Parvodicin, a novel glycopeptide from a new species, Actinomadura parvosata: discovery, taxonomy, activity and structure elucidation.

An extensive taxonomic investigation identified strain SK&F-AAJ-271 as a new species, designated Actinomadura parvosata. Fermentations of this organism produce a complex of acidic, lipophilic glycopeptide antibiotics, the parvodicins. Structures for seven of the isolated components were derived from a combination of mass spectral, high-field NMR and chemical techniques. The O-acetyl functionality present in two of the isolated components is a structural feature unique among the known members of this class of antibiotics. The parvodicins are active in vitro against a range of Gram-positive bacteria. The most active parvodicin, C1, produces high serum levels in vivo and has the potential for a long duration of action.

Actinoidin A2, a novel glycopeptide: production, preparative HPLC separation and characterization.

An unidentified Nocardia sp. (SK&F-AAJ-193) was isolated and found to produce actinoidin A and a novel analog which we have named actinoidin A2. This new glycopeptide antibiotic differs from actinoidin A by the presence of rhamnose instead of acosamine. This analog was isolated using Dianion HP-20 resin followed by a specific glycopeptide affinity column (Affigel-10-D-Ala-D-Ala). The purification was accomplished using preparative ion-pairing chromatography. Actinoidin A2 is active against Staphylococcus aureus and coagulase-negative Staphylococci although it is less potent than actinoidin A.

Kibdelins (AAD-609), novel glycopeptide antibiotics. II. Isolation, purification and structure.

A new glycopeptide antibiotic complex was isolated from the fermentation culture of Kibdelosporangium aridum subsp. largum (SK&F AAD-609) by affinity chromatography on a D-alanyl-D-alanine agarose column. This major components of the complex were resolved by preparative reversed-phase HPLC. Mild acid hydrolysis showed that the new antibiotics have the same mannosyl aglycon (2) as the aridicins. FAB mass spectrometry, isoelectric focusing, potentiometric titration and carbohydrate and fatty acid analyses were used to determine the structures of the five major components of the complex. These studies showed that the kibdelins differ from the aridicins only in the oxidation level at the C-6 position of the amino sugar. Kibdelin A (5), B (6), C1 (7), C2 (8) and D (9) are a series of N-acylglucosamine analogs containing saturated straight and branched chain C10-C12 fatty acids whereas, in kibdelin D the fatty acid component is (Z)-4-decenoic acid.

Aridicins, novel glycopeptide antibiotics. II. Isolation and characterization.

A new antibacterial antibiotic complex, aridicin, was produced by a new genus, Kibdelosporangium aridum (SK&F-AAD-216). The individual factors, aridicins A, B and C, were isolated from the fermentation broth by an Amberlite XAD-7 resin extraction and purified by preparative reversed phase HPLC. The aridicins were found to be novel members of the glycopeptide class of antibiotics as exemplified by ristocetin and vancomycin, based on chemical and spectroscopic data, their molecular weights as determined by FAB mass spectrometry (1,786, 1,800 and 1,814), the detection of actinoidinic acid in their acid hydrolysates, and detailed TLC and HPLC comparisons with representative members of this class.

Chlorocardicin, a monocyclic beta-lactam from a Streptomyces sp. II. Isolation, physico-chemical properties and structure determination.

Chlorocardicin, a novel monocyclic beta-lactam, was isolated from the fermentation broth of a Streptomyces sp. by the use of non-ionic porous resin and reverse phase chromatography. This chlorine-containing antibiotic is structurally related to nocardicin A. Its physico-chemical characteristics and detailed NMR analysis are described.