Glycosylation principle

Evidence for a glycosyl-enzyme intermediate of finite lifetime with inverting a-D-glycosidases, and details of its reaction, came from studies with 2,6-anhydro-l-deoxyhept-l-enitols and glycosyl fluorides. - Analysis of hydration and hydrolysis products on the one hand, and of glycosyla-tion products on the other, indicated an intermediate that could be approached by water from the yff-face only of the ring, and by other glycosyl acceptors only from the a-face (see Schemes 4 and 5 This can be considered a proof of the principle of microscopic reversibility of chemical reactions. 

The glycals are easily converted into the 1,2-dihalo-derivatives, which in principle can act as glycosyl donors. However, these derivatives have not found wide application in glycoside synthesis, mainly because of the low facial selectivity in the initial addition of the electrophilic species [143-145]. In an example of a successful application, 2-deoxy-2-bromo-a-D-glucopyranosyl bromide [146] has been shown to give predominantly the 2-deoxy-P-D-glucopyranosides in silver-triflate-promoted reactions with alcohols. 

The solid-phase synthesis of glycopeptides was first realized by applying the polymeric benzyl ester principle of Merrifield. According to this methodology, Lavielle and associates (50) used 7V-(tm-butyloxycarbonyl)-<9-glycosyl serine derivative 153 for condensation with resin-linked alanine 154. 

However, certain limitations do exist that need to be considered. Although enzymes necessary for post-translational modifications can be added, in principle there is currently no productive system available for the preparation of glycosylated proteins, although some interesting results have already been obtained [161]. Also, the expression of functional membrane proteins in quantities necessary for structural analysis will be a challenging task for the future. 

The enzymatic glycosylation of natural products can be performed in principle by glycosidases, glycosyltransferases, and some other glycoside-processing enzymes -sometimes called transglycosidases. 

It would, in principle, be possible to convert the polyol 115 into the 6"-deoxy sugar 118, a direct precursor of /3-acarbose. However, we decided that it would be better to reassess the whole synthesis and reasoned that a 1,6-epithio sugar such as 119 would be an ideal pivot for a synthesis of acarbose the amine 81 could easily be introduced at C-4, the sulfur at C-1 allows for activation to produce a glycosyl donor ready for attachment to the disaccharide alcohol 113 and, finally, desulfurization at C-6 leads to the necessary methyl group. 

Opdenakker, G., Rudd, P., Pouting, C., Dwek, R. (1993) Concepts and principles of glycobiology. FASEB J. 7, 1330-1337. This review considers the genesis of glycoforms, functional roles for glycosylation, and structure-function relationships for several glycoproteins. 

The chymotiypsin reaction is one example of acyl group transfer (see Fig. 6-21). Glycosyl group transfers involve nucleophilic substitution at C-l of a sugar ring, which is the central atom of an acetal. In principle, the substitution could proceed by an SnI or Sn2 path, as described for the enzyme lysozyme (see Fig. 6-25). 

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