SEMISYNTHETIC MACROLIDIC ANTIBIOTICS, MICROBIOLOGICAL PROCESS FOR THEIR PREPARATION AND RELATED MICROORGANISM, NOVEL INTERMEDIATE COMPOUNDS FOR THEIR PREPARATION AND RELATED PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

摘要

From the fermentation carried, out with mutants blocked in the synthesis respective of erythromycin and of oleandomycin, namely Streptomyces erythreus ATCC 31772 and Streptomyces antihioticus ATCC 51771, using as the substrate a derivative of erythronolide A, namely (BS)-8-fluoroerythronolide A, a derivative of erythronolide B, namely (8S)-8-fluoroerythronolide B, or a derivative Df 3-0-mycarosyl-erythronolide B, namely 3-0-mycarosyl-(8S)-fluoroerythronolide B, the corresponding (8S-8-fluoro derivatives of the erythrornycins A,B, C and D, as well as 3-0-oleandrosyl-5-desosaminyl-(8S)-8-fluornerythrnnolide A and 3-0-oleandrosyl-?-0-desosarminyl-(8S)-8-fluoroerythronolide B, all beloning to the class of thc macrolide antibiotics are obtained. The preparation of the aforesaid substrate comprises the convention of erthronolide A, erythronolide B or ?-0-mycarosyl-erythronolide B into the corresponding hemiacetal, the reaction of the latter with a compound capable of generating electrophlic fluorine and the opeaning of the resulting acetal with aqueous acid.