ENEDIYNES AS ANTITUMOR COMPOUNDS - SYNTHESIS OF TETRAHYDROPYRIDINE DERIVATIVES

Enediyne anticancer antibiotics are a rapidly emerging class of compou nds derived from natural sources. Many synthetic approaches for the co nstruction of simpler compounds containing this pharmacophore have rec ently been published. Most of these approaches use the quinoline ring as the heterocyclic moiety. In this paper, we describe a synthetic rou te for the preparation of enediyne systems 14 and 15, which include in their structure a tetrahydropyridine ring and are related to dynemici n A. Their stereochemistries were determined using NOESY and COSY-NMR. Finally, compounds derived from linkage to intercalating carriers, su ch as a fluorene ring to enediyne 15 or a naphthalimide ring to acycli c enediyne 6, were prepared.