Lipase-catalyzed resolution of 2-fluorodecanoic acid

Tranel, Frank; Haufe, Günter

doi:10.1016/s0957-4166(99)00572-8

Cited by 10 publications

(3 citation statements)

References 66 publications

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“…As a result, biocatalysts are gaining more and more attention and enzymatic kinetic resolution plays an important role in producing enantiomerically pure compounds in this field. − However, in the preparation of enantiopure FCAs by the biocatalytic method, to the best of our knowledge, the most recent report concerns chemoenzymatic synthesis of FCAs via aldolase-catalyzed fluoropyruvate addition to diverse adehydes, which complements previous aldol-catalyzed reactions . Research prior to these developments was restricted to the use of carboxylic acid derivatives such as carboxylic acid esters, , dicarboxylic acids, and nitriles as substrates (Scheme a). Even in these cases, the drawbacks often include narrow substrate scope or difficulties in implementing large-scale preparations.…”

Section: Introductionmentioning

confidence: 99%

Semirational Design of Fluoroacetate Dehalogenase RPA1163 for Kinetic Resolution of α-Fluorocarboxylic Acids on a Gram Scale

et al. 2020

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Here the synthetic utility of fluoroacetate dehalogenase RPA1163 is explored for the production of enantiomerically pure (R)-α-fluorocarboxylic acids and (R)-α-hydroxylcarboxylic acids via kinetic resolution of racemic α-fluorocarboxylic acids. While wild-type (WT) RPA1163 shows high thermostability and fairly wide substrate scope, many interesting yet poorly or moderately accepted substrates exist. In order to solve this problem and to develop upscaled production, in silico calculations and semirational mutagenesis were employed. Residue W185 was engineered to alanine, serine, threonine, or asparagine. The two best mutants, W185N and W185T, showed significantly improved performance in the reactions of these substrates, while in silico calculations shed light on the origin of these improvements. Finally, 10 α-fluorocarboxylic acids and 10 α-hydroxycarboxylic acids were prepared on a gram scale via kinetic resolution enabled by WT, W185T, or W185N. This work expands the biocatalytic toolbox and allows a deep insight into the fluoroacetate dehalogenase catalyzed C–F cleavage mechanism.

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Section: Introductionmentioning

confidence: 99%

Semirational Design of Fluoroacetate Dehalogenase RPA1163 for Kinetic Resolution of α-Fluorocarboxylic Acids on a Gram Scale

et al. 2020

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“…1.1.3). Although this enzyme is very attractive for deracemization of valuable organic intermediates, [6][7][8][9][10][11] combinatorial engineering is limited by problems of expression. In the natural host B. cepacia, the lipase gene (lip), encoding the extracellular lipase, is located in an operon together with the hp gene encoding a lipase-specific foldase (Lif) essential for folding of the protein.…”

Section: Introductionmentioning

confidence: 99%

Small-Scale Production of Burkholderia cepacia ATCC21808 Lipase Adapted to High-Throughput Screening

Puech-Guenot¹,

Lafaquière²,

Guieysse³

et al. 2008

SLAS Discovery

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“…Enantiomerically enriched fluorinated carboxylic acids have mostly been synthesized by lipase-catalyzed hydrolysis of the corresponding esters . There are also some examples of enantioselective esterifications of carboxylic acids or transesterifications of esters . Optically active fluorinated alcohols have been obtained analogously.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Optically Active Vicinal Fluorohydrins by Lipase-Catalyzed Deracemization

Wölker

Haufe

2002

J. Org. Chem.

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Three microbial lipases have been used to deracemize trans-2-fluorocycloalkanols 2 both by hydrolysis of the corresponding acetates 3 or chloroacetates 4 and by esterification of the fluorohydrins 2 using vinyl acetate and vinyl chloroacetate, respectively. Pseudomonas cepacia lipase was the most selective for the six- and the seven-membered-ring compounds, while the lipase from Candida rugosa was most useful for the eight-membered-ring compounds. Both lipases transform the (R)-enantiomers preferentially. In contrast the lipase from Candida antarctica hydrolyzed the esters of trans-2-fluorocyclohexanol 2a and esterified the fluorohydrin itself with very low enantiopreference for the (R)-isomers. The seven- and the eight-membered ring esters and the corresponding fluorohydrins were also transformed with low, but reverse, enantioselectivity.

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Lipase-catalyzed resolution of 2-fluorodecanoic acid

Cited by 10 publications

References 66 publications

Semirational Design of Fluoroacetate Dehalogenase RPA1163 for Kinetic Resolution of α-Fluorocarboxylic Acids on a Gram Scale

Semirational Design of Fluoroacetate Dehalogenase RPA1163 for Kinetic Resolution of α-Fluorocarboxylic Acids on a Gram Scale

Small-Scale Production of Burkholderia cepacia ATCC21808 Lipase Adapted to High-Throughput Screening

Synthesis of Optically Active Vicinal Fluorohydrins by Lipase-Catalyzed Deracemization

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