Antineoplastic agents 453. Synthesis of pancratistatin prodrugs

George Pettit, B. Orr, S. Ducki

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

A new and efficient synthesis of the (+)-pancratistatin phosphate prodrug (2a) has been accomplished. Selective protection (tetraacetate 4) of (+)-pancratistatin (1a) 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.

Original languageEnglish (US)
Pages (from-to)389-395
Number of pages7
JournalAnti-Cancer Drug Design
Volume15
Issue number6
StatePublished - Dec 1 2000

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Keywords

  • Anticancer
  • Pancratistatin
  • Phosphate prodrugs
  • Phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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