Synthesis of a cyclobutanone analogue of a β-lactam antibiotic

Abstract

A route has been developed which allows cyclobutanone analogues of β-lactam antibiotics to be synthesized and is illustrated by the synthesis of 6-oxo-7β-phenylacetamido-2-oxabicyclo-[3.2.0]heptane-4α-carboxylic acid. Although this analogue (which contained some 7α-epimer) did not show significant antibacterial activity it was a weak inhibitor of Streptomyces R61 D,D-carboxypeptidase and a time-dependent inhibitor of E.coli R-TEM and B. cereus type l β-lactamases. 7β-Chloro-6-oxo-2-oxabicyclo[3.2.0]heptane-4α-carboxylic acid also exhibited time-dependent inhibition of these β-lactamases.