Development of synthetic methodologies to access novel fused polycyclic frameworks

杂环化合物是最重要的一类分子，其结构多样，并且普遍存在于各种合成药物、生物活性天然产物、药物、农用化学品和其他商业材料中。其中吲哚核被广泛认为是“特权骨架”，是许多天然产物和生物活性化合物中普遍存在的亚结构。吲哚类多环化合物由于其特殊的重要性，作为药物化学家开发治疗药物的基础材料而受到特别的关注。围绕吲哚核心的过多的生物活性继续成为开发新方法以发现有用化合物和增加杂环多样性的驱动力。因此，开发具有多种取代模式的吲哚的有效和实用的合成的需要具有重要意义。我的研究计划的目标是探索和发展新的和有效的合成方法吲哚稠多环杂环轴承各种取代模式。为了实现这一目标，我建议利用过渡金属催化，具有C-C多重键的底物，活性中间体和级联/多米诺环加成反应的化学。长期目标是将我的计划扩展到天然产物，药物制剂和独特的材料合成，同时将方法开发方面多样化到其他重要的杂环。 这些研究将导致新的吲哚为基础的分子结构与有趣的生物学特性和三维拓扑结构。这些分子还可以进一步用作模板，用于按照基于靶标的合成方法合成所需框架的化合物。特别注意将绿色属性（如，清洁和定量转化，温和的条件下，催化剂回收，原子经济，一锅级联反应，和低废物产生）在我的实验室开发的方法，以提高其实际和商业的重要性。在这一奋进中，高素质人才的培训将是至关重要的，并致力于我们的公平，多样性和包容性价值观。

Heterocyclic compounds are one of the most important classes of molecules that are structurally diverse and found ubiquitously in a variety of synthetic drugs, bioactive natural products, pharmaceuticals, agrochemicals and other commercial materials. Among them the indole core, widely regarded as "privileged framework," is a prevalent substructure in many natural products and biologically active compounds. Owing to their special significance, indole-based polycyclic compounds attract special attention as a building block for the development of therapeutic agents by medicinal chemists. A plethora of bioactivities surrounding the indole core continue to be a driving force in the development of new methodology to find useful compounds and increase the heterocyle diversity. Thus, the need for development of efficient and practical syntheses of indoles bearing a variety of substitution patterns is of great significance. The objective of my research program is to explore and develop novel and efficient synthetic methodology of indole-fused polycyclic heterocycles bearing a variety of substitution patterns. To achieve this, I am proposing to exploit the chemistries of transition metal catalysis, substrates having C-C multiple bonds, reactive intermediates and cascade/domino cycloaddition reactions. The long-term goal is to expand my program towards natural product, pharmaceutical agents and unique materials synthesis, while diversifying methodology development aspects to other important heterocycles. The proposed studies will lead to novel indole-based molecular architectures with interesting biological properties and 3-D topologies. These molecules could also further serve as template for synthesizing compounds of desired frameworks following a target based synthesis approach. Particular attention will be given to incorporating green properties (such as, clean and quantitative conversion, mild conditions, catalyst recycling, atom economy, one-pot cascade reactions, and low waste production) to methodologies developed in my laboratory in order to advance their practical and commercial importance. Training of highly qualified personnel will be of utmost importance during this endeavor with a commitment to our values of equity, diversity, and inclusion.