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Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol
Ceramides and their analogs have a regulatory effect on inflammatory cytokines expression. It was found that a kind of ceramides analog synthesized from phenylglycinol could inhibit the production of cytokine TNF-α. However, two active hydrogen groups are present in the phenylglycinol molecule. It i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987038/ https://www.ncbi.nlm.nih.gov/pubmed/32039186 http://dx.doi.org/10.3389/fbioe.2019.00486 |
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author | Sun, Meina Nie, Kaili Wang, Fang Deng, Li |
author_facet | Sun, Meina Nie, Kaili Wang, Fang Deng, Li |
author_sort | Sun, Meina |
collection | PubMed |
description | Ceramides and their analogs have a regulatory effect on inflammatory cytokines expression. It was found that a kind of ceramides analog synthesized from phenylglycinol could inhibit the production of cytokine TNF-α. However, two active hydrogen groups are present in the phenylglycinol molecule. It is difficult to control the process without hydroxyl group protection to dominantly produce amide in the traditional chemical synthesis. A selective catalytic the amidation route of phenylglycinol by lipases was investigated in this research. The results indicated that the commercial immobilized lipase Novozym 435 has the best regio-selectivity on the amide group. Based on the experimental results and in silico simulation, it was found that the mechanism of specific N-acyl selectivity of lipase was not only from intramolecular migration and proton shuttle mechanism, but also from the special structure of active site of enzyme. The optimal reaction yield of aromatic amide compound in a solvent-free system with lipase loading of 15 wt% (to the weight of total substrate) reached 89.41 ± 2.8% with very few of byproducts detected (0.21 ± 0.1% ester and 0.64 ± 0.2% diacetylated compound). Compare to other reported works, this work have the advantages such as low enzyme loading, solvent free, and high N-acylation selectivity. Meanwhile, this Novozym 435 lipase based synthesis method has an excellent regio-selectivity on most kinds of amino alcohol compounds. Compared to the chemical method, the enzymatic synthesis exhibited high regio-selectivity, and conversion rates. The method could be a promising alternative strategy for the synthesis of aromatic alkanolamides. |
format | Online Article Text |
id | pubmed-6987038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69870382020-02-07 Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol Sun, Meina Nie, Kaili Wang, Fang Deng, Li Front Bioeng Biotechnol Bioengineering and Biotechnology Ceramides and their analogs have a regulatory effect on inflammatory cytokines expression. It was found that a kind of ceramides analog synthesized from phenylglycinol could inhibit the production of cytokine TNF-α. However, two active hydrogen groups are present in the phenylglycinol molecule. It is difficult to control the process without hydroxyl group protection to dominantly produce amide in the traditional chemical synthesis. A selective catalytic the amidation route of phenylglycinol by lipases was investigated in this research. The results indicated that the commercial immobilized lipase Novozym 435 has the best regio-selectivity on the amide group. Based on the experimental results and in silico simulation, it was found that the mechanism of specific N-acyl selectivity of lipase was not only from intramolecular migration and proton shuttle mechanism, but also from the special structure of active site of enzyme. The optimal reaction yield of aromatic amide compound in a solvent-free system with lipase loading of 15 wt% (to the weight of total substrate) reached 89.41 ± 2.8% with very few of byproducts detected (0.21 ± 0.1% ester and 0.64 ± 0.2% diacetylated compound). Compare to other reported works, this work have the advantages such as low enzyme loading, solvent free, and high N-acylation selectivity. Meanwhile, this Novozym 435 lipase based synthesis method has an excellent regio-selectivity on most kinds of amino alcohol compounds. Compared to the chemical method, the enzymatic synthesis exhibited high regio-selectivity, and conversion rates. The method could be a promising alternative strategy for the synthesis of aromatic alkanolamides. Frontiers Media S.A. 2020-01-22 /pmc/articles/PMC6987038/ /pubmed/32039186 http://dx.doi.org/10.3389/fbioe.2019.00486 Text en Copyright © 2020 Sun, Nie, Wang and Deng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Sun, Meina Nie, Kaili Wang, Fang Deng, Li Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol |
title | Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol |
title_full | Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol |
title_fullStr | Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol |
title_full_unstemmed | Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol |
title_short | Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol |
title_sort | optimization of the lipase-catalyzed selective amidation of phenylglycinol |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987038/ https://www.ncbi.nlm.nih.gov/pubmed/32039186 http://dx.doi.org/10.3389/fbioe.2019.00486 |
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