Linkers oligosaccharide synthesis

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 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. 

L. G. Melean, W. C. Haase and P. H. Seeberger, A novel 4,5-dibromooctane-l,8-diol linker for solid-phase oligosaccharide synthesis, Tet. Lett., 2000, 41, 4329 1333. 

Fig. 2. Application of the polyethylene glycol-co-monomethyl ether (MPEG) solid support with an a,a -dioxyxylyl (DOX) diether linker for oligosaccharide synthesis in solution.

Scheme 6.1.24. Oligosaccharide synthesis on a solid support using the DBOD linker.

Andrade RB, Plante OJ, Melean LG, Seeberger PH. Solid-phase oligosaccharide synthesis Preparation of complex structures using a novel linker and different glycosylating agents. Org. Lett. 1999 1 1811-1814. 

Fukase, K, Nakai, Y, Egusa, K, Porco, J A, Kusumoto, S, A novel oxidatively removable linker and its application to a-selective solid-phase oligosaccharide synthesis on a macroporous polystyrene support, Synlett, 1074-1078, 1999. 

A simple formylacetal (CH2) has also been used as a linker for oligosaccharide synthesis on MPEG. This small linker allows the hindered hydroxyls, such as the 4-hydroxy group of glucose, to be installed on the MPEG [60]. The formylacetal linker is stable under the acidic conditions mostly used for glycosylation, but it is readily cleaved by Lewis acids (TMSI or Ce(OTf)x) or trifluoroacetic acid. A simplified work-up and purification procedure was also reported by use of the solid acid catalyst. 

Scheme 6.192 shows the o-nitrobenzyl moiety used as a photolabile linker in the solid-phase oligosaccharide synthesis on a polystyrene (PS) support.1208 After the synthesis of the protected oligosaccharide 404, PS attached to the photoremovable group is removed by photolysis and the final product is obtained by hydrogenolysis. Such a strategy could be promising for combinatorial synthesis of oligosaccharide libraries. 

To increase the stability of p-alkoxybenzyl resins to acids, Porco and Kusumoto introduced the p-acylaminobenzyl linker [68], which they found to be suitable for anchoring glycosides for oligosaccharide synthesis (Scheme 17.26). 

Scheme 17.26 Use of the p-acylaminobenzyl linker in anchoring glycosides for oligosaccharide synthesis.

Considerable effort has been made in recent years to improve the yields of oligosaccharide synthesis. The selection of the appropriate functional resin is, in many cases, crucial to the outcome of oligosaccharide syntheses. Here, we briefly review the functional resins that have been used for oligosaccharide synthesis. The chapter is divided into two main sections First the most common insoluble and soluble resins applied in oligosaccharide synthesis are reviewed and then the different types of linkers applied in oligosaccharide synthesis are summerized. Two subsections are dedicated to ionic liquids (Section 20.3.3), representing a special case of soluble resins , and magnetic parhcles (Section 20.2.3), which are considered a relatively new concept of insoluble solid supports. 

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