Impact of variation of the acyl group on the efficiency and selectivity of the lipase-mediated resolution of 2-phenylalkanols

Foley, Aoife; Gavin, Declan P.; Joniec, Ilona; Maguire, Anita R.

doi:10.1016/j.tetasy.2017.08.002

Cited by 7 publications

(7 citation statements)

References 54 publications

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“…Hydrolases can be used to resolve remote stereocentres 35–37 , and have been particularly important biocatalysts in the context of resolution of APIs and pharmaceutical intermediates 33,34,39,60 . In some cases, more than one stereocentre can be resolved 38 .…”

Section: Discussionmentioning

confidence: 99%

Genome mining and characterisation of a novel transaminase with remote stereoselectivity

Gavin

Reen

Rocha-Martín

et al. 2019

Sci Rep

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Microbial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir. Here we report a novel ω-transaminase discovered in a marine sponge Pseudovibrio sp. isolate. Remote stereoselection using a transaminase has been demonstrated for the first time using this novel protein. Application to the resolution of an intermediate in the synthesis of sertraline highlights the synthetic potential of this novel biocatalyst discovered through genomic mining. Integrated chemico-genomics revealed a unique substrate profile, while molecular modelling provided structural insights into this ‘first in class’ selectivity at a remote chiral centre.

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Section: Discussionmentioning

confidence: 99%

Genome mining and characterisation of a novel transaminase with remote stereoselectivity

Gavin

Reen

Rocha-Martín

et al. 2019

Sci Rep

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“…Having established that 26D could be used for a transformation which was not readily achieved with existing biocatalysts, its substrate scope was further investigated. We had previously examined a panel of hydrolase enzymes in the kinetic resolution of 2‐phenylalkanols . Excellent enantiopurities were obtained for a number of alcohol products when CAL‐B was used as the biocatalyst.…”

Section: Resultsmentioning

confidence: 99%

“…A range of ester substrates was screened, with the substituent on the β‐carbon (R 1 ) as well as the substituent (R 2 ) on the carboxylic acid moiety of the ester being varied (Table ). Product ee was poor to moderate, although in some instances hydrolysis was seen for substrates ( 14 and 15) which were not processed by CAL‐B (Table , entries 4 and 5), further highlighting the different profile in terms of the enzyme's substrate scope.…”

Section: Resultsmentioning

confidence: 99%

“…We had previously examined a panel of hydrolase enzymes in the kinetic resolution of 2phenylalkanols. [23] Excellent enantiopurities were obtained for a number of alcohol products when CAL-B was used as the biocatalyst. In contrast, esterase 26D was a poor biocatalyst for the resolution of 2-phenylalkanols.…”

Section: Full Papermentioning

confidence: 99%

“…Compounds 1, 3-5, 7-12, 15, 18, 21, 23-24 and 27-29 were synthesised according to previously reported methods. [19,23,26,31] Details of all compounds synthesised are given in the SI.…”

Section: Lipase-catalysed Hydrolysis Reactionsmentioning

confidence: 99%

See 2 more Smart Citations

Identification of an Esterase Isolated Using Metagenomic Technology which Displays an Unusual Substrate Scope and its Characterisation as an Enantioselective Biocatalyst

et al. 2019

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Evaluation of an esterase annotated as 26D isolated from a marine metagenomic library is described. Esterase 26D was found to have a unique substrate scope, including synthetic transformations which could not be readily effected in a synthetically useful manner using commercially available enzymes. Esterase 26D was more selective towards substrates which had larger, more sterically demanding substituents (i. e. isopropyl or tert-butyl groups) on the β-carbon, which is in contrast to previously tested commercially available enzymes which displayed a preference for substrates with sterically less demanding substituents (e.g. methyl group) at the β-carbon.

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The Impact of Recent Developments in Technologies which Enable the Increased Use of Biocatalysts

Foley

Maguire

2019

Eur J Org Chem

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While biocatalytic transformations are very powerful in enantioselective synthesis, frequently occurring under mild conditions, and proceed with extraordinary selectivity, there are practical challenges associated with the use of biocatalysis, such as limited substrate scope, stability, and reusability. Recent technological developments, for example immobilization, continuous flow, and molecular biology, all contribute towards enhancing the use of enzymes in synthesis.

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Impact of variation of the acyl group on the efficiency and selectivity of the lipase-mediated resolution of 2-phenylalkanols

Cited by 7 publications

References 54 publications

Genome mining and characterisation of a novel transaminase with remote stereoselectivity

Genome mining and characterisation of a novel transaminase with remote stereoselectivity

Identification of an Esterase Isolated Using Metagenomic Technology which Displays an Unusual Substrate Scope and its Characterisation as an Enantioselective Biocatalyst

The Impact of Recent Developments in Technologies which Enable the Increased Use of Biocatalysts

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