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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Main Authors: Ye Zheng, Zhenyu Chen, Guy J. Clarkson, Stephen A. Marshall, Jianliang Xiao, Christopher J. Schofield, Martin Wills, Andrew V. Stachulski
Format: Article
Language:English
Published: The Royal Society 2025-02-01
Series:Royal Society Open Science
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Online Access:https://royalsocietypublishing.org/doi/10.1098/rsos.241607
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Summary: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.
ISSN:2054-5703