Nuclear analogs of β-lactam antibiotics. VII. Synthesis of 2-isocephems

Abstract

The synthesis of 7-β-phenoxyacetamido-3-methyl-Δ3-2-isocephem-4-carboxylic acid 14b and its corresponding α-sulfoxide 15 and sulfone 17 is described. Treatment of the bismesylates 4a, 4b, and 10 with hydrogen sulfide triethylamine gave the corresponding 7-β-amino-Δ3-2-isocephems 12a–c which were coupled with phenoxyacetic acid to yield the amides 13a–c. Hydrogenolysis of 13b and c gave the acids 14a–b which were active as antibiotics. Compound 14b was oxidized to its sulfoxide 15 with sodium metaperiodate and to its sulfone 17 with m-chloroperbenzoic acid. Conversion of 13c to its sulfoxide 16b followed by halogenation gave the 1α-chloro sulfoxide 18 which was converted to the acid 19. The stereochemical assignments in the 2-isocephem series are discussed.