Kinetic analysis for lipase-catalyzed hydrolysis of (R,S)-1,2,4-triazolides derived from N-Cbz-proline and (R,S)-N-Cbz-pipecolic acid

A kinetic model is proposed for modeling the time-course conversions of lipase-catalyzed hydrolytic resolution of (R,S)-N-Cbz-proline 1,2,4-triazolide (1) and (R,S)-N-Cbz-pipecolic 1,2,4-triazolide (2) in water-saturated MTBE at 45 °C, in which effects of non-enantioselective hydrolysis from acid products and background water as well as enzyme inhibition from the (S)-acid product for hydrolyzing (R)-1,2,4-triazolide are considered. A comparison of the kinetic constants for the hydrolysis of 1, 2, and (R,S)-N-2-phenylpropionyl-1,2,4-triazole (3) is further made, showing that the lower enzyme enantioselectivity for 2 and 3 is attributed to the lower enzyme activity for the fast-reacting (S)-2 and higher activity for the slow-reacting (S)-3 in comparison with the reactivity of (S)-1 and (R)-1, respectively.

► The hydrolysis of (R,S)-1,2,4-triazolide derived from N-Cbz-proline via lipase was modeled.
► The analysis was extended to (R,S)-1,2,4-triazolide derived from N-Cbz-pipecolic acid.
► Agreements between experimental data and theoretical results were demonstrated.
► The lipase performances were compared via the kinetic constants and molecular structures of the substrates.