A practical conversion of an azetidinone to penem: Synthesis of Sch 34343

Abstract

A synthesis of penems from azetidinone 1 is described in detail. This synthesis is used to prepare multikilo batches of (5R,6S)-2-[[-(carbamoyloxy)ethyl]thio]-6-[(R)-1-hydroxyethyl]penem-3-carboxylic acid (10), (Sch 34343). It is practical as all chemical steps progress in high yields, and isolation of all unstable intermediates is avoided. The eight step conversion of (3S,4R)-3-[(R)-1-hydroxyethyl]-4-triphenylmethylthio-2-azetidinone (1) to penem 10 via intermediacy of stable, solid (3S,4R)-1-[[(allyloxy)carbonyl]methyl]-3[(R)-hydroxyethyl]-4- (argentiothio)-2-azetidinone (4), and (3S,4R)-1-[[(allyloxy)carbonyl]methyl]-3- [(R)-1-hydroxyethyl]-4-β-naphthoxy (thiocarbonyl)thio-2-azetidinone (5) is achieved in 43% yield.