title: Regio- and Stereoselective Aliphatic-Aromatic Cross-Benzoin Reaction: Enzymatic Divergent Catalysis.
abstract: The catalytic asymmetric synthesis of chiral 2-hydroxy ketones by using different thiamine diphosphate dependent enzymes, namely benzaldehyde lyase from Pseudomonas fluorescens (PfBAL), a variant of benzoylformate decarboxylase from Pseudomonas putida (PpBFD-L461A), branched-chain 2-keto acid decarboxylase from Lactococcus lactis (LlKdcA) and a variant of pyruvate decarboxylase from Acetobacter pasteurianus (ApPDC-E469G), was studied. Starting with the same set of substrates, substituted benzaldehydes in combination with different aliphatic aldehydes, PfBAL and PpBFD-L461A selectively deliver the (R)- and (S)-2-hydroxy-propiophenone derivatives, respectively. The (R)- and (S)-phenylacetylcarbinol (1-hydroxy-1-phenylacetone) derivatives are accessible in a similar way using LlKdcA and ApPDC-E469G, respectively. In many cases excellent stereochemical purities (>98 % enantiomeric excess) could be achieved. Hence, the regio- and stereochemistry of the product in the asymmetric aliphatic-aromatic cross-benzoin reaction can be controlled solely by choice of the appropriate enzyme or enzyme variant.
authors: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors: Maryam
authors: M
authors: Beigi
authors: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors: Ekaterina
authors: E
authors: Gauchenova
authors: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors: Lydia
authors: L
authors: Walter
authors: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors: Simon
authors: S
authors: Waltzer
authors: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors: Fabrizio
authors: F
authors: Bonina
authors: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors: Thomas
authors: T
authors: Stillger
authors: IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany.
authors: Dörte
authors: D
authors: Rother
authors: IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany.
authors: Martina
authors: M
authors: Pohl
authors: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany. michael.mueller@pharmazie.uni-freiburg.de.
authors: Michael
authors: M
authors: Müller
mesh_terms: D000091:Acetobacter / Q000201:enzymology*; D000096:Acetone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000446:Aldehyde-Lyases / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D001573:Benzoin / Q000737:chemistry; D055162:Biocatalysis; D002262:Carboxy-Lyases / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D006910:Hydroxypropiophenone / Q000138:chemical synthesis* / Q000737:chemistry; D013294:Lactococcus lactis / Q000201:enzymology*; D011551:Pseudomonas fluorescens / Q000201:enzymology*; D016958:Pseudomonas putida / Q000201:enzymology*; D013237:Stereoisomerism; D013835:Thiamine Pyrophosphate / Q000737:chemistry
chemical_list: D000447:Aldehydes; D006910:Hydroxypropiophenone; D000096:Acetone; C035293:1-hydroxy-1-phenyl-2-propanone; D002262:Carboxy-Lyases; D000446:Aldehyde-Lyases; C059416:benzaldehyde lyase; D001573:Benzoin; D013835:Thiamine Pyrophosphate
keywords: C−C coupling; asymmetric synthesis; biocatalysis; thiamine diphosphate; vitamin B1