New tricyclic systems as photosensitizers towards triple negative breast cancer cells.

AbstractNineteen pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones were synthesized as new tricyclic systems in which the pyridine ring is annelated to the 6,7-dihydroindolizin-8(5H)-one and 5,6,7,8-tetrahydro-9H-pyrrole[1,2-a]azepine-9-one moieties to obtain potential photosensitizing agents. They were tested for their photoantiproliferative activity on a triple-negative breast cancer cell line, MDA-MB-231, in the dark and under UVA light (2.0 J/cm2). We demonstrated that their toxicity, only when exposed to light, was primarily due to the generation of reactive oxygen species while their photodegradation products were not responsible for their activity. The mos…

Shaping 1,2,4-Triazolium Fluorinated Ionic Liquid Crystals

The synthesis and thermotropic behaviour of some di-alkyloxy-phenyl-1,2,4-triazolium trifluoromethane-sulfonate salts bearing a seven-carbon atom perfluoroalkyl chain on the cation is herein described. The fluorinated salts presenting a 1,2,4-triazole as a core and differing in the length of two alkyloxy chains on the phenyl ring demonstrated a typical liquid crystalline behaviour. The mesomorphic properties of this set of salts were studied by differential scanning calorimetry and polarized optical microscopy. The thermotropic properties are discussed on the grounds of the tuneable structures of the salts. The results showed the existence of a monotropic, columnar, liquid crystalline phase…

Chemistry of Fluorinated Oxadiazoles and Thiadiazoles

A literature survey of the chemistry of fluorinated oxadiazoles and thiadiazoles is presented. The core part on synthetic procedures is given by type of heterocycle and includes recent developments up to the end of 2012. Reactivity is discussed when induced by the presence of the fluorinated moiety. Selected examples of bioactive compounds and applications are illustrated.

Presence and biodistribution of perfluorooctanoic acid (PFOA) in Paracentrotus lividus highlight its potential application for environmental biomonitoring

AbstractThe first determination of presence and biodistribution of PFOA in ninety specimens of sea urchin Paracentrotus lividus from two differently contaminated sites along Palermo’s coastline (Sicily) is reported. Analyses were performed on the sea urchins’ coelomic fluids, coelomocytes, gonads or mixed organs, as well as on seawater and Posidonia oceanica leaves samples from the collection sites. PFOA concentration ranged between 1 and 13 ng/L in seawater and between 0 and 794 ng/g in P. oceanica. The analyses carried out on individuals of P. lividus from the least polluted site (A) showed PFOA median values equal to 0 in all the matrices (coelomic fluid, coelomocytes and gonads). Conver…

Synthesis of new fluorinated low molecular weight (LMW) gelators

Fluorinated and pegylated polyaspartamide derivatives to increase solubility and efficacy of Flutamide

New fluorinated amphiphilic copolymers based on a biocompatible polyaspartamide have been prepared in order to obtain polymeric micelles useful for delivering anticancer drugs. In particular, α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) has been derivatized with polyethylene glycol (PEG(2000)) and ethylendiamine (EDA). Both these portions form the hydrophilic part of the copolymer, while the hydrophobic moiety is given by 1,2,4-oxadiazoles: 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole (PPOX) or 3-carboxyethyl-5-pentadecafluoroheptyl-1,2,4-oxadiazole (CPOX). Copolymers named PHEA-PEG(2000)-EDA-PPOX and PHEA-PEG(2000)-EDA-CPOX have been prepared with various degrees of derivati…

Rearrangements of 1,2,4-Oxadiazole: “One Ring to Rule Them All”

[Figure not available: see fulltext.] 1,2,4-Oxadiazoles are heterocycles characterized by low aromaticity and the presence of a weak O–N bond and are widely studied due to their tendency to rearrange into more stable heterocyclic compounds. This review covers literature from the last fifteen years, highlighting the general features of 1,2,4-oxadiazoles and their applications. Regarding the reactivity, the development of classical reactions (thermal and photochemical rearrangements) is presented in terms of synthetic utility and mechanistic insight. Among the relevant rearrangement reactions, the Boulton–Katritzky Rearrangement (BKR), Migration – Nucleophilic Attack – Cyclization (MN…

Fluorinated Heterocyclic Compounds. A Photochemical Approach to a Synthesis of Polyfluoroaryl-1,2,4-triazoles.

The reaction of some fluorinated 1,2,4-oxadiazoles in the presence of methylamine or propylamine has been investigated. The irradiation in methanol or acetonitrile leads with acceptable yields to the corresponding fluorinated 1- methyl- or 1-propyl-1,2,4-triazole.

A new palladium(II)-catalyzed [3,3] aza-Claisen rearrangement of 3-allyloxy-5-aryl-1,2,4-oxadiazoles

Abstract A new efficient palladium(II)-catalyzed [3,3] aza-Claisen, formal sigmatropic rearrangement of 3-allyloxy-5-aryl-1,2,4-oxadiazoles was developed. The mechanism was studied by analyzing the regiochemical and stereochemical course of the reaction. The results obtained indicated the intervention of a cationic pallada-cycle similar to the one postulated for the Cope rearrangement of 1,5-dienes.

Synthesis of trifluoromethylated 2-benzoyl- and 2-aminoimidazoles from ring rearrangement of 1,2,4-oxadiazole derivatives

Abstract Fluoroalkylated 2-ylamino-imidazoles have been synthesized by reaction of 3-amino-5-phenyl-1,2,4-oxadiazole with fluorinated β-dicarbonyl compounds and subsequent base-induced Boulton–Katritzky Rearrangement (BKR) of the isolated β-enaminocarbonyl intermediate. Alternatively, one-pot reactions performed in the presence of Montmorillonite K10 favoured the condensation at the 3-amino moiety of the oxadiazole and, in some cases, allowed the direct synthesis of 2-benzoylamino-imidazoles. Hydrolysis of 2-benzoylamino-imidazoles easily yielded fluorinated 2-amino-imidazoles targets.

Trasformazioni eterocicliche di 1,2,4-ossadiazoli fluorurati come substrati dielettrofili

ChemInform Abstract: Synthesis of 4(5)-Phenacyl-imidazoles from Isoxazole Side-Chain Rearrangements.

The reaction must be carried out under nitrogen atmosphere in deoxygenated solvent to prevent the oxidation of the imidazole products.

Antibacterial activity and HPLC analysis of extracts from Mediterranean brown algae

The antibacterial activity of methanolic extracts of eight Mediterranean brown algae belonging to the genera Cystoseira sensu lato, Dictyopteris and Padina was investigated. Extracts from Sargassaceae showed antibacterial activity. Specifically, Carpodesmia crinita and Carpodesmia brachycarpa extracts inhibited the growth of the Gram-positive strain Kocuria rhizophila whereas Cystoseira compressa and Carpodesmia amentacea extracts showed antibacterial activity against the Gram-positive strains, Kocuria rhizophila and Staphylococcus aureus. None of them inhibited the growth of the Gram-negative bacterium Escherichia coli. The extracts of Cystoseira sp. pl. and Treptacantha ballesterosii did …

Effect of protonation and deprotonation on the gas phase reactivity of fluorinated 1,2,4-triazines

Positive and negative electrospray mass spectrometry (MS), in-time and in-space MS n experiments, high-resolution and accurate mass measurements obtained with an Orbitrap, together with density functional theory calculations have been used to study the gas-phase ion chemistry of a series of fluorinated 1,2,4-triazines. As a result of low-energy collision-induced dissociations, occurring in an ion trap and in a triple quadrupole, their protonated and deprotonated molecules show interesting features depending on the nature and structure of the precursor ions. The occurrence of elimination/hydration reactions produced by positive ions in the ion trap is noteworthy. Decompositions of deprotonat…

Chaperonotherapy for Alzheimer’s Disease: Focusing on HSP60

This review will analyze growing evidence suggesting a convergence between two major areas of research: Alzheimer’s disease (AD) and chaperonopathies. While AD is a widely recognized medical, public health, and social problem, the chaperonopathies have not yet been acknowledged as a related burden of similar magnitude. However, recent evidence collectively indicates that such possibility exists in that AD, or at least some forms of it, may indeed be a chaperonopathy. The importance of considering this possibility cannot be overemphasized since it provides a novel point of view to examine AD and potentially suggests new therapeutic avenues. In this review, we focus on the mitochondrial chape…

NOVEL ANTAGONISTS FOR AN Hsp60-BASED ANTICANCER CHAPERONOTHERAPY

The Heat shock proteins (Hsps) are nowadays considered the most important cell chaperones, which result overexpressed in response to a number of cell stress stimuli.In tumor cells, when Hsp60 accumulates in the cytosol, without mitochondrial release, it exerts an anti-apoptotic effect, by inhibiting pro-caspase-3 (pC3) activation. In this context, our study aims to elucidate the structural details of the interaction between Hsp60 and pC3 and to design novel antagonists able to specifically block this interaction. The analysis of virtual screening results highlights the 4-(3-chloro-4-fluorophenylamino)- 6-[(1H-imidazol-4-yl-methyl)-3-carbonitrile-quinolines of type 1 and the N-{5-[1H-imidazo…

A Novel Graphene Oxide-Silica Nanohybrid, Highly Functionalized by Organic Fluorotails

GO-based composites have attracted increasing attention due to their improved properties: in this context Silica-GO nanohybrids are currently used in many fields, ranging from biomedicine to optoelectronics. In recent years growing interest of the materials community has been posed on the functionalization of graphene materials with fluorine: Fluorinated graphene oxide has been proven to be the first carbon material for Magnetic Resonance Imaging without the addition of magnetic nanoparticles,1 moreover, has proven to absorb NIR-laser energy and efficiently transform it into heat, so that fluorinated graphene oxide has been suggested as a contrast agent for MRI, ultrasound and photoacoustic…

Anticancer potential of novel α,β-unsaturated γ-lactam derivatives targeting the PI3K/AKT signaling pathway.

Abstract Six recently synthesized alkyl (Z)-2-(2-oxopyrrolidin-3-ylidene)acetates were evaluated for their potential as cytotoxic and anticancer agents. All compounds were tested in the ERα positive MCF-7, triple negative MDA-MB-231, and Her2+ SKBR-3 breast cancer cell lines. The most lipophilic derivatives, bearing the 4-isopropylphenyl (2) or 4-tert-butylphenyl (3) group at the γ-lactam nitrogen, proved to be cytotoxic against all the cancer cell lines tested (IC50 values ranging from 18 to 63 μM), exerting their greatest activity in SKBR-3 cells, with IC50 values of 33 and 18 μM, respectively. Biological studies showed that the cytotoxic effects of 2 and 3 are accompanied by apoptotic de…

1,2,4-Ossadiazoli come “nitrogen-donor” nella sintesi foto-indotta di aziridine

Chemical composition, cytotoxic effects, antimicrobial and antibiofilm activity of Artemisia arborescens (Vaill.) L. growing wild in the province of Agrigento, Sicily, Italy

Artemisia arborescens (Vaill.) L. is a perennial shrubby plant growing along the coastal strips of the Mediterranean region. It is used in traditional medicine. Its essential oil and solvent extracts exhibit a very interesting chemotherapeutic potential, which makes this plant useful in maintaining human health. The goal of this study was to determine the phytochemical composition of the petroleum ether and methanol extracts, as well as to evaluate anticancer activities and antimicrobial and biofilm formation reduction. Thirty-nine phytochemical compounds in negative ion mode, and 25 in positive ion mode were identified by HPLC-ESI-QTOF-MS. All four extracts reduced the viability of human M…

Hsp60 Inhibitors and Modulators

In this chapter, we focus on the 60 KDa Heat Shock Protein (Hsp60) and discuss some of its biological, molecular and pathological features. The structural and mechanistic aspect of the Hsp60 folding cycle will be also presented. We further illustrate how Hsp60 may be involved in many diseases and therefore considered as an effective therapeutic or theranostic target. Finally, the state-of-the-art on the development of Hsp60 and bacterial GroEL inhibitors and modulators of their expression will be illustrated. This is discussed in the light of a negative chaperonotherapy, and the consequent development of inhibitors, as well as positive chaperonotherapy, in the event its excessive activity i…

Editorial (Thematic Issue: Current and Perspective Therapeutic Strategies for Alzheimer's Disease).

Fluoropolymer Based on a Polyaspartamide containing 1,2,4-Oxadiazole Units: A Potential Artificial Oxygen (O2) Carrier

Abstract In this preliminary work we have prepared a fluorinated polymer capable of solubilizing an appreciable amount of O(2) and, at the same time, maintaining a higher water solubility than perfluoroalkanes investigated as injectable O(2) carriers. In particular, we describe the synthesis and characterization of a new macromolecular conjugate obtained by derivatization of alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) with 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole, called PHEA-F. This new water soluble fluoropolymer was prepared in high yield using a simple procedure. It was characterized by FT-IR and UV-vis spectrophotometry, (19)F-NMR and SEC measurements. O(2) so…

Synthesis of Isoxazoline Derivatives through Boulton–Katritzky Rearrangement of 1,2,4-Oxadiazoles

The base-induced rearrangement of 1,2,4-oxadiazoles into isoxazoline derivatives is reported. This represents the first example of a three-atom side-chain rearrangement that involves a saturated CCO side chain at C-3 of the oxadiazole. Nonaromatic 3-amino-isoxazoline derivatives are obtained in good yields. Interestingly, this reaction occurs through the rearrangement of aromatic oxadiazoles to form less stable bonds than those that are broken.

Sintesi di nuovi low molecular weight (LMW) hydrogelators fluorurati

Trasformazioni eterocicliche di 1,2,4-ossadiazoli fluorurati in reazioni ANRORC-like

Synthesis of fluorinated first generation starburst molecules containing a triethanolamine core and 1,2,4-oxadiazoles

Abstract 5-Pentafluorophenyl-1,2,4-oxadiazoles, differently substituted at C(3), have been synthesized and used to functionalize the aliphatic primary hydroxyl functionalities of triethanolamine, under mild conditions. UV–visible absorption and emission spectra are reported, for both tri- and difunctionalised molecules, showing their potential applications as light-emitters in optoelectronic devices.

Solvent dependent photochemical reactivity of 3-allyloxy-1,2,4-oxadiazoles

Anrorc rearrangements of fluorinated 1,2,4-oxadiazoles as an expedient route to fluorinated heterocycles

Photoluminescent decoration of iron oxide magnetic nanoparticles for dual-imaging applications

A selective functionalization of dopamine amino group with the photoluminescent 7-nitroben-zofurazan was achieved through a one-pot protection-functionalization-deprotection sequence. The resulting fluorescent catecholic ligand was used as a capping agent for iron oxide nanoparticles thus obtaining photoluminescent magnetic nanoparticles (PL-MNPs). The PL-MNPs were then embedded into PLGA-b-PEG polymeric nanocarriers which quenched the emission of the capping agent. Full recovery of fluorescence was observed after disassembling the polymeric layer of the nanoparticle, thus supporting the use of PL-MNPs as a multifunctional system for targeted drug delivery.

NOVEL SMALL MOLECULES THAT BIND AND/OR MODULATE DIFFERENT FORMS OF TAU OLIGOMERS

The present invention relates to novel small molecules of Formulas I, II, III, IIIa, IIIb, and IV and pharmaceutically acceptable salts thereof, as well as the preparation and the use thereof.

Composti eterociclici fluorurati. Un approccio fotochimico alla sintesi di chinazolin-4-oni

Designing fluorous domains. Pyridinium salts bearing a perfluoroalkylated oxadiazole moiety

Composti curcumin-like come agenti neuro-protettori. Interazione con HSP60

La Malattia di Alzheimer rappresenta una sfida fondamentale del XXI secolo per la salute pubblica. Le terapie attualmente utilizzate per la cura dell’Alzheimer si basano sugli aspetti sintomatici della patologia [1]. Un importante ruolo nella malattia è rivestito dalle Heat shock proteins (HSPs), proteine che presiedono al controllo del ripiegamento proteico [2]. Recentemente, è stato dimostrato che HSP60 media la traslocazione del Precursore della Proteina Amiloide (APP) e del Peptide Beta Amiloide (Aβ) nei mitocondri, portando alla perdita della funzionalità dell’organulo [3]. Nel campo degli approcci delle terapie potenziali, la curcumina sta emergendo come lead compound per lo sviluppo …

Composti eterociclici fluorurati. Sintesi di 2-ammino-pirimidine N-ossido e 1,2,4-triazine

ASYMMETRIC SYNTHESIS OF LINEZOLID THROUGH CATALYZED HENRY REACTION

Linezolid 1 is an antibacterial oxazolidinone approved by FDA in 2000 for the treatment of fastidious bacterial infections.1 The asymmetric synthesis of Linezolid-like molecules make use of the chiral pool approach, through the so-called Manninen reaction.2 This strategy requires the use of BuLi, low temperature and a long elaboration of the acetamide chain. Curiously, the only catalyzed approach toward the asymmetrical synthesis of Linezolid was just recently reported, and belongs to the use of proline-derived catalysts in aldol reactions as the key step.3 This procedure is quite interesting except for the low yield. Here we report a new synthesis of Linezolid, based on a Cu(II)-catalyzed …

Synthesis and chemical characterization of CuII, NiII and ZnII complexes of 3,5-bis(2′-pyridyl)-1,2,4-oxadiazole and 3-(2′-pyridyl)5-(phenyl)-1,2,4-oxadiazole ligands

Abstract The synthesis and structural characterization of Ni II , Cu II and Zn II complexes of two chelating 1,2,4-oxadiazole ligands, namely 3,5-bis(2′-pyridyl)-1,2,4-oxadiazole (bipyOXA) and 3-(2′-pyridyl)5-(phenyl)-1,2,4-oxadiazole (pyOXA), is here reported. The formed hexacoordinated metal complexes are [M(bipyOXA) 2 (H 2 O) 2 ](ClO 4 ) 2 and [M(pyOXA) 2 (ClO 4 ) 2 ], respectively (M = Ni, Cu, Zn). X-ray crystallography, 1 H and 13 C NMR spectroscopy and C, N, H elemental analysis data concord in attributing them an octahedral coordination geometry. The two coordinated pyOXA ligands assume a trans coplanar disposition, while the two bipyOXA ligands are not. The latter result is a possib…

Synthesis of fluoroalkylated imidazoles through rearrangement of N-(1,2,4-oxadiazol-3-yl)-beta-enaminoketones

Sintesi e reattività di composti eterociclici fluorurati

Recent Advances in 1,2,4-Oxadiazole Chemistry

An ANRORC approach to the synthesis of perfluoroalkylated 1,2,4-triazole-carboxamides

A series of perfluoroalkyl-1,2,4-triazole-carboxamides has been obtained through an ANRORClike rearrangement (Addition of Nucleophile, Ring-Opening and Ring-Closure) of 5- perfluoroalkyl-1,2,4-oxadiazole-3-carboxamides with methylhydrazine or hydrazine. The initial addition of the bidentate nucleophile to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring opening and ring closure, leads to the formation of triazoles in good yield under mild experimental conditions. In some cases, a competitive ANRORC-enlargement reaction to form 1,2,4-triazin-6-ones was also observed. Obtained carboxamidotriazoles have also been explored as precursors for the synthesis of 3(5)-perfluoroal…

Fluorinated heterocyclic compounds from ring-to-ring transformations of O-N bond containing azoles

Chimica in fase gassosa di ioni radicali, cationi e anioni prodotti da ossime di 1,2,4-triazine fluorurate

ChemInform Abstract: Synthesis of Tetrasubstituted 4,4′-Biimidazoles.

Highly substituted 4,4′-biimidazoles were synthesized, in good to excellent yields, through a multicomponent imidazole ring synthesis by using imidazol-4-yl-ethane-1,2-diones as starting materials. The obtained compounds were preliminarily tested as chromogenic and fluorescent sensors for heavy metals.

A novel copper compound, CuNV110, induces apoptosis in tumor cells by dissociation of the Hsp60- pro-caspase 3 complex

The biological activity of CuNV1110, a novel copper chemical compound, has been recently studied on cancer cells and it has been showed that it reduces the cell viability, in a dose and time dependent manner, and induces cell apoptosis. In this study we evaluated the possible mechanisms by which CuNV1110 induces cell apoptosis. In particular we looked at its effects on Hsp60 levels and caspase 3 activation. We used an in vitro model of a pulmonary mucoepidermoid carcinoma (NCI-H292 cells). We found that CuNV1110 reduces the cell viability and induces cell apoptosis in a dose/time dependent manner. Then, we found that Hsp60 levels decrease with the increasing concentrations of CuNV110; by co…

CuNV1110 induces dissociation of the Hsp60-pro-caspase 3 complex and activation of apoptosis in tumor cells

Sintesi e valutazione biologica di 1,2,4-ossadiazoli analoghi del Linezolid

Synthesis of isoxazoline derivatives by Boulton-Katritzky Rearrangements

Synthesis of fluorinated 1,2,4-oxadiazin-6-ones through ANRORC rearrangement of 1,2,4-oxadiazoles

Abstract The reaction of 3-ethoxycarbonyl-5-perfluoroalkyl-1,2,4-oxadiazoles with hydroxylamines has been investigated, evidencing the possibility of competitive reaction paths. Nucleophilic addition of hydroxylamine to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring-opening and ring-closure with enlargement, leads to high yield and in very mild experimental conditions to the formation of 5-hydroxyamino-3-perfluoroalkyl-6 H -1,2,4-oxadiazin-6-ones, one of these presenting water gelation ability. In turn, reactions with N -methylhydroxylamine lead the exclusive formation of 4-perfluoroacylamino-2-methyl-2 H -1,2,5-oxadiazol-3-ones through the well known Boulton–Katritzk…

Sintesi one-pot di N-ossidi di 2-ammino-pirimidine fluorurate. Riarrangiamenti competitivi “four-atom side-chain” di 1,2,4-ossadiazoli

Recent Advances in the Chemistry of 1,2,4-Oxadiazoles

1,2,4-Oxadiazoles experienced an almost 80-year long period of scientific lethargy before they tickled the curiosity of chemists. The study of chemical and photochemical reactivity of 1,2,4-oxadiazoles opened the way to a series of applications in heterocyclic synthesis. Today, 1,2,4-oxadiazoles are known in medicinal chemistry for their use as bioisosters of esters and amides. Furthermore, fluorinated 1,2,4-oxadiazoles have been applied in materials science either by themselves or for the targeted modification of polymers and macromolecules. Overall, the synthesis of 1,2,4-oxadiazoles can be planned to fine-tune their properties for featured applications. Their versatility, either as start…

ChemInform Abstract: Photochemical Functionalization of Allyl Benzoates by C-H Insertion.

The photoreactivity of allyl benzoates, containing an electron-rich double bond, has been explored by irradiation at 305 nm in different solvents. Solvent addition products arising from an insertion of the alpha H–C bonds of THF, dioxane, and i-PrOH to the allylic double bond was realized. The observed reactivity depended on reaction conditions and substitution pattern of the substrate. A DFT study on this unusual reaction was performed allowing the formulation of two mechanistic pathways.

Nuovi Riarrangiamenti Boulton-Katritzky di derivati 1,2,4-ossadiazolici contenenti un atomo di carbonio nucleofilo in catena laterale

Sintesi di 1,2,4-triazine fluorurate mediante riarrangiamento ANRORC-enlargement di perfluoroalchil-1,2,4-ossadiazoli

FDA-Approved Fluorinated Heterocyclic Drugs from 2016 to 2022

The inclusion of fluorine atoms or heterocyclic moiety into drug structures represents a recurrent motif in medicinal chemistry. The combination of these two features is constantly appearing in new molecular entities with various biological activities. This is demonstrated by the increasing number of newly synthesized fluorinated heterocyclic compounds among the Food and Drug Administration FDA-approved drugs. In this review, the biological activity, as well as the synthetic aspects, of 33 recently FDA-approved fluorinated heterocyclic drugs from 2016 to 2022 are highlighted.

Uncatalyzed photofunctionalization of C-H bonds

Sintesi di nuovi bent-core LC fluorurati

Sintesi di sali di azolil-piridinio contenenti catene perfluoroalchiliche o alchiliche: alcune proprietà e potenziali applicazioni

Ionic self assembly in the design of fluorinated ionic liquid crystals (ILCs)

Ionic liquid crystals are a class of compounds containing anions and cations, that combine the properties of liquid crystals and ionic liquids[1]. In the conventional design of ionic liquid crystalline compounds, an ionic core is connected with mesogenic groups via chemical covalent bonding . Alternatively, in ionic compounds, strong electrostatic interactions between cation and anion can be used to build up liquid crystalline order at supramolecular level. This general approach, called ionic self-assembly (ISA), allows one to create ionic phases and mesophases with highly organized supramolecular order [2]. In this context, a new series of fluorinated ionic liquids (ILs) and ionic liquid c…

ChemInform Abstract: Synthesis of Isoxazoline Derivatives Through Boulton-Katritzky Rearrangement of 1,2,4-Oxadiazoles.

This is the first report of the rearrangement of 1,2,4-oxadiazole with saturated C—C—O side chains and an unusual example of an irreversible rearrangement that allows the formation of nonaromatic heterocycles.

ChemInform Abstract: Synthesis of Trifluoromethylated 2-Benzoyl- and 2-Aminoimidazoles from Ring Rearrangement of 1,2,4-Oxadiazole Derivatives.

Abstract Fluoroalkylated 2-ylamino-imidazoles have been synthesized by reaction of 3-amino-5-phenyl-1,2,4-oxadiazole with fluorinated β-dicarbonyl compounds and subsequent base-induced Boulton–Katritzky Rearrangement (BKR) of the isolated β-enaminocarbonyl intermediate. Alternatively, one-pot reactions performed in the presence of Montmorillonite K10 favoured the condensation at the 3-amino moiety of the oxadiazole and, in some cases, allowed the direct synthesis of 2-benzoylamino-imidazoles. Hydrolysis of 2-benzoylamino-imidazoles easily yielded fluorinated 2-amino-imidazoles targets.

ChemInform Abstract: Exploiting the CNC Side Chain in Heterocyclic Rearrangements: Synthesis of 4(5)-Acylamino-imidazoles.

A new variation on the Boulton-Katritzky reaction is reported, namely, involving use of a CNC side chain. A novel Montmorillonite-K10 catalyzed nonreductive transamination of a 3-benzoyl-1,2,4-oxadiazole afforded a 3-(alpha-aminobenzyl)-1,2,4-oxadiazole, which was condensed with benzaldehydes to afford the corresponding imines. In the presence of strong base, these imines underwent Boulton-Katritzky-type rearrangement to afford novel 4(5)-acylaminoimidazoles.

SYNTHESIS AND EVALUATION OF CURCUMIN ANALOGUES AS NEURO-PROTECTIVE AGENTS FOR THE ALZHEIMER'S DISEASE

The Alzheimer's disease (AD) is the most common form of senile dementia.1 The most important role in AD is played by the aggregation process of beta-amyloid peptide (Aß), responsible for the cytotoxic effects.2 In this context, the purpose of this study was to synthesize new dicarbonyl compounds 1 structurally related to curcumin3, with anti-aggregation activity against Aß.Parallel studies involve the synthesis of heterocyclic-based curcumin-like molecules that are currently under investigation by means of in silico protocols in order to rationalize the ligand-biological target interactions.

Dimethyl 2,2′-[Carbonylbis(azanediyl)](2S,2′S)-bis[3-(4-hydroxyphenyl)propanoate]

The thus‐far unknown ureic derivative dimethyl 2,2′‐[carbonylbis(azanediyl)](2S,2′S)‐ bis[3‐(4‐hydroxyphenyl)propanoate] has been efficiently synthesized by enantiospecific oxidative carbonylation of readily available L‐tyrosine methyl ester, using a very simple catalytic system (PdI2 in conjunction with KI) under relatively mild conditions (100 °C for 5 h in DME as the solvent and under 20 atm of a 4:1 mixture CO‐air).

ChemInform Abstract: Tandem Reactions of 1,2,4-Oxadiazoles with Allylamines.

Two novel thermal rearrangements are presented: the addition of allylamine (II) to oxadiazoles proceeds via ring-opening followed by cycloaddition.

Synthesis, antiproliferative activity, and in silico insights of new 3-benzoylamino-benzo[ b ]thiophene derivatives

A new series of 3-benzoylamino-5-imidazol-5-yl-benzo[b]thiophenes and the parent amino derivatives were synthesized and screened as antitumor agents. All tested compounds showed concentration-dependent antiproliferative activity profile against HeLa cell line, exhibiting GI50 values in the low micromolar range. The most active compounds were tested in cell cycle perturbation experiments. A rapid accumulation of cells in the G2/M phase, with a concomitant reduction of cells in both the S and G0/G1 phases, was observed, suggesting that cell exposure to selected derivatives produces mitotic failure. To rationalize the biological results, the 3-benzoylamino-benzo[b]thiophenes were analyzed thro…

Curcumin-Like Compounds as Neuroprotective Agents: Interactions with HSP60 and Amyloid Beta Peptide

Alzheimer’s Disease (AD) represents a fundamental challenge for public health in the 21st century. Current AD therapies largely focus on symptomatic aspects of the clinical pathology, but they have yet to demonstrate any major impact on the disease progression [1]. The most important role of the research aimed at fighting the AD is the development of neuro-protective agents, able to interfere with the protein aggregation process whose clinical signature is represented by the plaques deposition. An important role in AD’s framework could be played by Heat shock proteins (HSPs), highly regulated proteins that mediate the proteins proper folding and promote recovery of their native conformation…

Polyfluoroalkyl viologen-based Ionic Liquid Crystals

Studio dell’effetto dei sostituenti sul riarrangiamento fotoindotto di diaril-1,2,4-ossadiazoli in zeolite NaY

Asymmetric synthesis and biological evaluation of 1,2,4-Oxadiazoles analogues of Linezolid

Oxazolidinones are a class of antibacterial agents which displayed activity againist a variety of gram-positive pathogens and are highly potent against multidrug-resistant bacteria. Linezolid is the first oxazolidinone antibiotic approved for clinical use but linezolid resistance began to appear. 1,2,4 – Oxadiazoles are known bioactive heterocycles whose activity has been often associated to their bioisosterism with amide or ester functionalities [1]. As results of a research project on the molecular design of heterocycle – based antibacterials to contrast Multi-Drug Resistance (MDR) [2], we report the synthesis of 1,2,4 - Oxadiazole analogues of Linezolid. The synthesis has been achieved b…

Multicomponent Synthesis of Benzothiophen-2-acetic Esters by a Palladium Iodide Catalyzed S-cyclization – Alkoxycarbonylation Sequence

A catalytic carbonylative approach to the multicomponent synthesis of benzothiophene derivatives from simple building blocks [1-(2-(methylthio)phenyl)prop-2-yn-1-ols, carbon monoxide, and an alcohol)] is presented. It is based on an S-cyclization-demethylation-alkoxycarbonylation-reduction sequence promoted by the PdI2/KI catalytic system, occurring under relatively mild conditions (40 atm, 80 °C, 15 h). Benzothiophene-2-acetic esters are obtained in moderate to good yields (35–70%) starting from variously substituted substrates in combination with different alcohols as external nucleophiles (17 examples). (Figure presented.).

Iodocyclization of 2-Methylthiophenylacetylenes to 3-Iodobenzothiophenes and their coupling Reactions under More Sustainable Conditions

We report the first example of iodocyclization of readily available 2-methylthiophenylacetylenes in a deep eutectic solvent (ChCl/urea 1/2, mol/mol) as recyclable and more sustainable solvent with respect to the classical VOCs employed so far. The process successfully afforded a variety of 3-iodobenzothiophenes in good to high yields starting from differently substituted substrates, with the possibility to recycle the DES several times without appreciable lowering of the product yield. The 3-iodothiophenes thus synthesized are known to be important precursors of biologically active molecules and functionalized heterocycles, and were successfully employed for performing representative Sonoga…

Synthesis of trifluoromethylated 2-benzoyl- and 3-aminoimidazoles from ring rearrangement of 1,2,4-oxadiazole derivative

Fluoroalkylated 2-ylamino-imidazoles have been synthesized by reaction of 3-amino-5-phenyl-1,2,4-oxadiazole with fluorinated b-dicarbonyl compounds and subsequent base-induced BoultoneKatritzky Rearrangement (BKR) of the isolated b-enaminocarbonyl intermediate. Alternatively, one-pot reactions performed in the presence of Montmorillonite K10 favoured the condensation at the 3-amino moiety of the oxadiazole and, in some cases, allowed the direct synthesis of 2-benzoylamino-imidazoles. Hydrolysis of 2-benzoylamino-imidazoles easily yielded fluorinated 2-amino-imidazoles targets.

CHEMICAL CHARACTERIZATION AND BIOLOGICAL PROPERTIES OF MACROALGAE EXTRACTS

Marine species are a rich source of bioactive molecules and among them, it is known that marine algae produce different secondary metabolites for which different biological activities such as: immunomodulatory (Raposo et al., 2016), antioxidant (Fisch et al., 2003) and antimicrobial (Pinteus et al., 2015) were demostrated. The aim of this study was chemical charac- terize the extracts of three macroalgae species: Carpodesmia crinite (Duby, Orellana & Sansón, 2019), Carpodesmia brachy- carpa (J. Agardh, Orellana & Sansón 2019, WoRMS, 2023), Ericaria brachycarpa (J. Agardh, Molinari & Guiry, 2020), Asparagopsis taxiformis (Delile) Trevisan 1845) to evaluate also their biological a…

Five-to-Six Membered Ring-rearrangements in the Reaction of 5-Perfluoroalkyl-1,2,4-oxadiazoles with Hydrazine and Methylhydrazine

The hydrazinolysis reaction of 5-perfluoroalkyl-1,2,4-oxadiazoles with hydrazine or methylhydrazine as bidentate nucleophiles has been investigated. The reaction occurred through the addition of the bidentate nucleophile to the C(5)-N(4) double bond of the 1,2,4-oxadiazole followed by ring-opening and ring-closure (ANRORC) involving the second nucleophilic site of the reagent. This ring-closure step could involve either the original C(3) of the 1,2,4-oxadiazole (giving a five-to-five membered ring rearrangement) or an additional electrophilic center linked to it (exploiting a five-to-six membered ring rearrangement). An alternative initial nucleophilic attack may involve the additional elec…

Lower rim arylation of calix[n]arenes with extended perfluorinated domains

Abstract Exhaustive O-arylation of p-tert -butylcalix[ n ]arenes 2 ( n  = 4–8) with an excess of 3-pentadecafluoroheptyl-5-pentafluorophenyl-1,2,4-oxadiazole 3 and K 2 CO 3 in refluxing acetonitrile provides an easy entry to a new family of perfluorinated calix[ n ]arenes 1 . The cyclic tetramer furnishes a mixture of cone , partial cone , and 1,2-alternate conformers, while the larger macrocycles afford single products. The structures of all new compounds are substantiated by NMR techniques and MALDI-TOF mass spectral data. Single-crystal X-ray diffraction studies on the pentamer derivative 1b reveal a distorted cone-in conformation of the calixarene cup.

Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo

Currently, Klebsiella pneumoniae is a pathogen of clinical relevance due to its plastic ability of acquiring resistance genes to multiple antibiotics. During K. pneumoniae infections, lipopolysaccharides (LPS) play an ambiguous role as they both activate immune responses but can also play a role in immune evasion. The LPS O2a and LPS O2afg serotypes are prevalent in most multidrug resistant K. pneumoniae strains. Thus, we sought to understand if those two particular LPS serotypes were involved in a mechanism of immune evasion. We have extracted LPS (serotypes O1, O2a and O2afg) from K. pneumoniae strains and, using human monocytes ex vivo, we assessed the ability of those LPS antigens to in…

Synthesis, Reactivity, Biological Activity and Applications of Fluorinated Oxadiazoles and Thiadiazoles

A literature survey of the chemistry of fluorinated oxadiazoles and thiadiazoles is presented. The core part on synthetic procedures is given by type of heterocycle and includes recent developments up to the end of 2012. Reactivity is discussed when induced by the presence of the fluorinated moiety. Selected examples of bioactive compounds and applications are illustrated.

Sintesi di un nuovo sensore fluorescente selettivo per Hg2++ contenente ossadiazoli fluorurati

Synthesis and characterization of a series of alkyl-oxadiazolylpyridinium salts as perspective ionic liquids

The synthesis of a series of 1,2,4-oxadiazolyl-N-methylpyridinium salts differing in the length and the position of the alkyl chain in the heterocyclic ring and the counter ions is reported. Some features of this new family of salts as perspective ionic liquids are described and the influence of the varying moieties in the modulation of the properties is discussed.

Synthesis and chemical characterization of CuII, NiII and ZnII complexes of 3,5-bis(20-pyridyl)-1,2,4-oxadiazole and 3-(20-pyridyl)5-(phenyl)-1,2,4-oxadiazole ligands

The synthesis and structural characterization of NiII, CuII and ZnII complexes of two chelating 1,2, 4-oxadiazole ligands, namely 3,5-bis(20-pyridyl)-1,2,4-oxadiazole (bipyOXA) and 3-(20-pyridyl)5- (phenyl)-1,2,4-oxadiazole (pyOXA), is here reported. The formed hexacoordinated metal complexes are [M(bipyOXA)2(H2O)2](ClO4)2 and [M(pyOXA)2(ClO4)2], respectively (M = Ni, Cu, Zn). X-ray crystallography, 1H and 13C NMR spectroscopy and C, N, H elemental analysis data concord in attributing them an octahedral coordination geometry. The two coordinated pyOXA ligands assume a trans coplanar disposition, while the two bipyOXA ligands are not. The latter result is a possible consequence of the format…

SINTESI DI IMIDAZOLI E 4,4’-BISIMIDAZOLI FUNZIONALIZZATI, TRAMITE REAZIONI DI RIARRANGIAMENTO DI ISOSSAZOLI

Nanopiattaforme di Ossido di Grafene perfluorurate: materiali biocompatibili con affinità per l'ossigeno

L’attacco covalente di molecule perfluorurate su ossido di graphene (GO) via sostituzione nucleofila aromatica ha consentito una facile funzionalizzazione delle lamelle di GO.1,2 La performance delle nanopiattaforme perluorurate (GOF) nell’uptake e rilascio di ossigeno è stata valutata in condizioni di pH fisiologico a differenti concentrazioni e temperature, dimostrando una maggiore affinità del materiale perfluorurato GOF rispetto al GO pristino. Anche a basse concentrazioni GOF ha mostrato valori di uptake di ossigeno a saturazione e velocità di diffusione superiori ad altri materiali proposti in letteratura per ingegneria tissutale, per l’ossigenazione cellulare durante la rigenerazione…

Recent development in fluorinated antibiotics

This chapter presents the most recent results in the development of fluorinated antibioticsby taking into consideration modern challenges of multidrug-resistant pathogens. After a brief introduction on the direct and indirect effects of fluorine and fluorinated moieties in regulating biological activity, the chapter is developed in three main subsections discussing the two major classes of fluorinated antibiotics, fluoroquinolones and oxazolidinones, plus an overview of recent research on the antibiotic activity of fluorinated analogs of tetracyclines, peptidomimetics, triazoles, and nucleosides. Discussed aspects include: (1) Synthesis and challenges posed by the introduction of fluorinate…

Synthesis of Heteroaromatics via Rearrangement Reactions

Synthesis and biological evaluation of 1,4-oxadiazole analogues of Linezolid

Sintesi di ossadiazoli fluorurati come nuovi Low molecular weight hydrogelators

Fluorinated Heterocyclic Compounds. A Photochemical Approach to a Synthesis of Fluorinated Quinazolin-4-ones

An efficient and generalized photochemical methodology for the preparation of fluorinated quinazolin-4-ones is described. Depending on the starting substrate, quinazolin-4-ones bearing a perfluoroalkyl- or perfluoroaryl- substituent in position 2 or fluorine atoms on any positions of the benzo-fused moiety can easily be obtained. 5-Aryl-3-perfluoroalkylpentafluorophenyl- or 5-polyfluoroaryl-3-phenyl(methyl)-1,2,4-oxadiazoles, respectively, can be considered as ideal precursors that can be transformed into the target quinazolin-4-ones by irradiation in the presence of triethylamine (TEA) (at λ = 313 nm) or pyrene (at λ = 365 nm) in dry methanol or acetonitrile as solvent. Some mechanistic co…

Sintesi di Low Molecular Weight Gelators (LMWG) Fluorurati

Structure and Stability of Hsp60 and Groel in Solution

Molecular chaperones are a class of proteins able to prevent non-specific aggregation of mitochondrial proteins and to promote their proper folding. Among them, human Hsp60 is currently considered as a ubiquitous molecule with multiple roles both in maintaining health conditions and as a trigger of several diseases. Of particular interest is its role in neurodegenerative disorders since it is able to inhibit the formation of amyloid fibrils.Hsp60 structure was considered, until recent years, analogue to the one of its bacterial homolog GroEL, one of the most investigated chaperones, whose crystallographic structure is a homo-tetradecamer, made up of two seven member rings. On the contrary, …

Microreattori fluorurati. Studio della reazione "ene" con ossigeno singoletto in zeolite NAY modificata con cationi fluoroorganici

Synthesis of Fluorinated Bent-Core Mesogens (BCMs) Containing the 1,2,4-Oxadiazole Ring

New fluorinated bent-core mesogens containing the 1,2,4-oxadiazole or 1,2,4-triazole nucleus have been synthesized taking advantage of the ANRORC (Addition of Nucleophile, Ring-Opening, Ring-Closure) reactivity of 5-perfluoroalkyl-1,2,4-oxadiazoles. Physical state changes of the obtained compounds were characterized through DSC, POM, and SAXS. Besides the formation of a smectic mesophase, a novel behavior as organic molecular glass was evidenced for some 1,2,4-oxadiazole derivatives.

Fluoroarylation of hydroxylated molecules with 5-pentafluorophenyl-1,2,4-oxadiazoles

Synthesis and characterization of new azoles as building blocks for functional ionic systems

Experimental and DFT studies on competitive heterocyclic rearrangements. part 2: A one-atom side-chain versus the classic three-atom side-chain (Boulton-Katritzky) ring rearrangement of 3-acylamino-1,2,4-oxadiazoles

The experimental investigation of the base-catalyzed rearrangements of 3-acylamino-1,2,4-oxadiazoles evidenced a new reaction pathway which competes with the well-known ring-degenerate Boulton- Katritzky rearrangement (BKR). The new reaction consists of a one-atom side-chain rearrangement that is base-activated, occurs at a higher temperature than the BKR, and irreversibly leads to the corresponding 2-acylamino-1,3,4-oxadiazoles. An extensive DFT study is reported to elucidate the proposed reaction mechanism and to compare the three possible inherent routes: (i) the reversible three-atom side-chain ring-degenerate BKR, (ii) the ring contraction-ring expansion route (RCRE), and (iii) the one…

ChemInform Abstract: 1,2,4-Oxadiazole Rearrangements Involving an NNC Side-Chain Sequence.

The thermal rearrangement of N-1,2,4-oxadiazol-3-yl-hydrazones into 1,2,4-triazole derivatives is reported. This represents the first example of a three-atom side-chain rearrangement involving an NNC sequence linked at the C(3) of the oxadiazole. The reactions carried out under solvent-free conditions produced good to high yields of the final products.

Insight on [1,3]thiazolo[4,5-e]isoindoles as tubulin polymerization inhibitors

A series of [1,3]thiazolo[4,5-e]isoindoles has been synthesized through a versatile and high yielding multistep sequence. Evaluation of the antiproliferative activity of the new compounds on the full NCI human tumor cell line panel highlighted several compounds that are able to inhibit tumor cell proliferation at micromolar-submicromolar concentrations. The most active derivative 11g was found to cause cell cycle arrest at the G2/M phase and induce apoptosis in HeLa cells, following the mitochondrial pathway, making it a lead compound for the discovery of new antimitotic drugs.

Anti-inflammatory properties of lemon-derived extracellular vesicles are achieved through the inhibition of ERK/NF-κB signalling pathways

Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti-inflammatory drugs prompt the identification of new therapeutic strategies. Plant-derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed-phase high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (RP-HPLC-ESI-Q-TOF-MS). To investigate whether LEVs have a protective role on the inflammatory process, murine a…

1,2,4-Oxadiazole rearrangements involving an NNC side-chain sequence.

The thermal rearrangement of N-1,2,4-oxadiazol-3-yl-hydrazones into 1,2,4-triazole derivatives is reported. This represents the first example of a three-atom side-chain rearrangement involving an NNC sequence linked at the C(3) of the oxadiazole. The reactions carried out under solvent-free conditions produced good to high yields of the final products.

Streptomyces coelicolor extracellular vesicles

This study may reveal the importance of extracellular vesicles in the physiology of S. coelicolor and may also have important biotechnological implications.

Un nuovo riarrangiamento [3,3] sigmatropico di 3-allilossi-5-fenil-1,2,4-ossadiazoli catalizzato da Pd(II)

Fotochimica organica in zeolite: dalle fotoossidazioni ai riarrangiamenti eterociclici

Sintesi di 1,2,4-ossadiazoli fluorurati analoghi del Linezolid come potenziali anti-batterici

L'aumentata multidrug resistance tra i batteri patogeni Gram-positivi ha riacceso l'interesse verso la ricerca di nuove classi strutturali di antibiotici attivi nei confronti di batteri multiresistenti.1 Il Linezolid, appartenente alla classe degli ossazolidinoni, è il capostipite di una nuova generazione di anti-batterici di sintesi attivi contro patogeni Gram-positivi.2 La ricerca di nuovi analoghi del Linezolid risulta quanto mai attuale dato il recente riscontro di fenomeni di resistenza batterica a tale farmaco.3 In questo contesto, verranno presentati alcuni risultati preliminari relativi allo sviluppo di nuove metodologie di sintesi per l’ottenimento di composti eterociclici fluorura…

Synthesis, computational evaluation and pharmacological assessment of acetylsalicylic esters as anti-inflammatory agents

A convenient approach to the synthesis of alkyl esters of aspirin (ASA-OR) has been developed. The synthesis of ASA-OR has been realized in two steps: (1) direct esterification of salicylic acid with alcohols in the presence of dicyclohexylcarbodiimide to give alkyl salicylates (SAL-OR); (2) acetylation of SAL-OR with acetyl chloride to yield ASA-OR. Molecular mechanics simulations, performed to calculate the kinetic radii of several ASA-OR, indicated that the pentyl and hexyl acetylsalicylates possess the best properties to cross cell membranes. The in vitro biological tests demonstrate their anti-inflammatory activity, superimposable to that of aspirin. The results of our study suggest th…

Applications of ring rearrangements involving a participating side chain for the synthesis of five-membered heterocycles

FLUORINATED DERIVATIVES OF A POLYASPARTAMIDE BEARING POLYETHYLENE GLYCOL CHAINS AS OXYGEN CARRIERS

Abstract In this paper the synthesis and characterization of new fluorinated polymers based on a polyaspartamide bearing polyethylene glycol (PEG) chains, are reported. The starting material was the α,β-poly(N-2-hydroxyethyl)- dl -aspartamide (PHEA), a water soluble and biocompatible polymer, that has been derivatized with both polyethylene glycol (with a molecular weight of 2000 Da) and 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole. By varying the amount of the fluorinated oxadiazole, three samples have been prepared and characterized by FT-IR, 1H NMR, 19F NMR and UV–VIS spectroscopy. Size exclusion chromatography analysis of these copolymers revealed the occurrence of a self-asso…

Novel Sources of Biodiversity and Biomolecules from Bacteria Isolated from a High Middle Ages Soil Sample in Palermo (Sicily, Italy)

: The urban plan of Palermo (Sicily, Italy) has evolved throughout Punic, Roman, Byzantine, Arab, and Norman ages until it stabilized within the borders that correspond to the current historic center. During the 2012 to 2013 excavation campaign, new remains of the Arab settlement, directly implanted above the structures of the Roman age, were found. The materials investigated in this study derived from the so-called Survey No 3, which consists of a rock cavity of subcylindrical shape covered with calcarenite blocks: it was probably used to dispose of garbage during the Arabic age and its content, derived from daily activities, included grape seeds, scales and bones of fish, small animal bon…

Fluorinated heterocycles from 1,2,4-oxadiazole precursors. Synthesis of 3-amino-indazoles

Novel ANRORC rearrangements of 1,2,4-oxadiazoles

Synthesis of tetrasubstituted-4,4'-biimidazoles with perspective heavy-metal sensing ability

ChemInform Abstract: A New Palladium(II)-Catalyzed [3,3] Aza-Claisen Rearrangement of 3-Allyloxy-5-aryl-1,2,4-oxadiazoles.

Substituted derivatives such as (Ib,c) react with very high degree of stereochemistry explained by a cationic palladacycle intermediate similar to the one postulated for the Cope-rearrangement of 1,5-dienes.

ChemInform Abstract: Synthesis of Amino-1,2,4-triazoles by Reductive ANRORC Rearrangements of 1,2,4-Oxadiazoles.

The hydrazinolysis of the oxadiazoles under optimized conditions allows a general synthesis of functionalized aminotriazole products which are of interest due to the biological activity of the heterocyclic system.

Exploiting the CNC Side Chain in Heterocyclic Rearrangements: Synthesis of 4(5)-Acylamino-imidazoles

A new variation on the Boulton-Katritzky reaction is reported, namely, involving use of a CNC side chain. A novel Montmorillonite-K10 catalyzed nonreductive transamination of a 3-benzoyl-1,2,4-oxadiazole afforded a 3-(alpha-aminobenzyl)-1,2,4-oxadiazole, which was condensed with benzaldehydes to afford the corresponding imines. In the presence of strong base, these imines underwent Boulton-Katritzky-type rearrangement to afford novel 4(5)-acylaminoimidazoles.