2-Thioalkyl Penems: An Efficient Synthesis of Sulopenem, a (5R,6S)-6-(1(R)-Hydroxyethyl)-2--2-penem Antibacterial

Article abstract of DOI:10.1021/jo00042a010

A practical synthesis of potent penem antibacterials, CP-70,429 (1) (sulopenam) and CP-81,054 (2), is described. (L)-Aspartic acid was utilized to generate both the (3S)- and (3R)-thiolanylthio side chains of (5R,6S)-6-(1-(R)-hydroxyethyl)-2-<(cis-1-oxo-3-thiolanyl)thio>-2-penem-3-carboxylic acids 1 and 2.This synthetic pathway provided in high yield enantiopure thioacetate intermediates 15 and 19.To accommodate the fragile side chain sulfoxide moiety of the targeted β-lactams, standard penem synthetic methodology was modified to facilitate the conversion of 15 and 19 to 1 and 2.The reactive chloroazetidinone 4b was utilized to generate key azetidinone trithiocarbonate intermediate 22 which contains the requisite penem side chain.A chemoselective oxalofluoride-based azetidinone N-acylation procedure, which avoids sulfoxide O-acylation, was required for the conversion of 22 to the penem framework.