Shengbin Zhou1, Jiang Wang, Xia Chen, José Luis Aceña, Vadim A Soloshonok, Hong Liu. 1. State Key Laboratory of Drug Research, CAS Key Laboratory of Receptor Research Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203 (P. R. China).
Abstract
The first chemical method for resolution of N,C-unprotected β-amino acids was developed through enantioselective formation and disassembly of nickel(II) complexes under operationally convenient conditions. The specially designed chiral ligands are inexpensive and can be quantitatively recycled along with isolation of the target β-substituted-β-amino acids in good yields and excellent enantioselectivity. The method features a broad synthetic generality including β-aryl, β-heteroaryl, and β-alkyl-derived β-amino acids. The procedure is easily scaled up, and was used for the synthetically and economically advanced preparation of the anti-diabetic drug sitagliptin.
The first chemical method for resolution of N,C-unprotected β-amino acids was developed through enantioselective formation and disassembly of n class="Chemical">nickel(II) complexes under operationally convenient conditions. The specially designed chiral ligands are inexpensive and can be quantitatively recycled along with isolation of the target β-substituted-β-amino acids in good yields and excellent enantioselectivity. The method features a broad synthetic generality including β-aryl, β-heteroaryl, and β-alkyl-derived β-amino acids. The procedure is easily scaled up, and was used for the synthetically and economically advanced preparation of the anti-diabetic drug sitagliptin.