Semisynthetic aminoglycoside antibacterials. 6. Synthesis of sisomicin, Antibiotic G-52, and novel 6'-substituted analogues of sisomicin from aminoglycoside 66-40C.

The discovery of aminoglycoside 66-40C, a novel dimeric, unsaturated imine produced by Micromonospora inyoensis, afforded a versatile intermediate for the synthesis of a variety of sisomicin analogues modified at the 6' position. The conversion of 66-40C into sisomicin, antibiotic G-52, and a series of novel 6'-substituted analogues of sisomicin is described, and the biological activity of the products is discussed.

Biological activity of SCH 21420, the 1-N-S-alpha-hydroxy-beta-aminopropionyl derivative of gentamicin B.

Sch 21420, the 1-N-HAPA derivative of gentamicin B, has been compared to gentamicin, tobramycin and amikacin in a variety of in vitro and in vivo tests. Based on studies with a large number of sensitive and resistant bacteria, it was shown that Sch 21420 has a spectrum and potency essentially the same as that of amikacin. Serum levels in mice, rats, and dogs are similar to those of other aminoglycosides. Sch 21420 was found to be markedly less toxic than amikacin in chronic renal function tests in rats and thus appears to have an advantageously improved therapeutic index compared to amikacin.

A new broad spectrum aminoglycoside antibiotic, G-52, produced by Micromonospora zionensis.

G-52 is a new broad spectrum aminoglycoside produced by a species of the genus Micromonospora, Micromonospora zionensis. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be quite similar to that of verdamicin and gentamicin but is differentiated from them by its increased activity against 6'-N-acetylating strains.

Kijanimicin (Sch 25663), a novel antibiotic produced by Actinomadura kijaniata SCC 1256. Fermentation, isolation, characterization and biological properties.

A novel antibiotic complex has been isolated form the fermentation broth of a new species of Actinomadura, A. kijaniata SCC 1256. The complex was separated form the broth by a solvent extraction procedure and consists of 1 major component, designated kijanimicin, and 3 minor components. Kijanimicin was isolated form the complex by column chromatography and/or preparative high pressure liquid chromatography. Structurally the compound is a unique, large acid enol antibiotic and possesses an unusual in vitro spectrum of activity against some Gram-positive and anaerobic microorganisms. In vivo it has also shown interesting activity against malaria.

The hazimicins, a new class of antibiotics. Taxonomy, fermentation, isolation, characterization and biological properties.

The hazimicins, a new class of broad spectrum antibiotics with at least 2 active components (5 and 6), were isolated from the fermentation of Micromonospora echinospora var challisensis SCC 1411. The complex was separated from the broth by a solvent extraction procedure, and the individual components were separated by column chromatography. The two primary active components are isomers, with unique structures shown to be di-tyrosine analogs containing two isonitrile groups. The antibiotic has in vitro activity against Gram-positive and Gram-negative bacteria, and in vitro activity against yeasts and dermatophytes.

A novel tetracycline from Actinomadura brunnea. Fermentation, isolation and structure elucidation.

A novel tetracycline antibiotic, Sch 33256, was isolated from a culture broth of a new species of Actinomadura. The antibiotic was isolated by solvent extraction, Sephadex G-25 column chromatography and crystallization. The structure was determined by comparison of the spectra with that of chlortetracycline. Spectroscopic analysis of the compound yielded 2'-N-methyl-8-methoxychlortetracycline as the proposed structure.

A novel phenazine antifungal antibiotic, 1,6-dihydroxy-2-chlorophenazine. Fermentation, isolation, structure and biological properties.

A novel, solvent extractable, antibiotic complex has been purified from the fermentation broth of an unusual member of the genus Streptosporangium. Two of the major components were isolated from the complex by alumina column chromatography. One of the components was identified as a previously reported compound, 1,6-dihydroxyphenazine. The other component was a novel chlorine containing phenazine, 1,6-dihydroxy-2-chlorophenazine, which exhibited broad spectrum antifungal activity in vitro against dermatophytes and Candida.