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Development of New Strategies for Chemical Synthesis and Study of Complex Natural Products

化学合成新策略的开发和复杂天然产物的研究

基本信息

批准号：
10797757
负责人：
Mohammad Movassaghi
金额：
$ 5.87万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

项目摘要

Project Summary/Abstract The detailed study of the fundamental chemistry and biological properties of complex natural products provides critical insight toward understanding their mode of action and enables development of new approaches for treatment of various human ailments. This research program focuses on the development of efficient and concise strategies for the total chemical syntheses of structurally complex and biologically active natural products. The target compounds are selected based on novelty of molecular architecture and associated challenges, paucity of prior synthetic studies, abundance of opportunities for development of new synthetic strategies and methodologies, possession of significant biological activity, and the potential for future chemical and biological studies. The systematic discovery, development, and application of new synthetic strategies and methodologies explored in this program continue to provide synthetic samples of rare and precious compounds for structure validation and detailed examination of their chemistry and biology. This program focuses on synthetic studies of the rich families of complex natural products including cyclotryptamine, diketopiperazine, and monoterpene indole alkaloids. A central interest is the development of generalizable directed, regioselective, stereoselective, and efficient union of complex fragments providing late-stage couplings to secure challenging linkages, including complete stereocontrol at quaternary stereogenic centers. Convergent and guided assembly of advanced fragments is complemented by development and application of new highly selective chemical transformations for the rapid generation of molecular complexity. These transformations include new methods for amide derivatization, azaheterocycle syntheses, cascade bond–forming reactions involving enamines, stereoretentive hydroxylation of complex substrates, and stereocontrolled sulfidation made possible through employing new reagents and conditions developed in this program. This program's access to potently bioactive collection of families of complex alkaloids and related derivatives continues to enables exciting biochemical collaborative investigations. The array of synthetic molecules accessed through this program behold great promise as new bioactive compounds and mechanistic tools, and these compounds are continually evaluated and examined through multidisciplinary collaborations.

项目总结/摘要详细研究复杂天然产物的基本化学和生物学性质，产品提供了关键的洞察力，有助于理解其行动模式，开发治疗各种人类疾病的新方法。本研究该计划的重点是制定有效和简洁的战略，为总化学合成结构复杂和具有生物活性的天然产物。目标化合物的选择基于分子结构的新奇和相关的挑战，缺乏以前的合成研究，丰富的发展机会，新的合成策略和方法，具有显著的生物活性，以及未来化学和生物学研究的潜力。系统的发现，开发和应用新的合成策略和方法，计划继续提供稀有和珍贵化合物的合成样品，验证和详细检查它们的化学和生物学。该计划的重点是包括环色胺在内的复杂天然产物的丰富家族的合成研究，二酮哌嗪和单萜吲哚生物碱。一个核心利益是发展可推广的定向的、区域选择性的、立体选择性的和有效的络合物的结合碎片提供后期耦合，以确保具有挑战性的联系，包括完整的四元立体中心的立体控制。会聚和引导组装先进的片段是通过开发和应用新的高选择性的化学转化，快速生成复杂的分子。这些转化包括酰胺衍生化，氮杂杂环合成，涉及烯胺的级联成键反应，络合物的立体保留羟基化通过使用新试剂，在这个项目中开发的条件。这个项目可以获得复杂生物碱和相关衍生物家族的集合继续使令人兴奋的生物化学合作研究。通过访问的合成分子阵列该计划作为新的生物活性化合物和机械工具，这些化合物通过多学科的方法不断进行评估和检查，合作。