Synthesis of 2-Deoxy-2-[(3R)-3-Hydroxyacyl]Amino-4-O-Phosphono-3-O-[(3R)-3-Tetradecanoyloxytetradecanoyl]-D-Glucopyranose Derivatives Related to Bacterial Lipid A

ABSTRACT Lipid A subunit analogs, the 4-O-phosphono-D-glucosamine derivatives (14-16: GLA 93-95) which carry 2-N-linked 3-hydroxyacyl groups, were synthesized. 2-(Trimethylsilyl)ethyl 2-amino-2-deoxy-4,6-O-isopropylidene-s-D-glucopyranoside (1) was transformed into 2-(trimethylsilyl)ethyl 2-amino-6-O-tert-butyldimethylsilyl-2-deoxy-4-O-diphenylphosphono-3-O-[(3R)-3-tetradecanoyloxytetradecanoyl]-s-D-glucopyranoside (7) through several steps. N-Acylation of 7 with 3-hydroxyl fatty acids gave the corresponding 8-10, which were converted, via the cleavage of protecting groups, into a series of desired compounds.