Syntheses of the (±)-[n]-gingerols (pungent principles of ginger) and related compounds through regioselective aldol condensations: relative pungency assays

Abstract

The deprotonation of trimethylsilylzingerone (13) by lithium di-isopropylamide at –78 °C has been found to be regioselective (92 : 8 in favour of less-substituted enolate): the anion was condensed with alkanals and acyl imidazoles to give convenient syntheses of the (±)-[2]–[10]- and -[12]-gingerols (1) and [4]-, [6]-, and [8]-gingerdiones (9). Similarly, 3-methoxy-4-trimethylsilyloxybenzylideneacetone (17) gave the (±)-[2]–[10]-dehydrogingerols (8) and [4]-, [6]-, and [8]-dehydrogingerdiones (10).

The aldol reaction to [6]-gingerol and methyl [6]-gingerol was also conducted through a vinyloxyborane or through the enol silyl ether (TiCl₄ catalysis). Results of organoleptic assays on these compounds are discussed, and the relation between pungency in the gingerols and in capsaicin is commented on. The aldol method was also used to synthesise the natural β-ketols(±)-daphneolone (25) and (±)-hexahydrocurcumin (4).