The total synthesis of a nuclear analogue of the penicillin—cephalosporin antibiotics

Abstract

A route has been developed for the synthesis of nuclear analogues of the penicillins and cephalosporins from heterocyclic α-amino-acids. The route is illustrated by the synthesis of (2R,6R,7S)-8-oxo-7-phenylacetamido-1-azabicyclo[4,2,0]octane-2-carboxylic acid (19) from pyridine-2-carboxylic acid. A key step in the synthesis involves the photolysis of a diazo-compound and stereoselective intramolecular insertion by the transient carbene intermediate, so generating the required fused β-lactam heterocyclic system.