Direct Experimental Evidence for the High Chemical Reactivity of alpha- and beta-Xylopyranosides Adopting a (2,5)B Conformation in Glycosyl Transfer

The effect of a (2,5)B boat conformation on xyloside reactivity has been investigated by studying the hydrolysis and glycosylation of a series of synthetic xyloside analogues based on a 2-oxabicyclo[2.2.2] octane framework, which forces the xylose analogue to adopt a (2,5)B conformation. The locked beta-xylosides were found to hydrolyze 100-1200 times faster than methyl beta-D-xylopyranoside, whereas the locked alpha-xylosides hydrolyzed up to 2 x 10(4) times faster than methyl alpha-D-xylopyranoside. A significant rate enhancement was also observed for the glycosylation reaction. The high reactivity of these conformers can be related to the imposition of a (2,5)B conformation, which ap-proximates a transition state (TS) boat conformation. In this way, the energy penalty required to go from the chair to the TS conformation is already paid. These results parallel and support the observation that the GH-11 xylanase family force their substrate to adopt a (2,5)B conformation to achieve highly efficient enzymatic glycosidic bond hydrolysis.