Kinetic resolution of diarylmethanols using a mutated variant of lipase CALB

Engström, Karin; Vallin, Michaela; Hult, Karl; Bäckvall, Jan‐E.

doi:10.1016/j.tet.2012.06.040

Cited by 13 publications

(12 citation statements)

References 24 publications

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“… 167 Following this study, the group of Bäckvall and Hult explored CALB W104 as the resolving enzyme for diarylmethanols; however, satisfactory E values were only obtained for substrates where the two aryl substituents differed significantly in size. 168 As a result, the development of a DKR protocol for the latter substrate class was never pursued. The group of Kim and Park recently solved the DKR of this substrate class by using ruthenium complex 8 together with activated lipoprotein lipase.…”

Section: Methods For Improving Enzymes As Biocatalystsmentioning

confidence: 99%

Chemoenzymatic Dynamic Kinetic Resolution: A Powerful Tool for the Preparation of Enantiomerically Pure Alcohols and Amines

2015

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Chemoenzymatic dynamic kinetic resolution (DKR) constitutes a convenient and efficient method to access enantiomerically pure alcohol and amine derivatives. This Perspective highlights the work carried out within this field during the past two decades and pinpoints important avenues for future research. First, the Perspective will summarize the more developed area of alcohol DKR, by delineating the way from the earliest proof-of-concept protocols to the current state-of-the-art systems that allows for the highly efficient and selective preparation of a wide range of enantiomerically pure alcohol derivatives. Thereafter, the Perspective will focus on the more challenging DKR of amines, by presenting the currently available homogeneous and heterogeneous methods and their respective limitations. In these two parts, significant attention will be dedicated to the design of efficient racemization methods as an important means of developing milder DKR protocols. In the final part of the Perspective, a brief overview of the research that has been devoted toward improving enzymes as biocatalysts is presented.

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Section: Methods For Improving Enzymes As Biocatalystsmentioning

confidence: 99%

Chemoenzymatic Dynamic Kinetic Resolution: A Powerful Tool for the Preparation of Enantiomerically Pure Alcohols and Amines

2015

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“…However, the efficient enzymatic KR of diarylmethanols is still challenging because of their high steric hindrance and similarity in size of two aromatic substituents, especially the diarylmethanols substituted by pyridyl and phenyl. Indeed, only 27–74% ee values and 2–10 E values were observed using 2‐, 3‐ and 4‐pyridyl(phenyl)methanols as substrates under the catalysis of W104A (Figure 1b) [8] …”

Section: Figurementioning

confidence: 99%

“…Indeed, only 27-74% ee values and 2-10 E values were observed using 2-, 3-and 4pyridyl(phenyl)methanols as substrates under the catalysis of W104A ( Figure 1b). [8] Previous results with CALB and other enzymes suggest that apart from steric effects, electronic and solvation effects can also affect the binding of the substrates in enzymes and correspondingly their enantioselectivity. [10] Accordingly, we considered the electronic effects between enzyme and substrates may be more crucial to selectivity than steric attributes in these cases of diarylmethanols with one phenyl and one pyridyl group.…”

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confidence: 99%

Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols

Lou

et al. 2021

Adv Synth Catal

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Herein, we developed an electronic effect-guided rational design strategy to enhance the enantioselectivity of Candida antarctica lipase B (CALB) mutants towards bulky pyridyl(phenyl) methanols. Compared to W104A mutant previously reported with reversed S-stereoselectivity toward sec-alcohols, three mutants (W104C, W104S and W104T) displayed significant improvement of Senantioselectivity in the kinetic resolution (KR) of various phenyl pyridyl methyl acetates due to the increased electronic effects between pyridyl and polar residues. The electronic effects were also observed when mutating other residues surrounding the stereospecificity pocket of CALB, such as T42A, S47A, A281S or A281C, and can be used to manipulate the stereoselectivity. A series of bulky pyridyl(phenyl) methanols, including S-(4-chlorophenyl)(pyridin-2-yl) methanol (S-CPMA), the intermediate of bepotastine, were obtained in good yields and ee values.

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“…The latter enzyme, CalB W104A, was created by rational design to show reversed enantioselectivity towards secondary alcohols . CalB W104A has been applied to resolve various secondary alcohols …”

Section: Introductionmentioning

confidence: 99%

“…[6,7] CalB W104A hasb een applied to resolve various secondary alcohols. [6][7][8][9] SC is as erine proteasen aturally secreted from Bacillusl icheniformis. [10] SC is industrially applied as an ingredient in various detergent products.…”

Section: Introductionmentioning

confidence: 99%

Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering

2017

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Generally, the catalytic activity of subtilisin Carlsberg (SC) for transacylation reactions with secondary alcohols in organic solvent is low. Enzyme immobilization and protein engineering was performed to improve the enantioselectivity of SC towards secondary alcohols. Possible amino-acid residues for mutagenesis were found by combining available literature data with molecular modeling. SC variants were created by site-directed mutagenesis and were evaluated for a model transacylation reaction containing 1-phenylethanol in THF. Variants showing high E values (>100) were found. However, the conversions were still low. A second mutation was made, and both the E values and conversions were increased. Relative to that shown by the wild type, the most successful variant, G165L/M221F, showed increased conversion (up to 36 %), enantioselectivity (E values up to 400), substrate scope, and stability in THF.

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Kinetic resolution of diarylmethanols using a mutated variant of lipase CALB

Cited by 13 publications

References 24 publications

Chemoenzymatic Dynamic Kinetic Resolution: A Powerful Tool for the Preparation of Enantiomerically Pure Alcohols and Amines

Chemoenzymatic Dynamic Kinetic Resolution: A Powerful Tool for the Preparation of Enantiomerically Pure Alcohols and Amines

Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols

Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering

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