a one-pot reaction sequence.

Strecker reactions with hexacyanoferrates as non-toxic cyanide sources

The Strecker reaction is the most widely applied three-component reaction. Although highly useful for the preparation of α-amino nitriles, α-amino acids, hydantoins and numerous related compounds, the need for the application of toxic sources of HCN limits its application in both academic and industrial settings. Here, we present a facile protocol for Strecker reactions using a mixture of potassium ferri- and ferrocyanides as a non-toxic substitute.

Visible‐Light‐Induced Cleavage of C−S Bonds in Thioacetals and Thioketals with Iodine as a Photocatalyst

Rücktitelbild: Eine regio- und diastereoselektive anodische Aryl-Aryl-Kupplung in der biomimetischen Totalsynthese von (−)-Thebain (Angew. Chem. 34/2018)

Synthesis and Isolation of Enantiomerically Enriched Cyclopenta[b]benzofurans Based on Products from Anodic Oxidation of 2,4-Dimethylphenol

The anodic treatment of 2,4-dimethylphenol offers a powerful and direct method for the construction of a dehydrotetramer with four contiguous stereocentres on a multigram scale. The installation of propellanes on this scaffold using enantiomerically pure carbonyl compounds leads to a mixture of diastereomers. This mixture is easily separable using standard chromatography and gives rise to optically pure cyclopenta[b]benzofurans which are important scaffolds in a variety of natural products. The synthesis is easy to perform and allows a reliable access to chiral compounds with very high enantiomeric excess. It was possible to determine the absolute configuration of these compounds by compari…

Book Review: Glycoscience Chemistry and Chemical Biology. Vols. I–III. Edited by Bertram Fraser-Reid, Kuniaki Tatsuta and Joachim Thiem

Flow photochemistry of azosulfones: application of “Sunflow” reactors

A high-yielding modular access to the lamellarins: synthesis of lamellarin G trimethyl ether, lamellarin η and dihydrolamellarin η.

A Regio- and Diastereoselective Anodic Aryl-Aryl Coupling in the Biomimetic Total Synthesis of (-)-Thebaine.

The biosynthesis of thebaine is based on the regioselective, intramolecular, oxidative coupling of (R)-reticuline. For decades, chemists have sought to mimic this coupling by using stoichiometric oxidants. However, all approaches to date have suffered from low yields or the formation of undesired regioisomers. Electrochemistry would represent a sustainable alternative in this respect but all attempts to accomplish an electrochemical synthesis of thebaine have failed so far. Herein, a regio- and diastereoselective anodic coupling of 3',4',5'-trioxygenated laudanosine derivatives is presented, which finally enables electrochemical access to (-)-thebaine.

Light Induced C-C Coupling of 2-Chlorobenzazoles with Carbamates, Alcohols, and Ethers.

A light induced, transition-metal-free C-C coupling reaction of 2-chlorobenzazoles with aliphatic carbamates, alcohols, and ethers is presented. Inexpensive reagents, namely sodium acetate, benzophenone, water, and acetonitrile, are employed in a simple reaction protocol using a cheap and widely available 25 W energy saving UV-A lamp at ambient temperature.

One-Pot Synthesis of Trisubstituted 1,2-Amino Alcohols from Deprotonated α-Amino Nitriles

A short synthesis of N,1,2-trisubstituted vicinal amino alcohols by 1,2-addition of deprotonated N-monosubstituted α-amino nitriles to aldehydes and subsequent one-pot reduction of the intermediates with borane–THF is described. This procedure leads to the predominant formation of the anti-configured products. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Cover Feature: Visible Light‐Induced Sulfonylation/Arylation of Styrenes in a Double Radical Three‐Component Photoredox Reaction (Chem. Eur. J. 38/2019)

Anti-inflammatory tetraquinane diterpenoids from a Crinipellis species.

The small pro-inflammatory 10kDa chemokine CXCL10 (Interferon-inducible protein 10, IP-10) plays an important role in mediating immune responses through the activation and recruitment of leukocytes such as T cells, eosinophils, monocytes and NK cells to the sites of inflammation. Elevated levels of CXCL10 have been associated with chronic inflammatory and infectious diseases and therefore CXCL10 represents an attractive target for the development of new anti-inflammatory drugs. In a search for anti-inflammatory compounds from fungi inhibiting the inducible CXCL10 promoter activity, four new tetraquinane diterpenoids, crinipellin E (1), crinipellin F (2), crinipellin G (3) and crinipellin H …

Cytotoxicity of Secondary Metabolites from Dracaena viridiflora Engl &amp; Krause and their Semisynthetic Analogues

The MeOH extract of Dracaena viridiflora was found to display significant cytotoxicity against some cancer cell lines. Systematic phytochemical investigation of this extract led to the isolation and structure elucidation of ten secondary metabolites including five spirostane (1-5) and one furostane (6) steroidal saponins. Furthermore, some acetylated spirostane analogues and three previously unreported derivatives with the 22,26-epoxycholesta-5,22-diene skeleton (15-17) were prepared from trillin (1), prosapogenin A of dioscin (2) and dioscin (4) by reaction with ZnCl 2/Ac 2O. Among the isolated and semisynthetic compounds, dioscin showed the most potent cytotoxicity against A549, Jurkat an…

One-Pot Synthesis of Polysubstituted Pyrrolidines from Aminonitriles

α-Aminonitriles with a mono- or unsubstituted amino group as well as a-(alkylideneamino)nitriles can be employed as easily accessible α-aminocarbanion equivalents. Their α-deprotonation yields stabilized carbanions, whichundergo smooth 1,4-addition to α,β-unsaturated carbonyl compounds. The resulting δ-ketoα-aminonitriles can be reductively cyclized to form polysubstituted pyrrolidines.

Total Synthesis of (+)-Phenguignardic Acid, a Phytotoxic Metabolite ofGuignardia bidwellii

(+)-Phenguignardic acid, a phytotoxic metabolite of the grape black rot fungus Guignardia bidwellii was synthesized, as well as its enantiomer, in eight steps from (R)-phenyllactic acid and 3-phenylprop-2-yn-1-ol. The formation of the carboxylate at a late stage, to avoid enolization of the precursor used in the central acetalization step, proved to be crucial. The synthesis of the natural product allowed the unabiguous assignment of its hitherto unknown absolute configuration.

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

The Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic 1,3-dienes was investigated. A series of novel monofluorinated norbornenes was prepared in up to 97% yield. The reaction with 1,3-cyclohexadiene permits the preparation of monofluorinated bicyclo[2.2.2]oct-2-enes. The kinetic data of the reactions with 1,3-cyclopentadiene and 1,3-cyclohexadiene were used to calculate activation parameters. Furthermore, the synthetic utility of the cycloadducts obtained was demonstrated.

Structure, Biosynthesis, and Bioactivity of Photoditritide from Photorhabdus temperata Meg1

A new cyclic peptide photoditritide (1), containing two rare amino acid d-homoarginine residues, was isolated from Photorhabdus temperata Meg1 after the nonribosomal peptide synthetase encoding gene pdtS was activated via promoter exchange. The structure of 1 was elucidated by HR-MS and NMR experiments. The absolute configurations of amino acids were determined according to the advanced Marfey's method after hydrolysis of 1. Bioactivity testing of 1 revealed potent antimicrobial activity against Micrococcus luteus with an MIC value of 3.0 μM and weak antiprotozoal activity against Trypanosoma brucei rhodesiense with an IC50 value of 13 μM. Additionally, the biosynthetic pathway of 1 was als…

Sterelactones: New Isolactarane Type Sesquiterpenoids with Antifungal Activity from Stereum sp. IBWF 01060

Four members of a new family of tetracyclic sesquiterenoids possessing the isolactarane skeleton have been isolated from mycelial cultures of Stereum sp. IBWF 01060. Their structure elucidation and their antifungal activity against several plant pathogens as well as other microorganisms are reported.

Phenguignardic acid and guignardic acid, phytotoxic secondary metabolites from Guignardia bidwellii.

Bioactivity-guided isolation led to the identification of phenguignardic acid (2), a new phytotoxic secondary metabolite from submerged cultures of grape black rot fungus, Guignardia bidwellii. The compound is structurally related to guignardic acid (1), a dioxolanone moiety-containing metabolite isolated previously from Guignardia species. However, in contrast to guignardic acid, which is presumably synthesized from deamination products of valine and phenylalanine, the biochemical precursor for the biosynthesis of the new phytotoxin appears to be exclusively phenylalanine. Guignardic acid was also found in extracts of cultures from Guignardia bidwellii. The phytotoxic activities of both co…

Oxacyclododecindione, a Novel Inhibitor of IL-4 Signaling from Exserohilum rostratum

In a screening program for new metabolites from fungi inhibiting the IL-4 mediated signal transduction, a novel chlorinated macrocyclic lactone, designated as oxacyclododecindione, was isolated from fermentations of the imperfect fungus Exserohilum rostratum. The structure was determined by a combination of spectroscopic techniques. Oxacyclododecindione inhibits the IL-4 induced expression of the reporter gene secreted alkaline phosphatase (SEAP) in transiently transfected HepG2 cells with IC50 values of 20-25 ng/ml (54-67.5 nM). Studies on the mode of action of the compound revealed that the inhibition of the IL-4 dependent signaling pathway is caused by blocking the binding of the activat…

Visible-Light Organophotoredox-Catalyzed Synthesis of Precursors for Horner-Type Olefinations

A new polyketide from the bark of Hypericum roeperianum Schimp. (Hypericaceae)

The isolation and spectroscopic data of a hitherto undescribed polyketide (1) from Hypericum roeperianum Schimp. (Hypericaceae) together with six known compounds (2–7) is herein reported. The struc...

One-pot synthesis of polysubstituted indolizines by an addition/cycloaromatization sequence.

Indolizines carrying various substituents in positions 5-8 were obtained from readily available 2-(1H-pyrrol-1-yl)nitriles and α,β-unsaturated ketones or aldehydes in a one-pot procedure. Michael addition of the deprotonated aminonitriles to the acceptors followed by acid-catalyzed electrophilic cyclization produces 5,6-dihydroindolizine-5-carbonitriles. From these stable intermediates, substituted indolizines were obtained via base-induced dehydrocyanation.

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

A synthesis of fluorinated pyrimidines under mild conditions from amidine hydrochlorides and the recently described potassium 2-cyano-2-fluoroethenolate was developed. A broad substrate scope was tested and mostly excellent yields were obtained. The synthesis of fluorinated aminopyrazoles from the same fluorinated precursor could be demonstrated but proceeded with lower efficiency.

ChemInform Abstract: A One-Pot Cascade to Protoberberine Alkaloids via Stevens Rearrangement of Nitrile-Stabilized Ammonium Ylides.

This method gives access to quaternary protoberberines including naturally occurring pseudopalmatine (IIIf) and pseudoepiberberine (IIIg).

ChemInform Abstract: Rearrangements of Nitrile-Stabilized Ammonium Ylides

Rearrangements of nitrile-stabilized ammonium ylides are useful reactions for the construction of alkylamines, nitrogen heterocycles, or carbonyl compounds. In spite of their attractive synthetic potential, they are much less frequently used than rearrangements of ammonium ylides either carrying charge-stabilizing carbonyl groups or being devoid of additional stabilization of the negative charge. This review focuses on different classes of rearrangements of nitrile-stabilized ammonium ylides as well as their application in synthetic organic chemistry. 1 Introduction 2 [1,2]-Stevens Rearrangements 3 [2,3]-Sommelet–Hauser Rearrangement 4 [2,3]-Stevens Rearrangements 5 Competitive [1,2]-, [2,3…

A new ceramide from the leaves of Lannea schimperi (Hochst. ex A.Rich.) Engl.

A new ceramide is being reported herein together with six known compounds from the methanol extract of the leaves of Lannea schimperi (Hochst. ex A.Rich.) Engl. The metabolites were obtained through repeated open column chromatography and were characterized by spectroscopic and spectrometric techniques. The radical-scavenging activity of the crude extract and isolated compounds was evaluated using the DPPH radical. The obtained results suggest the studied species as prominent candidate to fight reactive oxygen species (ROS).

Total Synthesis of Phenanthroindolizidine Alkaloids by Combining Iodoaminocyclization with Free Radical Cyclization

A concise and modular synthesis of phenanthroindolizidine alkaloids was achieved by combining iodoaminocylization with a free radical cyclization approach. The route described allowed the preparation of (±)-tylophorine, (±)-antofine, and (±)-deoxypergularinine in six steps. When commercially available l-prolinol was used as a chiral building block, (S)-(+)-tylophorine was also synthesized in 49% yield and >99% ee over five linear steps.

Copper-Catalyzed One-Pot Synthesis of 3-(N -Heteroarenyl)acrylonitriles through Radical Conjugated Addition of β-Nitrostyrene to Methylazaarenes

ChemInform Abstract: Microwave-Assisted Synthesis of 1,3-Disubstituted β-Carbolines from α-(Alkylideneamino)nitriles and Gramine.

The title reaction produces indole derivatives of type (V) whose cyclization leads to formation of the desired alkaloid skeletons.

A Copper‐Catalyzed Synthesis of Pyrroles through Photochemically Generated Acylazirines

ChemInform Abstract: Total Synthesis of (+)-Phenguignardic Acid, a Phytotoxic Metabolite of Guignardia bidwellii

(+)-Phenguignardic acid, a phytotoxic metabolite of the grape black rot fungus Guignardia bidwellii was synthesized, as well as its enantiomer, in eight steps from (R)-phenyllactic acid and 3-phenylprop-2-yn-1-ol. The formation of the carboxylate at a late stage, to avoid enolization of the precursor used in the central acetalization step, proved to be crucial. The synthesis of the natural product allowed the unabiguous assignment of its hitherto unknown absolute configuration.

Xylochemistry--Making Natural Products Entirely from Wood.

The first total synthesis of the dimeric berberine alkaloid ilicifoline (ilicifoline B) is reported. Its carbon skeleton is constructed from ferulic acid, veratrole, and methanol. The synthesis reported herein employs starting materials solely derived from wood. The natural product is thus constructed entirely from renewable resources. The same strategy is applied to a formal total synthesis of morphinan alkaloids. The use of wood-derived building blocks (xylochemicals) instead of the conventional petrochemicals represents a sustainable alternative to classical synthetic approaches.

Cover Feature: Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention (Chem. Eur. J. 3/2021)

Eine gekreuzte Aldiminkupplung zur diastereoselektiven Synthese von unsymmetrischen 1,2-Diaminen

Mimonoside D: a new triterpenoid saponin from Mimosa diplotricha Sauvalle (Fabaceae)

A new triterpenoid saponin (Mimonoside D: 3-O-��-L-arabinopyranosyl-3��-hydroxyolean-12-en-28-oic acid 28-O-��-D-xylopyranosyl-(1���2)-��-D- glucopyranoside ester (1)) was isolated from the aerial parts of Mimosa diplotricha Sauvalle together with nine known compounds: 7,4���-dihydroxyflavone (2), kaempferol (3), lupeol (4), betulinic acid (5), ��-sitosterol (6), ��-sitosterol-3-O-��-D-glucopyranoside (7), lutein (8), 5,2���-dihydroxy-7,4���,5���-trimethoxyflavone (9) and vitexin (10). Their structures were elucidated on the basis of spectroscopic (1 D and 2 D nuclear magnetic resonance) and high-resolution mass spectrometric data as well as by comparison of their spectral data with those o…

Heterocycles from α-aminonitriles.

Owing to their various modes of reactivity, α-aminonitriles represent versatile building blocks for the construction of a wide range of nitrogen heterocycles. The present Concept article focuses on synthetic methodologies using their bifunctional nature which is the basis of their reactivity as α-amino carbanions and as iminium ions. Reactions exclusively taking place on either the amine or on the nitrile moiety will not be considered.

(±)-alternarlactones A and B, two antiparasitic alternariol-like dimers from the fungus alternaria alternata P1210 isolated from the halophyte salicornia sp.

Two new dimeric compounds of the alternariol class, (±)-alternarlactones A (1) and B (2), were isolated along with 11 known compounds from the fungus Alternaria alternata P1210. Their structures were elucidated with the assistance of long-range HSQMBC to address inadequate cross-peaks in HMBC that result from the highly dense quaternary carbons, as well as theoretical calculations. All isolated altenuisol derivatives were screened for their antiparasitic activities, which provide a preliminary structure-activity relationship of this class of compounds against neglected tropical diseases.

“Clickable PEG” via anionic copolymerization of ethylene oxide and glycidyl propargyl ether

A straight forward synthesis of poly(ethylene glycol) (PEG) with multiple alkyne groups distributed along the polymer chain is introduced. Direct access to clickable PEG is achieved by the monomer-activated anionic ring-opening copolymerization (AROP) of ethylene oxide (EO) with glycidyl propargyl ether (GPgE). Notably for successful polymerization no protection of the alkyne unit is required owing to the mild reaction conditions. Defined PEG-co-PGPgE and PGPgE (co)polymers with PDIs of 1.18–1.60 and molecular weights of Mn = 3000–9500 g mol−1 were prepared. In situ1H NMR kinetic studies revealed remarkably disparate reactivity ratios of rEO = 14.8 and rGPgE = 0.076, representing a pronounc…

One-Pot Synthesis of (±)-Crispine A and Its C-Ring-Substituted Analogs

A straightforward access to crispine A and C-ring-substituted analogs by 1,4-addition of a deprotonated α-amino nitrile to α,β-unsaturated carbonyl compounds is described. If the reduction step is omitted, substituted 5,6-dihydropyrrolo[2,1-a]isoquinolines can be obtained. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

(Z)-Amino­(2-methyl-3-oxoisoindolin-1-yl­idene)acetonitrile

The asymmetric unit of the title compound, C11H9N3O, contains two independent and nearly identical molecules (A and B). Molecule A can be transformed to B using a rotation of approximately 85&amp;#176; around the [111] direction. Each A molecule is connected to three B molecules via N&amp;#8212;H...N and N&amp;#8212;H...O hydrogen bonds and vice versa. Centrosymmetrically related molecules of the same residue form &amp;#960;&amp;#8211;&amp;#960; interactions with centroid&amp;#8211;centroid distances of 4.326&amp;#8197;(1) and 3.826&amp;#8197;(1)&amp;#8197;&amp;#197; for the benzene rings of molecules A and B, respectively.

ChemInform Abstract: A Highly Active System for the Metal-Free Aerobic Photocyanation of Tertiary Amines with Visible Light: Application to the Synthesis of Tetraponerines and Crispine A.

A highly efficient metal-free catalytic system for the aerobic photocyanation of tertiary amines with visible light is reported. The use of air as terminal oxidant offers an improved safety profile compared with pure oxygen, the used compact fluorescent lamp (CFL) light sources are highly economical, and no halogenated solvents are required. This system not only proves to be effective for a wide variety of trialkylamines, pharmaceuticals, and alkaloids but remarkably also allows the lowest catalyst loading (0.00001 mol% or 0.1 ppm) ever reported for an organic dye. Bruylants reactions and C-alkylation/decyanations were performed on the obtained α-aminonitriles to demonstrate the postfunctio…

Haloperoxidase Mimicry by CeO2−xNanorods Combats Biofouling

CeO2-x nanorods are functional mimics of natural haloperoxidases. They catalyze the oxidative bromination of phenol red to bromophenol blue and of natural signaling molecules involved in bacterial quorum sensing. Laboratory and field tests with paint formulations containing 2 wt% of CeO2-x nanorods show a reduction in biofouling comparable to Cu2 O, the most typical biocidal pigment.

Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones

Through variation of our previously published total synthesis of two highly active anti-inflammatory macrolactones from the oxacyclododecindione family (J. Tauber, M. Rohr, T. Walter, G. Erkel and T. Opatz, Org. Biomol. Chem., 2015, 13, 7813-7821), seven new representatives of this compound class were prepared. Substitution of the 14-hydroxy group in oxacyclododecindione with a methyl substituent provided a readily accessible non-natural analogue which has similar pharmacological properties to the scarcely available natural product. Since the producible amount of substance is therefore no longer restricted by low fermentation yields, extensive in vivo studies become possible for the first t…

A five-step synthesis of (±)-tylophorine via a nitrile-stabilized ammonium ylide.

The Stevens rearrangement of a nitrile-stabilized ammonium ylide is the key step of a very short and practical synthesis of the phenanthroindolizine alkaloid (±)-tylophorine. The method requires only five linear steps and is devoid of any protecting group manipulations.

Facile Preparation of 3-Amino-4-(arylamino)-1H-isochromen-1-ones (IV) by a New Multicomponent Reaction.

ChemInform Abstract: One-Pot Synthesis of Pyrrole-2-carboxylates and -carboxamides via an Electrocyclization/Oxidation Sequence.

An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.

Front Cover: Synthesis and Unusual NMR-Spectroscopic Behavior of a Strained Bicyclic Ammonium Salt (Eur. J. Org. Chem. 10/2018)

ChemInform Abstract: One-Pot Synthesis of Polysubstituted Indolizines by an Addition/Cycloaromatization Sequence.

Indolizines carrying various substituents in positions 5-8 were obtained from readily available 2-(1H-pyrrol-1-yl)nitriles and α,β-unsaturated ketones or aldehydes in a one-pot procedure. Michael addition of the deprotonated aminonitriles to the acceptors followed by acid-catalyzed electrophilic cyclization produces 5,6-dihydroindolizine-5-carbonitriles. From these stable intermediates, substituted indolizines were obtained via base-induced dehydrocyanation.

The Creolophins: A Family of Linear Triquinanes fromCreolophus cirrhatus (Basidiomycete)

Complicatic acid and five novel linear triquinanes were isolated from mycelial cultures of Creolophus cirrhatus. The creolophins A, C, D, and E represent a novel type of highly oxidized triquinane sesquiterpenoids. Whereas those compounds with a secondary alcohol moiety in ring A are stable, the exomethylene ketone creolophin E (5) partly dimerized during workup to form the decacyclic 1,4-dioxepin-6-one neocreolophin (6). Compounds 5 and 6 display cytotoxic activities against several tumor cell lines.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Synthesis of Highly Substituted 2-13C-Imidazolium Salts and Metal NHC ­Complexes for the Investigation of Electronic Unsymmetry by NMR

Complexes of unsymmetrically substituted N-heterocyclic carbenes with NMR-active metals (Ag, Hg, Pt) with or without a 13C-label in the 2-position were synthesized by aldimine cross coupling and analyzed with respect to the scalar couplings between the metal center or C2 and the other ring atoms.

CCDC 1831234: Experimental Crystal Structure Determination

Related Article: Alexander Lipp, Dorota Ferenc, Christoph Gütz, Mario Geffe, Nina Vierengel, Dieter Schollmeyer, Hans J. Schäfer, Siegfried R. Waldvogel, Till Opatz|2018|Angew.Chem.,Int.Ed.|57|11055|doi:10.1002/anie.201803887

CCDC 1995804: Experimental Crystal Structure Determination

Related Article: Natália Menezes Moreira, Lorena S. R. Martelli, Kiyara I.R. de Julio, Julio Zukerman-Schpector, Till Opatz, Arlene Correa|2020|Eur.J.Org.Chem.|2020|4563|doi:10.1002/ejoc.202000673

CCDC 1998325: Experimental Crystal Structure Determination

Related Article: Carina Weber, Nina Vierengel, Thorsten Walter, Torsten Behrendt, Tobias Lucas, Gerhard Erkel, Till Opatz|2020|Org.Biomol.Chem.|18|5906|doi:10.1039/D0OB00958J

CCDC 897109: Experimental Crystal Structure Determination

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CCDC 861603: Experimental Crystal Structure Determination

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CCDC 1049822: Experimental Crystal Structure Determination

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CCDC 1998326: Experimental Crystal Structure Determination

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CCDC 1891336: Experimental Crystal Structure Determination

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CCDC 898755: Experimental Crystal Structure Determination

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CCDC 1047644: Experimental Crystal Structure Determination

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CCDC 1008269: Experimental Crystal Structure Determination

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CCDC 945345: Experimental Crystal Structure Determination

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CCDC 1497003: Experimental Crystal Structure Determination

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CCDC 1946259: Experimental Crystal Structure Determination

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CCDC 1998324: Experimental Crystal Structure Determination

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CCDC 1824011: Experimental Crystal Structure Determination

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CCDC 1894341: Experimental Crystal Structure Determination

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CCDC 1946260: Experimental Crystal Structure Determination

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CCDC 1047645: Experimental Crystal Structure Determination

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CCDC 897110: Experimental Crystal Structure Determination

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CCDC 1483914: Experimental Crystal Structure Determination

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CCDC 1412268: Experimental Crystal Structure Determination

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CCDC 601965: Experimental Crystal Structure Determination

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CCDC 897106: Experimental Crystal Structure Determination

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CCDC 945347: Experimental Crystal Structure Determination

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CCDC 1055316: Experimental Crystal Structure Determination

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CCDC 1981158: Experimental Crystal Structure Determination

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CCDC 1917091: Experimental Crystal Structure Determination

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CCDC 1484250: Experimental Crystal Structure Determination

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CCDC 962065: Experimental Crystal Structure Determination

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CCDC 1862408: Experimental Crystal Structure Determination

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CCDC 1454207: Experimental Crystal Structure Determination

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CCDC 1055315: Experimental Crystal Structure Determination

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CCDC 1049823: Experimental Crystal Structure Determination

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CCDC 1483913: Experimental Crystal Structure Determination

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CCDC 962066: Experimental Crystal Structure Determination

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CCDC 1497004: Experimental Crystal Structure Determination

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CCDC 1976456: Experimental Crystal Structure Determination

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CCDC 1894340: Experimental Crystal Structure Determination

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CCDC 813647: Experimental Crystal Structure Determination

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CCDC 1484249: Experimental Crystal Structure Determination

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CCDC 863302: Experimental Crystal Structure Determination

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CCDC 1831233: Experimental Crystal Structure Determination

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CCDC 1484253: Experimental Crystal Structure Determination

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CCDC 1483912: Experimental Crystal Structure Determination

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CCDC 2081480: Experimental Crystal Structure Determination

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CCDC 1047647: Experimental Crystal Structure Determination

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CCDC 1497005: Experimental Crystal Structure Determination

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CCDC 1894339: Experimental Crystal Structure Determination

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CCDC 1831232: Experimental Crystal Structure Determination

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CCDC 945348: Experimental Crystal Structure Determination

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CCDC 1976455: Experimental Crystal Structure Determination

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CCDC 1008268: Experimental Crystal Structure Determination

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CCDC 1831236: Experimental Crystal Structure Determination

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CCDC 1585828: Experimental Crystal Structure Determination

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CCDC 897107: Experimental Crystal Structure Determination

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CCDC 942767: Experimental Crystal Structure Determination

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CCDC 1484252: Experimental Crystal Structure Determination

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CCDC 1484251: Experimental Crystal Structure Determination

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CCDC 1831235: Experimental Crystal Structure Determination

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CCDC 945346: Experimental Crystal Structure Determination

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CCDC 1521512: Experimental Crystal Structure Determination

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CCDC 1484248: Experimental Crystal Structure Determination

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CCDC 1541882: Experimental Crystal Structure Determination

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CCDC 1004248: Experimental Crystal Structure Determination

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