Continuous flow biocatalyzed process enhanced production of (R)-1,2-propanediol mediated by Immobilized Candida Antarctica Lipase B

Enantiomerically pure (R)-1,2-propanediol has important applications as a building block in the manufacture of pharmaceutical products such as antiviral agents and pheromones.1 Several strategies have been successfully applied to the resolution of (R,S)-1,2-propanediol (1) and its derivatives. Taking advantage of the ability of some lipase to resolve racemic mixtures with a high level of stereoselectivity, some authors have applied it on the resolution of (R,S)-1 using bulky ether protecting groups on the primary alcohol in order to enhance selectivity on kinetic and dynamic resolution.2 However, the methodologies developed so far suffers from long reaction times leading to the desired product (up to 24 hours). In our continuous effort on developing biocatalyzed continuous-flow process as key green emerging research area for sustainable manufacturing,3 we reported our results on the kinetic resolution of (R,S)-1- (trityloxy)propan-2-ol, (R,S)-2, using a packed-bed containing lipase B from Candida antarctica immobilized on acrylic resin (Novozyme435) on continuous-flow. The continuous flow reactors allowed to reduce the reaction time, going from 6 h in batch to 7 min in flow, keeping the values of conversion and selectivity during the reaction procedure (49% and >99% conversions and enantiomeric excess, respectively) and increasing the productivity of the process in all stages. In addition, the continuous flow reactor increased the productivity of kinetic resolution of (R,S)-2 to 300% in comparison with batch reactor, after its optimization, and allowed continuous operation for 8 h in the kinetic resolution reaction.