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Third-party-funded project

Title:
Selective oxyfunctionalization

Project management at the University of Würzburg:

Participating scientists:

Abstract:
Enzymatic and microbial catalyses were used for selective oxyfunctionalizations. Alpha-Oxidase (I) from pea, glycolate oxidase (II) from spinach and several lipases (III) were employed for the production of optically active 2-hydroxy acids.
With purified (I) enantiomerically pure (R)-2-hydroxy acids (C12-C20) were obtained by direct dioxygenation in the presence of Sn(II)chloride. Substrates without any significant hydrophobic substituents such as short-chain carboxylic acids or dicarboxylic acids were not transformed by (I). The alpha-hydroxylation failed in the presence of a double bound or hetero atom nearby (less than three C atoms) the carboxylic function. The enzymatic kinetic resolution of chiral 2-hydroxy acids by enantioselective oxidation with molecular oxygen in the presence of (II) led also to the production of enantiomerically pure 2-hydroxy acids. Sterical hindering by a methyl, hydroxy or phenyl group nearby the 2-hydroxy group was not accepted by the enzyme. The enzymatic kinetic resolution by (II) with subsequent enantioselective reduction of 2-oxo acids using D-lactate dehydrogenase (Lactobacillus leichmanii) resulted in an one-pot-production of (R)-enantiomers (ee > 94%). By this tandem reaction the (R)-enantiomer was obtained quantitatively from the racemate.
The microbial lipases from Candida antartica and Burkholderia sp. were found to be efficient biocatalysts for the synthesis of optically active 2-hydroxy acids by enantioselective acetylation. Also with these enzymes the selectivity was lowered in the presence of a double bound or a hetero atom nearby the 2-hydroxy functionality.
The kinetic resolution of chiral hydroperoxides was performed for the first time with bacteria and fungi. Using Bacillus subtilis enantiomer enrichments up to 88% ee were reached. Studies carried out with Aspergillus niger revealed the presence of several peroxidases with different stereoselectivity.
Finally, a broad series of arylalkanes and alkanes was transformed by Bacillus megaterium to alcohols exhibiting ee values from 50-99%. The regioselectivity could be modified by the use of cytochrom P450 inductors. With substrates showing side chains > 5 C atoms and with all alkanes under study also small amounts of ketones were observed which were formed by oxidation of the produced alcohols. The microbial studies were continued by the soil bacterium Stenotrophomonas maltophilia that converted exogenously added fatty acids (C8-C22) by chain-shortening selectively to 3-(R)-hydroxy fatty acids.
Stereocontrol and determinations of absolute configurations were performed by chromatographic-spectroscopic techniques as well as the exciton coupled circular dichroism (ECCD) method.

Key words:
    Oxyfunctionalization
    Hydroxy acids
    alpha-oxidase
    Glycolate oxidase
    Lipases
    Dioxygenation
    Candida antarctica
    Burkholderia sp.
    Bacillus subtilis
    Aspergillus niger
    Stenotrophomonas maltophilia
    Hydroperoxides
    Kinetic resolution
    Exciton-CD

Projekt period: from 01.1999 to 12.2001

Funding institution:
DFG ,Granting date: 01.10.1999

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