Nuclear analogs of β-lactam antibiotics. III. Synthesis of 1,3-dimethyl-Δ3-O-2-isocephems

Abstract

The synthesis of 1-.alpha.-methyl and 1-.beta.-methyl isomers of 7-.beta.-phenoxyacetamido-1,3-dimethyl-.DELTA.3 -0-2-isocephem-4-carboxylic acids (14.alpha. and 14.beta.) is described. Treatment of the amine with methacrolein followed by cycloaddition gave a compound which was ozonolyzed to yield the methyl ketones 6. Upon reduction of 6 there was obtained a mixture of isomeric alcohols which were resolved by column chromatography, converted to their mesylates and hydrolyzed. Conversion of each isomer to the corresponding 0-2-isocephems, followed by azide reduction, coupling of the amines to phenoxyacetic acid and removal of the ester blocking groups gave 14.alpha. and 14.beta.. An attempt to prepare the gem-dimethyl compound failed. The structural assignments to 14.alpha. and 14.beta.. are discussed.