Asymmetric Synthesis of Highly Functional Pyrrolidines

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This project addresses the development of new synthetic methodology for asymmetric azomethine ylide cycloadditions. By increasing the efficiency and generality of this reaction, with a particular emphasis on asymmetric synthesis, the resulting methodology will enable the efficient assembly of a variety of complex pyrrolidine structures found in many bioactive natural products and synthetic analogs. The 1,3-dipolar cycloaddition reactions to be studied will involve both acyclic and cyclic azomethine ylides. The influence of resident substrate chirality, chiral auxiliaries, and chiral catalysts on the stereochemical outcome will be examined in detail. Efficient target-oriented syntheses of the antitumor antibiotics cyanocycline A and bioxalomycin will be developed, with longer-term applicability to the synthesis of the structurally related dnacins.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Philip P. Garner of the Department of Chemistry at Case Western Reserve University. Professor Garner and his students are developing new methods for the efficient and controlled synthesis of cyclic nitrogen-containing compounds. The resulting methods are then utilized in the construction of relevant naturally occurring compounds, thereby illustrating the power of the new synthetic methods, providing access to larger quantities of compounds than may be obtained from natural sources, and facilitating the synthesis of unnatural analogues that may lead to the future discovery of next generation pharmaceuticals. The project brings together graduate and undergraduate students from diverse cultural backgrounds to work together towards common goals and provides an opportunity for graduate students to serve as mentors to the undergraduates.