Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives.
Zheng Y., Chen Z., Clarkson GJ., Marshall SA., Xiao J., Schofield CJ., Wills M., Stachulski AV.
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.