Antineoplastic agents 453. Synthesis of pancratistatin prodrugs.
A new and efficient synthesis of the (+)-pancratistatin phosphate prodrug (2a) has been accomplished. Selective protection (tetraacetate 4) of (+)-pancratistatin (la) was followed by phosphorylation (to 5) with dibenzyl chlorophosphite (prepared in situ from dibenzyl phosphite). Cleavage of the acetate (with sodium methoxide) and benzyl (by hydrogenolysis) protecting groups followed by concomitant reaction with two equivalents of sodium methoxide afforded a good yield of disodium (+)-pancratistatin phosphate (2a). Further increases in yields of the prodrug (2a) were realized by avoiding heat in the final purification steps. Fourteen (2b-o) additional metal and ammonium cation derived phosphate prodrugs were also synthesized.
Pettit
G R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe 85287-2404, USA.
Orr
B
B
Ducki
S
S
D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared
D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D007546:Isoquinolines; D011355:Prodrugs; C044997:pancratistatin