R. Brecht et al., Novel allocolchicinoids with an eight membered B-ring: Design, synthesis and inhibition of tubulin assembly, BIO MED CH, 8(3), 2000, pp. 557-562
Several B-ring variations of O-methyl androbiphenyline (8), newly accessibl
e from (-)-(M,7S)-colchicine via photooxygenation and subsequent endoperoxi
de-transformation, were synthesized and evaluated for their inhibitory effe
cts on tubulin assembly in vitro. The amino-allocolchicinoid (9), a key com
pound 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 rearra
ngement. Surprisingly both do not notably affect tubulin assembly, despite
obvious structural similarities with active analogues of the thiocolchicine
- and azasteganacin-series. (C) 2000 Elsevier Science Ltd. All rights reser
ved.