Oligosaccharide linkers

The novel L-lysine modified cross-linked chitosan resin containing imine linkers [15] has been studied by the 13C CP MAS spectroscopy.31 However, as some ambiguous results were obtained and the resin was insoluble, instead of the resin a soluble model compound, derivative of chitosan oligosaccharide, has been obtained and investigated. 

Scheme 2.7 Oligosaccharides assembled on solid phase via glycal assembly. The asterisk denotes the achorage site of the first glycal to the solid support via SiPtfe linker.

It has long been recognized that polymeric supports for oligosaccharide synthesis do not need to be insoluble.33 Wang et al. applied the sulfoxide glycosylation method to the synthesis of disaccharide 79 (Scheme 3.14). The key feature of this work was the base-labile linker. Sulfoxide 74 was used to glycosylate polyethylene glycol... 

These authors developed the use of a 4-alkyloxybenzyl ether-type linker attached to the Merrifield resin via an ester function that allowed the cleavage of the oligosaccharides under two different conditions. Using the reactivity of the activated... 

These results demonstrate that O-glycosyl trichloroacetimidate-based oligosaccharide synthesis on solid support may eventually become a valuable alternative to solution-phase synthesis because useful experience is available for the selection of the polymer support and choice of the linker system and the glycosyl donor. Further standardization of the building blocks and the protective group pattern will finally provide the yields and the anomeric control in order to successfully plan automated syntheses of oligosaccharides also in a combinatorial manner. 

The power of the HR-MAS method for on-resin analysis has been further underscored in the development of new linkers. Without this method, only indirect analytical data after removal from the resin was available. Direct assessment of the resin-bound linker greatly facilitated the introduction of a 4,5-dibromo octane- 1,8-diol linker that was converted into an octane-1,8-diol linker cleavable by olefin metathesis at the end of the synthesis.6 The disappearance and reappearance of the olefinic protons as well as the growing oligosaccharide chain was clearly visible in the H spectrum (Fig. 8.7).7... 

TABLE 9.2 Major Linkers Used in Single-Solution Oligosaccharide Synthesis0... 

Many other linkers besides those listed above have been developed for two-phase synthesis of oligosaccharides on insoluble supports, and it can be expected that at least some of them will be tested on soluble supports. It should be kept in mind that MPEG-supported syntheses can be easily scaled up therefore, any relationship between both types of polymer supports will be cooperative rather than mutually exclusive. Such linkers will most probably include dialkyl- or diaryl-silyl linkers,10,41 3 and linkers cleavable by photolysis such as the o-nitrobenzyl group and its modifications.44 16... 

A linker originally designed for solid-phase synthesis of peptides is the backbone amide linker (11) (BAL), this anchoring approach has now been extended to the combinatorial synthesis of diverse amide [31], hydroxamate [32], oligosaccharide [33] and heterocyclic small molecule libraries [34-36]. 

Silyl linkers (Tab. 3.5) have successfully been used for the synthesis of natural products [96, 97], oligosaccharides [98], oligonucleotides [99] and in peptide synthesis [100]. 

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