Stereoselective Access to Iminosugar C, C-Glycosides from 6-Azidoketopyranoses

International audienceWe report the synthesis of iminosugar C,C-glycosides starting from 6-azidoketopyranoses. Their Staudinger-azaWittig-mediated cyclization provided bicyclic N,O-acetals, which were stereoselectively opened with AllMgBr to afford β-hydroxyazepanes with a quaternary carbon α to the nitrogen. Their ring contraction via a β-aminoalcohol rearrangement produced the six-membered l-iminosugars with two functional handles at the pseudoanomeric position. Inversion of the free OH at the azepane level furnished the d-iminosugars

Access to l- and d-Iminosugar C-Glycosides from a d-gluco-Derived 6-Azidolactol Exploiting a Ring Isomerization/Alkylation Strategy.

International audienceA flexible synthetic access to six-membered l- and d-iminosugar C-glycosides is reported starting from the easily available 6-azido-6-deoxy-2,3,4-tri-O-benzyl-d-glucopyranose precursor. This methodology involves a highly diastereoselective tandem ring enlargement/alkylation and a stereocontrolled ring contraction. It allows an efficient synthesis of iminosugar C-glycosides displaying structural diversity at both C-1 and C-6

Evaluation of nonnatural L-iminosugar C,C-glycosides, a new class of C-branched iminosugars, as glycosidase inhibitors

International audienceCapitalizing on a previously developed Staudinger/azaWittig/Grignard (SAWG)-ring contraction sequence that furnished protected six-membered L-iminosugar C,C-glycosides bearing an allyl group and various substituents at the pseudoanomeric position, the synthesis and glycosidase inhibition of a small library of six- and seven-membered L-iminosugar C,C-glycosides is reported. Their hydrogenolysis or cyclization by RCM followed by deprotection afforded eleven L-iminosugars including spirocyclic derivatives. All compounds adopt a 1C4 conformation in solution according to NMR data. Compared to previously reported branched L-iminosugars, the L-iminosugar C,C-glycosides reported herein were less potent glycosidase inhibitors. However, some of these compounds showed micromolar inhibition of human lysosome β-glucocerebrosidase suggesting that such iminosugars could be useful to access potent CGase inhibitors by adjusting the structure/length of the pseudoanomeric substituents

HF-Induced Intramolecular C -Arylation and C -Alkylation/Fluorination of 2-Aminoglycopyranoses

International audienc

Toward the Supramolecular Cyclodextrin Dimers Using Nucleobase Pairs

International audienceThe synthesis of eleven new cyclodextrin derivatives having nucleobase moiety - thymin-1-yl, adenin-9-yl, and guanin-9-yl - is described. These two moieties are linked by different spacers, such as aminoethyl and 1,2,3-triazolyl group. Direct nucleophilic substitution and 1,3-dipolar cycloaddition were performed in good yields (13-73%) for some of the synthesized compounds

Synthesis and chelation study of a fluoroionophore and a glycopeptide based on an aza crown iminosugar structure

International audienceCapitalizing on a recently reported iminosugar-based aza-crown (ISAC) accessed by a double Staudinger azaWittig coupling reaction, we have expanded the structural diversity of this new family of sweet cyclam analogs. Replacement of the two secondary amines linking the iminosugar units by two amide bonds obtained a cyclodimerization by with BOP and DIPEA led to a macrocycle that did not demonstrate efficient Zn2+ chelation unlike the parent ISAC. Introduction of two pyrene moieties on the secondary amines of the parent ISAC yielded a new fluoroionophore that selectively binds Hg2+ in methanol