Glycosylation reactions principles

In the first part of this review, the basic principles of chemical glycosylation reactions are discussed this way the advantages of 0-glycosyl trichloroacetimidates and related systems as glycosyl donors become obvious. Many new methods for the generation of 0-glycosyl trichloroacetimidates and for their use as glycosyl donors have been introduced which are... 

Several comprehensive reviews have been devoted to the use of 0-glycosyl trichloroacetimidates in glycosylation reactions. In this overview, so far the basic principles of the glycosylation methods, the strengths of the trichloroacetimidate method, differences to other methods, and methodological variations have been discussed. In this chapter recent applications of this method in complex glycoconjugate synthesis will be highlighted. 

Deacetalization and dethioacetalization. Dimethyl acetals, 4-p-methoxy-phenyl-l,3-dioxolanes are cleaved withDDQ in the presence of water. For deprotection of thioacetals under mild conditions photochemical assistance seems advantageous. The same reaction principle of deacetalization can be extended to ether exchange. Thus alcohol protection is possible by mixing with 2,2-dimethoxypropane in the presence of DDQ, and proximal diols are converted to acetonides. Replacement of anomeric arylmethoxyl groups by this method complements other glycosylation procedures. 

In principle, this strategy can also be extended to other glycosylation reactions. However, it must be assured that the anomeric centre can be readily activated, if possible in one step, to the glycosyl donor and that a... 

As each glycosylation reaction may produce two anomers, many studies are directing at the development of strategies to control the stereochemistry of glycosylation reactions. However, the latter topic is not the focus of this chapter, so only general principles of the stereochemistry of glycosylation reactions are discussed. 

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 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). 

In addition to the Hilbert-Johnson reaction, the so-called mercuri process,37 and, less frequently, the cyclization procedure of Shaw et a/.,53 64 have been used for the synthesis of nucleosides and their derivatives. l-Peracylglycosyl-4-alkoxy-2(l//)-pyrimidinones, the intermediates of the Hilbert-Johnson reaction, can be, in principle, prepared 56,56 also by the mercuri process, namely by reaction of 4-ethoxy-2(lZ/)-pyrimidinone chloromercuri salt with the corresponding halogenoses, but this method is of less importance because of the contamination of iV-l-glycosyl derivatives with the 0-2 isomers, namely, with 2-peracylglycosyloxy-4-alkoxypyrimidines. The advantageous features of the mercuri process in comparison with the Hilbert-Johnson reaction might be formulated as follows. 

Besides the activators mentioned thus far, several additional promoters have been introduced and are summarized in Table 4.6. These include protic and Lewis acids (such as TfOH [290,291]), pyridinium p-toluenesulfonate (PPTS) [292,293], and ZnBr2 [294]. A different type of activation, based on reversible reaction of the promoter with the glycosyl acceptor, was developed by Schmidt [295] and based on this principle, chloral was introduced as a promoter. Activation under essentially neutral conditions can also be achieved using LiC104 [126,158]. 

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