Synthesis of14C-labelled 7α-methoxycephalosporin derivative (CS-1170)

Sodium 7β-Cyanomethylthioacetamido-7α-14C-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (CS-1170), a new cephamycin derivative was prepared for metabolic studies. The key reaction involves the methoxylation of the diphenylmethyl 7-(3, 4-di-tert-butyl-4-oxo-2, 5-cyclohexadien-1-ylen)-methylimino-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (I) with 14CH3OH to diphenylmethyl 7β-(3, 5-di-tert-butyl-4-hydroxybenzylideneamino)-7α-14C-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (II). Cleavage of the Schiff base, acylation followed by hydrolysis produced the desired radioactive drug. The overall radiochemical yield was 14%, at a specific activity of 12.7 uCi/mg.