Nuclear analogs of β-lactam antibiotics. II. Synthesis of O-2-isocephems

Abstract
The preparation by total synthesis of a new class of .beta.-lactam antibiotics is reported. Conversion of alcohol 1b to its mesylate followed by hydrolysis of the acetal to the enol 1b and base-catalyzed ring closure gave benzyl 7-.beta.-azido-.DELTA.3-O-2-isocephem-4-carboxylate. Similarly prepared were the 3-methyl, 3-benzyl, and 3-phenethyl analogs. Reduction of the azides followed by coupling of the resultant amines with phenoxyacetic acid and removal of the benzyl groups by hydrogenolysis gave acids which exhibited high antibacterial activity. Structural assignments to the O-2-isocephems which were made on the basis of their spectral characteristics (IR, UV and NMR) are discussed.

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