IE38626L - Everinomycin derivatives - Google Patents

Abstract

1454548 Everninomicin derivatives SCHERICO Ltd 10 Dec 1973 [14 Dec 1972 9 July 1973] 57152/73 Heading C2C Novel antibiotic everninomicin derivatives having the general Formula (I) wherein X is a nitroso group, a hydroxylamino group or a nitrone group derivable from the hydroxylamino group, Y is hydrogen or a hydroxy group, and Z is the group when Y is hydroxy, or hydrogen or the group when Y is hydrogen, and pharmaceutically acceptable salts thereof, are prepared by reducing everninomicin B, C or D at the nitro group (i.e. the group corresponding to X) to give a mixture of the corresponding nitroso derivative and hydroxylamino derivative, isolating the required reduction product, and if required, converting the hydroxylamino derivative into the corresponding nitrone by reaction with an aldehyde, or subjecting the hydroxylamino derivative to appropriate oxidation to convert it to the corresponding nitroso derivative, or subjecting the nitroso derivative to appropriate reduction to convert it to the corresponding hydroxylamino derivative. Reduction of the everninomicin B, C or D at the nitro group is effected with aluminium amalgam in aqueous C 1-4 alkanol. Aldehydes used for preparation of the nitrone may be formaldehyde, acetaldehyde, propanol, heptanal, decanal, dodecanal, cyclopropanecarbaldehyde, cyclopentanecarbaldehyde, cyclohexanecarbaldehyde, 3-cyclohexylcarbaldehyde, benzaldehyde, phydroxybenzaldehyde, tolylcarbaldehydes, 3- phenylpropanal, 1- and 2-naphthalene carbaldehydes, 2 - furfuraldehyde, thienylcarbaldehyde, thiazolylcarbaldehyde, pyrazinylcarbaldehyde, and pyranylcarbaldehyde. The oxidation of the hydroxylamino derivative to the nitroso derivative may be effected with alkali metal hypobromite or atmospheric oxygen in the presence of aqueous alkali. The salts of the inventive compounds include those of alkali and alkaline earth metals, (Na, K, Ca), aluminium, triethylamine, procaine, dibenzylamine, N-benzylbetaphenethylamine, N,N<SP>1</SP> - dibenzylethylenediamine, N,N<SP>1</SP> - bis - dehydroabietyl - ethylenediamine, N-ethylpiperidine and N-methylglucamine. The preparation of everninomicins B, C and D by aerobically cultivating Micromonospora carbonacea var. carbonacea or var. aurantiaca is described. The inventive compounds and their salts have antibacterial activity and are formulated into antibiotically active pharmaceutical compositions with an acceptable diluent or carrier. [GB1454548A]