Synthesis of a β-lactam related to the cephalosporins

Abstract

An improved synthesis of pyrrolidine-2,4-dione (tetramic acid) is described. The addition of its 3-diazo-derivative to dibenzyl acetylenedicarboxylate gave a mixture of (E)- and (Z)-adducts. U.v. irradiation of the mixture promoted both the photolytic Wolff rearrangement and the isomerisation of the (Z)- to the (E)-isomer, so that in the presence of t-butyl carbazate a single β-lactam (8) was obtained. Transformation of the t-butoxycarbonylhydrazide into a phenylacetamido side-chain was accomplished by a previously used procedure, and catalytic hydrogenolysis of the benzyl ester groups gave 2-(2-oxo-3-phenylacetamidoazetidin-1-yl)maleic acid (3; R = H).