(–)-Keramaphidin B, a member of the manzamine alkaloid class of natural products, was first isolated in 1994 from the marine sponge <i>Amphimedon sp</i>. The compound exhibits potent cytotoxicity against P388 murine leukemia cells and KB human epidermoid carcinoma cells. Moreover, (–)-keramaphidin B possesses a pentacyclic framework including 11- and 13-membered macrocyclic rings, four stereogenic centers with one quaternary center, and a highly congested [2.2.2] azabicyclic core, rendering it a formidable target for total synthesis studies. This presentation will describe our laboratory’s ongoing efforts toward the total synthesis of (–)-keramaphidin B. The key step of our approach leverages a strain-promoted, inverse electron-demand Diels–Alder cycloaddition of a transiently-generated cyclic allene to form the azadecalin core and a quaternary stereocenter. The intricacies of this step, in addition to late-stage studies, will be described.

Progress toward the total synthesis of (–)-Keramaphidin B

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.