Two new aminoglycoside antibiotics, sporaricins A (C17H35N5O5) and B (C15H32N4O4) produced by a rare actinomycetales, Saccharopolyspora hirsuta subsp. kobensis have been isolated by column chromatography on a cation-exchange resin. Sporaricin A is highly active against Gram-positive and Gram-negative bacteria including aminoglycoside-resistant strains.
Morphological, cultural and physiological characteristics of a new nocardioform actinomycete are reported. The microorganism which produces the antibiotic complex sporaricin1) has been selectively isolated from a sample of soil obtained from Kobe City, Hyogo Prefecture, Japan. By whole-cell analysis of the actinomycete, meso-diaminopimelic acid, arabinose and galactose were identified. But lipid LCN-A (lipid characteristic of Nocardia) and nocardomycolic acid were not detected. The taxonomic characteristics of this strain is closely related to the genus of Saccharopolyspora, described by LACEY and GOODFELLOW2). Based on the taxonomic comparison with Saccharopolyspora hirsuta ATCC 27875, the strain was considered to be a subspecies of Saccharopolyspora hirsuta. Therefore, the proposed subspecies is named Saccharopolyspora hirsuta subsp. kobensis.
The structures of sporaricins A and B have been determined to be 2-amino-1-O-(2, 6-diamino-2, 3, 4, 6, 7-pentadeoxy-β-L-lyxo-heptopyranosyl)-2, 3, 5-trideoxy-5-( N-glycyl-N-methylamino)-4-O-methyl-D-chiro-inositol and 2-amino-1-O-(2, 6-diamino-2, 3, 4, 6, 7-pentadeoxy-β-L-lyxo-heptopyranosyl)-2, 3, 5-trideoxy-4-O-methyl-5-methylamino-D-chiro-inositol, respectively.
Capsimycin is a new antifungal antibiotic produced by a strain of Streptomyces sp. C 49-87. The active substance in the fermented broth was isolated by solvent extraction followed by silica gel column chromatography. The antibiotic melts at 186°C (decomp.) and has a molecular formula C30H40N2O6. It exhibits marked inhibitory activity against Phytophthora capsici (Leaf blight disease of cucumber) and Pythium: debaryamum (Damping-off disease of cucumber).
Three antibiotics possessing cytotoxic properties were isolated from a strain of Streptomyces griseus (FCRC-57). One was found to be identical with griseorhodin A.2-6) A second, FCRC-57-U, was found to be identical to griseorhodin C7). FCRC-57-G is a new antibiotic structurally related to griseorhodins A and C, and is active against KB cells in vitro. The structure of this new antibiotic was determined using mass spectrom/etry, proton and carbon nuclear magnetic resonance spectroscopy and synthesis.
A strain of Myxococcus coralloides producing an antibiotic capable of inhibiting growth of Gram-positive bacteria was isolated. Antibiotic production occurred during vegetative growth but not during myxospore formation. The antibiotic was extracted from the growth medium with chloroform and purified by adsorption on silicic acid and by preparative silica gel thin-layer chromatography. The purified antibiotic showed a resistance to heat, acid, alkali and proteolytic enzymes. Chromatographic and electrophoretic behavior as well as infrared, ultraviolet and mass spectra are presented.
p-Hydroxyphenylacetaldoxime (HPAAO) (anti and syn forms) obtained by fermentation arid its analogs chemically synthesized were tested for their activities to inhibit various glycosidases. HPAAO inhibited bovine liver β-galactosidase in a competitive manner at pH 17.0 with an apparent Ki value of 8×10-8 M. HPAAO also inhibited various mammalian β-glycosidases which had pH optima between 6.0 and 8.0. The syn form of HPAAO was found to be more active than the anti form against bovine liver neutral β-galactosidase. It was concluded that the oxime moiety of HPAAO and its analogs was essential for their enzyme-inhibiting activity and the activities of aromatic or aliphatic oxime derivatives were dependent on the number of carbon atoms in their alkyl-chains.
Six isoflavonoids having β-galactosidase inhibiting activity were isolated from the culture filtrate of Streptomyces xanthophaeus. Their structures were determined by spectral analyses to be daidzein, daidzein 7-α-L-rhamnoside, daidzein 4', 7-di-α-L-rhamnoside, genistein, genistein 7-α-L-rhamnoside and genistein 4', 7-di-α-L-rhamnoside.
Glycosidation of 2, 3, 6-trideoxy-3-trifluoroacclamido-4-O-tritluoroacetyl-α-D-arabino-hexopyranosyl chloride (19) (or the corresponding 4-p-nitrobenzoate, 20) with daunomycinone under KOENIGS-KNORR conditions afforded, after separation of the anomers and removal of the protecting groups, the individual target glycosides 8 (α anomer; major product) and 9 (β; minor) in acceptable yields. In contrast, the title diamino sugar, suitably protected with N-trifluoroacetyl and O-acetyl (or O-p-nitrobenzoyl) groups, underwent stereospecific coupling to the anthracycline aglycon by the glycal procedure to give, after deprotection, the α glycoside 12. All three analogs were assayed in vivo against P388 lymphocytic leukemia. They showed little (T/C 125 for 8; T/C 115 for 9) or no (compound 12) activity, but were essentially devoid of toxicity at the dose-levels tested.
The conversion of ε-rhodomycinone to its 11-methyl ether via selective hydrolysis of the 4, 6, 7, 11-tetraacetate is described. This series of reactions was used as a model for the conversion of carminomycin to its 11-methyl ether. The anti-tumor activity of the latter compound was less than that of both carminomycin and its 4-methyl ether (daunomycin).