Synthesis of a pentasaccharide and a heptasaccharide corresponding to an ovarian glycoprotein; studies towards glycosylations

Abstract

The syntheses of pentasaccharide I and heptasaccharide II, which correspond to an ovarian O-glycoprotein, are presented. The protected pentasaccharide 1 was prepared by condensing a trisaccharide donor 18c with a disaccharide acceptor ( 8b, while condensation of the same trisaccharide donor ( 18c) with a tetrasaccharide acceptor ( 25b) provided the protected heptasaccharide 2. Special attention was paid to the deblocking of the protected derivatives 1 and 2 to give I and II, respectively. The β-bonds in 8b and 25b were prepared by using glycosyl donors with non-participating groups at C-2, which were earlier applied for the synthesis of α-glycosides. For the synthesis of the trisaccharide donor ( 18c), condensations of several activated Galα(1->3)Gal disaccharides with protected GlcNAc residues were compared. It was found that the α/β ratio and the yield of this glycosylation are influenced by the leaving group at the anomeric centre, the character of the participating acyl group and, in particular, by the unfavourable steric interaction between donor and acceptor. In order to reduce this steric interaction between donor and acceptor, the conformation of the GlcNAc acceptor was changed to the 1,6-anhydro derivative 16, which afforded in the glycosylation with glycosyl bromide 13c a high yield of the desired trisaccharide 17.