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1. 发明申请

US20110256585A1 MUTANT PENICILLIN G ACYLASES 有权
公开(公告)号：US20110256585A1
公开(公告)日：2011-10-20
申请号：US13141877
申请日：2009-12-22
申请人： Jan Metske Van Der Laan , Harold Monro Moody , Thomas Van Der Does
发明人： Jan Metske Van Der Laan , Harold Monro Moody , Thomas Van Der Does
IPC分类号： C12P37/00 , C07H21/04 , C12N1/21 , C12N15/63 , C12P35/00 , C12N9/78
CPC分类号： C12N9/84 , C12P35/04 , C12P37/04
摘要： The present invention relates to a mutant prokaryotic penicillin G acylase derived from a wild-type penicillin G acylase characterized in that the mutant is having an amino acid substitution at one or more amino acid positions selected from the group consisting of amino acid positions A3, A77, A90, A144 A192, B24, B109, B148, B313, B460 and B488 according to the amino acid numbering of the Escherichia coli penicillin G acylase having the amino acid sequence depicted in SEQ ID No: 1.
摘要翻译：本发明涉及源自野生型青霉素G酰基转移酶的突变型原核青霉素G酰基转移酶，其特征在于突变体在选自氨基酸位置A3，A77的一个或多个氨基酸位置具有氨基酸取代，A90，A144A192，B24，B109，B148，B313，B460和B488，其具有SEQ ID No：1所示的氨基酸序列的大肠杆菌青霉素G酰基转移酶的氨基酸编号。

2. 发明申请

US20110104748A1 PROCESS FOR THE PREPARATION OF BETA-LACTAM COMPOUNDS 有权
标题翻译：制备BETA-LACTAM化合物的方法
公开(公告)号：US20110104748A1
公开(公告)日：2011-05-05
申请号：US12528695
申请日：2008-03-10
申请人： Thomas Van Der Does , Harold Monro Moody , Theodorus Johannes Godfried Maria Van Dooren
发明人： Thomas Van Der Does , Harold Monro Moody , Theodorus Johannes Godfried Maria Van Dooren
IPC分类号： C12P37/00 , C12P35/00 , C07C229/28
CPC分类号： C12P35/04 , C07D499/21 , C07D501/22 , C12P35/06 , C12P37/04
摘要： The present invention describes a process for the synthesis of a semi-synthetic β-lactam compound from a nucleus and a side chain selected from the group consisting of D-phenylglycine and D-dihydro-phenylglycine in the form of a side chain ester and an enzyme catalyzing the coupling of the side chain ester to the nucleus characterized in that the side chain ester is not isolated as a solid intermediate.
摘要翻译：本发明描述了一种从侧链中合成半合成β-内酰胺化合物的方法，所述核和侧链选自D-苯基甘氨酸和D-二氢 - 苯基甘氨酸，其为侧链酯形式，催化侧链酯与核的偶联的酶，其特征在于侧链酯不作为固体中间体分离。

3. 发明申请

US20100311113A1 CHEMO-ENZYMATIC PEPTIDE SYNTHESIS VIA C-TERMINAL ESTER INTERCONVERSION 有权
标题翻译：化学合成肽通过C末端反应器合成
公开(公告)号：US20100311113A1
公开(公告)日：2010-12-09
申请号：US12682653
申请日：2008-10-09
申请人： Peter Jan Leonard Mario Quaedflieg , Timo Nuijens , Claudia Cusan , Harold Monro Moody , Theodorus Johannes Godfried Maria Van Dooren
发明人： Peter Jan Leonard Mario Quaedflieg , Timo Nuijens , Claudia Cusan , Harold Monro Moody , Theodorus Johannes Godfried Maria Van Dooren
IPC分类号： C12P21/00
CPC分类号： C12P7/62 , C12P13/02 , C12P13/04 , C12P13/06 , C12P13/08 , C12P13/12 , C12P13/222 , C12P21/02
摘要： The invention relates to a method for preparing an optionally N-protected amino acid C-terminal ester or an optionally N-protected peptide C-terminal ester, comprising transesterifying the C-terminal t-alkyl ester of the amino acid or the C-terminal t-alkyl ester of the peptide with an alcohol (other than the t-alcohol corresponding to the t-alkyl group of the ester) in the presence of a hydrolytic enzyme (E.C. 3).The invention further relates to a method for preparing a peptide comprising coupling an activated, N-protected, amino acid C-terminal ester or an optionally N-protected peptide C-terminal ester with an optionally C-terminal protected amino acid or an optionally C-terminal protected peptide via a peptide bond, in the presence of an enzyme catalysing peptidic bond formation.
摘要翻译：本发明涉及一种制备任选N-保护的氨基酸C-末端酯或任选N-保护的肽C-末端酯的方法，该方法包括将氨基酸或C末端的C末端叔烷基酯酯交换在水解酶（EC 3）的存在下，该肽与醇（除了对应于酯的叔烷基的叔醇以外）的叔烷基酯。本发明还涉及一种制备肽的方法，其包括将活化的N-保护的氨基酸C-末端酯或任选N-保护的肽C末端酯与任选C末端保护的氨基酸或任选的C 在催化肽键形成的酶存在下通过肽键进行末端保护的肽。

4. 发明申请

US20100055749A1 PROCESS FOR THE PRODUCTION OF CLAVULANIC ACID 审中-公开
标题翻译：生产CLAVULANIC酸的方法
公开(公告)号：US20100055749A1
公开(公告)日：2010-03-04
申请号：US12517139
申请日：2007-11-29
申请人： Thomas Van Der Does , Piotr Wnukowski , Bengt Olof Mathias Danielsson , Harold Monro Moody
发明人： Thomas Van Der Does , Piotr Wnukowski , Bengt Olof Mathias Danielsson , Harold Monro Moody
IPC分类号： C12P17/18
CPC分类号： C12P17/188
摘要： The present invention relates to a process for preparation of a pharmaceutically acceptable metal salt of clavulanic acid comprising the steps of (a) fermenting of a microorganism capable of producing and excreting the clavulanic acid into the broth; (b) removing biomass and other solid material from the clavulanic acid containing fermentation broth obtained in step (a); (c) acidifying the solution obtained after step (b) to a pH between 1 and 3 and extracting the acidified solution with a partly or fully water-immiscible solvent and separating the clavulanic acid containing extract; (d) mixing the clavulanic acid containing extract obtained in step (c) with a metal donor and at least one additional cosolvent to result in an insoluble, preferably crystalline metal clavulanate salt with a yield of at least 80%; and (e) separating the insoluble, preferably crystalline, metal clavulanate salt from the mixture obtained in step (d).
摘要翻译：本发明涉及一种制备药学上可接受的克拉维酸的金属盐的方法，包括以下步骤：（a）将能够产生和排泄所述棒酸的微生物发酵到所述肉汤中; （b）从步骤（a）获得的含有棒酸的发酵液中除去生物质和其它固体物质; （c）将步骤（b）中获得的溶液酸化至1至3之间的pH，并用部分或完全与水不混溶的溶剂萃取酸化溶液并分离含有克拉维酸的提取物; （d）将步骤（c）中获得的含有克拉维酸的提取物与金属供体和至少一种额外的共溶剂混合，得到不溶性，优选结晶的克拉维酸盐，产率至少为80％; 和（e）从步骤（d）中获得的混合物中分离不溶性，优选结晶的金属克拉维酸盐。

5. 发明申请

US20150112057A1 NOVEL CRYSTALLINE CEFOPERAZONE INTERMEDIATE 审中-公开
标题翻译：新型水晶CEFOPERAZONE中间件
公开(公告)号：US20150112057A1
公开(公告)日：2015-04-23
申请号：US14128818
申请日：2012-06-21
申请人： Harold Monro Moody , Claudia Cusan , Edwin Gerard Ijpeij
发明人： Harold Monro Moody , Claudia Cusan , Edwin Gerard Ijpeij
IPC分类号： C07D501/57 , C12P35/00
CPC分类号： C07D501/57 , C12P35/00
摘要： The present invention relates to a crystalline form of an intermediate for cefoperazone of formula (1) and to a process for the preparation thereof by enzymatic condensation of a 3′-thiosubstituted β-lactam nucleus with a phenylglycine derivative.
摘要翻译：本发明涉及式（1）的头孢哌酮的中间体的结晶形式及其通过3'-取代的β-内酰胺核与苯基甘氨酸衍生物的酶促缩合制备的方法。

6. 发明申请

US20100063312A1 PROCESS FOR THE PREPARATION OF AMINO ACID METHYL ESTERS 有权
标题翻译：制备氨基酸甲酯的方法
公开(公告)号：US20100063312A1
公开(公告)日：2010-03-11
申请号：US12528691
申请日：2008-03-10
申请人： Harold Monro Moody
发明人： Harold Monro Moody
IPC分类号： C07C229/40
CPC分类号： C07C227/18 , C07C2601/16 , C07C229/32 , C07C229/36
摘要： The present invention describes a process for the synthesis of an amino acid methyl ester comprising the following steps: (a) refluxing a reaction mixture comprising a free amino acid, methanol and a strong acid; (b) concentrating the mixture; (c) adding methanol; (d) repeating steps a-c one or more times.
摘要翻译：本发明描述了合成氨基酸甲酯的方法，包括以下步骤：（a）回流包含游离氨基酸，甲醇和强酸的反应混合物; （b）浓缩混合物; （c）加入甲醇; （d）重复步骤a-c一次或多次。

7. 发明授权

US06287799B1 Process for the preparation of a&bgr;-lactam antibiotic 失效
标题翻译：制备abeta-lactam抗生素的方法
公开(公告)号：US06287799B1
公开(公告)日：2001-09-11
申请号：US09529569
申请日：2000-04-18
申请人： Theodorus Johannes Godfried Marie Van Dooren , Johanna Christina Maria Smeets , Harold Monro Moody
发明人： Theodorus Johannes Godfried Marie Van Dooren , Johanna Christina Maria Smeets , Harold Monro Moody
IPC分类号： C12P3504
CPC分类号： C12P35/04 , C12P37/04
摘要： Process for the preparation of a &bgr;-lactam antibiotic in which a &bgr;-lactam nucleus is subjected to an enzymatic acylation reaction with the aid of an acylation agent at a molar ratio of acylation agent/&bgr;-lactam nucleus of less than 2.5, with the acylation agent and/or the &bgr;-lactam nucleus being supersaturated in the reaction mixture during at least part of the acylation reaction. In the process, a concentrated slurry or solution, for instance, of the &bgr;-lactam nucleus and/or the acylation agent with a different pH or a higher temperature than the pH or temperature at which the acylation reaction is carried out is added to the reaction mixture during the acylation reaction. Both the &bgr;-lactam nucleus and the acylation agent may be supersaturated in the reaction mixture.
摘要翻译：制备β-内酰胺抗生素的方法，其中β-内酰胺核在借助于酰化剂的酰化剂/β-内酰胺核的摩尔比小于2.5的条件下进行酶酰化反应，其中酰化剂和/或β-内酰胺核在至少部分酰化反应中在反应混合物中过饱和。在此过程中，将浓缩的浆液或溶液，例如β-内酰胺核和/或具有与进行酰化反应的pH或温度不同的pH或更高温度的酰化剂加入到酰化反应中的反应混合物。 β-内酰胺核和酰化剂都可以在反应混合物中过饱和。

8. 发明申请

US20130217659A1 PROCESS FOR THE CRYSTALLISATION OF CEFADROXIL MONOHYDRATE 审中-公开
标题翻译：环丙沙酮单盐酸盐结晶过程
公开(公告)号：US20130217659A1
公开(公告)日：2013-08-22
申请号：US13846784
申请日：2013-03-18
申请人： Carlos Enrique LENHARD , Harold Monro MOODY , Theodorus Johannes Godfried Maria VAN DOOREN
发明人： Carlos Enrique LENHARD , Harold Monro MOODY , Theodorus Johannes Godfried Maria VAN DOOREN
IPC分类号： C07D501/20
CPC分类号： C07D501/20 , C07D501/12 , C07D501/22
摘要： Cefodroxil monohydrate is formed by a processing which includes a) bringing an aqueous solution of cefadroxil monohydrate to a pH of between 7 to 9 with a suitable titrant; b) lowering the pH to a value of between 5 and 6.5 to obtain a suspension of cefadroxil monohydrate in crystal form; and c) isolating the cefadroxil monohydrate in crystal form from the suspension obtained in step b). The cefadroxil monohydrate thereby obtained exhibits a CIE b value of below 6, and advantageously a CIE b value of below 12 when stored at a temperature of 25° C. for at least 1 month.
摘要翻译：通过以下处理形成头孢司肟一水合物，其包括：a）用合适的滴定剂将头孢羟氨酸一水合物的水溶液调至pH7至9之间; b）将pH降低至5至6.5之间的值以获得晶体形式的头孢羟氨酸一水合物的悬浮液; 和c）从步骤b）中获得的悬浮液中分离晶体形式的头孢羟氨酸一水合物。由此获得的头孢羟氨酸一水合物在25℃的温度下储存至少1个月时，其CIE b值低于6，有利地为低于12的CIE b值。

9. 发明授权

US08450084B2 Chemo-enzymatic peptide synthesis via C-terminal ester interconversion 有权
标题翻译：通过C端酯相互转化的化学酶肽合成
公开(公告)号：US08450084B2
公开(公告)日：2013-05-28
申请号：US12682653
申请日：2008-10-09
申请人： Peter Jan Leonard Mario Quaedflieg , Timo Nuijens , Claudia Cusan , Harold Monro Moody , Theodorus Johannes Godfried Maria Van Dooren
发明人： Peter Jan Leonard Mario Quaedflieg , Timo Nuijens , Claudia Cusan , Harold Monro Moody , Theodorus Johannes Godfried Maria Van Dooren
IPC分类号： C12P21/06 , C12P7/62
CPC分类号： C12P7/62 , C12P13/02 , C12P13/04 , C12P13/06 , C12P13/08 , C12P13/12 , C12P13/222 , C12P21/02
摘要： The invention relates to a method for preparing an optionally N-protected amino acid C-terminal ester or an optionally N-protected peptide C-terminal ester, comprising transesterifying the C-terminal t-alkyl ester of the amino acid or the C-terminal t-alkyl ester of the peptide with an alcohol (other than the t-alcohol corresponding to the t-alkyl group of the ester) in the presence of a hydrolytic enzyme (E.C. 3).The invention further relates to a method for preparing a peptide comprising coupling an activated, N-protected, amino acid C-terminal ester or an optionally N-protected peptide C-terminal ester with an optionally C-terminal protected amino acid or an optionally C-terminal protected peptide via a peptide bond, in the presence of an enzyme catalysing peptidic bond formation.
摘要翻译：本发明涉及一种制备任选N-保护的氨基酸C-末端酯或任选N-保护的肽C-末端酯的方法，该方法包括将氨基酸或C末端的C末端叔烷基酯酯交换在水解酶（EC 3）的存在下，该肽与醇（除了对应于酯的叔烷基的叔醇以外）的叔烷基酯。本发明还涉及一种制备肽的方法，其包括将活化的N-保护的氨基酸C-末端酯或任选N-保护的肽C末端酯与任选C末端保护的氨基酸或任选的C 在催化肽键形成的酶存在下通过肽键进行末端保护的肽。

10. 发明授权

US08071330B2 Process for the synthesis of cefaclor 有权
标题翻译：头孢克洛合成方法
公开(公告)号：US08071330B2
公开(公告)日：2011-12-06
申请号：US11794119
申请日：2005-12-23
申请人： Harold Monro Moody , Theodorus Johannes Godfried Maria Van Dooren
发明人： Harold Monro Moody , Theodorus Johannes Godfried Maria Van Dooren
IPC分类号： C12P35/04
CPC分类号： C12P35/04 , C07D501/58 , C12P35/00
摘要： The present invention relates to a process for the synthesis of cefaclor, which process comprises reacting 7-amino-3-chloro cephalosporanic acid (7-ACCA) with D-phenylglycine in activated form (PGa) in the presence of an enzyme in a reaction mixture to form cefaclor, wherein at least part of 7-ACCA and/or PGa are added to the reaction mixture during the course of the reaction. The invention also relates to an aqueous mixture comprising an amount of cefaclor of >10 (w/w) %, an amount of 7-amino-3-chloro cephalosporanic acid of
摘要翻译：本发明涉及一种头孢克洛的合成方法，该方法包括使7-氨基-3-氯头孢菌酸（7-ACCA）与活性形式的D-苯基甘氨酸（PGa）在酶的存在下反应混合物以形成头孢克洛，其中在反应过程中将7-ACCA和/或PGa的至少一部分加入到反应混合物中。本发明还涉及包含一定量的头孢克洛> 10（w / w）％，7-氨基-3-氯头孢菌酸的量<2（w / w）％和D量（w / w）％的苯基甘氨酸和从该水性混合物中回收头孢克洛的方法。本发明还涉及在400nm（A400）下的吸光度小于0.250的晶体形式的头孢克洛。

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