Biocatalysed Concurrent Chiral Synthesis through Parallel Interconnected Kinetic Asymmetric Transformations

ANA RIOZ-MARTÍNEZ; FABRICIO R. BISOGNO; CRISTINA RODRÍGUEZ; GONZALO DE GONZALO; IVÁN LAVANDERA; DANIEL E. TORRES PAZMIÑO; MARCO W. FRAAIJE; VICENTE GOTOR

Berna, Suiza

Congreso; BIOTRANS 2009; 2009

  Processes in Organic Chemistry often have to deal with enantio- or diastereomeric mixtures. Different biocatalytic strategies have been developed in order to successfully achieve the resolution of stereoisomers, like the kinetic resolution (KR) or the parallel kinetic resolution (PKR). Recently, novel methodologies such as dynamic kinetic resolutions (DKR), enantio-convergent processes (ECP) or cyclic deracemisations (CycD) are becoming more relevant. Finally, a method to transform diastereomers into only one final stereoisomeric product has been described: dynamic kinetic asymmetric transformation (DYKAT).1 Biocatalytic processes using redox enzymes have been developed in the last years due to the high selectivities obtained employing mild and environmental friendly conditions. Examples of these oxidoreductases are alcohol dehydrogenase (ADHs) and Baeyer-Villiger monooxygenases (BVMOs). The synthesis of chiral secondary alcohols via reduction of ketones or oxidative kinetic resolutions of rac-alcohols using ADHs has gained increasing interest.2 BVMOs are flavoproteins able to catalyse the oxidation of carbonyl compounds and different heteroatoms.3 Despite the advantages provided by these enzymes, their use in isolated form remains impeded due to the high costs related to the nicotinamide cofactor needed by these redox biocatalysts. Thus, various methods have been explored in order to regenerate the coenzymes NAD(P)H or NAD(P)+. These methodologies have several drawbacks such as harmful effects on the biocatalyst, remaining high costs and loss of material.4   Herein we describe a new concept which allows the concurrent formation of chiral organic compounds, thereby minimising the quantity of reagents employed (Scheme 1). By starting from two racemic compounds, two redox enzymes (an ADH plus a BVMO) and a catalytic amount of coenzyme (acting as connector of both biotransformations), we have been able to obtain in a one-pot process, three chiral compounds in a strict parallel fashion. This novel approach has been described as Parallel Interconnected Kinetic Asymmetric Transformations (PIKAT).5