Procedures for the Analyses of Dolastatins 10 and 15 by High Performance Liquid Chromatography

Abstract
A series of HPLC procedures were evaluated for assessing the purity of dolastatin 10 (1) and dolastatin 15 (2) samples. Interestingly two readily interconvertible (ambient temperature) dolastatin 10 (1) conformers were detected using a potassium dihydrogen phosphate buffered solvent (methanol-water) with a C8 reversed-phase column. A solvent system composed of acetonitrile-2-propanol-water containing sodium 1-hexanesulfonate was found especially useful for evaluating the purity of dolastatin 10 and 15 specimens. Useful HPLC procedures were also found for detecting diastereomeric isomers in the key dolastatin 10 synthetic intermediate Boc-(S, R, R)-Dap-(S)-Doe using β-cyclodextrin in 3:2 methanol-water.