Practical Synthesis of 1β-Methylcarbapenem Antibiotics : Side-Chain Substitution Reaction of 2-Arylsulfinyl and 2-Arylsulfonyl Carbapenems

Abstract

The C-2 side-chain substitution reaction of a sulfoxide and a sulfone derived from a p-nitrobenzyl (1R, 5S, 6S)-6-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-[2-(diethylcarbamoyl)phenylthio]-1-methylcarbapen-2-em-3-carboxylate with various mercaptans progressed smoothly in the presence of magnesium bromide. Bromomagnesium thiolate prepared from mercaptans proved to be especially effective for the substitution reaction and gave precursors of 1β-methylcarbapenem antibiotics in high yield.