α Hydroxylation of Carboxylic Acids with Molecular Oxygen Catalyzed by the α Oxidase of Peas (Pisum s ativum):  A Novel Biocatalytic Synthesis of Enantiomerically Pure (R)-2-Hydroxy Acids

• Published in: Journal of the American Chemical Society 1998-11, Vol.120 (43), p.11044-11048
• Main Authors: Adam, Waldemar, Boland, Wilhelm, Hartmann-Schreier, Jenny, Humpf, Hans-Ulrich, Lazarus, Michael, Saffert, Alexander, Saha-Möller, Chantu R, Schreier, Peter
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja981252r

The substrate selectivities of the α oxidation of saturated, unsaturated, and heteroatom-containing (oxygen, sulfur) carboxylic acids 1 by the enzyme extract of peas (Pisum sativum) indicate that this biotransformation proceeds highly enantioselectively. For the first time, the synthesis of optically pure 2-hydroxy acids 2 has been achieved on the semipreparative scale (1 mmol) by α hydroxylation of long-chain carboxylic acids with molecular oxygen, catalyzed by the α oxidase of peas. For derivatives with sulfur atom in the chain, no sulfoxidation is observed. The functionalities (carbon double and triple bonds, oxygen, and sulfur atoms) must be at least three carbon atoms away from the carboxylic acid group to achieve efficient asymmetric hydroxylation. The absolute configuration of the 2-hydroxy acids 2 was assigned by comparison of the gas-chromatographic data with that of authentic reference compounds and by application of the exciton-coupled-circular-dichroism (ECCD) method. This unprecedented asymmetric biocatalytic methodology should be valuable for the preparation of enantiomerically pure (R)-2-hydroxy acids.