Antineoplastic agents 463. Synthesis of combretastatin A-3 diphosphate prodrugs.
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 (10a-l) was readily achieved. Both the diphosphate sodium (10a) and potassium salts (10c) displayed aqueous solubility in excess of 220 mg/ml at room temperature and good cancer cell line inhibitory activity.
Pettit
G R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe 85287-2404, USA.
Minardi
M D
MD
Boyd
M R
MR
Pettit
R K
RK
D000840:Anisoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013267:Stilbenes; D013329:Structure-Activity Relationship
D000840:Anisoles; D000890:Anti-Infective Agents; D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D013267:Stilbenes; C440905:combretastatin A3