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

(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 eng...

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Bibliographic Details
Published in:Green chemistry : an international journal and green chemistry resource : GC 2017, Vol.19 (2), p.380-384
Main Authors: Sehl, Torsten, Bock, Saskia, Marx, Lisa, Maugeri, Zaira, Walter, Lydia, Westphal, Robert, Vogel, Constantin, Menyes, Ulf, Erhardt, Martin, Mueller, Michael, Pohl, Martina, Rother, Dorte
Format: Article
Language:English
Subjects:
Asymmetry
Bonding
Carbon-carbon composites
Derivatives
Enzymes
Ingredients
Optimization
Synthesis
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Summary:(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.
ISSN:1463-9262
1463-9270
1463-9270
DOI:10.1039/c6gc01803c