(R,S)-2-chlorophenoxyl pyrazolides as novel substrates for improving lipase-catalyzed hydrolytic resolution.
The best reaction condition of Candida antartica lipase B as biocatalyst, 3-(2-pyridyl)pyrazole as leaving azole, and water-saturated methyl t-butyl ether as reaction medium at 45°C were first selected for performing the hydrolytic resolution of (R,S)-2-(4-chlorophenoxyl) azolides (1-4). In comparison with the kinetic resolution of (R,S)-2-phenylpropionyl 3-(2-pyridyl)pyrazolide or (R,S)-α-methoxyphenylacetyl 3-(2-pyridyl)pyrazolide at the same reaction condition, excellent enantioselectivity with more than two order-of-magnitudes higher activity for each enantiomer was obtained. The resolution was then extended to other (R,S)-3-(2-pyridyl)pyrazolides (5-7) containing 2-chloro, 3-chloro, or 2,4-dichloro substituent, giving good (E > 48) to excellent (E > 100) enantioselectivity. The thermodynamic analysis for 1, 2, and 4-7 demonstrates profound effects of the acyl or leaving moiety on varying enthalpic and entropic contributions to the difference of Gibbs free energies. A thorough kinetic analysis further indicates that on the basis of 6, the excellent enantiomeric ratio for 4 and 7 is due to the higher reactivity of (S)-4 and lower reactivity of (R)-7, respectively.
Institute of Biochemical and Biomedical Engineering, Chang Gung University, Kwei-Shan Tao-Yuan, Taiwan.
Min-fang
MF
Kao
Pei-yu
PY
Lu
Jou-yan
JY
Kao
Pei-yun
PY
Wang
An-chi
AC
Wu
Shau-Wei
SW
Tsai
D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000737:chemistry*; D012997:Solvents; D013379:Substrate Specificity; D013816:Thermodynamics
D011720:Pyrazoles; D012997:Solvents; D008049:Lipase