Methods for and Synthesis of Natural Product Hybrids for Medicinal Chemistry Applications

本建议涉及与合成有机化学科学有关的化学。有机化学是一门研究有机（即主要由碳、氢、氮和氧原子构成）分子结构的科学。就像建筑师设计建筑，工程师和建筑工人根据设计来建造一样，合成有机化学家设计通往有机分子的路线，并构建有机分子。由于自然界创造的有机分子的复杂性，合成有机化学家需要新的方法（工具）来构建这些新分子。一旦这些工具被设计出来，它们就会在复杂的分子合成过程中进行测试。**本研究项目包括新方法的开发，可用于生产化合物，以增加对人类疾病的了解或治疗。催化的基本问题包括研究催化炔-二烯Diels-Alder过程（Rh或Ni），利用Csp亲核试剂（Pd）拦截有机金属碎片，双吲哚（Rh）的串联活化和双吲哚（Pd）的串联形成。功能性天然产物如分子（基于高度生物活性天然产物）将用于探索与人类健康有关的生物结构，特别是疟疾和癌症。**所描述的研究将为对学术、工业和生物技术职位感兴趣的HQP提供重要的高级培训。接受过这些技术培训的HQP通常会在与新药物和新材料的发现相关的领域工作。因此，通过在合成有机化学领域训练的HQP的努力，社会得到了许多好处。

This proposal deals with chemistry related to the science of synthetic organic chemistry. The science of organic chemistry is the science that examines the construction of organic (meaning built mostly of carbon, hydrogen, nitrogen and oxygen atoms) molecules. Similar to an architect designing a building, and engineers and construction workers building it based on that design, synthetic organic chemists design routes to, and build, organic molecules. Because of the complexity of organic molecules that Nature makes, synthetic organic chemists require new methods (the tools) to build these new molecules. Once these tools are designed, they are tested in the course of a complex molecule synthesis. **This research program embraces the development of new methodology that can be harnessed to produce compounds with a goal for increased understanding, or treatment, of human disease. Fundamental questions in catalysis include the study of catalyzed alkyne-diene Diels-Alder processes (Rh or Ni), interception of organometallic fragments using Csp nucleophiles (Pd), tandem activations of bisindoles (Rh) and tandem formations of bisindoles (Pd). Functional natural product like molecules (based on highly bioactive natural products) will be used to explore biological constructs related to human health, specifically malaria and cancer. **The described research will provide crucial advanced training for HQP interested in academic, industrial and biotechnology positions. HQP trained in these techniques traditionally end up working in fields related to the discovery of new medicines and new materials. Consequently, society receives many benefits through the efforts of HQP trained in the field of synthetic organic chemistry.