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. 45, No. 9, 1997
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■ The First Syntheses of Antiviral, Cytotoxic 6-Cyano-5-methoxy- and -12-methylindolo[2,3-a]carbazoles, and Related Indolo[2,3-a]carbazoles from Indigo
Hiroyuki Hayashi, Shinobu Ohmoto, and Masanori Somei*
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
The first simple total syntheses of 6-cyano-5-methoxy- (1a) and -12-methylindolo[2,3-a]carbazole (1b) are attained from indigo (2) in only five and six steps, respectively. Preparations of 5-hydroxy- (13), 5-bromoindolo[2,3-a]carbazole (14), and a novel spiro compound (7) are also included.
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■ 1,3-Dipolar Cycloaddition of 3-Arylidenechromanone -1-thiochromanone and -flavanone: Regio- and Stereoselective Formation of Spiroheterocycles
L'ubor Fisera,* Libuse Jarosková, Albert Lévai, Eva Jedlovská, Gábor Tóth, and Monika Poláková
*Department of Organic Chemistry, Slovak University of Technology, SK-812 37 Bratislava, Slovakia
Abstract
The cycloaddition of nitrile oxides, nitrones, and nitrile imines to 3-arylidenechromanone (1), -flavonone (5), -1-thiochromanone (2) and -1-tetralone (3) proceeds regio- and stereoselectively under the formation of spiro-substituted isoxazole and pyrazole derivatives.
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■ One-Step Transformation of 2- or 3-(1-Hydroxyalkyl)-2,3-dihydrobenzofurans to the Acylbenzofurans with N-Bromosuccinimide
Hideaki Suzuki, Hideyuki Tsutsui, Atsuyuki Kano, Satoru Katoh, Tadashi Morita, Kiyoshi Matsuda, Norihiro Iibuchi, and Masashi Ogawa*
*Central Research Division, Tobishi Pharmaceutical Co., Ltd., 1-7-1, Suehiro-cho, Ome, Tokyo, 198, Japan
Abstract
The one-step transformation of 2- or 3-(1-hydroxyalkyl)-2,3-dihydrobenzofurans (1 or 2) to the 2- or 3-acylbenzofurans (5 or 6) with N-bromosuccinimide was performed with good yields. The reaction is characterized to take place via the continuous bromination-dehydrobromination process. Yields are dependent on the solvent and the kind of additive compounds as a scavenger of the hydrogen bromide by-produced during the reaction.
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■ Asymmetric Dihydroxylation onto the α,β-Unsaturated Carboxylic Ester Derivatives of Camptothecin
Keiko Tagami,* Shuzo Takagi, Shigeki Sano, Motoo Shiro, and Yoshimitsu Nagao
*Faculty of Pharmaceutical Science, Mukogawa-Women's University, 11-68 Koushien Kyuban-Cho, Nishinomiya, Hyogo 663-8179, Japan
Abstract
Dihydroxyalkanoic ester derivatives (4a,b) and (5a,b) of 20S-camptothecin (1) were diastereoselectively synthesized by exploiting osmium-catalyzed asymmetric dihydroxylation based on the Sharpless procedure. The absolute configuration of the newly formed chiral centers, the 2’ and 3’ positions of the 20-alkanoyl side chain of 4a,b and 5a,b was determined by the chemical correlation with the known chiral dihydroxyalkanoic acids.
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■ Behaviour of N-Benzenesulphonyloxy- and N-Acetoxy-2,3-quinoxalinedicarboximides towards Some Nucleophiles
Mohamed Salah Kamel Youssef* and Mohamed Saad Abbady
*Chemistry Department, Faculty of Science, Assiut University, Assiut 71516, Egypt
Abstract
The reaction of N-benzenesulphonyloxy- and N-acetoxy-2,3-quinoxalinedicarboximides with different nucleophilic reagents have been investigated.
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■ Syntheses of N-Substituted 2,5-Piperazindiones
Antonio Rafael Tapia-Benavides,* Hugo Tlahuext, and Rosalinda Contreras*
*Centro de Investigaciones Químicas, Universidad A. del Estado de Hidalgo, Carretera Pachuca-Tulancingo Km 4.5. U. Universitaria, Pachuca Hidalgo. C.P. 42074, Mexico, D.F.
Abstract
The synthesis of 2,5-piperazindiones, 1,6-dimethoxycarbonylmethyl-2,5-piperazindione (1a), 1,6-di-α-methylbenzylcarboxamidomethyl-2,5-piperazindione (1b), 1,6-dibenzhydrylcarboxamidomethyl-2,5-piperazindione (1c) and 1,6-di-2-(1-phenylbenzimidazoyl)methyl-2,5-piperazindione (1d), is reportd. The cyclic dipeptide (1a) was obtained from the auto-condensation of the dimethyliminodiacetate promoted by triethylborane or triphenylsilane. Compounds (1b-1d) were prepared by refluxing iminodiacetic acid and the corresponding amine. The X-Ray diffraction structure of (1a) reveals boat conformation for its 2,5-piperazindione ring.
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■ Renewable Functionalized Pyridines Derived from Microbial Metabolites of the Alkaloid (S)-Nicotine
Jean-Paul Roduit, Alain Wellig, and Andreas Kiener*
*Department of Process Research, LONZA Ltd., P.O. box CH-3930 Visp, Switzerland
Abstract
(S)-Nicotine, which is present in concentrations of 2-8% in dried leaves of certain tobacco plants, was used as a starting material for the biocatalytic production of renewable functionalized pyridines. Key microbial metabolites of (S)-nicotine, such as 6-hydroxy-(S)-nicotine and 4-[(6-hydroxypyridine)-3-yl]-4-oxobutyrate were used in subsequent chemical steps for the preparation of a wide variety of 2,5-di- or 2,3,5-tri-substituted pyridines.
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■ Studies on Quinones. Part 31. Synthesis and Cyclization of Substituted 2-Acetylamino-1,4-benzoquinones
Jaime A. Valderrama* and M. Florencia González
*Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Correo 22, Santiago, Chile
Abstract
The synthesis of 4-acetylamino-5-hydroxybenzo[b]furans (7a), (7b), (13), and their oxidative furan ring opening to the corresponding substituted 2-acetylamino-1,4-beznoquinones (1a), (1b), and (2) are reported. The acid-induced cyclization of quinones (1a) and (2) to afford N-heterocyclic quinones (15) and (16) is also described.
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■ Efficient One-Pot Synthesis of 7-Azacoumarins by Knoevenagel Reaction Using Water as Reaction Medium
Gianluca Brufola, Francesco Fringuelli,* Oriana Piermatti, and Ferdinando Pizzo*
*Dipartimento di Chimica, Laboratorio di Chimica Organica, Universita de Perugia, Via Elce di Sotto 8, 06100 Perugia, Italy
Abstract
3-Substituted 5-hydroxymethyl-8-methyl-7-azacoumarins were prepared by a Knoevenagel reaction of pyridoxal hydrochloride with acetonitriles in a one-pot procedure in a water-only medium. The reactions occurred in heterogeneous phase with much better yields than those obtained in a homogeneous alcoholic medium.
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■ Studies on the Synthesis of Substituted 3,6-Dioxoperhydropyrrolo[1,2-a]pyrazines as Non-peptide Scaffolds for Peptidomimetics
Mercedes Martín-Martínez, Ma Teresa García-López, Rosario Herranz, and Rosario González-Muñiz*
*Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, E-28006 Madrid, Spain
Abstract
Intramolecular reductive amination of 4-keto diesters, derived from Z-Xaa-Yaa dipeptides, and subsequent γ-lactamization is a versatile method for the preparation of 3,6-dioxoperhydropyrrolo[1,2-a]pyrazines bearing amino acid side chains at C-1, C-4 and C-7 positions, as Xaa-Yaa-Zaa (Yaa ≠ Gly) tripeptide mimetics.
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■ Synthesis of Pyrimido[5'',4'':5',6']pyrido[2',3':4,5]thieno[2,3-c]pyridazine and Pyridazino[4',3':4,5]thieno[3,2-b][1,8]naphthyridine, New Tetraheterocyclic Ring Systems
José M. Quintela,* Ma. Carmen Veiga, Carlos Peinador, and Liliana Gonzalez
*Departamento de Química Fundamental Industrial, Facultad de Ciencias, Universidad de La Coruña, Campus de A Zapateria, s/n, E-15071, La Coruña, Spain
Abstract
Preparation of a number of pyrimido[5",4":5’,6’]pyrido[2’,3’:4,5]thieno[2,3-c]pyridazine derivatives (4a-h) has been effected by reaction of appropriately heterocyclic aminonitrile precursor (1) and N,N-dimethyldichloromethyleniminium chloride. In addition, pyridazino[4’,3’:4,5]thieno[3,2-b][1,8]naphthyridines (9a-i), were prepared via the Friedländer synthesis of the N-heteroaromatic carbaldehyde (8) with acyclic, cyclic, heterocyclic or α,β-unsaturated ketones and other active methylene compounds.
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■ Inversion of Enantioselectivity in the Diels-Alder Synthesis of 2-Azabicyclo- [2.2.1]hept-5-en-3-one from Cyclopentadiene and Chiral Sulfonyl Cyanides
José M. Blanco, Olga Caamaño, Franco Fernández,* Xerardo García-Mera, Isabel Nieto, and José E. Rodríguez-Borges
*Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15706, Santiago de Compostela, Spain
Abstract
Diels-Alder cycloaddition of (1R,3S,4S)-3-methanesulfonyl cyanide to cyclopentadiene, followed by treatment with AcOH/H2O, afforded an 11% ee of (+)-(1S)-2-azabicyclo[2.2.1]hept-5-en-3-one [(+)-ent-1]. The analogous process from (1R,3R,4S)-3-methanesulfonyl cyanide afforded an estimated 12% ee of (-)-1.
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■ The Total Synthesis of the Pavine Alkaloid Thalimonine
Varol Pabuccuoglu and Manfred Hesse*
*Organisch-chemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
Abstract
The synthesis of the pavine alkaloid (±)-thalimonine (1) by the acid-mediated cyclization of the corresponding 1,2-dihydroisoquinoline (10) is reported. The latter compound was synthesized by a multistep reaction from 4-methoxy-2,3-methylenedioxybenzaldehyde. The resolution of (±)-1 to its (-)-enantiomer was performed.
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■ Reaction of 1-Benzylindole-2,3-dicarboxylic Anhydride with Wittig Reagents
Yasuyoshi Miki,* Hiroko Hachiken, Yoshiko Sugimoto, and Norihide Yanase
*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan
Abstract
Reaction of 1-benzylindole-2,3-dicarboxylic anhydride with methylenetriphenylphosphorane (Ph3P=CH2) and carbethoxymethylenetriphenylphosphorane (Ph3P=CHCOOEt) gave [2-(3-carboxyindol-2-yl)-2-oxoethylidene]triphenylphosphorane derivatives, which were converted to cyclopenta[b]indol-3-ones after decarboxylation and treatment with aldehydes. On the other hand, the anhydride reacted with carbethoxyethylidenetriphenylphosphorane (Ph3P=C(Me)COOEt) to afford a mixture of two enol lactones.
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■ Synthesis of Hetero[1,2,4]thiadiazine 1,1-Dioxides
M. Esther Arranz, Salvador Vega,* and Juan A. Díaz
*Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, E-28006 Madrid, Spain
Abstract
The synthesis of several representatives of the new thieno- and pyrazolo[1,2,4]thiadiazine 1,1-dioxides ring systems is described. It was carried out by cyclization of the isocyanates (4) formed in the Curtius rearrangement of acyl azides (3). The reactivity of these new rings towards some electrophilic reagents was also explored.
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■ Photochemical Behaviour of Halogenoheterocyclic Derivatives. The Alternative between Arylation and Dehalogenation Reactions
Maurizio D'Auria
*Dipartamento di Chimica, Universita della Basilicata, Via N. Sauro 85, 85100 Potenza, Italy
Abstract
Semiempirical calculations on the transient intermediates involved in the irradiation of halogenoheterocyclic derivatives showed that the difference between the heat of formation of the substrates and the heat of formation of the radical intermediates derived from the cleavage of the C-X bond can be a useful parameter to justify the observed chemical behaviour towards the arylation reaction or the dehalogenation reaction.
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■ Antifeeding Limonoids from Melia toosendan
Jian-Bo Zhou, Yuji Minami, Fumio Yagi, Kenjiro Tadera, and Munehiro Nakatani*
*Department of Chemistry and Bioscience, Faculty of Science, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan
Abstract
A new limonoid, azedarachin B, with a C-19/C-29 bridged acyl acetal structure was isolated as an insect antifeedant from the root bark of Melia toosendan along with seven known limonoids. The structure of azedarachin B was elucidated by spectroscopic and chemical means and the antifeedant property was also studied.
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■ Aza-azulanones as 4π Electron Components in [4+2] Cycloaddition Reactions with a Cyclic C7H6-System
Satoshi Suzuki, Yoshihiro Fukui, Takaya Tsuchinaga, Hajime Tsunekawa, and Katsuhiro Saito*
*Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Abstract
Reactions of a cyclic C7H6-system, a tautomer of 1,2,4,6-cycloheptatetraene and 2,4,6-cycloheptatrienylidene, with N-(p-substituted phenyl)aza-azulanones afforded two types of [4+2] type cycloadducts, where the seven-membered ring moieties of the aza-azulanones played 4 π electrons parts. The reactions were investigated with terms of MO calculations.
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■ Diels-Alder Reaction of 5-Triisopropylsilyl-2-vinylfuran and 2-Triethylsilyl-4-vinylfuran. Steric Shielding by the Trialkylsilyl Group
Laura S. Avalos, Aída Benítez, Joseph M. Muchowski, Margarita Romero, and Francisco X. Talamás*
*Syntex S.A. de C.V., División de Investigación, Apartado Postal 272 (CIVAC), Jiutepec, Morelos, México, cp 62500, Mexico, D.F.
Abstract
The Diels-Alder reaction of 5-triisopropylsilyl-2-vinylfuran (1b) and 2-triethylsilyl-4-vinylfuran (4b) with acetylenic and olefinic dienophiles occurs with high site specificity in the extraannular mode to produce trialkylsilyl benzofuran derivatives.
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■ A Convenient Synthetic Entry into 7-Aza-2,2-diphenyl-2-silabicyclo[3.3.0]octane Derivatives
Dominique Damour, Fabrice Dhaleine, Anne Morgat, Marc Vuilhorgne, and Serge Mignani*
*Rhone-Poulenc Rorer S.A., Centre de Recherche de Vitry-Alfortville, 13 Quai Jules Guesde, 94400, Vitry-sur-Seine, France
Abstract
7-Aza-2,2-diphenyl-2-silabicyclo[3.3.0]octane derivatives (5-7) are obtained from intermolecular [3+2] cycloaddition reactions between 1,1-diphenyl-1-silacyclopent-2-enes (3) and (4) and the azomethine ylide (2) which was generated in situ from trimethylamine N-oxide.
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■ A New Hydroxystilbene Tetramer Named Isohopeaphenol from Vitis vinifera 'Kyohou'
Junko Ito, Masatake Niwa,* and Yoshiteru Oshima
*Faculty of Pharmacy, Meijo University, 150 Yagoto, Tempaku-ku, Nagoya, Aichi 468-8503, Japan
Abstract
A new hydroxystilbene tetramer named isohopeaphenol was isolated from the cork of Vitis vinifera ‘Kyohou’ and its structure was elucidated on the basis of spectroscopic evidence.
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■ Crude Drugs from Aquatic Plants. VI. On the Alkaloid Constituents of Chinese Nupharis Rhizoma, the Dried Rhizoma of Nuphar pumilum (TIMM.) DC. (Nymphaceae): Structures and Rearrangement Reaction of Thiohemiaminal Type Nuphar Alkaloids
Masayuki Yoshikawa,* Toshiyuki Murakami, Shuji Wakao, Atsushi Ishikado, Nobutoshi Murakami, Johji Yamahara, and Hisashi Matsuda
*Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
Abstract
From chinese Nupharis Rhizoma, the dried rhizoma of Nuphar pumilum (TIMM.) DC. (Nymphaceae), four thiohemiaminal type nuphar alkaloids with potent immunosuppressive activity, 6-hydroxythiobinupharidine, 6,6’-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B, 6’-hydroxythionuphlutine B, have been isolated together with nine inactive nuphar alkaloids. The configurations of the 6- and 6’-hydroxyl groups in those thiohemiaminal type nuphar alkaloids were confirmed on the basis of their 2D-NMR analysis. During the course of chemical elucidation of those thiaspirane type dimeric sesquiterpene alkaloids, new arragement reaction of the thiaspirane ring in thiohemiaminal type alkaloids with 6-hydoxyl group was found and the reaction pathway was discussed. By using this rearrangement reaction, 6-hydroxythionuphlutine B was chemically related with 6-hydroxythiobinupharidine, so that the absolute stereostructures of thionuphlutine B and its related compounds such as 6-hydroxythionuphlutine B, 6’-hydroxythionuphlutine B, and thionuphlutine B β-sulfoxide, were characterized.
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■ Cyclocondensation of Cyanohydrins with Aldehydes or Ketones
Jean-François Stambach,* Louis Jung, and Raymond Hug
*Laboratoire de Chimie Thérapeutique, Université Louis Pasteur, U.F.R. des Sciences Pharmaceutiques, 74, route du Rhin, BP 24, 67401 ILLKIRCH Cedex, France
Abstract
Cyanohydrins (1) are easily condensed with aldehydes or ketones (2) in anhydrous strong acidic conditions to give 1,3-oxazolidin-4-ones (3a-i) in good yields. The mechanism of this cyclocondensation is discussed.
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■ 6,12-Methanodipyrano[4,3-b:4,3-f]dioxocine-1,7-dione: The Reactivity towards Nitrogen Nucleophiles
Jan Svetlik,* Vladimir Hanus, Irene M. Lagoja, and Joachim G. Schantl
*Department of Analytical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, SK-83232 Bratislava, Slovakia
Abstract
The reaction of the title compound (1) with hydrazine hydrate induces a complex ring transformation affording 3,4,6-trimethyl-1H-indazole-7-carboxylic acid (2) and (3-methyl-1H-pyrazol-5-yl)acetic acid hydrazide (3). The product structures have been elucidated by 2D-NMR techniques, and a mechanistic rationalization of this multistep reaction is presented. Methylhydrazine converts compound (1) into (1,3-dimethyl-1H-pyrazol-5-yl)acetic acid (12), while phenyl hydrazine fails to affect 1.
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■ Synthesis of Pyrazolo[1,5-a]quinolines and Related Reduced Derivatives
David Barrett
*Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 2-1-6 Kashima, Yodogawa-ku, Osaka 532, Japan
Abstract
The synthetic approaches employed for the preparation of pyrazolo[1,5-a]quinolines and related hydrogenated derivatives are reviewed.