Selective targeting of collagen IV in the cancer cell microenvironment reduces tumor burden

Goodpasture antigen-binding protein (GPBP) is an exportable1 Ser/Thr kinase that induces collagen IV expansion and has been associated with chemoresistance following epithelial-to-mesenchymal transition (EMT). Here we demonstrate that cancer EMT phenotypes secrete GPBP (mesenchymal GPBP) which displays a predominant multimeric oligomerization and directs the formation of previously unrecognized mesh collagen IV networks (mesenchymal collagen IV). Yeast two-hybrid (YTH) system was used to identify a 260SHCIE264 motif critical for multimeric GPBP assembly which then facilitated design of a series of potential peptidomimetics. The compound 3-[4''-methoxy-3,2'-dimethyl-(1,1';4',1'')terphenyl-2'…

Sesquiterpene lactones and lignans from Artemisia arborescens

The aerial parts of Artemisia arborescens yielded, in addition to several known compounds, a new guaianolide, a new homoditerpene endoperoxide, a new lignan of the sesamin type and a new azulene derivative.

A Versatile Synthesis of Fluorinated Uracils in Solution and on Solid-Phase.

[reaction: see text] An efficient and convenient two-step synthesis of new fluorinated uracils is described. The first step involves the condensation of an ester enolate with a fluorinated nitrile to furnish fluorinated beta-enamino esters. In turn, these compounds react with organic isocyanates or isothiocyanates to give C-6 fluorinated uracils or thiouracils, respectively, in excellent yields. This synthesis has been successfully adapted to solid-phase conditions with high diversity, thereby facilitating the creation of small (thio)uracil libraries.

Synthesis and evaluation of microtubule assembly inhibition and cytotoxicity of prenylated derivatives of cyclo-l-Trp-l-Pro

The synthesis of three isoprenylated derivatives of cyclo-L-Trp-L-Pro is described. These substances have been evaluated for cytotoxic activity in rat normal fibroblast 3Y1 cells and have also been evaluated in vitro for the inhibition of microtubule assembly.

First Fluorous Synthesis of Fluorinated Uracils

This paper describes a novel fluorous synthesis of fluorinated uracils 4. In this new protocol, fluorous alcohols 1, which are used as fluorous tags, are acetylated to yield acetates 2, which in turn are treated with a base to form their enolates. These are then reacted with fluorinated nitriles to furnish tagged β-enamino esters 3. Although this condensation step had been performed easily in previous solution and solid-phase syntheses, it proved to be very elusive in the fluorous version. Meticulous control of the reaction conditions was thus essential in order to achieve satisfactory yields of β-enamino esters 3. The final treatment of compounds 3 with isocyanates or isothiocyanates effic…

Solution-, solid-phase, and fluorous synthesis of beta,beta-difluorinated cyclic quaternary alpha-amino acid derivatives: a comparative study.

The diastereoselective synthesis of cyclic beta,beta-difluorinated alpha-amino acid derivatives bearing a quaternary stereocenter is described. The process relies on the chemo- and diastereoselective addition of allylic organometallic reagents to fluorinated alpha-imino esters and a subsequent ring-closing metathesis reaction (RCM). Complete selectivity in the nucleophilic addition was achieved with (R)-phenylglycinol methyl ether as a chiral auxiliary. The resulting amino acids were introduced into peptide chains, which could facilitate the preparation of potentially bioactive dipeptide derivatives. In addition, the solution synthesis of these cyclic fluorinated alpha-amino acids was succe…

ChemInform Abstract: Asymmetric Synthesis of Fluorinated Amino Macrolactones Through Ring-Closing Metathesis.

The synthesis of new chiral fluorinated amino and azamacrolactones of types 1 and 2 is described. A ring-closing metathesis (RCM) reaction constitutes the key step in this methodology, which uses fluorinated amino alcohols 7 as starting materials. The influence of the CF2 group, which is located in the alpha-position relative to the carbon bearing the amino group, on the efficiency of the RCM reaction is noteworthy. This method allows for the preparation of the desired fluorinated macrolactones in excellent yields.

Analysis of Rabbit Vascular Responses to DBI, an Ingol Derivative Isolated from Euphorbia canariensis

Abstract We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to DBI (10−8 - 3 × 10−5 m) were obtained cumulatively in both arteries at resting tension and active tone (KC1, 50 mm). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca2+-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10−4 m) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10−4 m) inhibited the maximum contraction of …

Sesquiterpene lactones from iranian Artemisia species

Abstract The aerial parts of Artemisia turcomanica and A. deserti yielded two new germacranolides, a new guaianolide, and several known mono- and sesquiterpenes.

ChemInform Abstract: Solution-, Solid-Phase, and Fluorous Synthesis of β,β-Difluorinated Cyclic Quaternary α-Amino Acid Derivatives: A Comparative Study.

The diastereoselective synthesis of cyclic β,β-difluorinated α-amino acid derivatives bearing a quaternary stereocenter is described. The process relies on the chemo- and diastereoselective addition of allylic organometallic reagents to fluorinated α-imino esters and a subsequent ring-closing metathesis reaction (RCM). Complete selectivity in the nucleophilic addition was achieved with (R)-phenylglycinol methyl ether as a chiral auxiliary. The resulting amino acids were introduced into peptide chains, which could facilitate the preparation of potentially bioactive dipeptide derivatives. In addition, the solution synthesis of these cyclic fluorinated α-amino acids was successfully adapted to…

Jatrophane derivatives and a rearranged jatrophane from Euphorbia terracina

Abstract The aerial parts of Euphorbia terracina yielded 11 new jatrophane derivatives as well as a further diterpene displaying the novel 1(15 → 14) abeo -jatrophane framework.

Sesquiterpene lactones and dihydroflavonols from Andryala and Urospermum species

Abstract The aerial parts of two Andryala species yielded several guaianolides and guaianolide glycosides, three of them being new. The aerial parts of Urospermum dalechampii yielded several known germacranolides and the new dihydroflavonol 3- O -methyltaxifolin.

Sesquiterpenes from Centaurea aspera

Abstract The aerial parts of two subspecies of Centaurea aspera L. (Asteraceae) yielded the germacranolides 1a – h , 2 , 3 , 4 and 5 , the elemane derivatives 6d and 6f , the lignan matairesinol, the degraded terpene loliolide, and the onopordopicrin–valine dimeric adduct 7 . From these, compounds 1e , 3 and 6d are natural products. The chemical composition of the two subspecies is very similar, a circumstance which does not support a taxonomic subdivision of the species.

Synthesis of fluorinated allylic amines: Reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides with fluorinated imines

A new synthesis of fluorinated allylamines through the reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides (as vinyl anion equivalents) with imines and imino esters has been described. The process includes a TBAF-mediated fragmentation of 2-(trimethylsilyl)ethyl sulfones to afford the desired allylic amines. When the reaction is performed with the corresponding sulfoxides, the fragmentation takes place under the addition conditions, affording the final products in a single step. (C) 2007 Elsevier B.V. All rights reserved.

Synthesis and biological evaluation of cyclic derivatives of combretastatin A-4 containing group 14 elements

Several tricyclic compounds inspired by the structure of combretastatin A-4 and bearing group 14 elements have been synthesized by homocoupling lithiated aryl fragments followed by ring-closing metathesis. These tricyclic compounds and their diolefin precursors were evaluated for their antiproliferative action on the tumor cell lines HT-29, MCF-7, HeLa and A-549 and on the non-tumor cell line HEK-293. In addition, their effects on the cell cycle were also measured. The tricyclic compounds show antiproliferative activity similar to that of combretastatin A-4, even though they are not so active in arresting the cell cycle. However, some diolefin precursors are able to cause accumulation of ce…

ChemInform Abstract: Cross-Metathesis Reactions as an Efficient Tool in the Synthesis of Fluorinated Cyclic β-Amino Acids.

The synthesis of enantiomerically pure, cyclic, gamma,gamma-difluorinated beta-amino acids with various ring sizes has been carried out with a cross-metathesis (CM) reaction being one of the key steps, followed by a Dieckmann-type condensation to bring about the cyclization. Subsequent catalytic hydrogenation under microwave irradiation with (-)-8-phenylmenthol as a chiral auxiliary led to the successful chemo- and diastereoselective chemical reduction of the resulting cyclic beta-enamino esters. The efficiency and scope of the CM reaction with different types of fluorinated imidoyl chlorides and unsaturated esters has also been studied in order to determine the optimal reaction conditions …

Terracinolides from Euphorbia terracina

Abstract The aerial parts of Euphorbia terracina yielded five new bishomoditerpene lactones, named terracinolides C-G, which display the novel C 22 17-ethyljatrophane framework.

Sesquiterpene lactones and acetylenes from Artemisia reptans

Abstract The aerial parts of Artemisia reptans yielded a new thiophene acetylene, four new guaianolides, a new acyclic sesquiterpene related to davanone and several known compounds.

Oplopanone derivatives monoterpene glycosides from Artemisia sieberi

Abstract The aerial parts of Artemisia sieberi yielded three new oplopanone derivatives, three new monoterpene glycosides, a new germacrane alcohol and a monoterpene acid related to nerolidol.

Synthesis of a New Fluorinated Oxazolidinone and Its Reactivity as a Chiral Auxiliary in Aldol Reactions.

A new enantiomerically pure fluorinated oxazolidinone has been prepared from a fluorinated imidoyl chloride and an optically pure sulfoxide. The diastereoselective reduction of the β-iminosulfoxide thus formed followed by elimination of the sulfoxide and cyclization of the created aminoalcohol furnishes the desired product. The fluorinated oxazolidinone was subsequently used as a chiral auxiliary in Aldol reactions. We also found that the selective formation of the syn-Evans and syn-non-Evans diastereoisomer can be controlled by adjusting the Lewis acid/base ratio.

Cross-Metathesis Reactions as an Efficient Tool in the Synthesis of Fluorinated Cyclic β-Amino Acids

The synthesis of enantiomerically pure, cyclic, gamma,gamma-difluorinated beta-amino acids with various ring sizes has been carried out with a cross-metathesis (CM) reaction being one of the key steps, followed by a Dieckmann-type condensation to bring about the cyclization. Subsequent catalytic hydrogenation under microwave irradiation with (-)-8-phenylmenthol as a chiral auxiliary led to the successful chemo- and diastereoselective chemical reduction of the resulting cyclic beta-enamino esters. The efficiency and scope of the CM reaction with different types of fluorinated imidoyl chlorides and unsaturated esters has also been studied in order to determine the optimal reaction conditions …

Influence of conformational factors on acid-catalyzed cyclizations of germacranolides: Molecular structure of the cyclization products of gallicin and 8α-hydroxygallicin (shonachalin a)

Acid-catalyzed cyclization of the natural germacranolide gallicin (8) yielded, among other products, the 1,4-epoxyeudes-manolide 9, which has a trans-fused decaline system. Under the same conditions the closely related germacranolide shonachalin A (8α-hydroxygallicin) (3) cyclized to the eudesmanolide 4 with a cis fused decaline system. The structures of these cyclization products were secured by means of chemical correlations and X-ray diffraction analyses.

Comparative Analysis of the Vascular Actions of Diterpenes Isolated from Euphorbia canariensis

Abstract We have analysed the effects of 2,3-diepiingol 7,12-diacetate-8-isobutyrate (compound 1), ingenol-3-angelate-17-benzoate (compound 2), ingenol-3-angelate-17-benzoate-20-acetate (compound 3) and 3,5,7,8,9,15-hexahydroxyjatropha-6(17),11-dien-14-one-5,8-bis(2-methylbutyrate)-7-(2-methylpropionate) (compound 4), four diterpenes isolated from E. canariensis, on the isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to these compounds were obtained cumulatively in both arteries at resting tension and active tone (KCl, 50 mM). At resting tension a concentration-dependent contraction was induced by the four compounds. In the basilar …

Oxygenated germacranes from Santolina chamaecyparissus

The polar fraction of an extract of Santolina chamaecyparissus ssp. squarrosa yielded six new germacrane derivatives and a novel seco-germacrane lactone. The structures have been derived from spectral data, X-ray diffraction and chemical correlations.

Tiratricol neutralizes bacterial endotoxins and reduces lipopolysaccharide-induced TNF-alpha production in the cell.

Contains fulltext : 70610.pdf (Publisher’s version ) (Closed access) The screening of a commercially available library of compounds has proved a successful strategy for the identification of a lead compound in a drug discovery programme. Here, we analysed 880 off-patent drugs, which initially comprised the Prestwick Chemical library, as sources of bacterial endotoxin neutralizers. We identified 3,3',5-triiodo-thyroacetic acid (tiratricol) as a non-antibacterial compound that neutralizes the toxic lipopolysaccharide.

A Synthetic Model for the [4+2] Cycloaddition in the Biosynthesis of the Brevianamides, Paraherquamides, and Related Compounds

Abstract The reactivity of model systems for the proposed [4+2] cycloaddition in the biosynthesis of the brevianamides, paraherquamides, and marcfortines is explored. The model for the intermolecular reaction reveals that the cycloaddition takes place under mild conditions only if activated, very reactive dienophiles are used. When relatively unreactive dienophiles such as cyclopentene and cyclohexene are used, harsh reaction conditions and/or a Lewis acid catalyst are necessary for the reaction. In contrast, the model for the intramolecular reaction demonstrates that the cycloaddition takes place within a few hours at room temperature, even in the absence of a Lewis acid catalyst. Conclusi…

N-(Diphenylmethylene)benzenesulfonamide andN-(Diphenylmethylene)-4-methylbenzenesulfonamide

[10398-99-9] C19H15NO2S (MW 332.42) InChI = 1S/C19H15NO2S/c21-23(22,18-14-8-3-9-15-18)20-19(16-10-4-1-5-11-16)17-12-6-2-7-13-17/h1-15H InChIKey = LECLPBHPQOFADH-UHFFFAOYSA-N (reagent used as an activated imine) Physical Data: mp 119–120 °C. Form Supplied in: colorless crystals. Not commercially available. Purification: recrystalization from CH3OH. [10399-00-5] C20H17NO2S (MW 346.45) InChI = 1S/C20H17NO2S/c1-16-12-14-19(15-13-16)24(22,23)21-20(17-8-4-2-5-9-17)18-10-6-3-7-11-18/h2-15H,1H3 InChIKey = ODLFJRFKAOOIKO-UHFFFAOYSA-N (reagent used as an activated imine) Physical Data: mp 103–104 °C1; 102–103 °C2; 101–102 °C5; 103 °C6; 102–104 °C.7 Solubility: soluble in pyridine, dimethylformamide, …

Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Both a face-selective and a non-face-selective mode of formation of quaternary centers of isoprene-derived structural moieties of the natural alkaloid paraherquamide A (1) have been discovered by feeding experiments on Penicillium fellutanum with [U-13 C6 ]-glucose and [13 C2 ]-acetate. The labeling patterns suggest that the methyl groups (C22, C23) are introduced in a non-face-selective manner by a reverse prenyl transferase. The C5 unit comprising the dioxepin moiety retains stereochemical integrity indicative of a single, face-selective addition of the phenolic group to the dimethylallyl group.

An efficient entry to optically active anti- and syn-beta-amino-alpha-trifluoromethyl alcohols.

The reaction of chiral 5,6-dihydro-2H-1,4-oxazin-2-ones with TMSCF3 in the presence of a suitable activator leads to trifluoromethyl lactols, which can be selectively reduced to anti-beta-amino-alpha-trifluoromethyl alcohols. The corresponding syn diastereoisomers are obtained when the starting imines are reduced and the nitrogen atom is conveniently protected. In addition, a novel rearrangement of the CF3 group in the lactol intermediates has been observed. This represents a formal CF3 addition to the imine function in the starting substrates.

ChemInform Abstract: Organocatalytic anti-Selective Mannich Reactions with Fluorinated Aldimines: Synthesis of anti-γ-Fluoroalkyl-γ-amino Alcohols.

The asymmetric Mannich reaction between fluoroalkyl aldimines and aldehydes catalyzed by α,α-diphenylprolinol trimethylsilyl ether is reported. The corresponding Mannich adducts were reduced in situ to afford anti-β-alkyl-γ-fluoroalkyl-γ-amino alcohols in moderate yields and with very high diastereo- and enantioselectivities. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

ChemInform Abstract: Studies on the Biosynthesis of Paraherquamide. Construction of the Amino Acid Framework.

Abstract It has been previously established in this laboratory that the β-methyl-β-hydroxyproline moiety of the potent anthelmintic agent paraherquamide A, is biosynthetically derived from l -isoleucine. The downstream events from l -Ile to paraherquamide A have now been investigated. The synthesis of [1- 13 C]-labeled l -β-methylproline is described by means of a Hoffman–Loeffler–Freytag reaction sequence from [1- 13 C]- l -Ile. This amino acid is shown to be a direct biosynthetic precursor to paraherquamide A by feeding and incorporation experiments in growing cultures of Penicillium fellutanum . Three tryptophan-containing dipeptides of l -β-methylproline have been constructed: [ 13 C 2 …

Sesquiterpene lactones, lignans and aromatic esters from Cheirolophus species

Abstract The aerial parts of five Cheirolophus species yielded three new guaianolides, a new lignan and three new aromatic esters, together with other known compounds of the same type.

Diastereoselective synthesis of fluorinated, seven-membered beta-amino acid derivatives via ring-closing metathesis.

[reaction: see text] Cis and trans seven-membered gamma,gamma-difluorinated beta-amino acid derivatives (III) have been prepared with a sequence that starts with imidoyl halides (I), which are condensed with suitable ester enolates to give intermediates (II). These, in turn, can be cyclized by means of a ring-closing olefin metathesis reaction and the product stereoselectively reduced to yield compounds (III) in good overall yields.

Role of the gem-Difluoro Moiety in the Tandem Ring-Closing Metathesis−Olefin Isomerization:  Regioselective Preparation of Unsaturated Lactams

Careful selection of the metathesis catalyst, solvent, and reaction conditions allows for the efficient and regioselective synthesis of isomeric fluorinated and nonfluorinated lactam derivatives II and III from precursor amides I through a ring-closing metathesis (RCM) reaction or a tandem RCM-isomerization protocol, respectively. The presence of the gem-difluoro moiety in the starting materials exerts a pivotal effect by directing the isomerization step, making the overall tandem transformation a regioselective process. The scope, limitations, and synthetic usefulness of this protocol are also discussed.

Asymmetric synthesis of fluorinated cyclic beta-amino acid derivatives through cross metathesis.

The asymmetric synthesis of several fluorinated cis-2-aminocycloalkane carboxylic acids (cis-2-ACACs) with a cross metathesis (CM) reaction as the key step has been carried out, constituting the first time a metathesis protocol has been undertaken with fluorinated imidoyl chlorides. Subsequent chemoselective hydrogenation of the olefin moiety, Dieckmann condensation, and stereoselective reduction of the iminic double bond afforded the corresponding beta-amino esters with several ring sizes. The asymmetric version of the process was achieved by using (-)-8-phenylmenthol as a chiral auxiliary.

Improved Regioselectivity in Pyrazole Formation through the Use of Fluorinated Alcohols as Solvents: Synthesis and Biological Activity of Fluorinated Tebufenpyrad Analogs

The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity. Fil: Fustero, Santos. Universidad de Valencia; España Fil…

Highly enantioselective synthesis of fluorinated gamma-amino alcohols through proline-catalyzed cross-Mannich reaction.

A new, simple route for the synthesis of fluorinated beta-alkyl gamma-amino alcohols in optically pure form in only two steps and featuring proline catalysis from inexpensive and readily available starting materials is described. The applied strategy allows for the introduction of diversity into both the beta-fluoroalkyl and alpha-alkyl groups of these compounds. [reaction: see text]

Synthesis of new fluorinated Tebufenpyrad analogs with acaricidal activity through regioselective pyrazole formation.

In previous studies, our group has shown that the use of fluorinated alcohols such as trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation from 1,3-diketone with methylhydrazine. We have now applied this synthetic method to the preparation of new fluorinated pyrazoles, which have then been used as synthetic intermediates in the preparation of fluorinated analogs of Tebufenpyrad, a commercial acaricide. These compounds display a strong acaricidal activity that is either comparable to or better than that of the commercial compound.

ChemInform Abstract: Fluorous TBAF: A Convenient and Selective Reagent for Fluoride-Mediated Deprotections.

A fluorous analogue of TBAF has been developed for its use in the clean removal of silicon-derived protecting groups. Purification of the crude mixtures by fluorous solid-phase extractions allowed alcohols, amines, and carboxylic acids to be obtained in high purity, with no need of chromatographic separations. The moderate reactivity of fluorous TBAF was exploited in selective deprotections of several bifunctional molecules.

Reverse und „normale”︁ Prenyltransferasen haben unterschiedliche Seitenselektivitäten bei der Biosynthese von Paraherquamid

Sowohl eine seitenspezifische als auch eine seitenunspezifische Bildung quartarer C-Zentren aus von Isopren abgeleiteten Strukturelementen im Alkaloid Paraherquamid A 1 wurden durch [U-13C6]Glucose- und [13C2]Acetat-Futterungsexperimente mit Penicilliumfellutanum entdeckt. Aus dem Markierungsmuster last sich ableiten, das die Methylgruppen (C22, C23) seitenunspezifisch durch eine Reverse Prenyltransferase eingefuhrt werden. In der C5-Einheit, die den Dioxepinrest umfast, bleibt die relative Konfiguration erhalten, was fur eine einzige, seitenspezifische Addition einer Phenoleinheit an die Dimethylallylgruppe spricht.

Absolute Configurations of Three Naturally Occurring Acetylenic Spiroacetal Enol Ethers

The absolute configurations of three 6,7-oxygenated acetylenic spiroacetal enol ethers were determined by using the kinetic method of Horeau. The results were confirmed by the circular dichroism of the compounds in correlation with the corresponding 6,7-epoxide.

Fluorous (Trimethylsilyl)ethanol:  A New Reagent for Carboxylic Acid Tagging and Protection in Peptide Synthesis

Starting with a fluorous analogue of 2-(trimethylsilyl)ethanol, we have designed an easy method for preparing a new fluorous tag ((F)TMSE) for the protection of carboxylic acids. Because mild conditions are employed in the tag cleavage (TBAF in the presence of 4 A molecular sieves, which prevent racemization), this tag can be advantageously used in the synthesis of peptides and modified peptides, as we have demonstrated with several examples, including the fluorous synthesis of short alpha- and beta-peptides as well as of modified fluorinated retropeptides.

Biomimetic diels–alder cyclizations for the construction of the brevianamide, paraherquamide, sclerotamide, asperparaline and VM55599 ring systems

Abstract A potentially bio-mimetic Diels–Alder cyclization to construct the bicyclo[2.2.2] ring system common to the paraherquamides, marcfortines, sclerotamides, brevianamides, VM55599, and asperparaline is reported. Epi-deoxybrevianamide E (22) is converted into the corresponding lactim ether (23) and then oxidized with DDQ to provide an azadiene (24) which is tautomerized in the presence of base to azadiene 25 which, spontaneously cyclizes to give a 2:1 mixture of cycloadducts 26 and 27. These cycloadducts are each in turn, converted into d , l -C-19-epi-brevianamide A (20) and d , l -brevianamide B (6). The stereochemical implications of the [4+2] cycloaddition is discussed in the conte…

An efficient synthesis of new fluorinated uracil derivatives.

A series of potentially biologically active fluorinated uracil derivatives has been prepared in three steps from oxazolines and fluorinated nitriles with good chemical yields. Fustero Lardies, Santos, Santos.Fustero@uv.es ; Sanz Cervera, Juan Francisco, Juan.F.Sanz@uv.es ; Asensio Martinez, Amparo, Amparo.Asensio@uv.es

Sesquiterpene lactones from Artemisia lucentica

Abstract The aerial parts of Artemisia lucentica yielded, in addition to several known compounds, a bicyclic monoterpene ketone, two germacranolides, an eudesmanolide, a 10- epi neudesmanolide, a 2-norelemanolide and three bisabolene derivatives. The stereochemistry of a germacranolide, described as 2α-hydroxyartemorin in a previous investigation of the species, has now been corrected and the compound has been renamed lucentolide.

Synthesis and biological evaluation of new bicyclic fluorinated uracils through ring-closing metathesis.

Two families of bicyclic fluorinated uracils have been prepared starting from a gem-difluorinated unsaturated nitrile, by means of a ring-closing metathesis reaction to form the new ring, which is fused at the C-5/C-6 or N-1/C-6 positions of the uracil moiety. The selective formation of olefin regioisomers in the metathesis process can be controlled according to the reaction conditions (catalyst, solvent, and temperature). The acaricidal activities of the resulting compounds have also been investigated.

Jatrophane and tigliane diterpenes from the latex of Euphorbia obtusifolia

The latex of Euphorbia obtusifolia var. obtusifolia yielded twelve new diterpene polyesters. Seven of them displayed the jatrophane framework and five were 4-deoxyphorbol esters. A further isolated tigliane diterpene, a derivative of 4-epi-4-deoxyphorbol, was most likely an artifact of the isolation procedure. All structures were established with the aid of spectroscopic methods.

An efficient synthesis of new fluorinated uracil derivativesElectronic supplementary information (ESI) available: general procedures for the preparation of compounds 3, 6 ,7, 8 and 9. See http://www.rsc.org/suppdata/cc/b3/b300796k/

A series of potentially biologically active fluorinated uracil derivatives has been prepared in three steps from oxazolines and fluorinated nitriles with good chemical yields.

Organocatalyticanti-Selective Mannich Reactions with Fluorinated Aldimines: Synthesis ofanti-γ-Fluoroalkyl-γ-amino Alcohols

The asymmetric Mannich reaction between fluoroalkyl aldimines and aldehydes catalyzed by α,α-diphenylprolinol trimethylsilyl ether is reported. The corresponding Mannich adducts were reduced in situ to afford anti-β-alkyl-γ-fluoroalkyl-γ-amino alcohols in moderate yields and with very high diastereo- and enantioselectivities. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

New Fluorinated 1,3-Vinylogous Amidines as Versatile Intermediates: Synthesis of Fluorinated Pyrimidin-2(1H)-ones.

The condensation of the azaenolates derived from readily available ketimines with fluorinated nitriles offers an efficient and straightforward entry to new fluorinated 1,3-vinylogous amidines. These versatile compounds, in turn, react with triphosgene to yield new fluorinated pyrimidin-2(1H)-ones in high yields.

Solution versus Fluorous versus Solid-Phase Synthesis of 2,5-Disubstituted 1,3-Azoles. Preliminary Antibacterial Activity Studies

A small library of compounds with an oxa(thia)zole scaffold and structural diversity in both positions 2 and 5 has been synthesized. Double acylation of a protected glycine affords intermediate α-amido-β-ketoesters, which in turn can be dehydrated to afford 1,3-oxazoles or reacted with Lawesson’s reagent to furnish 1,3-thiazoles. This procedure was designed with its adaptation to fluorous techniques in mind. Thus, when a protected glycine with a fluorous tag in the ester moiety is used as a starting material, the synthesis can be easily completed without column chromatography purification of intermediate compounds with good to excellent yields, thus affording a suitable entry to the prepara…

New approaches to the synthesis of organofluorine nitrogenated derivatives

Fluorinated carboxylic acids are valuable building blocks for several types of organofluorine nitrogenated derivatives. In this review paper, several strategies that use these compounds as starting materials are described. First, fluorinated seven-membered cyclic β-amino esters can be diastereoselectively synthesized from these compounds with a ring-closing metathesis (RCM) reaction as the key step. The use of the RCM reaction in a different approach enables the preparation of fluorinated cyclic α-amino acid derivatives. Fluorinated carboxylic acids also constitute the starting material for the asymmetric synthesis of fluorinated allylic amines. Finally, a solution and solid-phase synthesis…

Germacranolides and a monoterpene cyclic peroxide from Artemisia fragrans

Abstract The aerial parts of Artemisia fragrans collected in Armenia yielded a new cyclic monoterpene peroxide with the irregular santolinyl framework, together with several known germacranolides. Comparison with previously published chemical results suggests these may actually have been performed on a different, although closely related species.

Asymmetric Synthesis of New β,β-Difluorinated Cyclic Quaternary α-Amino Acid Derivatives

The synthesis of new beta,beta-difluorinated cyclic quaternary alpha-amino acid derivatives 1 in which a ring-closing metathesis reaction (RCM) constitutes the key step is described. The approach employs imidoyl chlorides 3 as fluorinated building blocks, and the overall process involves the stereoselective creation of a quaternary stereocenter. Complete selectivity was achieved when (R)-phenylglycinol methyl ether was used as chiral auxiliary, allowing for the preparation of new six-membered cyclic fluorinated alpha-amino acids as single enantiomers.

ChemInform Abstract: Synthesis of Fluorinated Allylic Amines: Reaction of 2-(Trimethylsilyl)ethyl Sulfones and Sulfoxides with Fluorinated Imines.

A new synthesis of fluorinated allylamines through the reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides (as vinyl anion equivalents) with imines and imino esters has been described. The process includes a TBAF-mediated fragmentation of 2-(trimethylsilyl)ethyl sulfones to afford the desired allylic amines. When the reaction is performed with the corresponding sulfoxides, the fragmentation takes place under the addition conditions, affording the final products in a single step.

A Concise, Asymmetric Synthesis of Tetramic Acid Derivatives

[reaction: see text] A simple, asymmetric synthesis of tetramic acid derivatives is described in this paper. The key step is a carbonyl transfer from carbonyldiimidazole (CDI) to alpha-diimines (I) to form N-alkyl-4-alkylamino-5-methylenepyrrol-2-ones (II). In turn, these compounds can be easily transformed into tetramic acid derivatives (III) in two additional steps.

Studies on the biosynthesis of paraherquamide. Construction of the amino acid framework

Abstract It has been previously established in this laboratory that the β-methyl-β-hydroxyproline moiety of the potent anthelmintic agent paraherquamide A, is biosynthetically derived from l -isoleucine. The downstream events from l -Ile to paraherquamide A have now been investigated. The synthesis of [1- 13 C]-labeled l -β-methylproline is described by means of a Hoffman–Loeffler–Freytag reaction sequence from [1- 13 C]- l -Ile. This amino acid is shown to be a direct biosynthetic precursor to paraherquamide A by feeding and incorporation experiments in growing cultures of Penicillium fellutanum . Three tryptophan-containing dipeptides of l -β-methylproline have been constructed: [ 13 C 2 …

Recent Advances in the Synthesis of Pyrazoles. A Review

Pyrazole (Figure 1), a five-membered, two-nitrogen-containing heterocycle ring, is widely found as the core structure in a large variety of compounds that possess important agrochemical and pharmac...

An efficient synthesis of uracil derivatives from 2-alkyl-Δ2-oxazolines and nitriles

An efficient and convenient synthesis of new fluorinated and non-fluorinated uracils is described herein. The condensation of nitriles with enolates generated from 2-alkyl-Δ 2 -oxazolines (I) affords fluorinated β-enamino acid derivatives, which react with triphosgene to give an isomeric mixture of oxazolopyrimidinones. These can then be easily transformed into a single C-6 pyrimidindione derivative through reaction with a suitable nucleophile.

Asymmetric synthesis of fluorinated amino macrolactones through ring-closing metathesis

The synthesis of new chiral fluorinated amino and azamacrolactones of types 1 and 2 is described. A ring-closing metathesis (RCM) reaction constitutes the key step in this methodology, which uses fluorinated amino alcohols 7 as starting materials. The influence of the CF2 group, which is located in the alpha-position relative to the carbon bearing the amino group, on the efficiency of the RCM reaction is noteworthy. This method allows for the preparation of the desired fluorinated macrolactones in excellent yields.

Ingenane and lathyrane diterpenes from the latex of Euphorbia canariensis

The latex of Euphorbia canariensis yielded, in addition to five known ingenol esters, the ingenane derivatives ingenol 3-angelate 5,20-diacetate and 5-deoxyingenol 3-angelate 20-acetate, and the lathyrane derivatives 2,3-diepiingol 7,12-diacetate 8-benzoate, 2,3-diepiingol 7,12-diacetate 8-isobutyrate and 2-epiingol 3,7,12-triacetate 8-benzoate. The structures were established with the aid of spectroscopic methods, mainly NMR, and molecular mechanics calculations. They were also supported by the results of some chemical transformations.

Fluorous TBAF: A Convenient and Selective Reagent for Fluoride-Mediated Deprotections

A fluorous analogue of TBAF has been developed for its use in the clean removal of silicon-derived protecting groups. Purification of the crude mixtures by fluorous solid-phase extractions allowed alcohols, amines, and carboxylic acids to be obtained in high purity, with no need of chromatographic separations. The moderate reactivity of fluorous TBAF was exploited in selective deprotections of several bifunctional molecules.

Identification of the Iodination and Bromination Products of 3-Hydroxybenzaldehyde: Preparation of 5-Hydroxy-2-iodobenzaldehyde

The monohalogenation products of 3-hydroxybenzaldehyde (1) are useful synthons for the preparation of more complex molecules.1–4 For example, the introduction of a halogen allows the use of a Suzuk...

Studies on the Biosynthesis of Paraherquamide: Synthesis and Incorporation of a Hexacyclic Indole Derivative as an Advanced Metabolite

New Fluorinated Peptidomimetics through Tandem Aza-Michael Addition to α-Trifluoromethyl Acrylamide Acceptors: Synthesis and Conformational Study in Solid State and Solution

A range of partially modified retro (PMR) psi[NHCH(2)] peptide mimetics containing a hydrolytically stable CH(2)CH(CF(3))CO unit have been synthesized. The first kind of peptidomimetics is obtained from the highly efficient aza-Michael addition of different amines to alpha-trifluoromethyl acrylamide acceptors. Subsequent deprotection of the amino group furnishes the key common intermediate for the synthesis of other families of peptidomimetics: dipeptides, tripeptides, peptidomimetics containing a urea moiety, and structures containing two units of alpha-trifluoromethyl-beta(2)-alanine. Finally, a conformational study of several of the newly synthesized peptidomimetics, performed with the a…

Stereoselective Synthesis of Fluorine-Containing β-Amino Acids

ChemInform Abstract: Solution versus Fluorous versus Solid-Phase Synthesis of 2,5-Disubstituted 1,3-Azoles. Preliminary Antibacterial Activity Studies.

A small library of compounds with an oxa(thia)zole scaffold and structural diversity in both positions 2 and 5 has been synthesized. Double acylation of a protected glycine affords intermediate alpha-amido-beta-ketoesters, which in turn can be dehydrated to afford 1,3-oxazoles or reacted with Lawesson's reagent to furnish 1,3-thiazoles. This procedure was designed with its adaptation to fluorous techniques in mind. Thus, when a protected glycine with a fluorous tag in the ester moiety is used as a starting material, the synthesis can be easily completed without column chromatography purification of intermediate compounds with good to excellent yields, thus affording a suitable entry to the …

CCDC 1514944: Experimental Crystal Structure Determination

Related Article: Raul Blasco, Carmen Ramírez de Arellano, Juan F. Sanz-Cervera|2017|Org.Prep.Proced.Int.|49|265|doi:10.1080/00304948.2017.1320924