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 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.
Authors
- Martin Wills (ORCID: https://orcid.org/0000-0002-1646-2379)
- Ye Zheng (ORCID: https://orcid.org/0000-0001-9620-7302)
- Andrew V. Stachulski (ORCID: https://orcid.org/0000-0002-5100-8884)
- Stephen Marshall (ORCID: https://orcid.org/0000-0001-7678-4989)
- Christopher John Schofield (ORCID: https://orcid.org/0000-0002-0290-6565)
- Guy J. Clarkson (ORCID: https://orcid.org/0000-0003-3076-3191)
- Zhenyu Chen (ORCID: https://orcid.org/0000-0001-7714-9936)
- Jianliang Xiao (ORCID: https://orcid.org/0000-0003-2010-247X)
Institutions
- Mansfield University (US)
- University of Liverpool (GB)
- Oxford Research Group (GB)
- University of Warwick (GB)
- University of Oxford (GB)
Publication Details
- Journal
- Royal Society Open Science
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1098/rsos.241607
- Primary Topic
- Asymmetric Hydrogenation and Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- Advantage West Midlands
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- European Regional Development Fund