Is the ring conformation the most critical parameter in lipase-catalysed acylation of cycloalkanols?

Abstract

CAL-B catalysed the resolution of several five and six-membered cyclic β-hydroxy esters efficiently with the exception of the cis-cyclohexanol (±)-4. When employing molecular modelling techniques the conformation turned out to be the most important determinant for their reactivity towards O-acetylation. In all cases, the R enantiomers reacted faster than the S enantiomers since the reactive intermediates of the former can adopt more favourable ring conformations and thus experience less steric hindrance in the active site. Furthermore, the minimised structure for the main conformer of R-4 showed that the axial hydrogens in the 3 and 5-positions with respect to the hydroxyl group prevent the enzymatic reaction.