Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent
In order to modify amino acids, the C-terminus carboxylic acid usually needs to be protected, typically as a methyl ester. However, standard cleavage of methyl esters requires either highly basic or acidic conditions, which are not compatible with Fmoc or acid-labile protecting groups. This highligh...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/9/2788 |
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| author | Renaud Binette Michael Desgagné Camille Theaud Pierre-Luc Boudreault |
| author_facet | Renaud Binette Michael Desgagné Camille Theaud Pierre-Luc Boudreault |
| author_sort | Renaud Binette |
| collection | DOAJ |
| description | In order to modify amino acids, the C-terminus carboxylic acid usually needs to be protected, typically as a methyl ester. However, standard cleavage of methyl esters requires either highly basic or acidic conditions, which are not compatible with Fmoc or acid-labile protecting groups. This highlights the need for orthogonal conditions that permit selective deprotection of esters to create SPPS-ready amino acids. Herein, mild orthogonal ester hydrolysis conditions are systematically explored using calcium(II) iodide as a protective agent for the Fmoc protecting group and optimized for a broad scope of amino esters. Our optimized reaction improved on the already known trimethyltin hydroxide, as it produced better yields with greener, inexpensive chemicals and a less extensive energy expenditure. |
| first_indexed | 2024-03-10T03:54:32Z |
| format | Article |
| id | doaj.art-48d75769994749249959009301e76c8a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:54:32Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-48d75769994749249959009301e76c8a2023-11-23T08:49:43ZengMDPI AGMolecules1420-30492022-04-01279278810.3390/molecules27092788Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective AgentRenaud Binette0Michael Desgagné1Camille Theaud2Pierre-Luc Boudreault3Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC J1H 5N4, CanadaDepartment of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC J1H 5N4, CanadaDepartment of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC J1H 5N4, CanadaDepartment of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC J1H 5N4, CanadaIn order to modify amino acids, the C-terminus carboxylic acid usually needs to be protected, typically as a methyl ester. However, standard cleavage of methyl esters requires either highly basic or acidic conditions, which are not compatible with Fmoc or acid-labile protecting groups. This highlights the need for orthogonal conditions that permit selective deprotection of esters to create SPPS-ready amino acids. Herein, mild orthogonal ester hydrolysis conditions are systematically explored using calcium(II) iodide as a protective agent for the Fmoc protecting group and optimized for a broad scope of amino esters. Our optimized reaction improved on the already known trimethyltin hydroxide, as it produced better yields with greener, inexpensive chemicals and a less extensive energy expenditure.https://www.mdpi.com/1420-3049/27/9/2788green chemistryester hydrolysisFmocamino acidsolid-phase synthesismedicinal chemistry |
| spellingShingle | Renaud Binette Michael Desgagné Camille Theaud Pierre-Luc Boudreault Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent Molecules green chemistry ester hydrolysis Fmoc amino acid solid-phase synthesis medicinal chemistry |
| title | Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent |
| title_full | Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent |
| title_fullStr | Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent |
| title_full_unstemmed | Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent |
| title_short | Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent |
| title_sort | efficient fmoc protected amino ester hydrolysis using green calcium ii iodide as a protective agent |
| topic | green chemistry ester hydrolysis Fmoc amino acid solid-phase synthesis medicinal chemistry |
| url | https://www.mdpi.com/1420-3049/27/9/2788 |
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