Enzymatic kinetic resolution of benzylic alcohols performed in continuous flow bioreactor

Secondary benzylic alcohols are chiral building blocks of wide use in the synthesis of pharmaceuticals and they can be produced with great enantioselectivity when performing enzymatic kinetic resolution (EKR), a technique that utilizes enzymes and appropriate reaction conditions to induce a much faster reactivity by one enantiomer than for another, allowing separation. Aiming for more efficient methodologies, the enzymes were immobilized in calcium alginate beads, which were used to pack a homemade bioreactor where we performed the EKR of secondary benzylic alcohols by the hydrolysis of the corresponding esters in continuous flow. Using (rac)-1-phenylethyl acetate as a model substrate, we obtained 45% conversion and >99% enantiomeric excess for (R)-1-phenylethanol with Burkholderia cepacia lipase. With such excellent results, the same system was applied to a series of similar substrates and good conversion and enantioselectivity were observed. Enzyme reuse was also evaluated to raise even more the productivity of the developed bioreactor.