Isolation and identification of new anthracycline antibiotics, rubomycins F and H.
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Antibiotics, Antineoplastic↗
Biomedical subjects
N P Potapova
Publications and source records attributed to N P Potapova.
[Isolation and evaluation of the structure of the new anthracycline antibiotics rubomycins F and H].
The rubomycin complex produced by Streptomyces coeruleorubidus 4-157 was studied and the two novel anthracyclines i.e. rubomycins F and H were isolated. The study of the physicochemical properties of the novel antibiotics in comparison with rubomycin C (daunomycin) and the specially prepared 3'-N-carbmethoxyrubomycin C showed that rubomycin F was 3'-N-carbethoxydaunomycin and rubomycin H was 3'-N-carbmethoxydaunomycin. Therefore, rubomycins F and H are novel representatives of natural anthracyclines undescribed previously.
Bacillus↗
[The structure and antimicrobial activity of the partial degradation products of the antibiotic eremomycin].
Antimicrobial activity of partial degradation products of eremomycin, a new glycopeptide antibiotic, was studied. The products formed by eremomycin deglycosylation (deseremosaminyl eremomycin, eremosaminyl aglycone and aglycone) and elimination of the chlorine atom from the molecule aglycone moiety (dechloroeremomycin). The spectral data in favour of the compounds structure are presented. It was found that partial degradation led to a decrease in the antimicrobial activity of the antibiotic. Dechloreremomycin had the highest activity among the products. Its MIC for the methicillin-resistant strains of Staphylococcus aureus was only twice as low as that of the initial antibiotic.
Anti-Bacterial Agents↗
[Albofungin formation by a strain isolated as a result of fusion of protoplasts of organisms producing aminoglycoside antibiotics].
Strain 344 synthesizing an antibiotic complex was isolated after fusion of the protoplasts of Streptomyces monomycini producing monomycin and Streptomyces kanamyceticus producing kanamycin. The major component of the complex was identified with albofungin and the minor one was suggested to be chloralbofungin. In the cultures of strain 344 variants forming monomycin were detected. After regeneration of the protoplasts of the parent strains there were isolated no stable clones synthesizing antibiotics differing from monomycin and kanamycin.
Anti-Bacterial Agents↗
[The structure of the aglycon of eremomycin--a new antibiotic of the polycyclic glycopeptide group].
Eremomycin is shown to be a new representative of the group of polycyclic glycopeptides. By the amino acid composition it is close to vancomycin but by the structure of triphenoxytriaminotricarboxylic acid it differs from vancomycin. Monodechlorovancomycinic acid was detected in eremomycin. On the basis of the data obtained in studies on the amino acid sequence and the molecule functional groups the structural formula of eremomycin aglycon was assigned. It is demonstrated that the chlorine-containing phenylserine fragment of monodechlorovancomycin acid is located in the N-end region of the aglycon peptide chain.
Amino Acid Sequence↗
[Structure of eremosamine--an amino sugar from the antibiotic eremomycin].
A new amino sugar named eremosamine was isolated from hydrolysate of eremomycin, an antibiotic belonging to the group of polycyclic glycopeptides. Crystalline derivatives of the amino sugar i. e. methyleremosaminide and methyl-N,O-acetyleremosaminide (alpha- and beta-anomers) were prepared. The data on PMR study and optic properties of the compounds showed that eremosamine had the structure of 2,3,6-tridesoxy-3-amino-3-C-methyl-L-arabinohexose.
Amino Sugars↗
[New derivatives of carminomycin and rubomycin].
For preparing new semisynthetic analogs of anthracycline antibiotics, hydrolysis of 13-dimethylketals of 14-bromrubomycin and 14-brom-arminomycin in solution of diluted hydrochloric acid was studied. It was shown that such hydrolysis yielded 14-chlorrubomycin and 14-chlorcarminomycin. Conditions for separating the mixture of 14-chlor- and 14-bromrubomycins and the mixture of 14-chlor- and 14-bromcarminomycins by HPLC were developed. Interaction of 14-chlorine derivatives of rubomycin and carminomycin with potassium formate in the presence of the crown ether yielded 14-formyloxy derivatives of rubomycin and carminomycin. Interaction of rubomycin and carminomycin with formic acid in the presence of N-oxysuccinimide and dicyclohexylcarbodiimide resulted in formation of N-formyl derivatives of rubomycin and carminomycin.
Carubicin↗
[Structure of the antibiotic virenomycin].
To identify the structure of virenomycin, a new antitumor antibiotic consisting of components V and M, its acetyl and permethyl derivatives, as well as products of acid methanolysis and their derivatives were obtained. The IR-, NMR- and mass-spectra of the above compounds are presented. Based on an analysis of the spectral data the structure of virenomycin is suggested.
Antibiotics, Antineoplastic↗
[Structure of actinoidins A and B].
The sequence of the amino acid residues in the peptide chain of aglycone was shown on the basis of the data concerning the splitting of actinoidin aglycon and the products of its partial acid hydrolysis by various methods. It was found that the free COOH-group of actinoidin belonged to he glycine residue of the dioxyphenyl nucleus of actinoidinic amino acid. The site of the actinosamine attachment to aglycon was determined. The final structure of actinoidins A and B is suggested.
Amino Acid Sequence↗
[Separation and characteristics of the components of the antibiotic virenomycin].
The composition of virenomycin, a new antitumor antibiotic was studied. Two components V and M were detected with high resolution liquid chromatography and thin layer chromatography on siluphol (Czechoslovakia) and silica gel (Merk, BRD). A preparative method for separation of the antibiotic components with the use of chromatography on columns with silica gel was developed. Biological and physicochemical properties of separate components were studied to show that they significantly differed by their antibacterial action in vitro: virenomycin V was 2 to 4 times more active than virenomycin M against a number of microbes. The physicochemical properties of the components are similar. It was shown with mass spectrometry that the molecular weight of virenomycin is 12 units higher than that of virenomycin M. The PMR spectra showed that this difference is due to the presence of a vinyl group in the chromophore moiety of the virenomycin V molecule and a methyl group at the similar site of the virenomycin M molecule.
Antibiotics, Antineoplastic↗
[Synthesis and properties of the N-ethyl derivatives of carminomycin and rubomycin].
N-Monoethyl derivatives of carminomycin, rubomycin, 13-dihydrocarminomycin and 13-dihydrorubomycin were synthesized by condensation of their amino groups with acetic aldehyde in the presence of sodium boron hydride. The respective N,N-diethyl derivatives of the antibiotics were formed as by-products of the reaction. New compounds such as N-ethylcarminomycin, N,N-diethylcarminomycin, N-ethyl-13-dihydrocarminomycin, N,N-diethyl-13-dihydrocarminomycin, N-ethylrubomycin and N-ethyl-13-dihydrorubomycin were synthesized. Antibacterial activity of N-ethyl- and N,N-diethyl derivatives of carminomycin and rubomycin determined with the use of Bac. mycoides as the test microbe was 40-50 per cent and that of N-ethyl- and N,N-diethyl-13-dihydro-derivatives was 15-30 per cent of the activity of the respective antibiotics, carminomycin and rubomycin.
Alkylation↗
[Production of 14-substituted derivatives of carminomycin and rubomycin].
14-Bromocarminomycin and 14-bromorubomycin were treated with alkali metal salts and nitrogen heterocycles to obtain 14-acetoxycarminomycin, 14-octamoylhydroxycarminomycin, 14-salicyloylhydroxycarminomycin, 14-salicyloylhydroxyrubomycin, 14-chinaldinoylhydroxyrubomycin and rubomycin 14-N-phthalimide, rubomycin 14-N-pyridinium bromide and 14-N-imidazolylrubomycin. It was shown that the reaction rate of the nucleophilic substitution in the acetone medium could be increased with the use of crown ethers of sodium iodide. Under such conditions 14-iodinecarminomycin and 14-iodinerubomycin, two intermediate products, partially reduced to the initial antibiotics, i.e. carminomycin and rubomycin. 14-Acetoxycarminomycin had the highest activity against Bac. mycoides, used as a test microbe. It amounted to 50 per cent, while the activity of the other derivatives did not exceed 25 per cent of the activity of the initial antibiotics.
Bacillus↗
[Revision of the structure of ristomycinic and actinoidinic amino acids].
The structures of ristomycin and actinoidine amino acids described earlier were revised. Crystalline derivatives of the amino acids and the products of their oxidation were prepared. The study on the spectral properties of the compounds showed that ristomycin and actinoidine amino acids had the structures of 3-(2'-hydroxy-5'-glycyl-phenoxy)-4-methyl-5-hydroxyphenylglycine and 2-(2'-hydroxy-5'-glycyl-phenyl)-3,5-dioxyphenylglycine respectively. They did not differ from deaminodicarboxylic acids prepared with ristocetin, vancomycin and actionoidine.
Chemical Phenomena↗
[Structure of carminomycins II and III].
Carminomycins II and III, the main components of the carminomycin complex were isolated in pure state. Their crystalline exalates and acetate of cardminomycin II were prepared. The PMR spectra of both carminomycins and the 13C-NMR spectra of the oxalates were obtained. The molecular weights of the antibiotics were determined by mass-spectrometry. On the basis of the PMR spectra it was shown that carminomycins II and III had similar structures and differed in the stereoisomerism of the nitrogen-free fragment linked to the amino sugar. This was confirmed by the 13C-NMR spectra. The above fragment (C7H15O3) is analogous to the fragment of baumycins A1 and A2 described earlier.
Acetates↗
[Minor components from the carminomycin complex].
Three components differing by their properties from the carminomycins described earlier were isolated from the carminomycin complex. Comparison of the IR and UV spectra, as well as chromatographic and physicochemical properties of 2 of them showed that they were dihydrocarminomycin and its aglycone or dihydrocarminomycinone, which was prepared earlier by synthesis. The third component was a chromophore belonging to 1,4,6-trihydroxyanthraquinone. Investigation of its IR spectrum, physicochemica properties and PMR spectrum showed it to be carboxymethylethylcarminomycinone identical to epsilon-rodomycinone. The data were confirmed by 13C-NMR spectrometry.
Carubicin↗
The structure of nocamycin, a new antitumor antibiotic.
The structure of nocamycin, a new antitumor antibiotic, has been elucidated with the aid of mass- and PMR-spectroscopic investigation of the antibiotic and its various chemical transformation products. Nocamycin is structurally related to tirandamycins.
Antibiotics, Antineoplastic↗
[Triaminotricarboxylic amino acid oxidation productions of actinoidin and ristomycin].
Aromatic acids with three benzene nuclei bound through oxygen were obtained from actinoidin and ristomycin on their oxydation with permanganates of methylated aglycones and peptides. The structures of the methyl esters of these acids were determined by spectral methods. They are the following: methyl-3,5-bis-(4-methoxycarbonyl-phenoxy)-4-methoxybenzoate (from ristomycin) and methyl-3-(2-chlor-4-methoxycarbonyl-phenoxy)-5-(4-methoxycarbonyl-phenoxy)-4-methoxybenzoate (from actinoidin). The compounds are the aromatic parts of the molecules of the unusual triaminotricarboxylic amino acids present in the aglycones of all antibiotics of the group of polycyclic glycopeptides.
Acetylation↗
[Physicochmemical characteristics of the new antineoplastic antibiotic, nocamycin].
Nocamycin is produced by Nocardiopsis syringae. It is recovered from the culture fluid by extraction with chloroform. The molecular weight of the crystalline antibiotic is 503, its melting point is 147--149 degrees, [alpha]20 degrees D = --50 degrees (c. 0.21, chloroform), lambdamax235 and 348 nm(E1%sm= = 150 and 420), the summation formula is C26 H33NO9, the biological activity is 100000 Units/mg with respect to Bacillus mycoides. Nocamycin forms salts with alkalies soluble in water. On hydrolysis with an alkali it forms carbonic acid having no ester bond (IP spectrum) and methoxylic group present in the antibiotic molecule. Nocamycin is a new natural substance.
Antibiotics, Antineoplastic↗