Colchicine and Related Compounds

A new synthesis of dibenzcycloheptatrienes has been developed. The method provides a route to derivatives unsymmetrically substituted in the lateral nuclei and is based upon the stepwise oxidation of the appropriate 9- or 10-methyl phenanthrenes. Thus 2:3:4:7-tetramethoxy-10-methyl phenanthrene has been oxidised to 9:12:13:14-tetramethoxy-3:4:5:6-dlbenzcyclohepta-1:3:5-trien-7-one which has been shown, by direct comparison, to be identical with a degradation product of colchicine, isolated by Barton, Cook and Loudon. Accordingly the dibenzcycloheptatriene structure of certain colchicine degradation products has been synthetically established. In an attempt to elucidate the aromatisation of colchiceine, the bromination of this primary hydrolysis product has been re-investigated. A weakly acidic bromo-derivative obtained in this manner is isomeric with tribromo-colchiceine and apparently distinct from the tribromo-carboxylic acid described by Windaus. Methylation of this compound has afforded a methyl ether (or ester), isomeric with tribromo-colchicine