Antineoplastic agents 453. Synthesis of pancratistatin prodrugs

George Pettit, B. Orr, S. Ducki

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 - 2000

Fingerprint

Prodrugs
Antineoplastic Agents
Phosphates
Methanol
Phosphites
Hydrogenolysis
Phosphorylation
Ammonium Compounds
Purification
Cations
Acetates
Hot Temperature
Metals
pancratistatin

Keywords

  • Anticancer
  • Pancratistatin
  • Phosphate prodrugs
  • Phosphorylation

ASJC Scopus subject areas

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

Cite this

Antineoplastic agents 453. Synthesis of pancratistatin prodrugs. / Pettit, George; Orr, B.; Ducki, S.

In: Anti-Cancer Drug Design, Vol. 15, No. 6, 2000, p. 389-395.

Research output: Contribution to journalArticle

Pettit, George ; Orr, B. ; Ducki, S. / Antineoplastic agents 453. Synthesis of pancratistatin prodrugs. In: Anti-Cancer Drug Design. 2000 ; Vol. 15, No. 6. pp. 389-395.
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