Asymmetric Synthesis of alpha-Amino Acids

本研究的重点将是发展实现以下天然产物的不对称全合成所需的合成方法：(1)应用于spirotryprostatin A的不对称全合成的亚甲酰基偶极环加成反应；(2)分子内硝基环加成应用于柱精子蛋白酶；(3) mannich型反应构建α、β -二氨基酸及其在不对称全合成卷曲霉素1B中的应用；(4)多肽异构体方法的进一步发展及其在非对称全合成亮色素中的应用；(5)内酯同源化方法在n -乙酰神经氨酸不对称全合成中的应用；(6)发展立体选择方法构建具有三个连续立体中心的肽同位体；(7) α -烷基异丝氨酸衍生物制备方法的发展；(8)开发了新的分子内偶极环加成反应，应用于帕劳胺的不对称全合成；(9)非对映选择性醛醇和内酯功能化方法应用于具有表面选择性的分子内SN2环化反应的奎宁的短时间、不对称全合成。有了这个更新奖，有机和大分子化学项目支持科罗拉多州立大学化学系的罗伯特·m·威廉姆斯博士的研究。威廉姆斯教授将专注于复杂的、光学纯的、密集功能化的氨基酸和氨基酸衍生物的不对称合成。该方法将扩展到具有有趣和重要生物学特性的天然产物的制备。该研究对制药行业以及研究生和博士后的培养具有广泛的影响。

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.