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(申请人提供)：该研究项目的目标是在合成复杂生物活性分子的过程中发现和开发新的反应方法。我们建议的研究将集中在能够合成许多生物活性、多环天然产物中普遍存在的核心结构和立体化学亚基的技术的研究和优化。我们开发的工艺将用于合成各种结构，目前还没有有效的合成路线图。重要的是，本申请中提供的方法在本文描述的上下文之外将是有用的，并将为合成化学的从业者(在学术、政府和工业实验室中)配备一组新的重要工具，以访问用于合成的对映体丰富和功能多样的化学构建块。在这项赠款申请中提出的研究集中在a)开发新的由Ir和Pd催化的立体选择性烷基化反应以产生用于合成的密集取代基块，b)开发由钯催化的共轭加成过程，c)利用这些新方法来合成稠环、螺环和桥环体系阵列，以及d)这些新策略在合成多种天然和非天然生物活性小分子中的应用。具体地说，我们概述了异苯丙氨酸A、丝兰酚A-E和松柏烷二萜类化合物的合成方法。这些分子不仅从生物学角度来说很重要，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、与医学相关的结构，b)合成它们的通用平台，以及c)将影响许多不同应用的新的合成方法。