Syntheses and biological evaluation of irciniastatin A and the C1-C2 alkyne analogue.
Syntheses of both natural (+)- and unnatural (-)-irciniastatin A (aka psymberin) as well as a C1-C2 alkyne analogue of (+)-irciniastatin A have been achieved. The key features of the syntheses include a highly regioselective epoxide-opening reaction and a late-stage assembly of C1-C6, C8-C16, and C17-C25 fragments. (+)-Alkymberin retained a high level of cytotoxicity, whereas (-)-irciniastatin A showed almost no activity. These results suggest that (+)-alkymberin could be a useful enantio-differential probe for mode-of-action study.
Watanabe
Tsubasa
T
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan.
Imaizumi
Takamichi
T
Chinen
Takumi
T
Nagumo
Yoko
Y
Shibuya
Masatoshi
M
Usui
Takeo
T
Kanoh
Naoki
N
Iwabuchi
Yoshiharu
Y
D000480:Alkynes / Q000737:chemistry*; D003374:Coumarins; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013379:Substrate Specificity
D000480:Alkynes; D003374:Coumarins; D011753:Pyrones; C498383:psymberin