Antineoplastic agents 393. Synthesis of the trans-isomer of combretastatin A-4 prodrug.
The (E)-stilbene isomer (2a) of the (Z)-combretastatin A-4 prodrug (1b) was efficiently prepared from (E)-combretastatin A-4 by a reaction sequence employing phosphorylation (dibenzyl chlorophosphite), cleavage (trimethyliodosilane) of the benzyl ester and reaction of the resulting phosphoric acid with sodium methoxide. The sodium phosphate product (2c) was also found to be an important side-product, presumably from iodine-catalyzed isomerization, when the analogous synthetic route was used to obtain the combretastatin A-4 prodrug (1b). The phosphoric acid precursor of prodrug 1b derived from (Z)-combretastatin A-4 (1a) was converted into a series of metal cation and ammonium cation salts to evaluate effects on human cancer cell growth, antimicrobial activities and solubility behavior.
Pettit
G R
GR
Cancer Research Institute, Arizona State University, Tempe 85287-2494, USA.
Rhodes
M R
MR
Herald
D L
DL
Chaplin
D J
DJ
Stratford
M R
MR
Hamel
E
E
Pettit
R K
RK
Chapuis
J C
JC
Oliva
D
D
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D013267:Stilbenes; C058728:fosbretabulin