Partial synthesis and antitubulin activity of minor colchicum alkaloids: N-acetoacetyl-deacetylcolchicine and 2-demethylspeciosine (speciocolchine).

Two minor Colchicum alkaloids, N-acetoacetyl-deacetylcolchicine [1] and 2-demethylspeciosine [7], were synthesized. The diacetate 8 of 2-demethylspeciosine was also prepared. The antitubulin activity of these compounds, in comparison to colchicine, was measured. N-Acetoacetyl-deacetylcolchicine [1] has in vitro activity similar to that of colchicine. Both 2-demethylspeciosine [7] and the diacetate 8 were considerably less potent inhibitors of tubulin polymerization.