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A new antibacterial antibiotic complex, aridicin, was produced by a new genus, Kibdelosporangiun: 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.The aridicins are a new complex of cell-wall active antibiotics produced by fermentation of a new genus Kibdelosporangium ariduin (SK&F-AAD-216, ATCC 39323), isolated from a soil sample collected near Pima, Arizona1). The antibiotic complex was isolated from fermentation broth by acid precipitation and chromatography on Amberlite XAD-7. The individual components were separated and purified by preparative reversed phase high performance liquid chromatography (HPLC). Chemical characterization of the components indicated that they were novel glycopeptide antibiotics2) related to vancomycin3,4), ristocetin5,6), avoparcin7) and teicoplanin8). In this report the isolation and characterization of aridicins A, B and C are reported. Isolation and PurificationThe antibiotic complex was isolated from the fermentation broth as outlined in Scheme 1. Precipitation at pH 3 and redissolution at pH 7 provided a 10-fold volume reduction with high recovery in the preliminary isolation step. This solution was passed through an Amberlite XAD-7 column and eluted with 60 % acetonitrile -water to yield a crude extract after concentration in vacuo. The overall recovery from broth after these two steps was in excess of 80 % with an accompanying volume reduction of 100-fold. Further purification was effected by preparative reversed phase HPLC. The frequently reported multistep schemes for the purification of polar, water soluble fermentation products often yield products in low recovery and, being limited in capacity, are difficult to scale-up. However, reversed phase HPLC, a useful analytical tool for monitoring antibiotic production, isolation and purification, also has great potential as a preparative tool for isolating and purifying the sesame products, often in one step9,10,11). An analytical HPLC chromatogram of the crude extract is shown in Fig. 1, with the major components indicated by peaks A, B and C. This separation was readily scaled-up to preparative level (Fig. 2) on Whatman Partisil Prep 40 ODS-3 packing (37' 60 Jim) I Present Address: SeaPharm ,

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Chlorocardicin, a novel monocyclic j-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.In the course of an investigation directed toward the discovery of cell-wall active antibiotics, a novel monocyclic /3-lactam antibiotic related to nocardicin A (1) was isolated. A description of the producing organism and the fermentation conditions used are reported in the preceding paper1) . The present paper describes the isolation and chemical characterization of this new product, chlorocardicin (2). The titers of chlorocardicin in fermentation broths and various fractions obtained during the purification procedure were best determined by high performance liquid chromatography (HPLC). A preclean-up of the broth samples was needed before injecting onto the HPLC. This was achieved by acidification of 5 ml of clarified broth to pH 3 with phosphoric acid and passage onto a Water's Sep-Pak (C18), followed by washing with 2 x 5 ml of phosphate buffer (0.01 M, pH 3) and then elution with 5 ml of a 1:1 mixture of methanol -water. Appropriate dilutions were made and samples injected onto the HPLC. These assays were performed using a Beckman Model 345/165 HPLC instrument equipped with an Altex Ultrasphere-ODS (5 pm) column (4.6 mm ID x 15 cm) with UV detection at 275 nm. The mobile phase was a gradient of acetonitrile and 0.1 % aqueous trifluoroacetic acid at a flow rate of 1 ml/minute (15% acetonitrile for 5 minutes followed by a steep gradient to 25% acetonitrile

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. The 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), C, (7), C2 (8) and D (9) are a series of N-acylglucosamine analogs containing saturated straight and branched chain C,,-C,; fatty acids whereas, in kibdelin D the fatty acid component is (Z)-4-decenoic acid.