Cryptophycin affinity labels: synthesis and biological activity of a benzophenone analogue of cryptophycin-24

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).