Models for enzyme-catalysed phosphate transfer: comparisons of reactivity towards a neighbouring hydroxy group for phosphodiester anions and acids. General base catalysis of the cyclisation of a hydroxyalkyl phosphate triester

Abstract

Methylation of phenyl 1,2-isopropylidene-β-D-xylofuranose 3′-phosphate increases the rate of intramolecular cyclisation by a factor of over 10⁵. This confirms previous estimates of the effect of protonation on the reactivity of phosphate diesters towards a neighbouring hydroxy group, which depend on the correct assignment of kinetically equivalent mechanisms, and makes available reliable data on the magnitude of the effect for reactions catalysed by a range of general acids and bases. General base catalysis is characterised for the intramolecular cyclisation of one diastereoisomer (7b) of methyl phenyl 1,2-isopropylidene-β-D-xylofuranose 3′-phosphate triester: the Brønsted β is 0.65 and catalysis is enhanced by the proximity of the positive centres of suitable diamine monocations.