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

Abstract

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.

α-Oxidation of Fatty Acids in Higher Plants

“…On the basis of this result, a 2-hydroperoxide was proposed as an intermediate in ␣-oxidation (42). This hypothesis was recently supported by the finding that incubations of fatty acids with a preparation from pea leaves carried out in the presence of stannous chloride afforded enantiomerically pure 2(R)-hydroxy acids at the expense of aldehydes (43), and very recently by the isolation of 2(R)-hydroperoxypalmitic acid in incubations of palmitic acid with the ␣-oxidation system from the green alga U. pertusa (44).…”

An HASApf–redoxin complex causing asymmetric catalytic oxidation via the regenerative formation of a reactive oxygen species

“…3). 7, 16 There is an interesting phenomenon in the broad acquisition of HASApf gene [Pseudomonas fluorescens Pf-5] by the pea plant (PP). 19 Therefore, the evidence for the principal involvement of Fe(IV) = O was confirmed by the decrease of the high spin signal (g = 6 → g = 4.3 and 2); 20 the catalytic cycle between Fe(II) heme and Fe(IV) = O heme has never been reported.…”

“…9d Specifically, ME are activated by a buffered glycine reaction solution ( pH 9.0-10.0). 16 ð1Þ 12 In addition, an iron electron-transfer system may be incorporated as an oxygen-driven catalytic system for asymmetric oxidation.…”

7.07 α-Oxygenation of Carbonyl Compounds

“…30 Some examples give excellent enantioselectivity, although the scope of the reaction remains rather narrow and the yields were sometimes poor due to byproduct formation. 31 An engineered microbial cytochrome P450 was reported to catalyze the a-hydroxylation of benzylic esters with good selectivities. 32 …”