Glycosylations typical reactions

In the first case, typical reactions are the formation of the methyl fi-D-glucoside from a-D-glucopyranosyl fluoride and of its 2-amino-2-deoxy derivative from 2-amino-2-deoxy-a-D-glucopyranosyl fluoride, on treatment with sodium methoxide in methanol. The products from the reaction of aqueous bases with the glycosyl fluorides depend on the concentration of alkali. At low concentrations, the normal hydrolysis products are formed. At higher concentrations of base, if the proper (trans) steric relation exists between C-6 and the fluorine atom at C-1, anhydro compounds are formed, as in (21) from (20). 

Glycosylation transfer reaction catalyzed by GGTase is divided into four types hydrolysis reaction, cychzation reaction, couphng reaction and disproportionation reaction, in which the coupling reaction in some documents is also known as the open-loop reaction. The direction of glycosylation reaction catalyzed by the GGTase depends on the reaction rate constant of the four types of reaction. Typically, the rate constant of cychzation reaction is greater than that of the hydrolysis reaction, and therefore the direction of the reaction is mainly to produce GD (Fig. 2.3). 

Copper-based Lewis acids can be applied to various kinds of reaction. While Cu1 complexes catalyze acetal formation (Scheme 44), Cu(OTf)2 is used for formation of glycosyl bonds. 86,187 Since the ability of Cu(OTf)2 to be chelated by the substrate is essential for the reaction, typical Lewis acids such as BF3-OEt2 and Me3SiOTf are ineffective. 

Anomeric halides follow the typical reactivity order F < Cl < Br < I for nucleophilic substitutions. They have been used in stereoselective O-glycosylation, nucleophilic displacement, and carbanion as well as in radical reactions. 

Although aliphatic alcohols are typically poor acceptors in the Mitsunobu-type glycosylation, Szarek and coworkers have highlighted one advance to this end [95]. For the triphenylphosphine and diethylazodicarboxylate promoted glycosylation of a monosaccharide acceptor, the addition of mercuric bromide is necessary to promote the reaction. For example, the (1,6)-disaccharide 44 was obtained in 80% yield using this modified Mitsunobu protocol. Unlike previous examples with phenol or N-acceptors, preactivation of the hemiacetal donor was performed for 10 min at room temperature prior to addition of the aliphatic alcohol nucleophile. 

A typical procedure calls for reaction of the hemiacetal donor with dicydohexyl carbodiimide and copper(I) chloride (0.1 equiv) at 80 °C, followed by an addition of the acceptor and continued heating. As an early demonstration of this protocol, oc-riboside 86 was prepared in moderate yield but with exclusive stereoselectivity [141]. Further measures were required for the glycosylation of monosaccharide acceptors, such as addition of p-toluenesulfonic add (0.1 equiv) to promote the formation of disaccharide 87 [144]. The method was more suitably applied to the synthesis of O-acyl glycopeptides, as evidenced by the formation of 88 in 60% yield [143,144]. Various peptides with non-nudeophilic side chains were found to be amenable to this stereoselective reaction. The [3-selectivity was suggested to arise from a preponderance of the a-isourea intermediate 85 in the activation step. 

To facilitate the analysis of random glycosylation reactions, all six possible products (13-18) were synthesized as reference standards to simplify the determination of product distributions.11 These standards could be separated on a PAC column permitting direct analysis of mixtures by HPLC. A typical chromatogram of a separation of a random glycosylation is shown in Figure 12.9. 

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