Total Synthesis of a Novel 2‐Thiabicyclo[3.2.0]heptan‐6‐one Analogue of Penicillin N.

Abstract

Abstract A route has been developed which allows synthesis of novel cyclobutanone analogues of penicillin. This is illustrated by the synthesis of (1R,4R,5R,5′R,7S)-( 1b ) and (1S,4S,5S,5′R,7R)-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.