Practical Synthesis of a 1β-Methylcarbapenem, J-111, 225, Using 4-Mercapto-2-[4-(N-methylaminomethyl)phenyl]pyrrolidine as a Precursor

Abstract

An effective and practical procedure for the synthesis of J-111, 225 (1), a new 1β-methylcarbapenem, was developed using 4-mercapto-2-[4-(N-methylaminomethyl)phenyl]pyrrolidine (2a) as a precursor. The coupling reaction of 2a with p-nitrobenzyl (PNB)-protected 1β-methylcarbapenem enolphosphate 3a and successive removal of PNB group afforded J-111, 225 (1) in significantly increased yield compared to the ordinary procedure using a C-2 side-chain thiol with amino-protective groups.