COMBRETASTATIN A-3 PRODRUG

摘要

A new and more efficient synthesis of combretastatin A-3 (2a) was completed (8.4% overall yield) starting from methyl gallate and isovanillin with aldehyde 5 and phosphonium salt 8 as key intermediates. Conversion of combretastatin A-3 (2a) to a series of diphosphate prodrugs (lOa -lOl) containing selected anions was achieved. Both the diphosphate sodium (lOa) a nd potassium salts (lOc) displayed aqueous solubility in excess of 220 mg/ml at room temperature and good cancer cell line inhibitory activity.