Reaction of Glyconitriles with Organometallic Reagents: Access to Acyl ß-C-Glycosides.

A new strategy for the synthesis of acyl ß-C-glycosides is described. The reactivity of glyconitriles toward organometallic reagents such as organomagnesium or organolithium derivatives was studied, affording acyl ß-C-glycosides in moderate to good yields. In this study, glycal formation was efficiently prevented by deprotonating the hydroxyl group in position 2 of the glyconitriles during the process.

Synthesis and glycosidase inhibitory activity of 1-amino-3,6-anhydro-1-deoxy-D-sorbitol derivatives.

3,6-Anhydro-1-(aryl or alkylamino)-1-deoxy-D-sorbitol derivatives have been prepared in four steps from isosorbide, a by-product from the starch industry. The inhibitory activities of these new compounds have been evaluated towards 13 glycosidases. A first lead-compound was identified, which inhibited beta-N-acetylglucosaminidase from bovine kidney (82% inhibition at 1mM).

3-fluoro- and 3,3-difluoro-3,4-dideoxy-KRN7000 analogues as new potent immunostimulator agents: total synthesis and biological evaluation in human invariant natural killer T cells and mice.

We propose here the synthesis and biological evaluation of 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues 8 and 9, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T(H)1 or T(H)2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation.

Polymer-supported catalysts: enantioselective hydrogenation and hydrogen transfer reduction.

Different types of heterogenized catalysts were involved in asymmetric reactions. Hydrogen transfer reduction was performed with amino alcohols derived from poly((S)-(GMA-co-EGDMA or DVB)) and hydrogenation with BINAP grafted onto PEG or copolymerized with isocyanates as ligands. Attempts of catalysts recycling are reported.

Synthesis of a new water-soluble C(2)-symmetric chiral diamine: preliminary investigation of its catalytic properties for asymmetric hydrogenation under biphasic conditions.

A water-soluble version of N,N'-dimethyl-1,2-diphenylethane-1,2-diamine was prepared by introduction of phosphonic acid moieties on the para position of the aromatic rings. Preliminary investigation of the catalytic properties of the iridium complex of this ligand under biphasic conditions showed that this system compared well with the homogeneous counterpart for the asymmetric hydrogenation of ketones but with noticeably higher reaction rates for the biphasic system.