Novel process for the fermentative production of cephalosporin

A method for the recovery of an N-substituted cephalosporanic acid compound of the general formula (I):

• 5
• wherein
• R0 is hydrogen or C1-3 alkoxy;
• Y is CH2, oxygen, sulphur, or an oxidised form or sulphur;
• R1 is any of the groups selected from the group consisting of
• hydrogen,
• hydroxy,
• halogen,
• saturated or unsaturated, straight or branched alkyl (1-5 carbon atoms;
• optionally replaced by one or more heteroatoms), optionally substituted with hydroxy, halogen, aryl, alkoxy (1-3 carbon atoms), or acyl;
• alkoxy (1-3 carbon atoms;
• optionally replaced by one or more heteroatoms), optionally substituted with hydroxy or halogen;
• or
• cycloalkyl (3-8 carbon atoms) optionally substituted with hydroxy, halogen, amino;
• aryl;
• heteroaryl;
• and
• R2 is selected from the group consisting of adipyl (1,4-dicarboxybutane), succinyl, glutaryl, adipyl, pimelyl, suberyl, 2-(carboxyethylthio)acetyl, 3-(carboxy-ethylthio)propionyl, higher alkyl saturated and higher alkyl unsaturated dicarboxylic acids,
• from a complex mixture comprising in addition to the compound of the general formula 6-aminopenicillanic acid (6-APA) and optionally one or more N-substituted β-lactam compounds,
• comprising the steps of:
• (a) acidifying the complex mixture to a pH below 6.5 and maintaining the mixture below said pH at a temperature of between 10° C. and 150° C.;
• and/or
• (b) contacting the complex mixture with a carbon dioxide source;
• and
• (c) recovering the cephalosporanic acid compound of the formula (I) from the mixture obtained after steps (a) and/or (b).