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1. 发明申请

WO03076640A8 A PROCESS FOR THE PREPARATION OF CEPHALOSPORAN ACID DERIVATIVES FROM CEPHALOSPORIN C 审中-公开
标题翻译： CEPHALOSPORIN C制备CEPHALOSPORAN酸衍生物的方法
公开(公告)号：WO03076640A8
公开(公告)日：2004-07-22
申请号：PCT/EP0302621
申请日：2003-03-10
申请人： BIOFERMA MURCIA S A , GUISAN SEIJAS JOSE M , FERNANDEZ LAFUENTE ROBERTO , FERNANDEZ LORENTE GLORIA , BETANCORT LORENA DUTRENIT , HUERTAS HIDALGO AURELIO , GONZALEZ MATEO CESAR
发明人： GUISAN SEIJAS JOSE M , FERNANDEZ LAFUENTE ROBERTO , FERNANDEZ LORENTE GLORIA , BETANCORT LORENA DUTRENIT , HUERTAS HIDALGO AURELIO , GONZALEZ MATEO CESAR
IPC分类号： C07D501/04 , C07D501/20 , C12P35/02 , C12N9/06 , C12N9/08 , C12N9/80 , C12N11/02 , C12N11/18 , C12P35/06 , C12P39/00
CPC分类号： C12P35/02
摘要： A process for the preparation of cephalosporin acid derivatives comprises the step of enzymatically converting cephalosporin C into 7 cephalosporin acid derivatives in the presence of two biocatalysts, wherein one biocatalyst comprises co-immobilised D-amino acid oxidase and a catalase enzyme, and the other biocatalyst comprises immobilised glutaryl acylase.
摘要翻译：一种制备头孢菌素酸衍生物的方法包括在两种生物催化剂存在下将头孢菌素C酶促转化为7种头孢菌素酸衍生物的步骤，其中一种生物催化剂包括共固定的D-氨基酸氧化酶和过氧化氢酶，另一种生物催化剂包括固定化戊二酰酰化酶。

2. 发明申请

WO2004020652A3 AN ENZYMATIC PROCESS FOR PREPARING BETA-LACTAMS 审中-公开
标题翻译：用于制备BETA-LACTAMS的酶化方法
公开(公告)号：WO2004020652A3
公开(公告)日：2004-05-06
申请号：PCT/EP0309661
申请日：2003-08-29
申请人： BIOFERMA MURCIA S A , GIESECKE ULRICH EBERHARD
发明人： GIESECKE ULRICH EBERHARD
IPC分类号： C12P35/00 , C12P35/02 , C12P35/04
CPC分类号： C12P35/00 , C12P35/02 , C12P35/04
摘要： An enzymatic process under kinetical control for preparing ß-lactams, by coupling the 7-amino group of 7-ACA with the carboxylic function of TZH activated as methyl- or ethylester. The process comprises using a penicillin amidase or a-amino acid esterase as free enzyme or in any suitable immobilised form; applying at least 100 mmol/l 7-ACA, applying TZH activated as ester a 1 - 3 fold molar ratio, and adjusting the pH to 6.0 - 8.0 and the temperature to 0 - 30°C. For direct 3-processing of the enzymatically synthesised TZ-7-ACA with heterocyclic thiols in aqueous solution at pH 6.0 - 8.5 and 50 - 75°C a dark brown colour is formed. Surprisingly this can be avoided, if 7-ACA is removed almost completely, advantageously by salting out the 7-derivative of 7-ACA. In said process the heterocylic thiol is MMTD or 2MTD and the formed product is cefazolin or ceftezol.
摘要翻译：通过将7-ACA的7-氨基与作为甲基或乙基酯活化的TZH的羧基官能团偶联制备β-内酰胺的酶反应过程。该方法包括使用青霉素酰胺酶或α-氨基酸酯酶作为游离酶或以任何合适的固定形式; 施用至少100mmol / l 7-ACA，施用活化为酯的1-3倍摩尔比的TZH，并将pH调节至6.0-8.0，温度为0-30℃。对于在pH 6.0-8.5和50-75℃的水溶液中用酶杂合的TZ-7-ACA与杂环硫醇的直接三步加工，形成深褐色。令人惊奇的是，如果7-ACA几乎完全除去，有利的是通过盐析7-ACA的7-衍生物，这是可以避免的。在所述方法中，杂环硫醇是MMTD或2MTD，形成的产物是头孢唑啉或头孢唑醇。

3. 发明申请

WO02086143A3 ENZYMATIC PROCESS FOR PREPARING CEPHALOSPORIN DERIVATIVES 审中-公开
标题翻译：用于制备CEPHOROSPORIN衍生物的酶法
公开(公告)号：WO02086143A3
公开(公告)日：2003-01-09
申请号：PCT/EP0204354
申请日：2002-04-18
申请人： BIOFERMA MURCIA S A , SANCHEZ-FERRER ALVARO , LOPEZ-MAS JOSE ANICETO , GARCIA-CARMONA FRANCISCO
发明人： SANCHEZ-FERRER ALVARO , LOPEZ-MAS JOSE ANICETO , GARCIA-CARMONA FRANCISCO
IPC分类号： C12P35/06 , C07D498/04 , C07D501/00 , C07D501/04 , C07D501/12 , C07D501/14 , C07D501/18 , C07D501/36 , C12P35/02
CPC分类号： C07D501/00
摘要： An enzymatic process for preparing 3-thiolated 7-aminocephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C of the formula (I), to form a 3-thiolated-glutaryl-7-ACA of the formula (II) and enzymatically converting a compound of formula (II) to form a 3-thiolated-7-ACA of the formula (III) wherein R is a heterocyclic group comprising at least one nitrogen atom and R1 And R2 are both hydrogen atoms or one of them is a hydrogen atom and the other is an acyl donor.
摘要翻译：制备3-硫醇化的7-氨基头孢烷酸衍生物的酶法包括以下步骤：将式（I）的3-硫醇化头孢菌素C酶化转化成式（II）的3-硫醇 - 戊二酰基-7-ACA，并且将式（II）化合物酶促转化成式（III）的3-硫醇化-7-ACA，其中R是包含至少一个氮原子的杂环基，且R 1和R 2都是氢原子或其中之一是氢原子，另一个是酰基供体。

4. 发明申请

WO2004020650A3 AN ENZYMATIC PROCESS FOR PREPARING BETA-LACTAMS 审中-公开
标题翻译：制备β-内酰胺的酶促方法
公开(公告)号：WO2004020650A3
公开(公告)日：2004-11-18
申请号：PCT/EP0309659
申请日：2003-08-29
申请人： BIOFERMA MURCIA S A , GIESECKE ULRICH EBERHARD
发明人： GIESECKE ULRICH EBERHARD
IPC分类号： C12P35/00 , C12P35/02 , C12P35/04
CPC分类号： C12P35/00 , C12P35/02 , C12P35/04
摘要： An enzymatic process under kinetical control for preparing b-lactams, by coupling the 7-amino group of a cephalosporin nucleus with the carboxylic function of an acetic acid derivative consisting of a residue with p-electrons, a short spacer and a carboxylic function activated as methyl- or ethylester. The process comprises using a penicillin amidase or a-amino acid esterase as free enzyme or in any suitable immobilised form; applying at least 100 mmol/l cephalosporin nucleus as long as it is soluble, otherwise 50 - 100 % of its maximum solubility is charged, applying the acetic acid activated as ester in a 1 - 3 fold molar ratio, and adjusting the pH to 6.0 - 8.0 and the temperature to 0 - 30 DEG C.
摘要翻译：通过将头孢菌素核的7-氨基与由具有p电子的残基，短间隔基和羧酸官能团组成的乙酸衍生物的羧基官能团偶联而制备β-内酰胺的动力学控制下的酶促过程，甲基 - 或乙基酯。该方法包括使用青霉素酰胺酶或α-氨基酸酯酶作为游离酶或以任何合适的固定形式使用; 只要其可溶性为至少100mmol / l头孢菌素核，否则加入其最大溶解度的50-100％，应用以1-3倍摩尔比酯化的乙酸，并调节pH至6.0 - 8.0，温度为0-30℃

5. 发明申请

WO02085914A2 A PROCESS FOR PREPARING 3-CEPHALOSPORANIC ACID DERIVATIVES USING alpha -KETOACID DERIVATIVES 审中-公开
标题翻译：一种使用α-酮二酸衍生物制备3-巯基苯甲酸衍生物的方法
公开(公告)号：WO02085914A2
公开(公告)日：2002-10-31
申请号：PCT/EP0204353
申请日：2002-04-18
申请人： BIOFERMA MURCIA S A , SANCHEZ-FERRER ALVARO , LOPEZ-MAS JOSE ANICETO , GARCIA-CARMONA FRANCISCO
发明人： SANCHEZ-FERRER ALVARO , LOPEZ-MAS JOSE ANICETO , GARCIA-CARMONA FRANCISCO
IPC分类号： C12P35/06 , C07D498/04 , C07D501/00 , C07D501/04 , C07D501/12 , C07D501/14 , C07D501/18 , C07D501/36 , C12P35/02
CPC分类号： C07D501/00
摘要： A process for preparing cephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C compound of formula (III) into a 3-thiolated- alpha -ketoadipyl-7-aminocephalosporanic acid derivative of formula (IV), wherein R is a heterocyclic group comprising at least a nitrogen atom. Compounds of formula (IV) are used in the preparation of cephalosporin C antibiotics and derivatives thereof.
摘要翻译：制备头孢菌酸衍生物的方法包括以下步骤：将式（III）的3-硫醇化头孢菌素C化合物酶化为式（Ⅳ）的3-巯基-α-酮缩水甘油基-7-氨基头孢烷酸衍生物，其中R为至少包含氮原子的杂环基。式（IV）化合物用于制备头孢菌素C抗生素及其衍生物。

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