Expanding the scope of the successive ring expansion strategy for macrocycle and medium-sized ring synthesis : unreactive and reactive lactams

New methods are described that expand the scope of the Successive Ring Expansion (SuRE) with respect to synthetically challenging lactams. A protocol has been developed for use with 'unreactive' lactams, enabling SuRE reactions to be performed on subsrates that fail under previously established conditions. Ring expansion is also demonstarted on 'reactive' lactams derived from iminosugars for the first time. The new SuRE methods were used to prepare a diverse array of medium-sized and macrocyclic lactams and lactones, which were evaluted in an anti-bacterial assay against E. coli BW25113WT

Synthèse stéréosélective d'acides aminocyclobutanecarboxyliques (préparation de dérivés de la sérine et de l'ornithine)

Le travail rapporté concerne la synthèse stéréosélective d'acides alpha-aminocyclobctanecarboxyliques béta-substitués, notamment deux dérivés cyclobutaniques d'aminoacides naturels (ornithine, sérine). Ces acides aminés ont des activités biologiques potentielles. L'étape clé de leur synthèse est une réaction asymétrique de Strecker sur des cyclobutanones 2-substituées. La première partie expose deux nouvelles méthodes de synthèse de cyclobutanones 2-substituées opt. actives. La première est basée sur une transestérification enzymatique de la 2-hydroxyclobutanone ou de dérivés pour donner l'alcool et l'acétate correspondants énantiopurs avec d'excellents excès énantiomériques. Ces deux composés sont ensuite transformés en les deux énantiomères de la 2-benzyloxycyclobutanone. La deuxième méthode est basée sur l'alkylation asymétrique d'imines ou hydrazones chirales dérivées de la cyclobutanone. Les diverses 2-alkyl-cyclobutanones opt. actives, dont certaines sont détectées dans les aliments irradiés, sont obtenues avec de bons rdts et de bons excès énantiomériques. La seconde partie décrit la synthèse d'analogues cyctobutaniques de la serine et de l'otnithine dont l'étape clé est une réaction de Strecker sur des cyclobutanones chirales ou racémiques. La diastéréosélectivé de cette réaction en fonction des conditions expérimentales est précisée. L a configuration absolue de chaque aminonitrile obtenu est déterminée par diffraction de RX. Ces nitriles donnent pour la première fois en 3 étapes les analogues de la serine et de l'omithine. Dans cette partie est aussi rapportée une séquence asymétrique one-pot alkylation-Strecker pour obtenir rapidement des acides aminés.This work deals with the stereoselective synthesis of alpha-aminocyclobutanecarboxylic acids in particular two cyclobutanic derivatives of natural amino acids: ornithine and serine. These aminoacids could potentially have biological properties. In the new pathway the key-step is based on a stereoselective one-pot asymmetric Strecker-reaction from 2-substituted cyclobutanones. In the first part, we report two new synthetic methods of optically active 2-substituted cyclobutanones. The first one is based on enzymatic transesterification of 2-hydroxyclobutanone or derivatives to give corresponding enantiopure alcohol and acetate with good yields and excellent enantiomeric excesses. Both compounds are transformed in few steps into both enantiomers of 2-benzyloxycyclobutanone. The second method describes an asymmetric alkylation of chiral imines or hydrazones prepared from cyclobutanones. Thus optically active 2-alkyl-cyclobutanones, some of them are detected in irradiated foodstuffs, are obtained with good yields and good enantiomeric excesses. In the second part, we describe the synthesis of cyclobutanic amino acid analogues of serine and ornithine. The key-step is an asymmetric Strecker reaction from chiral or racemic cyclobutanones, in which the diastereoselectivity under various conditions is specified and absolute configurations of amino nitriles are determined by X-ray crystallographic analysis. These amino nitriles give for the first time in 3 steps serine and ornithine derivatives. In this part we also report a one-pot asymmetric alkylation-Strecker reaction to obtain optically active beta-alkylated amino nitriles, which are potentially precursors of aminoacids.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Stereocontrolled synthesis of polyhydroxylated bicyclic azetidines as a new class of iminosugars

We report herein the development of a stereodivergent route towards polyhydroxylated bicyclic azetidine scaffolds, namely 6-azabicyclo[3.2.0]heptane derivatives. The strategy hinges on a common bicyclic β-lactam precursor, which is forged by way of a rare example of a cationic Dieckmann-type reaction, followed by IBX-mediated desaturation. Substrate-controlled diastereoselective oxidations then allow the divergent preparation of novel iminosugar mimics

Synthesis of a new class of iminosugars based on constrained azaspirocyclic scaffolds by way of catalytic C–H amination

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One-Pot, Highly Stereoselective Synthesis of Dithioacetal-α,α-Diglycosides

A one-step access to dithioacetal-α,α-diglycosides is reported. The synthetic strategy is based on the thioacetalization of aldehydes or ketones via highly stereoselective ring-opening of 1,6 anhydrosugars with bis(trimethylsilyl)sulfide