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.