Glycosylation rate-limiting step

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. 

Another popular promoter for glycosylation with thioglycosides is the reagent dimethyl(methylthio)sulfonium triflate (DMTST).60 A comparison between DMTST and NIS/TfOH for the formation of sialoglycoconjugates demonstrated that the iodine system provided superior yields and anomeric selectivity in nearly all cases.61 The yields and stereoselectivity also increased with an increase in solvent polarity, suggesting that enhanced stabilization of the oxacarbenium intermediate, the rate-limiting step in glycosylation, was responsible for the increased... 

D. Kahne et al. developed a one-pot multicomponent stereoselective synthesis for the trisaccharide portion of cyclamycin 0 using the Kahne glycosidation.The reactivity of the glycosyl donor was tuned (the rate limiting step is the triflation of the sulfoxide) and the p-methoxyphenyl sulfoxide was activated first. The trisaccharide was obtained in an overall 25% yield with complete a-selectivity. 

Glycosylation is the rate-limiting step even with activated substrates... 

The concentration of dolichyl phosphate in eukaryotic tissues is very low and is probably rate-limiting for the glycosylation processes. Variation of the concentration in the endoplasmic-reticulum membranes is a possible way of controlling the rate of glycosylation. It is important to point out that the early steps in the dolichol biosynthesis are common to such other prenyl derivatives in plants as steroids, essential oils, hormones, phytol, and carotenes (see Scheme 1), and parameters affecting those reactions that may control the dolichol to dolichyl phosphate step could be another mechanism for regulation of the level of dolichyl phosphate. 

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