Establishing a route for the synthesis of ipomoeassin F analogs containing a modified aglycone.

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

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. Based on cytotoxicity assays of other members of the ipomoeassin family, it is known that changes to the aglycon can greatly affect the biol. activity. With that in mind, a route was established to introduce a terminal hydroxyl group into the aglycon of Ipomoeassin F which can be used as a handle to make modifications and to synthesize a small library of analogs. These analogs will be screened in a no. of cancer cell lines to gain more insight into the function of the aglycon on the biol. activity of ipomoeassin F and potentially be used to produce a chem. probe for target identification.