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

Summary, in English

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 2, 4 and 5 were determined by dynamic H-1 NMR analysis. The compounds 2, 3, 4 and 7a exhibit moderate inhibition of tubulin polymerization, according to in vitro turbidity studies, whereas 5 was inactive.

• Author: Ulf Berg; Håkan Bladh; Konstantin Mpampos
• Department/s: Centre for Analysis and Synthesis
• Publishing year: 2004
• Language: English
• Pages: 2125-2130
• Publication/Series: Organic and Biomolecular Chemistry
• Volume: 2
• Issue: 14
• Links: http://dx.doi.org/10.1039/b402840f
• Document type: Journal article
• Publisher: Royal Society of Chemistry
• Topic: Organic Chemistry
• Status: Published
• ISBN/ISSN/Other: ISSN: 1477-0539