Stone Elizabeth A, Hosseinzadeh Parisa, Craven Timothy W, Robertson Michael J, Han Yaodong, Hsieh Sheng-Ying, Metrano Anthony J, Baker David, Miller Scott J
Department of Chemistry, Yale University, New Haven, CT, 06520, USA.
Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
ACS Catal. 2021 Apr 16;11(8):4395-4400. doi: 10.1021/acscatal.1c01097. Epub 2021 Mar 25.
Studying the relationship between catalyst conformational dynamics and selectivity in an asymmetric reaction is a challenge. In this study, cyclic peptides were computationally designed to stabilize different ground state conformations of a highly effective, flexible tetrapeptide catalyst for the atroposelective bromination of -aryl quinazolinones. Through a combination of computational and experimental techniques, we have determined that dynamic movement of the lead catalyst plays a crucial role in achieving high enantioselectivity in the reaction of study. This approach may also serve as a valuable method for investigating the mechanism of other peptide-catalyzed transformations.
研究不对称反应中催化剂构象动力学与选择性之间的关系是一项挑战。在本研究中，通过计算设计了环状肽，以稳定一种高效、灵活的四肽催化剂的不同基态构象，用于 -芳基喹唑啉酮的阻转选择性溴化反应。通过计算和实验技术相结合，我们确定了先导催化剂的动态运动在该研究反应中实现高对映选择性方面起着关键作用。这种方法也可能成为研究其他肽催化转化机制的一种有价值的方法。
