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. 36, No. 6, 1993
Published online:
■ One-Pot Synthesis of Heterocage Compounds
Akikazu Kakehi* and Suketaka Ito
*Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan
Abstract
The reaction of some pyridinium 1-(methylthiothiocarbonyl)methylides bearing an ethoxycarbonyl group at the ylidic carbanion with dimethyl acetylenedicarboxylate in chloroform at room temperature gave smoothly 3-methylthio-4-thia-1-azatetracyclo[5.4.0.05,11.06,8]undeca-2,9-diene-2,5,6-tricarboxylic esters in moderate yields.
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■ Asymmetric Synthesis of α-Substituted 5-Hydroxytryptophan Derivatives
David Crich* and Linda B. L. Lim
*Department of Chemistry (M/C 111), University of Illinois at Chicago, 801 West Taylor St. , Chicago, IL 60607-7061, U.S.A.
Abstract
5-Hydroxytryptophan was converted to pyrroloindole (3), which on deprotonation with LDA and subsequent reaction with alkyl halides gave the C-2 alkylated derivatives (6-9) cleanly with retention of configuration. Reversion to the 5-hydroxytryptophan skeleton was then achieved by stirring in trifluoroacetic acid and deprotection by treatment with sodium in liquid ammonia followed by saponification.
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■ An Approach to Optically Active Pyrrolizidines by an Intramolecular Michael Reaction
Tatsunori Sato, Ken-ichiro Matsubayashi, Katsuhiro Tsujimoto, and Masazumi Ikeda*
*Kyoto Pharmaceutical University, Misasagi-Shichonocho, Yamashina, Kyorto 607-8414, Japan
Abstract
Treatment of a diastereomeric mixture (5:3) of the α-phenylsulfinylacetamide (3) with a catalytic amount of sodium ethoxide in ethanol at 0 °C for 10 min gave the bicyclic lactams (4a) and (4b) in high total yield but with extensive racemization. The cyclization of the diastereomerically pure sulfoxide (3) followed by chromatographic separation of the resulting lactams (4a) and (4b) and desulfurization of each lactam gave (1S,8S)-(-)- and (1R,8R)-(+)-ethyl hexahydro-3-oxo-3H-pyrrolizin-1-ylacetates (6), respectively. The (-)-isomers of 6 has already been transformed into (-)-trachelanthamidine (8).
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■ 3-Aryl-3H-1,2-benzodithioles. Synthesis and Reaction with Dichlorocarbene and Carbenoid
Shin-ichi Chida and Ryu Sato*
*Department of Applied Chemistry and Molecular Science, Faculty of Engineering, Iwate University, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan
Abstract
New stabel 3H-1,2-benzodithiole derivatives, 3-aryl-3H-1,2-benzodithioles, were synthesized. While the reaction of the 3-aryl-3H-1,2-benzodithioles with CH2I2-Et2Zn gave methylene-inserted products 4-aryl-2,4-dihydro-1,3-benzodithiines, the reaction with dichlorocarbene afforded unexpected products 2-chloro-3-arylbenzo[b]thiophenes.
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■ Novel Reactions of Carbohydrate Dithianes: 1,4-Dithiepins via a 1,4-Alkoxy Relay
Sherman T. Waddell,* Timothy A. Blizzard, and George A. Doss
*Merck Research Laboratories, 50G-231, P.O. Box 2000 Rahway, NJ 07065, U.S.A.
Abstract
When heated, 1,3-dithiane derivatives of common sugars which bear a mesylate at the 5-position (and are otherwise O-methylated) form 1,4-dithiepins by a novel mechanism in which ring expansion is coordinated with intramolecular relay of the 2-alkoxy group to the 5 position. Addition of a nucleophile such as azide to the reaction produces novel structures resulting from the trapping of intermediates along the pathway.
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■ Reactivity of Isoquinoline Alkaloids with Benzyne
Manuel Paz, Carlos Saá, Enrique Guitián, Luis Castedo,* and José Manuel Saá
*Departamento de Química Orgánica, Sección de Alcaloides del C.S.I.C, Facultad de Química, Universidad de Santiago, 15706 Santiago de Compostela, Spain
Abstract
Benzyne reacts with tertiary aporphines, benzylisoquinolines and cularines by successive β and α eliminations, giving rise to N,N-diphenylarylethylamines. Secondary aporphines (noraporphines) yield N-phenylnoraporphines. Whereas dehydroaporphines undergo α elimination, the corresponding nordehydroaporphines suffer both C and N phenylations by way of an ene reaction followed by N-phenylation of the resulting 7-phenyldehydronoraporphine (aporphine numbering).
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■ An Investigation on the Use of Furan Derivatives to Obtain Thermotropic Compounds
Giovanna Costa, Alessandro Gandini,* Sergio Morinelli, and Barbara Valenti
*Materiaux Polymères, Ecole Française de Papeterie et des Industries Graphiques (INPG), BP 65 - 38402 Saint Martin d’Hères, France
Abstract
A systematic investigation of the mesogenic potential of furan derivatives in terms of geometrical and polar structural characteristics has been carried out. Symmetrical compounds obtained from furancarboxylic acids and hydroquinone or 4,4’-dihydroxybiphenyl, and from 2,5-furandicarboxylic acid and several paraalkoxyphenols were prepared, in order to obtain esters bearing furan rings either in the terminal or in the central position. When the furan ring is the core of the molecule geometric features play a predominant role on the thermal behavior and the mesophase formation is inhibited. When the furan heterocycles are appended to an aromatic core the detrimental role is less manifest, but still present, as shown by comparing the thermal properties of furan derivatives with those of the corresponding fully aromatic compounds.
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■ Synthesis and Characterization of a Series of 5H-Benzo[a]phenoxazin-5-one Derivatives as Potential Antiviral/Antitumor Agents
Kanti G. Bhansali* and Alan M. Kook
*College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas 77251, U.S.A.
Abstract
A series of 1,2-benzo-3-phenoxazone also known as 5H-benzo[a]phenoxazin-5-one (1a-1c) were synthesized and characterized by 1- and 2-D nmr, mass spectrometry and computer simulation on readily available, inexpensive software. It is proposed that these molecules intercalated in GC rich DNA regions and that internal hydrogen bonding caused by a molecule of water in the salt will help to anchor these actinomycin D-like antibiotic into these locations.
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■ N-Sulfonylbenzotriazoles. Part 2. Reactions of 1,1’-Sulfonyldibenzotriazole and 1-Benzenesulfonyl-1,2,4-triazole with Alcohols; a New Approach to N-Alkylbenzotriazoles and N-Alkyl-1,2,4-triazoles
Alan R. Katritzky,* Gui-Fen Zhang, Juliuzs Pernak, and Wei-Qiang Fan
*Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-2046, U.S.A.
Abstract
1,1’-Sulfonyldibenzotriazole (3) reacts with sodium alkoxides to give N-alkylbenzotriazoles. With alkanols, benzotriazolium alkyl sulfates are produced. 1-Benzenesulfonyl-1,2,4-triazole with the sodium salts of alcohols gives 1-alkyl-1,2,4-triazoles. The mechanisms of these reactions are discussed.
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■ Preparation of a Novel Type of Ligands Incorporating Two or Three 1,3,4-Thiadiazole Units
Pedro Molina,* Alberto Tárraga, Isidora Díaz, Arturo Espinosa, and Carmen Gaspar
*Departamento de Química Orgánica, Facultad de Química, Universidad de Murcia, Campus de Espinardo, E-30071, Murcia, Spain
Abstract
The 1,3,4-thiadiazole annelation based on the reaction of acyl chlorides with methyl 2-methyldithiocarbazate followed by cyclization with perchloric acid and further reaction with primary amines, allows the preparation of a novel kind of ligands bearing two or three 1,3,4-thiadiazole rings connected either by an aliphatic, aromatic or heteroaromatic bridge.
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■ Progress towards a Practical Total Synthesis of Calabar Alkaloids: Total Synthesis of (-)-Esermethole and (-)-Physovenol Methyl Ether from (3S)-1,3-Dimethyl-3-carboxymethyl-5-methoxyoxindole
Qian-sheng Yu, Wei-ming Luo, Yi-qun Li, and Arnold Brossi*
*National Institute of Diabetes and Digestive and Kidney, National Institute of Health, Bethesda, MD 20892, U.S.A.
Abstract
Chemical resolution of the oxindoleacetic acid (7) with brucine in water yielded the acid (7a) of (3S)-absolute configuration. Acid (7a), in using conventional methods, was converted into nitrile (8a), lactone (9a) and amides (10a), and (11a) respectively. Amide (10a), on reduction with LAH in refluxing THF, directly yielded (-)-esermethole (12a), and amide (11a) similarly gave (-)-N1-benzylnoresermethole (13a). Reduction of ester (6a) with LAH in refluxing THF yielded (-)-physovenol methyl ether (14a).
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■ Synthesis of Indolo[1,2-b]isoquinolinediones; Reduction of 2-[(Substituted Phenyl)methylidene]-3-oxo-2,3-dihydroindole
Jean-Yves Mérour,* Simone Piroëlle, and Françoise Cossais
*Laboratoire de Chimie Bioorganique et Analytique, URA-CNRS N° 499,UFR Sciences Université d‘Orléans, 45067 Orleans Cedex 2, France
Abstract
Indolo[1,2-b]isoquinoline-5,12-dione and the isomeric 6,12-dione have been prepared respectively from 1-sulfonylindole and 1-acetyl-2-[(2-methoxycarbonylphenyl)methylidene]-3-oxo-2,3-dihydroindole; the reduction of 1-acetyl-2-[(substituted phenyl)methylidene]-3-oxo-2,3-dihydroindole and their oxygen analogs with sodium borohydride have been studied.
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■ Synthesis of Chiral 3-Substituted 2,4(1H,3H)-Quinazolinediones
Perséphone Canonne,* Mohamed Akssira,* Abdelaziz Dahdouh, Hicham Kasmi, and Mohamed Boumzebra
*Département de Chimie, Université Laval, Cité Universitaire, Québec, G1K 7P4, Canada
Abstract
2-Carbomethoxyphenyl isocyanate and 6-nitro-2-carbomethoxyphenyl isocyanate were generated in situ from half-esters, and then converted into the corresponding quinazolinediones using α-amino acids. This useful annelation process was found to be a general method for the formation of various chiral 3-substituted quinazolinediones.
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■ Synthesis of 2,3,5,6,7,8-Hexahydro-3-amino-2-thioxo[1]benzothieno[2,3-d]pyrimidin-4(1H)-one and Derivatives of the New Heterocyclic System 7,8,9,10-Tetrahydro-3H,11H-[1]benzothieno[2’,3’:4,5]pyrimido[2,1-b][1,3,4]thiadiazin-11-one
Andrea Santagati,* Maria Santagati, and Maria Modica
*Istituto di Chimica Farmaceutica e Tosshicologica, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy
Abstract
A versatile compound, 2,3,5,6,7,8-hexahydro-3-amino-2-thioxo[1]benzothieno[2,3-d]pyrimidin-4(1H)-one (4), was synthesized from ethyl 4,5,6,7-tetrahydro-2-isothiocyanato-1-benzothiophene-3-carboxylate (1). Derivatives of a heterocyclic linear system having the 1,3,4-thiadiazine ring were obtained from the key intermediate (4).
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■ Nucleophilic Substitution Reactions on Chlorinated Thiophene Derivatives as Basis for the Synthesis of Thienoanellated O,N- and S,N-Heterocycles
Isolde Puschmann and Thomas Erker*
*Institute of Pharmaceutical Chemistry, University of Vienna, Währinger Strasse 10, A-1090 Vienna, Austria
Abstract
The reactivity of 5-acetyl-2-chloro-3-nitrothiophene with amines, alcohols, thiols and bifunctional compounds, as well as reactions of methyl 5-chloro-4-nitro-2-thiophenecarboxylate with various hydrazides are described. These substitution reactions provide an easy access to thienoanellated heterocycles.
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■ A Simple and General Approach for the Synthsis of 2-Substituted 4-Ethoxycarbonylfuran
Ramesh C. Anand* and Vibha Singh
*Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India
Abstract
A four step strategy has been devised to synthesize 2-substituted 4-ethoxycarbonylfuran starting from an aldehyde.
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■ Synthesis of Pyrazino[1,2-a:4,5-a’]di[1,8]naphthyridine and Pyrazino[1,2-a][1,8]naphthyridines
Vicente Ojea and José Ma Quintela*
*Departamento de Química Fundamentale Industrial, Facultad de Ciencias, Universidad de La Coruña, Campus de A Zapateria, s/n, E-15071, La Coruña, Spain
Abstract
A series of 3-alkyl-, 3-aryl- and 3-hetarylhexahydro-1H-pyrazino[1,2-a][1,8]naphthyridines (4) were prepared from 2-(4-substituted 1-piperazinyl)-3-formylpyridines (2) by condensation with malononitrile and subsequent thermal cyclization. Octahydro[1,2-a:4,5-a’]di[1,8]naphthyridine (7) was also obtained.
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■ Agelorins A and B, and 11-Epi-fistularin-3, Three New Antibacterial Fistularin-3 Derivatives from the Tropical Marine Sponge Agelas oroides
Gabriele M. König and Anthony D. Wright*
*Department of Pharmacy, Swiss Federal Institute of Technology (ETH), Universitatstrasse 16, CH-8092, Zurich, Switzerland
Abstract
From the dichloromethane and methanol extracts of the tropical marine sponge Agelas oroides three fistularin-3 derivatives (1-3) were isolated. The structures of all isolates were determined by interpretation of their spectroscopic data. All isolates were found to show antibacterial activity.
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■ Components of the Root Bark of Morus insignis Bur. 3. Structures of Three New Isoprenylated Xanthones Morusignins I, J, and K and an Isoprenylated Flavone Morusignin L.
Yoshio Hano, Tsuyoshi Okamoto, Katsue Suzuki, Masami Negishi, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Three new isoprenylated xanthones, morusignins I (1), J (2), and K (3) as well as a new isoprenylated flavone, morusignin L (4) were isolated from the root bark of Morus insignis Bur. (Moraceae), collected in Paraguay. The structures of morusignins I -L were shown to be 1 - 4, respectively, on the basis of spectroscopic data.
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■ Aromatic Annulations via Benzotriazol-1-ylphenylthiomethane as a 1,1-Dipole Synthon Equivalent
Alan R. Katritzky,* Zhijun Yang, Jamshed N. Lam, and Darren J. Cundy
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-2046, U.S.A.
Abstract
The title compound readily deprotonates and reacts with appropriate electrophiles to form derivatives which upon subsequent treatment with Lewis acids undergo ring closure to afford fused aromatics.
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■ Substituent Influenced Alkylation of 3-Substituted 5-Hydroxypyrazoles: Claisen Rearrangement of 5-Allyoxypyrazoles
Ki-Jun Hwang,* Chan-Mo Yu, Young-Dae Gong, and Kyung-Ho Park
*Korea Research Institute of Chemical Technology, P.O.Box 9, Daedeog Danji, Daejoen 305-606, Korea
Abstract
Conspicuous substituent effects of 3-substituted 5-hydroxypyrazoles in the process of alkylation and subsequent [3,3]-sigmatropic rearrangement of the resulting alkylated products are described.
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■ Imidazole Derivatives, Part VIII. Stereoselective Formation of 1-[(E) 3-(1-Imidazolyl)-2-alkenoyl]imidazoles
Hans-Joachim Knölker* and Abdel-Aziz El-Ahl
*Institute für Organic Chemie, Universität Karlsruhe , Richard-Willstätter-Allee, 7500 Karlsruhe, Germany
Abstract
The reaction of propynoic, 2-butynoic, and 3-butynoic acids with 1,1’-carbonyldiimidazole stereoselectively provides the corresponding 1-[(E) 3-(1-imidazolyl)-2-alkenoyl]imidazoles.
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■ A Friedländer Approach to 3-Substituted 2,5,8-(1H)-Quinolinetriones
Ma del Mar Blanco, Carmen Avendaño,* Nieves Cabezas, and J. Carlos Menédez
*Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain
Abstract
An efficient method is proposed for the preparation of 3-substituted carbostyrilquinone derivatives, based on Friedländer synthesis of the 5,8-dialkoxyquinolines followed by cerium ammonium nitrate oxidative demethylation.
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■ An Alternative Method for Synthesis of the CC-1065 Pharmacophore, 1,2,7,7a-Tetrahydrocycloprop[1,2-c]indol-4-one
Yuqiang Wang and J. William Lown*
*Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
Abstract
The synthesis of the CC-1065 pharmacophore, 2-(1-methylpyrrole-2-carbonyl)-1,2,7,7a-tetrahydrocycloprop[1,2-c]indol-4-one (17), is described. The methods reported here provide an alternative route for the synthesis of compounds possessing the biologically active 1,2,7,7a-tetrahydrocycloprop[1,2-c]indol-4-one (CI) functionality.
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■ Photochemistry of Bufadienolide: Occurrence of Three Tautomers in the Photolysis of Resibufogenin
Takahiro Tanase, Nobutoshi Murakami, Akito Nagatsu, and Jinsaku Sakakibara*
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
The photolysis of resibufogenin (1) in MeOH was found to give a fairly labile mixture of three tautomers (2a-c) by the 1H nmr spectral analysis including difference NOE experiments.