| 王艳,辛嘉英,于佳琪.脂肪酶催化一步酯化协同拆分合成S-萘普生淀粉酯前药[J].分子催化,2015,(5):476-481 |
| 脂肪酶催化一步酯化协同拆分合成S-萘普生淀粉酯前药 |
| One Step Esterification synergy resolution synthesis (S)- Naproxen starch ester by lipase in solvent system |
| 投稿时间：2015-09-07 修订日期：2015-10-09 |
| DOI： |
| 中文关键词: 外消旋萘普生，S-萘普生淀粉酯，脂肪酶，酯化协同拆分 |
| 英文关键词:Racemic Naproxen, (S)- Naproxen starch ester, Lipase, Esterification synergy resolution |
| 基金项目: |
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| 摘要点击次数: 1936 |
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| 中文摘要: |
| 利用CRL脂肪酶选择性催化外消旋萘普生甲酯与玉米淀粉进行转酯化反应合成光学纯S-萘普生淀粉酯前药，同时达到拆分外消旋萘普生的目的。考察了有机溶剂、脂肪酶用量、底物浓度比、反应温度对酯化协同拆分反应的影响，结果表明在异辛烷中脂肪酶CRL可以催化S-萘普生甲酯与淀粉发生转酯化反应同时完成外消旋萘普生的拆分，并且在脂肪酶用量为10%、底物浓度比为1:3、异辛烷用量为15mL、反应温度为60℃的条件下反应6d，外消旋萘普生甲酯的转化率为27.2%，产物对应体过量值eep高达99.4%可以作为萘普生的前药进行应用。 |
| 英文摘要: |
| A enzymatic esterification synthesis process has been developed to directly prepare starch ester prodrug of (S)-Naproxen from racemic naproxen methyl ester using lipase as the biocatalysis in the organic solvent. The slow release macromolecular (S)-Naproxen prodrug has been synthesised to improve the efficacy of racemic naproxen and overcome its side effects. With carefully selection of the raction medium (isooctane, 15mL), the ration of starch to racemic naproxen methyl ester (1:3), lipase (Candida Rugosa Lipase , CRL, 10%) and the temperature (65 oC), a high conversion rate (27.4%) and enantiomeric excess of product (99.4%) was obtained. The product was quantified using High Performance Liquid Chromatograph (HPLC) and the structure were characterized by FT-IR spectra and 1H NMR spectra. The (S)-Naproxen starch ester that enantiomeric excess was more than 95% could be synthesised by the stereo selectivity of CRL in isooctane medium and that could be used as pro-drug. The stereo selectivity of Candida rugosa lipase was greatly influenced by the substrate ratio that improved with the increase of the amount of acemic naproxen methyl ester. |
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