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: 6989051
• 负责人: ANNA G WENZEL
• 金额: $ 3.26万
• 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 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989051
• 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。虽然烯烃复分解化学在钌亚烷基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。该提案概述了一个新的家庭的发展，容易获得的，对映选择性钌复分解催化剂，基于氨基酸手性。这些催化剂将用于实现不对称闭环复分解（ARCM），以形成不饱和杂环胺，在天然产物的制备中的重要构件。为了说明这种方法，提出了一种对映选择性路线的抗生素剂（-）-sedamine的所有四个非对映体的快速组装。此外，在这类新的易位催化剂的手性金属中心的效果将探索在控制E/Z非对映体控制烯烃交叉易位，易位在天然产物合成中的一个重要应用。