Concerted general acid and nucleophilic catalysis of acetalhydrolysis. A simple model for the lysozyme mechanism

Abstract

The monoanion is the most reactive ionic form of the symmetrical formaldehyde acetal of 4-hydroxybenzofuran-3-carboxylic acid 1. The evidence is consistent with a mechanism in which the carboxylate anion acts as a nucleophile to assist the general acid catalysed cleavage of the C–O bond to the leaving group: the initial product is the cyclic acylal 5 and the extra acceleration derived from the participation of the neighbouring nucleophile (through an unpromising 7-membered ring) contributes some two orders of magnitude to a total rate enhancement of almost five orders of magnitude over the rate expected for specific acid catalysis.