公开(公告)号：US07588913B2

公开(公告)日：2009-09-15

申请号：US10562345

申请日：2004-07-01

申请人： Dennis Heemskerk ,  Anja Gerarda Margaretha Hogenboom ,  Carlos Enrique Lenhardt ,  Harold Monro Moody ,  Theodorus Johannes Godfried Maria Van Dooren

发明人： Dennis Heemskerk ,  Anja Gerarda Margaretha Hogenboom ,  Carlos Enrique Lenhardt ,  Harold Monro Moody ,  Theodorus Johannes Godfried Maria Van Dooren

IPC分类号： C12P35/04 ,  C07D501/22

CPC分类号： C07D501/00 ,  C12P35/04

摘要： The present invention describes a process for preparing cephradine, said process comprising reacting 7-aminodesacetoxy cephalosporanic acid (7-ADCA) with D-dihydrophenylglycine in activated form (DHa) in the presence of an enzyme in a reaction mixture to form cephradine, resulting in a conversion of 7-ADCA into cephradine of at least 70%, wherein the concentration D-dihydrophenylglycine (DH) in the reaction mixture is below 2 wt.%, wherein the conversion of 7-ADCA into cephradine & equals; (nCEF/n7-ADCA)*100%, wherein nCEF=quantity of cephradine formed (in mole); and n7-ADCA=total quantity of 7-ADCA added to reaction mixture (in mole). The invention also describes a process for the preparation of cephradine hydrate characterised in that the process comprises: —reacting 7-amino acid desacetoxy cephalosporanic acid (7-ADCA) with DHa in the presence of an enzyme in a reaction mixture to form cephradine; —preparing an aqueous solution comprising at least part of the cephradine; and crystallising the cephradine from said aqueous solution. The invention further describes cephradine hydrate obtainable by a process according to invention. The invention also describes cephradine hydrate with an absorbance at 450 nm of below 0.050.

摘要翻译： 本发明描述了一种制备头孢拉定的方法，所述方法包括使7-氨基二乙酰氧基头孢菌酸（7-ADCA）与活化形式的二氢苯基甘氨酸（DHa）在酶的存在下在反应混合物中反应形成头孢拉定，得到 将7-ADCA转化为至少70％的头孢拉定，其中反应混合物中D-二氢苯基甘氨酸（DH）的浓度低于2重量％，其中7-ADCA转化成头孢拉定等于; （nCEF / n7-ADCA）* 100％，其中nCEF =形成的头孢拉定量（以摩尔计）; 和n7-ADCA =加入到反应混合物中的7-ADCA的总量（以摩尔计）。 本发明还描述了一种制备头孢拉定水合物的方法，其特征在于该方法包括：在反应混合物中，在酶的存在下，用7-氨基酸脱乙酰氧基头孢菌酸（7-ADCA）与DHa反应形成头孢拉定; - 制备包含至少一部分头孢拉定的水溶液; 并从所述水溶液中结晶头孢拉定。 本发明还描述了通过根据本发明的方法获得的头孢拉定水合物。 本发明还描述了在450nm处的吸光度低于0.050的头孢拉定水合物。