Solid-phase glycosidations

Figure 8.4 Process of solid-phase glycoside synthesis. In the process, X = linker which is later incorporated into the pol5mer matrix A = activating group for anomeric hydroxyl Y = temporary anomeric hydroxyl protecting group Tr = tiityl, and R = semipermanent protecting group for secondary hydroxyls. The wavy bond represents either a- or P-anomeric configuration...

Solid phase NMR techniques have advanced to the point where there are routine techniques for following reactions and confirming structures on all common resin materials. Natural abundance gel phase and NMR are used for assessing intermediate structures in solid phase synthesis [21-23]. NMR has proved useful for determining anomeric configuration in a solid phase glycosidation reaction [24]. 

Scheme 5.63 Use of glycals in solid-phase synthesis of glycosides.

The fhioethyl group present in the anchor group of (40) was activated by treatment with N-iodosuccinimide (NIS) followed by displacement with a variety of alcohols (44-46). To prove the possible application of this linker in solid phase carbohydrate synthesis, protected glycosides (47) and (48) were coupled to linker (40) and released enzymatically. Flitsch et al. also described the immobilization and enzymatic cleavage on a variety of amines [41]. Nevertheless, the application of this enzyme-labile hnker group in multi-step syntheses on the solid phase and subsequent enzyme-initiated release from the polymeric support has not been described yet. 

Andre, S. Pei, Z. Siebert, H.-C. Ramstrom, O. Cabins, H.-J. Glycosyl-disulfides from dynamic combinatorial libraries as O-glycoside mimetics for plant and endogenous lectins Their reactivities in solid-phase and cell assays and conformational analysis by molecular dynamics simulations. Bioorg. Med. Chem. 2006,14, 6314-6326. 

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