Asymmetric Synthesis of alpha-Amino Acids

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The focus of this research will be the development of the synthetic methodology necessary to achieve the asymmetric total synthesis of the following naturalproducts: (1) azomethine ylid dipolar cycloaddition reactions as applied to the asymmetric total synthesis of spirotryprostatin A; (2) intramolecular nitrone cycloadditions as applied to cylindrospermopsin; (3) Mannich-type reactions to construct alpha, beta-diamino acids and application to the asymmetric total synthesis of capreomycin 1B; (4) further development of peptide isostere methodologies and application to the asymmetric total synthesis of leuhistin; (5) lactone homologation methodology development as applied to the asymmetric total synthesis of N-acetylneuraminic acid; (6) development of stereoselective methods to construct peptide isosteres with three contiguous stereogenic centers; (7) development of methodology to prepare alpha-alkyl-isoserine derivatives; (8) development of novel intramolecular azomethine ylid dipolar cycloaddition reactions for application to the asymmetric total synthesis of palauamine; (9) diastereoselective aldol and lactone functionalization methods for application to a short, asymmetric total synthesis of quinine featuring a facially selective intramolecular SN2 cyclization reaction.With this renewal award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Robert M. Williams of the Department of Chemistry at Colorado State University. Professor Williams will focus his work on the asymmetric synthesis of complex, optically pure, densely functionalized amino acids and amino acid derivatives. The methodology will be extended to the preparation of natural products having interesting and important biological properties. The research has broad impacts for the pharmaceutical industry and for the training of graduate and postdoctoral students.