Syntheses and biological evaluation of irciniastatin A and the C1-C2 alkyne analogue

Org Lett. 2010 Mar 5;12(5):1040-3. doi: 10.1021/ol1000389.

Abstract

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.

MeSH terms

  • Alkynes / chemistry*
  • Coumarins
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Pyrones / chemical synthesis*
  • Pyrones / chemistry
  • Pyrones / pharmacology*
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Alkynes
  • Coumarins
  • Pyrones
  • psymberin