A series of new derivatives of 7-aminocephalosporanic acid in which the acetoxymethylfunction at C3 has been replaced with a heteroaromatic carbonylthiomethylmoiety and the 7-amino group has been acylated with D-phenylglycine has beenprepared. Many of these derivatives were well absorbed following oral administrationto mice.
A new metabolite, KD16-U1, has been isolated from the culture of Streptomyces filipinensis. The structure of the metabolite elucidated in this paper has been found to be closely related to shikimic acid.
A method of determining histidine decarboxylase activity was established. Inthis method, 14C-histamine was separated from 14C-histidine by Amberlite CG-resincolumn in the ammonium form. Lecanoric acid was obtained by screening histidine-decarboxylaseinhibitors produced by microorganisms. It is the first isolation of thiscompound from fungi. The inhibition by lecanoric acid was competitive with histidineand noncompetitive with pyridoxal phosphate. Lecanoric acid did not inhibitaromatic amino acid decarboxylase. Though lecanoric acid was hydrolyzed easilyboth in vivo and in vitro, its structure yielded an information useful in developinghistidine decarboxylase inhibitors of a new structural type.
A search for precursors of lasalocid A has led to the isolation and X-ray crystallographic analysis of an isomer of the antibiotic. The isomer differs from lasalocid A in both the size and absolute configuration of the terminal cyclic ether. These differences lead to speculation on the nature of cyclization mechanisms involved in the biosynthesis of lasalocid A and the other polyether antibiotics.
Maridomycin III, a macrolide antibiotic, was reduced at the aldehyde group to 18-dihydromaridomycin III by culture broth of Nocardia mexicana IFO 3927. 9-Propionylmaridomycin III and josamycin were also reduced to 18-dihydro-9-propionylmaridomycin III and 18-dihydrojosamycin, respectively, by the same strain. The structures of the reduction products were elucidated from the results of their IR, NMR and mass spectra. Antimicrobial activities of the reduction products against Gram-positive bacteria were about 1/10 of their substrates.
The hexaene macrolide candihexin produced by the mutant 18A2 of Streptomyces viridoflavus IMRU 3685 has been found to be a complex of two component fractions which we have named candihexins I and II. Extraction and purification methods have been developed for preparation of pure candihexin complex. Separation of the component fractions has been achieved by solvent fractionation and partition column chromatography. Candihexins I and II differ in solubility in organic solvents but have similar UV spectra. Candihexin I is active in vitro against yeasts and filamentous fungi with minimal inhibitory concentrations of 1-6μ/ml. Candihexin II is essentially inactive.
OS-3256-B is a new member of azaamino acid substances obtained from the culture filtrate of Streptomyces candidus var. azaticus which was reported in a previous paper. This antibiotic is remarkably effective against experimental murine tumors such as S-180 tumor and leukemia L-1210. The antibiotic is also obtainable from alazopeptin by chemical transformation.
By treatment of 8-hydroxyerythromycin A in an aprotic solvent with ethylene carbonate in the presence of K2CO3, two cyclic carbonates of 8-hydroxyerythromycin A with molecular formulae of C38H65NO15 and C39H63NO16, respectively, were obtained. Analytical, spectral and chemical data indicated their structures to be the 11, 12-cyclic carbonate of 8-hydroxyerythromycin A and the 8, 9; 11, 12-dicyclic dicarbonate of 8-hydroxyerythromycin A 69-hemiketal, respectively. The respective compounds have antibacterial activities against Bacillus pumilus (in erythromycin A units) corresponding to 500μg/mg and 1, 250μg/mg. Similar treatment of the methyl9 6-ketal of 8-hydroxyerythromycin A yields the 11, 12-cyclic carbonate. Acid hydrolysis of the latter is another route providing the 11, 12-cyclic carbonate of 8-hydroxyerythrornycin A, mentioned above.
Acidolin was isolated from skimmilk cultured for 48 hours with Lactobacillus acidophilus (CHR. HANSEN's Laboratory strain 2181). It was extracted from the skimmilk with methanol and acetone and was further concentrated and purified by Sephadex G-25 gel filtration, high voltage electrophoresis, and thin-layer chromatography on silica gel. Ultraviolet, infrared, nuclear magnetic resonance, and mass spectra results are presented for the antibiotic. Acidolin has a low molecular weight (-200), is acidic in nature, possesses a yellow-brown color, and is highly hygroscopic and thermostable. Acidolin exhibits antimicrobial activity against enteropathogenic organisms and sporeformers and only limited activity against lactic-acid bacteria. It is non-toxic to tissue culture cells (H-Ep-2) and is more active against vaccinia than polio virus.