Programmable syntheses of Polycyclic Natural Products via a Polyfunctional Intermediate Approach

Please join Yale Chemistry for a Silliman Seminar in Organic Chemistry with Pengfei Hu, Assistant Professor at Westlake University.

Summary: Concise and scalable syntheses of complex bioactive molecules provide the foundation for studying structural-activity relationships, preparing analogs, and advancing therapeutical potential. To address this challenge, we have developed a versatile platform strategy centered on polyfunctional intermediates equipped with orthogonally reactive groups. This approach facilitates streamlined C–C bond formations with minimal protecting group and functional group manipulations, enabling concise and scalable routes to polycyclic natural products of diverse biosynthetic origins. Applying this method, we achieved concise syntheses of marine (nor)diterpenoid scarbrolide A and havellockate, as well as the triterpenoid glycinoeclepin A—a picomolar soybean cyst nematode hatching factor. Furthermore, we have expanded this strategy through a chemoenzymatic approach, repurposing simple substituted benzene as a non-canonical triene-type polyfunctional intermediate. This enabled a 16-step, scalable and stereoselective synthesis of tetrodotoxin, a celebrated natural alkaloid with nanomolar sodium channel blocking properties.

Bio: Pengfei Hu earned his PhD at University of Chicago in August 2019 under the supervision of Prof. Scott A. Snyder. From September 2019 to March 2021, Pengfei conducted postdoc research with Prof. Phil S. Baran at Scripps Research, where he was a Hewitt Foundation Fellow working on synthetic electrochemistry. He is currently an assistant professor at Westlake University since April 2021. His research interests include total synthesis of bioactive natural products, synthetic electrochemical chemistry, and medicinal chemistry. For more information on Prof. Hu’s research: Hu Lab Website.

Hosted by Prof. Seth Herzon.

Sponsored by the Mrs. Hepsa Ely Silliman Memorial Fund.