The Synthesis of Bioactive Natural Products as a Driving Force for Discovery in Organic Chemistry

生物活性天然产物的合成作为有机化学发现的驱动力

基本信息

批准号：
10406108
负责人：
BRIAN M STOLTZ
金额：
$ 37.42万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2027-03-31
项目状态：
未结题

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 wide 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 stereoselective reactions that produce densely substituted building blocks for synthesis, b) the development of transition metal catalyzed reactions for asymmetric alkylation, acylation, and hydrogenation processes, c) the development of these novel methods specifically for the preparation of building blocks containing all-carbon quaternary stereocenters and arrays of stereocenters, and d) the implementation of these new tactics in the syntheses of highly complex, bioactive natural products. 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：合成目前尚无有效方法的多种结构综合路线图。重要的是，本申请中提出的方法将是在本文描述的上下文之外有用，并将武装合成的实践者化学（在学术、政府和工业实验室）与一套新的获得对映体丰富且功能多样的化学结构的重要工具用于合成的块。本拨款申请中提出的研究重点是 a) 的开发新的立体选择性反应，产生密集取代的结构单元合成，b）过渡金属催化不对称反应的发展烷基化、酰化和氢化过程，c) 这些新型化合物的开发专门用于制备含全碳结构单元的方法四元立体中心和立体中心阵列，以及 d) 这些的实现合成高度复杂的生物活性天然产物的新策略。这些分子不仅从生物学的角度来看很重要，而且还充当我们新技术的试验场。作为这种方法的结果，我们将可以访问 a) 新颖的、医学相关的结构，b) 一个通用平台合成，以及c）新的合成方法将影响许多不同的领域应用程序。