Synthesis of Neu5Ac-and Neu5Gc-alpha-(2 -> 6 ')-lactosamine 3-aminopropyl glycosides

In order to prepare 3-aminopropyl glycosides of Neu5Ac-alpha-(2 --> 6')-lac tosamine trisaccharide 1, and its N-glycolyl containing analogue Neu5Gc-alp ha-(2 -->,6')-lactosamine 2, a series of lactosamine accepters with two, th ree, and four free OH groups in the galactose residue was studied in glycos ylations with a conventional sialyl donor phenyl [methyl 5-acetamido-4,7,8, 9-tetra-O-acetyl-3,5-dideoxy-2- thio-D-glycero-alpha- and beta -D-galacto-2 -nonulopyranosid]onates (3) and a new donor phenyl [methyl 4,7,8,9-tetra-0- acetyl-5-(N-tert-butoxycarbonylacetamido)-3, 5-dideoxy-2-thio-D-glycero-alp ha- and beta -D-galacto-2-nonulopyranosid]onates (4), respectively. The lac tosamine 4',6'-diol acceptor was found to be the most efficient in glycosyl ation with both 3 and 4: while imide-type donor 4 gave slightly higher yiel ds with all accepters, and isolation of the reaction products was more conv enient. In the trisaccharides, obtained by glycosylation with donor 4, the 5-(N-tert-butoxycarbonylacetamido) moiety in the neuraminic acid could be e fficiently transformed into the desired N-glycolyl fragment, indicating tha t such protected oligosaccharide derivatives are valuable precursors of sia lo-oligosaccharides containing N-modified analogues of Neu5Ac. (C) 2001 Els evier Science Ltd. All rights reserved.