Stereochemical variations on the colchicine motif. Peracid oxidation of thiocolchicone. Synthesis, conformation and inhibition of microtubule assembly.
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.
Berg
Ulf
U
Organic Chemistry 1, Dept. of Chemistry, Lund University, P.O. Box 124, S-22100 Lund, Sweden. ulf.berg@orgk1.lu.se
Bladh
Hakan
H
Mpampos
Konstantinos
K
D003078:Colchicine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects*; D008968:Molecular Conformation; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014404:Tubulin / Q000737:chemistry
D016877:Oxidants; D014404:Tubulin; D003078:Colchicine