Simple Conversion of Colchicine into Demecolcine

Abstract

Abstract N ‐Deacetylcolchiceine ( 7 ), readily available from colchicine ( 1 ), was converted into N ‐trifluoroacetyl‐deacetylcolchiceine ( 8 ). Methylation of 8 with methyl iodide in the presence of potassium carbonate afforded a mixture of N ‐trifluoroacetyl‐demecolcine ( 10 ) and its isomer 11 . The mixture of 10 and 11 was detrifluoroacetylated and separated by chromatography to afford demecolcine ( 2 ) and isodemecolcine ( 12 ). A more practical route to 2 started with 8 , and gave N ‐trifluoroacetyl‐deacetylcolchicine ( 13 ) and its isomer 14 after O ‐methylation with diazomethane. N ‐Methylation of 13 and 14 with methyl iodide and potassium carbonate afforded 10 and 11 . The overall yield in the conversion of colchicine ( 1 ) into demecolcine ( 2 ) via 7, 8 and 13 was 55%.