Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives
Hydroxylated amino acids and their derivatives, including those found in proteins, are important in biology and medicinal chemistry. Incubation of N-acetyl-l-arginine with clavaminic acid synthase, a key oxygenase in clavulanic acid biosynthesis, affords a (3R)-hydroxylated product that is identical...
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| Format: | Article |
| Language: | English |
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The Royal Society
2025-02-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.241607 |
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| author | Ye Zheng Zhenyu Chen Guy J. Clarkson Stephen A. Marshall Jianliang Xiao Christopher J. Schofield Martin Wills Andrew V. Stachulski |
| author_facet | Ye Zheng Zhenyu Chen Guy J. Clarkson Stephen A. Marshall Jianliang Xiao Christopher J. Schofield Martin Wills Andrew V. Stachulski |
| author_sort | Ye Zheng |
| collection | DOAJ |
| description | Hydroxylated amino acids and their derivatives, including those found in proteins, are important in biology and medicinal chemistry. Incubation of N-acetyl-l-arginine with clavaminic acid synthase, a key oxygenase in clavulanic acid biosynthesis, affords a (3R)-hydroxylated product that is identical to material obtained by total synthesis from Boc-beta alanine. The key step employed dynamic kinetic resolution (DKR) of a β-ketoester precursor, achieved in high diastereomeric and enantiomeric excess using an (R)-SEGPHOS/Ru(II) catalyst. The results highlight the utility of DKR for the preparation of C-3 hydroxylated amino acid derivatives. |
| format | Article |
| id | doaj-art-4460ca8ab8384b5d81567d8a0e964e80 |
| institution | DOAJ |
| issn | 2054-5703 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj-art-4460ca8ab8384b5d81567d8a0e964e802025-08-20T03:02:06ZengThe Royal SocietyRoyal Society Open Science2054-57032025-02-0112210.1098/rsos.241607Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivativesYe Zheng0Zhenyu Chen1Guy J. Clarkson2Stephen A. Marshall3Jianliang Xiao4Christopher J. Schofield5Martin Wills6Andrew V. Stachulski7Department of Chemistry, University of Warwick, Coventry CV4 7AL, UKDepartment of Chemistry, University of Liverpool, Crown Street, Liverpool L69 7ZD, UKDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UKDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UKDepartment of Chemistry, University of Liverpool, Crown Street, Liverpool L69 7ZD, UKDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UKDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UKDepartment of Chemistry, University of Liverpool, Crown Street, Liverpool L69 7ZD, UKHydroxylated amino acids and their derivatives, including those found in proteins, are important in biology and medicinal chemistry. Incubation of N-acetyl-l-arginine with clavaminic acid synthase, a key oxygenase in clavulanic acid biosynthesis, affords a (3R)-hydroxylated product that is identical to material obtained by total synthesis from Boc-beta alanine. The key step employed dynamic kinetic resolution (DKR) of a β-ketoester precursor, achieved in high diastereomeric and enantiomeric excess using an (R)-SEGPHOS/Ru(II) catalyst. The results highlight the utility of DKR for the preparation of C-3 hydroxylated amino acid derivatives.https://royalsocietypublishing.org/doi/10.1098/rsos.241607asymmetric synthesisbiotransformationhydroxy amino-acidsantibioticscatalysis |
| spellingShingle | Ye Zheng Zhenyu Chen Guy J. Clarkson Stephen A. Marshall Jianliang Xiao Christopher J. Schofield Martin Wills Andrew V. Stachulski Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives Royal Society Open Science asymmetric synthesis biotransformation hydroxy amino-acids antibiotics catalysis |
| title | Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives |
| title_full | Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives |
| title_fullStr | Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives |
| title_full_unstemmed | Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives |
| title_short | Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives |
| title_sort | dynamic kinetic resolution mediated synthesis of c 3 hydroxylated arginine derivatives |
| topic | asymmetric synthesis biotransformation hydroxy amino-acids antibiotics catalysis |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.241607 |
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