: Isolation and structure of halistatin 1 from the eastern Indian Ocean marine sponge Phakellia carteri

Abstract

A highly potent new polyether macrolide antimitotic agent designated halistatin 1 (5) was isolated (8.8×10 -7 % yield) from Phakellia carteri. The marine sponge was located in coastal areas of the Republic of the Comoros, and it was also found to contain halichondrin B (3) and homohalichondrin B (4). Structure elucidation of halistatin 1 (5) was achieved primarily by employing extensive high-field (400 and 500-MHz) 2D NMR techniques. Halistatin 1, like halichondrin B and homohalichondrin B, caused the accumulation of cells arrested in mitosis, inhibited tubulin polymerization, and inhibited the binding of radiolabeled vinblastine and GTP to tubulin