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

The syntheses of 2-aminoethyl glycosides of the pentasaccharides Neu5Ac-alp ha (2 --> 3)-Gal-beta (3(1 --> 4)-GlcNAc-beta (3(1 --> 3)-Gal-beta (1 --> 4 )-Glc and Neu5Ac-alpha (2 --> 3)-Gal-beta (1 --> 3)-GlcNAc-beta (1 --> 3)-G al-beta (1 --> 4)-Glc, their asialo di-, tri-, and tetrasaccharide fragment s, and analogues included a systematic study of glycosylation with variousl y protected mono- and disaccharide donors derived from N-trichloroacetyl-D- glucosamine of galactose, lactose, and lactosamine glycosyl acceptors beari ng benzoyl protection around the OH group to be glycosylated. Despite the. low reactivity of these acceptors, stereo specificity 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 beta -acet ate donor was inactive. In NIS-TfOH-promoted glycosylation with the thiogly cosides, the use of TfOH in catalytic amount led to rapid formation of the corresponding oxazoline, but the quantity of TfOH necessary for further eff icient coupling with an acceptor depended on the reactivity of the donor, v arying 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 pro ducts, the N-trichloroacetyl group was easily converted into N-acetyl by al kaline hydrolysis followed by N-acetylation. (C) 2001 Elsevier Science Ltd. All rights reserved.