SYNTHESIS OF ANTINEOPLASTIC CHEMOTHERAPEUTIC AGENTS

Virtually all of the chemistry related to this research program has its genesis in and its ultimate long range goal as the total synthesis of natural products which are -- either directly themselves or as members of families of natural compounds -- of immediate interest and of potential use deriving from their biological properties as antineoplastic agents. It is hoped that in the course of such research, synthesis routes emerge which either provide directly or allow others access to intermediate compounds, derivatives, and analogs which will be candidates for testing of biological activity. The specific compounds to be studied include Allamandin (A), Bactobolin (B), Sesbanimide (C) and Echinosporin (D). Key chemical features of these syntheses include study of the intramolecular photochemical 2 + 2 cycloaddition of Beta-alkenylamino-Alpha-formylacrylates; new route to chiral, hydroxylated, cyclohexenone derivatives; nuclophilic additions of the enolate anions from Alpha-acylaminoacetone analogs; a method for control of 1, 3-stereorelationships across a C(2)-keto group; a symmetry controlled approach to D in which the symmetry is broken by thermodynamic preference for one of three interconvertible hydrocarbon skeletons; and the elaboration of pyruvate ester derivatives to synthetic advantage.