An efficient synthesis of a C16 side chain benzophenone analogue of cryptophycin-24 using a crotylboration reaction and Heck coupling as key steps is described. In an in vitro tubulin assembly assay, the benzophenone analogue of the β isomer (IC50=7.4 μM) is twice as active as cryptophycin-24 (IC50=15 μM).
Bibliographical noteFunding Information:
We thank the National Institutes of Health (NCI) for financial support (CA 70369). The Department of the Army is acknowledged for post-doctoral fellowships from the Breast Cancer Research Program to M. E. and R. V. This work was supported in part by the Kansas Technology Enterprise Corporation through the Centers of Excellence Program.