Lipase-Catalyzed Production of (S)‑Carprofen Enhanced by Hydroxyethyl-β-cyclodextrins: Experiment and Optimization
Lipase-Catalyzed Production of (S)‑Carprofen Enhanced by Hydroxyethyl-β-cyclodextrins: Experiment and Optimization
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羟乙基-β-环糊精增强的脂肪酶催化 (S)-卡洛芬生产：实验与优化
DOI：
10.1021/acs.oprd.9b00009
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发表时间：
2019
影响因子：
3.4
通讯作者：
唐课文
中科院分区：
文献类型：
--
作者：
袁欣;刘光勇;张盼良;许卫凤;唐课文
研究了在水介质中脂肪酶催化水解（R，S）-卡洛芬甲酯（CPOMe）生成（S）-卡洛芬（CP）的立体选择性拆分。通过对其它8种脂肪酶的比较，筛选出了催化活性最高的南极假丝酵母脂肪酶A（CALA）。加入羟乙基-β-环糊精（HE-β-CD）以提高（R，S）-CPOMe的溶解度，使底物转化率从11.12%显著提高到30.84%。采用响应面法（RSM）考察了pH值、酶浓度、HE-β-CD浓度、反应温度、底物用量、反应时间等因素对底物转化率（c）和产物对映体过量（eep）的影响。结果表明，最佳反应条件为：pH 6.0，CALA 40 mg/mL，底物0.05 mmol/L，HE-β-CD 35 mmol/L，搅拌速度600 rpm，反应温度76 °C，反应时间30 h。在上述条件下，得到目标产物（S）-CP，对映体过量为96.24%，总转化率为46.07%。
Stereoselective resolution of (R,S)-carprofen methyl ester (CPOMe) by lipase-catalyzed hydrolysis to (S)-carprofen (CP) was investigated in an aqueous medium. With the highest catalytic activity,Candida antarcticaLipase A (CALA) was selected as catalyst compared with eight other lipases. Hydroxyethyl-β-cyclodextrin (HE-β-CD) was added to enhance the solubility of (R,S)-CPOMe, which significantly raised the conversion of substrate from 11.12% to 30.84%. Response surface methodology (RSM) was adopted to evaluate the influence of factors on the substrate conversion (c) and enantiomeric excess of product (eep), such as pH, concentrations of enzyme and HE-β-CD, temperature, substrate loading, and reaction time. The optimal conditions were obtained, including pH 6.0, 40 mg/mL CALA, 0.05 mmol substrate, 35 mmol/L HE-β-CD, agitation speed of 600 rpm, temperature of 76 °C, and reaction time of 30 h. Under the above conditions, (S)-CP as the desired product was obtained with an enantiomeric excess of 96.24% and overall conversion of 46.07%.