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

项目概要/摘要： 本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学。我们提出的 研究将集中在调查和优化技术，使 在许多生物活性， 多环天然产物。我们开发的过程将在 合成了目前没有有效方法的多种结构 合成路线图。重要的是，本申请中提出的方法将是 在本文所述的上下文之外是有用的，并且将武装合成药物的从业者。 化学（在学术，政府和工业实验室）与一套新的 获得对映体富集和功能多样的化学结构的重要工具 用于合成的块。 在这项拨款申请中提出的研究重点是a）开发 新的立体选择性反应，产生密集取代的积木， 合成，B）过渡金属催化的不对称合成反应的发展 烷基化、酰化和氢化方法，c）开发这些新的 专门用于制备含全碳的结构单元的方法 四元立体中心和立体中心阵列，以及d）这些的实施 高度复杂的生物活性天然产物合成的新策略。这些 分子不仅从生物学的角度来看是重要的，它们还作为一种 我们新技术的试验场由于这种做法，我们将 有机会获得a）新的、医学相关的结构，B）一个通用平台， c）新的合成方法，将影响许多不同的 应用.

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.