The Synthesis of Bioactive Polycyclic Natural Products

生物活性多环天然产物的合成

基本信息

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
项目类别：
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

项目摘要

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（由适用提供）：该研究计划的目的是在合成复杂的生物活性分子的途径中发现和开发新的反应方法。我们提出的研究将重点介绍技术的投资和优化，这些技术能够在许多生物活性，多环天然产物中综合核心结构和立体化学亚基。我们开发的过程将在综合各种结构中找到效用，目前尚无有效的合成路线图。重要的是，本应用程序中提出的方法将在本文所述的环境之外有用，并将使用合成化学的实践者（在学术，政府和工业实验室中）使用一套新的重要工具，以访问启用启用和功能多样的化学构建块的合成块。 The research proposed in this grant application is focused on a) the development of new iridium- and palladium-catalyzed stereoselective alcohol reactions that produce desemly 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多种天然和非天然生物活性小分子的合成中的新策略。具体而言，我们概述了用于异巴金A，Yuccaols A-E和Abietane Digital-penoids的方法。这些分子不仅从生物学的角度很重要，而且还可以作为我们新技术的测试基础。由于这种方法，我们将可以访问a）a）新颖的，药物相关的结构，b）其合成的一般平台以及c）将影响许多潜水员应用的新合成方法。