Collect. Czech. Chem. Commun. 2006, 71, 1532-1548

Synthesis of a 1α,4'-Di-O-allylated, 2,3,2',3'-Tetra-O-tetradecylated Lipid A Mimic and Its 4-O-(4-Methoxybenzyl) Precursor

Marek Baráth, Mária Petrušová, Ján Hirsch and Ladislav Petruš*

Institute of Chemistry, Slovak Academy of Sciences, 845 38 Bratislava, Slovakia


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-1α and C-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)-α-D-glucopyranoside (1) and methyl 4,6-O-benzylidene-α-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 β-(1→6)-glycosidic bond, α-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.

Keywords: Carbohydrates; Lipid A mimics; Trichloroacetimidate synthesis; Disaccharides; Glycosidations; Liposaccharides; Bacterial toxins.

References: 31 live references.