Anomeric control, problem

Additional problems of anomeric phosphorylation are the control of anomeric selectivity and the increased lability of the products. The preparation of anomeric sugar phosphates can be accomplished via two distinct methods. The first commences with a free anomeric hydroxyl and can be considered as a standard phosphorylation. The second approach... 

The anomeric effect is of prime consideration in synthetic carbohydrate chemistry in fact, some of the most important problems in this area, for example, the synthesis of oligosaccharides and carbohydrate-containing antibiotics, involve an understanding of the reactivity and properties of the anomeric center. In a detailed article concerned with the influence of reactant structure and solvent on glycoside synthesis, Schuerch explores how the anomeric effect of a number of reactants influences the course of kinetically controlled glycosidations. 

To overcome the problems derived from formation of anomeric mixtures when O-benzylated glycosyl halides are used as precursors, Ledford and Carreira52 have disclosed an elegant synthesis of 2,3,4-tri-O-benzyl-a-D-glucopyranosyl isothiocyanate (10) based on the use of l,6-anhydro-2,3,4-tri-0-benzyl-/t-i)-glucopyranose (9) as the glycosyl donor. Treatment of 9 with tetra-n-butylammonium thiocyanate and boron trifluoride-etherate complex provided 10 in 50% yield with total control of the anomeric configuration (Scheme 5). 

Enzymatic approaches to glycoside synthesis may circumvent these problems. Enzymes (i.e. nucleoside glycosyl transferases) are stereospecific and regioselective catalyzing glycosyl transfer reaction under mild conditions. Extensive protection-deprotection schemes are unnecessary and the control of anomeric configuration is managed. 

Stereo-controlled synthesis of fructofuranosides is regarded as a difficult problem, even with a participating group next to the anomeric center [36], The study of TMSOTf-catalyzed glycosylation using fructofuranosyl phosphite showed that a- or P-selectivity was highly dependent on the properties of the acceptor (Figure 7) [36]. 

The first hurdle which must be overcome in the chemical synthesis of sugar nucleotides is the preparation of anomerically pure sugar phosphates. In sialic acid there is no neighboring group which can control the stereoselective phosphorylation of the C-2 center to form the desired P-phosphates selectively. Optimization of protecting groups and phosphorylation protocols led to modest improvements only of the a/p ratios. This problem is not yet solved satisfactorily. 

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