Biomedical subjects
Publications and source records attributed to A Brossi.
It is shown that geneserine [2] and geneseroline [4] convert with acid into salts of physostigmine N-oxide [3] and geneseroline N-oxide [5], respectively. Structure assignments were made on the basis of chemical conversions, 1H-nmr analysis of 2-5, and an X-ray analysis of 5 as its hydrochloride.
(+/-)-Norarmepavine [3] [corrected] prepared by Bischler-Napieralski synthesis afforded, on reaction with (S)-(-)-1-phenylethylisocyanate, ureas 4 and 5 which were separated and purified by crystallization from EtOH and 70% HOAc. Alcoholysis of 4 and 5 with sodium butoxide in n-BuOH afforded (S)-norarmepavine [3a] and (R)-norarmepavine [3b] [corrected], respectively. Hplc analysis of ureas prepared from 3a and 3b with (S)-(-)-1-phenylethylisocyanate showed them to be optically pure alkaloids. Refluxing 3a and 3b with 48% HBr afforded the hydrobromide salts of (S)-norcoclaurine [1a] and its (R)-isomer 1b, respectively.
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.