Total synthesis and biological evaluation of the C-11 epimer of ipomoeassin F

by Barber, Eric; Zong, Guanghui; Aljewari, Hazim; Shi, Wei

Ipomoeassin F, a resin glycoside isolated from the leaves of Ipomoea squamosa, has been to shown to have a cytotoxicity in the low nanomolar range for a no. of cell lines. Despite its high bioactivity, little is known about its mode of action. The macrolide ipomoeassin F consists of a disaccharide moiety linked through an intramol. esterification to a 16-carbon fatty-acid derived aglycon. The aglycon contains a sole chiral center at C11 in the S configuration. In an effort to gain insight into the activity of this natural product, we synthesized an epimer with a change in configuration at this sole chiral center to explore the effect of the stereochem. on the activity. This epimer of ipomoeassin F was then subjected to a few biol. assays in human cells and compared to the previously synthesized natural product. The results showed a decrease in activity for the epimer by greater than 30 fold for all cell lines indicating the importance of the stereochem. of the compd.