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Updated: Feb 7, 2026

Curation of Computational Chemical Libraries Demonstrated with Alpha-Amino Acids
Published on: April 13, 2022
Chemical Resolution of C, N-Unprotected α-Substituted β-Amino Acids Using Stable and Recyclable Proline-Derived
Shuni Wang1,2, Yong Nian1,2, Shengbin Zhou1,2
1State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road , Shanghai 201203 , China.
Abstract:
We report the first purely chemical method for the resolution of C, N-unprotected racemic α-substituted β-amino acids (β2-AAs) using thermodynamically stable and recyclable chiral proline-derived ligands. The ligands and racemic β2-AAs along with Ni(II) could form a pair of Ni(II) complex diastereoisomers with a desirable diastereoselectivity (dr up to 91:9). Enantiomerically pure C, N-unprotected β2-AAs could be obtained by simple hydrolysis of an isolated favored Ni(II) complex. The method featured unique versatility compared with enzymatic approaches and characterized by its broad synthetic generality, good stereochemical outcome, and mild reaction conditions, thus making it a powerful supplement in the field of chemical resolution of β2-AAs.
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