HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Regular Issue
Vol. 29, No. 9, 1989
Published online:
■ Synthesis of Alkaloids, Cleistopholine, Oxylopine (Isoursuline), and Ursuline
Junko Koyama,* Teruyo OKatani, Kiyoshi Tagahara, and Hiroshi Irie
*Kobe Women’s College of Pharmacy, Motoyamakita, Higashinad, Kobe, Hyogo 658, Japan
Abstract
Synthesis of alkaloids, cleistopholine, oxylopine (isoursuline), ursuline, and related compounds by application of a method for constructing cycloalkenopyridines was described and the synthesis revealed that the structure of oxylopine should be revised to 6-hydroxy-5-methoxyonychine from 5-hydroxy-6-methoxyonychine.
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■ The Sinthesis and Chemical Properties of 11H-Cyclohepr[b]indeno[2,1-d]pyrrole
Makoto Nitta, Yukio Iino, and Kaoru Kamata*
*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
The reaction of N-(3-indenyl)iminotributylphosphorane with 2-chlorotropone gave novel 11H-cyclohept[b]indeno[2,1-d]pyrrole, which was converted to the corresponding ketone and alcohol. The chemical properties of the three compounds were studied.
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■ C3-Acylation of Indoles via C3-Lithiation Directed by the C2-Carboxyl Group
Yuusaku Yokoyama, Masahiko Uchida, and Yasuoki Murakami*
*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
N-Protected indole-2-carboxylic acid (1) was lithiated at the 3-position using sec-BuLi in the presence of an additive (HMPA) in THF, and then acylated at that position regioselectively by subsequent treatment with ester or DMF in moderate yields.
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■ A Regioselective Synthesis Method of Tri- and Tetrahalogenoindoles and Its Application for the Total Syntheses of Marine Alkaloids
Toshiharu Ohta and Masanori Somei*
*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
Various novel tri- and tetrahalogenoindole derivatives are produced based on the regioselective thallation-halogenation method. Syntheses of 2,3,4,7-tetrahalogenated type indoles, which are believed to be marine alkaloids, are achieved for the first time.
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■ Crystal Structures of Two Trimers of 1,4-Benzothiazine
Ettore Novellino,* Luciano Mayol, Francesco Chioccara, Alfonso Bavoso, Antonello Santini, and Carlo Pedone
*Facolta’ di Farmacia, Universita, Via D. Montesano, 49-80131, Italy
Abstract
Crystal and molecular structures of two diastereoisomeric trimers of 1,4-benzothiazine, the parent system of the key intermediate in biosynthesis of phaeomelanins, were unambiguously determined by nOe’s experiments and X-ray analysis.The relative configuration of the asymmetric centers has been determined. The two compounds show inverted configurations at the chiral atom C(4) leading to different overall shapes of the molecules.
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■ Improves Synthesis of (±)-Praeruptorin A and Other Khellactone Esters by Solvent-free DCC Reactions
Swati Bal-Tembe,* Dilip N. Bhedi, and Noel J. de Souza
*Department of Chemistry, Research Centre, Hoechst India Limited, Mulund, Bombay 400 080, India
Abstract
Esters of 4’-acetylkhellactone such as (+)-praeruptorin A (2) were synthesised in considerably improved yields through use of a low temoerature solvent-free DCC esterification reaction.
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■ Reactions of Ca, O-Dilithioximes with Functionalized Carbonyl Compounds. Part 1. Reaction with 1,2-Diketones
Ahmad Q. Hussein, Adil A. Jarrar, and Ahmad S. Madi
*Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan
Abstract
Cα,O-Dilithioximes 2 add to symmetrical 1,2-diketones to give the 5,6-dihydroxy-1,2-oxazine derivatives 5. Under acidic conditions.the latter heterocycles undergo dehydration accompanied by ring contraction to 5-acyl-δ’-lsoxazolines 6.
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■ Nortenuipine-2’β-N-oxide, a New Bisbenzylisoquinoline Alkaloid from Daphnandra dielsii
Ahmed M. Galal, Colin, D. Critchett, I. Ralph C. Bick, Subramaniam Sotheeswaran, Cong-yuan Gao, Fu-tyan Lin, Francis K. Duah, Emil W. Fu, Lan K. Wong, and Paul L. Schiff, Jr.*
*Department of Pharmaceutal Science, School of Pharmacy, University of Pittsburgh, University of Pittsburgh, U.S.A.
Abstract
Repeated chromatography of the nonquaternary alkaloid fraction of an extract of the bark of Daphandra dielsii Perk. (Monimiaceae) over silica gel afforded the new bisbenzylisoquinoline alkaloid (-)-nortenuipine-2’β -N-oxide (1) which was characterized by a consideration of physicochemical data and reduction to (-)-nortenuipine. In addition, seven other bisbenzylisoquinoline alkaloids of known structure were isolated and identified.
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■ Reaction of Hydrazine Derivatives with Methylsulphonyl Chloride. Synthesis of Alkenylpyrazoles
Vicente Gotor,* Rosario Brieva, Ángel Aguirre, S. García-Granda, and F. Gómez-Beltrán
*Departamento de Química Orgánica, Facultad de Química, Universidad de Oviedo, Oviedo 33071, Spain
Abstract
The reaction of hydrazine derivrtives with methylsulphonyl chloride led to new 2-methylsulphonylhydrazine derivatives which were cyclized to alkenylpyrazoles. The structure of an important product was confirmed by a X-ray analysis.
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■ Cyclisations Using Methyl(bismethylthio)sulphonium Salts. Part 6. Synthesis of 2-Methylthiomethylated Tetrahtdrofurans
Giuseppe Capozzi,* Stefano Menichetti, Mario Nicastro, and Maurizio Taddei
*Dipartimento di Chimica Organica "Ugo Schiff", Università di Firenze, Via Gino Capponi 9, I-50121 Firenze, Italy
Abstract
The reaction of methyl (bismethylthio) solphonium hexachloroantimonate (1) with δ-hydroxyalkenes (2) gives 2-methylthiomethyl-substituted tetrahydrofurans (3).
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■ New Reactivity of Stable Indole-2,3-quinodimethane Equivalents: [4+2]Cycloaddition, Cycloreversion, Sigmatropic Rearrangement, and Elimination Processes in the Reactions of 1,4-Dimethylpyrano[3,4-b]indole-3-one and 1-Methylpyrido[3,4-b]indol-3-one with CC-Dienophiles
Houshang Erfanian-Abdoust and Ulf Pindur*
*Department of Chemistry and Pharmacy, Institute of Pharmacy, University of Mainz, Saarstrasse 21, D-55122 Mainz, Germany
Abstract
The reactions of 1,4-dimethylpyrano[3,4-b]indol-3-one (1a) with tetracyanoethylene and N-phenylmaleimide give the variously functionalized carbazole derivatives 3-7 and 9-12 via [4+2] cycloaddition, [4+2] cycloreversion, and some sigmatropic rearrangements. The Diels-Alder reactions of 1-methylpyrido [3,4-b] indol-3-one (1b) with several CC-dienophiles also give rise to the interesting carbazoles 14-18. In the latter case, the primarily formed cycloadducts can be isolated and, in reactions of 1b with unsymmetrical dienophiles, the products are formed in high regioselectivities.
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■ Synthesis of a 3-Acetoxy-6-phenylpyrone and Its Conversion to a Pyrido[1,4]benzodiazepine
David J. Wustrow and Wendell Wierenga*
*The Upjohn Company, Kalamazoo, MI 49001a, U.S.A.
Abstract
3-Acetoxy-6-(2-nitro-3,4,5-trimethoxyphenyl)-4-pyrone (5) was prepared via condensation of 3-acetoxy-4-methoxy-3-buten-2-one (2) with the appropriate benzoyl chloride and acid catalyzed cyclization. The intermediate pyrone was converted to the target, 6-oxo-2,5,9,10,11-pentamethoxy-1,2,3,6-tetrahydropyrido[1,6-d][1,4]benzodiazepine (1).
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■ A Convenient One Pot Synthesis of 3-Thiosubstitutes Coumarins
Vinod Kumar Ahluwalia,* Mohamad Alauddin, Chandra Has Khanduri, and Vimal Deep Mehta
*Department of Chemistry, University of Delhi, Delhi-110 007, India
Abstract
Several 3-thiosubstituted coumarins (5) are prepared by the reaction of thioacetonitriles (2) with o-hydroxybenzaldehydes (3) in ethanol using catalytic amount of sodium hydroxide followed by acidic hydrolysis of intermediate imines (4).
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■ Synthesis of Derivatives of 3,4-Dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one
P. Kong Thoo Lin and D. M. Brown
*MRC Labratorys of Molecular Biology, Hills Road, Cambridge, CB2 2QH, U.K.
Abstract
In model experiments seeking a pyrimidine which had the hydrogen-bonding potential of both thymine and cytosine synthetic routes to the bicyclic 3,4-dihydro-6H,8H-pyrimido[4,5][1,2]oxazin-7-one 2 ring system have been investigated. 1-Methyl-5-(2-bromoefhyl)uracil 3 was converted to the 5-(2-phthalimido-oxyethyl) derivative 9 and then to the corresponding 4-triazolo derivative 10. Ammonia in dioxan afforded 6-methyl-3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one 11. The ring closure of 4-oxyimino-5-(2-chloroethyl)pyrimid-2-ones was also investigated, yielding 1,6-dimethyl- and 1-benzyl-6-methylpyrimido[4,5-c][1,2]oxazin-7-one, but not the parent structure 11.
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■ Nitrosation of 1-Alkylisoquinolines and Their N-Oxides and Configurational Assignments of Their Oximes
Yoshinobu Tagawa, Hiromi Arakawa, and Yoshinobu Goto*
*Faculty of Pharmaceutical Sciences, Fukuoka University, Nakamura, Jonan-ku, Fukuoka, 814-0180, Japan
Abstract
Nitrosation of 1-methyl-, 1-ethylisoquinoline and their N-oxides with alkyl nitrite was studied under various conditions, and the following three systems, (t-BuONO and t-BuOK in THF), (t-BuONO and t-BuOK in liq. NH3) and (t-BuONO and n-BuLi-t-BuOK in THF), were found to be generally effective for nitrosation of not only isoquinolines but also pyridine and quinoline derivatives. The δOH-δCH=N and δOH values were shown to be reliable criterions for assigning configurations of aldoximes and methylketoximes in these series. The semi-empirical molecular orbital calculations (MNDO method) about the reactivity of isoquinoline derivatives and the stability of ketoximes were in good qualitative agreement with the experimental results.
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■ Structures of Six Isoprenoid-substituted Flavonoids, Gancaonins F, G, H, I, Glycyrol, and Isoglycyrol from Xibei Licorice (Glycyrrhiza Sp.)
Toshio Fukai, Qing-Hua Wang, Taro Kitagawa, Kazunao Kusano, Taro Nomura,* and Yoichi Iitaka
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Four new isoprenoid-substituted flavonoids, gancaonins F, G, H, and I, along with two known compounds, glycyrol and isoglycyrol, were isolated from the Xibei licorice (Glycyrrhiza sp.). Structures of gancaonins F, G, H, and I were shown to be 3-6, respectively, on the basis of spectral evidence. From the X-ray crystalloqraphic analysis, spectroscopic data, and chemical evidence, the structures 1” and 2’ for isoglycyrol and glycyrol should be revised to the structures 1 and 2, respectively.
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■ Addition of Arylzirconium Tributoxides to 17-Ketosteroids
Virendra Kumar* and Malcolm R. Bell
*Sterling Winthrop Pharmaceuticals Research Division, Rensselaer, New York, 12144, U.S.A.
Abstract
Reaction of 17-oxoandrost-2,4-dieno[2,3-d]isoxazole 3 with arylzirconium tributoxides gives the corresponding C-17 aryl carbinols. Arylzirconium tributoxides are selective nucleophiles towards readily enolizable 17-ketosteroids and are less basic than lithium and Grignard reagents.
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■ Amination and Nitrosation of Quinolines and Their N-Oxides
Yoshinobu Tagawa, Toshio Yoshida, Noriko Honjo, and Yoshinobu Goto*
*Faculty of Pharmaceutical Sciences, Fukuoka University, Nakamura, Jonan-ku, Fukuoka, 814-0180, Japan
Abstract
4-Ethylquinoline 1-oxide reacted with isopropyl nitrite and sodium amide in liquid ammonia to give 2-amino-4-ethylquinoline 1-oxide as the main product. Similar amination occurred also with lepidine 1-oxide and quinoline 1-oxide, but only the corresponding oximes were formed from reactions of 4-ethylquinoline and lepidine under the same conditions. Isopropyl nitrite was shown to be most potent as oxidant compared with other oxidants used in such amination. The difference of reactivity between quinoline 1-oxides and quinolines was explained in terms of δδHBF and LUMO energies, calculated by semi-empirical molecular orbital calculation (MNDO method).
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■ Alkaloids from Cynanchum hancockianum (Maxim.) Al. Iljimski. (Asclepidaceae)
Xian Li,* Junpen Peng, Masayuki Onda, Yaeko Konda, Mieko Iguchi, and Yoshihiro Harigaya
*School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641, Japan
Abstract
Two alkaloids have been isolated from Cynanchum hancockianum (Maxim.) Al. Iljinski. (Asclepiadaceae) grown in the Inner Mongolia. These alkaloids are identified to be antofine and de-6-O-methylantofine by a combination of highresolution (1H, 400 MHz; 13C, 100.6 MHz) nmr and chiroptical (ord and cd) spectroscopy.
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■ Modified Synthesis of Monocyclic 1,2,3-Triazine and Cycloaddition Reaction with Enamine: The Application to the Synthesis of Alkaloids, Tortuosamine, N-Formyltortuosamine and N-Acetyltortuosamine
Teruyo Okatani,* Junko Koyama, and Kiyoshi Tagahara
*Kobe Women’s College of Pharmacy, Motoyamakita, Higashinad, Kobe, Hyogo 658, Japan
Abstract
Monocyclic 1,2,3-triazines were obtained by periodate oxidation of 1-aminopyrazoles in good reproducibilities and yields. The Diels-Alder reaction of 1,2,3-triazine with several enamines was carried out to afford 2,3-disubstituted pyridines. As an application of this method, we accomplished the synthesis of alkaloids, tortuosamine, N-formyltortuosamine and N-acetyltortuosamine.
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■ Synthesis of 3-Aryl-4-acetyl-1H-pyrazolo[3,4-b]pyridines and 3-Aryl-4-acetyl-1H-pyrazolo[4,3-c]pyridines
Emile BIsagni,* Marilys Rautureau, and Christiane Huel
*URA 1387 CNRS, Section de Recherche, Institut Curie, Bat 110-112, Centre Universitaire 91405 Orsay, France
Abstract
4-Acetyl-2-chlor-3-lithiopyridine ethylene glycol ketal and 2-acetyl-4-chloro-3-lithiopyridine ethylene glycol ketal were reacted with aromatic aldehydes and oxidation of the resulting alcohols provided the corresponding 3-aroylpyridines. These intermediates were transformed by hydrazine hydrate to 4-acetyl-3-aryl-1H-pyrazolo[3,4-b]- and -[4,3-c]pyridine ethylene glycol ketals, which afforded the title compounds, respectively, by acid hydrolysis.
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■ A Concise Route to (S)-Phenylalanine from (R)-Epichlorohydrin
Seiichi Takano,* Masashi Yanase, and Kunio Ogasawara
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
A concise route to (S)-phenylalanine has been established starting from (R)-epichlorohydrin.
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■ Synthesis of 2,4-Diarylthio-5-N-alkyl-N-phenylaminooxazoles. A Novel Class of Oxazole Derivatives
Ricardo Bossio, Stefano Marcaccini,* Robert Pepino, Cecilia Polo, and Tomás Torroba
*Dipartimento di Chimica Organica "Ugo Schiff", Università di Firenze, Via Gino Capponi 9, I-50121 Firenze, Italy
Abstract
The reaction between N-alkylisocyanoacetanilides, arylsulfenyl chlorides and NEt3 afforded 2,4-diarylthio-5-N-aIkyI-N-phenylaminooxazoIes, a hitherto unknown class of oxazole derivatives.
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■ The Practical Synthsis of N-Protected Allylamine: The Isoxazoline Route to Statine Analogue
Takahide Nishi* and Yasuhiro Morisawa
*Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Abstract
The facile, practical synthesis of optically active N-protected allylamine from α-amino acid is described. The evolution of this work in the synthesis of statine analogue using [3+2] cycloaddition reaction is detailed.
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■ Synthesis of 1-Arylthiocarbonyl-4-isopropylamino-2,5-dihydro-1H-imidazole-2-thiones, a Novel Class of Imidazole Derivatives
Ricardo Bossio,* Stefano Marcaccini, Roberto Pepino, Cecilia Polo, Tomás Torroba, and Giovanni Valle
*Dipartimento di Chimica Organica "Ugo Schiff", Università di Firenze, Via Gino Capponi 9, I-50121 Firenze, Italy
Abstract
The reaction between N-isopropylisocyanoacetamide (IV) and arylsulfenyl thiocyanates (IIIa-e) provides a useful route to 1-arylthiocarbonyl-4-isopropylamino-2,5-dihydro-1H-imidazole-2-thiones (Va-e), a novel class of imidazole derivatives, whose structure was determined by X-ray analysis.
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■ Enantiodivergent Synthesis of Both Enantiomers of Ibuprofen from (2S,3S)-3-Phenylglycidol
Seiichi Takano,* Masashi Yanase, and Kunio Ogasawara
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Enantiodivergent synthesis of both enantiomers of ibuprofen, a potent orally active anti-inflammatory agent, has been first established using (2S,3S)-3-phenylglycidol as a common starting material.