482
3
Chemical Glycosylation Reactions
field resin (PS–Suc-CO 2 H) by a chemoselective ester formation (→ 18c and 18f). Alkaline
hydrolysis released the octasaccharide from the resin and also all other ester groups were
cleaved. By further known transformations [118] the octasaccharide fragment 18g, containing
the structural motif of the regular region of heparin, was obtained.
An interesting comparative study between solution phase synthesis and synthesis of the same
oligosaccharides on MPEG as soluble support was carried out by the Furneaux group [119].
This study clearly reflected the incompatibility of MPEG as a soluble support with some common reagents, reaction conditions, and choice of standard protecting groups. Hence, the shortcomings associated with this support seem to outbalance the merits [119,120].
To avoid some limitations of PEGs, as for instance low loading, hyperbranched polyester such
as Boltorn H40 and H50 have been successfully investigated in glycosylation reactions with
O-glycosyl trichloroacetimidates [121]. For simple mono- and disaccharide synthesis optimization of the reaction conditions led to practically quantitative transformations.
5 Recent Applications of O-Glycosyl Trichloroacetimidates
in Complex Oligosaccharide and Glycoconjugate Synthesis
Several comprehensive reviews have been devoted to the use of O-glycosyl trichloroacetimidates in glycosylation reactions. In this overview, so far the basic principles of the glycosylation methods, the strengths of the trichloroacetimidate method, differences to other methods,
and methodological variations have been discussed. In this chapter recent applications of this
method in complex glycoconjugate synthesis will be highlighted.
5.1 Glycolipids
Glycosphingolipid synthesis has remained a target of great interest because of the biological
importance of these compounds. Assembly of the sugar residues with O-glycosyl trichloroacetimidates as donors and attachment of the ceramide residue via the azidosphingosine glycosylation procedure [122,123] has become the method of choice. On the basis of this approach,
aminodeoxy analogs of globotriosyl ceramide [124], globo- and isoglobotriosides bearing cinnamoylphenyl tags [125], and a quite practical globotriose synthesis [126], which is essentially
based on O-acyl protection, have been carried out. An efficient glycosylation protocol for the
attachment of an α-linked galactosamine residue for asialo GM2 synthesis has been reported [127]. A novel ether-bridged GM3 lactone analog has been successfully prepared and used
in antibody-based cancer therapy studies [128]. Also ganglioside GD3 was synthesized [129];
comparison with bovine-brain derived GD3 showed that the effects in GD3-triggered uncoupling of mitochondrial respiration and induction of apoptosis in oligodendrocytes are very
similar. Also ganglioside mimics for binding studies with myelin-associated glycoprotein were
prepared [130].
The lacto- and neolacto-series of glycosphingolipids also attracted further attention. The synthesis of the lacto-N-neotetraose and lacto-N-tetraose building blocks has been improved by
using the N-dimethylmaleoyl protecting group [131]. A total synthesis of the natural antigen 19k involved in a hyperacute rejection response to xenotransplants has been carried out as
3
Chemical Glycosylation Reactions
field resin (PS–Suc-CO 2 H) by a chemoselective ester formation (→ 18c and 18f). Alkaline
hydrolysis released the octasaccharide from the resin and also all other ester groups were
cleaved. By further known transformations [118] the octasaccharide fragment 18g, containing
the structural motif of the regular region of heparin, was obtained.
An interesting comparative study between solution phase synthesis and synthesis of the same
oligosaccharides on MPEG as soluble support was carried out by the Furneaux group [119].
This study clearly reflected the incompatibility of MPEG as a soluble support with some common reagents, reaction conditions, and choice of standard protecting groups. Hence, the shortcomings associated with this support seem to outbalance the merits [119,120].
To avoid some limitations of PEGs, as for instance low loading, hyperbranched polyester such
as Boltorn H40 and H50 have been successfully investigated in glycosylation reactions with
O-glycosyl trichloroacetimidates [121]. For simple mono- and disaccharide synthesis optimization of the reaction conditions led to practically quantitative transformations.
5 Recent Applications of O-Glycosyl Trichloroacetimidates
in Complex Oligosaccharide and Glycoconjugate Synthesis
Several comprehensive reviews have been devoted to the use of O-glycosyl trichloroacetimidates in glycosylation reactions. In this overview, so far the basic principles of the glycosylation methods, the strengths of the trichloroacetimidate method, differences to other methods,
and methodological variations have been discussed. In this chapter recent applications of this
method in complex glycoconjugate synthesis will be highlighted.
5.1 Glycolipids
Glycosphingolipid synthesis has remained a target of great interest because of the biological
importance of these compounds. Assembly of the sugar residues with O-glycosyl trichloroacetimidates as donors and attachment of the ceramide residue via the azidosphingosine glycosylation procedure [122,123] has become the method of choice. On the basis of this approach,
aminodeoxy analogs of globotriosyl ceramide [124], globo- and isoglobotriosides bearing cinnamoylphenyl tags [125], and a quite practical globotriose synthesis [126], which is essentially
based on O-acyl protection, have been carried out. An efficient glycosylation protocol for the
attachment of an α-linked galactosamine residue for asialo GM2 synthesis has been reported [127]. A novel ether-bridged GM3 lactone analog has been successfully prepared and used
in antibody-based cancer therapy studies [128]. Also ganglioside GD3 was synthesized [129];
comparison with bovine-brain derived GD3 showed that the effects in GD3-triggered uncoupling of mitochondrial respiration and induction of apoptosis in oligodendrocytes are very
similar. Also ganglioside mimics for binding studies with myelin-associated glycoprotein were
prepared [130].
The lacto- and neolacto-series of glycosphingolipids also attracted further attention. The synthesis of the lacto-N-neotetraose and lacto-N-tetraose building blocks has been improved by
using the N-dimethylmaleoyl protecting group [131]. A total synthesis of the natural antigen 19k involved in a hyperacute rejection response to xenotransplants has been carried out as