Loading patent…
AssigneePierrel S.p.A.
InventorsLuciano Toscano, Leonardo M. Cappelletti
Estimating the term…
From the fermentation carried, out with mutants blocked in the synthesis respectively of erythromycin and of oleandomycin, namely Streptomyces erythreus ATCC 31772 and Streptomyces antibioticus ATCC 31771, using as the substrate a derivative of erythronolide A, namely (8S)-8-fluoroerythronolide A, a derivative of erythronolide B, namely (8S)-8-fluoroerythronolide B, or a derivative of 3-O-mycarosyl-erythronolide B, namely 3-O-mycarosyl-(8S)-fluoroerythronolide B, the corresponding (8S)-8-fluoro derivatives of the erythromycins A, B, C and D, as well as 3-O-oleandrosyl-5-desosaminyl-(8S)-8-fluoroerythronolide A and 3-O-oleandrosyl-5-O-desosaminyl-(8S)-8-fluoroerythronolide B, all belonging to the class of the macrolide antibiotics are obtained. The preparation of the aforesaid substrate comprises the convention of erythronolide A, erythronolide B or 3-O-mycarosyl-erythronolide B into the corresponding hermiacetal, the reaction of the latter with a compound capable of generating electrophlic fluorine and the opening of the resulting acetal with aqueous acid.
(8S)-8-fluoroerythronolide A, having the formula:
(8S)-8-fluoroerythronolide A-6,9;9,11-acetal, having the formula:
8,9-anhydroerythronolide A 6,9-hemiacetal, having the formula:
(8S)-8-fluoroerythronolide B, having the formula:
(8S)-8-fluoroerythronolide B-6,9;9,11-acetal, having the formula:
3-O-mycarosyl-(8S)-8-fluoroerythronolide B, having the formula:
3-O-mycarosyl-(8S)-8-fluoroerythrnolide B-6,9;9,11-acetal having the formula:
3-O-mycarosyl-8,9-anhydroerythronolide B-6,9-hemiacetal having the formula:
(8S)-8-fluoroerythromycin A, having the formula ##STR15## or the pharmaceutically acceptable salts thereof.
(8S)-8-fluoroerythromycin B, having the formula ##STR16## or the pharmaceutically acceptable salts thereof.
(8S)-8-fluoroerythromycin C, having the formula ##STR17## or the pharmaceutically acceptable salts thereof.
(8S)-8-fluoroerythromycin D, having the formula ##STR18## or the pharmaceutically acceptable salts thereof.
3-O-oleandrosyl-5-O-desosaminyl-(8s)-8-fluoroerythronolide A, having the formula ##STR19## or the pharmaceutically acceptable salts thereof.
3-O-oleandrosyl-5-O-desosaminyl-(8S)-8-fluoroerythronolide B, having the formula ##STR20## or the pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.