Development of synthetic methodologies to access novel fused polycyclic frameworks

杂环化合物是一类结构多样的重要分子，广泛存在于各种合成药物、生物活性天然产物、药品、农用化学品和其他商业材料中。其中，吲哚核心被广泛认为是“特权框架”，是许多天然产物和生物活性化合物中普遍存在的亚结构。由于其特殊的意义，吲哚基多环化合物作为药物化学家开发治疗剂的基石而受到特别的关注。围绕吲哚核心的大量生物活性继续成为寻找有用化合物和增加杂环多样性的新方法发展的推动力。因此，开发具有多种取代型的吲哚的高效实用的合成方法具有重要意义。我的研究计划的目标是探索和发展具有多种取代模式的吲哚-融合多环杂环的新颖高效的合成方法。为了实现这一目标，我建议利用过渡金属催化的化学，具有C-C多键的底物，反应中间体和级联/多米诺环加成反应。长期目标是将我的项目扩展到天然产物，药物制剂和独特材料合成，同时将方法开发方面多样化到其他重要的杂环。提出的研究将导致新颖的基于吲哚的分子结构，具有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作为模板，根据基于靶标的合成方法合成所需框架的化合物。将特别关注将绿色特性（例如，清洁和定量转化，温和的条件，催化剂回收，原子经济，一锅级联反应和低废物产生）与我实验室开发的方法相结合，以提高其实际和商业重要性。在这一过程中，培养高素质的人才将是至关重要的，我们将秉承公平、多元化和包容的价值观。

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.