We analyze the mechanisms of stereo- and regioselective reactions used in natural product synthesis. To capture the small energy differences that give rise to selectivity, we develop methods for exhaustive conformational searches of transition states.

Based on synthetic routes designed by transition-state calculations, we carry out total synthesis of natural products. In particular, we target aminoimidazole alkaloids, highly functionalized and complex natural products, to develop efficient strategies for framework construction and achieve total synthesis.

We determine the structures of natural products that are difficult to resolve by spectroscopy alone using ECD and NMR computations. We also work on efficient conformational analyses that can reproduce the conformational diversity of natural products to enable higher-fidelity simulation of spectroscopic data.

Targeting bioactive macrocyclic polyketides and medium-sized peptides with flexible conformations, we design structurally simplified analogs via conformational analyses and synthesize them to create functional molecules.

We are developing a Python library ACCeL to efficiently process massive computational data arising from conformational diversity.