45 results on '"Aquayamycin"'
Search Results
2. A Metal-Free β-Stereoselective Synthesis of 2-Deoxy-C-arylglycosides: Synthesis of 5-Aza Analogues of Aquayamycin
- Author
-
Yu Yang, Saifeng Qiu, Jianbo Zhang, Yuling Mei, Nan Jiang, Guo Hong, and Wan Zhang
- Subjects
chemistry.chemical_classification ,Aquayamycin ,chemistry.chemical_compound ,Glycosylation ,chemistry ,Stereochemistry ,Organic Chemistry ,Iodide ,Glycoside ,Stereoselectivity ,Glycosyl - Abstract
A convenient protocol for the β-stereoselective synthesis of 2-deoxy-C-arylglycosides has been developed. This reaction takes place in one step by using I2/Et3SiH to activate a glycosyl acetate to generate a glycosyl iodide intermediate in situ, which is captured by a naphthol; this is followed by a Fries-like O-to-C glycoside rearrangement to afford a β-C-aryl glycoside selectively. The approach is applicable to a wide range of naphthol moieties, and its utility was demonstrated in syntheses of 5-aza analogues of aquayamycin.
- Published
- 2021
3. Baikalomycins A-C, New Aquayamycin-Type Angucyclines Isolated from Lake Baikal Derived Streptomyces sp. IB201691-2A
- Author
-
Irina Voitsekhovskaia, Constanze Paulus, Charlotte Dahlem, Yuriy Rebets, Suvd Nadmid, Josef Zapp, Denis Axenov-Gribanov, Christian Rückert, Maxim Timofeyev, Jörn Kalinowski, Alexandra K. Kiemer, and Andriy Luzhetskyy
- Subjects
natural products ,angucycline ,aquayamycin ,glycosyltransferase ,Lake Baikal ,Streptomyces ,Biology (General) ,QH301-705.5 - Abstract
Natural products produced by bacteria found in unusual and poorly studied ecosystems, such as Lake Baikal, represent a promising source of new valuable drug leads. Here we report the isolation of a new Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk Benedictia baicalensis. In the course of an activity guided screening three new angucyclines, named baikalomycins A–C, were isolated and characterized, highlighting the potential of poorly investigated ecological niches. Besides that, the strain was found to accumulate large quantities of rabelomycin and 5-hydroxy-rabelomycin, known shunt products in angucyclines biosynthesis. Baikalomycins A–C demonstrated varying degrees of anticancer activity. Rabelomycin and 5-hydroxy-rabelomycin further demonstrated antiproliferative activities. The structure elucidation showed that baikalomycin A is a modified aquayamycin with β-d-amicetose and two additional hydroxyl groups at unusual positions (6a and 12a) of aglycone. Baikalomycins B and C have alternating second sugars attached, α-l-amicetose and α-l-aculose, respectively. The gene cluster for baikalomycins biosynthesis was identified by genome mining, cloned using a transformation-associated recombination technique and successfully expressed in S. albus J1074. It contains a typical set of genes responsible for an angucycline core assembly, all necessary genes for the deoxy sugars biosynthesis, and three genes coding for the glycosyltransferase enzymes. Heterologous expression and deletion experiments allowed to assign the function of glycosyltransferases involved in the decoration of baikalomycins aglycone.
- Published
- 2020
- Full Text
- View/download PDF
4. Total Synthesis of Aquayamycin.
- Author
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Kusumi, Shunichi, Nakayama, Harunobu, Kobayashi, Takumi, Kuriki, Hajime, Matsumoto, Yuka, Takahashi, Daisuke, and Toshima, Kazunobu
- Subjects
- *
REDUCTION of ketones , *NAPHTHOQUINONE , *ANTIBIOTICS assay , *KETONES , *INTRAMOLECULAR catalysis - Abstract
An efficient and practical total synthesis of aquayamycin has been accomplished. The highly oxidized and stereochemically complex tetracyclic ring system was constructed using three key reactions: 1) highly diastereoselective 1,2-addition of C-glycosyl naphthyllithium to a cyclic ketone, 2) indium-mediated site-selective allylation-rearrangement sequence of naphthoquinone, and 3) diastereoselective intramolecular pinacol coupling. This synthetic strategy offers a novel and efficient pathway to prepare aquayamycin-type angucycline antibiotics. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
5. Baikalomycins A-C, New Aquayamycin-Type Angucyclines Isolated from Lake Baikal Derived sp. IB201691-2A
- Author
-
Voitsekhovskaia, Irina, Paulus, Constanze, Dahlem, Charlotte, Rebets, Yuriy, Nadmid, Suvd, Zapp, Josef, Axenov-Gribanov, Denis, Rückert, Christian, Timofeyev, Maxim, Kalinowski, Jörn, Kiemer, Alexandra K, Luzhetskyy, Andriy, and HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
- Subjects
natural products ,angucycline ,Lake Baikal ,aquayamycin ,glycosyltransferase ,Streptomyces - Abstract
Natural products produced by bacteria found in unusual and poorly studied ecosystems, such as Lake Baikal, represent a promising source of new valuable drug leads. Here we report the isolation of a new Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk Benedictia baicalensis. In the course of an activity guided screening three new angucyclines, named baikalomycins A-C, were isolated and characterized, highlighting the potential of poorly investigated ecological niches. Besides that, the strain was found to accumulate large quantities of rabelomycin and 5-hydroxy-rabelomycin, known shunt products in angucyclines biosynthesis. Baikalomycins A-C demonstrated varying degrees of anticancer activity. Rabelomycin and 5-hydroxy-rabelomycin further demonstrated antiproliferative activities. The structure elucidation showed that baikalomycin A is a modified aquayamycin with β-d-amicetose and two additional hydroxyl groups at unusual positions (6a and 12a) of aglycone. Baikalomycins B and C have alternating second sugars attached, α-l-amicetose and α-l-aculose, respectively. The gene cluster for baikalomycins biosynthesis was identified by genome mining, cloned using a transformation-associated recombination technique and successfully expressed in S. albus J1074. It contains a typical set of genes responsible for an angucycline core assembly, all necessary genes for the deoxy sugars biosynthesis, and three genes coding for the glycosyltransferase enzymes. Heterologous expression and deletion experiments allowed to assign the function of glycosyltransferases involved in the decoration of baikalomycins aglycone.
- Published
- 2020
6. λ3-Iodane-mediated arenol dearomatization. Synthesis of five-membered ring-containing analogues of the aquayamycin ABC tricyclic unit and novel access to the apoptosis inducer menadione
- Author
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Lebrasseur, Nathalie, Fan, Gao-Jun, Oxoby, Mayalen, Looney, Matthew A., and Quideau, Stéphane
- Subjects
- *
AROMATIC compounds , *RING formation (Chemistry) , *NAPHTHALENE , *CANCER cells - Abstract
Abstract: The λ3-iodane [bis(trifluoroacetoxy)]iodobenzene (BTI)-mediated oxidative dearomatization of 2-alkoxyarenols with soft external carbon-based nucleophiles constitutes a rapid access to highly functionalized naphthoid cyclohexa-2,4-dienones. These synthons can serve as valuable intermediates in the construction of the angularly-oxygenated benz[a]naphthalene ABC ring system of aquayamycin- and SS-228Y-type antibiotic angucyclinones, and analogues thereof. This methodology led to the elaboration of five-membered A ring-containing analogues of this ABC tricyclic unit. In addition, the BTI-mediated oxidative activation of 2-methylnaphthol can be exploited to prepare menadione (i.e. vitamin K3), known to induce apoptosis and autoschizis, a novel type of cancer cell death. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
7. Synthesis and antitumor activities of aquayamycin and analogues of derhodinosylurdamycin A
- Author
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Padam P. Acharya, Jianglong Zhu, Sandip Janda, and Hem Raj Khatri
- Subjects
Aquayamycin ,Glycosylation ,Stereochemistry ,Protein subunit ,Organic Chemistry ,Disaccharide ,Oligosaccharides ,Anthraquinones ,Antineoplastic Agents ,Chemistry Techniques, Synthetic ,Biochemistry ,Guanidines ,chemistry.chemical_compound ,Structure-Activity Relationship ,chemistry ,Cell culture ,Cell Line, Tumor ,Cytotoxic T cell ,Moiety ,Humans ,Physical and Theoretical Chemistry ,Growth inhibition ,Drug Screening Assays, Antitumor - Abstract
Total syntheses of aquayamycin (3) and a number of analogues of angucycline antitumor antibiotic derhodinosylurdamycin A bearing various 2-deoxy sugar subunits (4–7) have been achieved. These molecules (3–7) were synthesized based on a convergent strategy for the synthesis of derhodinosylurdamycin A (2) previously reported from our group. In particular, our recently developed mild cationic gold-catalyzed glycosylation with S-but-3-ynyl thioglycoside donors was employed for the synthesis of analogues (6 and 7) bearing disaccharide subunits containing α-L-olivoside and α-L-olioside moiety, respectively. Aquayamycin (3), analogues (4–7), and our previously synthesized derhodinosylurdamycin A (2) were then submitted to the Development Therapeutics Program of the National Cancer Institute of National Institutes of Health for the NCI-60 Human Tumor Cell Lines Screening using standard protocols. It was found that derhodinosylurdamycin A (2), aquayamycin (3), and three other analogues (5–7) bearing sugar subunits did not show significant antiproliferative activity against those cancer cell lines. Interestingly, analogue (4) bearing no sugar subunit demonstrates good potential for growth inhibition and cytotoxic activity against a variety of human cancer cell lines.
- Published
- 2019
8. Total synthesis of the natural furanones
- Author
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Zhiwen Wan
- Subjects
chemistry.chemical_compound ,Aquayamycin ,chemistry ,Furan ,Halenaquinone ,Total synthesis ,Organic chemistry ,Ring (chemistry) - Abstract
v GENERAL INTRODUCTION 1 Dissertation Organization 1 CHAPTER 1. FURAN SYNTHESIS VIA A 4 + 1 RING BUILDING STRATEGYAN APPROACH TO 2,4-DL\CYLFURANS 2 Introduction 2 Results and Discussion 6 Conclusion 10 Experiments 10 References 14 CHAPTER 2. TOTAL SYNTHESIS OF HIBISCONE C 17 Introduction 17 Results and Discussion 19 Conclusion 26 Experiments 26 References 31 CHAPTER 3. SYNTHETIC APPROACH TO NATURAL ANALOGUES OF HALENAQUINONE 32 Introduction 32 Results and Discussion 41 Conclusion 51 Experiments 52 References 57 CHAPTER 4. A SYNTHETIC APPROACH TO AQUAYAMYCIN 60 Introduction 60 Results and Discussion 68 Conclusion 74 Experiments 74 References 79 CHAPTERS. GENERAL CONCLUSION ACKNOWLEDGEMENTS 82 83
- Published
- 2018
9. Total Synthesis of Aquayamycin
- Author
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Hajime Kuriki, Yuka Matsumoto, Takumi Kobayashi, Daisuke Takahashi, Shunichi Kusumi, Kazunobu Toshima, and Harunobu Nakayama
- Subjects
Aquayamycin ,Naphthyllithium ,Molecular Structure ,010405 organic chemistry ,Pinacol ,Stereochemistry ,Organic Chemistry ,Total synthesis ,Anthraquinones ,General Chemistry ,Ketones ,010402 general chemistry ,Ring (chemistry) ,01 natural sciences ,Indium ,Catalysis ,Naphthoquinone ,0104 chemical sciences ,Anti-Bacterial Agents ,Cyclic ketone ,chemistry.chemical_compound ,chemistry ,Intramolecular force ,Oxidation-Reduction - Abstract
An efficient and practical total synthesis of aquayamycin has been accomplished. The highly oxidized and stereochemically complex tetracyclic ring system was constructed using three key reactions: 1) highly diastereoselective 1,2-addition of C-glycosyl naphthyllithium to a cyclic ketone, 2) indium-mediated site-selective allylation-rearrangement sequence of naphthoquinone, and 3) diastereoselective intramolecular pinacol coupling. This synthetic strategy offers a novel and efficient pathway to prepare aquayamycin-type angucycline antibiotics.
- Published
- 2016
10. Baikalomycins A-C, New Aquayamycin-Type Angucyclines Isolated from Lake Baikal Derived Streptomyces sp. IB201691-2A.
- Author
-
Voitsekhovskaia, Irina, Paulus, Constanze, Dahlem, Charlotte, Rebets, Yuriy, Nadmid, Suvd, Zapp, Josef, Axenov-Gribanov, Denis, Rückert, Christian, Timofeyev, Maxim, Kalinowski, Jörn, Kiemer, Alexandra K., and Luzhetskyy, Andriy
- Subjects
DEOXY sugars ,STREPTOMYCES ,LAKES ,NATURAL products ,ECOLOGICAL niche ,HYDROXYL group - Abstract
Natural products produced by bacteria found in unusual and poorly studied ecosystems, such as Lake Baikal, represent a promising source of new valuable drug leads. Here we report the isolation of a new Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk Benedictia baicalensis. In the course of an activity guided screening three new angucyclines, named baikalomycins A–C, were isolated and characterized, highlighting the potential of poorly investigated ecological niches. Besides that, the strain was found to accumulate large quantities of rabelomycin and 5-hydroxy-rabelomycin, known shunt products in angucyclines biosynthesis. Baikalomycins A–C demonstrated varying degrees of anticancer activity. Rabelomycin and 5-hydroxy-rabelomycin further demonstrated antiproliferative activities. The structure elucidation showed that baikalomycin A is a modified aquayamycin with β-d-amicetose and two additional hydroxyl groups at unusual positions (6a and 12a) of aglycone. Baikalomycins B and C have alternating second sugars attached, α-l-amicetose and α-l-aculose, respectively. The gene cluster for baikalomycins biosynthesis was identified by genome mining, cloned using a transformation-associated recombination technique and successfully expressed in S. albus J1074. It contains a typical set of genes responsible for an angucycline core assembly, all necessary genes for the deoxy sugars biosynthesis, and three genes coding for the glycosyltransferase enzymes. Heterologous expression and deletion experiments allowed to assign the function of glycosyltransferases involved in the decoration of baikalomycins aglycone. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
11. Langkocyclines: novel angucycline antibiotics from Streptomyces sp. Acta 3034
- Author
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Vikineswary Sabaratnam, Jutta Wiese, Cheau-Yee Foo, Roderich D. Süssmuth, Geok Yuan Annie Tan, Johannes F. Imhoff, Bahar Kalyon, Hans-Peter Fiedler, and John M Pinto
- Subjects
DNA, Bacterial ,Models, Molecular ,Aquayamycin ,Stereochemistry ,Molecular Sequence Data ,Streptomyces lanatus ,Oligosaccharides ,Anthraquinones ,Antineoplastic Agents ,Gram-Positive Bacteria ,DNA, Ribosomal ,Streptomyces ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,RNA, Ribosomal, 16S ,Drug Discovery ,Animals ,Humans ,Polycyclic Aromatic Hydrocarbons ,Phylogeny ,Soil Microbiology ,Pharmacology ,Strain (chemistry) ,biology ,Malaysia ,Biological activity ,Hep G2 Cells ,Sequence Analysis, DNA ,16S ribosomal RNA ,biology.organism_classification ,Anti-Bacterial Agents ,chemistry ,Biochemistry ,Streptomyces psammoticus ,Rhizosphere ,NIH 3T3 Cells ,Bacteria - Abstract
Langkocyclines A1-A3 and B1 and B2, five new angucycline antibiotics produced by Streptomyces sp. Acta 3034, were detected in the course of our HPLC-diode array screening. The producing strain was isolated from the rhizospheric soil of a Clitorea sp. collected from Burau Bay, Langkawi, Malaysia, and was characterized by morphological, physiological and chemotaxonomic features in addition to 16S ribosomal RNA gene sequence information. Strain Acta 3034 is closely related to Streptomyces psammoticus NBRC 13971(T) and Streptomyces lanatus NBRC 12787(T). Langkocyclines consist of an angular tetracyclic benz[a]anthracene skeleton and hydrolyzable O-glycosidic sugar moieties. The yellow-colored A-type langkocyclines differ in their aglycon from the blue-lilac-colored B-type langkocyclines. The A-type langkocycline aglycon is identical to that of aquayamycin and urdamycin A. The chemical structures of the langkocyclines were elucidated by HR-MS, 1D and 2D NMR experiments. They are biologically active against Gram-positive bacteria and exhibit a moderate antiproliferative activity against various human tumor cell lines.
- Published
- 2013
12. Angucycline antibiotics and its derivatives from marine-derived actinomycete Streptomyces sp. A6H
- Author
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Qin Lele, Qianqian Wang, Zhijuan Hu, Zhen Chen, Wanjing Ding, and Zhongjun Ma
- Subjects
Aquayamycin ,biology ,010405 organic chemistry ,Stereochemistry ,medicine.drug_class ,Organic Chemistry ,Antibiotics ,Plant Science ,biology.organism_classification ,medicine.disease_cause ,Antimicrobial ,01 natural sciences ,Biochemistry ,Streptomyces ,Semisynthesis ,Combinatorial chemistry ,0104 chemical sciences ,Analytical Chemistry ,010404 medicinal & biomolecular chemistry ,Hydrolysis ,chemistry.chemical_compound ,chemistry ,Staphylococcus aureus ,medicine ,Fermentation - Abstract
Vineomycin A1 (1) and B2 (2) were isolated from the culture broth of marine actinomycete Streptomyces sp. A6H. Five hydrolysis products were obtained by rational hydrolysis and methanolysis of the fermentation extract. Their structures were characterised as aquayamycin (3), vineomycinone B2 (4), 9-C-D-olivosyltetrangulol (5), 7-O-methylgaltamycinone (6) and vineomycinone B2 methyl ester (7). In addition to these compounds, two ester derivatives, vineolactone A (8) and vineomycinone B2 benzyl ester (9) of compound 4 were generated semisynthetically. Compound 6 is a new analogue of galtamycinone, while compounds 8 and 9 are new members of vineomycins. Cytotoxic activities and antimicrobial activities were determined for all compounds. The results indicate that only compound 1 showed significant activities with IC50 value of 0.34 μM against H1975 and MIC value of 4 μg/mL against Staphylococcus aureus.
- Published
- 2016
13. λ3-Iodane-mediated arenol dearomatization. Synthesis of five-membered ring-containing analogues of the aquayamycin ABC tricyclic unit and novel access to the apoptosis inducer menadione
- Author
-
Nathalie Lebrasseur, Matthew A. Looney, Gao-Jun Fan, Mayalen Oxoby, and Stéphane Quideau
- Subjects
chemistry.chemical_classification ,Aquayamycin ,Chemistry ,Stereochemistry ,Organic Chemistry ,Synthon ,Iodobenzene ,Ring (chemistry) ,Biochemistry ,chemistry.chemical_compound ,Menadione ,Nucleophile ,Drug Discovery ,Autoschizis ,Tricyclic - Abstract
The λ3-iodane [bis(trifluoroacetoxy)]iodobenzene (BTI)-mediated oxidative dearomatization of 2-alkoxyarenols with soft external carbon-based nucleophiles constitutes a rapid access to highly functionalized naphthoid cyclohexa-2,4-dienones. These synthons can serve as valuable intermediates in the construction of the angularly-oxygenated benz[a]naphthalene ABC ring system of aquayamycin- and SS-228Y-type antibiotic angucyclinones, and analogues thereof. This methodology led to the elaboration of five-membered A ring-containing analogues of this ABC tricyclic unit. In addition, the BTI-mediated oxidative activation of 2-methylnaphthol can be exploited to prepare menadione (i.e. vitamin K3), known to induce apoptosis and autoschizis, a novel type of cancer cell death.
- Published
- 2005
14. [Untitled]
- Author
-
Peter Frese, Ulrich Flörke, and Karsten Krohn
- Subjects
Aquayamycin ,Bicyclic molecule ,Stereochemistry ,Ammonium nitrate ,Organic Chemistry ,chemistry.chemical_element ,General Chemistry ,Catalysis ,Samarium ,Cerium ,chemistry.chemical_compound ,chemistry ,Samarium diiodide ,Aldol reaction ,Biomimetic synthesis ,Organic chemistry - Abstract
The first synthesis of the racemic 8-deoxy WP 3688-2 angucycline antibiotic (3), with characteristic cis-hydroxy groups at C-4 a and C-12 b, is reported. Key steps involve the coupling, mediated by samarium diiodide, of the bicyclic trione 37 to the tricyclic cis-diol 39. Biomimetic aldol cyclization of the corresponding dione 41 gave a mixture of the tetracyclic cis- and trans-3,4 a-diols 42 and 43, which were oxidized by cerium ammonium nitrate to the quinones 45 and 3. The synthetic compounds 45 and 3 corresponded in configuration to the angucycline antibiotics aquayamicin (1) and WP 3688-2 (2), respectively.
- Published
- 2000
15. Synthetic study of aquayamycin. Part 1: Synthesis of 3-(phenylsulfonyl)phthalides possessing a β-C-olivoside
- Author
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Mitsujiro Tanabe, Takashi Matsumoto, Toshiyuki Hamura, Yokusu Kuriyama, Hiroki Yamaguchi, and Keisuke Suzuki
- Subjects
Aquayamycin ,Silylation ,Stereochemistry ,Organic Chemistry ,Acetal ,Ketene ,Regioselectivity ,Total synthesis ,Biochemistry ,Aryne ,Cycloaddition ,chemistry.chemical_compound ,chemistry ,Drug Discovery - Abstract
An efficient synthetic route to 3-(phenylsulfonyl)phthalides possessing a β- C -olivoside was developed by exploiting the regioselective [2+2] cycloaddition of benzyne with ketene silyl acetal. The compounds are useful in the total synthesis of the angucyclines, including aquayamycin.
- Published
- 2000
16. Synthetic study of aquayamycin. Part 2: Synthesis of the AB ring fragment
- Author
-
Takeshi Nakamura, Tadayoshi Konegawa, Mitsujiro Tanabe, Hiroki Yamaguchi, Takashi Matsumoto, and Keisuke Suzuki
- Subjects
chemistry.chemical_classification ,Aquayamycin ,Ketone ,Cyclohexane ,Stereochemistry ,Organic Chemistry ,Ring (chemistry) ,Biochemistry ,Combinatorial chemistry ,Turn (biochemistry) ,chemistry.chemical_compound ,chemistry ,Bromide ,Cyclohexenone ,Drug Discovery ,Derivative (chemistry) - Abstract
A highly oxygen-functionalized cyclohexenone 2 , the AB ring fragment for the aquayamycin synthesis, was efficiently synthesized via stereoselective addition of allylzinc bromide to ketone 3a which, in turn, was available from the optically pure cyclohexane 1,2,3-triol derivative 5 .
- Published
- 2000
17. Syntheses and biological evaluation of new glyco-modified angucyclin-antibiotics
- Author
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Lutz F. Tietze, Andreas Kirschning, Guang-wu Chen, Gerald Dräger, and Ingrid Schuberth
- Subjects
Xanthine Oxidase ,Aquayamycin ,Glycosylation ,Silylation ,Cell Survival ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Anthraquinones ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Chemical synthesis ,Colony-Forming Units Assay ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Benz(a)Anthracenes ,Tumor Cells, Cultured ,Animals ,Humans ,Glycosides ,Enzyme Inhibitors ,Protecting group ,Glycosyl donor ,Molecular Biology ,Antibiotics, Antineoplastic ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Organic Chemistry ,Aromatization ,Anti-Bacterial Agents ,0104 chemical sciences ,Quinone ,chemistry ,Tetracyclines ,Molecular Medicine - Abstract
The synthesis of novel aquayamycin-derived angucycline antibiotics 13a–d has been achieved. Glycosylation of aquayamycin (6) using 2-selenoglycosyl acetate 7 as glycosyl donor proceeded in excellent yield but attempts to reductively remove the selenyl group led to rearrangement or further aromatization of the aglycon. As a consequence of these results, it became possible to prepare urdamycinone B (10) starting from aquayamycin (6). In addition, silyl protected d -olivals 12a,b were attached to the C-glycoside domain of aquayamycin (6) under protic conditions. As expected, the hydroxy and phenol groups of the benz[a]anthracene framework of 6 did not react under the glycosylation conditions employed. Stepwise removal of the silyl protecting group starting with tetrabutyl ammonium fluoride followed by use of the HF/pyridine complex suppressed a possible rearrangement of the aglycon and successfully terminated the sequence. The new angucycline-antibiotics 13a and 13b are some of the most potent xanthine oxidase inhibitors known and show cytotoxic activity with ED50-values in the range of 12.6–2.9×10−6 M
- Published
- 2000
18. Synthetic Study of Aquayamycin. Part 3: First Total Synthesis
- Author
-
Takashi Matsumoto, Yoshizumi Yasui, Hiroki Yamaguchi, Mitsujiro Tanabe, and Keisuke Suzuki
- Subjects
chemistry.chemical_classification ,Aquayamycin ,Pinacol ,Stereochemistry ,Organic Chemistry ,Total synthesis ,Biochemistry ,Aldehyde ,Phthalide ,chemistry.chemical_compound ,chemistry ,Cyclohexenone ,Intramolecular force ,Drug Discovery - Abstract
The first total synthesis of aquayamycin (1) has been accomplished. The crucial steps include (1) the Hauser reaction between 3-(phenylsulfonyl)phthalide 3 and cyclohexenone 4 to make up the linear BCD tricycle, and (2) the intramolecular pinacol coupling of keto aldehyde 7 to the full tetracyclic framework.
- Published
- 2000
19. Synthesis of angularly-fused aromatic antibiotics. Preparation of the ABC ring system of aquayamycin
- Author
-
Zhiwen Wan and George A. Kraus
- Subjects
chemistry.chemical_classification ,Aquayamycin ,chemistry.chemical_compound ,Ketone ,chemistry ,Stereochemistry ,Intramolecular force ,Organic Chemistry ,Drug Discovery ,Ring (chemistry) ,Biochemistry ,Cyanohydrin - Abstract
An approach to the ABC ring system of aquayamycin which incorporates a selectively protected cis-diol unit is described. The key step is an intramolecular addition of the anion of a protected cyanohydrin to a ketone.
- Published
- 1997
20. Saquayamycins G-K, cytotoxic angucyclines from Streptomyces sp. Including two analogues bearing the aminosugar rednose
- Author
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Markos Leggas, Tamer A. Ahmed, Khaled A. Shaaban, and Jürgen Rohr
- Subjects
Male ,Aquayamycin ,Stereochemistry ,Pharmaceutical Science ,Kentucky ,Anthraquinones ,Antineoplastic Agents ,Streptomyces ,Article ,Analytical Chemistry ,Streptomyces nodosus ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Tetrasaccharide ,Humans ,Mayamycin ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,Saquayamycin ,biology ,Molecular Structure ,Organic Chemistry ,Amino Sugars ,biology.organism_classification ,Aglycone ,Complementary and alternative medicine ,chemistry ,Aminosugar ,Molecular Medicine ,Drug Screening Assays, Antitumor - Abstract
The angucycline group of antibiotics is one of the largest groups of polycyclic aromatic polyketides, rich in chemical scaffolds and biological activities, predominantly anticancer and antibacterial.1–3 Saquayamycins,4–8 urdamycins,9–17 and landomycins,18–24 are well known angucycline antitumor antibiotics. The structures of both saquayamycins and urdamycins contain the same aquayamycin (17)25–27 as aglycone with the C-glycosidic sugar D-olivose attached at C-9 of the angucycline chromophore. So far, seven saquayamycin analogues were reported from Streptomyces spp. Saquayamycins differ from urdamycins by their saccharide patterns, which are attached at C-9 and C-3 positions in the saquayamycins, but at C-9- and C-12b-positions in urdamycins. Saquayamycins A-D (7–10) were first isolated from Streptomyces nodosus MH190-16F3 and were reported as platelet aggregation inhibitors.4 Saquayamycins A-B (7–8) contain three different O-glycosidically linked deoxysugars, L-rhodinose, L-aculose, and L-cinerulose (only in saquayamycin B). Saquayamycin A (7) was reported to be unstable to acid, and even contact with silica gel led to its conversion to saquayamycin B (8). Saquayamycins A1 (11), B1 (6), and C1 (12) were generated by partial acid hydrolysis of saquayamycins A-C (7–9), respectively.4 The two isomers, saquayamycins E (13) and F (14) were produced by Actinomyces strain MK290-AF1 and reported to inhibit the FPTase from bovine brain with IC50 values of 1.8 and 2.0 μM, respectively.5 They differ slightly from the saquayamycins A (7) and C (9) with respect to their sugar moieties. The saquayamycin analogue A-7884 (16) was isolated from the Streptomyces sp. #AM1699; it has a trisaccharide side chain connected at C-9, which contains an L-rhodinose sugar moiety between the first sugar, a C-glycosidic bound D-olivose, and L-aculose of saquayamycin A1 (11).28 Compound 16 showed inhibitory activity in the inducible nitric oxide synthase (iNOS) assay with IC50 values of 43.5 μM, better than saquayamycin A1 (11; IC50 values of 101.2 μM).28 Recently, the largest saquayamycin analogue, saquayamycin Z (15), was reported from Micromonospora sp. strain Tu6368.6 Saquayamycin Z (15) contains tetra- and pentasaccharide side chains linked at C-3- and C-9-positions of the benz[a]anthracene core. The tetrasaccharide side chain of saquayamycin Z (15) is striking due to the presence of an L-oliose, which is not a usual sugar constituent of the angucyclines.6, 29 Very recently, Ren et al., reported three novel members of the angucycline family named N05WA963 A, B and D, with the same aglycones as in the moromycins A (18) and B (19), except for an additional methoxy group attached at C-5.30 N05WA963 A, B and D were reported to have antiproliferative effects on a panel of cancer cell lines such as SW620 (colon cancer), K-562 (chronic myelogeneous leukemia), MDA-MB-231 (estrogen receptor negative breast cancer), YES-4 (esophageal cancer), T-98 and U251SP (both glioblastomae). To study the structure-activity relationship (SAR) of this saquayamycin group of antibiotics, we looked for further saquayamycin analogues produced by Streptomyces sp. K40-1, the strain earlier reported as the producer of moromycins A-B (18–19).7 The saccharide attachments in moromycins A (18) and B (19) are like those of saquayamycins B (8) and B1 (6), respectively, however, their tetracyclic angucyclinone core has an aromatic ring B, and thus no angular hydroxy groups at C-4a and C-12b positions. We found five new metabolites, designated as saquayamycins G-K (1–5), produced by repeated fermentations of the same strain, along with saquayamycin B1 (6), which was previously not described as a natural product, and known saquayamycins. Two of the new angucyclines, saquayamycins H (2) and I (3), bear the unusual aminosugar rednose, which was found for the first time in an angucycline compound. Aminosugar-containing angucyclines are very rare, and previously only three examples had been reported, namely the marmycins A and B,31, 32 and mayamycin.33 The marmycins contain an unusual branched and doubly (C- and N)-linked aminosugar, 3-epi-, 4-epi-vancosamine, and mayamycin contains a unique C-glycosidically linked aminosugar, N-demethylangolosamine, attached at the C-5-position of the benz[a]anthracenone core.
- Published
- 2012
21. Investigations on the biosynthesis of the angucycline group antibiotics aquayamycin and the urdamycins A and B. Results from the structural analysis of novel blocked mutant products
- Author
-
Györgyi Udvarnoki, K. Eckardt, Steve D. Sorey, John M. Beale, Monika Schoenewolf, G. Schumann, Christina Wagner, and Juergen Rohr
- Subjects
Aquayamycin ,biology ,Strain (chemistry) ,Streptomycetaceae ,Stereochemistry ,Organic Chemistry ,Mutant ,Streptomyces fradiae ,biology.organism_classification ,chemistry.chemical_compound ,Biosynthesis ,chemistry ,Actinomycetales ,Bacteria - Abstract
In order to investigate mid and early biosynthetic steps of angucycline group antibiotics, approximately 400 mutants ofthe urdamycin producer Streptomyces fradiae (strain Tu 2717) were prepared, of which ca. 10% were selected for further investigations. The selection criterion, i.e., the consideration of only pale-colored metabolite-producing blocked mutants, yielded several mutants whose block was in close proximity to the known late-stage biosynthetic steps
- Published
- 1993
22. Lipase-Catalyzed Asymmetrization of Diacetate of Meso-2-(2-Propynyl)cyclohexane-1,2,3-triol toward the Total Synthesis of Aquayamycin
- Author
-
Keisuke Suzuki, Takashi Matsumoto, Takeshi Sugai, Takeshi Nakamura, Hiroki Yamaguchi, and Tadayoshi Konegawa
- Subjects
Aquayamycin ,biology ,Cyclohexane ,Chemistry ,Meso compound ,Propynyl ,Organic Chemistry ,Total synthesis ,chemistry.chemical_compound ,Hydrolysis ,biology.protein ,Organic chemistry ,Triol ,Lipase - Published
- 2001
23. ChemInform Abstract: Synthesis of Angularly-Fused Aromatic Antibiotics. Preparation of the ABC Ring System of Aquayamycin
- Author
-
George A. Kraus and Zhiwen Wan
- Subjects
chemistry.chemical_classification ,Aquayamycin ,chemistry.chemical_compound ,Ketone ,chemistry ,Stereochemistry ,Intramolecular force ,General Medicine ,Ring (chemistry) ,Unit (ring theory) ,Cyanohydrin - Abstract
An approach to the ABC ring system of aquayamycin which incorporates a selectively protected cis-diol unit is described. The key step is an intramolecular addition of the anion of a protected cyanohydrin to a ketone.
- Published
- 2010
24. ChemInform Abstract: Synthetic Study of Aquayamycin. Part 3. First Total Synthesis
- Author
-
Mitsujiro Tanabe, Keisuke Suzuki, Yoshizumi Yasui, Takashi Matsumoto, and Hiroki Yamaguchi
- Subjects
Coupling (electronics) ,chemistry.chemical_classification ,chemistry.chemical_compound ,Aquayamycin ,chemistry ,Pinacol ,Computational chemistry ,Cyclohexenone ,Intramolecular force ,Total synthesis ,General Medicine ,Aldehyde ,Phthalide - Abstract
The first total synthesis of aquayamycin (1) has been accomplished. The crucial steps include (1) the Hauser reaction between 3-(phenylsulfonyl)phthalide 3 and cyclohexenone 4 to make up the linear BCD tricycle, and (2) the intramolecular pinacol coupling of keto aldehyde 7 to the full tetracyclic framework.
- Published
- 2001
25. ChemInform Abstract: Synthetic Study of Aquayamycin. Part 2. Synthesis of the AB Ring Fragment
- Author
-
Keisuke Suzuki, Hiroki Yamaguchi, Takashi Matsumoto, Takeshi Nakamura, Mitsujiro Tanabe, and Tadayoshi Konegawa
- Subjects
Turn (biochemistry) ,chemistry.chemical_classification ,chemistry.chemical_compound ,Aquayamycin ,Ketone ,Cyclohexane ,chemistry ,Bromide ,Cyclohexenone ,Stereochemistry ,General Medicine ,Ring (chemistry) ,Derivative (chemistry) - Abstract
A highly oxygen-functionalized cyclohexenone 2 , the AB ring fragment for the aquayamycin synthesis, was efficiently synthesized via stereoselective addition of allylzinc bromide to ketone 3a which, in turn, was available from the optically pure cyclohexane 1,2,3-triol derivative 5 .
- Published
- 2001
26. ChemInform Abstract: Synthetic Study of Aquayamycin. Part 1. Synthesis of 3-(Phenylsulfonyl)phthalides Possessing a β-C-Olivoside
- Author
-
Hiroki Yamaguchi, Yokusu Kuriyama, Keisuke Suzuki, Mitsujiro Tanabe, Toshiyuki Hamura, and Takashi Matsumoto
- Subjects
chemistry.chemical_compound ,Aquayamycin ,chemistry ,Silylation ,Stereochemistry ,Acetal ,Ketene ,Total synthesis ,Regioselectivity ,Organic chemistry ,General Medicine ,Aryne ,Cycloaddition - Abstract
An efficient synthetic route to 3-(phenylsulfonyl)phthalides possessing a β- C -olivoside was developed by exploiting the regioselective [2+2] cycloaddition of benzyne with ketene silyl acetal. The compounds are useful in the total synthesis of the angucyclines, including aquayamycin.
- Published
- 2001
27. Synthetic studies of the angucycline antibiotics. Reaction of a quinone methide produced from a benz[a]anthracene with molecular oxygen
- Author
-
Kyungjin Kim, Joseph H. Reibenspies, and Gary A. Sulikowski
- Subjects
Aquayamycin ,medicine.drug_class ,Crystal chemistry ,Organic Chemistry ,Antibiotics ,Epoxide ,chemistry.chemical_element ,Benz(a)anthracene ,Quinone methide ,Oxygen ,Quinone ,chemistry.chemical_compound ,chemistry ,medicine ,Organic chemistry - Abstract
Molecular oxygen-based procedures for the stereocontrolled introduction of oxygen functionality present in the antitumor antibiotics aquayamycin (1) and SF 2315B (2) are described
- Published
- 1992
28. Biosynthetic origin of the oxygen atoms of aquayamycin: aspects for the biosynthesis of the urdamycin family and for aquayamycin-containing angucycline antibiotics in general
- Author
-
Györgyi Udvarnoki, Juergen Rohr, Reinhard Machinek, and Thomas Henkel
- Subjects
Aquayamycin ,biology ,medicine.drug_class ,Streptomycetaceae ,Stereochemistry ,Organic Chemistry ,Antibiotics ,Streptomyces fradiae ,biology.organism_classification ,chemistry.chemical_compound ,Oxygen atom ,Biosynthesis ,chemistry ,medicine ,Moiety ,Actinomycetales - Abstract
Experiments with 18 O 2 and [1- 13 C, 18 O 2 ]acetate determined the biosynthetic origin of the oxygen atoms of aquayamycin (1), which is the aglycon moiety of the urdamycins A (2, kerriamycin B) and G (3, OM 4842) and the most frequently occuring aglycon among the angucyclines
- Published
- 1992
29. Total synthesis of angucyclines. Part 16: 8-Deoxy-urdamycinone F, a nonaromatic angucycline antibiotic of the aquayamycin type
- Author
-
Peter Frese and Karsten Krohn
- Subjects
Aquayamycin ,Hydroquinone dimethyl ether ,medicine.drug_class ,Stereochemistry ,Organic Chemistry ,Antibiotics ,food and beverages ,Total synthesis ,Biochemistry ,Hydroxylation ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,medicine - Abstract
CAN oxidation (in two steps) of the hydroquinone dimethyl ether 1 gave a hydroxylation product 4 , identical in substitution pattern and relative stereochemistry with the quinoid part of urdamycinone F ( 6 ).
- Published
- 2001
30. Kerriamycins A, B and C, New Isotetracenone Antibiotics
- Author
-
Kazuo Furihata, Kazuyoshi Adachi, Haruo Seto, Noboru Otake, Takafumi Iwakiri, Yoichi Hayakawa, and Kanji Imamura
- Subjects
Aquayamycin ,biology ,medicine.drug_class ,Stereochemistry ,Chemistry ,Antibiotics ,Chromophore ,biology.organism_classification ,General Biochemistry, Genetics and Molecular Biology ,Ehrlich ascites carcinoma ,chemistry.chemical_compound ,Biochemistry ,medicine ,Spectral analysis ,General Agricultural and Biological Sciences ,Streptomyces violaceolatus ,Chemical decomposition ,Bacteria - Abstract
Three new antibiotics were obtained from the culture filtrate of an actinomycete identified as Streptomyces violaceolatus, and were named kerriamycins A, B and C, respectively. The structures of these kerriamycins were elucidated by NMR spectral analysis and chemical degradation, which revealed that each kerriamycin was composed of a common chromophore identified as aquayamycin and two or three mols of hexoses. The kerriamycins inhibited the growth of Gram-positive bacteria and prolonged the survival periods of mice bearing Ehrlich ascites carcinoma.
- Published
- 1987
31. The absolute configuration of P-1894B, a potent prolyl hydroxylase inhibitor
- Author
-
Eiji Mizuta, Hisayoshi Okazaki, Toyokazu Kishi, and Kazuhiko Ohta
- Subjects
chemistry.chemical_classification ,Aquayamycin ,Stereochemistry ,Absolute configuration ,General Chemistry ,General Medicine ,chemistry.chemical_compound ,Aglycone ,chemistry ,Drug Discovery ,Monosaccharide ,Streptomyces albogriseolus ,Catalytic hydrogenation ,Chemical decomposition - Abstract
The previous X-ray-crystallographic determination of the relative configuration of P-1894B, a potent prolyl hydroxylase inhibitor isolated from the culture broth of Streptomyces albogriseolus, was extended by means of chemical and spectral studies. The absolute configuration of P-1894B (1) was established from the absolute configuration of two constituent monosaccharides, L-aculose (3) and L-rhodinose (4), produced by chemical degradation of 1. The absolute configuration of the aglycone part (aquayamycin) was also established as 2. The stereostructure of the reduction product (11) obtained by the catalytic hydrogenation of 1 was also elucidated.
- Published
- 1984
32. Metabolic products of microorganisms. 234 Urdamycins, new angucycline antibiotics from Streptomyces fradiae. I Isolation, characterization and biological properties
- Author
-
Hans Zähner, Axel Zeeck, Jürgen Rohr, and Hannelore Drautz
- Subjects
Aquayamycin ,Magnetic Resonance Spectroscopy ,Chemical Phenomena ,Stereochemistry ,Anthraquinones ,010402 general chemistry ,01 natural sciences ,Mice ,chemistry.chemical_compound ,Drug Discovery ,Animals ,Glycosides ,Antibacterial agent ,Pharmacology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Streptomycetaceae ,Glycoside ,Streptomyces fradiae ,biology.organism_classification ,Streptomyces ,Anti-Bacterial Agents ,3. Good health ,0104 chemical sciences ,Chemistry ,Aminoglycosides ,Aglycone ,chemistry ,Fermentation ,Actinomycetales ,Bacteria - Abstract
The colored urdamycins A to F, six new angucycline antibiotics produced by Streptomyces fradiae strain Tü 2717, were detected by chemical screening. They are biologically active against Gram-positive bacteria and stem cells of murine L1210 leukemia. The urdamycins are glycosides and differ in their aglycones, which can be liberated by acidic hydrolysis besides the sugars D-olivose and L-rhodinose. The structure of the main compound, urdamycin A, follows from the spectroscopic and chemical data in connection with an X-ray analysis. The aglycone urdamycinone A is identical with aquayamycin. The structures of urdamycin B, E, F and partial structures of urdamycin C and D, will be presented in a subsequent paper. The new term "angucycline/angucyclinone" is used for an increasing group of related antibiotics.
- Published
- 1986
33. The absolute configuration of P-1894B (vineomycin A1), a potent prolyl hydroxylase inhibitor
- Author
-
Hisayoshi Okazaki, Kazuhiko Ohta, and Toyokazu Kishi
- Subjects
Aquayamycin ,chemistry.chemical_compound ,biology ,chemistry ,Enzyme inhibitor ,Stereochemistry ,Drug Discovery ,biology.protein ,Absolute configuration ,General Chemistry ,General Medicine ,Sugar ,Chemical decomposition - Abstract
The absolute configuration of P-1894B (vineomycin A1 (I)), a potent prolyl hydroxylase inhibitor, has been established as I from the absolute configuration of two sugar moieties (II, VI) obtained by chemical degradation of I.
- Published
- 1982
34. Inhibition of brain tryptophan 5-monooxygenase by aquayamycin
- Author
-
Hamao Umezawa, Hitoshi Fujisawa, Sachiko Okuno, and Osamu Hayaishi
- Subjects
Oxygenase ,Aquayamycin ,Hydrolases ,Stereochemistry ,Iron ,Guinea Pigs ,Biophysics ,Ascorbic Acid ,Acetates ,Benzoates ,Biochemistry ,chemistry.chemical_compound ,Lysine monooxygenase ,Benz(a)Anthracenes ,Animals ,Sulfhydryl Compounds ,Molecular Biology ,Carbon Isotopes ,Chemistry ,Lysine ,Pteridines ,Imidazoles ,Tryptophan ,Substrate (chemistry) ,Cell Biology ,Monooxygenase ,Tryptophan Oxygenase ,Anti-Bacterial Agents ,Kinetics ,Metapyrocatechase ,Oxygenases ,Brain Stem - Abstract
Aquayamycin inhibits partially purified tryptophan 5-monooxygenase of guinea-pig brainstem about 40 and 80% at 0.1 and 1 μM respectively. The inhibition is not competitive with respect to substrate, DMPH4∗∗ or Fe++ but is reversed by DTT∗∗. Tryptophan 2,3-dioxygenase was also inhibited almost completely at 2 μM, but other oxygenases including metapyrocatechase, protocatechuate 3,4-dioxygenase, lysine monooxygenase and imidazoleacetate monooxygenase were not inhibited at all at 1 μM.
- Published
- 1970
35. STUDIES ON A NEW ANTIBIOTIC PIGMENT, AQUAYAMYCIN
- Author
-
Saburo Ayukawa, Hamao Umezawa, Takeshi Hara, Tomio Takeuchi, Masa Hamada, Toshiharu Nagatsu, Masaji Sezaki, and Yoshiro Okami
- Subjects
Spores ,Aquayamycin ,Magnetic Resonance Spectroscopy ,Infrared Rays ,Ultraviolet Rays ,medicine.drug_class ,Gram-positive bacteria ,Antibiotics ,Rat Sarcoma ,Orange (colour) ,Microbiology ,Mice ,chemistry.chemical_compound ,Tissue culture ,Pigment ,Culture Techniques ,Drug Discovery ,medicine ,Animals ,Carcinoma, Ehrlich Tumor ,Sarcoma, Yoshida ,Hydroxyquinone ,Pharmacology ,Antibiotics, Antineoplastic ,Bacteria ,biology ,Spectrum Analysis ,Pigments, Biological ,biology.organism_classification ,Streptomyces ,Culture Media ,Rats ,Microscopy, Electron ,chemistry ,Biochemistry ,visual_art ,visual_art.visual_art_medium ,Chromatography, Thin Layer - Abstract
A new antibiotic pigment named aquayamycin, which inhibits growth of Gram positive bacteria, Ehrlich carcinoma in mice, and Yoshida rat sarcoma cells in tissue culture, was isolated from Streptomyces misawanensis nov. sp. Hamada et Okami. It was obtained as orange yellow crystals having the molecular formula C30-31H34-40O12. From the physical and chemical properties, aquayamycin was concluded to be a new antibiotic pigment of hydroxyquinone structure.
- Published
- 1968
36. Chemistry of enzyme inhibitors of microbial origin
- Author
-
H. Umezawa
- Subjects
Aquayamycin ,Chemical Phenomena ,Tyrosine 3-Monooxygenase ,General Chemical Engineering ,Neuraminidase ,Dopamine beta-Hydroxylase ,Structure-Activity Relationship ,chemistry.chemical_compound ,Papain ,Chymotrypsin ,Enzyme Inhibitors ,chemistry.chemical_classification ,biology ,General Chemistry ,Dopastin ,Pepsin A ,Anti-Bacterial Agents ,Culture Media ,Chemistry ,Enzyme ,chemistry ,Biochemistry ,Oudenone ,biology.protein ,Antipain ,Trypsin Inhibitors ,Oligopeptides ,Pepstatin ,Fusaric acid - Abstract
Study of antibiotics has furnished interesting materials to chemistry of natural products. I initiated the screening study of enzyme inhibitors produced by microorganisms and isolated leupeptin and antipain inhibiting trypsin and papain, chymostatin inhibiting chymotrypsin, pepstatin inhibiting pepsin, panosialin inhibiting sialidases, oudenone inhibiting tyrosine hydroxylase, dopastin inhibiting dopamine 3-hydroxylase, aquayamycin and chrothiomycin inhibiting tyrosine hydroxylase and dopamine J3-hydroxylase. Structures and syntheses of most of these compounds have been studied. I also found dopamine 3-hydroxylase-inhibiting activity of fusaric acid and oosponol, and xanthineoxidase inhibiting activity of 5-formyluracil which were produced by microorganisms. Chemical study of enzyme inhibitors has given useful information on the structure/activity relation. The effect of pepstatin on stomach ulcer, and the hypotensive effect of oudenone and fusaric acid have been observed clinically. Enzyme inhibitors produced by microorganisms are the most valuable new area extended from antibiotics and will furnish new materials interesting in chemistry. biosynthesis, pharmacology, and utility. Research on antibiotics has contributed to the chemistry of natural products, furnishing materials of interesting structures, chemical syntheses, biosyntheses and of interesting bioactivity. However, because the field has been so extensively studied, the probability of discovering new antibiotics, especially new and useful agents, is now significantly reduced. In these circumstances, it is felt that the most valuable contribution would be to extend these studies to a new and potentially more fruitful area. In 1965, in the hope of exploiting a new area, I initiated the screening of enzyme inhibitors in culture filtrates of microorganisms, with the collaboration of Doctors Takeuchi, Aoyagi, Kondo, Maeda, Hamada, Takita and others in my laboratories, Doctor Nagatsu, Department of Biochemistry, Dental School of Aichi Gakuin University, Nagoya, and Doctor Ohno, Basic Research Laboratories, Toray Industries. At present, the structures of small molecular compounds can be determined rapidly, and their syntheses accomplished in a short period of time. This recent progress in the chemistry of natural products through the use of physical methods is a driving force in the study of enzyme inhibitors in microbial culture filtrates. The structures elucidated stimulate the study of 129
- Published
- 1973
37. INHIBITION OF DOPAMINE β-HYDROXYLASE BY AQUAYAMYCIN
- Author
-
Saburo Ayukawa, Hamao Umezawa, and Toshiharu Nagatsu
- Subjects
Pharmacology ,chemistry.chemical_classification ,Aquayamycin ,Stereochemistry ,Dopamine ,Tyramine ,Substrate (chemistry) ,Ascorbic Acid ,Inhibitory postsynaptic potential ,Ascorbic acid ,Anti-Bacterial Agents ,Mixed Function Oxygenases ,chemistry.chemical_compound ,Enzyme ,Fumarates ,chemistry ,Biochemistry ,Spectrophotometry ,Drug Discovery ,Dopamine β hydroxylase ,medicine ,Calcium ,Chelation ,medicine.drug - Abstract
Aquayamycin was found to be one of the most potent inhibitors of dopamine β-hydroxylase. Aquayamycin at 4×10-7 M inhibited the enzyme by 50% with a Ki value of 2.1×10-7 M. The inhibitionwas non-competitive with substrate and was not affected by cof actors, i.e. ascorbic acid or fumarate. The inhibitory mechanism is possibly due to chelating action of aquayamycin on protein-bound copper. However, the addition of Cu++ did not reverse the inhibition.
- Published
- 1968
38. Function of glycosyltransferase genes involved in urdamycin A biosynthesis
- Author
-
G. Weitnauer, Eva Künzel, Andreas Bechthold, Lucia Westrich, Axel Trefzer, Sigrid Stockert, Ku U. Bindseil, Uwe Rix, Jürgen Rohr, J. Fuchser, and D. Hoffmeister
- Subjects
Aquayamycin ,Genetic Vectors ,Molecular Sequence Data ,Clinical Biochemistry ,Mutant ,Anthraquinones ,Biology ,Biochemistry ,chemistry.chemical_compound ,Bacterial Proteins ,Biosynthesis ,Drug Discovery ,Gene cluster ,Glycosyltransferase ,Urdamycin ,Cloning, Molecular ,Frameshift Mutation ,Molecular Biology ,Gene ,Pharmacology ,Deoxysugar ,Antibiotics, Antineoplastic ,Glycosyltransferase Gene ,Angucycline antibiotics ,Glycosyltransferases ,Sequence Analysis, DNA ,General Medicine ,Streptomyces fradiae ,biology.organism_classification ,Streptomyces ,Anti-Bacterial Agents ,Aminoglycosides ,chemistry ,Multigene Family ,biology.protein ,Molecular Medicine ,Gene Deletion - Abstract
Background: Urdamycin A, the principle product of Streptomyces fradiae Tu2717, is an angucycline-type antibiotic. The polyketide-derived aglycone moiety is glycosylated at two positions, but only limited information is available about glycosyltransferases involved in urdamycin biosynthesis. Results: To determine the function of three glycosyltransferase genes in the urdamycin biosynthetic gene cluster, we have carried out gene inactivation and expression experiments. Inactivation of urdGT1a resulted in the predominant accumulation of urdamycin B. A mutant lacking urdGT1b and urdGT1c mainly produced compound 100-2. When urdGT1c was expressed in the urdGT1b / urdGT1c double mutant, urdamycin G and urdamycin A were detected. The mutant lacking all three genes mainly accumulated aquayamycin and urdamycinone B. Expression of urdGT1c in the triple mutant led to the formation of compound 100-1, whereas expression of urdGT1a resulted in the formation of compound 100-2. Co-expression of urdGT1b and urdGT1c resulted in the production of 12b-derhodinosyl-urdamycin A, and co-expression of urdGT1a , urdGT1b and urdGT1c resulted in the formation of urdamycin A. Conclusions: Analysis of glycosyltransferase genes of the urdamycin biosynthetic gene cluster led to an unambiguous assignment of each glycosyltransferase to a certain biosynthetic saccharide attachment step.
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- View/download PDF
39. Identification of the aglycon part of vineomycin A1 with aquayamycin
- Author
-
Omura Satoshi, Haruo Tanaka, Nobutaka Imamura, Nobuo Ikekawa, and Katsumi Kakinuma
- Subjects
Hydrolysis ,Aquayamycin ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Stereochemistry ,Drug Discovery ,Streptomyces matensis ,Identification (biology) ,General Chemistry ,General Medicine - Abstract
Vineomycin A1 (formerly OS-4742 A1) produced by Streptomyces matensis subsp. vineus, is an antibacterial and antitumor antibiotic. The aglycon part obtained by mild hydrolysis turned out to be identical with aquayamycin, and its 13C-NMR assignment was also determined.
- Published
- 1981
40. Saquayamycins, new aquayamycin-group antibiotics
- Author
-
Masaya Imoto, Yoshinowri Watanabe, Takeshi Uchida, Keiko Miura, Toshiko Dobashi, Masa Hamada, Hamao Umezawa, Tomio Takeuchi, Naoko Matsuda, Tsutomu Sawa, and Hiroshi Naganawa
- Subjects
Aquayamycin ,Chemical Phenomena ,medicine.drug_class ,Antibiotics ,Anthraquinones ,Streptomyces ,Microbiology ,chemistry.chemical_compound ,Streptomyces nodosus ,Drug Discovery ,medicine ,Animals ,Antibacterial agent ,Pharmacology ,chemistry.chemical_classification ,Antibiotics, Antineoplastic ,biology ,Bacteria ,Leukemia P388 ,Glycoside ,biology.organism_classification ,Chemistry ,chemistry ,Biochemistry ,Fermentation - Abstract
From the culture broth of Streptomyces nodosus MH190-16F3, four new antibiotics have been isolated, and named saquayamycins A, B, C and D. The compounds are glycosides of aquayamycin, and among aquayamycin-group antibiotics they are most closely related to P-1894B (vineomycin A1). All saquayamycins act on Gram-positive bacteria and inhibit the growth of adriamycin-sensitive and adriamycin-resistant P388 leukemia cells.
- Published
- 1985
41. Biosynthesis of vineomycins A1 and B2
- Author
-
Satoshi Omura, Katsumi Kakinuma, Nobuo Ikekawa, Haruo Tanaka, and Nobutaka Imamura
- Subjects
Pharmacology ,Aquayamycin ,Antibiotics, Antineoplastic ,Magnetic Resonance Spectroscopy ,Chemical Phenomena ,Stereochemistry ,Chemistry ,Decarboxylation ,Metabolite ,Streptomyces matensis ,Anthraquinones ,Nuclear magnetic resonance spectroscopy ,Anthraquinone ,Streptomyces ,chemistry.chemical_compound ,Biosynthesis ,Drug Discovery ,Bond cleavage - Abstract
Biosynthetic studies of the antibacterial and antitumor antibiotics vineomycins A1 (1) and B2 (2), produced by Streptomyces matensis subsp. vineus, were carried out by labeling experiments with [1-13C]- and [1,2-18C2]sodium acetate followed by 18C NMR spectroscopy. The results show that the benz[a]anthraquinone chromophore of 1 is derived from a decacetate metabolite with decarboxylation at the carboxyl end and that 2 is formed via C-C bond cleavage of 1. Isolation of rabelomycin from the fermentation broth of the same strain suggests a close biosynthetic relationship among the simple benz[a]anthraquinone antibiotics such as rabelomycin, tetrangomycin, aquayamycin, a C-glycosylated benz[a]anthraquinone, and vineomycins. These biosynthetic data prompted us to reconsider the previously published structure of the antibiotic SS-228Y, which has not been revised.
- Published
- 1982
42. The structure of aquayamycin
- Author
-
H. Umezawa, M. Sezaki, K. Maeda, S. Kondo, and M. Ohno
- Subjects
Aquayamycin ,chemistry.chemical_compound ,Chemistry ,chemistry ,Chemical Phenomena ,Organic Chemistry ,Drug Discovery ,Benz(a)Anthracenes ,Biochemistry ,Combinatorial chemistry ,Derivative (chemistry) ,Anti-Bacterial Agents - Abstract
The structure of a new antibiotic, aquayamycin, has been established as derivative of benze[ a ]-anthracene by spectroscopic and degradative experiments.
- Published
- 1970
43. Inhibition of tyrosine hydroxylase by aquayamycin
- Author
-
Masaji Sezaki, Hamao Umezawa, Tomio Takeuchi, Saburo Ayukawa, Toshiharu Nagatsu, and Takeshi Hara
- Subjects
Pharmacology ,Aquayamycin ,Carbon Isotopes ,Chromatography ,Strong inhibitor ,Tyrosine hydroxylase ,Chemistry ,Iron ,Molecular biology ,Anti-Bacterial Agents ,Mixed Function Oxygenases ,chemistry.chemical_compound ,Spectrophotometry ,Drug Discovery ,Tyrosine - Abstract
Aquayamycin was found to be a strong inhibitor of tyrosine hydroxylase. It inhibits tyrosine hydroxylase by 50 % at 3.7×10-7M. The inhibition is noncompetitive with tyrosine. The inhibition by 4×10-7 Maquayamycin increases when the concentration of 2-amino-4-hydroxy-6, 7-dimethyltetrahydropteridine is increased from 2×10-4M to 1×10-3M. The inhibition of tyrosine hydroxylase by aquayamycin is reversed by Fe++.
- Published
- 1968
44. The mechanism of inhibition of tryptophan 2,3-dioxygenase by aquayamycin
- Author
-
Sachiko Okuno, Hitoshi Fujisawa, and Mitsuhiro Nozaki
- Subjects
Aquayamycin ,Chemical Phenomena ,Light ,Stereochemistry ,Biophysics ,chemistry.chemical_element ,Ascorbic Acid ,Biochemistry ,Oxygen ,Ferrous ,chemistry.chemical_compound ,Pseudomonas ,medicine ,Benz(a)Anthracenes ,Sulfites ,Molecular Biology ,Pyrans ,chemistry.chemical_classification ,Chemistry ,Tryptophan ,Substrate (chemistry) ,Cell Biology ,Ascorbic acid ,Anti-Bacterial Agents ,Radiation Effects ,Kinetics ,Enzyme ,Spectrophotometry ,Oxygenases ,Ferric ,Oxidation-Reduction ,medicine.drug ,Polarography - Abstract
Summary The ferric form of tryptophan 2,3-dioxygenase was strongly inhibited by aquayamycin at 1.5 μ M , when assayed spectrophotometrically by following the formation of the product in the presence of ascorbic acid. This inhibition appears to be attributable to the exhaustion of oxygen in the incubation mixture due to a rapid oxidation of ascorbic acid, which was stimulated by aquayamycin. The ferrous form of the enzyme was also inhibited about 70% by aquayamycin at 15 μ M . The latter inhibition was found to be competitive with respect to the substrate, tryptophan. Mechanisms of the inhibition of tryptophan 2,3-dioxygenase by aquayamycin is discussed.
- Published
- 1971
45. [Untitled]
- Subjects
0301 basic medicine ,Microbiology (medical) ,Aquayamycin ,biology ,010405 organic chemistry ,biology.organism_classification ,01 natural sciences ,Microbiology ,Streptomyces ,0104 chemical sciences ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Aglycone ,chemistry ,Biosynthesis ,Biochemistry ,Virology ,Glycosyltransferase ,Gene cluster ,biology.protein ,Heterologous expression ,Gene - Abstract
Natural products produced by bacteria found in unusual and poorly studied ecosystems, such as Lake Baikal, represent a promising source of new valuable drug leads. Here we report the isolation of a new Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk Benedictia baicalensis. In the course of an activity guided screening three new angucyclines, named baikalomycins A–C, were isolated and characterized, highlighting the potential of poorly investigated ecological niches. Besides that, the strain was found to accumulate large quantities of rabelomycin and 5-hydroxy-rabelomycin, known shunt products in angucyclines biosynthesis. Baikalomycins A–C demonstrated varying degrees of anticancer activity. Rabelomycin and 5-hydroxy-rabelomycin further demonstrated antiproliferative activities. The structure elucidation showed that baikalomycin A is a modified aquayamycin with β-d-amicetose and two additional hydroxyl groups at unusual positions (6a and 12a) of aglycone. Baikalomycins B and C have alternating second sugars attached, α-l-amicetose and α-l-aculose, respectively. The gene cluster for baikalomycins biosynthesis was identified by genome mining, cloned using a transformation-associated recombination technique and successfully expressed in S. albus J1074. It contains a typical set of genes responsible for an angucycline core assembly, all necessary genes for the deoxy sugars biosynthesis, and three genes coding for the glycosyltransferase enzymes. Heterologous expression and deletion experiments allowed to assign the function of glycosyltransferases involved in the decoration of baikalomycins aglycone.
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