两相体系中全细胞转化法制备托莫西汀中间体
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摘要
研究了磷酸盐缓冲液/有机溶剂两相体系中,热带假丝酵母Candida tropicalis CGMCC NO.15016不对称还原3-羰基-3-苯基丙酸乙酯制备(R)-3-羟基-3-苯基丙酸乙酯的过程.利用二硝基水杨酸(DNS)法研究了有机溶剂对细胞的毒性,采用单因素法考察了相体积比、温度、磷酸盐缓冲液pH、底物浓度和菌体浓度等对不对称还原转化的影响,确定了V(磷酸盐缓冲液)∶V(邻苯二甲酸二丁酯两相体系)=1∶1为最佳反应体系,在最优转化条件下,转化率及对映体过剩值均可达到100%.
(R)-3-hydroxy-3-ethyl phenylpropinate was synthesized by asymmetric reduction of 3-carbonyl-3-ethyl phenylpropinate with Candida tropicalis CGMCC NO.15016 as catalyst in phosphate buffer/organic solvent diphasic system.The DNS method was used to detect the toxicity of organic solvent to cells.The effects of different factors on the asymmetric reduction,such as the volume ratio of phosphate buffer to the organic phase,temperature,phosphate buffer pH,substrate concentration and cell concentration were investigated by single factor method.The conversion and enantiometric excess values can reach 100%in the optimum reaction system.
(R)-3-hydroxy-3-ethyl phenylpropinate was synthesized by asymmetric reduction of 3-carbonyl-3-ethyl phenylpropinate with Candida tropicalis CGMCC NO.15016 as catalyst in phosphate buffer/organic solvent diphasic system.The DNS method was used to detect the toxicity of organic solvent to cells.The effects of different factors on the asymmetric reduction,such as the volume ratio of phosphate buffer to the organic phase,temperature,phosphate buffer pH,substrate concentration and cell concentration were investigated by single factor method.The conversion and enantiometric excess values can reach 100%in the optimum reaction system.
引文
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[2]BYMASTER F P,KATNER J S,NELSON D L,et al.Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat:apotential mechanism for efficacy in attention deficit hyperactivity disorder[J].Neuropsychopharmacology,2002,27(5):699-711.
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[4]WOHLGEMUTH R.Asymmetric biocatalysis with microbial enzymes and cells[J].Current opinion in microbiology,2010,13(3):283-292.
[5]梅建凤,罗丽琴,王鸿,等.化学—酶法合成胸苷的研究[J].浙江工业大学学报,2014,42(2):172-177.
[6]娄文勇,郭强,郁惠蕾,等.近平滑假丝酵母细胞催化乙酰基三甲基硅烷不对称还原反应[J].催化学报,2009,30(12):1276-1280.
[7]王普,任峰,黄金,等.含离子液体介质中生物拆分制备S-(+)-2,2-二甲基环丙烷甲酸[J].浙江工业大学学报,2013,41(4):409-413.
[8]杜理华,徐亮亮,成柄灼.一种脂肪酶催化柚皮苷酯化反应的研究[J].浙江工业大学学报,2017,45(1):51-55.
[9]何军邀,孙志浩,郑璞,等.水/有机溶剂两相体系微生物催化不对称还原制备(S)-4-氯-3-羟基丁酸乙酯[J].高校化学工程学报,2007,21(2):310-315.
[10]蒋群,姚善径,梅乐和.固定化酵母在有机溶剂中的耐受性研究[J].浙江化工,2001,32(4):16-19.
[11]徐玉,王晓婷,娄文勇,等.含水有机溶剂体系中固定化Acetobacter sp.CCTCC M209061细胞催化乙酰乙酸乙酯不对称还原反应[J].现代食品科技,2014,30(7):31-37.
[12]吴义辉,伍玉甜,何丽瑜.药物在辛醇-水体系分配系数的应用[J].今日药学,2000,10(4):12-14.