Synthetic Studies

1,6-Anhydro-N-Acetyl-β-D-Glucosamine in Oligosaccharide Synthesis: II. The Synthesis of the Spacered Ley Tetrasaccharide

N. E. Byramova1#, A. B. Tuzikov1, T. V. Tyrtysh1 and N. V. Bovin1

#Phone: (495) 330-74-92; e-mail:

1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia

Received: April 3, 2006; in final form: May 11, 2006

Abstract. 3-Aminopropyl glycoside of 3,2′-di-O-α-L-fucosyl-N-acetyllactosamine (Ley tetrasaccharide) was synthesized. The glycosyl donor, 2-O-acetyl-2,4,6-tri-O-benzoyl-α-D-galactopyranosyl bromide, was coupled with glycosyl acceptor, 1,6-anhydro-2-acetamido-2-deoxy-β-D-glucopyranose or its 3-O-acetyl derivative, to give the corresponding N-acetyllactosamine derivatives in 20 and 71% yields, respectively. The glycosyl donor was synthesized from 1,2-di-O-acetyl-3,4,6-triO-benzoyl-D-galactopyranose, which was obtained by the treatment of benzobromogalactose with sodium borohydride to yield 1,2-O-benzylidene derivative and subsequent removal of benzylidene group and acetylation. Acidic methanolysis of the disaccharide derivatives resulted in the selective removal of one or both acetyl groups to give the disaccharide acceptor bearing hydroxy groups at C3 of the glucosamine residue and C2 of the galactose residue. The introduction of fucose residues in these positions by the treatment with tetrabenzylfucopyranosyl bromide resulted in a tetrasaccharide derivative, which was converted into 3,2′-di-O-α-L-fucopuranosyl-1,6-anhydro-N-acetyllactosamine peracetate after substitution of acetyl groups for benzoyl and benzyl groups. Opening of the anhydro ring by acetolysis resulted in peracetate, which was then converted into the corresponding oxazoline derivative by two steps. Glycosydation of the oxazoline derivative with 3-trifluoroacetamidopropan-1-ol and removal of O-acetyl and N-trifluoroacetyl protective groups resulted in a free spacered Ley tetrasaccharide.

Key words: 1,6-anhydro-GlcNAc, glycosylation, oligosaccharides, tumor-associated antigens

Russian Journal of Bioorganic Chemistry 2007, 33 (1): 99-109