Enediynes as antitumor compounds: Synthesis of tetrahydropyridine derivatives

Enediyne anticancer antibiotics are a rapidly emerging class of compounds derived from natural sources. Many synthetic approaches for the construction of simpler compounds containing this pharmacophore have recently been published. Most of these approaches use the quinoline ring as the heterocyclic moiety. In this paper, we describe a synthetic route for the preparation of enediyne systems 14 and 15, which include in their structure a tetrahydropyridine ring and are related to dynemicin A. Their stereochemistries were determined using NOESY and COSY-NMR. Finally, compounds derived from linkage to intercalating carriers, such as a fluorene ring to enediyne 15 or a naphthalimide ring to acyclic enediyne 6, were prepared.