Total enzymatic resolution of racemic 2-(4-methoxybenzyl)-1-cyclohexanols and 2-(4-methoxybenzyl)-1-cyclopentanols

Total resolution of the racemic cis- and trans-2-(4-methoxybenzyl)-1-cyclohexanols and 2-(4-methoxybenzyl)-1-cyclopentanols with Candida antarctica lipase B-catalysed transesterification was reached: high temperature (80-100 °C) and aw<0.1 were a good combination to improve initial rates and to reach maximum (R)-alcohol conversion. The (S)-alcohol conversion was also enhanced by increasing temperature, and unlike the (R)-enantiomers, by increasing the water activity of the system (aw). Very high enantioselectivities (E>2000) of Novozym 435 towards the racemic molecules were obtained. Variations in aw, temperature and length of acyl donor chain did not alter the high enantiomeric ratio. The total resolution (e.e.>99.9% when conversion c=50%) of the four substrates was achieved by elongating the acyl part of the donor substrate. The accuracy in determining the enantiomeric ratio was discussed and hypotheses were raised concerning the apparent sequential order of conversion of the enantiomers.