Enantiospecific synthesis of aza-analogues of the N-acetylglucosamine-N-acetylmuramic acid repeating unit in peptidoglycan

Abstract

Two substituted piperidyl glycosides, the L-alanyl-D-glutamic acid derivative 22 and the L-alanyl-γ-D-glutamyl-L-lysine derivative 25, have been prepared as aza-analogues of the repeating disaccharide unit in peptidoglycan and screened as potential antibacterial agents. Starting from diacetoneglucose 1, the synthesis of an anomeric mixture of intermediate 5-O-benzyl-N-benzyloxycarbonyl-2,6-dideoxy-2,6-imino-3-O-(4-methoxybenzyl)-D-mannofuranosides 11α/11β(α:β ratio ∼1:1) is described. Their transformation into the 1,5-dideoxy-1,5-imino-D-mannitol 15 and its corresponding β-glycoside derivative 18, a common and advanced intermediate en route to the aza-analogues 22 and 25, is also described. Neither product showed any antibacterial activity.