Development of automated synthesis of oligosaccharides based on solid-phase methodology

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Solid-phase synthesis of oligosaccharides was investigated in order to develop automated synthesis of oligosaccharides. The most fundamental problem in solid-phase oligosaccharide synthesis is heterogeneity of polymer supports that causes insufficient glycosylation on solid support. Two new methods were developed for efficient solid-phase synthesis of oligosaccharides in the present study.The one is a new catch-and-release method of isolation for products using a specific reaction. Desired compounds possessing the 4-azido-3-chlorobenzyl group were selectively isolated from a crude mixture by means of the facile reaction between the azido group and polymer-supported phosphine. This method was successfully applied to the solid-phase synthesis of an oligosaccharide elicitor. Glcβ1-3Glcβ1-3 (Glcβ1-6)Glcβ1-3Glc was synthesized via elongation of saccharide chain on solid-support, cleavage of the protected oligosaccharide from the resin, catch-and-release isolation, and final deprotection.The other is selection of reactive region on polymer supports by using Sonogashira coupling reaction of glycosyl acceptors having an alkyne function with iodobenzamide on supports. Alkynylmethyl glycoside or alkyne ester was used as linker parts. These linkers were cleaved by treatment of Co_2(CO)_8 and TFA. The latter linker was also cleaved under basic conditions. The glycosylation reaction smoothly proceeded on the selected area of the supports to give the desired glycosides in quantitative yields.Automated synthesis of oligosaccharides was carried out by using commercially available multipurpose synthesizer.