Novel Ruthenium Catalysts for Metathesis Stereocontrol

描述（由申请人提供）：由于立体异构体表现出的生理特性的多样性，现在要求在药物团的合成中进行对映选择性和非对映选择性控制。虽然烯烃复分解化学在烷基烯钌催化剂的开发中经历了一次复兴，但一般的立体化学控制仍然是一个挑战。本提案概述了基于氨基酸手性的新家族易于获得的对映选择性钌复分解催化剂的发展。这些催化剂将用于不对称合环复合反应（ARCM）生成不饱和杂环胺，这是制备天然产物的重要组成部分。为了说明这种方法，提出了一种快速组装抗生素剂(-)-sedamine的所有四种非对映体的对映选择途径。此外，还将探讨手性金属中心在这类新型反应催化剂中的作用，以控制烯烃交叉反应中的E/Z非对映控制，这是天然产物合成中的重要应用。

DESCRIPTION (provided by applicant): Enantioselective and diastereoselective control in the synthesis of pharmacophores is now mandated due to the diversity of physiological properties exhibited by stereoisomers. Although olefin metathesis chemistry has undergone a renaissance in the development of ruthenium alkylidene catalysts, general stereochemical control remains a challenge. This proposal outlines the development of a new family of readily accessible, enantioselective ruthenium metathesis catalysts, based on amino acid chirality. These catalysts will be used to effect asymmetric ring closing metathesis (ARCM) to form unsaturated heterocyclic amines, important building blocks in the preparation of natural products. To illustrate this methodology, an enantioselective route for the rapid assembly of all four diastereomers of the antibiotic agent (-)-sedamine is proposed. Additionally, the effect of the chiral metal center in this new class of metathesis catalysts will be explored in controlling E/Z diastereocontrol in olefin cross-metathesis, an important application of metathesis in natural product synthesis.