title: An efficient lipase-catalyzed enantioselective hydrolysis of (R,S)-azolides derived from N-protected proline, pipecolic acid, and nipecotic acid.
abstract: In the Candida antarctica lipase B-catalyzed hydrolysis of (R,S)-azolides derived from (R,S)-N-protected proline in water-saturated methyl tert-butyl ether (MTBE), high enzyme activity with excellent enantioselectivity (V                 (S)                 V                                    (R)                             (-1)                  > 100) for (R,S)-N-Cbz-proline 1,2,4-triazolide (1) and (R,S)-N-Cbz-proline 4-bromopyrazolide (2) was exploited in comparison with their corresponding methyl ester analog (3). Changing of the substrate structure, water content, solvent, and temperature was found to have profound influences on the lipase performance. On the basis of enzyme activity and enantioselectivity and solvent boiling point, the best reaction condition of using 1 as the substrate in water-saturated MTBE at 45 °C was selected and further employed for the successful resolution of (R,S)-N-Cbz-pipecolic 1,2,4-triazolide (5) and (R,S)-N-Boc-nipecotic 1,2,4-triazolide (9). Moreover, more than 89.1 % recovery of remained (R)-1 is obtainable in five cycles of enzyme reusage, when pH 7 phosphate buffers were employed as the extract at 4 °C.
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Wu
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Pen
authors.forename: Pei-Yun
authors.initials: PY
authors.lastname: Wang
authors.forename: Shau-Wei
authors.initials: SW
authors.lastname: Tsai
mesh_terms: D055162:Biocatalysis; D005656:Fungal Proteins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D015394:Molecular Structure; D009557:Nipecotic Acids / Q000737:chemistry*; D010875:Pipecolic Acids / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D005656:Fungal Proteins; D009557:Nipecotic Acids; D010875:Pipecolic Acids; C030278:nipecotic acid; D011392:Proline; D008049:Lipase; C431349:lipase B, Candida antarctica; C031345:pipecolic acid