Quantitative comparison of chiral catalysts selectivity and performance: A generic concept illustrated with cyclododecanone monooxygenase as baeyer-villiger biocatalyst

Contribución equivalente como primer autor: Fink, Michael J. y Rial, Daniela V. Within this work a generic tool for chiral catalyst evaluation is established based on the application-oriented properties activity and selectivity; the concept aims at quantitatively comparing catalyst performance in general on a multitude of substrates. It is designed and intended to serve as decision guidance for challenges in catalysis and comprehensible information extraction from already recorded but unrefined data sets. The underlying algorithm assigns function points to catalytic entities via a statistically solid model possessing high flexibility and generates a relative ranking. This is coupled to an automated iterative refinement process towards maximum information content of results employing Shannon entropy optimization. Consequently, the developed workflow facilitates high distinguishability between catalysts even in low-scattering data sets. The numerical ranking is complemented by a clearly arranged graphic representation permitting facile and reliable visual interpretation of generality or niche capabilities of catalysts. Usefulness of the title concept is demonstrated by the performance evaluation of cyclododecanone monooxygenase, a highly versatile Baeyer-Villiger enzyme. To retain broad applicability, an open-source MATLAB® script is provided in electronic form.Fil: Fink, Michael J.. Vienna University of Technology; AustriaFil: Rial, Daniela Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas Centro Científico Tecnológico - CONICET -Rosario. Instituto de Biologia Molecular y Celular de Rosario; ArgentinaFil: Kapitanova, Petra. Vienna University of Technology; AustriaFil: Lengar, Alenka. Institute Of Applied Synthetic Chemistry; AustriaFil: Rehdorf, Jessica. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG);Fil: Cheng, Qiong. No especifíca;Fil: Rudroff, Florian. Vienna University of Technology; AustriaFil: Mihovilovic, Marko D.. Vienna University of Technology; Austri

An Enzymatic Toolbox for the Kinetic Resolution of 2-(Pyridin-x-yl)but-3-yn-2-ols and Tertiary Cyanohydrins

The kinetic resolution of a series of acetates of tertiary alcohols bearing a nitrogen substituent has been studied by using several recombinant carboxyl esterases and variants thereof expressed in E. coli. Most of the enzymes were active in the conversion of these tertiary alcohols and excellent enantioselectivities were achieved in the synthesis of three 2-(pyridin-x-yl)but-3-yn-2-ols with the nitrogen atom in the pyridine ring in the 2′-, 3′-, and 4′-positions. The resolution of tertiary cyanohydrins proved to be more difficult as the enantioselectivity of the enzymes was generally lower. Nevertheless, (S)-1-cyano-2,2,2-trifluoro-1- phenylethyl acetate was obtained with 99% ee. The results show that the limited substrate range of the individual enzymes in the synthesis of a series of tertiary alcohols can be efficiently overcome by using a combination of different enzymes. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA