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  • Novel allocolchicinoids with an eight membered B-ring: design, synthesis and inhibition of tubulin assembly.

Novel allocolchicinoids with an eight membered B-ring: design, synthesis and inhibition of tubulin assembly.

Bioorganic & medicinal chemistry (2000-03-25)
R Brecht, G Seitz, D Guénard, S Thoret
ABSTRACT

Several B-ring variations of O-methyl androbiphenyline (8), newly accessible from (-)-(M,7S)-colchicine via photooxygenation and subsequent endoperoxide-transformation, were synthesized and evaluated for their inhibitory effects on tubulin assembly in vitro. The amino-allocolchicinoid (9), a key compound in this study, was transformed to the highly potent ketone 10 and by oxidation with H2O2/Na2WO4 to a mixture of syn/anti-oximes, like 11 and 12. These could easily be transformed to hitherto unknown allocolchicinoids 13 and 14 with an eight membered B-ring lactam obtained via a Beckmann rearrangement. Surprisingly both do not notably affect tubulin assembly, despite obvious structural similarities with active analogues of the thiocolchicine- and azasteganacin-series.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Thiocolchicine, ≥97% (HPLC)