Synthesis and biological evaluation of 10, 11-Dihydrodictyostatin, a potent analogue of the marine anticancer agent dictyostatin

By employing a diverted total synthesis strategy with late-stage intermediates, 10,11-dihydrodictyostatin ( 5) was prepared and evaluated in vitro for growth inhibition against a range of human cancer cell lines, including the NCI/ADR Taxol-resistant cell line. This novel dictyostatin analogue was found to retain potent antimitotic activity, with a comparable profile to discodermolide and Taxol, functioning by microtubule stabilization and G2/M arrest. These SAR studies provide further insight into the interaction between dictyostatin ( 1) and its tubulin target.

This document is the accepted manuscript version of a published work that appeared in final form in Journal of Natural Products after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/np070547s. This article may be cited as: Paterson, I., Gardner, N. M., Poullennec, K. G., & Wright, A. E. (2008). Synthesis and biological evaluation of 10, 11-Dihydrodictyostatin, a potent analogue of the marine anticancer agent dictyostatin. Journal of Natural Products, 71(3), 364-369. doi:10.1021/np070547s

Florida Atlantic University. Harbor Branch Oceanographic Institute contribution #1775.