Synthesis and biological evaluation of oxoapratoxin E and its C30 epimer

Abstract

30R- and 30S-oxazoline analogues of apratoxin E have been prepared with late-stage formation of an oxazoline ring. These two compounds have a potent inhibitory effect on HCT-116 cell proliferation with IC50 values of 345 and 638nM, respectively. These results suggest that apratoxin E oxazoline bioisosteres are approximately 6-fold less potent than their thiazoline parent compounds. A positive impact of the 30R conformation on antiproliferative activity was also observed, with approximately 2-fold enhancement when compared to the 30S epimer.