Late-stage modification of C-3 tigoyl moiety of ipomoeassin F to enable SAR studies.

by Whisenhunt, Lucas; Zong, Guanghui; Hu, Zhijian; Aljewari, Hazim; Shi, Wei

The resin glycoside Ipomoeassin F is potent against multiple cancer cell lines with IC50 values in the single-digit nanomolar range. Still, the resin glycoside's mechanism of action is largely missing. A few systematic SAR studies have been performed to investigate the peripheral oxygenation, acylation patterns, and other potential pharmacophoric "hot spots." However, few studies have been performed on the C-2 hydroxyl and C-3 tigoyl portions of the glucoside moiety to investigate their potential importance. Previously a 19-linear step synthesis route was designed to modify the C-3 tigoyl moiety in the penultimate step. This work highlights the synthesis route, while showing some of the C-3 glucosyl modified analogs synthesized from the route. These C-3 glucosyl modified analog will give significant insight into the C-3 importance to the cytotoxicity of Ipomoeaessin F and potentially help to understand the mechanism of action of a promising therapeutic agent.