Antineoplastic agents 320: Synthesis of a practical pancratistatin prodrug

George Pettit, S. Freeman, M. J. Simpson, M. A. Thompson, M. R. Boyd, M. D. Williams, G. R. Pettit, D. L. Doubek

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Owing to its sparingly soluble properties, the potential anticancer drug pancratistatin (1) resisted conventional drug formulation procedures and the synthesis of a water-soluble prodrug became necessary. That important objective for further pre-clinical development was met by devising a route to a disodium phosphate derivative (5). The key step in the synthesis of the phenolic phosphate was phosphorylation of 1,2,3,4-tetraacetoxy-pancratistatin (2) with dibenzyloxy(N,N-diisopropylamido)-phosphine. Subsequent oxidation with m-chloroperbenzoic acid afforded phosphate 4a. Hydrogenolysis of the benzyl esters followed by base-catalysed hydrolysis of the acetate groups led to the water-soluble prodrug 5 in high yield.

Original languageEnglish (US)
Pages (from-to)243-250
Number of pages8
JournalAnti-Cancer Drug Design
Volume10
Issue number3
StatePublished - 1995

ASJC Scopus subject areas

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

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    Pettit, G., Freeman, S., Simpson, M. J., Thompson, M. A., Boyd, M. R., Williams, M. D., Pettit, G. R., & Doubek, D. L. (1995). Antineoplastic agents 320: Synthesis of a practical pancratistatin prodrug. Anti-Cancer Drug Design, 10(3), 243-250.