Eli Lilly and Company

R Michael Molloy

Manuel Debono

Robert L Hamill

Raymond C Yao

Anne H Dantzig

Dennis R Berry

Ramakrishnan Nagarajan

Amelia A Schabel

Patrick J Baker

Khadiga Z Farid

Milton J Zmijewski

Gary G Marconi

Charles M Deber

Douglas R Pfeiffer

Ann H Hunt

Robert M Logan

Donner F Babcock

Two new groups of A-21978C cyclic peptides, anhydro- and isomer-A21978C peptide derivatives, have antibacterial activity and are useful as intermediates. The two groups are prepared via transpeptidation of the parent cyclic peptides. Pharmaceutical formulations containing the new peptides as active ingredients and methods of treating infections caused by susceptible Gram-positive bacteria with the formulations are also provided. The invention also provides an antibacterial composition containing the new drug substance LY 146032 in substantially pure form.

Anhydro-and isomer-a-21978c cyclic peptides

A82846-related glycopeptide compounds are prepared by treating an antibiotic selected from A82846 components A, B and C with trifluoroacetic acid to remove 1) the .alpha.-L-O-4-epi-vancosaminyl group attached to the disaccharide; 2) the (.alpha.-L-O-4-epi-vancosaminyl-.beta.-O-glucosyl) disaccharide group or 3) both the disaccharide group and the .alpha.-L-O-4-epi-vancosaminyl group attached to the peptide core from these antibiotics. The compounds have antibacterial activity, especially against Gram-positive microorganisms.

A-82846-type glycopeptide antibiotics

Anhydro- and isomer-A-21978C cyclic peptides

New glycopeptides prepared by biotransformation of a vancomycin-type antibiotic by an Acinomadura citrea culture (NRRL 18382), which are useful intermediates, and methods of preparing the biotransformed intermediates by adding a vancomycin-type glycopeptide to a growing culture of Actinomadura citrea NRRL 18382 and continuing fermentation under submerged aerobic conditions, are provided.

Biotransformation of glycopeptide antibiotics

Fermentation product A87689 is produced by a strain of Amycolatopsis mediterranei selected from NRRL 18815 and NRRL 18851, or an A87689-producing mutant thereof. A87689, its C.sub.1-6 -alkyl ether and C.sub.1-6 -alkanoyl ester derivatives and pharmaceutically acceptable salts thereof are phospholipase A.sub.2 inhibitors that are useful as antiinflammatory agents. Fermentation products known as BU-3889V, its components and pharmaceutically acceptable salts thereof, are phospholipase A.sub.2 inhibitors that are also useful as antiinflammatory agents.

A87689 compounds

A87689 compounds employed as a phospholipase A.sub.2 (PLA.sub.2)

Amycolatopsis mediterranei strains useful to prepare A87689 compounds

Novel glycopeptide derivatives of formula 1 and methods for their preparation from the glycopeptide antibiotics vancomycin, A51568A, A51568B, M43A and M43D, are provided. The new glycopeptide derivatives are useful antibacterial agents.

Glycopeptide derivatives

Method of preparing compounds of formula 1: ##STR1## by oxidative deamination of a glycopeptide antibiotic of formula 2: ##STR2## the antibiotic being selected from A35512 factors A, B, C, E and H, A35512B pseudoaglycone, actaplanin factors A, B.sub.1, B.sub.2, B.sub.3, C.sub.1a, C.sub.2a, C.sub.3, D.sub.1, D.sub.2, E.sub.1, G, K, L, M, N and O, actaplanin pseudoaglycone, A41030 factors A, B, C, D, E, F and G, A47934, ristocetin A and ristocetin A pseudoaglycone, novel compounds and compositions and methods of increasing feed-utilization efficiency in animals are provided.

Iodo-A-23187 derivatives, prepared by reaction of antibiotic A-23187 with iodine monochloride, and salts thereof, which are (1) useful biochemical tools for the study of transport of ions in cellular systems and (2) useful chemical tools for removal of recovery of ions.

Iodo-A-23187 derivatives

Bromo-A-23187 derivatives, prepared by reaction of antibiotic A-23187 with pyridinium hydrobromide perbromide and salts thereof, which are (1) useful biochemical tools for the study of transport of ions in cellular systems, and (2) useful chemical tools for removal and recovery of ions.

Bromo-A-23187 derivatives

Halo-A-23187 derivatives, prepared by reaction of antibiotic A-23187 with an N-halo-type halogenating agent, and salts thereof, which are (1) useful biochemical tools for the study of transport of ions in cellular systems, (2) useful chemical tools for removal and recovery of ions, and (3) potential cardiotonic agents.

Growing community of inventors

Danville, IN, United States of America

R Michael Molloy