Gram scale synthesis of A (type 2) and B (type 2) blood group tetrasaccharides through 1,6-anhydro-N-acetyl-β-D-glucosamine

Abstract Gram scale synthesis of A (type 2) and B (type 2) tetrasaccharides in the form of 3-aminopropyl glycosides is proposed starting from 3-O-benzoyl-1,6-anhydro-N-acetylglucosamine. Its galactosylation followed by re-protection gave lactosamine derivative with single free 2′-OH group in total yield 75%. Standard fucosylation and next run of re-protection in total yield 88% gave a trisaccharide Fuc-Gal-anhydroGlcNAc with single free 3′-OH group. Its standard α-galactosylation gave protected B (type 2) tetrasaccharide. For synthesis of correspondent A tetrasaccharide seven different 2-azido-2-deoxygalactosyl (GalN 3 ) donors were tested: 6-O-acetyl-3,4-O-isopropylidene-GalN 3 thioglycoside was shown to provide the best yield (89%) and stereoselectivity (α/β = 24:1). Further 1,6-anhydro cycle opening, spacer-arming and complete deprotection resulted in the target 3-aminopropyl glycosides of A (type 2) and B (type 2) tetrasaccharides, yields 87 and 85% correspondingly.