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

42 Citations (Scopus)

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

Fingerprint

Prodrugs
Antineoplastic Agents
phosphine
Phosphates
Drug Compounding
Hydrogenolysis
Phosphorylation
Water
Hydrolysis
Esters
Acetates
Derivatives
Oxidation
Pharmaceutical Preparations
pancratistatin

ASJC Scopus subject areas

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

Cite this

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

Antineoplastic agents 320 : Synthesis of a practical pancratistatin prodrug. / Pettit, George; Freeman, S.; Simpson, M. J.; Thompson, M. A.; Boyd, M. R.; Williams, M. D.; Pettit, G. R.; Doubek, D. L.

In: Anti-Cancer Drug Design, Vol. 10, No. 3, 1995, p. 243-250.

Research output: Contribution to journalArticle

Pettit, G, Freeman, S, Simpson, MJ, Thompson, MA, Boyd, MR, Williams, MD, Pettit, GR & Doubek, DL 1995, 'Antineoplastic agents 320: Synthesis of a practical pancratistatin prodrug', Anti-Cancer Drug Design, vol. 10, no. 3, pp. 243-250.
Pettit G, Freeman S, Simpson MJ, Thompson MA, Boyd MR, Williams MD et al. Antineoplastic agents 320: Synthesis of a practical pancratistatin prodrug. Anti-Cancer Drug Design. 1995;10(3):243-250.
Pettit, George ; Freeman, S. ; Simpson, M. J. ; Thompson, M. A. ; Boyd, M. R. ; Williams, M. D. ; Pettit, G. R. ; Doubek, D. L. / Antineoplastic agents 320 : Synthesis of a practical pancratistatin prodrug. In: Anti-Cancer Drug Design. 1995 ; Vol. 10, No. 3. pp. 243-250.
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