Antineoplastic Agents. 511. Direct Phosphorylation of Phenpanstatin and Pancratistatin

George Pettit, Noeleen Melody, Delbert L. Herald

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)322-327
Number of pages6
JournalJournal of Natural Products
Volume67
Issue number3
DOIs
StatePublished - Mar 2004

Fingerprint

Phosphorylation
antineoplastic agents
Antineoplastic Agents
phosphorylation
Phosphates
phosphates
Cations
Dicyclohexylcarbodiimide
sodium
X ray crystallography
X Ray Crystallography
Prodrugs
Chromatography
pyridines
cation exchange
X-ray diffraction
Sodium
Derivatives
chemical derivatives
pancratistatin

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Antineoplastic Agents. 511. Direct Phosphorylation of Phenpanstatin and Pancratistatin. / Pettit, George; Melody, Noeleen; Herald, Delbert L.

In: Journal of Natural Products, Vol. 67, No. 3, 03.2004, p. 322-327.

Research output: Contribution to journalArticle

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