IMPROVED SYNTHESIS OF ALPHA-L-FUC(1-]4)-BETA-D-GLCNAC AND ALPHA-L-FUC(1-]6)-BETA-D-GLCNAC BUILDING-BLOCKS - A CONVERGENT STRATEGY EMPLOYING 4-O-]6-O ACETYL MIGRATION - NOE DATA OF THE PROTECTED ALPHA-1,4-LINKED DISACCHARIDE

The synthesis of the two ethylthio disaccharide building blocks 10 and 17 was achieved by coupling of fucosyl bromide 9 with the acceptor alcohols 6 and 7 under in situ anomerization conditions. The selectively protected 2-deoxy-2-phthalimidoglucose derivative 7 was derived from 6 by utilizing an optimized acetyl migration reaction. The ethylthio function in disaccharides 10 and 17 was activated with bromine, and excess bromine was removed with cyclohexene. The sensitive 1,6-linkage in the disaccharide 10 proved to be stable under these activating conditions. The disaccharide bromides 11 and 18 were treated with methanol to afford after deblocking the methyl glycosides 16 and 23. Homonuclear H-1-NOE data were obtained for the protected 1,4-linked disaccharide 17 suggesting that its preferred solution conformation is rather similar to the solution conformation of the deblocked disaccharide 23 in aqueous solution as known from literature data.