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

这项建议涉及与合成有机化学有关的化学。有机化学是一门研究有机分子(主要由碳、氢、氮和氧原子构成)结构的科学。就像建筑师设计一座建筑，工程师和建筑工人在设计的基础上建造它一样，合成有机化学家设计并制造有机分子的路线。由于大自然制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。**这项研究计划包括开发新的方法学，可以用来生产化合物，目标是增加对人类疾病的理解或治疗。催化的基本问题包括催化的炔二烯Diels-Alder过程(Rh或Ni)，用CSP亲核试剂(Pd)截留金属有机碎片，双吲哚的串联活化(Rh)和串联形成双吲哚(Pd)。功能性天然产物等分子(基于高度生物活性的天然产物)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。**上述研究将为对学术、工业和生物技术职位感兴趣的HQP提供至关重要的高级培训。传统上，接受过这些技术培训的HQP最终会在与新药和新材料发现相关的领域工作。因此，通过在合成有机化学领域接受培训的HQP的努力，社会获得了许多好处。

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.