Novel Ruthenium Catalysts for Metathesis Stereocontrol

用于复分解立体控制的新型钌催化剂

• 批准号: 6738531
• 负责人: ANNA G WENZEL
• 金额: $ 3.97万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6738531
• 关键词: alkenes; aminoacid; catalyst; chemical synthesis; enzyme substrate; heterocyclic compounds; molecular assembly /self assembly; postdoctoral investigator; ruthenium; stereochemistry

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.

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，现在强制要求在药效团的合成中进行对映选择性和非对映选择性控制。尽管烯烃复分解化学在亚烷基钌催化剂的开发中经历了复兴，但一般的立体化学控制仍然是一个挑战。该提案概述了基于氨基酸手性的易于获得的对映选择性钌复分解催化剂新家族的开发。这些催化剂将用于实现不对称闭环复分解（ARCM），形成不饱和杂环胺，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 的所有四种非对映异构体的对映选择性途径。此外，还将探索这类新型复分解催化剂中手性金属中心在控制烯烃交叉复分解中的E/Z非对映控制方面的作用，这是复分解在天然产物合成中的重要应用。