Department of Chemistry Seminar -  Concise Synthesis of Natural Products Based on a Polyfunctional Intermediate Approach

Speaker: Professor Pengfei HU

Institution: Department of Chemistry, Westlake University, China

Hosted By: Prof. Hugh NAKAMURA

Abstract

Concise and scalable synthesis of complex bioactive molecules provide the foundation for studying their structural-activity relationships, preparing analogs, and advancing therapeutical potential. We present a versatile platform strategy based on polyfunctional intermediates featuring orthogonally reactive groups, facilitating streamlined C–C bond formations to access polycyclic polycyclic natural products with diverse biosynthetic origin. This includes the synthesis of marine diterpenoid scarbrolide A and havellockate, and a 15-step synthesis of triterpenoid glycinoeclepin A, a picomolar soybean cyst nematode hatching factor that previously require 25-39 steps. We further extended this strategy using chemoenzymatic tactics to differentiate groups of similar reactivity, achieving chemo- and stereo-selective sequential functionalization. This enables a 16-step, scalable and stereoselective synthesis of tetrodotoxin, a celebrated natural alkaloid with nanomolar sodium channel blocking properties that previously took 22-69 steps.