Wang Yan, Xin Jia Ying, Li Quan-Hui, Sun Li-Rui, Xia Chun-Gu
Key Laboratory for Food Science & Engineering, Harbin University of Commerce, Harbin, China.
Key Laboratory for Food Science & Engineering, Harbin University of Commerce, Harbin, China / State Key Laboratory for Oxo Synthesis & Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, China.
Pak J Pharm Sci. 2017 May;30(3(Suppl.)):955-960.
Inorder to brought S-naproxen into small intestine, an optically pure (S)-naproxen starch ester was produced by lipase through enantio-selective trans-esterification of racemic naproxen methyl ester with pretreatment starch in solvent system. With carefully selection of the reaction medium (isooctane), lipase (Carica Papaya Lipase, CPL) and the reaction mode (intermittent opening), a high conversion rate (48.6%) and enantiomeric excess of product (99.6%) was obtained. The slow release macromolecular (S)-Naproxen had been synthesized to improve the efficacy of racemic naproxen and overcome its side effects. The enanitomeric ratio of CPL (E=52.5) was higher than CRL (E=22) and greatly influenced by the byproduct methyl alcohol. The intermittent opening reaction mode was the effective way to remove the inhibition of methyl alcohol and to improve the enantio-selectivity of CPL. S-naproxen starch was confirmed by HPLC and H NMR. This method may also apply to preparation the other optically pure 2-phenylpropionic acid derivatives. S-naproxen starch was a new optically pure derivatives possessing emulsifying and slow release properties would be widely applied to the food, pharmaceutical and biomedical industries.
为了使S-萘普生进入小肠，通过脂肪酶在溶剂体系中使外消旋萘普生甲酯与预处理淀粉进行对映选择性酯交换反应，制备了光学纯的(S)-萘普生淀粉酯。通过仔细选择反应介质（异辛烷）、脂肪酶（木瓜脂肪酶，CPL）和反应模式（间歇开启），获得了较高的转化率（48.6%）和产物对映体过量值（99.6%）。合成了缓释大分子(S)-萘普生，以提高外消旋萘普生的疗效并克服其副作用。CPL的对映体比例（E=52.5）高于CRL（E=22），且受副产物甲醇的影响很大。间歇开启反应模式是消除甲醇抑制并提高CPL对映选择性的有效方法。通过高效液相色谱法和核磁共振氢谱对S-萘普生淀粉进行了确认。该方法也可应用于制备其他光学纯的2-苯基丙酸衍生物。S-萘普生淀粉是一种具有乳化和缓释性能的新型光学纯衍生物，将广泛应用于食品、制药和生物医学行业。
