Recent advances in o-sialylation
Boons, G.J.; Demchenko, A.V.
Chemical Reviews 100(12): 4539-4566
2000
ISSN/ISBN: 0009-2665 PMID: 11749357 Document Number: 7484
Despite recent progress in the chemical and enzymatic sialylation of saccharides, no approach has been reported that allows glycosylation of a wide range of acceptors in high yields and stereoselectivities. Anomeric chlorides of Neu5Ac offer the most reliable glycosyl donor for the preparation of glycosides of simple alcohols. 2-Thioalkyl, 2-thiophenyl, 2-xanthate, and 2-(dibenzyl) or 2-(diethyl)phosphites are the leaving groups of choice when more complex hindered sugar alcohols need to be sialylated. The best results are obtained when saccharide acceptors have a free diol or triol, and in many of these cases the sialylations proceed with excellent regioselectivities in combination with high yields and anomeric selectivities. Several glycosyl donors of Neu5Ac have been prepared that have an auxiliary at C-3. These auxiliaries control the anomeric selectivity of a glycosylation by neighboring group participation. Glycosyl donors that possess an equatorial S-phenylparticipating auxiliary at C-3 and thioalkyl leaving group at C-2 generally give the best yields and R-anomeric selectivities especially when applied for the glycosylation of sterically hindered alcohols. A 3-O-phenylthiocarbonyl auxiliary also gives excellent yields and stereoselectivities. The major drawbacks of indirect methods are the additional chemical steps required for introduction and removal of the auxiliary at C-3. Furthermore, the introduction of a C-3 auxiliary in many cases proceeds with poor stereoselectivity rate. Despite these drawbacks, the indirect methods offer the most reliable approach for the synthesis of the dimer Neu5AcR(2 f 8)Neu5Ac. Several R(2 f 6)- and R(2 f 3)-sialyltransferases have been used for oligosaccharide synthesis, and the most attractive approach involves in situ regeneration of CMP-Neu5Ac. The substrate specificity of these enzymes precludes the synthesis of a wide range of sialooligosaccharides. Sialidases have also been used for the preparation of sialosides. These enzymes have less restricted substrate specificities, but yields and regioselectivities are in most cases low. Recent progress allows chemical, enzymatic, or chemoenzymatic synthesis of complex sialooligosaccharides. Each synthetic target, however, should be regarded as a research project, and several reaction conditions, methods, or strategies may need to be examined to obtain an efficient synthetic approach. Most synthetic efforts have been directed to the glycosylation of Neu5Ac. Less effort has been spent on the preparation of sialosides that have an Nglycolyl moiety (Neu5Gc) or have an acetyl, lactoyl, methyl, or phosphate at one of the hydroxyls.
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