Asymmetric Synthesis of Strychnos and Aspidosperma Alkaloids

Temple University, Philadelphia PA

Investigators

Abstract

AWARD ABSTRACT In this project funded by the Chemical Synthesis program of the Chemistry Division, Professor Rodrigo B. Andrade of Temple University (Department of Chemistry) is studying the development of new chemical reactions to quickly build complex nitrogen-containing molecules. An overarching goal is increasing the efficiency of making complex molecules having broad societal impact by minimizing the overall number of synthetic steps. An overwhelming number of such molecules are biologically active, and can be employed in molecular biology to understand biochemical pathways or directly applied in medicine to better understand disease on a molecular level. The chemical insight can then be applied in therapeutic regimes. To test the scope of these new methods, several complex molecules derived from nature are being prepared in the laboratory. During the development and application of these new methods, undergraduate and graduate students, including those from underrepresented groups, are being trained in the discipline of complex molecules synthesis. This project systematically studies and applies a novel domino Michael/Mannich [4+2] annulation method to the synthesis of complex molecules. In Aim 1, the nucleophilic and electrophilic components of the method are being examined to determine the reaction scope. In Aim 2, the method is applied to the asymmetric total syntheses of the Aspidospermatan-type alkaloids (+)-epi-condyfoline, (+)-condyfoline, (+)-lagunamine, (+)-epi-lagunamine, (+)-condylocarpine, (+)-isocondylocarpine, and (+)-tubotaiwine. In Aim 3, the method is used to develop the asymmetric total syntheses of the bis-Aspidosperma alkaloids (-)-conophylline and (-)-conophyllidine.