title: Stereochemical variations on the colchicine motif. Peracid oxidation of thiocolchicone. Synthesis, conformation and inhibition of microtubule assembly.
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.
authors.affiliation: Organic Chemistry 1, Dept. of Chemistry, Lund University, P.O. Box 124, S-22100 Lund, Sweden. ulf.berg@orgk1.lu.se
authors.forename: Ulf
authors.initials: U
authors.lastname: Berg
authors.forename: Hakan
authors.initials: H
authors.lastname: Bladh
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mpampos
mesh_terms: 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
chemical_list: D016877:Oxidants; D014404:Tubulin; D003078:Colchicine