【摘要】 (R)-3,5-双三氟甲基-1-苯乙醇是合成神经激肽1受体拮抗剂阿瑞匹坦的关键手性醇中间体.通过筛选得到一株氧化微杆菌C3(Microbacterium oxydans C3),其能不对称还原底物3,5-双三氟甲基苯乙酮为(R)-3,5-双三氟甲基-1-苯乙醇.在底物浓度为5 g/L时,生物转化反应40 h,能达到>99%的ee值和95%的底物转化率.底物浓度提高到50 g/L时,生物转化的ee值依然保持99%,并能达到56%的底物转化率.利用该氧化微杆菌C3对其他含氟苯乙酮衍生物进行生物转化反应,同样得到了较高的立体选择性和底物转化率.更多还原

【Abstract】 The isolated microorganism Microbacterium oxydans C3 reduced 3,5-bis(trifluoromethyl)-acetophenone at 5 g/L to(R)-3,5-bis(trifluoromethyl)-1-phenethanol,a pharmaceutically alcohol intermediate for the synthesis of Aprepitant,a potent human NK-1 receptor antagonists,in 40 h.The bioreaction had desirable enantioselectivity(> 99% enantiomeric excess [ee]) and 95% conversion.When the substrate concentration reached 50 g/L,the bioreaction afforded(R)-3,5-bis(trifluoromethyl)-1phenethanlo with 56% conversion and 99% ee.The usefulness of M.oxydans C3 was further demonstrated by the bioreduction of several fluorinated acetophenones with good conversion and excellent enantioselectivity.更多还原