Designing Multi-enzymatic Systems for the Preparation of Optically Active Molecules
The combination of multiple biocatalysts applied to cascade protocols is very plausible as enzymes usually operate under similar reaction conditions concerning pH, temperature and solvent medium. From an operational point of view, the application of these methodologies presents several advantages over the classic step-by-step design. As they are performed in the same vessel (‘one-pot’), there is no need for intermediate purification, and therefore costs, operating time and waste are reduced, improving the atom economy and the overall process yield. These protocols allow rapid complexity generation, the shifting of reaction equilibria, and the elimination of inhibition problems or the minimisation of the decomposition of unstable intermediates. In this chapter, we have chosen to adopt a fairly broad conception of recently described multi-enzymatic cascades, including concurrent or sequential biocatalytic ‘one-pot’ systems, even if some of the steps involve chemocatalysis and/or spontaneous (non-catalysed) transformations. Particularly, we will focus on reaction designs which provide the final products in enantioenriched form, although a few non-stereoselective examples will also be reported due to their outstanding synthetic relevance and applicability. While most of the examples described can be classified into four main types of cascade systems, namely linear-, parallel-, orthogonal-, and cyclic-cascades, or into combinations of them, some other examples will cover dynamic and enantioconvergent transformations.