Catalyst-Free Site Selective Hydroxyalkylation of 5-Phenylthiophen-2-amine with α-Trifluoromethyl Ketones through Electrophilic Aromatic Substitution

An original and effective approach for achieving trifluoromethyl hydroxyalkylation of 5-phenylthiophen-2-amine using α-trifluoromethyl ketones is described. In the last few years, reaction of Friedel-Crafts had been widely used to realize hydroxyalkylation on heterocycles such as indoles or thiophenes by means of Lewis acid as catalyst. Additionally, amine functions are rarely free when carbonyl reagents are used because of their tendency to form imines. This is the first time that a site-selective electrophilic aromatic substitution on C3 atom of an unprotected 5-phenylthiophen-2-amine moiety is reported. The liberty to allow reaction in neutral conditions between free amine is valuable in a synthesis pathway. The reaction proceeds smoothly using an atom-economical metal-and catalyst-free methodology in good to excellent yields. A mechanism similar to an electrophilic aromatic substitution has been proposed

Ethynylglycine synthon, a useful precursor for the synthesis of biologically active compounds: an update: Part I: preparations of ethynylglycine synthon

International audienceThe ethynylglycine synthon {(R)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-ethynyloxazolidine} is a chiral compound with valuable synthetic interest. An update on the different routes for its synthesis is reviewed and discussed

New developments in the synthesis of acetylenic analogues of glutamate

International audienceGlutamate ((S)-Glu)is the major excitatory amino acid in the central nervous system. It acts by stimulating ionotropic and metabotropic glutamate receptors (iGluR and mGluR respectively). Glutamate has been shown to be involved not only in many neuropathologies such as anxiety, pain, ischemia, Parkinson's disease, epilepsy and schizophrenia. More recently, mGlu receptors have also been detected in non-neuronal cells suggesting that they could be implicated in carcinogenesis. mGlu receptors are G-protein-coupled receptors and eight subtypes (mGluR1 to 8) have been identified and classified into three groups (I-III) based upon sequence homology, transduction mechanism and pharmacological profile. Because of their modulating properties, mGlu receptors are recognized as promising therapeutic targets and many ligands (agonists and antagonists) have been prepared to better understand the pharmacology of mGlu receptors in order to selectively activate the different groups and subtypes of receptors. An -amino acid moiety can be found in all mGlu receptors competitive ligands and most of the side chains hold an acidic function. Examination of the glutamate binding site in the mGlu receptors and pharmacological data of some ligands shows that sterically constrained structures with an optimal distance between functional groups could lead to potent and selective new ligands. It is known that introducing an unsaturation in a biologically active structure could modify the conformation of the molecule and thus the biological activity. In this respect, the synthesis of new acetylenic analogues of glutamate will be described

Synthesis of acetylenic analogue of phenylalanine.

International audienceα -alkyl α-amino acids constitute an interesting class of non proteinogenic amino acids and are used to build new peptidic sequences with enhanced properties in various physiologically active peptides and proteins. The additional alkyl substituent could prevent the free rotation of the residue's side chain leading to unique folding when incorporated into peptides. Peptides containing quaternary α-amino acids also tend to have increased hydrophobicity, as well as an increased stability toward both chemical and metabolic decompositions. Unsaturated a-amino acids have turned out to be especially important building blocks for these studies due to the diverse reactivities of the multiple bonds and their ability to introduce biologically active functionalities. b,c-unsaturated amino acid derivatives have received crucial attention since they are important enzyme inhibitors. a-vinyl glycine is known to inhibit pyridoxal phosphate dependant enzymes in particular decarboxylase. Moreover,a-ethynyl amino acids are described such as potential suicide inhibitors of glutamic acid decarboxylase in particular ethynyl glycine is a well-known natural antibiotic and a suicide substrate for alanine racemase. Given this background, we herein report the synthesis of DL-ethynyl phenylalanine starting from DL-benzylserine in 9 steps

Synthesis of a Novel Rhizobitoxine-Like Triazole-Containing Amino Acid

International audienceThe synthesis of the four stereoisomers of a new 1,2,3-tri-azole analogue of rhizobitoxine from serine is described. The key step is a Huisgen 1,3-dipolar cycloaddition on an ethynylglycine synthon

Synthesis of cis-5-Trifluoromethylproline from L-Glutamic Acid

International audienceThe diastereoselective synthesis of cis-5-trifluoromethylproline (5-Tfm-Pro) from l-glutamic acid is described. 5-Tfm-Pro could be obtained through a seven-step linear sequence. Trifluoromethylation of the glutamic-derived ester or aldehyde and subsequent reduction of the cyclic imine are the key steps in the synthesis

Insulating board from short asbestos fibre

Peer reviewed: YesNRC publication: Ye

Analysis of the Volatile Organic Compounds of Tillandsia flowers by HS-SPME/GC-MS

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Synergistic Effects of Novel Naphthoquinone Derivatives Against Clinical Methicilin-Resistant Staphylococcus aureus Strain

International audienceThe emergence of multidrug resistant (MDR) bacteria requires interest in the medical field and thereby an urgent need to develop efficient and specific methods in targeting unique bacterial cellular processes. Menadione (Vitamin K3) showed interesting properties as membrane integrity, two-component system and efflux pump disruptor. Novel series of 1,4-naphthoquinone based on menadione have been designed and synthesized starting from juglone and naphthazarin, following a Minisci-type reaction

Analysis of the Volatile Organic Compounds of Tillandsia flowers by HS-SPME/GC-MS

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