Antineoplastic agents. 511. Direct phosphorylation of phenpanstatin and pancratistatin.
Selective phosphorylation of phenpanstatin (3a) with tetrabutylammonium dihydrogen phosphate and dicyclohexylcarbodiimide in pyridine followed by cation-exchange chromatographic procedures was found to provide an efficient route to a new series (3b-3d) of promising 3,4-O-cyclic phosphate prodrugs designated phenpanstatin phosphates. Application of analogous reaction conditions to pancratistatin (1a) led to a mixture of monophosphate derivatives where sodium pancratistatin 4-O-phosphate (4a) was isolated and the structure confirmed by X-ray crystallography. Modification of the reaction conditions allowed direct phosphorylation of pancratistatin followed by cation-exchange chromatography to afford sodium pancratistatin 3,4-O-cyclic phosphate (5a), which was selected for preclinical development.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA.
Melody
Noeleen
N
Herald
Delbert L
DL
D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry*; D002852:Chromatography, Ion Exchange; D018360:Crystallography, X-Ray; D007546:Isoquinolines / Q000737:chemistry*; D015394:Molecular Structure; D010766:Phosphorylation; D010946:Plants, Medicinal / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis*
D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D007546:Isoquinolines; D011355:Prodrugs; C484200:phenpanstatin; C044997:pancratistatin