Formation of disaccharides related to heparin and heparan sulfate by chemical modification of maltose

Abstract

Maltose has been converted into 4- O-(2-amino-2-deoxy-α- d-glucopyranosyl)- l-idopyranuronic acid, 4- O-(2-amino-2-deoxy-α- d-glucopyranosyl)- d-glucopyranose, and 4- O-α- d-glucopyranosyl- l-idopyranose, the first two disaccharides being related structurally to biose sequences in heparin and heparan sulfate. Used as the starting material was a major product of the kinetic acetonation of maltose, namely, 2,3:5,6-di- O-isopropylidene-4- O-(4,6- O-isopropylidene-α- d-glucopyranosyl)- aldehydo- d-glucose dimethyl acetal. It was subjected to a sequence of transformations that included the introduction of a 2′-amino-2′-deoxy function into the glucosyl group, the inversion of C-5 in the glucose residue to give the l- ido configuration, oxidation at position 6, and cyclisation of the acyclic dimethyl acetal to give the desired pyranuronic acid. In the formation of the latter, the 5- O-levulinoyl substituent was found to be less prone to acyl migration to O-6 than more conventional ester groups. The relative acid labilities of the O-isopropylidene and dimethyl acetal groups are compared, and conformations of the acyclic residues of some disaccharide derivatives are discussed.