Obtaining of β-Hydroxyesters through Dynamic Processes Catalysed by Alcohol Dehydrogenases

IVÁN LAVANDERA; ANÍBAL CUETOS; ANA RIOZ-MARTÍNEZ; FABRICIO R. BISOGNO; BARBARA MAUTNER; CRISTINA RODRÍGUEZ; GONZALO DE GONZALO; WOLFGANG KROUTIL; VICENTE GOTOR

SICILIA

Conferencia; BIOTRANS 2011; 2011

BIOTRANS

In the last few years, the employment and development of dynamic protocols in order to obtain enantio- or diastereomerically pure compounds starting from easily available racemic starting material has largely increased. In this sense, more and more processes involving enzymatic and homogeneous catalysis in dynamic conditions are designed to achieve successful transformations to synthesise optically pure high-added value derivatives.[1]One of the most typical examples of a dynamic process is the reduction of α-substituted β-ketoesters (Scheme 1) to obtain the corresponding alcohols with high diastereomeric excesses (des).[2] This process has been successfully achieved using both metal- and enzyme catalysis due to high acidity of the α-hydrogen that ensures a fast substrate racemisation even at neutral pHs (Scheme 1).Scheme 1. Bioreduction of α-substituted β-ketoesters affording a mixture of diastereomeric alcohols employing ADHs.Concerning the bioreduction of these and related derivatives, the first examples were shown employing whole cells such as baker’s yeast, and although in some cases excellent conversions and enantiomeric excesses (ees) were achieved, the presence of several active enzymes also depleted the selectivity in many cases.[2] More recently, the development of these dynamic protocols using purified or overexpressed alcohol dehydrogenases (ADHs),[3] has overcome this problem although in hand with efficient techniques to recycle the expensive cofactor needed in these processes. Herein we would like to show the use of several purified and overexpressed ADHs applied to the bioreduction of several α-substituted β-ketoesters in order to obtain the corresponding alcohols with excellent enantiomeric and diastereomeric excesses. Obviously, depending on the enzyme and the substrate structure, different results were observed and they will be discussed to gain a deeper insight into the different possibilities that these biocatalysts can provide.