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.
申请公布号
WO02102766(A3)
申请公布日期
2003.04.03
申请号
WO2002US19085
申请日期
2002.06.17
申请人
ARIZONA BOARD OF REGENTS;PETTIT, GEORGE, R.;MINARDI, MATHEW, D.