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.