CHIRAL CATALYSTS DESIGNED TO CATALYZE ORGANIC REACTIONS

描述：（申请人的摘要）该计划的目标是 的发现、发展、应用和机理阐明 用于有机合成的选择性催化反应。 特别是， 这项研究的重点是催化反应，产生光学 从非手性或外消旋起始原料得到活性产物。 临界 绝对立体化学在药物功能中的重要性提供了 这一努力背后的驱动力。 我们开发手性催化剂的主要方法 涉及合成可及手性配位的设计， 化合物. 多种空间和电子可调的手性Schiff 碱配体用作催化活性的第一- 以及第二行过渡金属和主族金属。 一类重要 这些复合物中的一种，即所谓的萨伦复合物，已经被证明 有效地用于高对映选择性催化环氧化共轭 烯烃和环氧化物的开环。 通过积极的 筛选不同类型的手性配合物， 机械驱动的设计，具体的反渗透系统，这一建议 概述了一种方法，以发现清洁，实用， 对映选择性催化剂，用于极宽范围的反应， 亲核试剂和亲电试剂。 在这项研究的一个关键方面，我们还建议将这些新的 方法，以广泛的合成目标分类。 我们概述战略 用于实际产生有价值的手性结构单元， 环氧化物和氮杂环丙烷; 药物相关化合物VX-478和生物素;全合成 muconin，一种中等复杂性的天然产物;和固相 结构和功能多样性的合成， 药理学相关的图书馆 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.