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

Abstract

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.