Selective epimerization of l-chiro-inositol to l-muco- and d-chiro-inositol derivatives Original Research Article

In a one step procedure, l-1-O-benzyl-2-O-methyl-chiro-inositol (1) was acetalized to the l-muco-inositol derivatives 2, 3 and d-2-O-benzyl-3-O-cyclohexylcarbamoyl-4-deoxy-4-(N,N′-dicyclohexylureido)-1-O-methyl-5,6-O-trichloroethylidene-chiro-inositol (4). Complete conversion of l-1-O-benzyl-6-O-cyclohexylcarbamoyl-3-O-formyl-2-O-methyl-4,5-O-trichloroethylidene-muco-inositol (3) into l-1-O-benzyl-6-O-cyclohexylcarbamoyl-2-O-methyl-4,5-O-trichloroethylidene-muco-inositol (2) is feasible by deformylation in boiling methanolic triethylamine. Furthermore, stepwise deprotection of 2 and 4 is described. Thus, compounds 5, 10, and 7 were obtained by decarbamoylation of 2, 4, and 6, respectively, with boiling methanolic sodium methoxide. The trichloroethylidene group of l-1-O-benzyl-2-O-methyl-4,5-O-trichloroethylidene-muco-inositol (5) was removed in a two step procedure (hydrodechlorination–deacetalization) via the ethylidene acetal 7 to give l-1-O-benzyl-2-O-methyl-muco-inositol (9). On refluxing d-chiro-inositol derivative 4 with 99% acetic acid, the ureido moiety was cleaved generating d-2-O-benzyl-4-cyclohexylamino-3-O-cyclohexylcarbamoyl-4-deoxy-1-O-methyl-5,6-O-trichloroethylidene-chiro-inositol (11). By contrast, cleavage of the ureido moiety of 10 was relatively difficult. The corresponding d-2-O-benzyl-4-cyclohexylamino-4-deoxy-1-O-methyl-5,6-O-trichloroethylidene-chiro-inositol (12) was only formed in small amounts. The structures of 1, 3 and 10 were confirmed by X-ray analysis.