Asymmetric synthesis of (S)-phenylacetylcarbinol – closing a gap in C–C bond formation

 

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC01803C, Communication
Torsten Sehl, Saskia Bock, Lisa Marx, Zaira Maugeri, Lydia Walter, Robert Westphal, Constantin Vogel, Ulf Menyes, Martin Erhardt, Michael Muller, Martina Pohl, Dorte Rother
By the combination of biocatalyst design and reaction engineering, the so far not stereoselectively accessible (S)-phenylacetylcarbinol could be enzymatically synthesized with product concentrations >48 g L-1 and an enantiomeric excess up to 97%.
Asymmetric synthesis of (S)-phenylacetylcarbinol – closing a gap in C-C bond formation

Asymmetric synthesis of (S)-phenylacetylcarbinol – closing a gap in C–C bond formation

*Corresponding authors
aInstitute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, Leo-Brandt-Str. 1, 52425 Jülich, Germany
E-mail: do.rother@fz-juelich.de
bHERBRAND PharmaChemicals GmbH, Brambachstr. 31, 77723 Gegenbach, Germany
cAlbaNova University Center, Royal Institute of Technology – School of Biotechnology, Roslagstull 21, Stockholm, Sweden
d
Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Albertstrasse 25, 79104 Freiburg, Germany
e
Merz Pharma GmbH & Co. KGaA, Am Pharmapark, D-06861 Dessau-Rosslau, Germany
f
Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
g
TRUMPF GmbH+Co.KG, Ditzingen Johann-Maus-Straße 2, 71254 Ditzingen, Germany
h
Enzymicals AG, Walther-Rathenau-Str 49a, 17489 Greifswald, Germany
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC01803C

(S)-Phenylacetylcarbinol [(S)-PAC] and its derivatives are valuable intermediates for the synthesis of various active pharmaceutical ingredients (APIs), but their selective synthesis is challenging. As no highly selective enzymes or chemical catalysts were available, we used semi-rational enzyme engineering to tailor a potent biocatalyst to be >97% stereoselective for the synthesis of (S)-PAC. By optimizing the reaction and process used, industrially relevant product concentrations of >48 g L−1 (up to 320 mM) were achieved. In addition, the best enzyme variant gave access to a broad range of ring-substituted (S)-PAC derivatives with high stereoselectivity, especially for meta-substituted products.
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///////////Asymmetric synthesis, (S)-phenylacetylcarbinol, C-C bond formation

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