Stereochemical variations on the colchicine motif. Peracid oxidation of thiocolchicone. Synthesis, conformation and inhibition of microtubule assembly

Org Biomol Chem. 2004 Jul 21;2(14):2125-30. doi: 10.1039/b402840f. Epub 2004 Jun 30.

Abstract

When 7-oxodesacetamidothiocolchicine (1) was treated with various peroxides in order to afford a Baeyer-Villiger rearrangement, a complex mixture of products was formed, which included the sulfoxide, (2) and sulfone, (3). When peracetic acid was used two additional products were formed; a C-ring lactone (4) and a ring-contracted allocolchicine derivative (5). The sulfoxide (2) was semi-preparatively resolved into enantiomers by chromatography on microcrystalline triacetylcellulose. Rotational barriers around the A-C pivot bond of, and were determined by dynamic 1H NMR analysis. The compounds, and exhibit moderate inhibition of tubulin polymerization, according to in vitro turbidity studies, whereas was inactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colchicine* / analogs & derivatives
  • Colchicine* / chemistry
  • Colchicine* / pharmacology
  • Microtubules / drug effects*
  • Molecular Conformation
  • Oxidants / chemistry*
  • Oxidation-Reduction
  • Stereoisomerism
  • Tubulin / chemistry

Substances

  • Oxidants
  • Tubulin
  • Colchicine