Antineoplastic agents 442. Synthesis and biological activities of dioxostatin

George Pettit, J. W. Lippert, M. R. Boyd, P. Verdier-Pinard, E. Hamel

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

A high-yield regioselective synthesis of (E)-combretastatin A-1 2b was completed using methoxymethyl (MOM) protection and a Wadsworth-Emmons reaction as key steps. In turn, (E)-stilbene 11 was converted by convenient syntheses to both (S,S)- and (R,R)-1, 3-dioxolanes 5a and 6a. A Sharpless asymmetric dihydroxylation reaction was employed for preparation of intermediates (S,S)-12 and (R,R)-13. The (4S,5S)-4-(2′,3′-dihydroxy-4′-methoxyphenyl)-5- (3″,4″,5″-trimethoxyphenyl)-1, 3-dioxolane 5a was found to be a highly potent inhibitor of microtubule assembly (IC50 = 0.59 μM) and was designated dioxostatin. Conversion to sodium phosphate 17 (P388 lymphocytic leukemia cell line: ED50 = 0.2 μg/ml) provided a very useful water-soluble prodrug.

Original languageEnglish (US)
Pages (from-to)361-371
Number of pages11
JournalAnti-Cancer Drug Design
Volume15
Issue number5
StatePublished - Dec 1 2000

Keywords

  • Asymmetric dihydroxylation
  • Dioxostatin
  • Dioxostatin prodrug
  • Tubulin binding agent

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Antineoplastic agents 442. Synthesis and biological activities of dioxostatin'. Together they form a unique fingerprint.

  • Cite this

    Pettit, G., Lippert, J. W., Boyd, M. R., Verdier-Pinard, P., & Hamel, E. (2000). Antineoplastic agents 442. Synthesis and biological activities of dioxostatin. Anti-Cancer Drug Design, 15(5), 361-371.