Kibdelin D

A new subspecies of Kibdelosporangium aridum subsp. largum (SK&F AAD-609), was isolated and shown to produce novel glycopeptides related to aridicins, but containing a homologous series of glycolipids based on N-acylglucosamine. These compounds showed improvements over the aridicins in in vitro activity and were effective in mouse protection studies against a range of Gram-positive bacteria, including methicillin resistant staphylococci. Pharmacokinetic studies indicated that they have high serum concentrations and long-acting potential. The kibdelin complex modified rumen metabolism in a manner favorable for growth promotion.

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.