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：
8183101
负责人：
BRIAN M STOLTZ
金额：
$ 29.79万
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 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8183101
关键词：
Actins Alkaloids Alkylation Angiotensin II Anti-Inflammatory Agents Anti-inflammatory Antineoplastic Agents Applications Grants Architecture Area Biological Biological Factors Biology Breathing CCR5 gene California Cells Chemicals Chemistry Complex Copper Coupling Cyclosporins Development Discipline Elements Family Government HIV Human Immunosuppressive Agents In Situ Industry Inhibitory Concentration 50 Institutes Lactams Lactones Lignans Malonates Medicine Metals Methodology Methods Microfilaments Molecular Organic Synthesis Organometallic Chemistry Paclitaxel Palladium Platelet Aggregation Inhibition Platelet aggregation Preparation Process Production Reaction Research Rest Route Science Structure Synthesis Chemistry System Techniques Technology Testing Work arm base c new chemical synthesis communesin B design enolate interest leukemia metal complex method development new technology novel novel strategies programs protonation rocaglamide silvestrol small molecule tool treatment strategy

Actins Alkaloids Alkylation Angiotensin II Anti-Inflammatory Agents Anti-inflammatory Antineoplastic Agents Applications Grants Architecture Area Biological Biological Factors Biology Breathing CCR5 gene California Cells Chemicals Chemistry Complex Copper Coupling Cyclosporins Development Discipline Elements Family Government HIV Human Immunosuppressive Agents In Situ Industry Inhibitory Concentration 50 Institutes Lactams Lactones Lignans Malonates Medicine Metals Methodology Methods Microfilaments Molecular Organic Synthesis Organometallic Chemistry Paclitaxel Palladium Platelet Aggregation Inhibition Platelet aggregation Preparation Process Production Reaction Research Rest Route Science Structure Synthesis Chemistry System Techniques Technology Testing Work arm base c new chemical synthesis communesin B design enolate interest leukemia metal complex method development new technology novel novel strategies programs protonation rocaglamide silvestrol small molecule tool treatment strategy

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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 development of methods 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 academics, government, and industry) with a new set of important tools to access crucial building blocks for synthesis. The research proposed in this grant application is focused on a) the development of new palladium- and copper-catalyzed enantio-selective alkylation and protonation reactions that produce important building blocks for synthesis, b) the utilization of these novel methods for the synthesis of fused, spiro, and bridged ring system arrays, and c) the implementation of these new tools in the syntheses of numerous natural and non-natural bioactive small molecules. Specifically, we outline approaches to variecolin, przewalskin B, the rocaglate lignans, and the communesin alkaloids. These molecules are important from a biological standpoint, but 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 benefit a host of diverse applications. PUBLIC HEALTH RELEVANCE: At the core of chemistry rests the power to manipulate the elements for the preparation of specific arrays of atoms in a predictable and reliable fashion. As synthetic chemists, our capacity to construct molecules with exquisite precision is unique in the sciences. In this proposal we outline a number of new approaches toward constructing important linkages and implementing these methods in highly complex situations of relevance to human medicine.

描述（由申请人提供）：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。我们提出的研究将集中于在许多生物活性，多环天然产物中普遍存在的核心结构和立体化学亚基的方法的发展。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上下文之外有用，并将使用合成化学（在学者，政府和行业中）使用一套新的重要工具来访问合成关键的构件。本赠款应用中提出的研究集中在a）开发新的钯和铜催化的对照烷基化的烷基化和质子化反应，这些反应产生了重要的构成块，b）这些新颖的方法利用这些新方法来合成这些新方法，以及这些新型，以及这些新型及其新工具的构成工具，以及c）的自然构成工具，并构成了新的工具，即构成的构成工具，构成了这些工具的构成工具，该工具是构成的。小分子。具体而言，我们概述了Variecolin，Przewalskin B，Rocaglate Lignans和Communesin生物碱的方法。从生物学的角度来看，这些分子很重要，但也是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）新的合成方法，这些方法将使许多不同的应用程序受益。公共卫生相关性：从化学的核心中，以可预测且可靠的方式来制备特定原子阵列的要素。作为合成化学家，我们以精确精度构建分子的能力在科学中是独一无二的。在此提案中，我们概述了在与人类医学相关的高度复杂情况下建立重要联系并实施这些方法的许多新方法。