Editorial

Jump to: Research, Review

3 pages, 168 KiB

Open AccessEditorial

Enzyme-Mediated Stereoselective Synthesis

by Stefano Serra

Catalysts 2019, 9(9), 763; https://doi.org/10.3390/catal9090763 - 11 Sep 2019

Viewed by 1756

Abstract

All of us know very well the importance of the catalysis in organic synthesis [...] Full article

(This article belongs to the Special Issue Enzyme-Mediated Stereoselective Synthesis)

Research

Jump to: Editorial, Review

17 pages, 1949 KiB

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

by Stefano Serra and Davide De Simeis

Catalysts 2018, 8(9), 362; https://doi.org/10.3390/catal8090362 - 28 Aug 2018

Cited by 13 | Viewed by 4138

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)

► Show Figures

Graphical abstract

11 pages, 2103 KiB

Open AccessFeature PaperArticle

Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones

by Francesca Tentori, Elisabetta Brenna, Danilo Colombo, Michele Crotti, Francesco G. Gatti, Maria Chiara Ghezzi and Giuseppe Pedrocchi-Fantoni

Catalysts 2018, 8(8), 308; https://doi.org/10.3390/catal8080308 - 29 Jul 2018

Cited by 13 | Viewed by 4002

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)

► Show Figures

Graphical abstract

11 pages, 1224 KiB

Open AccessArticle

Stereoselective Enzymatic Reduction of 1,4-Diaryl-1,4-Diones to the Corresponding Diols Employing Alcohol Dehydrogenases

by Ángela Mourelle-Insua, Gonzalo De Gonzalo, Iván Lavandera and Vicente Gotor-Fernández

Catalysts 2018, 8(4), 150; https://doi.org/10.3390/catal8040150 - 06 Apr 2018

Cited by 8 | Viewed by 4388

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)

► Show Figures

Graphical abstract

14 pages, 2207 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Use of Lactobacillus rhamnosus (ATCC 53103) as Whole-Cell Biocatalyst for the Regio- and Stereoselective Hydration of Oleic, Linoleic, and Linolenic Acid

by Stefano Serra and Davide De Simeis

Catalysts 2018, 8(3), 109; https://doi.org/10.3390/catal8030109 - 09 Mar 2018

Cited by 17 | Viewed by 6570

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)

► Show Figures

Graphical abstract

12 pages, 1405 KiB

Open AccessArticle

Microbial Kinetic Resolution of Aroma Compounds Using Solid-State Fermentation

by Filip Boratyński, Ewa Szczepańska, Aleksandra Grudniewska and Teresa Olejniczak

Catalysts 2018, 8(1), 28; https://doi.org/10.3390/catal8010028 - 16 Jan 2018

Cited by 20 | Viewed by 5281

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)

► Show Figures

Figure 1

12 pages, 2895 KiB

Open AccessArticle

Immobilized Burkholderia cepacia Lipase on pH-Responsive Pullulan Derivatives with Improved Enantioselectivity in Chiral Resolution

by Li Xu, Guli Cui, Caixia Ke, Yanli Fan and Yunjun Yan

Catalysts 2018, 8(1), 13; https://doi.org/10.3390/catal8010013 - 09 Jan 2018

Cited by 16 | Viewed by 4337

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 ee_s 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)

► Show Figures

Graphical abstract

Review

Jump to: Editorial, Research

25 pages, 2271 KiB

Open AccessReview

Recent Advances in ω-Transaminase-Mediated Biocatalysis for the Enantioselective Synthesis of Chiral Amines

by Mahesh D. Patil, Gideon Grogan, Andreas Bommarius and Hyungdon Yun

Catalysts 2018, 8(7), 254; https://doi.org/10.3390/catal8070254 - 21 Jun 2018

Cited by 133 | Viewed by 17333

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)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Enzyme-Mediated Stereoselective Synthesis

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (8 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI