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

Anticancer Drug Des. 1998 Dec;13(8):981-93.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemical synthesis*
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Chromatography, High Pressure Liquid
  • Humans
  • Microbial Sensitivity Tests
  • Prodrugs / chemical synthesis*
  • Prodrugs / isolation & purification
  • Prodrugs / pharmacology
  • Stereoisomerism
  • Stilbenes / chemical synthesis*
  • Stilbenes / isolation & purification
  • Stilbenes / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Prodrugs
  • Stilbenes
  • fosbretabulin