Lipase‐catalyzed dynamic kinetic resolution of (<i>R</i>,<i>S</i>)‐fenoprofen thioester in isooctane

Chen, Chia‐Yin; Cheng, Yu‐Chi; Tsai, Shau‐Wei

doi:10.1002/jctb.625

Cited by 18 publications

(13 citation statements)

References 26 publications

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“…(Lu et al, 2002). b CRL purified by isopropanol and adsorbed on polypropylene powder (Chen et al, 2002). c Crude CRL without immobilization (Lin and Tsai, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…the acylation step were estimated from the variation of initial rates with substrate concentrations. Previous data of using Lipase MY (referring as crude CRL) or that immobilized on polypropylene powder were also employed as the biocatalyst for the comparison with PCPL performances (Chen et al, 2002;Chen and Tsai, 2000;Lu et al, 2002;Tsai and Wei, 1994).…”

Section: Kinetic Analysismentioning

confidence: 99%

“…As a continuation of the previous study on developing lipasecatalyzed resolution process for (S)-2-arylpropionic acids (Chang et al, 1999;Chen et al, 2002;Tsai, 2000, 2003), this study is aimed to explore the partially purified Carica papaya lipase (PCPL) as a potential biocatalyst for producing (R)-or (S)-profens from their thioesters (Scheme 1). Effects of the acyl moiety and leaving thiol of the thioester on the enzyme performance are first studied, from which an active site model is postulated and elucidated from the kinetic and thermodynamic analysis.…”

Section: Introductionmentioning

confidence: 99%

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Partially purifiedCarica papayalipase: a versatile biocatalyst for the hydrolytic resolution of (R,S)-2-arylpropionic thioesters in water-saturated organic solvents

Ng¹,

Tsai²

2005

Biotechnol. Bioeng.

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With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl thioesters in water-saturated isooctane as a model system, improvements of the specific lipase activity and thermal stability were found when a crude Carica papaya lipase (CPL) was partially purified and employed as the biocatalyst. The partially purified Carica papaya lipase (PCPL) was furthermore explored as an effective enantioselective biocatalyst for the hydrolytic resolution of (R,S)-profen thioesters in water-saturated organic solvents. The kinetic analysis in water-saturated isooctane indicated that both acyl donor and acyl acceptor have profound influences on the lipase activity, E-value, and enantioselectivity. Inversion of the enantioselectivity from (S)- to (R)-thioester was found for (R,S)-fenoprofen and (R,S)-ketoprofen thioesters that contained a bulky substituent at the meta-position of 2-phenyl moiety of the acyl part. Kinetic constants for the acylation step were furthermore estimated for elucidating the kinetic data and postulating an active site model. The thermodynamic analysis indicated that the enantiomer discrimination was driven by the difference of activation enthalpy (DeltaDeltaH) and that of activation entropy (DeltaDeltaS), yet the latter was dominated for most of the reacting systems. The postulated active site model was supported from the variation of DeltaDeltaH and DeltaDeltaS with the acyl moiety, in which a good linear enthalpy-entropy compensation relationship was also illustrated. A comparison of the performances between Candida rugosa lipase (CRL) and PCPL indicated that PCPL was superior to CRL in terms of the better thermal stability, similar or better lipase activity for the fast-reacting substrate, time-course-stability, and lower enzyme cost.

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“…(Lu et al, 2002). b CRL purified by isopropanol and adsorbed on polypropylene powder (Chen et al, 2002). c Crude CRL without immobilization (Lin and Tsai, 2000).…”

Section: Discussionmentioning

confidence: 99%

Section: Kinetic Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Partially purifiedCarica papayalipase: a versatile biocatalyst for the hydrolytic resolution of (R,S)-2-arylpropionic thioesters in water-saturated organic solvents

Ng¹,

Tsai²

2005

Biotechnol. Bioeng.

Self Cite

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“…Activation of a Candida rugosa lipase in the dynamic kinetic resolution of (R,S)-profen 2,2,2-trifluroethyl thioesters was also reported when adding trioctylamine as a racemization catalyst (Chang et al, 1999;Chen et al, 2002;Lin and Tsai, 2000). The contribution of improved enzyme activity and enantioselectivity has been attributed to the ion-pair formation between the base and acid product and by-product in an organic solvent, thereby preventing enzyme inhibition and attenuation by the acid.…”

Section: Introductionmentioning

confidence: 87%

Altering lipase activity and enantioselectivity in organic media using organo‐soluble bases: Implication for rate‐limiting proton transfer in acylation step

Chen

Tsai

2006

Biotech & Bioengineering

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With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl esters via a partially purified papaya lipase (PCPL) in water-saturated isooctane as the model system, the enzyme activity, and enantioselectivty is altered by adding a variety of organo-soluble bases that act as either enzyme activators (i.e., TEA, MP, TOA, DPA, PY, and DMA) or enzyme inhibitors (i.e., PDP, DMAP, and PP). Triethylamine (TEA) is selected as the best enzyme activator as 2.24-fold increase of the initial rate for the (S)-ester is obtained when adding 120 mM of the base. By using an expanded Michaelis-Menten mechanism for the acylation step, the kinetic analysis indicates that the proton transfer for the breakdown of tetrahedral intermediates to acyl-enzyme intermediates is the rate-limiting step, or more sensitive than that for the formation of tetrahedral intermediates when the enzyme activators of different pKa are added. However, no correlation for the proton transfers in the acylation step is found when adding the bases acting as enzyme deactivators.

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“…Various methods, including lipase-catalyzed kinetic resolution [17,18,19,20,21,22,23], have been proposed for the production of (S)-profens or their prodrugs. A facile dynamic kinetic resolution process has been developed recently, in which (S)-naproxen, (S)-suprofen or (S)-fenoprofen are obtained from (R, S)-thioester or (R, S)-oxoester in high yields and with good optical purities using Candida rugosa lipase and trioctylamine or NaOH as the catalysts [24,25,26,27]. However, several drawbacks to this process were found: the low solubility of water and profens in isooctane, and the inhibition of lipase by profens.…”

Section: Introductionmentioning

confidence: 99%

Process modeling of the lipase-catalyzed dynamic kinetic resolution of (R, S)-suprofen 2,2,2-trifluoroethyl thioester in a hollow-fiber membrane

Wang

Cheng

Tsai

2004

Bioprocess Biosyst Eng

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A Candida rugosa lipase immobilized on polypropylene powder was employed as the biocatalyst for the enantioselective hydrolysis of (R, S)-suprofen 2,2,2-trifluorothioester in cyclohexane, in which trioctylamine was added as the catalyst to perform in situ racemization of the remaining (R)-thioester. A hollow-fiber membrane was also integrated with the dynamic kinetic resolution process in order to continuously extract the desired (S)-suprofen into an aqueous solution containing NaOH. A kinetic model for the whole process (operating in batch and feed-batch modes) was developed, in which enzymatic hydrolysis and deactivation, lipase activation, racemization and non-enantioselective hydrolysis of the substrate by trioctylamine, and reactive extraction of (R)- and (S)-suprofen into the aqueous phase in the membrane were considered. Theoretical predictions from the model for the time-course variations of substrate and product concentrations in each phase were compared with experimental data.

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Lipase‐catalyzed dynamic kinetic resolution of (R,S)‐fenoprofen thioester in isooctane

Cited by 18 publications

References 26 publications

Partially purifiedCarica papayalipase: a versatile biocatalyst for the hydrolytic resolution of (R,S)-2-arylpropionic thioesters in water-saturated organic solvents

Partially purifiedCarica papayalipase: a versatile biocatalyst for the hydrolytic resolution of (R,S)-2-arylpropionic thioesters in water-saturated organic solvents

Altering lipase activity and enantioselectivity in organic media using organo‐soluble bases: Implication for rate‐limiting proton transfer in acylation step

Process modeling of the lipase-catalyzed dynamic kinetic resolution of (R, S)-suprofen 2,2,2-trifluoroethyl thioester in a hollow-fiber membrane

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