PROCESS FOR PREPARING ERYTHROMYCYLAMINE AND RESULTING PRODUCT

摘要

1275473 Erythromycin derivatives ELI LILLY & CO 29 Aug 1969 [29 Aug 1968] 43215/69 Heading C2A Erythromycylamine which melts at 125‹ to 127‹ C. and has the formula is prepared by catalytic hydrogenation of erythromycin oxime (IIa), erythromycin-hydrazine adduct (IIb) or the N1-isopropylidene derivative (IIc) of this adduct, which compounds have the general formula wherein R has the meanings The oxime and the hydrazine adduct are prepared by reacting erythromycin with hydroxylamine hydrochloride, and with hydrazine respectively, in a solvent such as methanol. The isopropylidene derivative is prepared by reacting the hydrazine adduct with acetone. These compounds are hydrogenated in an inert solvent such as acetic acid or preferably water containing 1 to 2% #-gluconolactone, glucoheptonolactone or other lactones of a sugar acid, using a noble metal catalyst such as platinum, palladium, ruthenium or rhodium, either as the free metal or the oxide. The oxime or hydrazine adduct are hydrogenated at about 500-2000 p.s.i., while pressures of 50-100 p.s.i. are preferably used in the caes of the isopropylidene derivative. By hydrogenating the isopropylidene derivative in a neutral medium, e.g. ethanol it may be converted to the corresponding N-isopropyl derivative of the erythromycin-hydrazine adduct. This represents an intermediate in the erythromycylamine formation and by further hydrogenation in an acidic medium the isopropyl derivative yields erythromycylamine. Pharmaceutical compositions having antibacterial activity against Gram-positive and Gramnegative micro-organisms comprise the antibiotic erythromycylamine together with a pharmaceutically acceptable diluent or carrier.