Theoretical Analysis of Multi-conformational Transition States and Diastereo/Regio-selective Reactions in Natural Product Synthesis

Abstract

Computational chemistry is a powerful tool for exploring the unique behavior of organic compounds. We have employed computational techniques to analyze mechanisms of diastereo- and regioselective reactions, which are key transformations in studies on natural product synthesis. Our approach involves ensuring conformational diversity when calculating the transition states of target reactions, allowing us to obtain many geometrically different transition states and systematic information on favorable and unfavorable geometries, which can lead to the identification of origins of the selectivity. In this account, we describe the protocol of a comprehensive search for transition states. The protocol was applied to the mechanistic analyses of the aza-spirocyclization in the total synthesis of fasicularin, the aldol reaction in the synthetic study of amphidinolide L, and the Au-mediated 6-exo-dig ether cyclization in the synthetic study of ent-formosalide A.

Graphical Abstract