Asymmetric Synthesis of alpha-Amino Acids

本研究的重点是发展实现以下天然产物的不对称全合成所必需的合成方法：（1）甲亚胺酰亚胺偶极环加成反应在spirotryprostatin A的不对称全合成中的应用;（3）构建α，β-二氨基酸的Mannich型反应及其在卷曲霉素1B不对称全合成中的应用：（4）肽电子等排体方法的进一步发展及其在亮组素不对称全合成中的应用;（5）开发用于N-乙酰神经氨酸的不对称全合成的内酯同系物化方法;（6）开发立体选择性方法以构建具有三个连续立体中心的肽电子等排体;（7）开发制备α-烷基-异丝氨酸衍生物的方法;（8）分子内偶氮甲亚胺叶立德偶极环加成反应在palauamine不对称全合成中的应用;（9）非对映选择性羟醛和内酯官能化方法应用于奎宁的短，不对称全合成，其特征在于表面选择性分子内SN 2环化反应。科罗拉多州立大学化学系的威廉姆斯博士说。 威廉姆斯教授的工作将集中在复杂的，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学生的培训产生了广泛的影响。

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.