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. 43, No. 1, 1996
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■ Synthesis of Optically Active O,O,O-Trimethylkorupensamines A and B
A.V. Rama Rao,* Mukund K. Gurjar, D. Venkata Ramana, and Abhay K. Chheda
*Indian Institute of Chemical Technology, Hyderabad 500 007, India
Abstract
Hydrolysis of benzofuran derivative (10) with concomitant aromatisation produced the biaryl system (11). Subsequent Sharpless asymmetric epoxidation of the cinnamyl alcohol (13) gave atropisomers (14) and (15) conveniently separated by chromatography. Independent derivatisation of naphthylisoquinoline ring with 14 and 15 furnished korupensamine analogues (18) and (19). Comparison of CD spectra with those of natural products assigned the stereostructures of 18 and 19.
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■ Selective Photo-Reduction of 1-Alkylisatins in Degassed Alcoholic Solutions
Jiro Tatsugi, Kenji Ikuma, and Yasuji Izawa*
*Department of Applied Chemistry, Aichi Institute of Technology, Yakusa, Toyota 470-03, Japan
Abstract
Irradiation of 1-alkylisatins (1) in degassed alcohols afforded 1-alkyl-3-hydroxyoxindoles (2) and 1-alkyloxindoles (3) as chemoselective photoproducts.
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■ Syntheses of Optically Active, Unusual, and Biologically Important Hydroxy-Amino Acids from D-Glucosamine
Katsuo Shinozaki, Kazuhiro Mizuno, and Yukio Masaki*
*Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502, Japan
Abstract
Manipulation of D-glucosamine as a chiral pool including stereoinversion of the C3-hydroxyl group, degradation of the C6-carbon, and/or one carbon homologation at the C1-position realized chiral syntheses of (2S,3S)-dihydroxy-(4S)-amino acid moieties, important structural components of a gastroprotective substance AI-77-B and a group of antitumor substances calyculins.
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■ A New Synthetic Route to the Tetracyclic Framework of Strychnos Alkaloids via Intramolecular Aldol Reaction
Süleyman Patir,* Peter Rosenmund, and Peter H. Götz
*Department of Sciense, Faculty of Education, Hacettepe University, TR-06525 Beytepe-Ankara, Turkey
Abstract
By treatment of 2,3,4,9-tetrahydrospiro[1H-carbazole-1,2’-[1,3]dithiolan]-4(9H)-one (1) with ethanolamine, followed by reduction of the corresponding imine (6) with NaBH4 to the amine (7) and benzoylation, N-benzoyl-N-(2-hydroxyethyl)-{2,3,4,9-tetrahydrospiro-[1H-carbazole-1,2’-(1,3)dithiolan]-4-yl}amine (8) is formed, which can be deprotected to 4-[benxoyl-(2-hydroxyethyl)amino]-2,3,4,9-tetrahydro-1H-carbazol-1-one (9). Oxidation of the primary hydroxyl group yields [benzoyl-(1-oxo-2,3,4,9-tetrahydrocarbazol-1-one-4-yl)amino]acetaldehyde (10), a key-intermediate for the cyclization to 2-benzoyl-4-hydroxy-1,2,3,4,5,7-hexahydro-1,5c-methanoazocino[4,3-b]indol-6-one (11), which represents the tetracyclic skeleton of Strychnos-type alkaloids.
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■ Base Catalyzed Condensation Reaction of Malononitrile and 2-Hydroxy-1-naphthaldehyde with Different Ketones
Ahmed A. Fadda, Mohammed T. Zeimaty, Margaret M. Gerges, Hala M. Refat, and Edward R. Biehl*
*Chemistry Department, Southern Methodist University, Dallas, TX 75205, U.S.A.
Abstract
Several derivatives of 2H-phenyl[f]chromene-2-carbonitrile, 2H-benzo[f]chromano[2,3,4:d,e]pyrido[2,3-d]pyrimidine, and benzo[g]-2-quinolone were prepared by the direct condensation of malononitrile with 2-hydroxy-1-naphthaldehyde in the presence of various ketones and ammonium acetate. The effect of solvent, ratio of reactant, and different basic catalysts were studied.
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■ On the Mechanism of Formation of Pyridines from α,β-Unsaturated Nitriles and Active Cyano Compounds
Antonio Lorente,* José L. Alvarez-Barbas, José L. Soto, Pilar Gómez-Sal, and Antonio Manzanero
*Department of Organic Chemistry, University of Alcalá, 28871 Alcalá de Henares (Madrid), Spain
Abstract
The mechanism of formation of pyridines from α,β-unsaturated nitriles and active cyano compounds has been investigated. These processes proceed through a Michael adduct which undergoes a regioselective cyclization to the corresponding heterocyclic compound. The regioselectivity of the heterocyclization processes is justified.
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■ Preparation of 2,4-Imidazolidinediones (Hydantoins) from α-Keto Hemithioacetal and Ureas
Jian Ping Zou,* Zhong E Lu, Li Hua Qiu, and Ke Qian Chen
*Department of Chemistry, Suzhou University, Suzhou 215006, Jiangsu Province, The People's Republic of China
Abstract
5-Phenyl-2,4-imidazolidinedione (3a) and 1-aryl-5-phenyl-2,4-imidazolidinediones (3b-d) have been synthesized from α-keto hemithioacetal and urea or arylureas.
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■ A Friedländer Approach to Polycondensed 1,8-Naphthyridine Derivatives
José Ma. Quintela,* Rosa Ma Arcas, Carmen Veiga, Carlos Peinador, Juan Vilar, and Vicente Ojea
*Departamento de Química Fundamental Industrial, Facultad de Ciencias, Universidad de La Coruña, Campus de A Zapateira, E-15071, La Coruña, Spain
Abstract
An efficient method is proposed for the preparation of a variety of polycondensed 1,8-naphthyridines from 2-amino-3-cyano-6-ethoxy-5-formyl-4-phenylpyridine (1) by Friedländer condensation with cyclic and heterocyclic ketones.
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■ Eschenmoser Reaction: An Unexpected Route to Tetrahydrothieno[2,3-b]pyridin-3-ones and Azepan-3-ones
Patrice Marchand, Christian Bellec, Marie-Claude Fargeau-Bellassoued, Cécile Nezry, and Gérard Lhommet*
*Université Pierre et Marie Curie, Laboratoire de Chimie des Hétérocycles, associe au CNRS, 4, Place Jussieu, 75252 Paris Cedex 05, France
Abstract
Eschenmoser condensation of various commercial secondary α-bromo esters (2) with six and seven membered thiolactams (1) surprisingly gives tetrahydrothieno[2,3-b]pyidin-3-ones and azepan-3-ones and azepan-3-ones (4), while ethyl bromoacetate yields, after sulfur extrusion, the expected cyclic β-enamino esters (3).
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■ Preparation of 2-Substituted 1,3-Bis(benzotriazol-1-yl)isoindolines by the Double Mannich Condensation Reaction of o-Phthalaldehyde with Primary Amines in the Presence of 1,2,3-1H-Benzotriazole
Ichiro Takahashi,* Mikio Tsuzuki, Hiroshi Yokota, Toshio Morita, Hidehiko Kitajima, and Kimio Isa
*Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910, Japan
Abstract
The preparation of isoindolines (1,3-dihydro-2H-isoindoles) possessing two reactive centers as mixed aminals is investigated. In the double Mannich condensation reaction of o-phthalaldehyde with a variety of primary amines in the presence of 1,2,3-1H-benzotriazole (Bt-H) in MeCN, Bt-substituted isoindolines are obtained in fair to good yields when anilines are used as amines.
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■ A Synthesis for Some New Thieno[2,3-b:4,5-b']dipyridines
Ma. Carmen Veiga, José Ma. Quintela,* and Carlos Peinador
*Departamento de Química Fundamental e Industrial, Facultad de Ciencias, Universidad de La Coruña, Campus de A Zapateira, E-15071, La Coruña, Spain
Abstract
An efficient method is proposed for the preparation of substituted thieno[2,3-b:4,5-b’]dipyridines (2a-h, 3a-g, and 5a-e), based on the Friedländer synthesis of 3-amino-5-cyano-7-ethoxy-2-formyl-4-phenylthieno[2,3-b]pyridine (1) with acyclic, cyclic, heterocyclic and α,β-unsaturated ketones. In addition, the reaction of 1 with guanidine sulfate yielded the fused triheterocyclic pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidine system (6).
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■ A Short Synthetic Route to Benzofurans. Syntheses of Naturally Occurring Euparin and Related Compounds
Akihiro Sogawa, Masao Tsukayama,* Hiroshi Nozaki, and Mitsuru Nakayama
*Department of Chemical Science and Technology, Faculty of Engineering, The University of Tokushima, Minamijosanjima, Tokushima 770, Japan
Abstract
Euparin (4a) and related benzofurans (4b-e, g) were synthesized by conversion of the corresponding o-(3-hydroxy-3-methylbutynyl)phenyl tosylates (2) in the presence of base into the 2-(1-hydroxy-1-methylethyl)benzofurans (3), followed by dehydration in high yields. 2-(1-Bromo-1-methylethyl)benzofurans (5g, h) were converted into 2,2-diemethylchromenes (6g, h) in good yields.
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■ Asymmetric Synthesis of (+)- and (-)-Eptazocine via an Enzymatic Reaction
Shunsaku Shiotani*, Hirohiko Okada, Takako Yamamoto, Kumiko Nakamata, Jun Adachi, and Hiromasa Nakamoto
*Department of Chemistry, Faculty of Science, Toyama University, Gofuku 3190, Toyama 930, Japan
Abstract
Starting from (R)-3-hydroxy-2-(p-methoxybenzyl)propyl acetate (R-(+)-4) prepared by enzymatic monoacetylation of 2-(p-methoxybenzyl)propane-1,3-diol (3) with lipase PS in the presence of vinyl acetate as an acetyl donor, lactones ((+)- and (-)-6) were obtained. Using the lactones, (+)- and (-)-eptazocine were synthesized.
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■ Ring Construction of Several Heterocycles with Phosphorus Pentoxide-Methanesulfonic Acid (PPMA)
Hidetsura Cho* and Shinsuke Matsuki
*Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1, Murasaki-cho, Takatsuki, Osaka, 569, Japan
Abstract
The cyclization reactions with CH3SO3H/P2O2 (PPMA) or CF3SO3H/P2O5 (PPTMA) at 80-100 °C for 3-10 min afforded several heterocycles (6,7-dihydropyrrolo[2,3-c]azepin-4,8-(1H,5H)-dione, 4-oxo-4,5,6,7-tetrahydrothianaphthene, carbostyril derivatives).
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■ Absolute Configuration of Optical Isomers of 2-(4-Chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic Acid (Rebamipide)
Jun Matsubara, Kenji Otsubo, Seiji Morita, Tadaaki Ohtani, Yoshikazu Kawano, and Minoru Uchida*
*Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Kagasuno 463-10, Kawauchi-cho, Tokushima 771-01, Japan
Abstract
The absolute configuration of enantiomers of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid [(±)-1, rebamipide] was assigned. The key intermediate, (S)-quinoline derivative [(S)-3], was prepared by palladium-catalyzed coupling reaction of 4-iodoquinoline with organozinc compound. This quinolinylalanine derivative was also synthesized from α-amino acid derivative of 2(1H)-quinolinone [(+)-4], which was able to convert into optically active rebamipide. Therefore the absolute configuration of (+)- and (-)-rebamipide was found to be R and S, respectively.
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■ Regioselective Cyclocondensations of Chlorocarbonylsulfenyl Chloride with Hydrazones: Effective Synthesis of a Class of Sulfur and Nitrogen Containing Heterocycles with -COS- Linkage
Yoo Tanabe*, Kei Mori, and Yoshinori Nishii
*School of Science, Kwansei Gakuin University, 1-1-155 Uegahara, Nishinomiya, Hyogo 662, Japan
Abstract
Regioselective cyclocondensations of several hydrazones with chlorocarbonylsulfenyl chloride afforded 1,3,4-(3H,6H)-thiadiazin-2-one derivatives and 3(2H)-(dimethylamino)thiazolones. The -COS- linkage was effectively incorporated into the S,N-containing heterocycles.
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■ Aryl Diazinyl Ketoximes: Synthesis and Configurational Assignment
Gottfried Heinisch, Wolfgang Holzer, Thierry Langer, and Peter Lukavsky
*Institute of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria
Abstract
Preparation of a series of new aryl diazinyl ketoximes (7a,b - 12a,b) required as synthetic building blocks is described. Separation of the E/Z-isomers obtained was achieved by means of chromatography, their configuration was assigned using nmr techniques. Moreover, procedures for the synthesis of the starting ketones (1b - 6b) are given.
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■ Swartziarboreols A-E, Five New Cassane Diterpenoids from Swartzia arborescens (Aubl.) Pittier
Bernadette Orphelin, Michèle Brum-Bousquet, François Tillequin*, Michel Koch, and Christian Moretti
*Laboratoire de Pharmacognosie de l'Université René Descartes, URA au CNRS n°1310, Faculté des Sciences Pharmaceutiques et Biologiques, 4, Avenue de l'Observatoire, F-75006 Paris, France
Abstract
Five new cassane diterpenoids, swartziarboreols A-E (1-5), have been isolated from Swartzia arborescens (Aubl.) Pittier. Their structures have been elucidated on the basis of spectroscopic data.
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■ 5-(α-Fluorovinyl)-N-tosylindole
Laxmikant A. Gharat and Arnold R. Martin*
*Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, U.S.A.
Abstract
A α-fluorovinyl (or α-fluoroethene) substituent was introduced into the indole 5-position using an "atypical" Heck reaction. 5-Iodoindole (4) is preferred over 5-bromoindole as the starting material. Protection of the indole nitrogen is necessary.
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■ Pseudoesters and Derivatives XXXVI. Reactions of Enolates of 5-Ethylthiofuran-2(5H)-ones with Aromatic Aldehydes: A Synthesis of Losigamone
M. Rosario Martín, M. Victoria Martín, Ana Martinez de Guereñu, and J. Luis Ortego
*Inst. de Química Orgánica General, Juan de la Cierva 3, Madrid 28006, Spain
Abstract
The furanones (3a) and (3b), key intermediates in our approach to losigamone (12), have been prepared by reaction of 2-chlorobenzaldehyde with the enolates (2A) and (2B) of the corresponding tetronic acid derivatives (2a) and (2b). The reductive conversion of 3b into 1 was carried out with Raney nickel. However, 3a remains unchanged after treatment with Reney nickel or aluminium amalgam. The addition of the enolates (2A) and (2B) to 2-chlorobenzaldehyde led in regioselective manner to the corresponding 5-hydroxyarylfuranones (3a) and (3b). Whereas the addition of 2B to benzaldehyde affords, in a 60:40 ratio, the C-5 and C-3 hydroxybenzylfuranones (7b) and (8b).
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■ Ring Transformation of Fused Pyridazines. IV. Reaction of Halo-substituted Fused Pyridazines with Ynamines
Ken-ichi Iwamoto*, Sumiko Suzuki, Etsuo Oishi, Akira Miyashita, and Takeo Higashino
*School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422, Japan
Abstract
Halo-substituted phthalazines reacted with two equivalents of ynamines to give penta-substituted pyridines through the N-N bond cleavage of pyridazine moiety. And it was proved that the N-N bond cleavage reaction of pyridazine ring is common to halo-substituted condensed pyridazines.
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■ Asymmetric Syntheses of (2R, 4S)-4-Amino-4-carboxy-2-methylpyrrolidine and (2R, 4S)-4-Amino-2-carboxy-2-ethylpyrrolidine as Novel 2-Alkyl-substituted (-)-Cucurbitine Analogues
Ken-ichi Tanaka*, Hirokazu Suzuki, and Hiroyuki Sawanishi
*Faculty of Pharmaceutical Science, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-11, Japan
Abstract
Asymmetric syntheses of (2R,4S)-4-amino-4-carboxy-2-methylpyrrolidine (1) and (2R,4S)-4-amino-4-carboxy-2-ethylpyrrolidine (2) as 2-alkyl-substituted (-)-cucurbitine analogues, have been achieved without disturbing C2 stereogenic center through a route including a diastereoselective Bucherer-Bergs reaction of 2-methyl- and 2-ethenyl-4-oxopyrrolidines (10) and (24), easily derived from trans-4-hydroxy-L-proline.
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■ Synthesis of Pyrazolo[1,5-b][1,2]benzisothiazoles
Joël Moyroud, Alain Chene, Jean-Luc Guesnet, and Jacques Mortier*
*Rhône-Poulenc Secteur Agro, Centre de recherches de la Dargoire, BP 9163, 69263 LYON Cedex 09, France
Abstract
The synthesis of some pyrazolo[1,5-b][1,2]benzisothiazoles is described. The route is based on the reaction between 3(5)-[2’-methylthiophenyl]pyrazoles and its derivatives with N-chlorosuccinimide.