Colchinol, synthesis

In 1950, Rapoport reported the first total synthesis of an important allocolchicine congener, ( )-colchinol methyl ether 51, Fig. (10) [93,94]. 

In the course of their synthesis of colchicine [102], Banwell and coworkers found that the tricyclic intermediate 74, Fig. (15), aromatized in the presence of //-toluenesulfonic acid to give the colchinol analogue 75 [103]. The methyl ester 76 and the previously described methyl ether 72 obtained from 75 were found to be potent inhibitors of tubulin polymerization. 

Limitations Most of the catalysts currently require imines derived from aromatic amines. N aryl amines are thus easily made (as in the synthesis of SCH48461) but if primary amines are the target, the N aryl group has to be removed (as in the synthesis of colchinol). 

This reactions have been successfully used in the synthesis of various naturally oecuring products including a number of isoquinoline alkaloids [19,23], bgnans [15-18,20,21], colchinol derivatives [22], and in several other instances. An interesting example is oxidative coupling of compound 372 to A/-acetylcolchinol (373) in 71% yield [22], respectively, Scheme 6. 

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