Total synthesis of a novel 2-thiabicyclo[3.2.0]heptan-6-one analogue of penicillin N

Abstract

A route has been developed which allows synthesis of novel cyclobutanone analogues of penicillin. This is illustrated by the synthesis of (1 R,4 R,5 R,5′ R,7 S)-( 1b ) and (1 S,4 S,5 S,5′ R,7 R)-7-[5′-amino-5′-carboxy]pentanamido]-2-thiabicyclo[3.2.0]heptan-6-one-4-carboxylate ( 1a ), an analogue of penicillin N. The key steps in the synthesis were the formation of the bicyclic structure via a [2+2] cycloaddition and the introduction of nitrogen at C7 via an intramolecular nitrene insertion.