The Synthesis of Bioactive Polycyclic Natural Products

生物活性多环天然产物的合成

• 批准号: 10063991
• 负责人: BRIAN M STOLTZ
• 金额: $ 34.85万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-02 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063991
• 关键词: Acylation; Alkaloids; Alkylation; Anti-Cholinergics; Applications Grants; Architecture; Area; Biological; Biology; Breathing; California; Carbon; Catalysis; Chemicals; Chemistry; Complement; Complex; Copper; Development; Discipline; Elements; Government; Human; Indole Alkaloids; Industrialization; Inorganic Chemistry; Institutes; Investigation; Iridium; Laboratories; Medicine; Methodology; Methods; Molecular; Molecular Biology; Monoterpenes; Multi-Drug Resistance; Natural Products; Nickel; Organic Chemistry; Organic Synthesis; Organometallic Chemistry; Palladium; Pharmaceutical Chemistry; Preparation; Process; Production; Public Health; Reaction; Research; Rest; Route; Science; Series; Structure; Synthesis Chemistry; System; Techniques; Technology; Testing; Work; arm; c new; chemical synthesis; cytotoxic; enolate; invention; new technology; novel; novel strategies; physical property; programs; research and development; 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 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 palladium- and iridium-catalyzed stereoselective alkylation reactions that produce densely substituted, acyclic building blocks for synthesis, b) the development of novel nickel- and copper-catalysis for asymmetric alkylation and acylation processes, c) the development of these novel methods specifically for the preparation of all-carbon quaternary stereocenters and arrays of quaternary centers, and d) the implementation of these new tactics in the syntheses of highly complex, bioactive bis-indole alkaloids. Specifically, we outline approaches to leucophyllidine, strempeliopidine, and norpleiomutine. 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： 该研究计划的目标是发现和开发新的反应 合成复杂生物活性分子的方法。我们提出的 研究将侧重于技术的调查和优化，使 合成许多生物活性中普遍存在的核心结构和立体化学亚基， 多环天然产物。我们开发的流程将在以下领域发挥作用： 多种结构的合成，目前还没有有效的合成方法 路线图。重要的是，本申请中提出的方法在外部也很有用 本文描述的上下文并将武装合成化学的实践者（在 学术、政府和工业实验室）拥有一套新的重要工具 获取对映体丰富且功能多样的化学构建模块进行合成。 本拨款申请中提出的研究重点是 a) 的开发 新的钯和铱催化的立体选择性烷基化反应，产生 用于合成的密集取代的非环状结构单元，b) 新颖的开发 用于不对称烷基化和酰化过程的镍和铜催化，c) 开发这些专门用于制备全碳的新方法 四元立构中心和四元中心阵列，以及 d) 的实施 这些新策略用于合成高度复杂的生物活性双吲哚生物碱。 具体来说，我们概述了 leucophyllidine、strempelopidine 和 去甲普利奥汀。这些分子不仅从生物学角度来看很重要， 它们也是我们新技术的试验场。其结果是 方法，我们将能够获得 a) 新颖的、医学相关的结构，b) 通用的 其合成平台，以及c）将影响许多领域的新合成方法 多样化的应用。