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1.发明公开公开(公告)号：US20240182884A1
公开(公告)日：2024-06-06
申请号：US18551160
申请日：2021-04-12
发明人： Hao HONG , Yi XIAO , Na ZHANG , Han LIN , Pong PAN , Williams VYASA , Liteng MA , Yuxia CUI , Yanyan GAO
IPC分类号： C12N11/084 , C12N9/02 , C12N9/04 , C12N9/06 , C12N9/10
CPC分类号： C12N11/084 , C12N9/0006 , C12N9/0016 , C12N9/0073 , C12N9/1096 , C12Y101/01 , C12Y104/01009 , C12Y114/13022 , C12Y206/01
摘要： The application provides an enzyme immobilization carrier and a preparation method thereof, an immobilized enzyme and a preparation method thereof. The above enzyme immobilization carrier is obtained by an amino modification or a cyanuric chloride modification of super-crosslinked polyvinyl alcohol. The use of the enzyme immobilization carrier provided by the application may effectively improve the stability and reusability of the immobilized enzyme. Moreover, due to the use of the form of enzyme covalent linkage, compared with an embedding method, the preparation method is no need for chemical reagent immersion and the like, it is beneficial to maintain the own activity of the enzyme, and promote the immobilized enzyme to have the better activity while the stability and reusability are kept.
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公开(公告)号：US20240117395A1
公开(公告)日：2024-04-11
申请号：US18275833
申请日：2021-07-06
发明人： Hao Hong , Gage James , Yi Xiao , Na Zhang , Xuecheng Jiao , Yulei Ma , Huiyan Mou , Zujian Wang , Kaihua Sun , Ru Jia , Fang Liu , Wenjing Liu
CPC分类号： C12P17/14 , C12N9/1096 , C12P13/001 , C12P17/12 , C12Y206/01
摘要： Provided is a method for synthesizing a chiral amine compound. A transaminase is used to transaminate a ketone substrate under the action of an amino donor, to obtain the chiral amine compound; and the conserved amino acid sequence region of the transaminase at least includes a region 1 (MAGLWCVN) and a region 2 (YNTFFKT). With the transaminase with the specific conserved amino acid sequence region to synthesize a large sterically hindered chiral amine, the enzyme catalytic reaction volume is small, the synthesizing route is short, the product yield is high, a high-cost noble metal is not required for catalysis under the synthesizing conditions, three wastes are reduced, and the production cost is saved.
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公开(公告)号：US20230235300A1
公开(公告)日：2023-07-27
申请号：US17997419
申请日：2020-05-29
发明人： Hao HONG , Gage JAMES , Yi XIAO , Na ZHANG , Xuecheng JIAO , Yulei MA , Huiyan MU , Shan CAO
CPC分类号： C12N9/1096 , C12N15/52 , C12N15/70 , C12P13/001 , C12Y206/01
摘要： Provided are a transaminase mutant and an application thereof. Compared with an amino acid sequence shown in SEQ ID NO:1, an amino acid sequence of the transaminase mutant includes at least one of the following mutation sites: L166, K149, K146, A168, H73, F133, H82, E24, V194, T294, A295, G235 and F236. The mutant of the present invention has the improved catalytic activity for a transammonization reaction of ketone substrates, and is suitable for industrial production of chiral amines.
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公开(公告)号：US20230021514A1
公开(公告)日：2023-01-26
申请号：US17782200
申请日：2019-12-27
发明人： Jiuyuan LI , Johnson MATT , Changfeng LI , Lutao JING , Arumugam BALASUBRAMANIAN , Xiaolong LEI , Zili ZHU
摘要： Disclosed are an etelcalcetide intermediate and a method for synthesizing etelcalcetide. The etelcalcetide intermediate is Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The method for synthesizing the etelcalcetide includes the following steps: using N-Boc-L-Cqs-OtBu as a starting material to generate a primary product of a formula (A) by means of a substitution reaction, herein R is S-Py or Cl; and performing a coupling reaction on the primary product and Fmoc-D-Cys-OH amino acid to obtain Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The key intermediate is used for synthesizing the etelcalcetide, which may improve the purity and the yield. It is important that the raw materials for synthesizing the key intermediate are cheap and readily available, and the process is simple.
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公开(公告)号：US20220259122A1
公开(公告)日：2022-08-18
申请号：US17618577
申请日：2019-06-11
发明人： Hao HONG , Jiangping LU , Enxuan ZHANG , Zhiqing LIU , Tao ZHANG
IPC分类号： C07C29/147 , C07B41/02
摘要： Disclosed are a borohydride reduction stabilizing system and a method for reducing an ester to an alcohol. The borohydride reduction stabilizing system includes: a borohydride reducing agent and a stabilizing agent for stabilizing the borohydride reducing agent. The borohydride reducing agent is sodium borohydride or potassium borohydride. The stabilizing agent is an alkali metal salt of an alcohol. By adding the alkali metal salt of the alcohol, such as sodium alkoxide or potassium alkoxide, on the basis of an existing sodium/potassium borohydride reducing agent, the sodium/potassium borohydride reducing agent may be kept stable without being decomposed under the condition of increased temperature, so that on the one hand, the reducing activity is maintained in a relatively high state, and the condition of excessive use is reduced, and on the other hand, the generation of hydrogen is reduced, and the process risks are reduced.
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公开(公告)号：US20220002683A1
公开(公告)日：2022-01-06
申请号：US17290749
申请日：2018-11-05
发明人： Hao HONG , Gage JAMES , Jiangping LU , Xuecheng JIAO , Na ZHANG , Kejian ZHANG , Rui LI , Yu ZHANG , Yiming YANG
摘要： An amino acid sequence of the monooxygenase mutant is obtained by mutation of an amino acid sequence shown in SEQ ID NO: 1, and the mutation at least includes one of the following mutation sites: 45-th site, 95-th site, 106-th site, 108-th site, 114-th site, 186-th site, 190-th site, 191-th site, 249-th site, 257-th site, 393-th site, 436-th site, 499-th site, 500-th site, 501-th site, 503-th site, 504-th site, 559-th site, and 560-th site.
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公开(公告)号：US10961516B2
公开(公告)日：2021-03-30
申请号：US16344779
申请日：2016-11-04
申请人： ASYMCHEM LABORATORIES (TIANJIN) CO., LTD. , ASYMCHEM LIFE SCIENCE (TIANJIN) CO., LTD. , TIANJIN ASYMCHEM PHARMACEUTICALS CO., LTD. , ASYMCHEM LABORATORIES (FUXIN) CO., LTD. , JILIN ASYMCHEM LABORATORIES CO., LTD.
发明人： Hao Hong , Gage James , Jiangping Lu , Na Zhang , Wenyan Yu , Fang Liu , Yanjun Li , Xin Huang , Juan Gao , Kejian Zhang , Yulei Ma , Junlu Wei
摘要： Provided are a proline hydroxylase and uses thereof. The proline hydroxylase comprises (a) a protein having the amino acid sequence as shown in SEQ ID NO: 2; (b) a protein having an amino acid sequence of SEQ HD NO: 2 with a mutation of one or more amino acids and having a proline hydroxylase activity; or (c) a protein retaining the mutation of one or more amino acids as in (b), and having the proline hydroxylase activity and having at least 78% homology with the amino acid sequence of the protein in (b). Protein having the amino acid sequence as shown in SEQ HD NO: 2 and mutants obtained by genetically engineering have higher catalytic specificity or significantly increased catalytic activity when compared to proline hydroxylases in prior art.
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公开(公告)号：US10544119B2
公开(公告)日：2020-01-28
申请号：US15309469
申请日：2014-08-04
申请人： Asymchem Laboratories (Tianjin) Co., Ltd. , Asymchem Life Science (Tianjin) Co., Ltd. , Tianjin Asymchem Pharmaceutical Co., Ltd. , Asymchem Laboratories (Fuxin) Co., Ltd. , Jilin Asymchem Laboratories Co., Ltd.
发明人： Hao Hong , Chaoyong Chen , Jiuyuan Li , Litao Shen , Lina Guo , Hongying Tian
IPC分类号： C07D319/06 , C12P7/62 , C07C51/367 , C07C67/30 , C07C67/313
摘要： The present invention relates to a preparation method for a chiral intermediate for use in statins, acquired with chloroacetic acid and benzyl alcohol as starting materials via a series of reactions, namely etherification, condensation, substitution, and asymmetric reduction. The preparation method provided in the present invention has a novel route of synthesis, allows an intermediate compound to be introduced conveniently into the chiral center of a glycol via enzyme reduction, and not only is low in costs, but also is reliable in quality. The route of synthesis provided in the present invention uses raw materials of low costs, has an easy to operate process, and provides a final product of great purity and high yield.
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公开(公告)号：US10131883B2
公开(公告)日：2018-11-20
申请号：US15309690
申请日：2014-08-04
申请人： ASYMCHEM LABORATORIES (TIANJIN) CO., LTD. , ASYMCHEM LIFE SCIENCE (TIANJIN) CO., LTD. , TIANJIN ASYMCHEM PHARMACEUTICAL CO., LTD. , ASYMCHEM LABORATORIES (FUXIN) CO., LTD. , JILIN ASYMCHEM LABORATORIES CO., LTD.
摘要： The application provides a Diketoreductase (DKR) mutant, its nucleotide coding sequence, and an expression cassette, recombinant vector and host cell containing the sequence, as well as a method for application of the mutant to the preparation of 3R,5S-dicarbonyl compound. An ee value of the obtained 3R,5S-dicarbonyl compound is higher than 99%, and a de value is about 90%. The DKR mutant is a key pharmaceutical intermediate, and particularly provides an efficient catalyst for synthesis of a chiral dicarbonyl hexanoic acid chain of a statin drug.
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10.发明申请INTERMEDIATE COMPOUND FOR PREPARING ROSUVASTATIN CALCIUM AND METHOD FOR PREPARING ROSUVASTATIN CALCIUM THEREFROM 有权用于制备罗司沙坦钙的中间体化合物及其制备罗素沙丁胺钙的方法公开(公告)号：US20170022169A1
公开(公告)日：2017-01-26
申请号：US15124083
申请日：2014-03-07
申请人： Asymchem Laboratories (Tianjin) Co., Ltd. , Asymchem Life Science (Tianjin) Co., Ltd. , Tianjin Asymchem Pharmaceutical Co., Ltd. , Asymchem Laboratories (Fuxin) Co., Ltd. , Jilin Asymchem Laboratories Co., Ltd.
发明人： Hao HONG , James GAGE , Jiuyuan LI , Litao SHEN , Lei ZHANG , Changming DONG
IPC分类号： C07D239/42
CPC分类号： C07D239/42 , C07B2200/13 , C07F9/6512 , Y02P20/55
摘要： Provided are an intermediate compound for preparing rosuvastatin calcium and a preparation method of the rosuvastatin calcium. The method comprises: using the foregoing intermediate compound as a raw material, and subjecting the raw material to a step of Wittig reaction, a step of protecting group removal and hydrolysis and a step of calcium salt formation, so as to obtain the rosuvastatin calcium. The product, which is prepared from the intermediate compound, can be substantially enhanced in stereoselectivity and also notably improved in purity and yield; in addition, the method for preparing rosuvastatin calcium from the intermediate compound is simple, convenient and low in cost.
摘要翻译： 提供了用于制备瑞舒伐他汀钙的中间体化合物和罗苏伐他汀钙的制备方法。 该方法包括：使用上述中间体化合物作为原料，并对原料进行维蒂希反应的步骤，保护基团除去和水解的步骤和钙盐形成步骤，以获得瑞舒伐他汀钙。 由中间体化合物制备的产物可以显着增强立体选择性，并且还显着提高了纯度和产率; 另外，从中间体化合物制备瑞舒伐他汀钙的方法简单，方便，成本低。
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