Use of Hydrolases in Organic Synthesis

A special issue of Catalysts (ISSN 2073-4344). This special issue belongs to the section "Biocatalysis".

Deadline for manuscript submissions: closed (15 July 2021) | Viewed by 6413

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Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Via Saldini 50, 20133 Milano, Italy
Interests: organic synthesis; biocatalysis; asymmetric synthesis; biologically active compounds; NMR spectroscopy; HPLC

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Guest Editor
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Via Saldini 50, 20133 Milano, Italy
Interests: organic synthesis; biocatalysis; asymmetric synthesis; biologically active compounds
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Special Issue Information

Dear Colleagues,

Starting from the 1960s, the use of purified enzymes has gained a great importance in fine chemicals, food, and pharmaceutical industries. The main reason for this increasing interest is the ability of purified enzymes to act as very efficient catalysts under mild reaction conditions displaying high chemo-, regio-, and enantioselectivity. Thus, shorter and “simpler” synthetic routes, implying a reduced use of protecting groups, can be planned, and the desired products can be obtained in higher yields thanks to a limited formation of byproducts. Moreover, the use of enzymes is an environmentally friendly approach matching the principles of Green Chemistry.

Among the six classes in which purified enzymes are divided, based on the reaction they catalyze, one is the most widely used by organic chemists: the class of hydrolases. As suggested by its name, this class collect enzymes that in nature are able to catalyze the reaction of cleavage of a very broad range of functional groups (i.e., esters, glycosides, anhydrides, amides, peptides, etc.) via the action of water. In addition to the advantages in common with the enzymes of the other classes, hydrolases have further attractive properties for the synthetic chemist: They do not need cofactors for their catalytic action, accept a broad range of substrates and, for many of them, are commercially available and stable in organic solvents. This means that this class of enzymes can be used not only for the hydrolysis of bonds, but also for their formation thanks to their ability to operate in “reverse mode” in organic solvents. For instance, lipases, esterases, proteases, and amidases, which are hydrolases of relevant interest in organic synthesis, can catalyze the hydrolysis or the formation of ester and amide bonds depending on the reaction conditions.

In conclusion, we can say that, when applicable, catalysis by means of hydrolases may offer attractive alternatives to classical synthetic methods due to its regio-, chemo- and stereoselectivity, low cost, ease of use, and environmentally compatible reaction conditions.

For all these reasons, this Special Issue on “Use of Hydrolases in Organic Synthesis” aims to collect papers and reviews that show the great versatility of hydrolases as useful tools for the synthesis of molecules such as, but not limited to, fine chemicals, biologically and pharmacologically active compounds, and agrochemicals.

Dr. Samuele Ciceri
Prof. Dr. Patrizia Ferraboschi
Guest Editors

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Keywords

  • Biocatalysis
  • Hydrolases
  • Lipases
  • Proteases
  • Esterases
  • Amidases
  • Organic synthesis
  • Fine chemicals
  • Biologically active compounds
  • Pharmacologically active compounds
  • Agrochemicals

Published Papers (2 papers)

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Research

9 pages, 1239 KiB  
Article
Novel (S)-Selective Hydrolase from Arthrobacter sp. K5 for Kinetic Resolution of Cyclic Amines
by Yuta Fukawa, Yuta Mizuno, Keisuke Kawade, Koichi Mitsukura and Toyokazu Yoshida
Catalysts 2021, 11(7), 809; https://doi.org/10.3390/catal11070809 - 01 Jul 2021
Cited by 3 | Viewed by 2224
Abstract
Chiral 2-methylpiperidine (2-MPI) is an important building block that has potential for applications in pharmaceuticals and pesticides. In this study, we observed that the hydrolase in Arthrobacter sp. K5 exhibits high (S)-selectivity toward rac-N-pivaloyl-2-MPI to yield (S [...] Read more.
Chiral 2-methylpiperidine (2-MPI) is an important building block that has potential for applications in pharmaceuticals and pesticides. In this study, we observed that the hydrolase in Arthrobacter sp. K5 exhibits high (S)-selectivity toward rac-N-pivaloyl-2-MPI to yield (S)-2-MPI with 80.2% enantiomeric excess (ee) in a 38.2% conversion. The hydrolase, which was identified by analyses of partial amino acid sequences of the purified enzyme and genome sequence of Arthrobacter sp. K5, exhibited moderate homology with amidohydrolases up to 67% (molinate hydrolase from Gulosibacter molinativorax). The hydrolase gene was overexpressed in Rhodococcus erythropolis. The recombinant cells produced (S)-2-MPI with 83.5% ee in a 48.4% conversion (E = 26.3) from 100 mM rac-N-pivaloyl-2-MPI. These results suggest the possibility of an efficient preparation of chiral 2-MPI in kinetic resolution. Full article
(This article belongs to the Special Issue Use of Hydrolases in Organic Synthesis)
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17 pages, 5458 KiB  
Article
(S)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates
by Samuele Ciceri, Patrizia Ferraboschi, Paride Grisenti, Shahrzad Reza Elahi, Carlo Castellano, Matteo Mori and Fiorella Meneghetti
Catalysts 2020, 10(8), 941; https://doi.org/10.3390/catal10080941 - 16 Aug 2020
Cited by 1 | Viewed by 3391
Abstract
A new chemoenzymatic method has been developed for the synthesis of (S)- and (R)-N-(6-hydroxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl) acetamide, two key synthons for the preparation of (S)-pramipexole, an anti-Parkinson drug, and its enantiomer dexpramipexole, which is currently under investigation [...] Read more.
A new chemoenzymatic method has been developed for the synthesis of (S)- and (R)-N-(6-hydroxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl) acetamide, two key synthons for the preparation of (S)-pramipexole, an anti-Parkinson drug, and its enantiomer dexpramipexole, which is currently under investigation for the treatment of eosinophil-associated disorders. These two building blocks have been obtained in good yields and high enantiomeric excess (30% and >98% ee for the R-enantiomer, and 31% and >99% ee for the S- one) through a careful optimization of the reaction conditions, starting from the corresponding racemic mixture and using two consecutive irreversible transesterifications, catalyzed by Candida antarctica lipase type A. Single crystal X-ray analysis has been carried out to unambiguously define the stereochemistry of the two enantiomers, and to explore in depth their three-dimensional features. Full article
(This article belongs to the Special Issue Use of Hydrolases in Organic Synthesis)
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