The Journal of Antibiotics

ISOLATION, CHARACTERIZATION AND STRUCTURES OF PA-46101 A AND B

MAKOTO MATSUMOTO, YOSHIMI KAWAMURA, YOHKO YOSHIMURA, YOSHIHIRO TERUI, ...

1990 Volume 43 Issue 7 Pages 739-747
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.739

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New antibiotics, PA-46101 A and B, were isolated from the culture broth of a Streptomycete. The molecular formulae of A and B were determined to be C₅₂H₇₀O₁₈ and C₆₁H₈₆O₂₂, -respectively, by elemental analyses, NMR and mass spectrometry. Their structures were elucidated by X-ray crystallography and NMR spectroscopy. These antibiotics are active in vitro against anaerobic Gram-positive and Gram-negative bacteria and also against a limited number of aerobic Gram-positive bacteria.

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A NOVEL ANTIFUNGAL ANTIBIOTIC, FR-900848

I. PRODUCTION, ISOLATION, PHYSICO-CHEMICAL AND BIOLOGICAL PROPERTIES

MASARU YOSHIDA, MASAMI EZAKI, MICHIZANE HASHIMOTO, MICHIO YAMASHITA, N ...

1990 Volume 43 Issue 7 Pages 748-754
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.748

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Streptoverticillium fervens produced a new antibiotic, FR-900848, which has a high specific activity against filamentous fungi. Purified by solvent extraction and column chromatography, the compound appears as colorless crystals. Its structure is C₃₂H₄₃N₃O₆, which consists of 5'-amino-5'-deoxy-5, 6-dihydrouridine with an unsaturated fatty acid having unprecedented four serial and one isolated cyclopropane rings.

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PRADIMICINS A, B AND C: NEW ANTIFUNGAL ANTIBIOTICS

I. TAXONOMY, PRODUCTION, ISOLATION AND PHYSICO-CHEMICAL PROPERTIES

KOJI TOMITA, MAKI NISHIO, KYOICHIRO SAITOH, HARUAKI YAMAMOTO, YUTAKA H ...

1990 Volume 43 Issue 7 Pages 755-762
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.755

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New antifungal antibiotics, pradimicins A, B and C were isolated from the culture broth of actinomycete strains proposed as Actinomadura hibisca. They are orange to red pigments containing a benzo[a]naphthacenequinone chromophore substituted with a D-alanine, an aminosugar and a D-xylose (pradimicins A and C).

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PRADIMICINS A, B AND C: NEW ANTIFUNGAL ANTIBIOTICS

II. IN VITRO AND IN VIVO BIOLOGICAL ACTIVITIES

TOSHIKAZU OKI, OSAMU TENMYO, MINORU HIRANO, KOZO TOMATSU, HIDEO KAMEI

1990 Volume 43 Issue 7 Pages 763-770
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.763

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Pradimicins A, B and C specify novel antibiotics produced by Actinomadura hibisca No. P157-2 (ATCC 53557) possessing potent and broad antifungal activity in vivo. They showed moderate in vitro antifungal activity against a wide variety of fungi and yeasts including clinically important pathogens, and were highly effective in systemic infection with Candida albicans in mice after iv and im administrations. Pradimicin A showed in vivo therapeutic activity against C. albicans, Cryptococcus neoformans and Aspergillus fumigatus in both normal and immunocompromized mice. 5-Fluorocytosine- and azole-resistant C. albicans strains were susceptible to pradimicin A. This antibiotic also demonstrated therapeutic efficacy against lung candidiasis and aspergillosis, vaginal candidiasis and skin Trichophyton mentagrophytes infection in mice with iv or topical treatment. The LD₅₀ values after a single iv or im administration were 120mg/kg and more than 400mg/kg, respectively. Against various cultured mammalian cells, pradimicin A was noncytotoxic at 100 or 500μg/ml, and showed potent anti-influenza virus activity with an IC₅₀ value of 6.8μg/ml.

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NEW ANTIFUNGAL ANTIBIOTICS, PRADIMICINS D AND E GLYCINE ANALOGS OF PRADIMICINS A AND C

YOSUKE SAWADA, MAKI NISHIO, HARUAKI YAMAMOTO, MASAMI HATORI, TAKEO MIY ...

1990 Volume 43 Issue 7 Pages 771-777
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.771

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New antifungal antibiotics pradimicins D and E were isolated from the culture filtrates of Actinomadura hibisca P157-2 (ATCC 53557) and its mutant A2660 (ATCC 53762). The structure of pradimicin D is N-[[(5S', 6S')-5-O-[4, 6-dideoxy-4-(methylamino)-3-O-(β-D-xylopyranosyl)-β-D-galactopyranosyl]-5, 6, 8, 13-tetrahydro-1, 6, 9, 14-tetrahydroxy-11l-methoxy-3-methyl-8, 13-dioxobenzo[a]naphthacen-2-yl]carbonyl]glycine, based on spectral analyses compared to pradimicin A. Pradimicin E is the des-N-methyl analog of pradimicin D. Pradimicins D and E were equal in activity to pradimicin A in vitro against a variety of fungi and in vivo against Candida albicans A9540 in mice.

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TRICHOMYCIN B, A POLYENE MACROLIDE FROM STREPTOMYCES

TADAAKI KOMORI

1990 Volume 43 Issue 7 Pages 778-782
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.778

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Two polyene macrolide, trichomycins A and B, were compared by physico-chemical and microbiological methods. The two antibiotics were found to have the same molecular formula, C₅₈H₈₄N₂O₁₈ (MW 1, 096), by elemental analysis and FAB-MS. However, ¹H and ¹³C NMR spectrometry studies indicated that the hydroxyl at C-5 of trichomycin A located on C-9 in trichomycin B.
Trichomycin B possessed lower activities against fungi and yeasts than those of trichomycin A.

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ISOLATION OF CEPAFUNGINS I, II AND III FROM PSEUDOMONAS SPECIES

JUN'ICHI SHOJI, HIROSHI HINOO, TOSHIYUKI KATO, TERUO HATTORI, KEIICHIR ...

1990 Volume 43 Issue 7 Pages 783-787
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.783

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New acylpeptide antibiotics named cepafungins I, II and III were isolated from the culture broth of a strain identified as Pseudomonas sp. These antibiotics are neutral substances, soluble in aqueous alcohols and dimethyl sulfoxide, and show UV maxima at 260.5nm. The IR spectra indicated these to be peptides. Molecular formulas C₂₈H₄₆N₄O₆, C₂₇H₄₄N₄O₆ and C₂₆H₄₂N₄O₆ for cepafungins I, II and III were indicated by elemental analysis and SI-MS. Cepafungins exhibited inhibitory activity against yeast and fungi, and antitumor activity against P388 leukemia in mice.

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STRUCTURES OF CEPAFUNGINS I, II AND III

YOSHIHIRO TERUI, JUNKO NISHIKAWA, HIROSHI HINOO, TOSHIYUKI KATO, JUN'I ...

1990 Volume 43 Issue 7 Pages 788-795
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.788

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Structures of interesting acylpeptide antibiotics cepafungins I, II and III were elucidated by NMR spectroscopic studies and some degradation experiments. The antibiotics contain a common peptide part that consists of threonine and two unusual amino acid residues, γ-hydroxylysine and 4-amino-2-pentcnoic acid. The unusual amino acid residues compose an interesting 12-membered ring with an exocyclic N-terminus to which the threonine is connected. Different fatty acyl groups connected to the N-terminus of the threonine distinguish the three cepafungins. The major component I and minor component III are new substance, but the minor component II has a structure identical with that of the recently reported antibiotic glidobactin A.

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QUINALDOPEPTIN, A NOVEL ANTIBIOTIC OF THE QUINOMYCIN FAMILY

SOICHIRO TODA, KOKO SUGAWARA, YUJI NLSHIYAMA, MASARU OHBAYASHI, NORIYU ...

1990 Volume 43 Issue 7 Pages 796-808
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.796

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Quinaldopeptin, a new type of quinomycin antibiotic, was isolated from the culture of Streptoverticillium album strain Q132-6. The antibiotic exhibited strong in vitro antimicrobial and cytotoxic activity and significantly prolonged the survival time of mice inoculated with a murine tumor. Quinaldopeptin is a symmetric cyclic peptide linked only by peptide bonds and differs from known antibiotics of the quinomycin family by the lack of ester linkage.

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THE STRUCTURE OF TAUTOMYCIN, A DIALKYLMALEIC ANHYDRIDE ANTIBIOTIC

XING-CHUN CHENG, MAKOTO UBUKATA, KIYOSHI ISONO

1990 Volume 43 Issue 7 Pages 809-819
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.809

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The chemical structure of tautomycin (C₄₁H₆₆O₁₃) was determined by chemical degradation, spectroscopic analysis and 2D INADEQUATE of tautomycin labeled with [1, 2-¹³C]acetate. Tautomycin exists in methanol - buffer solution (1% diethylamine - formic acid, pH7.3) as an equilibrium mixture of a 2, 3-dialkylmaleic anhydride and its dicarboxylic acid in a ratio of approximately 5:4.

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DIRECT INTRODUCTION OF A FORMAMIDO GROUP INTO THE 7α(6α)-POSITION OF CEPHALOSPORINS (PENICILLINS)

HAJIME KAMACHI, TAKAAKI OKITA, TETSURO YAMASAKI, TAKAYUKI NAITO

1990 Volume 43 Issue 7 Pages 820-829
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.820

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A novel direct introduction of a formamido group into the 7α(6α)-position of cephalosporins (penicillins) was achieved by treatment of 7β(6β-[(3, 5-di-tert-butyl-4-oxo-2, 5-cyclohexadien-1-ylidene)methylimino]cephem (penam) esters with N, N-bis(trimethylsilyl)formamide, followed by deblocking with Girard reagent T to give the corresponding 7α(6α)-foimamido-7β(6β-amino derivatives. Three 7α-formamidocephalosporins were prepared by the conventional N-acylation of 7α-formamidocephem. All of them were resistant to β-lactamases, showing similar MIC values against both of a pair of a β-lactamase-producing strain and the corresponding non or low-producing strain of the same species of bacteria, when tested on Staphylococcus aureus, Klebsiella pneurnoniae, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Enterobacter cloacae and Citrobacter freundii.

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DERIVATIVES OF SAQUAYAMYCINS A AND B

REGIO- AND DIASTEREOSELECTIVE ADDITION OF ALCOHOLS TO THE L-ACULOSE MOIETY

THOMAS HENKEL, AXEL ZEECK

1990 Volume 43 Issue 7 Pages 830-837
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.830

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In continuation of our structure-activity investigations on angucycline antibiotics we prepared derivatives of saquayamycins A (1) and B (4) by regio- and diastereoselective nucleophilic addition of different alcohols to the L-aculose moiety. Reversible protection of the 4'-hydroxy group in 1 by silylation allowed a derivatization at both L-aculose moieties without cyclization towards cinerulose B. The in vitro cytotoxic activity remained almost unchanged after variation at the L-aculose moieties whereas a change in the aglycone structure led to a total loss of the biological activity.

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3'-HYDROXYESORUBICIN SYNTHESIS AND ANTITUMOR ACTIVITY

WALDEMAR PRIEBE, NOURI NEAMATI, ROMAN PEREZ-SOLER

1990 Volume 43 Issue 7 Pages 838-846
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.838

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A novel route to 4'-deoxy anthracycline analogues has been developed starting from previously unavailable, optically active 4, 6-dideoxy-hex-1-enitol 9. Coupling of daunomycinone (11) or 14-O-tert-butyldimethylsilyladriamycinone (12) with glycosyl chloride 10 in Koenigs-Knorr condition gave mainly a anomers, which were successfully deblocked to final 3'-deamino-4'-deoxy-3'-hydroxydaunorubicin (7) and 3'-deamino-3'-hydroxyesorubicin (8). Analogues were evaluated in vitro against P388 and L1210 leukemia and M5076 cells and in vivo against P388 leukemia. Compared with doxorubicin (1), 3'-hydroxyesorubicin (8) showed in vitro similar cytotoxic potential and in vivo higher antitumor activity.

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SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF C-2 CARBOXYETHENYLTHIO-CARBAPENEMDERIVATIVES

MICHAEL J. BASKER, DAVID F. CORBETT, STEVEN COULTON, ROBERT SOUTHGATE

1990 Volume 43 Issue 7 Pages 847-857
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.847

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A number of C-2 carboxyethenylthio-carbapenem derivatives possessing either the (5R, 6R, 8S)- or the (5R, 6S, 8R)-stereochemistries have been prepared from the olivanic acids MM 22382 (1) and MM 22383 (4), respectively. Their in vitro antibacterial activities and stabilities to human kidney homogenate are superior to those of the parent compounds, particularly in the latter series.

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AMIKACIN ANALOGS WITH A FLUORINATED AMINO ACID SIDE CHAIN

HIDEAKI HOSHI, SHIMPEI ABURAKI, SEIJI IIMURA, TETSURO YAMASAKI, TAKAYU ...

1990 Volume 43 Issue 7 Pages 858-872
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.858

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The synthesis and biological activity of kanamycin A derivatives with an ω-amino-α-fluoroalkanoyl side chain on the 1-amino group are described. The fluorinated amino acids (4) for the side chain were prepared by fluorination of the α-hydroxy esters (2) with diethylaminosulfur trifluoride (DAST) with accompanying the Walden inversion. The reaction products varied with the amino protective groups employed, chain length of the alkanoic acids and the presence or absence of base. The fluorinated side chain was introduced to 1-free-NH₂ kanamycin A (12) by the conventional active ester method and subsequent deblocking reactions afforded the desired final products (13-17). Of the derivatives prepared, 1-N-[(S)-4-amino-2-fluorobutyryl]kanamycin A (2"'-deoxy-2"'-fluoroamikacin, 14) showed the best overall activity profile, nearly the same as that of amikacin. Preparation and antibacterial activity of several aminoglycoside antibiotics with the 1-N-(S)-4-amino-2-fluorobutyryl side chain are also discussed.

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MOLECULAR CLONING AND CHARACTERIZATION OF THE GENE CONFERRING CURROMYCIN RESISTANCE ON A CURROMYCIN NON-PRODUCING MUTANT DERIVED FROM STREPTOMYCES HYGROSCOPICUS 358AV2

MITSUO OGURA, TERUO TANAKA, HARUO SETO, NOBORU OTAKE

1990 Volume 43 Issue 7 Pages 873-882
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.873

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We cloned six different DNA fragments from a curromycin producing strain, Streptomyces hygroscopicus 358AV2, which confer curromycin-resistance on a curromycin non-producing and sensitive strain, S. hygroscopicus Rgll, a protoplast regenerant of the strain 358AV2. We studied the plasmid pSHR2 carrying one of the DNA fragments. By Southern blot analysis, the cloned DNA sequence in pSHR2 was found to be deleted in the Rgll genome. From the Rgll strain, a curromycin producing revertant A-4 was obtained, indicating that the structural genes for the curromycin biosynthesis and resistance are retained in the Rgll genome. Based on the existence of A-4 and the deletion of the DNA region corresponding to the cloned DNA sequence in the Rgll genome, we conclude that the cloned DNA sequence carries a regulatory gene governing curromycin-resistance but not the resistance gene itself. The smallest DNA region in pSHR2 conferring curromycin-resistance was sequenced, and it was found that there were two small open reading frames (ORF) on each strand of the cloned DNA. In-frame fusion of ORFs to the reporter gene lacZ revealed that one ORF designated cre was indeed translated in vivo. The putative gene product deduced from the cre ORF is a basic and hydrophilic protein having a calculated molecular weight of 6 kdaltons.

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BIOGENESIS OF CHROMOMYCIN A₃ BY STREPTOMYCES GRISEUS

ANTONIO MONTANARI, JOHN P. N. ROSAZZA

1990 Volume 43 Issue 7 Pages 883-889
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.883

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The biosynthesis of chromomycin A₃ was investigated using ¹³C-labeled acetates, methionine and glucose, and ¹³C, ¹⁸O-labeled acetate. ¹³C NMR spectral analysis demonstrated that: Aglycone assembly occurs by combining at least two polyketide chains; three of nine oxygen atoms of the aglycone originate from acetate precursor oxygen atoms; carbon methylations on the aromatic ring at C-7, on the chromose B sugar, and two O-methylations appear to be carried out by S-adenosyl-methionine requiring methyl transferases; and glucose is the precursor for all of the sugars.

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THE STRUCTURE OF TAUTOMYCETIN, A DIALKYLMALEIC ANHYDRIDE ANTIBIOTIC

XING-CHUN CHENG, MAKOTO UBUKATA, KIYOSHI ISONO

1990 Volume 43 Issue 7 Pages 890-896
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.890

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The chemical structure of tautomycetin (C₃₃H₅₀O₁₀) was determined by chemical degradation and spectroscopic evidence. Tautomycetin exists in methanol - buffer solution (1% diethylamine - formic acid, pH7.3) as an equilibrium mixture of a 2, 3-dialkylmaleic anhydride and its dicarboxylic acid. The structure of tautomycetin is similar to tautomycin in many respects.

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SARAMYCETIN, A THIAZOLYL PEPTIDE FROM A STREPTOMYCES SP.: CHEMICAL CHARACTERIZATION AND MOLECULAR WEIGHT DETERMINATION

R. COOPER, I. TRUUMEES, T. BARRETT, M. PATEL, J. SCHWARTZ, M. PUAR, P. ...

1990 Volume 43 Issue 7 Pages 897-900
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.897

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STRUCTURES OF THE ALKALINE HYDROLYSIS PRODUCTS OF PENEM ANTIBIOTIC, SUN5555

HIROMITSU IWATA, RIE TANAKA, MASAJI ISHIGURO

1990 Volume 43 Issue 7 Pages 901-903
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.901

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TRICHOMYCIN A, A HEPTAENE MACROLIDE: ISOLATION AND CHARACTERIZATION

TADAAKI KOMORI, YUKIYOSHI MORIMOTO

1990 Volume 43 Issue 7 Pages 904-906
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.904

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HYDRAZIDES-A NOVEL TYPE OF DERIVATIVES OF POLYENE MACROLIDE ANTIFUNGAL ANTIBIOTICS

JOLANTA GRZYBOWSKA, EDWARD BOROWSKI

1990 Volume 43 Issue 7 Pages 907-908
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.907

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BIOSYNTHETIC STUDIES ON OLEANDOMYCIN BY INCORPORATION OF THE CHEMICALLY SYNTHESIZED AGLYCONES

KUNIAKI TATSUTA, HIROKI GUNJI, SHUICHI TAJIMA, TAKASHI ISHIYAMA, SATOS ...

1990 Volume 43 Issue 7 Pages 909-911
Published: July 25, 1990
Released on J-STAGE: April 19, 2006

DOIhttps://doi.org/10.7164/antibiotics.43.909

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