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) and potassium salts (lOc) displayed aqueous solubility in excess of 220 mg/ml at room temperature and good cancer cell line inhibitory activity.
This application is the U.S. national stage of PCT/US02/19085 filed on Jun. 17, 2002, which claims the priority of U.S. Provisional Application Ser. No. 60/298,606 filed on Jun. 15, 2001, which are incorporated herein by reference.
