Innovative Tools for Chemical Synthesis: Cyclase-Inspired Catalysis, Shuttle Catalysis, and Tandem Catalysis

项目总结(摘自原MIRA奖GM127071) 该研究计划的重点是通过以下途径解决化学结构和反应性方面的差距 催化的力量。受金属酶的启发，我的实验室设计、研究和发明 化学合成的创新工具，克服了对手性辅助剂和 化学计量活化剂。所提出的交叉耦合方法的特点是使用 共同的官能团(例如，醛、胺、炔烃和烯烃)，并产生新的 碳-碳和碳-氮键具有极好的原子经济性。广泛的手性 主题可以通过这种方法访问，所获得的见解最终将增强我们的 控制化学反应和构建化学结构的能力。反过来，这些知识又极大地 增强我们发现治疗人类疾病的新药以及准备 这些药物的规模很大。该计划以许多新方向为特色，由 令人信服的初步数据，包括环酶激发的催化、穿梭催化和串联 催化作用。除了实用价值外，该程序还将提供对使用的基本见解 各种催化剂，包括Rh、Ru、Co和Ni，用于活化和 碳氢键功能化--现代有机研究中的一个长期挑战 化学

Project Summary (from the original MIRA award GM127071) This research program focuses on addressing gaps in chemical structure and reactivity through the power of catalysis. Inspired by metalloenzymes, my laboratory designs, studies, and invents innovative tools for chemical synthesis that overcome the need for chiral auxiliaries and stoichiometric activating agents. The cross-coupling methods proposed feature the use of common functional groups (e.g., aldehydes, amines, alkynes, and alkenes) and generate new carbon-carbon and carbon-nitrogen bond with excellent atom economy. A wide range of chiral motifs can be accessed by this approach and the insights gained will ultimately enhance our ability to control chemical reactivity and build chemical structures. In turn, this knowledge greatly augments our ability to discover new medicines for treating human diseases, as well as prepare these medicines on large scale. The program features many new directions supported by compelling preliminary data including cyclase-inspired catalysis, shuttle catalysis, and tandem catalysis. Besides the practical value, this program will provide fundamental insights into the use of various catalysts, including rhodium, ruthenium, cobalt, and nickel, for the activation and functionalization of carbon-hydrogen bonds—a long standing challenge in modern organic chemistry