Abstract
The stereoselective synthesis of 2α-methyl-and 2β-methyl-3-(substituted methyl)-cephalosporins via 2-methyl-3-formyloxymethylceph-2-em (5) and 2-methyl-3-acetoxymethylceph-2-em (16) from 2-methylene-3-acetoxymethylcephalosporin (1) is described. Reduction of 1 with zinc in acetic acid gave 2, 3-dimethylenecepham (2), while reduction with zinc in formic acid gave 5 and reduction with sodium borohydride gave 16. Hydrolysis of 5 gave 2-methyl-3-hydroxymethylceph-2-em (6), which was stereoselectively converted via 2-methyl-3-(heterocyclic thiomethyl) ceph-2-em (8) and 2-methyl-3-formyl-ceph-2-em (12) into the corresponding 2α-methyl-3-(substituted methyl) ceph-3-ems by oxidation with peracid. On the other hand, isomerization of 16 to the corresponding ceph-3-em by oxidation with peracid gave mainly the 2β-methyl isomer (55 : 1 ratio). Ozonolysis of 2 followed by treatment with diazomethane gave 2-oxo-3-methoxyceph-3-em (24).
