报告题目：Understanding Conformational Flexibility in Organic Chemistry by Computational Tools

报 告 人：邵慧玲 博士 加利福尼亚大学洛杉矶分校（UCLA）

报告时间：2023年7月27日 上午10:30-11:30

报告地点：勤园17-210

报告人简介：

邵慧玲，现任UCLA 兼职助理教授 ，Cram-Teacher-Scholar, Kendall N. Houk 课题组 （2022 至今）。 2019年博士毕业于美国匹兹堡大学，刘鹏课题组。2019-2021在明尼苏达大学Christopher Cramer课题组进行两年博士后研究。计划于明年入职西弗吉尼亚大学，任助理教授。

报告内容：

Analogous to dynamic effects in enzyme catalysis, the conformational flexibility of small molecules might also play a crucial role in organic chemistry. However, the dynamic nature of flexible molecules, exemplified by macrocyclic rings, poses a great challenge for experimental investigations. With advanced conformational sampling tools, we applied computational mechanistic studies to elucidate the effects of conformationally flexible molecules on reaction mechanisms in a) transition metal catalysis and b) peptide macrocyclization. First, in studying the Rh‒catalyzed alkene hydroboration reaction, we identified that a conformationally flexible TADDOL-derived phosphite ligand could effectively promote reactivity and control enantioselectivity in different elementary steps. Second, our mechanistic investigation on the intramolecular macrocyclization of peptide aldehydes revealed that conformational flexibility of the macrocyclic peptide ring, along with intramolecular hydrogen bonding, enabled a low energy, stereoselective zwitterionic mechanism. The next challenge in the field is to exploit the conformational flexibility of catalytic peptides, potentially leading to in silico design of new asymmetric peptide catalysts.