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.