Activation of glycosyl phosphates

Synthesis of glycosyl phosphates by exposure of hemiacetals to 81 activated derivatives of phosphoric acid... 

Synthesis of glycosyl phosphates by activation of the anomeric hydroxyl group... 

Synthesis of glycosyl phosphates by reaction of hemiacetals with activated phosphoric acid derivatives... 

It seemed of interest to check whether the type of biosynthetic mechanism involved may be related to the structure of the polymeric chain formed. In the block mechanism of chain assembly, formation of polyprenyl glycosyl diphosphates through transfer of glycosyl phosphate is a necessary step of the process. Thus far, only UDP-activated monosaccharides have been found to participate in this reaction (see Section 11,3). Consequently, the presence of a monosaccharide residue of this group in the main chain of a polymer may be regarded as a necessary condition for assembly of the chain through the block mechanism. 

Treatment of active vinyl glycosides with NIS/TMSOTf in CH2CI2 in the presence of dibenzyl phosphate gives good yield of glycosyl phosphates [184]. 

This chapter desribes the synthesis of glycosyl phosphates and their use as glycosylating agents. Their use in die construction of complex oligosaccharides, both in solution and on solid support, is presented. Their ease of synthesis in combination with their rapid activation have made them ideal glycosylating agents to be used for automated solid phase oligosaccharide synthesis. 

The activation of a phosphate group requires a stoichiometric amount of Lewis acid. Glycosyl phosphates can generally be stored for several months in the freezer without significant degradation. 

The typical and widely used procedure for the activation of the anomeric centre involves the initial preparation of acylated glycosyl halides, which are then subjected to SN2-like displacement by a phosphate anion in the presence of a silver-containing promoter and a base. 

Although addition of activated phosphoramidite to hemiacetals of manno-pyranoses under thermodynamic control has been reported to deliver exclusively a-phosphates in some cases,43 anomeric mixtures with preponderance of a-anomer have been reported in other examples.10,44 Since formation of phosphorotetrazolidite is a rate-limiting step of the process, initial activation of phosphoramidite followed by addition of nucleophilic hemiacetal should accelerate condensation and favour the formation of the thermodynamic a-product. Indeed, reaction of hemiacetal 101 with dibenzyl phosphorotetrazolidite assured exclusive a-selectivity of the resulting glycosyl phosphate 102.43 The accumulation in the reaction mixture of mildly acidic 1H-tetrazole, which is liberated upon reaction of tetrazolidite with hydroxylic component, could also favour predominant formation of the a-phosphate (Scheme 18, A). Conventional hydrogenolysis afforded the a-mannosyl phosphate 103. 

---