Enzymatic resolution of α-trifluoromethylated amines via kinetic resolution (KR), dynamic kinetic resolution (DKR) employing CALB-Pd/Al2O3, and a one-pot sequential process of KR/DKR/KR was investigated comparatively for the first time. Although CALB-catalyzed KR of α-trifluoromethylated amines with substituents of methyl (1a), isopropyl (1c), phenyl (1d) and benzyl group (1e) can provide good stereoselectivity factors E from 31 to >200 respectively, DKR and sequential process of KR/DKR/KR possess better practical application potential because of the higher conversion (62%–84%) and the similar enantiomeric excesses (90%–99%). The enantiopreference and inversion for the α-trifluoromethylated amines displayed by CALB were observed and explained by docking modes. Namely, for 1,1,1-trifluoro-2-propylamine (1a), the product amide with R-configuration was obtained, and the enantiopreference was converted to S for the amines (1b–1e) with substituents larger than methyl group. The catalysts recycle, and scale-up experiments were demonstrated successfully. All these results indicated the high efficiency and green feature of this enzymatic process, and its application significance.

A cascade reaction between aldehydes and indole catalyzed by lipase from porcine pancreas Type II (PPL) in solvent mixture at 50 °C was reported for the first time. Some control experiments had been designed to demonstrate that the PPL was responsible for the cascade reaction. After the optimization of the stepwise process, a series of bis(indolyl)alkanes were prepared in moderate to excellent yields under the catalysis of PPL.

•A facile, enzymatic synthesis protocol of l-amino acid ester prodrugs of azacitidine was developed.•A series of Boc-protected amino acid-azacitidine conjugates were prepared in good regioselectivity and yield.•Various factors which influence the catalytic efficiency were systematically investigated.•In vitro hydrolysis of prodrugs showed that the amino acid ester prodrugs had sustained release characteristic.A facile, enzymatic synthesis protocol of l-amino acid ester prodrugs of azacitidine was developed. Firstly, transesterification of azacitidine with Boc protected vinyl aminocarboxylates was performed under the catalysis of subtilisin in anhydrous pyridine at 50 °C. A series of Boc-protected amino acid-azacitidine conjugates were prepared in good regioselectivity and yield. Various factors which influence the catalytic efficiency were systematically investigated. And then, the obtained azacitidine derivatives were subjected to a deprotection process to give l-amino acid ester prodrugs of azacitidine. In vitro hydrolysis of prodrugs showed that the amino acid ester prodrugs had obvious sustained release characteristic. These characteristics will have potential value for clinic application.A facile, enzymatic synthesis protocol of l-amino acid ester prodrugs of azacitidine, which displayed sustained release characteristics, was successfully developed with good regioselectivity and yields.Download full-size image