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

Incorporation of a gamma-lactone ring into the structure of carbapenems is considered as a potential "trap" for metallo-beta-lactamases that destructively act on carbapenems. New carbapenems containing a (+/-)-4,4-dimethyl-3-mercaptodihydrofuran-2(3H)-one fragment at C-3 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 [alpha](D)(20)-34 degrees 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 C-3'-H proton of the lactone with the C-4-H and C-4-Me protons of the bicyclic carbapenems. [GRAPHICS] .