1,3-dipolar cycloadditions of aldehydes or Imines with carbonyl ylides generated from epoxides: Classical heating and microwave irradiation

International audienceCycloadditions of aldehydes with carbonyl ylides to give dioxolanes have been carried out without solvent under microwave irradiation. The reactions proceeded in similar yields and stereoselectivities, but in shorter reaction times, than those obtained in toluene at reflux using an oil bath. Cycloadditions conducted between imines and carbonyl ylides using the same protocol were less efficient because the oxazolidines formed proved unstable under the reaction conditions

Polar [3 + 2] cycloaddition of ketones with electrophilically activated carbonyl ylides. Synthesis of spirocyclic dioxolane indolinones.

International audienceThe [3 + 2] cycloaddition reaction between carbonyl ylides generated from epoxides and ketones (ethyl pyruvate, ethyl phenylglyoxylate, isatin, N-methylisatin and 5-chloroisatin) to give substituted dioxolanes and spirocyclic dioxolane indolinones was investigated. The effect of microwave irradiation on the outcome of the reaction was studied. The thermal reaction between 2,2-dicyano-3-phenyloxirane and N-methylisatin was theoretically studied using DFT methods. This reaction is a domino process that comprises two steps. The first is the thermal ring opening of the epoxide to yield a carbonyl ylide intermediate, whereas the second step is a polar [3 + 2] cycloaddition to yield the final spiro cycloadducts. The cycloaddition presents a low stereoselectivity and a large regio- and chemoselectivity. Analysis of the electrophilicity values and the Fukui functions of the reagents involved in the cycloaddition step allowed the chemical outcome to be explained

A combined experimental and theoretical study of the polar [3+2] cycloaddition of electrophilically activated carbonyl ylides with aldehydes and imines

International audienceNumerous 2,5-diaryl-1,3-dioxolane-4,4-dicarbonitriles and 2,4-diphenyl-1,3-oxazolidine-5,5- dicarbonitriles have been synthesized by [3+2] cycloaddition reactions between carbonyl ylides generated from epoxides, and aldehydes or imines. In contrast to the use of aldehydes (3,4,5- trimethoxybenzaldehyde, piperonal, 1-naphthaldehyde, indole-3-carboxaldehyde, furan-2- carboxaldehyde and thiophene-2-carboxaldehyde), the reactions performed with imines (N- (phenylmethylene)methanamine, N-(1,3-benzodioxol-5-ylmethylene)propylamine, N-(1,3-benzodioxol- 5-ylmethylene)butylamine and N-(1,3-benzodioxol-5-ylmethylene)benzylamine) proceed diastereoselectively. The effect of microwave irradiation on the outcome of the reaction was studied. The mechanism of these [3+2] cycloaddition reactions has been theoretically investigated using DFT methods. These cycloadditions, which have one-step mechanisms, consist of the nucleophilic attack of the aldehyde oxygen or imine nitrogen on the carbonyl ylide. For the reaction with aldehydes, a back donation effect is responsible for the unexpected reverse charge transfer found at the transition structure. The analysis of the reactivity indices indicates that the large electrophilic character of the carbonyl ylides induces them to act as strong electrophiles in these polar [3+2] cycloaddition reactions

Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells

International audienceBenzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2*TMEDA (TMEDA = N,N,N',N'-tetramethylethylenediamine, 1 equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3 equiv). Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81, 82, 67 and 42% yields, respectively. These yields are higher (10% more) than those obtained using ZnCl2*TMEDA (0.5 equiv) and LiTMP (1.5 equiv), except in the case of benzoxazole (10% less). The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2 equiv) and Cs2CO3 (2 equiv), and using acetonitrile as solvent (no other ligand) to provide after 24 h reflux the expected N-arylated azoles in yields ranging from 33 to 81%. Using benzotriazole also led to N-arylation products, but in lower 34, 39, 36 and 6% yields, respectively. A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72 h treatment at 10-5 M

Association of IL4 rs2070874, FoxP3 rs3761548 Polymorphisms with Keratoconus in Algeria

Purpose: The aim of this case–control study was to determine the impact of environmental factors on the predisposition to develop keratoconus in a sample of Western Algerian population. Subsequently, we were interested in the implication of two single nucleotide polymorphisms (SNPs) IL4 rs2070874 and FOXP3 rs3761548, previously described as contributing to the occurrence of allergy, in the development of keratoconus. Methods: The study included 70 unrelated KC cases and 70 controls originating from Western Algeria. DNA genotyping was done using predesigned probe-based allelic discrimination TaqMan® assays. Allele and genotype frequencies were compared between the cases and controls by Chi-square test and odds ratios with 95% confidence intervals. Results: A significant association between risk factors such as family history, atopy, eye rubbing, and the development of keratoconus was found in our sample. Smoking would provide a protective effect against the pathology. No statistically significant differences were found in the allele and genotype frequencies between cases and controls neither for IL4 rs2070874 nor for FOXP3 rs3761548. Conclusion: Our study provides, for the first time, a clear demonstration of the absence of association of the allergy-associated IL4 and FOXP3 polymorphisms with KC in a sample from Western Algerian population

Structure-property study of new [1,2,3]-triazole liquid crystalline derivatives

The synthesis of a new type of liquid crystalline compound derived from 1,2,3-triazole was achieved using Wittig reaction. Polarisedmicroscopy studies, X-ray scattering and differential scanning calorimetry analysis revealed that the target compounds exhibit enantiotropic liquid crystalline properties. Their mesomorphic behaviour is closely related to the nature of substituents in position N1 of the heterocycle, the length of the mesogenic core as well as the isomerisation nature (E/Z) of the double bond

A Practical Access to Novel 2-Amino-5-arylidene-thiazol-4-ones via Sulfur/nitrogen Displacement under Solvent-free Microwave Irradiations.

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Diastereospecific synthesis of new 4-substituted L-theanine derivatives.

International audienceConsidering the biological activity of L-theanine as a potent agonist of NMDA receptors, impacting on glutamatergic synapse activity, we have developed an asymmetric synthesis of new enantiomerically pure 4-substituted L-theanine derivatives. The key step is a stereospecific alkylation on a previously synthesized and correctly protected (S)-pyroglutamate

Investigation of structure-surface properties relationship of semi-fluorinated polymerizable cationic surfactants

International audienceNovel hybrid hydrocarbon/fluorocarbon ammonium type surfactant monomers (surfmers) of the general formula RF (CH2)l N(CH3)2(CH2)m OCOCH = CH2 with (RF = C4F9, C6F13, C8F17, l = 4, 6, 11, and m = 2-11) were synthesized and characterized. They exhibit very low surface tension as well as low critical micellar concentrations down to 1.39 10 5 mol/L. Special attention was focused on the effect of the polymerizable moiety, the length of the hydrocarbon spacers, and the fluorinated chains on surface activities of the reactive surfactants as compared to hydrocarbon surfmer analogs. Results indicate that the acrylic function has a pronounced effect on increasing the hydrophobic micelle character. This was confirmed by surface tensions and average surfaces occupied by these molecules at the water-gas interface. The micellar sizes were investigated by dynamic light scattering

Benzene ring containing cationic gemini surfactants: Synthesis, surface properties and antibacterial activity

International audienceNew quaternary ammonium gemini surfactants of the general formula CnH2n+1-Ph-NHCOCH2N+(CH3)(2)-(CH2)(s)- N+(CH3)(2)CH2CONH-Ph-CnH2n+1 (with n = 8, 10,12, 14,16 and s = 2,4, 6) have been synthesized by an efficient synthetic pathway based on the quaternization of N,N,N',N'-tetramethylalkylenediamine with 2-bromo-N-(4-(alkyloxy) phenyl) acetamides. Their surface properties were investigated by surface tension, electrical conductivity and dynamic light scattering (DLS) measurements. The study shows that the incorporation of a benzene ring in the hydrophobic tail prompts micelle formation which leads to a smaller cmc values in the range of 0.21-0.009 mM compared to analogous geminis bearing alkyl hydrophobic chains. The length of the spacer and the hydrophobic chain has a pronounced effect on the aggregation behavior of surfactants molecules. This was confirmed by the average surfaces occupied by these molecules at the water-air interface calculated from the Gibbs equation. The size of the aggregates was measured by employing dynamic light scattering technique. The antimicrobial activity of investigated surfactants was evaluated against three microorganisms: Staphylococcus aureus, Escherichia coli and Candida albicans. (C) 2017 Elsevier B.V. All rights reserved