Preparation of 7-chloro-6-demethyltetracycline

摘要

7-Chloro-6-demethyltetracycline is prepared by aerobically fermenting a tetracycline-producing or a 7-chlortetracycline-producing micro-organism of the genus Streptomyces in an aqueous nutrient medium containing chloride ion in the presence of a methylation inhibitor, in an amount between 10 mg. per litre and 1000 mg. per litre of the aqueous nutrient medium of formula: or a salt thereof with a base, e.g. alkali and alkaline earth metal salts, wherein R1 is H or NH2 and R2 is an unsubstituted phenyl, pyridinyl, triazinyl, pyridazinyl, pyrimidinyl or pyrazinyl radical or one of these radicals substituted by amino, chloro, methylthio or lower alkoxy or lower alkyl of 1 to 4 carbon atoms, or is: or The methylation inhibitor may be controlled by adding p-aminobenzoic acid and/or folic acid. Specified micro-organisms are the tetracycline- and 7-chloro-tetracycline-producing strains of Streptomyces aureofaciens. A list of suitable methylation inhibitors is given.