Synthesis and structure determination of diastereomeric carbapenems in the AdNE-reaction of (±)-4,4-dimethyl-3-mercaptodihydrofuran-2(3H)-one with chiral carbapenem enol phosphate

Abstract

Incorporation of a γ-lactone ring into the structure of carbapenems is considered as a potential “trap” for metallo-β-lactamases that destructively act on carbapenems. New carbapenems containing a (±)-4,4-dimethyl-3-mercaptodihydrofuran-2(3H)-one fragment at C3 have been synthesized. On chromatographing a mixture of the diastereomeric carbapenems on a column with silica gel deactivated with NEt3, a change of the ratio of isomers occurs. The remaining enantiomerically enriched (3S)-4,4-dimethyl-3-mercaptodihydrofuran-2(3H)-one with [α ]20D-34o was also isolated. The determining factor in the structural assignment of the diastereomeric carbapenems was the presence, in both diastereomers, of NOE interactions between the C3'-H proton of the lactone with the C4-H and C4-Me protons of the bicyclic carbapenems.