Synthesis of colchifoline from deacetylcolchiceine

Abstract

This paper is dedicated to Prof. Raymond U . Lemieux on the occasion of his 60th birthday MARIA A. IORIO, MARISA MOLINARI, and ARNOLD BROSSI. Can. J. Chem. 59,283 (1981). Treatment of a mixture of deacetylcolchicine and deacetylisocolchicine, obtained by diazomethane methylation of deacetylcolchiceine, with trifluoroacetylglycolyl chloride in pyridine, afforded directly colchifoline and isocolchifoline. The two ether isomers could be separated by chromatography and the material eluted first proved to be identical with colchifoline isolated from commercial samples of colchicine.MARIA A. IORIO, MARISA MOLINARI et ARNOLD BROSSI. Can. J. Chem. 59,283 (1981). Un melange de deac0tylcolchicine et de dtacttylisocolchicine, obtenu par la methylation de la deac6tylcolchiceine par le diazomethane, reagit avec le chlorure de trifluoroacetylglycolyle dans la pyridine et conduit directement a la colchifoline et a I'isocolchifoline. On peut stparer les deux ethers isomeres par chromatographie. Le premier produit elut est identique a la colchifoline que I'on a isole a partir d'un echantillon commercial de colchicine.[Traduit par le journal]Colchifoline (5) the N-acetyl group of colchicine. We now would like to report a synthesis of colchifoline (5) from deacetylcolchiceine (g), readily available from colchicine (3) (3).A mixture of 1 and 2 was obtained from deacetylcolchiceine (8) HCl into colchifoleine (9), glycolyl a h~d r o x~a c e t~l a t i n g illustrated with the same arrangements of the oxyagent, was prepared glycolic acid by treat-gen functionalities in ring C as in colchiceine (10) ment with trifluoroacetic anhydride and treatment of the acid with refluxing thionyl chloride in the (5). form of a colorless liquid (see Experimental). The Structure Assignments reaction mixture obtained after usual work-up wasThe colchicine-like nature of ring C in colseparated by chromatography over silica gel. The chifoline (5) and the iso structure of isocolchifoline first eluted material was identical with colchifoline (6) were evident from a comparison of their IH nmr (5), a minor contaminant of commercial colchicine spectra (aromatic protons) with those of reference (1). The second compound, obtained in at least substances (3, 4) reported recently (6-8). Mass equal amounts, was assigned the structure of spectra of colchifoline (5) and isocolchifoline (6) isocolchifoline (6). The two ethers 5 and 6 are con-showed the same fragmentation pattern with the

Synthesis and Evaluation of 2‐diazo‐3,3,3‐trifluoropropanoyl Derivatives of Colchicine and Podophyllotoxin as Photoaffinity Labels: Reactivity, Photochemistry, and Tubulin Binding

“…The known thiocolchicine derivatives N-deacetylthiocolchicine (Iorio et al,198 l), 2-demeth ylt hiocolchicine (S harma and Brossi, 1983), and 3-demethylcolchicine (Rossner et al, 1981) were prepared. Thiocolchifoline was prepared from N-deacetylthiocolchicine following a sequence analogous to that reported for colchifoline (Iorio et al, 1981). A new colchicine derivative incorporating a P-mercaptoethylthio group at C-10 was prepared to provide a nucleophilic substituent on the C-ring.…”