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

项目摘要/摘要： 这项研究计划的目标是发现和发展新的反应 合成复杂生物活性分子的方法学。我们的建议 研究的重点将是调查和优化能够使 合成许多生物活性物质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 合成各种各样的结构，目前还没有有效的方法 人工合成路线图。重要的是，本申请中提供的方法将是 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)，有一套新的 获取对映体丰富和功能多样化的化学建筑的重要工具 用于合成的块。 在这项赠款申请中提出的研究重点是a)发展 新的立体选择性反应，可产生密集取代的 B)过渡金属催化不对称反应的研究进展 烷基化、酰化和氢化工艺，c)这些新工艺的发展 专门用于制备含全碳的积木的方法 第四级立体中心和立体中心阵列，以及d)这些 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说很重要，它们也是一种 我们新技术的试验场。作为这种方法的结果，我们将 有机会获得a)新颖的、与医学相关的结构，b)为他们的 合成，以及c)新的合成方法，将影响许多不同的 申请。

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.