Enzymatic glycosidation sialylation

Scheme 9.11 Enzymatic transsialylation of four MPEG-DOXyl glycosides with sialidases from Vibrio cholerae and Salmonella typhimurium. V. cholerae sialylated in position 6 of the terminal monosaccharide units with yields of 12-17%, whereas S. typhimurium sialylated position 3 of the same monosaccharide units (yields 14-24%).

Complex alkaloid glycosides bearing, e.g., lactosyl (Lac), lactosaminidyl (Lac-NAc), or sialyl (Neu5Ac) moieties were required for immunomodulation tests (see below). Because of the paucity of starting material (alkaloid monoglycosides) and because of the need of regioselective glycosylation, only enzymatic reactions were practicable. 

Following the enzymatic synthesis of CMP-Neu5Ac, isolated a2-6-sialyl-transferases could be used to introduce sialic acid to the N-acetyl lactosamine derivates a-f in position 6. This afforded a series of trisaccharide derivates Neu5Aca2-6 Gal l-4GlcNAc l-R. The unblocked trisaccharide a [55], the methyl glycoside b [56], the -Asn derivative c [57], the pentapeptide derivative d [58], the allyl e [59], and the pent-4-enyl glycoside f [48] can be prepared in convincing yields (Fig. 6). 

Cell-surface sialic acid residues play important roles in diverse biological processes [86]. Sialic acids are usually found in terminal positions linked through an a-glyco-sidic linkage. The stereoselective synthesis of a-sialosides remains a challenge because the glycosides have the thermodynamically unfavorable equatorial orientation and the anomeric carbon is a very hindered quaternary center [4]. Enzymatic sialylation is, therefore, an attractive alternative means of preparation of a-sialosides in an efficient and stereocontrolled manner. 

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