Studies related to penicillins and cephalosporins. Part 6. Synthesis of the (±)-dinorpenicillin-spirocyclopentane system

Abstract

Diphenylmethyl and benzyl esters of (±)-6-azido-3-carboxypenam-2-spirocyctopentanes (18) and (20)–(23) have been obtained in a multi-step synthesis from 2-amino-2-(1-mercaptocyclopentyl)acetic acid (1). The penam backbone was completed through the formation of the 1,5-bond in a reductive annulation of chlorosulphenyt chlorides (14)–(17) with tin(II) chloride. The parent non-fused β-lactams (8)–(11) were prepared from diphenylmethyl or benzyl [1-(p-methoxybenzylthio)cyclopentyl]-2-[(methylthio)methylimino]acetate, (6) or (7), azidoacetyl chloride, and triethylamine. When (6) was used in this reaction, the 2-methylthio-3-azidoacetylthiazolidine-5-spirocyclopentanecarboxylic ester (12) and diphenylmethyl 2-azidoacetylamino-2-[(1-p-methoxybenzylthio)cyclopentyl]acetate (13) were isolated as by-products.