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1. 发明授权

US09512063B2 Process for the preparation of advantame 有权
标题翻译：制备优势的过程
公开(公告)号：US09512063B2
公开(公告)日：2016-12-06
申请号：US14848533
申请日：2015-09-09
申请人： Divi's Laboratories Limited
发明人： Murali Krishna Prasad Divi , Mysore Aswatha Narayana Rao , Shaik Nowshuddin
IPC分类号： C07C231/12 , C07K5/075 , C07C45/45
CPC分类号： C07C231/12 , C07C45/45 , C07C45/455 , C07C231/14 , C07K5/0613 , C07C237/12 , C07C47/277
摘要： A novelprocess for the preparation of N—[N-[3-(3-hydroxy-4-methoxyphenyl)-propyl]-L-α-aspartyl]-L-phenylalanine-1-methyl ester is described. It comprises, reacting isovanillin or its derivative with vinyl acetate followed by reductive condensation with L-[α-aspartyl]-L-phenylalanine-1-methyl ester.
摘要翻译：描述了制备N- [N- [3-（3-羟基-4-甲氧基苯基） - 丙基] -L-α-天冬氨酰基] -L-苯丙氨酸-1-甲酯的新方法。它包括使异喹啉腈或其衍生物与乙酸乙烯酯反应，然后与L- [α-天冬氨酰基] -L-苯丙氨酸-1-甲酯还原缩合。

2. 发明申请

US20160304439A1 PROCESS FOR THE PREPARATION OF ADVANTAME 有权
标题翻译：制备优点的方法
公开(公告)号：US20160304439A1
公开(公告)日：2016-10-20
申请号：US14848533
申请日：2015-09-09
申请人： Divi's Laboratories Limited
发明人： Murali Krishna Prasad Divi , Mysore Aswatha Narayana Rao , Shaik Nowshuddin
IPC分类号： C07C231/12 , C07C45/45
CPC分类号： C07C231/12 , C07C45/45 , C07C45/455 , C07C231/14 , C07K5/0613 , C07C237/12 , C07C47/277
摘要： A novelprocess for the preparation of N—[N-[3-(3-hydroxy-4-methoxyphenyl)-propyl]-L-α-aspartyl]-L-phenylalanine-1-methyl ester is described. It comprises, reacting isovanillin or its derivative with vinyl acetate followed by reductive condensation with L-[α-aspartyl]-L-phenylalanine-1-methyl ester.
摘要翻译：描述了制备N- [N- [3-（3-羟基-4-甲氧基苯基） - 丙基] -L-α-天冬氨酰基] -L-苯丙氨酸-1-甲酯的新方法。它包括使异喹啉腈或其衍生物与乙酸乙烯酯反应，然后与L- [α-天冬氨酰基] -L-苯丙氨酸-1-甲酯还原缩合。

3. 发明授权

US08389240B2 Method for producing α-L-aspartyl-L-phenylalanine-β-ester and method for producing α-L-aspartyl-L-phenylalanine-α-methyl ester 有权
公开(公告)号：US08389240B2
公开(公告)日：2013-03-05
申请号：US13528126
申请日：2012-06-20
申请人： Kenzo Yokozeki , Ayako Ohno , Seiichi Hara , Isao Abe
发明人： Kenzo Yokozeki , Ayako Ohno , Seiichi Hara , Isao Abe
IPC分类号： C12P21/06
CPC分类号： C07K5/0613 , A23L27/32 , C07K5/06113 , C12P21/02 , C12P21/06
摘要： A method of producing an α-L-aspartyl-L-phenylalanine-β-ester by forming the α-L-aspartyl-L-phenylalanine-β-ester from L-aspartic acid-α,β-diester and L-phenylalanine using an enzyme or enzyme-containing substance that has an ability to selectively link L-phenylalanine to an α-ester site of the L-aspartic acid-α,β-diester through a peptide bond.

4. 发明授权

US08247193B2 Method for producing α-L-aspartyl-L-phenylalanine-β-ester and method for producing α-L-aspartyl-L-phenylalanine-α-methyl ester 有权
标题翻译：制备α-L-天冬氨酰基-L-苯丙氨酸的方法和制备α-L-天冬氨酰基-L-苯丙氨酸-α-甲酯的方法
公开(公告)号：US08247193B2
公开(公告)日：2012-08-21
申请号：US13198075
申请日：2011-08-04
申请人： Kenzo Yokozeki , Ayako Ohno , Seiichi Hara , Isao Abe
发明人： Kenzo Yokozeki , Ayako Ohno , Seiichi Hara , Isao Abe
IPC分类号： C12P21/06
CPC分类号： C07K5/0613 , A23L27/32 , C07K5/06113 , C12P21/02 , C12P21/06
摘要： A method of producing an α-L-aspartyl-L-phenylalanine-β-ester by forming the α-L-aspartyl-L-phenylalanine-β-ester from L-aspartic acid-α,β-diester and L-phenylalanine using an enzyme or enzyme-containing substance that has an ability to selectively link L-phenylalanine to an α-ester site of the L-aspartic acid-α,β-diester through a peptide bond.
摘要翻译：通过从L-天冬氨酸-α，二酯和L形成α-L-天冬氨酰基-L-苯丙氨酸 - 乙酸酯制备α-L-天冬氨酰基-L-苯丙氨酸 - 酯的方法 - 苯丙氨酸，其使用具有通过肽键将L-苯丙氨酸选择性地连接到L-天冬氨酸-α，α-二酯的α-酯位点的酶或酶的物质。

5. 发明授权

US07960578B2 Method for the synthesis of peptides without solvent 有权
标题翻译：无溶剂合成肽的方法
公开(公告)号：US07960578B2
公开(公告)日：2011-06-14
申请号：US12531972
申请日：2008-03-21
申请人： Jean Martinez , Frédéric Lamaty , Valérie Declerck
发明人： Jean Martinez , Frédéric Lamaty , Valérie Declerck
IPC分类号： C07C229/00
CPC分类号： C07K1/06 , C07K1/061 , C07K5/06052 , C07K5/06078 , C07K5/0613 , Y02P20/55
摘要： The disclosure relates to a method for the synthesis of a compound of the formula (I) in which: n is an integer higher than or equal to 1; Rb and each Rn are independently a hydrogen atom, a C1-C6 arylalkyl group or a C1-C6 alkyl group substituted or not by an aryl group, —COOH, C1-C6, —COO-(alkyl), —CONH2, —SH, heteroaryl, —NH2, —NHC(NH)(NH2), C1-C6-s-(alkyl), —OH or phenol; Ra is a N-protective group; Rc is a ORd group in which Rd is a C1-C6 alkyl group or a NReRf group in which Re and Rf Re independently an N-protective group.
摘要翻译：本公开涉及合成式（I）化合物的方法，其中：n为高于或等于1的整数; Rb和Rn各自独立地为氢原子，C1-C6芳烷基或被芳基取代或未被芳基取代的C1-C6烷基，-COOH，C1-C6，-COO-（烷基），-CONH2，-SH ，杂芳基，-NH 2，-NHC（NH）（NH 2），C 1 -C 6 -S-（烷基），-OH或苯酚; Ra是N-保护基; Rc是其中Rd是C1-C6烷基或NReRf基团的ORd基团，其中Re和RfRe独立地是N-保护基团。

6. 发明申请

US20100016631A1 METHOD FOR THE SYNTHESIS OF PEPTIDES WITHOUT SOLVENT 失效
标题翻译：没有溶剂合成肽的方法
公开(公告)号：US20100016631A1
公开(公告)日：2010-01-21
申请号：US12531972
申请日：2007-03-21
申请人： Jean Martinez , Frédéric Lamaty , Valérle Declerck
发明人： Jean Martinez , Frédéric Lamaty , Valérle Declerck
IPC分类号： C07C229/34
CPC分类号： C07K1/06 , C07K1/061 , C07K5/06052 , C07K5/06078 , C07K5/0613 , Y02P20/55
摘要： The disclosure relates to a method for the synthesis of a compound of the formula (I) in which: n is an integer higher than or equal to 1; Rb and each Rn are independently a hydrogen atom, a C1-C6 arylalkyl group or a C1-C6 alkyl group substituted or not by an aryl group, —COOH, C1-C6, —COO-(alkyl), —CONH2, —SH, heteroaryl, —NH2, —NHC(NH)(NH2), C1-C6-s-(alkyl), —OH or phenol; Ra is a N-protective group; Rc is a ORd group in which Rd is a C1-C6 alkyl group or a NReRf group in which Re and Rf Re independently an N-protective group.
摘要翻译：本公开涉及合成式（I）化合物的方法，其中：n为高于或等于1的整数; Rb和Rn各自独立地为氢原子，C1-C6芳烷基或被芳基取代或未被芳基取代的C1-C6烷基，-COOH，C1-C6，-COO-（烷基），-CONH2，-SH ，杂芳基，-NH 2，-NHC（NH）（NH 2），C 1 -C 6 -S-（烷基），-OH或苯酚; Ra是N-保护基; Rc是其中Rd是C1-C6烷基或NReRf基团的ORd基团，其中Re和RfRe独立地是N-保护基团。

7. 发明授权

US06444251B1 Sweetener compositions containing aspartame and aspartame derivative 失效
标题翻译：含有阿斯巴甜和阿斯巴甜衍生物的甜味剂组合物
公开(公告)号：US06444251B1
公开(公告)日：2002-09-03
申请号：US09594039
申请日：2000-06-15
申请人： Akihiro Kishishita , Kazutaka Nagashima
发明人： Akihiro Kishishita , Kazutaka Nagashima
IPC分类号： A23L1236
CPC分类号： C07K5/06113 , A23L27/32 , C07K5/0613
摘要： A homogeneous sweetener composition containing aspartame (APM) and N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine methyl ester having tasting properties similar to sucrose, can be efficiently produced in high yields and with a high purity by reductive alkylation of APM with an at most equimolar amount 3,3-dimethylbutylaldehyde followed by separating the reducing agent from the liquid reaction mixture, and separating of the precipitated crystals of the sweetener composition.
摘要翻译：具有与蔗糖相似的品尝性能的含有阿斯巴甜（APM）和N- [N-（3,3-二甲基丁基）-L-α-天冬氨酰基] -L-苯丙氨酸甲酯的均匀的甜味剂组合物可以高产率有效地生产，通过用至多等摩尔量的3,3-二甲基丁醛的APM的还原烷基化，然后从液体反应混合物中分离还原剂，并分离出甜味剂组合物的沉淀的晶体，具有高纯度。

8. 发明申请

US20020025549A1 Synthesis and recovery of aspartame involving enzymatic deformylation step 失效
标题翻译：涉及酶的去甲酰化步骤的阿斯巴甜的合成和回收
公开(公告)号：US20020025549A1
公开(公告)日：2002-02-28
申请号：US09886476
申请日：2001-06-22
发明人： Peter J.L.M. Quaedflieg , Theodorus Sonke , Adolf F.V. Wagner
IPC分类号： C12P021/06
CPC分类号： C12P21/02 , C07K5/0613 , C12N9/80 , C12P41/007
摘要： The invention relates to the synthesis of aspartame involving enzymatic deformylation of an N-formyl-null-L-aspartyl-L-phenylalanine compound by treatment with an enzyme having formylmethionyl peptide deformylase activity and having as a co-factor group 5 to 11 bivalent metal ions. The invention also relates to selective preparation and recovery of aspartame from a mixture of N-formyl-null- and null-L-aspartyl-L-phenylalanine compounds by treatment with such enzyme. And finally, the invention relates to one-pot enzymatic synthesis of aspartame from N-formyl-L-aspartic acid and L- or D,L-phenylalanine methyl ester involving an enzymatic deformylation reaction simultaneously with an enzymatic coupling reaction, as well as to one-pot di- or oligopeptide synthesis by simultaneous enzymatic coupling and deformylation reactions in general.
摘要翻译：本发明涉及通过用具有甲酰基甲硫氨酰基肽去甲酰化酶活性的酶处理并具有5至11个二价金属的辅因子来合成涉及N-甲酰基-α-L-天冬氨酰基-L-苯丙氨酸化合物的酶促变性的天冬甜素离子。本发明还涉及通过用这种酶处理从N-甲酰基-α-和β-L-天冬氨酰基-L-苯丙氨酸化合物的混合物中选择性制备和回收阿斯巴甜。最后，本发明涉及一种来自N-甲酰基-L-天冬氨酸和L-或D，L-苯丙氨酸甲酯的一步法酶促合成涉及酶促变性反应同时进行酶偶联反应，以及通常通过同时酶偶联和变形反应来进行一锅二糖或寡肽的合成。

9. 发明授权

US6004768A Biosensors, extracorporeal devices and methods for detecting substances using crosslinked protein crystals 失效
标题翻译：生物传感器，体外装置和使用交联蛋白质晶体检测物质的方法
公开(公告)号：US6004768A
公开(公告)日：1999-12-21
申请号：US484238
申请日：1995-06-07
申请人： Manuel A. Navia , Nancy L. St. Clair
发明人： Manuel A. Navia , Nancy L. St. Clair
IPC分类号： A61K38/43 , A61K38/46 , C07K1/107 , C07K5/072 , C12M1/40 , C12N9/14 , C12N9/20 , C12N9/36 , C12N9/54 , C12N9/66 , C12N9/80 , C12N9/82 , C12N11/00 , C12Q1/00 , C12Q1/37 , G01N33/531 , C12Q1/34 , C12M1/34
CPC分类号： C12N9/2462 , C07K1/1077 , C07K5/0613 , C12N11/00 , C12N9/14 , C12N9/20 , C12N9/54 , C12N9/6448 , C12N9/80 , C12N9/82 , C12Q1/00 , C12Q1/003 , C12Q1/37 , G01N33/531 , A61K38/00 , Y10S435/817 , Y10S530/81
摘要： Proteins such as enzymes and antibodies are immobilized by crosslinking crystals of the proteins such as microcrystals having a cross-section of 10.sup.-1 mm or less with a multifunctional crosslinking agent. The crosslinked protein crystals may be lyophilized for storage. Crystals of an enzyme such as thermolysin, elastase, asparaginase, lysozyme, lipase or urease may be crosslinked to provide crosslinked enzyme crystals that retain at least 91% activity after incubation for three hours in the presence of a concentration of Pronase.TM. that causes the soluble uncrosslinked form of the enzyme to lose at least 94% of its initial activity under the same conditions. A preferred Pronase.TM.:enzyme ratio is 1:40. Crosslinked enzyme or antibody crystals may be used in an assay, diagnostic kit or biosensor for detecting an analyte, in an extracorporeal device for altering a component of a fluid, in producing a product such as using crosslinked thermolysin crystals to produce aspartame, in separating a substance from a mixture, and in therapy.
摘要翻译：蛋白质如酶和抗体通过用多官能交联剂交联具有10-1mm或更小截面的微晶的蛋白质的晶体来固定。交联的蛋白质晶体可以冻干以储存。可以交联酶，例如嗜热菌蛋白酶，弹性蛋白酶，天冬酰胺酶，溶菌酶，脂肪酶或脲酶的晶体以提供交联的酶晶体，其在浓度为Pronase TM的浓度存在下孵育3小时后保持至少91％的活性，其导致可溶性未交联形式的酶在相同条件下损失至少94％的初始活性。 Pronase TM：酶比为1:40。交联的酶或抗体晶体可用于用于检测分析物的测定，诊断试剂盒或生物传感器，用于改变流体组分的体外装置中，用于在产生例如使用交联的嗜热溶蛋白晶体产生阿斯巴甜的产物时分离物质从混合物和治疗。

10. 发明授权

US5902737A Process for the preparation of disodium benzyloxycarbonyl-L-aspartate from fumaric acid 失效
标题翻译：从富马酸制备苄氧羰基-L-天冬氨酸二钠的方法
公开(公告)号：US5902737A
公开(公告)日：1999-05-11
申请号：US934141
申请日：1997-09-19
申请人： Gerald Kirchner , Erik Salzbrenner , Christian Werenka , Wilhelmus Boesten
发明人： Gerald Kirchner , Erik Salzbrenner , Christian Werenka , Wilhelmus Boesten
IPC分类号： C07C229/24 , C07C271/22 , C07K5/06 , C07K5/075 , C12P13/20 , C12P13/04
CPC分类号： C07C271/22 , C07K5/0613 , C12P13/20
摘要： A process for the preparation of disodium Z-L-aspartate from fumaric acid, in whicha) fumaric acid is reacted with ammonia in an inert diluent in the presence of aspartase or aspartase-producing microorganisms to give ammonium L-aspartate thenb) the ammonium L-aspartate-containing solution is treated with sodium hydroxide, forming, depending on the amount of sodium hydroxide used, the mono- or disodium L-aspartate or a mixture thereof, andc) the eliminated ammonia is returned to a fumaric acid suspension, which is used as starting solution for further enzymatic reactions, and thend) the residual mono and/or disodium L-aspartate-containing solution is reacted with benzyloxycarbonyl chloride at a pH of between 9 and 14, with the simultaneous addition of sodium hydroxide, to form disodium Z-L-aspartate.
摘要翻译：一种从富马酸制备ZL-天冬氨酸二钠的方法，其中a）富马酸在惰性稀释剂中，在天冬氨酰胺酶或产生天冬氨酸的微生物存在下与氨反应得到L-天冬氨酸铵，然后b）铵L 含天冬氨酸的溶液用氢氧化钠处理，根据使用的氢氧化钠的量，L-天冬氨酸单钠盐或其混合物或其混合物形成，和c）将去除的氨返回到富马酸悬浮液中，其中用作进一步酶促反应的起始溶液，然后d）将残留的含有L-天冬氨酸的一价和/或二钠溶液与苄氧羰基氯反应，其pH为9至14，同时加入氢氧化钠至形成ZL-天冬氨酸二钠。

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