The indole alkaloids as anti-neoplastic pharmaceuticals are introduced. A general synthetic scheme for the preparation of the indole alkaloids and analogous compounds that can be evaluated for use in cancer chemotherapy is proposed. The key step in this general synthetic method involves the preparation of nitrogen-substituted 1,2- dihydropyridines. Previous work from other laboratories has implicated these intermediates in the biosynthesis of the indole alkaloids. These results suggest that an efficient and versatile synthesis of indole alkaloids and related compounds can be accomplished using nitrogen- substituted dihydropyridines. The diverse reactivity of dihydropyridines and the difficulties of incorporationg this ring system in a synthetic scheme are discussed. New synthetic methods for nitrogen- substituted dihydropyridines are proposed and techniques for masking the reactive dihydropyridine ring so that they can be used in a complex synthetic scheme are developed.
NIH ExPorter
NIH ExPorter