CN114539039A - 一种光-酶催化合成手性氟代苯乙醇的方法 - Google Patents
一种光-酶催化合成手性氟代苯乙醇的方法 Download PDFInfo
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Abstract
本发明公开了一种光‑酶催化合成手性氟代苯乙醇的方法。该方法包括以下步骤：a)将苯乙烯或取代苯乙烯、氟试剂、光催化剂加入反应体系，在氙灯照射下进行第一步反应；b)反应完成后，往a)的反应体系中加入产羰基还原酶的基因工程菌、D‑葡萄糖，进行第二步催化反应；c)反应完成后，以有机溶剂多次萃取，合并有机相，用无水硫酸钠干燥，过滤，回收溶剂得到目标粗产物；d)将目标粗产物进行过柱纯化，得到目标产物。本发明以光、酶催化相结合的方式，实现了不同种类的手性氟代苯乙醇的合成，原料成本低廉，以两步一锅的制备方法操作简便，反应过程条件温和、绿色环保、底物转化率高且立体选择性好。
Description
技术领域
本发明涉及手性邻氟醇的合成技术领域，具体涉及一种光-酶催化合成手性氟代苯乙醇的方法。
背景技术
氟原子具有原子半径小且电负性大的特点，在有机化合物中引入氟原子，可形成稳定的C-F键，且使化合物的物理、化学性质以及生物活性等发生变化，因而在医药、农药以及材料等各领域均有着重要的应用。其中，手性邻氟醇化合物作为合成如类固醇、类糖等天然产物类似物以及重要药物靶点的中间体，其合成方法的研究与改进也成为了一个重要的研究课题。
邻氟醇的传统化学合成方法，主要为烯烃或环氧化物的氟化，但由于立体选择性的限制，无法应用于手性邻氟醇的合成中。以酮还原酶还原α-氟代酮方法，以其高反应活性以及立体选择性，成为合成手性邻氟醇最有效的途径。而目前α-氟代酮的制备，大多依赖于有机金属催化剂或强氧化剂，制备成本高昂且生产过程易产生环境污染；Deng及其团队开发了以β-酮酸脱羧氟化的方法制备α-氟代酮，但β-酮酸性质不稳定，易分解为酮，需即制备即用，在实际应用中具有一定的限制。Wu及其团队开发了以β-酮酯为原料，以双酶串联催化合成手性邻氟醇，但原料β-酮酯价格较高，且合成路线的原子经济性较低，导致其应用成本较高。
基于目前手性邻氟醇合成方法的局限性，本发明希望开发一种高效、通用且环保的合成方法，并降低合成成本。
发明内容
本发明旨在针对现有技术的技术缺陷，提供一种光-酶催化合成手性α-氟代苯乙醇的方法。该方法以苯乙烯或取代苯乙烯为原料，通过氟试剂氟化得到消旋α-氟代苯乙醇、后以光催化氧化得到α-氟代苯乙酮，最后以不同立体选择性的羰基还原酶催化还原，实现光学纯的两种构型α-氟代苯乙醇及对应衍生物的合成(如化学方程式1)，并且合成过程通过两步一锅的方法实现。
本发明所述的两步一锅法，第一步为苯乙烯或取代苯乙烯的氟化以及光催化氧化串联反应，在苯乙烯或取代苯乙烯的反应体系中同时加入氟试剂与光催化剂，在光照下进行反应。第二步为羰基还原酶催化第一步产物的立体选择性还原，通过在反应体系中加入不同立体选择性的羰基还原酶实现两种构型α-氟代苯乙醇及对应衍生物的合成。
具体的，本发明提供的一种光-酶催化合成手性氟代苯乙醇的方法，包括以下步骤：
a)将苯乙烯或取代苯乙烯、氟试剂、光催化剂加入反应体系，在氙灯照射下进行第一步反应；
b)反应完成后，往a)的反应体系中加入产羰基还原酶的基因工程菌、D-葡萄糖，进行第二步催化反应；
c)反应完成后，以有机溶剂多次萃取，合并有机相，用无水硫酸钠干燥，过滤，回收溶剂得到目标粗产物；
d)将目标粗产物进行过柱纯化，得到目标产物。
优选的，所述的取代苯乙烯选自3-氯苯乙烯、4-氯苯乙烯、4-氟苯乙烯、4-溴苯乙烯、4-甲氧基苯乙烯中的一种或多种。
优选的，所述的氟试剂为1-氯甲基-4-氟-1,4-重氮化二环2.2.2辛烷双(四氟硼酸盐)，即Selectfluor试剂。
优选的，所述的光催化剂选自Tris(2,2-bipyridyl)ruthenium(II)chloridehexahydrate、fac-Tris(2-phenylpyridine)iridium[Ir(ppy)3]、Sodium anthraquinone-2-sulfonate、Riboflavin、Riboflavin tetrabutyrate、Eosin Y中的一种或多种。
本发明中光催化剂的筛选：分别将0.001mmol光催化剂溶于2mL水中，加入1mLα-氟代苯乙醇乙腈溶液中(10mmol/L)，在光照下以磁力搅拌12小时。反应结束后，分别取1mL反应溶液，以1mL乙酸乙酯萃取。取上层有机相，以气相色谱检测光催化反应的转化率。以Tris(2,2-bipyridyl)ruthenium(II)chloride hexahydrate、Riboflavin tetrabutyrate、Sodium anthraquinone-2-sulfonate(SAS)、fac-Tris(2-phenylpyridine)iridium[Ir(ppy)3]、Riboflavin为光催化剂，优选所述的光催化剂为Sodium anthraquinone-2-sulfonate(SAS)。
优选的，所述的苯乙烯或取代苯乙烯的浓度为250mmol/L，溶剂为乙腈；所述的氟试剂的浓度为220mmol/L，溶剂为水；所述的光催化剂的浓度为66mmol/L，溶剂为水；所述的苯乙烯或取代苯乙烯、氟试剂、光催化剂的体积比为4:5:3。
本发明所述的产羰基还原酶的基因工程菌，具体构建方法为：将羰基还原酶的基因进行基因合成，构建到能表达外源基因的质粒载体中，然后转化到能表达外源基因的宿主菌中，并对基因工程菌进行发酵培养，实现了羰基还原酶的异源表达。本发明提供的羰基还原酶Carbonyl reductase from Kluyveromyces thermotolerans(KtCR)的氨基酸序列如SEQ ID NO.1所示、carbonyl reductase from Ralstonia sp.(RasADH)的氨基酸序列如SEQ ID NO.2所示。
在本发明中，以LB培养基作为基因工程菌培养表达的碳源、氮源、无机和其他营养物质的介质，进行基因工程菌的培养以及羰基还原酶的表达，并以将培养基离心后得到的菌体细胞作为全细胞催化物。
优选的，所述的产羰基还原酶的基因工程菌的菌液与a)反应体系的体积比为(5～20):1，具体为5:1、20:1、10:1，优选10:1。
所述的产羰基还原酶的基因工程菌的菌液的制备步骤为：将产羰基还原酶的基因工程菌接到预培养基(LB培养基)中，进行预培养。将预培养菌液转接LB培养基中，培养至至OD600达到0.5～0.6，加入诱导剂IPTG诱导表达一段时间，离心收集沉淀的菌体。以100mM、pH 6.5的PBS缓冲液充分重悬收集到的菌体，得到菌液。
本发明的有益效果：本发明以光、酶催化相结合的方式，实现了不同种类的手性氟代苯乙醇的合成，原料成本低廉，以两步一锅的制备方法操作简便，反应过程条件温和、绿色环保、底物转化率高且立体选择性好。
附图说明
图1为(S)-α-氟代苯乙醇气相色谱表征。
图2为(R)-α-氟代苯乙醇气相色谱表征。
图3为(S)-α-氟代苯乙醇核磁谱图1H-NMR。
图4为(R)-α-氟代苯乙醇核磁谱图1H-NMR。
具体实施方式
以下实施例是对本发明的进一步说明，而不是对本发明的限制。
实施例1：羰基还原酶基因工程菌的构建和诱导表达
将羰基还原酶KtCR或RasADH的基因(由擎科生物科技有限公司合成)连接在pET28a载体上，酶切位点为NdeI、EcoRI，然后转入大肠杆菌BL21(DE3)感受态细胞中，挑取单克隆即得到重组菌。挑选平板上单菌落接种到20mL含34μg/mL卡那霉素的LB培养基中，培养12h左右作为种子液，按照1％v/v的接种量接种到400mL含34μg/mL卡那霉素的LB培养基中，37℃、200rpm振荡培养约4h至OD600达到0.5～0.6，加入终浓度为0.4mmol/L的异丙基-β-D-硫代半乳糖苷(IPTG)诱导表达，继续16℃振荡培养8h。以8000rpm离心5min，收集沉淀的菌体。将收集到的菌体充分重悬于200mL PBS缓冲液(100mM，pH 6.5)，得到菌液。
实施例2：α-氟代酮的合成
以苯乙烯或取代苯乙烯为原料，以为1-氯甲基-4-氟-1,4-重氮化二环2.2.2辛烷双(四氟硼酸盐)(Selectfluro)为氟化试剂，加入光催化剂，光照下得到α-氟代苯乙酮及其衍生物。
具体实验过程：
向schleck管中加入5mL水溶解的selectfluro试剂(220mmol/L)，加入4mL以乙腈溶解的苯乙烯(250mmol/L)或3-氯苯乙烯(250mmol/L)或4-氯苯乙烯(250mmol/L)或4-氟苯乙烯(250mmol/L)或4-溴苯乙烯(250mmol/L)或4-甲氧基苯乙烯(250mmol/L)，加入3mL水溶解的光催化剂SAS(66mmol/L)，以空气球通入反应空气，光照下以磁力搅拌4-12小时。取少量反应液，以适量乙酸乙酯萃取，以薄层色谱监测反应进程，至原料以及中间产物α-氟代苯乙醇消耗完全后，停止反应。得到α-氟代苯乙酮及其衍生物反应液。
实施例3：手性α-氟代苯乙醇的合成
分别取表达羰基还原酶RasADH、KtCR的重悬菌液60mL，加入1.5mmol D-葡萄糖以及6mL α-氟代苯乙酮反应液。混合均匀后，在200rpm，30℃条件下反应12h。反应结束后，以30mL乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥，过滤，以旋蒸除溶剂得粗产物，以手性气相色谱检测。检测结果为：以RasADH催化反应得到(S)-α-氟代苯乙醇，ee值98％，转化率为100％；以KtCR催化反应得到(R)-α-氟代苯乙醇，ee值99％，转化率为100％。手性气相色谱谱图为图1、图2。对两个产物分别进行过柱纯化，得到光学纯(S)-α-氟代苯乙醇及(R)-α-氟代苯乙醇，核磁谱图见图3、图4。其结构式如下：
实施例4：手性α-氟代苯乙醇的合成
分别取表达羰基还原酶RasADH、KtCR的重悬菌液60mL，加入1.5mmol D-葡萄糖以及3mLα-氟代苯乙酮反应液。混合均匀后，在200rpm，30℃条件下反应12h。反应结束后，以30mL乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥，过滤，以旋蒸除溶剂得粗产物，以手性气相色谱检测。检测结果为：以RasADH催化反应得到(S)-α-氟代苯乙醇，ee值95％，转化率为100％；以KtCR催化反应得到(R)-α-氟代苯乙醇，ee值96％，转化率为100％。对两个产物分别进行过柱纯化，得到光学纯(S)-α-氟代苯乙醇及(R)-α-氟代苯乙醇。
实施例5：手性α-氟代苯乙醇的合成
分别取表达羰基还原酶RasADH、KtCR的重悬菌液60mL，加入1.5mmol D-葡萄糖以及12mL α-氟代苯乙酮反应液。混合均匀后，在200rpm，30℃条件下反应12h。反应结束后，以30mL乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥，过滤，以旋蒸除溶剂得粗产物，以手性气相色谱检测。检测结果为：以RasADH催化反应得到(S)-α-氟代苯乙醇，ee值89％，转化率为22％；以KtCR催化反应得到(R)-α-氟代苯乙醇，ee值71％，转化率为13％。对两个产物分别进行过柱纯化，得到光学纯(S)-α-氟代苯乙醇及(R)-α-氟代苯乙醇。
实施例6：手性α-氟代-3-氯苯乙醇的合成
分别取表达羰基还原酶RasADH、KtCR的重悬菌液60mL，加入1.5mmol D-葡萄糖以及6mL α-氟代-3-氯苯乙酮反应液。混合均匀后，在200rpm，30℃条件下反应12h。反应结束后，以30mL乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥，过滤，以旋蒸除溶剂得粗产物，以手性气相色谱检测。检测结果为：以RasADH催化反应得到(S)-α-氟代-3-氯苯乙醇，ee值为98％，转化率为100％；以KtCR催化反应得到(R)-α-氟代-3-氯苯乙醇，ee值为99％，转化率为100％。对两个产物分别进行过柱纯化，得到光学纯(S)-α-氟代-3-氯苯乙醇及(R)-α-氟代-3-氯苯乙醇。其结构式如下：
实施例7：手性α-氟代-4-氯苯乙醇的合成
分别取表达羰基还原酶RasADH、KtCR的重悬菌液60mL，加入1.5mmol D-葡萄糖以及6mL α-氟代-4-氯苯乙酮反应液。混合均匀后，在200rpm，30℃条件下反应12h。反应结束后，以30mL乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥，过滤，以旋蒸除溶剂得粗产物，以手性气相色谱检测。检测结果为：以RasADH催化反应得到(S)-α-氟代-4-氯苯乙醇，ee值为99％，转化率为100％；以KtCR催化反应得到(R)-α-氟代-4-氯苯乙醇，ee值为97％，转化率为100％。对两个产物分别进行过柱纯化，得到光学纯(S)-α-氟代-4-氯苯乙醇及(R)-α-氟代-4-氯苯乙醇。其结构式如下：
实施例8：手性α-氟代-4-氟苯乙醇的合成
分别取表达羰基还原酶RasADH、KtCR的重悬菌液60mL，加入1.5mmol D-葡萄糖以及6mL a-氟代-4-氟苯乙酮反应液。混合均匀后，在200rpm，30℃条件下反应12h。反应结束后，以30mL乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥，过滤，以旋蒸除溶剂得粗产物，以手性气相色谱检测。检测结果为：以RasADH催化反应得到(S)-α-氟代-4-氟苯乙醇，ee值为98％，转化率为100％；以KtCR催化反应得到(R)-α-氟代-4-氟苯乙醇，ee值为99％，转化率为100％。对两个产物分别进行过柱纯化，得到光学纯(S)-α-氟代-4-氟苯乙醇及(R)-α-氟代-4-氟苯乙醇。其结构式如下：
实施例9：手性α-氟代-4-溴苯乙醇的合成
分别取表达羰基还原酶RasADH、KtCR的重悬菌液60mL，加入1.5mmol D-葡萄糖以及6mLα-氟代-4-溴苯乙酮反应液。混合均匀后，在200rpm，30℃条件下反应12h。反应结束后，以30mL乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥，过滤，以旋蒸除溶剂得粗产物，以手性气相色谱检测。检测结果为：以RasADH催化反应得到(S)-α-氟代-4-溴苯乙醇，ee值为>99％，转化率为100％；以KtCR催化反应得到(R)-α-氟代-4-溴苯乙醇，ee值为96％，转化率为100％。对两个产物分别进行过柱纯化，得到光学纯(S)-α-氟代-4-溴苯乙醇及(R)-α-氟代-4-溴苯乙醇。其结构式如下：
实施例10：手性α-氟代-4-甲氧基苯乙醇的合成
分别取表达羰基还原酶RasADH、KtCR的重悬菌液60mL，加入1.5mmol D-葡萄糖以及6mL a-氟代-4-甲氧基苯乙酮反应液。混合均匀后，在200rpm，30℃条件下反应12h。反应结束后，以30mL乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥，过滤，以旋蒸除溶剂得粗产物，以手性气相色谱检测。检测结果为：以RasADH催化反应得到(S)-α-氟代-4-甲氧基苯乙醇，ee值为98％，转化率为100％；以KtCR催化反应得到(R)-α-氟代-4-甲氧基苯乙醇，ee值为>99％，转化率为100％。对两个产物分别进行过柱纯化，得到光学纯(S)-α-氟代-4-甲氧基苯乙醇及(R)-α-氟代-4-甲氧基苯乙醇。其结构式如下：
以上仅是本发明的优选实施方式，应当指出的是，上述优选实施方式不应视为对本发明的限制，本发明的保护范围应当以权利要求所限定的范围为准。对于本技术领域的普通技术人员来说，在不脱离本发明的精神和范围内，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
序列表
<110> 广东省科学院微生物研究所（广东省微生物分析检测中心）
<120> 一种光-酶催化合成手性氟代苯乙醇的方法
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Claims (8)
1.一种光-酶催化合成手性氟代苯乙醇的方法，其特征在于，包括以下步骤：
a)将苯乙烯或取代苯乙烯、氟试剂、光催化剂加入反应体系，在氙灯照射下进行第一步反应；
b)反应完成后，往a)的反应体系中加入产羰基还原酶的基因工程菌、D-葡萄糖，进行第二步催化反应；
c)反应完成后，以有机溶剂多次萃取，合并有机相，用无水硫酸钠干燥，过滤，回收溶剂得到目标粗产物；
d)将目标粗产物进行过柱纯化，得到目标产物。
2.根据权利要求1所述的光-酶催化合成手性氟代苯乙醇的方法，其特征在于，所述的取代苯乙烯选自3-氯苯乙烯、4-氯苯乙烯、4-氟苯乙烯、4-溴苯乙烯、4-甲氧基苯乙烯中的一种或多种。
3.根据权利要求1所述的光-酶催化合成手性氟代苯乙醇的方法，其特征在于，所述的氟试剂为1-氯甲基-4-氟-1,4-重氮化二环2.2.2辛烷双(四氟硼酸盐)。
4.根据权利要求1所述的光-酶催化合成手性氟代苯乙醇的方法，其特征在于，所述的光催化剂选自Riboflavin tetrabutyrate、Eosin Y、fac-Tris(2-phenylpyridine)iridium[Ir(ppy)3]、Tris(2,2-bipyridyl)ruthenium(II)chloride hexahydrate、Sodiumanthraquinone-2-sulfonate、Riboflavin中的一种或多种。
5.根据权利要求4所述的光-酶催化合成手性氟代苯乙醇的方法，其特征在于，所述的光催化剂为Sodium anthraquinone-2-sulfonate。
6.根据权利要求1所述的光-酶催化合成手性氟代苯乙醇的方法，其特征在于，所述的苯乙烯或取代苯乙烯的浓度为250mmol/L；所述的氟试剂的浓度为220mmol/L；所述的光催化剂的浓度为66mmol/L；所述的苯乙烯或取代苯乙烯、氟试剂、光催化剂的体积比为4:5:3。
7.根据权利要求1所述的光-酶催化合成手性氟代苯乙醇的方法，其特征在于，所述的羰基还原酶为KtCR或RasADH，所述的KtCR的氨基酸序列如SEQ ID NO.1所示；所述的RasADH的氨基酸序列如SEQ ID NO.2所示。
8.根据权利要求1所述的光-酶催化合成手性氟代苯乙醇的方法，其特征在于，所述的产羰基还原酶的基因工程菌的菌液与a)反应体系的体积比为(5～20):1。
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| CN102876734A (zh) * | 2012-10-30 | 2013-01-16 | 华东理工大学 | 一种羰基还原酶、基因及其在不对称还原前手性羰基化合物中的应用 |
| CN109468346A (zh) * | 2018-06-01 | 2019-03-15 | 杭州馨海生物科技有限公司 | 一种(s)-1-(2-碘-5-氟苯基)乙醇的生物制备方法 |
-
2022
- 2022-03-08 CN CN202210219248.1A patent/CN114539039B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102876734A (zh) * | 2012-10-30 | 2013-01-16 | 华东理工大学 | 一种羰基还原酶、基因及其在不对称还原前手性羰基化合物中的应用 |
| CN109468346A (zh) * | 2018-06-01 | 2019-03-15 | 杭州馨海生物科技有限公司 | 一种(s)-1-(2-碘-5-氟苯基)乙醇的生物制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| MARTA BRAMBILLA等: "Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling of Secondary a-(Trifluoromethyl)benzyl Tosylates", 《ANGEW.CHEM.INT.ED》, vol. 56, pages 11981 - 11985 * |
| 周金龙等: "可见光诱导的醇的选择性氧化", 《高等学校化学学报》, no. 11, pages 2435 - 2441 * |
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