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Actaplanin (A4696), a new complex of broad spectrum Gram-positive antibiotics is produced by Actinoplanes inissouriensis. High performance liquid chromatography was used to show that this complex is composed of several actaplanins.Hydrolytic experiments with actaplanins A, B,, B., B3, C, and G showed that these actaplanins were composed of the same peptide core, an amino sugar and varying amounts of glucose, mannose and rhamnose. The neutral sugar content was determined for each actaplanin. A bioautographic study of aglycone formation during hydrolysis of the actaplanin complex showed that within a short time a simple mixture of two antimicrobially active hydrolysis products was obtained. These substances retained the antimicrobial spectrum and a high percentage of the antibiotic activity of the parent actaplanin complex.Methanolysis of the actaplanin complex as well as the individual actaplanins resulted in the selective loss of the neutral sugar moieties and the isolation of actaplanin T(pseudo)-aglyconethe core peptide which still retained an amino sugar group. The 1H NMR spectrum of this substance indicated a similarity to many features of ristocetin ?Ir aglycone. Hydrolytic studies showed that the amino sugar present in actaplanin was identical with L-ristosamine. It is concluded that the aglycone of actaplanin is a complex peptide composed of aromatic amino acids, and that the actaplanins each possess this aglycone and L-ristosamine but are differentiated by their neutral sugar composition. Actaplanin (A4696)**, a new complex of glycopeptide antibiotics produced by Actinoplanes missouriensis (ATCC 23342), exhibits strong inhibitory activity against a broad spectrum of Gram-positive bacteria.The isolation of the actaplanin complex showed that actaplanin was composed of several closely related glycopeptide components (hereafter referred to as actaplanins) by their chromatographic behavior.Several recent structural studies of glycopeptide antibiotics1~5) have shown that these antibiotics appear to hold several chemical features in common. Typically, glycopeptides give rise to an "aglycone," neutral sugars"') and an amino sugar upon mild hydrolysis',1-12). Furthermore, the aglycone is a complex peptide which retains the same amino acids present in the parent after total hydrolysis and also some of the antimicrobial activity of the parent.The purpose of the present study was to determine the general chemical characteristics of the actaplanin complex and to relate the differences and the similarities it bears to known members of its class". The chemical relationship between the various actaplanins has also been determined.

The glycopeptide antibiotic A35512B was isolated from Streptomyces candidus NRRL 8156 as the major active factor. Chemical degradation studies showed that mild acid hydrolysis resulted in the release, one molecule each, of four neutral sugars: rhamnose, fucose, glucose and mannose, as well as the liberation of a complex peptide core which retained all the amino acids and from which 3-amino-2,3,6-trideoxy-3-C-methyl-L-.rylo-hexopyranose, a new amino sugar, was isolated (2). Oxidative degradation of A35512B resulted in the isolation of a chlorodiphenylether (5), dimethyl 4-methoxyisophthalate (7) and methyl 3,5-bis-(4-methoxycarbonylphenoxy)-4-methoxybenzoate (6). The structure of 5 could not be conclusively elucidated but was shown to be either 5-chloro-2',3-dimethoxy-2,5'-dicarbomethoxy diphenylether (5a) or 2-chloro-2',3-dimethoxy-5,5'-dicarbomethoxy diphenylether (5b) by physical methods. This halogenated fragment was shown to arise from oxidation of constituent amino acid (10) which has the aromatic substitution pattern of fragment (5a or 5b). Base hydrolysis resulted in the isolation of a phenanthridine (9) which arose from 2',4,6-trihydroxybiphenyl-2,5'-diyldiglycine. These chemical degradation studies on A35512B showed that this antibiotic is closely related to the ristocetin class of antibiotics.The antibacterial antibiotic complex A35512 is produced by Streptomyces candidus NRRL 8156 from which several closely related factors have been isolated and characterized by MICHEL.la> These antibiotics possess high antimicrobial activity against Gram-positive bacteria and are ineffective against Gram-negative organisms2).The A35512 complex has been shown to be a member of the glycopeptide family of antibiotics of which vancomycin, ristocetin and actinoidin are prominent members3). Characterization work by MICHEL showed that this complex was composed of six closely related factors.l8) Each of these factors contained the identical complex amino acids (amino acid analysis of 6 N HCl total hydrolyzate). The complex released neutral sugars and a complex peptide upon mild acid hydrolysis. The antibiotic complex had several phenolic groups (UV spectrum) and a complex titration curve. These data were consistent with the conclusion that A35512 represented a complex of new glycopeptide antibiotics.The major factor, A35512B, was obtained in crystalline form. The present paper will summarize the chemical studies on this antibiotic and relate it to other members of the glycopeptide class of antimicrobial agents.Chemical Properties of A35512B When A35512B was hydrolyzed under mild conditions (0.5 N HCl, 4 hours, refiux) an antimicrobially active aglycone I (1) was formed, and a number of neutral sugars were released. These sugars were identified by paper and thin-layer chromatography as rhamnose, glucose, fucose and mannose. This