? This research program focuses on the development of new synthetic strategies for the synthesis of complex biologically active alkaloid natural products. The objective is not only to simply achieve the total syntheses of biologically relevant natural product targets, but also to explore and develop new synthetic approaches and reactions to address specific challenges in synthetic organic chemistry. The antiabortifacient asparagamine A, the anti-leukemic Cephalotaxus esters deoxyharringtonine and drupangtonine, and the potent vaso-dilator kobusine are the targets for chemical synthesis. All of these natural products exhibit potent yet distinct biological activities; however, they are all structurally characterized by a pyrrolidine ring embedded within a complex polycyclic architecture. This research program will investigate new methods and strategies for functionalized nitrogen-heterocycle synthesis, including azomethine ylide generation and cycloaddition via the O-sulfonylation or O-acylation of vinylogous amides for the preparation of complex pyrrolidines, as well as strain-accelerated [3,3]-sigmatropic rearrangement for the synthesis of complex benzazepines. Successful synthesis of these target molecules will not only lay the foundation for efficient and practical strategies for complex alkaloid synthesis, but will also provide access to rare natural products of biological interest and therapeutic potential in a variety of health areas, including: (1) the prevention of health risks associated with pre-term labor; (2) the treatment of leukemia; and (3) the treatment of high blood pressure and congestive heart failure induced by vasoconstriction. ? ?
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