A Multicomponent Mannich Reaction Catalyzed by Hydrolases Immobilized on Titanate Nanotubes

Abstract

AbstractThis study presents an innovative method for synthesizing β‐amino carbonylated compounds, specifically 2‐[phenyl(phenylamino)methyl] cyclohexanone, achieving high conversions and diastereomeric ratios. Using trypsin or α‐chymotrypsin in both free and immobilized forms on titanate nanotubes (NtsTi), synthesized through alkaline hydrothermal methods, successful immobilization yields were attained. Notably, α‐chymotrypsin, when free, displayed a diastereoselective synthesis of the anti‐isomer with 97 % conversion and 16 : 84 (syn : anti) diastereomeric ratio, which slightly decreased upon immobilization on NtsTi. Trypsin, in its free form, exhibited diastereoselective recognition of the syn‐isomer, while immobilization on NtsTi (trypsin/NtsTi) led to an inversion of diastereomeric ratio. Both trypsin/NtsTi and α‐chymotrypsin/NtsTi demonstrated significant catalytic efficiency over five cycles. In conclusion, NtsTi serves as an effective support for trypsin and α‐chymotrypsin immobilization, presenting promising prospects for diastereoselective synthesis and potential industrial applications. Furthermore, it offers promising prospects for the diastereoselective synthesis of 2‐[phenyl(phenylamino)methyl] cyclohexanone through multicomponent Mannich reaction and future industrial application.