Regio- and Stereoselective Aliphatic-Aromatic Cross-Benzoin Reaction: Enzymatic Divergent Catalysis

• Published in: Chemistry : a European journal Vol. 22; no. 39; pp. 13999 - 14005
• Main Authors: Beigi, Maryam, Gauchenova, Ekaterina, Walter, Lydia, Waltzer, Simon, Bonina, Fabrizio, Stillger, Thomas, Rother, Dörte, Pohl, Martina, Müller, Michael
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 19-09-2016; Wiley Subscription Services, Inc
• Subjects: Accessibility; Acetobacter - enzymology; Acetobacter pasteurianus; Acetone - analogs & derivatives; Acetone - chemical synthesis; Acetone - chemistry; Acetophenone; Aldehyde-Lyases - chemistry; Aldehydes; Aldehydes - chemistry; Aliphatic compounds; Asymmetric synthesis; Asymmetry; Benzaldehyde; Benzoin; Benzoin - chemistry; Benzoylformate decarboxylase; Biocatalysis; Carboxy-Lyases - chemistry; Catalysis; Catalysts; Chain branching; Chains; Chemical synthesis; Chemistry; Chemistry Techniques, Synthetic - methods; C−C coupling; Derivatives; Enzymes; Hydroxypropiophenone - chemical synthesis; Hydroxypropiophenone - chemistry; Ketones; Lactococcus lactis; Lactococcus lactis - enzymology; Phenylacetylcarbinol; Pseudomonas; Pseudomonas fluorescens; Pseudomonas fluorescens - enzymology; Pseudomonas putida; Pseudomonas putida - enzymology; Pyruvate decarboxylase; Pyruvic acid; Stereochemistry; Stereoisomerism; Substrates; Synthesis; Thiamine; Thiamine diphosphate; Thiamine Pyrophosphate - chemistry; vitamin B1; thiamine diphosphate; asymmetric synthesis; C−C coupling; biocatalysis; vitamin B1
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201602084

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.
Divergent biocatalysis: The catalytic asymmetric synthesis of chiral 2‐hydroxy ketones using different thiamine diphosphate dependent enzymes, namely PfBAL, PpBFD‐L461A, LlKdcA and ApPDC‐E469G, was studied (see scheme). The results show that the regio‐ and stereochemistry of the product in the reaction can be controlled solely by choice of the appropriate enzyme.