Antineoplastic agents 460. Synthesis of combretastatin A-2 prodrugs

George Pettit, Bryan R. Moser, Michael R. Boyd, Jean M. Schmidt, Robin Pettit, Jean Chapuis

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The original synthesis of combretastatin A-2 (1a) was modified to provide an efficient scale-up procedure for obtaining this antineoplastic stilbene. Subsequent conversion to a useful prodrug was accomplished by phosphorylation employing in situ formation of dibenzylchlorophosphite followed by cleavage of the benzyl ester protective groups with bromotrimethylsilane to afford the phosphoric acid intermediate 11. The latter was immediately treated with sodium methoxide to complete a practical route to the disodium phosphate prodrug (2a). The phosphoric acid precursor (11) of phosphate 2a was employed in a parallel series of reactions to produce a selection of metal and ammonium cation prodrug candidates. Each of the phosphate salts (2a-q) was evaluated with respect to relative solubility behavior, cancer cell growth inhibition and antimicrobial activity.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalAnti-Cancer Drug Design
Volume16
Issue number4-5
StatePublished - Aug 1 2001

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Keywords

  • Antineoplastic activity
  • Combretastatin A-2 prodrug
  • Phosphate esters

ASJC Scopus subject areas

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

Cite this

Pettit, G., Moser, B. R., Boyd, M. R., Schmidt, J. M., Pettit, R., & Chapuis, J. (2001). Antineoplastic agents 460. Synthesis of combretastatin A-2 prodrugs. Anti-Cancer Drug Design, 16(4-5), 185-193.