Antineoplastic agents 393. Synthesis of the trans-isomer of combretastatin A-4 prodrug

George Pettit, Monte R. Rhodes, Delbert L. Herald, Dai J. Chaplin, Michael R L Stratford, Ernest Hamel, Robin Pettit, Jean Chapuis, Deanna Oliva

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The (E)-stilbene isomer (2a) of the (Z)-combretastatin A-4 prodrug (1b) was efficiently prepared from (E)-combretastatin A-4 by a reaction sequence employing phosphorylation (dibenzyl chlorophosphite), cleavage (trimethyliodosilane) of the benzyl ester and reaction of the resulting phosphoric acid with sodium methoxide. The sodium phosphate product (2c) was also found to be an important side-product, presumably from iodine-catalyzed isomerization, when the analogous synthetic route was used to obtain the combretastatin A-4 prodrug (1b). The phosphoric acid precursor of prodrug 1b derived from (Z)-combretastatin A-4 (1a) was converted into a series of metal cation and ammonium cation salts to evaluate effects on human cancer cell growth, antimicrobial activities and solubility behavior.

Original languageEnglish (US)
Pages (from-to)981-993
Number of pages13
JournalAnti-Cancer Drug Design
Volume13
Issue number8
StatePublished - Dec 1 1998

Keywords

  • Antimicrobial agents
  • Antineoplastic agents
  • Phosphate esters
  • trans-combretastatin A-4 prodrug

ASJC Scopus subject areas

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

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    Pettit, G., Rhodes, M. R., Herald, D. L., Chaplin, D. J., Stratford, M. R. L., Hamel, E., Pettit, R., Chapuis, J., & Oliva, D. (1998). Antineoplastic agents 393. Synthesis of the trans-isomer of combretastatin A-4 prodrug. Anti-Cancer Drug Design, 13(8), 981-993.