Special Issue "Enzyme-Mediated Stereoselective Synthesis"

A special issue of Catalysts (ISSN 2073-4344).

Deadline for manuscript submissions: closed (31 July 2018)

Special Issue Editor

Guest Editor
Prof. Dr. Stefano Serra

Consiglio Nazionale delle Ricerche (C.N.R.), Istituto di Chimica del Riconoscimento Molecolare (ICRM), Milano, Italy
Website | E-Mail
Interests: organic synthesis; stereoselective synthesis; development of new synthetic methods; biotransformations and use of enzymes in organic synthesis; biogeneration of flavours and fragrances; natural products; synthesis and chemical characterization of APIs; antibiotics and biological active compounds

Special Issue Information

Dear Colleagues,

All of us know very well the importance of the catalysis in organic synthesis. Catalyzed reactions are usually preferred when planning a new synthetic approach and the choice of the proper catalyst is of pivotal relevance.

In this context, the use of biocatalysts in organic synthesis has grown steadily during the last fifty years. Nowadays chemists have become accustomed to the idea that the use of enzymes is essential in a modern synthetic laboratory. It does not matter if a given transformation is performed using whole cell microorganisms or using an isolated enzyme. In both cases the specific activity and selectivity of one or more enzymes is exploited. In fact, biocatalysts allow performing a number of chemical reactions with high regio- and stereoselectivity.

This Special Issue has been planned in order to collect original research papers, reviews and commentaries focused on the exploitation of enzymes stereoselectivity in organic synthesis. Contributions dealing with enzyme-mediated stereoselective synthesis of relevant chemicals, such as innovative materials, active pharmaceutical ingredients, natural products, flavours and fragrances and any other kind of bioactive compounds are welcome.

Dr. Stefano Serra
Guest Editor

Manuscript Submission Information

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Keywords

  • Stereoselective synthesis
  • Enzymes in organic synthesis
  • Enantioselectivity
  • Diastereoselectivity
  • Biocatalysis
  • Enzyme-mediated resolution of racemic compounds
  • Whole-Cells biocatalysis
  • Green chemistry

Published Papers (7 papers)

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Research

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Open AccessArticle Two Complementary Synthetic Approaches to the Enantiomeric Forms of the Chiral Building Block (2,6,6-Trimethyltetrahydro-2H-pyran-2-yl)methanol: Application to the Stereospecific Preparation of the Natural Flavor Linaloyl Oxide
Catalysts 2018, 8(9), 362; https://doi.org/10.3390/catal8090362
Received: 12 August 2018 / Revised: 24 August 2018 / Accepted: 26 August 2018 / Published: 28 August 2018
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Abstract
The enantiomeric forms of the alcohol (2,6,6-trimethyltetrahydro-2H-pyran-2-yl)methanol are potential chiral building blocks for the stereoselective synthesis of different natural terpenes. Here, we describe their preparation by means of two different synthetic approaches. The first is based on the stereospecific (+)-10-camphorsulfonic acid
[...] Read more.
The enantiomeric forms of the alcohol (2,6,6-trimethyltetrahydro-2H-pyran-2-yl)methanol are potential chiral building blocks for the stereoselective synthesis of different natural terpenes. Here, we describe their preparation by means of two different synthetic approaches. The first is based on the stereospecific (+)-10-camphorsulfonic acid (CSA)-catalyzed cyclization of (R)- and (S)-2-methyl-5-(2-methyloxiran-2-yl)pentan-2-ol, which were in turn synthesized from (R)- and (S)-linalool, respectively. The latter monoterpenes are easily available from the chiral pool, with different optical purity. As our synthesis makes use of the intermediate 2,6-dimethyloct-7-ene-2,6-diol, whose enantiopurity can be improved through fractional crystallization, we obtained (2,6,6-trimethyltetrahydro-2H-pyran-2-yl)methanol enantiomers in an almost enantiopure form. The second synthetic approach is based on the lipase-mediated resolution of the aforementioned tetrahydropyranyl alcohol, which was prepared in racemic form starting from the industrial intermediate, dehydrolinalool. In this work, we report a large-scale resolution procedure that exploits the opposite enantioselectivity of Novozym® 435 lipase and lipase AK in the acetylation reaction of (2,6,6-trimethyltetrahydro-2H-pyran-2-yl)methanol. The two enantiomeric forms of the latter alcohol were employed for the first stereoselective synthesis of both enantiomers of the flavor, linaloyl oxide (2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran). Full article
(This article belongs to the Special Issue Enzyme-Mediated Stereoselective Synthesis)
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Open AccessFeature PaperArticle Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones
Catalysts 2018, 8(8), 308; https://doi.org/10.3390/catal8080308
Received: 12 July 2018 / Revised: 24 July 2018 / Accepted: 25 July 2018 / Published: 29 July 2018
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Abstract
Chiral β-nitroalcohols are important building blocks in organic chemistry. The synthetic approach that is based on the enzyme-mediated reduction of α-nitroketones has been scarcely considered. In this work, the use of commercial alcohol dehydrogenases (ADHs) for the reduction of aromatic and aliphatic nitroketones
[...] Read more.
Chiral β-nitroalcohols are important building blocks in organic chemistry. The synthetic approach that is based on the enzyme-mediated reduction of α-nitroketones has been scarcely considered. In this work, the use of commercial alcohol dehydrogenases (ADHs) for the reduction of aromatic and aliphatic nitroketones is investigated. High conversions and enantioselectivities can be achieved with two specific ADHs, affording either the (S) or (R)-enantiomer of the corresponding nitroalcohols. The reaction conditions are carefully tuned to preserve the stability of the reduced product, and to avoid the hydrolytic degradation of the starting substrate. The further manipulation of the enantioenriched nitroalcohols into Boc-protected amminoalcohols is also described. Full article
(This article belongs to the Special Issue Enzyme-Mediated Stereoselective Synthesis)
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Open AccessArticle Stereoselective Enzymatic Reduction of 1,4-Diaryl-1,4-Diones to the Corresponding Diols Employing Alcohol Dehydrogenases
Catalysts 2018, 8(4), 150; https://doi.org/10.3390/catal8040150
Received: 18 January 2018 / Revised: 27 March 2018 / Accepted: 3 April 2018 / Published: 6 April 2018
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Abstract
Due to the steric hindrance of the starting prochiral ketones, the preparation of chiral 1,4-diaryl-1,4-diols through the asymmetric hydrogen transfer reaction has been mainly restricted to the use of metal-based catalysts, oxazaborolidines, or organocatalysts. Herein, we demonstrated the versatility of oxidoreductases, finding overexpressed
[...] Read more.
Due to the steric hindrance of the starting prochiral ketones, the preparation of chiral 1,4-diaryl-1,4-diols through the asymmetric hydrogen transfer reaction has been mainly restricted to the use of metal-based catalysts, oxazaborolidines, or organocatalysts. Herein, we demonstrated the versatility of oxidoreductases, finding overexpressed alcohol dehydrogenase from Ralstonia sp. (E. coli/RasADH) as the most active and stereoselective biocatalyst. Thus, the preparation of a set of 1,4-diaryl-1,4-diols bearing different pattern substitutions in the aromatic ring was achieved with complete diastereo- and enantioselectivity under mild reaction conditions. Full article
(This article belongs to the Special Issue Enzyme-Mediated Stereoselective Synthesis)
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Open AccessFeature PaperArticle Use of Lactobacillus rhamnosus (ATCC 53103) as Whole-Cell Biocatalyst for the Regio- and Stereoselective Hydration of Oleic, Linoleic, and Linolenic Acid
Catalysts 2018, 8(3), 109; https://doi.org/10.3390/catal8030109
Received: 22 February 2018 / Revised: 7 March 2018 / Accepted: 8 March 2018 / Published: 9 March 2018
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Abstract
Natural hydroxy fatty acids are relevant starting materials for the production of a number of industrial fine chemicals, such as different high-value flavour ingredients. Only a few of the latter hydroxy acid derivatives are available on a large scale. Therefore, their preparation by
[...] Read more.
Natural hydroxy fatty acids are relevant starting materials for the production of a number of industrial fine chemicals, such as different high-value flavour ingredients. Only a few of the latter hydroxy acid derivatives are available on a large scale. Therefore, their preparation by microbial hydration of unsaturated fatty acids, affordable from vegetable oils, is a new biotechnological challenge. In this study, we describe the use of the probiotic bacterium Lactobacillus rhamnosus (ATCC 53103) as whole-cell biocatalyst for the hydration of the most common unsaturated octadecanoic acids, namely oleic acid, linoleic acid, and linolenic acid. We discovered that the addition of the latter fatty acids to an anaerobic colture of the latter strain, during the early stage of its exponential growth, allows the production of the corresponding mono-hydroxy derivatives. In these experimental conditions, the hydration reaction proceeds with high regio- and stereoselectivity. Only 10-hydroxy derivatives were formed and the resulting (R)-10-hydroxystearic acid, (S)-(12Z)-10-hydroxy-octadecenoic acid, and (S)-(12Z,15Z)-10-hydroxy-octadecadienoic acid were obtained in very high enantiomeric purity (ee > 95%). Although overall conversions usually do not exceed 50% yield, our biotransformation protocol is stereoselective, scalable, and holds preparative significance. Full article
(This article belongs to the Special Issue Enzyme-Mediated Stereoselective Synthesis)
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Open AccessArticle Microbial Kinetic Resolution of Aroma Compounds Using Solid-State Fermentation
Catalysts 2018, 8(1), 28; https://doi.org/10.3390/catal8010028
Received: 14 December 2017 / Revised: 12 January 2018 / Accepted: 13 January 2018 / Published: 16 January 2018
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Abstract
A novel microbial approach to the production of enantiomerically enriched and pure aroma compounds based on kinetic resolution via solid-state fermentation is proposed. Twenty-five filamentous fungi were screened for lipase activity and enantioselective hydrolysis of a volatile racemic ester (1-phenylethyl acetate (1
[...] Read more.
A novel microbial approach to the production of enantiomerically enriched and pure aroma compounds based on kinetic resolution via solid-state fermentation is proposed. Twenty-five filamentous fungi were screened for lipase activity and enantioselective hydrolysis of a volatile racemic ester (1-phenylethyl acetate (1)) and several racemic lactones (trans and cis whisky lactones (4, 5), γ-decalactone (7), δ-decalactone (8), (cis-3a,4,7,7a-tetrahydro-1(3H)-isobenzofuranone) (9)). Solid-state fermentation was conducted with linseed and rapeseed cakes. Kinetic resolution afforded enantiomerically enriched products with high enantiomeric excesses (ee = 82–99%). The results highlight the potential economic value of solid-state fermentation using agroindustrial side-stream feedstocks as an alternative to more expensive processes conducted in submerged fermentation. Full article
(This article belongs to the Special Issue Enzyme-Mediated Stereoselective Synthesis)
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Open AccessArticle Immobilized Burkholderia cepacia Lipase on pH-Responsive Pullulan Derivatives with Improved Enantioselectivity in Chiral Resolution
Catalysts 2018, 8(1), 13; https://doi.org/10.3390/catal8010013
Received: 12 December 2017 / Revised: 5 January 2018 / Accepted: 5 January 2018 / Published: 9 January 2018
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Abstract
A kind of pH-responsive particle was synthesized using modified pullulan polysaccharide. The synthesized particle possessed a series of merits, such as good dispersity, chemical stability and variability of particle size, making it a suitable carrier for enzyme immobilization. Then, Burkholderia cepacia lipase (BCL),
[...] Read more.
A kind of pH-responsive particle was synthesized using modified pullulan polysaccharide. The synthesized particle possessed a series of merits, such as good dispersity, chemical stability and variability of particle size, making it a suitable carrier for enzyme immobilization. Then, Burkholderia cepacia lipase (BCL), a promising biocatalyst in transesterification reaction, was immobilized on the synthesized particle. The highest catalytic activity and immobilization efficiency were achieved at pH 6.5 because the particle size was obviously enlarged and correspondingly the adsorption surface for BCL was significantly increased. The immobilization enzyme loading was further optimized, and the derivative lipase was applied in chiral resolution. Under the optimal reaction conditions, the immobilized BCL showed a very good performance and significantly shortened the reaction equilibrium time from 30 h of the free lipase to 2 h with a conversion rate of 50.0% and ees at 99.2%. The immobilized lipase also exhibited good operational stability; after being used for 10 cycles, it still retained over 80% of its original activity. Moreover, it could keep more than 80% activity after storage for 20 days at room temperature in a dry environment. In addition, to learn the potential mechanism, the morphology of the particles and the immobilized lipase were both characterized with a scanning electron microscope and confocal laser scanning microscopy. It was found that the enlarged spherical surface of the particle in low pH values probably led to high immobilized efficiency, resulting in the improvement of enantioselectivity activity in chiral resolution. Full article
(This article belongs to the Special Issue Enzyme-Mediated Stereoselective Synthesis)
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Review

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Open AccessReview Recent Advances in ω-Transaminase-Mediated Biocatalysis for the Enantioselective Synthesis of Chiral Amines
Catalysts 2018, 8(7), 254; https://doi.org/10.3390/catal8070254
Received: 24 May 2018 / Revised: 16 June 2018 / Accepted: 19 June 2018 / Published: 21 June 2018
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Abstract
Chiral amines are important components of 40–45% of small molecule pharmaceuticals and many other industrially important fine chemicals and agrochemicals. Recent advances in synthetic applications of ω-transaminases for the production of chiral amines are reviewed herein. Although a new pool of potential ω-transaminases
[...] Read more.
Chiral amines are important components of 40–45% of small molecule pharmaceuticals and many other industrially important fine chemicals and agrochemicals. Recent advances in synthetic applications of ω-transaminases for the production of chiral amines are reviewed herein. Although a new pool of potential ω-transaminases is being continuously screened and characterized from various microbial strains, their industrial application is limited by factors such as disfavored reaction equilibrium, poor substrate scope, and product inhibition. We present a closer look at recent developments in overcoming these challenges by various reaction engineering approaches. Furthermore, protein engineering techniques, which play a crucial role in improving the substrate scope of these biocatalysts and their operational stability, are also presented. Last, the incorporation of ω-transaminases in multi-enzymatic cascades, which significantly improves their synthetic applicability in the synthesis of complex chemical compounds, is detailed. This analysis of recent advances shows that ω-transaminases will continue to provide an efficient alternative to conventional catalysis for the synthesis of enantiomerically pure amines. Full article
(This article belongs to the Special Issue Enzyme-Mediated Stereoselective Synthesis)
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