Stereoelectronic effects at oxygen. A very large effect on the hydrolysis of a conformationally locked acetal: implications for β-glycosidase mechanisms

Abstract

Acetal [6; R = 2,4-(NO₂)₂C₆H₃] is rigidly fixed in the equatorial conformation. As a result the lone-pair electrons on the ring oxygen cannot assist C–OR cleavage, and the compound is hydrolysed ca. 10¹³ times more slowly than a comparable axial tetrahydropyranyl acetal, allowing an estimate of 19 kcal mol^–1 for the stereoelectronic barrier to the cleavage of an equatorial tetrahydropyranyl acetal, or β-glucoside, in its ground-state chair conformation. A conformational change, of the sort originally proposed by Phillips and his co-workers for the lysozyme reaction, is thus shown to be an essential preliminary to the cleavage of any β-glycoside.