Schering Corporation

Olga Sarre

Ashit K Ganguly

Viyyoor Moopil Girijavallabhan

Stuart W McCombie

Yi-Tsung Liu

Patricia Cavender

Alan K Mallams

Doris P Schumacher

Randall R Rossman

Hans Reimann

Robert S Jaret

3-O-Glycosyl derivatives of 16-membered macrolides such as O-.alpha.-L-cladinosyl-(1.fwdarw.3)-12,13-dehydro-12,13-deoxorosaramicin, 2', 4',4''-tri-O-acetyl-O-(4'-O-phenoxyacetyl-.alpha.-L-cladinosyl)-(1.fwdarw. 3)-desmyconsin and pharmaceutically acceptable acid addition salts thereof useful as antibacterials are disclosed.

3-O-glycosyl 16-membered macrolide antibacterials and related derivatives

A compound represented by formula I ##STR1## wherein R is hydrogen, or ##STR2## wherein R.sup.1 is N-acylamino, N-alkylamino, N,N-dialkylamino, N-acyl-N-hydroxylamino, nitroso or the pharmaceutically acceptable salts thereof.

Substituted oligosaccharide antibodies

There is disclosed desevernitrose, acetamido, ethylamino and diethylamino derivatives of antibiotic 13-384 components 1 and 5 represented by the following formula ##STR1## wherein R is hydrogen, or ##STR2## wherein R.sup.1 is acetamide, ethylamine, diethylamine, N-hydroxylamino, nitroso or the pharmaceutically acceptable salts thereof.

Substituted oligosaccharide antibiotics

Desmycinosyl derivatives of 12,13-desepoxy-12,13-dehydro antibiotic AR-5 component 1 and 12,13-desepoxy-12,13-dehydro antibiotic AR-5 component 2 are useful antibacterial agents and may be converted to other such agents by processes analogous to those generally known in the art.

Macrolide antibacterial AR-5 components

Novel macrolide antibacterial derivatives of the components of the Antibiotic AR-5-complex are disclosed herein. The invention specifically relates to compounds wherein the macrolide ring and/or the two attached sugars are derivatized. Also disclosed are methods for the preparation of the derivatives and methods for the use thereof.

Derivatives of antibiotic AR-5 components

.beta.-Lactams having a substituted hydroxymethylene group at the position .alpha. to the lactam carbonyl group are prepared by reaction of an .alpha.-halo-.beta.-lactam with zinc or zinc amalgam in an anhydrous aprotic medium to produce an intermediate which in situ reacts with an appropriate aldehyde or ketone. Also described are novel penicillins and cephalosporins having useful antibacterial activity.

Synthesis of .beta.-lactams having a substituted hydroxymethylene group

.beta.-Lactams having a substituted hydroxymethylene group at the position .alpha. to the lactam carbonyl group are prepared by reaction of an .alpha.-halo-.beta.-lactam with zinc or zinc amalgam in an anhydrous aprotic medium to produce an intermediate which in situ reacts with an appropriate aldehyde or ketone. Also described are noval penicillins and cephalosporins having useful antibacterial activity.

6-(Substituted-hydroxymethylene penams)

Everninomicin B, C or D may be converted to amino derivatives by reductive means. The amino derivatives may, subsequently, be converted to novel N-acyl, N-alkyl or N,N-dialkyl derivatives. Alternatively, everninomicins B, C or D may be converted to N-acyl-N-hydroxylamino derivatives also by reductive means. The derivatives so-produced and the non-toxic pharmaceutically acceptable cationic salts thereof are novel and are antibacterial agents.

Aminoeverninomicin and derivatives thereof

Everninomicin antibiotics having a nitro function, e.g. everninomicin B, everninomicin C, and everninomicin D, upon treatment with aluminum amalgam in aqueous alkanol are converted to a mixture of at least two reduction products having antibacterial activity, said reduction products being an everninomicin having a nitroso function and an everninomicin having a hydroxylamino function. The nitrosoeverninomicins are also prepared by treating the corresponding hydroxylaminoeverninomicin with an oxidizing reagent selected from the group consisting of aerial oxidation in alkaline solution, and an alkali metal hypobromite in an aprotic solvent. The everninomicin reduction products and salts thereof are described as well as nitrone derivatives of the hydroxylaminoeverninomicins and salts thereof, all of which possess antibacterial activity. A preferred compound is hydroxylaminoeverninomicin D, particularly the sodium salt thereof.

Method of using reduction products of everninomicins as antibacterial

Described is a novel process for the preparation of 12,13-desepoxy-12,13-dehydrorosamicin by reducing rosamicin in a mineral acid solution containing Cr.sup.+.sup.+ cations. Rosamicin is an antibiotic elaborated by Micromonospora rosaria.

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Verona, NJ, United States of America

Olga Sarre