Stereospecific synthesis of a novel bicyclic β-lactam

Abstract

Reductive ozonization in methanol to suitably protected 1,2-glycals of readily available D-sugars led to 4-formates of lower sugars in the aldehyde form. An aza-Wittig type reaction with 2-methoxyethoxymethyl (MEM) azide converted these aldehydes to Schiff bases with multiple chiral centers. Stereospecific cis β-lactam formation was observed on reacting these Schiff bases with benzyloxyacetyl chloride and triethylamine. Mild acid hydrolysis of the formate group in the C-4 side chain led to (1R,2S,3R,7R,8S)-1,2,8-tribenzyloxy-3-benzyloxymethyl-4-oxanonam, a bicyclic β-lactam containing a hexahydro-3-oxazepine ring. The structure and absolute configuration of this β-lactam was determined by X-ray crystallography.