CHIRAL CATALYSTS DESIGNED TO CATALYZE ORGANIC REACTIONS

描述：(申请者摘要)该项目的目标是 核糖核酸的发现、发展、应用及机理阐明 用于有机合成的选择性催化反应。特别是， 这项研究的重点是光学产生的催化反应。 来自无手性或外消旋起始物质的活性产物。关键人物 绝对立体化学在药物功能中的重要性提供了主要 这一努力背后的驱动力。 我们开发手性催化剂的主要方法 涉及可合成的手性配位化合物的设计 化合物。多种空间和电子可调谐的手性席夫 碱性配体作为具有催化活性的第一和第二配体的络合物的模板。 以及第二排过渡金属和主族金属。一堂重要的课 在这些复合体中，所谓的萨伦复合体已经证明 共轭化合物的高对映选择性催化环氧化反应 环氧化物的烯烃和开环。通过组合具有侵略性的 不同类型手性配位化合物的筛选和 机械驱动的特定双金属系统的设计，这项建议 概述了发现干净、实用和 对映体选择性催化剂，用于非常广泛的反应 亲核者和亲电者。 在这项研究的一个关键方面，我们还建议将这些新的 方法可广泛应用于各种合成靶点。我们概述了战略 用于实际生成有价值的手性构建块，如 环氧化物和氮杂环丙烷的高效合成 与药物有关的化合物VX-478和生物素；全合成 丝胶蛋白，一种中等复杂性的天然产物；以及固相 合成结构和功能多样的化合物 与药理相关的图书馆。通过这样的努力，我们的目标是 提高我们发现的合成方法的相关性和实用性 生物有机和生物医学研究。

DESCRIPTION: (applicant's abstract) This program has as its objectives the discovery, development, application, and mechanistic elucidation of selective catalytic reactions of use in organic synthesis. In particular, the focus of this research is on catalytic reactions that generate optically active products from achiral or racemic starting materials. The critical importance of absolute stereochemistry in drug function provides the major driving force behind this effort. The principal approach we take to the development of chiral catalysts involves the design of synthetically accessible chiral coordination compounds. A variety of sterically and electronically tunable chiral Schiff base ligands serve as templates for complexes of catalytically-active first- and second-row transition metals and main group metals. One important class of these complexes, the so-called salen complexes, has already proven effective for highly-enantioselective catalytic epoxidation of conjugated olefins and ring-opening of epoxides. Through a combination of aggressive screening of different types of chiral coordination complexes and mechanistically-driven design of specific bimetallic systems, this proposal outlines an approach to the discovery of clean, practical, and enantioselective catalysts for an extremely wide range of reactions between nucleophiles and electrophiles. In a critical facet of this research, we also propose to apply these new methods to a broad assortment of synthetic targets. We outline strategies for the practical generation of valuable chiral building blocks such as epoxides and aziridines; the efficient synthesis of the pharmaceutically-relevant compounds VX-478 and biotin; the total synthesis of muconin, a natural product of moderate complexity; and the solid phase synthesis of structurally and functionally diverse and pharmacologically-revelant libraries. By such effort, our goal is to heighten the relevance and utility of the synthetic methods we discover to bioorganic and biomedical research.