The Synthesis of Bioactive Polycyclic Natural Products

生物活性多环天然产物的合成

• 批准号: 9140046
• 负责人: BRIAN M STOLTZ
• 金额: $ 31.51万
• 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 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9140046
• 关键词: Alkylation; Applications Grants; Architecture; Area; Biological; Biology; Breathing; California; Carbon; Carbonates; Catalysis; Chemicals; Chemistry; Complex; Development; Discipline; Diterpenes; Elements; Funding; Government; Health; Human; Institutes; Investigation; Iridium; Laboratories; Medicine; Methodology; Methods; Molecular; Natural Products; Organic Synthesis; Organometallic Chemistry; Palladium; Preparation; Process; Reaction; Reagent; Research; Route; Science; Structure; Synthesis Chemistry; System; Techniques; Technology; Testing; Work; arm; c new; carbonyl group; chemical synthesis; coping; interest; new technology; novel; novel strategies; physical property; programs; small molecule; tool

 DESCRIPTION (provided by applicant): 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 is currently no efficient synthetic roadmap. 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 iridium- and palladium-catalyzed stereoselective alkylation reactions that produce densely substituted building blocks for synthesis, b) the development of palladium- catalyzed conjugate addition processes, c) the utilization of these novel methods for the synthesis of fused, spiro, and bridged ring system arrays, and d) the implementation of these new tactics in the syntheses of multiple natural and non-natural bioactive small molecules. Specifically, we outline approaches to isopalhinine A, the yuccaols A-E, and the abietane diterpenoids. 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.

 描述（由申请人提供）：本研究计划的目的是发现和开发合成复杂生物活性分子的新反应方法。我们提出的研究将集中在调查和优化的技术，使许多生物活性，多环天然产物中普遍存在的核心结构和立体化学亚基的合成。我们开发的方法将在目前没有有效合成路线图的各种结构的合成中找到实用性。重要的是，本申请中提出的方法在本文所述的背景之外将是有用的，并且将用一组新的重要工具来武装合成化学的从业者（在学术、政府和工业实验室中），以获得用于合成的对映体富集的和功能多样的化学结构单元。本授权申请中提出的研究集中在a）开发新的铱和钯催化的立体选择性烷基化反应，其产生用于合成的密集取代的结构单元，B）开发钯催化的共轭加成方法，c）利用这些新方法合成稠合、螺环和桥环体系阵列，以及d）这些新策略在多种天然和非天然生物活性小分子的合成中的实施。具体而言，我们概述了方法，isopalhinine A，丝兰A-E，和松香烷二萜。这些分子不仅从生物学的角度来看很重要，它们也是我们新技术的试验场。作为这种方法的结果，我们将获得a）新颖的、医学相关的结构，B）用于其合成的通用平台，以及c）将影响许多不同应用的新合成方法。