The Synthesis of Bioactive Natural Products as a Driving Force for Discovery in Organic Chemistry

生物活性天然产物的合成作为有机化学发现的驱动力

• 批准号: 10406108
• 负责人: BRIAN M STOLTZ
• 金额: $ 37.42万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406108
• 关键词: Acylation; Alkylation; Applications Grants; Biological; Carbon; Chemicals; Chemistry; Complex; Development; Elements; Government; Human; Hydrogenation; Industrialization; Investigation; Laboratories; Medicine; Methodology; Methods; Natural Products; Organic Chemistry; Preparation; Process; Public Health; Reaction; Research; Route; Science; Structure; Synthesis Chemistry; Technology; Testing; Transition Elements; arm; bioactive natural products; driving force; new technology; novel; programs; tool

Project Summary/Abstract: The objective of this research program is to discover and develop new reaction methodology en route to the synthesis of complex bioactive molecules. Our proposed studies will focus on the investigation and optimization of technologies that enable the synthesis of core structural and stereochemical subunits prevalent in many bioactive, polycyclic natural products. The processes that we develop will find utility in the synthesis of a wide variety of structures for which there are currently no efficient synthetic roadmaps. Importantly, the methods presented in this application will be useful outside of the contexts described herein and will arm practitioners of synthetic chemistry (in academic, government, and industrial laboratories) with a new set of important tools to access enantioenriched and functionally diverse chemical building blocks for synthesis. The research proposed in this grant application is focused on a) the development of new stereoselective reactions that produce densely substituted building blocks for synthesis, b) the development of transition metal catalyzed reactions for asymmetric alkylation, acylation, and hydrogenation processes, c) the development of these novel methods specifically for the preparation of building blocks containing all-carbon quaternary stereocenters and arrays of stereocenters, and d) the implementation of these new tactics in the syntheses of highly complex, bioactive natural products. These molecules are not only important from a biological standpoint, they also serve as a testing ground for our new technologies. As a consequence of this approach, we will have access to a) novel, medicinally relevant structures, b) a general platform for their synthesis, and c) new synthetic methodology that will impact a host of diverse applications.

项目摘要/摘要： 该研究计划的目的是发现和发展新的反应 方法论在合成复杂生物活性分子的途径中。我们提出的 研究将侧重于对技术的研究和优化 在许多生物活性中普遍存在的核心结构和立体化学亚基的合成， 多环天然产品。我们开发的过程将在 当前没有高效的各种结构的综合 合成路线图。重要的是，本应用程序中介绍的方法将是 在本文所述的上下文之外有用，并将武装合成的实践者 化学（在学术，政府和工业实验室中） 访问对映体和功能多样的化学建筑的重要工具 合成的块。 本赠款申请中提出的研究重点是a） 新的立体选择反应产生密集取代的构件 合成，b）过渡金属催化反应的不对称反应的发展 烷基化，酰化和氢化过程，c）这些新颖的发展 专门用于制备包含全碳的构件的方法 第四纪立体中心和立体中心的数组，d）实施这些 高度复杂，生物活性天然产品的合成中的新策略。这些 分子不仅从生物学的角度很重要，而且还充当 我们的新技术的测试基础。由于这种方法，我们将 有访问a）新颖的药物相关结构，b）一个通用平台 综合，c）新的合成方法，将影响大量不同 申请。