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：
10365918
负责人：
BRIAN M STOLTZ
金额：
$ 35.12万
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 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10365918
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 chemical synthesis cytotoxic enolate invention new technology novel novel strategies physical property programs research and development tool

项目摘要

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。

项目成果

期刊论文数量（150）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（17）

The catalytic asymmetric total synthesis of elatol.

乙醇醇的催化不对称全合成。

DOI：
10.1021/ja710294k
发表时间：
2008-01-23
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
D. E. White;Ian C. Stewart;R. Grubbs;B. Stoltz
通讯作者：
B. Stoltz

Evolution of a unified, stereodivergent approach to the synthesis of communesin F and perophoramidine.

统一的、立体发散的合成 communesin F 和 perophoramidine 方法的演变。

DOI：
发表时间：
2015-01-02
期刊：
影响因子：
0
作者：
Han, Seo;Vogt, Florian;May, Jeremy A;Krishnan, Shyam;Gatti, Michele;Virgil, Scott C;Stoltz, Brian M
通讯作者：
Stoltz, Brian M

Asymmetric Synthesis of All-Carbon Quaternary Spirocycles via a Catalytic Enantioselective Allylic Alkylation Strategy.

通过催化对映选择性烯丙基烷基化策略不对称合成全碳季螺环。