Solution-phase glycosylation

A soluble aminomethylated polyethylene glycol and a succinoyl linker were used to support a 9-fluorenylmethyl group for solution-phase glycosylation by the sulfoxide method. With the help of temporary protection by a 6-O-triphenylmethyl ether, the method could be carried out iteratively to form disaccharides (Scheme 4.69) [379],... 

SCHEME 38.19. Pol3fmer-assisted solution-phase glycosylation of 2,6-dideox3fthioglycoside. 

Since glycosylated derivatives of this porphyrin core have been shown to be effective photosensitisers, inducing necrosis and/or apoptosis in several cancer cell lines, Drain s group used TPPF20 as a core platform to efficiently generate a variety of solution-phase combinatorial libraries.83 This... 

All the described solid-phase glycosylation protocols required long reaction times to proceed in reasonable yields because of the slower reaction kinetics on support than in solution. Furthermore, since no analytical means were available to monitor the progress of the reaction on the bead, development of optimal reaction conditions was difficult. The approach described by Guthrie and coworkers in the early 1970s for... 

Even controlled-pore glass (CPG) could be successfully employed as solid support with (9-glycosyl trichloroacetimidates as glycosyl donors. Thus, limitations of solvents and reaction temperatures in the glycosylation step, as experienced with the Merrifield resin, are restricted to those observed in solution-phase synthesis. Therefore, regio- and stereocontrol of the glycosylation reactions should be available from well-established solution-phase methodologies. 

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. 

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