Asymmetric Synthesis of alpha-Amino Acids

α-氨基酸的不对称合成

• 批准号: 0202827
• 负责人: Robert Williams
• 金额: $ 41万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0202827&HistoricalAwards=false
• 关键词: Asymmetric; Synthesis; alpha; Amino; Acids

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.

本研究的重点是发展实现下列天然产物不对称全合成所需的合成方法学：(1)用于螺环前列腺素A不对称全合成的亚甲基叶立德偶极环加成反应；(2)用于柱状精胺的分子内硝酮环加成反应；(3)构建α，β-二氨基酸的Mannich反应及其在卷曲霉素1B的不对称全合成中的应用；(4)进一步发展多肽异构体方法学并应用于亮氨酸的不对称全合成；(5)内酯同源反应方法学的发展，用于N-乙酰神经氨酸的不对称全合成；(6)开发立体选择性方法以构建具有三个连续立体生成中心的多肽同位素体；(7)开发制备α-烷基-异丝氨酸衍生物的方法学；(8)开发新型分子内氨甲亚胺叶立德偶极环加成反应，应用于不对称全合成帕劳胺；(9)非对映选择性羟醛和内酯官能化方法，应用于具有面选择性分子内SN2环化反应的短的不对称奎宁全合成。威廉姆斯教授将专注于复杂的、光学纯度高、官能化程度高的氨基酸和氨基酸衍生物的不对称合成。该方法将扩展到制备具有有趣和重要生物学特性的天然产品。这项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。