SYNTHETIC, CHEMICAL AND BIOLOGICAL STUDIES OF FR901464 ANALOGUES

[摘要] Since the total synthesis of FR901464 was achieved in our group, its structure-activity relationships were extensively studied through analogue syntheses. Here I described the syntheses and biological activities of two acetal analogues and two cyclopropane analogues. Although the acetal analogues were less potent than its parental analogue meayamycin, they retained nanomolar activity against MCF-7 cells. Meanwhile, the methyl groups on the acetal ring slightly influenced the activities of acetal analogues. The biological profiles of the two cyclopropane analogues suggested that FR901464 had no preference to bind to its targets with either face of the diene. I also developed an efficient strategy to synthesize the side chain with Ando's reagent. Subsequently, a convergent strategy was used to prepare acetal analogue, containing a total of 20 steps with 12 steps in the longest linear sequence.

[发布机构] the University of Pittsburgh

[效力级别] Biology