A Multicomponent Mannich Reaction Catalyzed by Hydrolases Immobilized on Titanate Nanotubes

This study presents an innovative method for synthesizing beta-amino carbonylated compounds, specifically 2-[phenyl(phenylamino)methyl] cyclohexanone, achieving high conversions and diastereomeric ratios. Using trypsin or alpha-chymotrypsin in both free and immobilized forms on titanate nanotubes (NtsTi), synthesized through alkaline hydrothermal methods, successful immobilization yields were attained. Notably, alpha-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 alpha-chymotrypsin/NtsTi demonstrated significant catalytic efficiency over five cycles. In conclusion, NtsTi serves as an effective support for trypsin and alpha-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. Trypsin and alpha-chymotrypsin were immobilized on titanate nanotubes (NtsTi); High conversion, diastereomeric ratio and excess enantiomeric were obtained for producing beta-aminoketones; Trypsin-free exhibited diastereopreference to the syn-isomer, while immobilized preparations to the anti-isomer; Both alpha-chymotrypsin free or immobilized show diastereopreference for anti-isomer; The catalytic efficiency in solvent-free medium were maintained for five consecutive cycles. image