Patent RU-2219182-C2 (RU)
Title: New method for enzymatic preparing cephalosporin
Inventor: BOGERS ILKO ADRIANUS LAMBERTUS
IPC: C07D463/20
Filed: 1999-03-26
Granted: 2003-12-20
Abstract: FIELD: biotechnology, biochemistry, antibiotics. SUBSTANCE: invention relates to new method for enzymatic preparing cephalosporin of the general formula (I)   wherein R 0  represents hydrogen atom or C 1-3 -alkoxy-group; Y represents CH 2 , oxygen, sulfur atom or oxidized form of sulfur; R 1  represents any of groups taken among the group including hydrogen atom, hydroxy-group, saturated or unsaturated halogenated hydrocarbon, direct of branched alkyl (1-5 carbon atoms optionally replaced with one or some heteroatoms) optionally substituted with hydroxy-group, halogen atom, aryl, alkoxy-group (1-3 carbon atoms) or acyl and so on; R 2  is taken among group including adipyl (1,4-dicarboxybutane), succinyl, glutaryl, pimelyl, suberyl, 2- (carboxyethylthio)-acetyl, 3-(carboxyethylthio)-propionyl, higher alkyl saturated and higher alkyl unsaturated dicarboxylic acids from complex mixture containing except for compound of the general formula (I), 6- aminopenicillanic acid (6-APA) and optionally one or some N-substituted β-lactam compounds. Method involves the following stages: (a) acidification of complex mixture up to pH value below 6,5 and keeping mixture at pH below of indicated value at temperature between 10 C and 150 C; and/or optional interaction of complex mixture with source of carbon dioxide; (c) isolation from mixture formed after stages (a) and/or (b) the derivative of cephalosporanic acid of the formula (I). Invention proposes also method for preparing compound of the formula (II)   wherein R 0  represents hydrogen atom or C 1-3 -alkoxy-group; Y represents CH 2 , oxygen, sulfur atom or oxidized form of sulfur; R 1  represents any group taken among the group including hydrogen atom, hydroxy-group, saturated or unsaturated halogenated hydrocarbon, direct or branched alkyl (1-5 carbon atoms optionally replaced with one or some heteroatoms) optionally substituted with hydroxy-group, halogen atom, aryl, alkoxygroup (1-3 carbon atoms) or acyl and so on. Method involves stages of isolation of compound of the formula (I) wherein R 0 , Y and R 1  have values indicated above; R 2  is taken among group including adipyl (1,4-dicarboxybutane), succinyl, glutaryl, pimelyl, suberyl, 2-(carboxyethylthio)-acetyl, 3-(carboxyehylthio)-propionyl, higher alkyl saturated and higher alkyl unsaturated dicarboxylic acid from complex mixture containing, except for compound of the general formula (I), 6-aminopenicillanic acid (6-APA) and optionally one or some N-substituted β-lactam compounds by: (a) acidification of complex mixture up to pH value below 6.5 and keeping mixture at pH below indicated value at temperature between 10 C and 150 C; and/or (b) optional interaction of complex mixture with source of carbon dioxide; and (c) isolation from mixture formed after stages (a) and/or (b) derivative of cephalosporanic acid of the formula (I); (d) deacylation of compound of the formula (I) to yield the conversion solution containing compound of the formula (II); and (e) isolation of compound of the formula (II) from solution. Invention provides new method for preparing cephalosporin. EFFECT: improved preparing method. 18 cl, 14 tbl, 10 ex