SYNTHESIS OF A 1alpha,4-DI-O-ALLYLATED,2,3,2',3'TETRA-O-TETRADECYLATED LIPID A MIMIC AND ITS 4-O-(4-METHOXYBENZYL) PRECURSOR

摘要

Compound 18 mimicking lipid A,containing D-glucose instead of D-glucosamine moieties in its gentiobiose skeleton,O-tetradecyl groups at the C-2,C-3,C-2' and C-3' instead of the ester-and amide-linked fatty acids,and O-allyl groups at the C-1alpha and G-4' replacing the phosphate groups,was synthesized by the Schmidt trichloroacetamidate method in a combined 8% yield of 13 steps.Allyl 4,6-O-(4-methoxybenzylidene)-alpha-D-glucopyranoside (1) and methyl 4,6-O-benzylidene-alpha-D-glucopyranoside (4) were starting materials for preparation of the respective O-alkylated and O-allylated glycosyl donor and sugar nucleophile.While boron trifluoride etherate in dichloromethane catalysed a highly preferential formation of the required beta-(1->6)-glycosidic bond,alpha-linked lipidodisaccharide was a major product when trimethylsilyl trifluoromethanesulfonate was used as a catalyst,in both cases independently of the anomeric configuration of the starting imidate.Prolonged treatment with acid catalysts in the coupling step was exploited also for a one-pot removal of the intermediate 4-O-(4-methoxybenzyl) protection of the target mimic 18 of lipid A.