Intermolecular General Acid Catalysis of Glycoside Hydrolysis

5 Intermolecular General Acid Catalysis of Glycoside Hydrolysis 

A glycosidase, lysozyme, was the first enzyme whose X-ray strueture was solved, and the meehanism of aetion proposed at the time (1966) postulated general aeid eatalysis by Glu35 the proton was transferred from Glu35 as the CA) bond of the substrate was broken. An example of intramoleeular general aeid eatalysis (the aeeelerated hydrolysis of salicyl p-D-glueopyranoside) was already known, but the lysozyme structure prompted a search for further model systems. 

2-(p-Nitrophenoxy)tetrahydropyran provides such an example. It exhibits a spontaneous reaction with k(30°C) of 8.8xl0 s . Such spontaneous hydrolyses have a j3ig value of —1.18. The pAa of /)-nitroanilinium ion (acid ArNHs ) is 1.0 and that of p-nitroaniline (acid ArNH2) is 18.9. If we assume the difference in values of protonated p-nitrophenol (acid ArOH2 ) and p-nitrophenol (acid ArOH) is the same as that between the analogous aniline and anilinium ion (17.9), then protonated 2-(p-nitrophenoxy)tetra-hydropyran ether is estimated to decompose with a rate constant of 8.8 X 10 X lO - or 1.1 x lO s, i.e. it is far too unstable to exist. 

The hydrolysis of p-nitrophenyl tetrahydropyranyl ether does indeed exhibit general acid catalysis with a Bronsted a of 0.5.  

The effect of altering oxocarbenium ion stability, acid strength and leaving group ability has been measured for dialkylacetals of the type ArCH(OR)(OR ), and also for arylbenzaldehyde acetals of the type PhCH 

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