Heterocyclic Ring Compounds for Alkaloid Synthesis

用于生物碱合成的杂环化合物

• 批准号: 7117978
• 负责人: Albert Padwa
• 金额: $ 3.82万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7117978
• 关键词: Diels Alder reaction; alkaloids; aspidosperma alkaloid; chemical addition; chemical synthesis; furans; ibogaine; method development; nitrogenous heterocyclic compound; vinca alkaloids

DESCRIPTION (provided by applicant): The overall objective of our research program involves the development of general, broadly applicable methods for the synthesis of novel heterocyclic systems. Emphasis is placed on the use of cycloaddition chemistry for the construction of a variety of biologically interesting molecules. Among the reactions to be studied are [4+2]-cycloaddition reactions of amido and thio-substituted furans and other heteroaromatics as a method for preparing novel azapolycyclic rings. The project will also focus on using a variety of novel thio reagents for intramolecular cyclization. A number of inter-and intramolecular variations of the tandem sequence will be explored which will provide access to the structural frameworks contained within the Amaryllidaceae, Aspidosperma, Erythrina, Sceletium, iboga, Ergot, Vinca and Strychnos alkaloids. These complex nitrogen containing substrates are of interest as synthetic targets due to the wide range of biological properties they exhibit. A variety of pharmacological effects, including sedative, hypotensive, neuromuscular blocking, CNS depressant and skin disorder properties are associated with these compounds. The various synthetic strategies outlined in the proposal will lead to the rapid assembly of the basic core skeleton of various alkaloids and will provide quantities of material for detailed biological assay. The generation of biologically active compounds by new synthetic methods remains an important part of both health related and chemical research.

描述（由申请人提供）：我们研究计划的总体目标涉及开发通用的、广泛适用的合成新型杂环系统的方法。重点是使用环加成化学来构建各种具有生物学意义的分子。待研究的反应包括酰胺基和硫代呋喃以及其他杂芳族化合物的[4+2]-环加成反应，作为制备新型氮杂多环的方法。该项目还将重点关注使用各种新型硫代试剂进行分子内环化。将探索串联序列的许多分子间和分子内变异，这将提供获取石蒜科、Aspidosperma、Erythrina、Sceletium、iboga、Ergot、Vinca 和 Strychnos 生物碱内包含的结构框架的途径。这些复杂的含氮底物由于它们表现出广泛的生物特性而作为合成靶标受到关注。这些化合物具有多种药理作用，包括镇静、降血压、神经肌肉阻滞、中枢神经系统抑制和皮肤病特性。该提案中概述的各种合成策略将导致各种生物碱的基本核心骨架的快速组装，并将为详细的生物测定提供大量材料。通过新的合成方法产生生物活性化合物仍然是健康相关和化学研究的重要组成部分。