Hydroxylation of compactin to pravastatin by micromonospora

Details Hydroxylation of compactin to pravastatin by micromonospora Hydroxylation of compactin to pravastatin by micromonospora

C - Chemistry, Metallurgy

12

P

C12P 7/42 (2006.01)

Patent

CA 2379015

The present invention relates to a new microbial process for the preparation of compound of formula (I) from a compound of general formula (II) wherein R stands for an alkali metal or ammonium ion, by the submerged culture of a strain which is able to 6.beta.-hydroxylate the compound of formula (II) in aerobic fermentation and by the separation and purification of the product of formula (I) formed in the course of the bioconversion. The latter comprises the cultivation of a <i>Micromonospora</i> strain which is able to 6.beta.- hydroxylate a compound of general formula (II) - wherein R is as defined above - at 25-32 ~C on a nutrient medium containing available carbon - and nitrogen sources and mineral salts, thereafter feeding the substrate to be transformed into the developing culture, then hydroxilating the substrate until finishing of the bioconversion, then separating the compound of formula (I) from the culture broth and, if desired, purifying the same.

La présente invention concerne un nouveau procédé microbien destiné à la préparation du composé de formule (I) à partir d'un composé représenté par la formule générale (II), dans laquelle R est un métal alcalin ou un ion ammonium. Ce procédé consiste à mettre en culture immergée une souche capable de provoquer la 6.beta.-hydroxylation d'un composé de formule (II) en fermentation aérobie, puis à séparer et à purifier le produit de formule (I) issu de la bioconversion. Cette dernière consiste à cultiver une souche de <i>Micromonospora</i> capable de provoquer la 6.beta.-hydroxylation d'un composé représenté par la formule générale (II), dans laquelle R est tel que défini ci-dessus, à 25-32 ·C dans un milieu nutritif contenant du carbone disponible ainsi que des sources d'azote et des sels minéraux, d'où l'alimentation d'un substrat à transformer en culture en développement, à hydroxyler ce substrat jusqu'à la fin de la bioconversion, puis à séparer ledit composé de formule (I) du bouillon de culture, voire à purifier ce dernier si nécessaire.

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