Enantioselective Synthesis of N-Heterocyclic Rings Using Thiourea-Based Catalysts

使用硫脲基催化剂对映选择性合成 N-杂环

• 批准号: 8213379
• 负责人: Connor L Martin
• 金额: $ 2.96万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-08-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8213379
• 关键词: Anions; Binding; Catalysis; Cyclization; Development; Goals; Ions; Methods; Nitrogen; Organic Chemistry; Preparation; Property; Reaction; Research; System; Therapeutic; Thiourea; base; catalyst; drug development; drug discovery; public health relevance; tool; vinylsilane

DESCRIPTION (provided by applicant): The development of new catalytic methods for stereocontrolled synthesis of bioactive compounds is an important goal of modern organic chemistry. The aim of the proposed research is to apply chiral thiourea- based catalysts to the development of new methods for the enantioselective synthesis of nitrogen-containing heterocycles. Specifically, this research seeks to extend the scope of the anion binding mode of thiourea catalysis, which has been applied in highly enantioselective arene-N-acyliminium ion cyclization reactions, to enantioselective cyclizations of non-aromatic @-nucleophiles onto prochiral N-acyliminium ions. New chiral thiourea catalysts will be prepared and examined in the context of several alternate modes of cyclization involving allyl- and vinylsilane nucleophiles. Because nitrogen-containing heterocycles are structural features of many natural and synthetic bioactive compounds with therapeutic properties, it is anticipated that the proposed research will provide chemists with useful new tools for the preparation of bioactive compounds and find applications in drug discovery and development. PUBLIC HEALTH RELEVANCE: The purpose of the proposed research is to apply thiourea-based catalysts to the development of new enantioselective methods for the synthesis of nitrogen-containing ring systems. As nitrogen-containing ring systems are commonly found in bioactive compounds, it is anticipated that the proposed research will ultimately provide chemists with new tools for the stereoselective synthesis of bioactive compounds and find applications in drug discovery and development.

描述（由申请人提供）：开发立体控制合成生物活性化合物的新催化方法是现代有机化学的重要目标。本研究的目的是将手性硫脲基催化剂应用于含氮杂环化合物的不对称选择性合成。具体而言，本研究旨在将硫脲催化的阴离子结合模式的应用范围扩展到非芳香亲核试剂与前手性N-酰基咪唑离子的对映选择性环化反应中，该模式已应用于高对映选择性的芳烃-N-酰基咪唑离子环化反应中.新的手性硫脲催化剂的制备和审查的情况下，涉及烯丙基和乙烯基硅烷亲核试剂环化的几种替代模式。由于含氮杂环是许多天然和合成的具有治疗性质的生物活性化合物的结构特征，预计所提出的研究将为化学家提供有用的新工具，用于制备生物活性化合物，并在药物发现和开发中找到应用。 公共卫生相关性：本研究的目的是将硫脲类催化剂应用于含氮环体系的对映选择性合成。由于含氮环系统通常存在于生物活性化合物中，预计拟议的研究将最终为化学家提供生物活性化合物的立体选择性合成的新工具，并在药物发现和开发中找到应用。