Method of production of lovastatin

C - Chemistry – Metallurgy – 12 – P

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C12P 17/06 (2006.01) C07D 309/30 (2006.01)

Patent

CA 2243592

The method finds application in the pharmaceutical industry. Lovastatin is derived by this method from culture broth by filtration at values of pH 9.5-13.0, included in a solid mass it is precipitated from the filtrate obtained, pH 2.5-4.0, in the presence of an inert filler, antioxidant and a non-miscible with water organic solvent. It is extracted and lactonized in the medium of a chlorine-containing organic solvent. The latter is concentrated, and the residue is dissolved in a mixture of solvents having different polarity. After cooling at -10-- 30°C, lovastatin is crystallized, dried and several times recrystallized.

Procédé trouvant application dans l'industrie pharmaceutique. Selon le procédé, la lovastatine est dérivée d'un bouillon de culture par filtration à des valeurs de pH 9,5 DIVIDED 13,0, et, comprise dans une masse solide, on la fait précipiter à partir du filtrat obtenu, à un pH de 2,5 DIVIDED 4,0, en présence d'une charge inerte, d'un antioxydant et d'un solvant organique non miscible à l'eau. Ensuite, on procède à l'extraction et la lactonisation de ladite lovastatine dans un solvant organique chloré. On concentre ce dernier, et on dissout le résidu dans un mélange de solvants de polarités différentes. Après refroidissement jusqu'à -10 DIVIDED -30 DEG C, on soumet la lovastatine à la cristallisation, au séchage et, à plusieurs reprises, à la recristallisation.

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