Effect of the Substituent and Amino Group Position on the Lipase‐Catalyzed Resolution of γ‐Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity
Abstract The kinetic resolution of N ‐ tert ‐butoxycarbonyl γ‐amino methyl esters bearing different stereocenters at alpha (γ 2 ), beta (γ 3 ), or gamma (γ 4 ) positions was carried out by enantioselective hydrolysis with Candida antarctica lipase B (CaLB) in 2‐methyl‐2‐butanol solvent. The results...
Published in: | European Journal of Organic Chemistry |
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Online Access: | http://dx.doi.org/10.1002/ejoc.202100712 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejoc.202100712 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ejoc.202100712 |
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crwiley:10.1002/ejoc.202100712 2024-06-02T07:58:05+00:00 Effect of the Substituent and Amino Group Position on the Lipase‐Catalyzed Resolution of γ‐Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity Ortega‐Rojas, Marina A. Castillo, Edmundo Razo‐Hernández, Rodrigo Said Pastor, Nina Juaristi, Eusebio Escalante, Jaime 2021 http://dx.doi.org/10.1002/ejoc.202100712 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejoc.202100712 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ejoc.202100712 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor European Journal of Organic Chemistry volume 2021, issue 34, page 4790-4802 ISSN 1434-193X 1099-0690 journal-article 2021 crwiley https://doi.org/10.1002/ejoc.202100712 2024-05-03T10:37:39Z Abstract The kinetic resolution of N ‐ tert ‐butoxycarbonyl γ‐amino methyl esters bearing different stereocenters at alpha (γ 2 ), beta (γ 3 ), or gamma (γ 4 ) positions was carried out by enantioselective hydrolysis with Candida antarctica lipase B (CaLB) in 2‐methyl‐2‐butanol solvent. The results show that the process is significantly less enantioselective for the γ 2 ‐amino methyl ester ( E =2.5), the γ 3 ‐amino methyl ester ( E =7.6), and the γ 4 ‐amino methyl ester ( E =8.3) when compared with the kinetic resolution of analogous N ‐protected β 3 ‐amino esters ( E >80). Based on these results, molecular docking studies were carried out, through which particular regions in the CaLB catalytic cavity were analyzed. The steric exclusion region composed of Ile189 and Val190 residues, together with the amino bonding region that induces a hydrogen bond with the Asp134 residue, appear to be responsible for the high selectivity in the resolution of carboxylic acid derivatives with beta stereocenters. This interaction is well preserved for β‐amino esters as substrates. By contrast, γ‐amino esters exhibit greater conformational diversity, so the effectiveness of the interaction is reduced, which apparently is responsible for the loss of enantioselectivity in the resolution process. Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library European Journal of Organic Chemistry 2021 34 4790 4802 |
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Wiley Online Library |
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language |
English |
description |
Abstract The kinetic resolution of N ‐ tert ‐butoxycarbonyl γ‐amino methyl esters bearing different stereocenters at alpha (γ 2 ), beta (γ 3 ), or gamma (γ 4 ) positions was carried out by enantioselective hydrolysis with Candida antarctica lipase B (CaLB) in 2‐methyl‐2‐butanol solvent. The results show that the process is significantly less enantioselective for the γ 2 ‐amino methyl ester ( E =2.5), the γ 3 ‐amino methyl ester ( E =7.6), and the γ 4 ‐amino methyl ester ( E =8.3) when compared with the kinetic resolution of analogous N ‐protected β 3 ‐amino esters ( E >80). Based on these results, molecular docking studies were carried out, through which particular regions in the CaLB catalytic cavity were analyzed. The steric exclusion region composed of Ile189 and Val190 residues, together with the amino bonding region that induces a hydrogen bond with the Asp134 residue, appear to be responsible for the high selectivity in the resolution of carboxylic acid derivatives with beta stereocenters. This interaction is well preserved for β‐amino esters as substrates. By contrast, γ‐amino esters exhibit greater conformational diversity, so the effectiveness of the interaction is reduced, which apparently is responsible for the loss of enantioselectivity in the resolution process. |
format |
Article in Journal/Newspaper |
author |
Ortega‐Rojas, Marina A. Castillo, Edmundo Razo‐Hernández, Rodrigo Said Pastor, Nina Juaristi, Eusebio Escalante, Jaime |
spellingShingle |
Ortega‐Rojas, Marina A. Castillo, Edmundo Razo‐Hernández, Rodrigo Said Pastor, Nina Juaristi, Eusebio Escalante, Jaime Effect of the Substituent and Amino Group Position on the Lipase‐Catalyzed Resolution of γ‐Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity |
author_facet |
Ortega‐Rojas, Marina A. Castillo, Edmundo Razo‐Hernández, Rodrigo Said Pastor, Nina Juaristi, Eusebio Escalante, Jaime |
author_sort |
Ortega‐Rojas, Marina A. |
title |
Effect of the Substituent and Amino Group Position on the Lipase‐Catalyzed Resolution of γ‐Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity |
title_short |
Effect of the Substituent and Amino Group Position on the Lipase‐Catalyzed Resolution of γ‐Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity |
title_full |
Effect of the Substituent and Amino Group Position on the Lipase‐Catalyzed Resolution of γ‐Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity |
title_fullStr |
Effect of the Substituent and Amino Group Position on the Lipase‐Catalyzed Resolution of γ‐Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity |
title_full_unstemmed |
Effect of the Substituent and Amino Group Position on the Lipase‐Catalyzed Resolution of γ‐Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity |
title_sort |
effect of the substituent and amino group position on the lipase‐catalyzed resolution of γ‐amino esters: a molecular docking study shedding light on candida antarctica lipase b enantioselectivity |
publisher |
Wiley |
publishDate |
2021 |
url |
http://dx.doi.org/10.1002/ejoc.202100712 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejoc.202100712 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ejoc.202100712 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
European Journal of Organic Chemistry volume 2021, issue 34, page 4790-4802 ISSN 1434-193X 1099-0690 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/ejoc.202100712 |
container_title |
European Journal of Organic Chemistry |
container_volume |
2021 |
container_issue |
34 |
container_start_page |
4790 |
op_container_end_page |
4802 |
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1800741347670360064 |