From Colchicine and Some of Its Derivatives to 1,2,3,9,10‐Pentamethoxybenzo[a]heptalenes

A two‐step synthesis of 4‐methylcolchicine (13), starting from colchicine (2), has been developed (Scheme 5). In three steps, 4‐ethylcolchicine (28) is also accessible from 2 (Scheme 8). Colchicine (2) and its derivatives 13 and 28 have been transformed into the benzo[a]heptalene derivatives 9, 18, and 34, respectively, by Hofmann degradation of the corresponding deacetylcolchiceine 3, 19, and 29, respectively, followed by methylation of the two O‐functions first with diazomethane and then with trimethoxonium tetrafluoroborate (Scheme 2 and 6). The thus formed tropylium salts gave, on deprotonation with Me3N in CHCl3, the expected pentamethoxybenzo[a]heptalenes 9, 18, and 34, respectively. X‐Ray crystal‐structure analysis of 9 (Fig.3) and 18 (Fig. 7), determination of the vicinal coupling constants of the H‐atoms at the heptalene skeleton as well as the measurement of the racemization rate of the new benzo[a]heptalenes revealed a marked influence of the substituent at C(4) on the degree of twisting of the heptalene skeleton. The absolute configuration of the resolved heptalenes was deduced from their long‐wavelength CD maxima around 350 nm. The heptalenes with a negative maximum in this range possess (7aP)‐configuration.