SYNTHESIS OF CYCLO-BIS[7-ALPHA, 12-ALPHA-DIACETOXY-3-BETA-DICYANOMETHYL-3-ALPHA-(4-METHYLENEPHENYL)CHOLANAMIDE] - A CHOLAPHANE WITH REDUCED FLEXIBILITY AND EXTERNALLY-DIRECTED FUNCTIONALITY

A second 'cholaphane' framework is manifested in the title compound 8, which has been prepared from methyl 3alpha, 7alpha, 12alpha-triacetoxycholanoate 9 in 23% overall yield. The synthesis involves the Knoevenagel condensation of ketone 11 with malononitrile to give dicyanomethylene derivative 12, equatorial-selective addition to the latter of an organocuprate derived from aryl bromide 1 5, conversion of the resulting adduct into amino acid 22, and cyclodimerisation. The framework of 8 has less conformational freedom and a better-defined cavity than the 'first-generation' cholaphanes 2, and also bears externally-directed functionality.