Antineoplastic agents, 122. Constituents of Combretum caffrum

An investigation of the South African tree Combretum caffrum (Combretaceae) for antineoplastic constituents was conducted by employing the astrocytoma bioassay (9ASK). By this approach and a combination of solvent partition, steric exclusion, and adsorption chromatographic procedures, a substance designated combretastatin [1a] was isolated and found to display significant (71-90% astrocyte reversal at 1-100 micrograms/ml dose levels) astrocyte reversal and murine P-388 lymphocytic leukemia (PS) cell growth inhibition (ED50 0.011 micrograms/ml). The structure of (-)-combretastatin was elucidated by X-ray crystal structure analysis and confirmed by total synthesis. The absolute configuration at C-10 was assigned the R-configuration on the basis of Horeau esterification techniques. Other prominent, albeit PS-inactive, constituents were found to be 3,3',4'-tri-O-methylellagic acid [2] and acacetin [3].