公开(公告)号：EP2298777A2

公开(公告)日：2011-03-23

申请号：EP09762643.6

申请日：2009-06-09

申请人： Enzytech, Ltd.

发明人： HWANG, Soon Ook ,  KIM, Young Jin

IPC分类号： C07D495/04

CPC分类号： C07D495/04

摘要： The present invention relates to a method for preparing Clopidogrel and its derivatives. More particularly, the present invention is a method for preparation of (S)-2-Clopidogrel and its derivatives, which are active inhibitors of platelet aggregation, from an optically active (S)-2-chlorophenyl glycine alkyl ester through hydrolysis of racemic 2-chlorophenylglycine alkyl esters using an enzyme. The present invention employs a simple procedure to prepare Clopidogrel and its derivatives. Because no chiral resolving agents are used except for a small amount of enzyme, the cost of preparation can be reduced. In addition, the present invention is suitable for synthesizing highly optical-active Clopidogrel and its derivatives on a large scale by using optically active (S)-2-chlorophenylglycine alkyl ester obtained in high yield as an intermediate, and is also environmentally friendly since no highly toxic reagents are employed.

摘要翻译： 本发明涉及氯吡格雷及其衍生物的制备方法。 更具体地说，本发明是通过外消旋2的水解从光学活性（S）-2-氯苯基甘氨酸烷基酯制备作为血小板聚集的活性抑制剂的（S）-2-氯吡格雷及其衍生物的方法 - 氯苯基甘氨酸烷基酯。 本发明采用简单的方法来制备氯吡格雷及其衍生物。 由于除了少量酶以外，不使用手性拆分剂，所以可以降低制备成本。 另外，本发明适用于通过使用以高收率获得的光学活性（S）-2-氯苯基甘氨酸烷基酯作为中间体大规模合成高度光学活性氯吡格雷及其衍生物，并且也是环保的 使用高毒性试剂。

公开(公告)号：EP2298777A4

公开(公告)日：2012-03-14

申请号：EP09762643

申请日：2009-06-09

申请人： ENZYTECH LTD

发明人： HWANG SOON OOK ,  KIM YOUNG JIN

IPC分类号： C07D495/04

CPC分类号： C07D495/04

公开(公告)号：EP3106465A4

公开(公告)日：2017-08-09

申请号：EP15746936

申请日：2015-02-05

申请人： ENZYTECH LTD

发明人： HWANG SOON OOK ,  YUN DAE MYOUNG

IPC分类号： C07F9/655 ,  C07C211/63 ,  C07F9/09 ,  C07F9/38 ,  C07F9/6574

CPC分类号： C07F9/10 ,  C07B2200/07 ,  C07F9/091 ,  C07F9/3808 ,  C07F9/65515 ,  C07F9/65742

摘要： The present invention relates to a method of preparing racemic or optically active D or L-±-glycerophosphorylcholine in large amounts by subjecting choline phosphate or a salt thereof, and racemic or optically highly pure (S) or (R)-3-halo-1,2-propanediol to a substitution reaction in a medium at high temperature in the presence of an inorganic base which increases the activity of the reaction. The method for preparing racemic or optically active D or L-±-glycerophosphorylcholine is cost-effective because of the use of starting materials which are inexpensive compared to those in a conventional method. Moreover, the method is simple and convenient because it is performed via a one-pot reaction without a separate purification process. In addition, it enables a large amount of racemic or optically active D or L-±-glycerophosphorylcholine, or a salt thereof, to be quantitatively produced in a medium without side reactions by using the inorganic base which increases the reaction activity.

摘要翻译： 本发明涉及一种通过将磷酸胆碱或其盐，以及外消旋或光学高度纯的（S）或（R）-3-卤代-β-甘油磷酸胆碱进行大量制备外消旋或旋光的D或L-甘油磷酸胆碱的方法， 1,2-丙二醇在高温下在无机碱存在下在介质中进行取代反应，这提高了反应的活性。 制备外消旋或光学活性的D或L-甘油磷酸胆碱的方法由于使用与常规方法相比便宜的原料而具有成本效益。 此外，该方法简单方便，因为其通过单罐反应进行而无需单独的纯化过程。 此外，通过使用提高反应活性的无机碱，它能够在没有副反应的介质中定量产生大量外消旋或旋光的D或L-甘油磷酸胆碱或其盐。

公开(公告)号：EP3106465B1

公开(公告)日：2019-04-10

申请号：EP15746936.2

申请日：2015-02-05

申请人： Enzytech, Ltd.

发明人： HWANG, Soon Ook ,  YUN, Dae Myoung

IPC分类号： C07F9/655 ,  C07C211/63 ,  C07F9/6574 ,  C07F9/09 ,  C07F9/38

公开(公告)号：EP3106465A1

公开(公告)日：2016-12-21

申请号：EP15746936.2

申请日：2015-02-05

申请人： Enzytech, Ltd.

发明人： HWANG, Soon Ook ,  YUN, Dae Myoung

IPC分类号： C07F9/09 ,  C07C211/63

CPC分类号： C07F9/10 ,  C07B2200/07 ,  C07F9/091 ,  C07F9/3808 ,  C07F9/65515 ,  C07F9/65742

摘要： The present invention relates to a method of preparing racemic or optically active D or L-α-glycerophosphorylcholine in large amounts by subjecting choline phosphate or a salt thereof, and racemic or optically highly pure (S) or (R)-3-halo-1,2-propanediol to a substitution reaction in a medium at high temperature in the presence of an inorganic base which increases the activity of the reaction. The method for preparing racemic or optically active D or L-α-glycerophosphorylcholine is cost-effective because of the use of starting materials which are inexpensive compared to those in a conventional method. Moreover, the method is simple and convenient because it is performed via a one-pot reaction without a separate purification process. In addition, it enables a large amount of racemic or optically active D or L-α-glycerophosphorylcholine, or a salt thereof, to be quantitatively produced in a medium without side reactions by using the inorganic base which increases the reaction activity.

摘要翻译： 本发明涉及一种通过使磷酸胆碱或其盐和外消旋或光学上高纯度（S）或（R）-3-卤代 - 吡咯烷酮制备外消旋或光学活性的D或L-±甘油磷酰胆碱的方法， 1,2-丙二醇在无机碱存在下在高温下在介质中进行取代反应，这增加了反应的活性。 制备外消旋或光学活性的D或L-±甘油磷酰胆碱的方法是成本有效的，因为使用与常规方法相比便宜的原料。 此外，该方法简单方便，因为它是通过一锅反应而不进行单独的纯化过程进行的。 此外，通过使用增加反应活性的无机碱，能够在无副反应的培养基中定量生成大量的外消旋或光学活性的D或L-±甘油磷酰胆碱或其盐。

公开(公告)号：EP1740714A1

公开(公告)日：2007-01-10

申请号：EP05764804.0

申请日：2005-04-27

申请人： Enzytech, Ltd.

发明人： HWANG, Soon Ook ,  CHUNG, Sun Ho

IPC分类号： C12P41/00

CPC分类号： C12P41/005 ,  C12P7/62 ,  C12P13/001 ,  C12P13/002

摘要： The present invention relates to process for the preparing of optically active ester derivatives and their acid derivatives which are used intensively as important chiral intermediates from racemic β-hydroxybutyl ester derivatives. In more detail, this invention relates to the process for preparing optically active β-hydroxybutyl ester derivatives and their acid derivatives by stere-ospecific hydrolysis of racemic β-hydroxybutyl ester derivatives using Upases or lipase-producing microorganisms in the aqeous phase or organic phase including aqeous solvent. The method of making optically active ester derivatives and their acid derivatives by hydrolysis of β-hydroxybutyl ester derivatives represented by the general formula 1 in scheme 1 is easier and more economical comparing to the conventional methods and the products have high optical purity. Also separation of ester derivatives from acid derivatives is easy after reaction. Thus this method is a useful process on the industrial scale.