Integration of (catalytic) reaction step is one of the key principles of Green Chemistry. It circumvents the work-up of intermediate products, and is an elegant way of orchestrating a step-wise conversion process. Mimicking how nature makes products within a cell.  Our lab has a large tradition of realizing (chemo)enzymatic cascade reactions .1,2

Biocatalytic cascades for oxyfunctionalization

Oxyfunctionalization reactions in general suffer from notorious non-selectivities, due to autoxidative side-reactions, and lack of regio-selectivity. The cofactors required in these cases need to be either circumvented (e.g. by using peroxygenases), or be regenerated in-situ. In all cases cascading of enzymatic reactions is a real advantage, for which flow-reactors can provide an advantage. The proof of principle of combining three biocatalytic steps in a so-called enzyme loaded polymersome continuous-flow batch reactor, including a final biocatalytic oxyfunctionalization, was reported in our labs for the combination of a lipase and glucose oxidase. 3

In a new FET-open project, together with our collaborators, an enzymatic cascade for the synthesis of ursodeoxycholic acid will be probed in flow reactors. Scalable sustainable production process is the goal. Direct orthogonal flow involving multiphase systems and novel solvents will be needed towards that goal.

  1. C. Simons, U. Hanefeld, I.W.C.E. Arends and T. Maschmeyer, A one-pot enantioselective chemo-enzymatic synthesis of amino acids in water, Adv. Synth. Catal. 348 (4-5) (2006) 471-475.
  2. M. Eckert, A. Brethon, Y.X. Li, R.A. Sheldon and I.W.C.E. Arends, Study of the efficiency of amino-functionalized ruthenium and ruthenacycle complexes as racemization catalysts in the dynamic kinetic resolution of 1-phenylethanol, Adv. Synth. Catal. 349 (2007) 2603-2607.
  3. H.M. de Hoog, I.W.C.E. Arends, A.E. Rowan, J.J.L.M. Cornelissen and R.J.M. Nolte, A hydrogel-based enzyme loaded polymersome reactor, Nanoscale 2 (2010) 709-716.