Antineoplastic agents. 511. Direct phosphorylation of phenpanstatin and pancratistatin.
Pettit GR, Melody N, Herald DL.
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA.
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.
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PMID: 15043403 [PubMed - indexed for MEDLINE]