Study of glycosylation with N-trichloroacetyl- d-glucosamine derivatives in the syntheses of the spacer-armed pentasaccharides sialyl lacto- N-neotetraose and sialyl lacto- N-tetraose, their fragments, and analogues

Abstract

The syntheses of 2-aminoethyl glycosides of the pentasaccharides Neu5Ac-α(2→3)-Gal-β(1→4)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc and Neu5Ac-α(2→3)-Gal-β(1→3)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc, their asialo di-, tri-, and tetrasaccharide fragments, and analogues included a systematic study of glycosylation with variously protected mono- and disaccharide donors derived from N-trichloroacetyl- d-glucosamine of galactose, lactose, and lactosamine glycosyl acceptors bearing benzoyl protection around the OH group to be glycosylated. Despite the low reactivity of these acceptors, stereospecificity and good to excellent yields were obtained with NIS–TfOH-activated thioglycoside donors of such type, or with AgOTf-activated glycosyl bromides, while other promotors, as well as a trichloroacetimidate donor, were less effective, and a β-acetate donor was inactive. In NIS–TfOH-promoted glycosylation with the thioglycosides, the use of TfOH in catalytic amount led to rapid formation of the corresponding oxazoline, but the quantity of TfOH necessary for further efficient coupling with an acceptor depended on the reactivity of the donor, varying from 0.07 equiv for a 3,6-di- O-benzylated monosaccharide derivative to 2.1 equiv for a peracetylated disaccharide one. In the glycosylation products, the N-trichloroacetyl group was easily converted into N-acetyl by alkaline hydrolysis followed by N-acetylation.