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. 55, No. 8, 2001
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■ Novel Specific Puromycin-sensitive Aminopeptidase Inhibitors: 3-(2,6-Diethylphenyl)-2,4(1H,3H)quinazolinedione and N-(2,6-Diethylphenyl)-2-amino-4H-3,1-benzoxazin-4-one
Hiroki Kakuta, Yukiko Koiso, Hiroyasu Takahashi, Kazuo Nagasawa, and Yuichi Hashimoto*
*Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Abstract
Novel specific PSA (puromycin-sensitive aminopeptidase) inhibitors, 3-(2,6-diethylphenyl)-2,4(1H, 3H)-quinazolinedione (3: PAQ-22) and N-(2,6-diethylphenyl)-2-amino-4H-3,1-benzoxazin-4-one (4: PAZOX-22), were designed and synthesized. These compounds are chemically much more stable than the known specific PSA inhibitor PIQ-22 (2), and the enzyme specificity and inhibitory activity to PSA are similar to those of 2. The inhibitory manner of these compounds was found to be a non-competitive mode by Lineweaver- Burk plot analysis.
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■ A Facile Synthesis of Spiro-cyclopentenones from Various 1-Alkynes and Cyclic exo-Methylene Compounds by Intermolecular Pauson-Khand Reaction
Miyuki Ishizaki,* Yasuhiro Kasama, Mieko Zyo, Yuka Niimi, and Osamu Hoshino*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
Abstract
Intermolecular Pauson-Khand reaction of various 1-alkynes with exo-methylene-piperidine and -cyclohexane derivatives was examined to give the title compounds in moderate to good yields.
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■ Alumina/Phosphorus Pentoxide (APP) as an Efficient Reagent for the Synthesis of 1,5-Benzodiazepines under Microwave Irradiation
Babak Kaboudin* and Kian Navaee
*Ministry of Science Research and Technology, Institute for Advanced Studies in Basic Sciences, Gava Zang, Zanjan 45195-159, Iran
Abstract
Alumina-supported phosphorus pentoxide was found to be an efficient reagent for the synthesis of 1, 5-benzodiazepine derivatives from phenylenediamine and ketones in the solvent-free condition under microwave irradiation. This method is an easy, rapid, and high-yielding reaction for the synthesis of 1, 5-bezodiazepines.
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■ Synthesis of Bis(7-dimethylamino-1-indolizinyl)methane Derivatives and Their Oxidation: As an Oxidative Chromogenic Reagent in Clinical Analysis
Yoshinori Tominaga,* Sachiko Itonaga, Tetsuya Kouno, and Yasuhiro Shigemitsu
*Center of Instrumental Analysis, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
Acid-catalyzed condensation of 7-dimethylaminoindolizines with aldehydes led to substituted bis(7-dimethylaminoindolizin-1-yl)methanes (3a-i) which were easily converted into substituted bis(7-dimethylaminoindolizin-1-yl)methyl cations (4a-i) by oxidation with DDQ. These triaryl cation dyes were converted to the new heterocyclic ring system, 12-dimethylamino-6,8-bis(ethoxycarbonyl)-2H-thiopyrano[3,2-a:5,6-a’]diindolizine-2-N,N-dimethylimi-nium perchlorates (5a, b), under reflux conditions in ethanol.
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■ Stereocontrolled Synthesis of 3-Hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepines by Means of Neighboring Group Participation
Michinori Karikomi, Kozue Ayame, and Takashi Toda*
*Department of Applied Chemistry, Faculty of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya 321-8585, Japan
Abstract
A novel stereocontrolled synthesis of 3-hydroxy-2,3,4,5-tetrahydro-1,5-Benzothiazepines (4) by means of neighboring group participation is described. The influence of solvents, additives, and substituents is also discussed.
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■ Indoles XIV. 4-Phenylpyrido[4,3-b]indoles and 5-Phenylazepino[4,5-b]indoles by Cyclisation of N-Indolylalkyl-ephedrine Derivatives — Scope and Stereoselectivity
Michael Decker, Rüdiger Faust, Maike Wedig, Martin Nieger, Ulrike Holzgrabe, and Jochen Lehmann*
*Institute of Pharmacy, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany
Abstract
4-Phenyltetrahydropyrido[4,3-b]indoles (1) and 5-phenylhexahydro-azepino[4,5-b]indoles (2) were obtained by cyclisation reactions starting from N-3-indolylmethylephedrines and N-3-indolylethylnorephedrines respectively, using conc. sulfuric acid (for 1) and PPA (for 2), the latter cyclisation yielding to the racemised azepinoindoles (2), whereas the previous one reacts to 1 in a remarkably stereoselective manner with double inversion = retention of its configuration, obviously going through a spirocyclic intermediate.
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■ Remarkably Easy Oxidation of Alkylzinc Reagents in Their Reactions with Electrophiles to Produce Alkoxylated Instead of the Expected Alkylated Products
Alan R. Katritzky* and Zhushou Luo
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, U.S.A.
Abstract
Alkylzinc reagents, in contrast to arylzinc reagents, react with two series of α-benzotriazolylalkylamines to give oxidized products formed by the incorporation of an atom of oxygen into the carbon-zinc bond even when the reactions are carried out under argon. Thus, benzotriazole derivatives of 4,5-disubstituted imidazolidinone (2) and N-Boc-2-benzotriazolylpyrrolidine (7) gave oxidized products (4a-b) and (8a-c), respectively. The abnormal reaction course was traced to molecular oxygen dissolved in the THF. The expected, unoxidized products (9a-d) were obtained under rigorous argon purge of the THF solvent and solutions.
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■ Novel Photocleavable Structures I: Synthesis of Hydroxyalkylphenone Analogues Electron-rich Heterocycles
Robert Liska
*Institute of Chemical Technology of Organic Materials, University of Technology Vienna, Getreidemarkt 9/162, 1060 Vienna, Austria
Abstract
A series of photoinitiating compounds with the general structure ArCOCMe2OH, where Ar is 2-furyl (1a), 3-furyl (1b), 2-thienyl (2a), 3-thienyl (2b), 2-pyrrolyl (3a) and 3-pyrrolyl (3b), were prepared. The heterocyclic precursors were substituted by Friedel-Crafts type reaction with isobutyric acid derivatives. Subsequent bromination and hydrolysis gave 1a, 2a and 3b. Derivatives 1b, 2b and 3a were obtained by reaction of organometallic intermediates of heterocyclic precursors with suitable nitriles or esters.
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■ A Combination of Friedel-Crafts and Lawesson Reactions to 5-Substituted 2,2’-Bithiophenes
M. Manuela M. Raposo* and Gilbert Kirsch
*Departamento de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Abstract
γ-Keto esters (2) derivatives of thiophene were obtained from hemi-succinic esters and transformed to the corresponding amides (4). Lawesson’s treatment of 2 and 4 gave the corresponding bithiophenes (5) with alkoxy or amino substituents.
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■ Medicinal Foodstuffs. XXVI. Inhibitors of Aldose Reductase and New Triterpene and Its Oligoglycoside, Centellasapogenol A and Centellasaponin A, from Centella asiatica (Gotu Kola)
Hisashi Matsuda, Toshio Morikawa, Hiroki Ueda, and Masayuki Yoshikawa*
*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan
Abstract
The methanolic extract from the aerial parts of Centella asiatica L. cultivated in Vietnam was found to inhibit rat lens aldose reductase. From the methanolic extract, a new olean-13-ene-type triterpene, centellasapogenol A, and its oligoglycoside, centellasaponin A, were isolated together with several known saponins and flavonoids. Their structures were elucidated on the basis of chemical and physicochemical evidence. In addition, a flavonol component, petuletin, was found to show potent inhibitory activity on aldose reductase.
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■ A New Asymmetric Synthesis of (R)-3-Methylpyrrolidine Alkaloids Starting from (S)-Malic Acid
Xiao Zheng, Pei Qiang Huang,* Yuan Ping Ruan, Albert W. M. Lee, and Wing Hong Chan
*Department of Chemistry, Xiamen University, Xiamen 361005, China
Abstract
Diastereoselective methylation of dimethyl (S)-malate (8) followed by two three-step reductive dehydroxylation procedures afforded dimethyl (R)-2-methylsuccinate (16) in 80.2% and 84.7% ee respectively, the later was further transformed into the natural enantiomers of ant venom alkaloids (R)-leptothoracine (1) and (R)-3-methyl-N-(2-phenylethyl)pyrrolidine (2) and (3R, 2’S)-3-methyl-N-(2-methylbutyl)pyrrolidine (3).
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■ Synthesis of Tetracyclic Dibenzo[c,f]azepine and Benzo[f]thieno[3,2-c]azepine Derivatives via N-Acyliminium Ion Cyclization
Jae Yeol Lee,* Nam Jun Baek, Sook Ja Lee, Hokoon Park, and Yong Sup Lee
*Division of Life Sciences, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 131-650, Korea
Abstract
Tetracyclic dibenzo[c,f]-4-oxopyrrolo[1,2-c]azepine (2a), dibenzo[c,f]-5-oxopiperido[1,2-c]azepine (2b), benzo[f]-4-oxopyrrolo[1,2-a]thieno[3,2-c]azepine (2c), and benzo[f]-5-oxopiperido[1,2-a]thieno[3,2-c]azepine (2d) were prepared through intramolecular N-acyliminium ion cyclization of hydroxylactams (3a-d) with aromatic or heteroaromatic rings such as benzene and thiophene as a p-nucleophile. In the case of furan ring, the hydroxylactams (3e, f) were completely decomposed under the acidic conditions (formic acid or methanesulfonic acid). Subsequent reduction of 2a-d with BF3·O(C2H5)2 and BH3·S(CH3)2 finally provided the tetracyclic dibenzo[c,f]pyrrolo[1,2-c]azepine (1a), dibenzo[c,f]piperido[1,2-c]azepine (1b), benzo[f]pyrrolo[1,2-a]thieno[3,2-c]azepine (1c), and benzo[f]piperido[1,2-a]thieno[3,2-c]azepine derivatives (1d) as analogues of mianserin.
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■ Heterocycles in Organic Materials Chemistry. Synthesis of Di-, Tri-, and Tetraimide Polycarboxylic Acids for Use in Organic Network Assembly
Ken S. Feldman,* Yanze Liu, Joe C. Saunders, Katherine M. Masters, and Robert F. Campbell
*Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, U.S.A.
Abstract
Seven linear divalent monomers, three bent divalent amide-containing monomers, 11 bent divalent ester-containing monomers, one planar trivalent monomer, and two tetrahedral tetravalent monomers were prepared by imide-forming condensation of the appropriate polyamine hub with a specially designed anhydride connector unit. These polyvalent polycarboxylic acid monomers were subjected to crystallization/photochemical crosslinking studies in an attempt to prepare periodic, covalent organic solids. Difficulties in achieving suitable crystals have so far frustrated efforts to reach this goal.
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■ A Simple Synthesis of Rutaecarpine
Seung Ho Lee, Seung Ill Kim, Jae Gyu Park, Eung Seok Lee, and Yurngdong Jahng*
*College of Pharmacy, Yeungnam University, Kyongsan 712-749, Korea
Abstract
Indoloquinazoline alkaloid rutaecarpine was efficiently synthesized by employing 9,10,11,12-tetrahydro-4H-pyrido[2,1-b]quina-zoline-4,9-dione as a key intermediate, whose 9-carbonyl group was introduced by benzylidene formation, followed by ozonolysis.
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■ One-Pot Synthesis of Indolequinone Derivatives from 2-Acylamino-1,4-naphtho(or benzo)quinones and Enamines
Koujirou Tanaka, Atsushi Takanohashi, Osamu Morikawa, Hisatoshi Konishi, and Kazuhiro Kobayashi*
*Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Abstract
1H-Benz[f]indole-4,9-diones (3) were prepared in a one-pot reaction in moderate to good yields by treating 2-acylamino-1,4-naphthoquinones (1) with enamines (2). The similar pyrrole ring formation reaction also took place on treatment of a 2-trifluoroacetylamino-1,4-benzoquinone (7) with enamines (2), giving 1H-indole-4,7-diones (8) in moderate yields. 4,9-Diacetoxy-1-acetyl-2 ethyl-3-methylbenz[f]indole (6) was isolated after treatment of the crude mixture obtained from the reaction of 2-acetylamino-1,4-naphthoquinone (1b) with 3 morpholino-2-pentene (2c) with acetic anhydride and pyridine under argon. This indicates that the initial products in these reactions proved to be the respective hydroquinone derivatives, the air oxidation of which yielded the indolequinones.
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■ Application of Hexamethylenetetramine in a Pictet-Spengler Type Reaction for Synthesis of Isoquinoline Derivatives
Iliyan Ivanov and Atanas Venkov*
*Department of Organic Chemistry, University of Plovdiv, 24, Tsar Assen Str. 4000 Plovdiv, Bulgaria
Abstract
Hexamethylenetetramine was used successfully as amino- and amidoalkylation cyclization reagent for the synthesis of 3,4-dihydroisoquinolines, tetrahydroisoquinolines and 1,4-dihydro-3(2H)-isoquinolinones. The reagent provides a simple and convenient pathway for the preparation of a range of these compounds.
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■ Behavior of Hydrazonoyl Chlorides towards the C=N Double Bond of Δ2-Pyrazolines. A Study on 2-(4-Nitro-phenyl)-2,3,3a,4,5,6-hexahydro-6-oxofuro[3,4-c]pyrazole
Giorgio Molteni* and Luisa Garanti
*Dipartimento di Chimica Organica e Industriale, Centro C.N.R. , Università degli Studi di Milano, via Golgi 19, 20133 Milano, Italy
Abstract
The reaction between title compound (3) and hydrazonoyl chlorides (4) was performed in the presence of triethylamine or silver salts. The product output was quite different depending upon the basic agent and, besides the formation of the novel pyrazolo[4,5-b]furo[3,4-c]pyrazole skeleton, a new degradative behavior of the pyrazoline ring has been observed.
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■ Synthetic Equivalent of α-Nitroformylacetic Acid
Nagatoshi Nishiwaki,* Hiromi Ohtomo, Mina Tamura, Kazushige Hori, Yasuo Tohda, and Masahiro Ariga*
*Department of Chemistry, Osaka Kyoiku University, 4-698-1 Asahigaoka, Kashiwara, Osaka 582-8582, Japan
Abstract
A novel synthetic procedure for 3-nitro-2-pyridone derivatives (2) is provided, which includes the ring transformation of 1,3-dinitroquinolizin-4-one (3) with ketones in the presence of ammonium acetate.
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■ Synthesis of 5-Substituted 7-Azaoxindoles via Palladium-catalyzed Reactions
Mui Cheung,* Robert N. Hunter III, Michael R. Peel, and Karen E. Lackey
*GlaxoSmithKline, Five Moore Drive, P.O. Box 13398, Research Triangle Park, North Carolina, 27709-3398, U.S.A.
Abstract
A synthesis of 5-substituted 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-ones (5-substituted 7-azaoxindoles) via palladium-catalyzed Suzuki coupling, Stille coupling, and carbonylation reactions is described.
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■ Diastereoselective Synthesis of trans-N-Benzyl-2-(2-methylphenyl)-6-phenyl-4-piperidone
Kaori Ishimaru* and Takakazu Kojima
*Department of Chemistry, The National Defense Academy, 1-10-20 Hashirimizu, Yokosuka 239-8686, Japan
Abstract
Diastereoselective synthesis of trans-N-benzyl-2-(2-methylphenyl)-6-phenyl-4-piperidone (6a) was performed by cycloaddition of the aldimine (1c) with 2-silyloxy-1,3-butadiene in the presence of trimethylsilyl triflate. The use of the p-trimethylsilyl substituent of the aromatic ring of the aldimine gave high diastereoselectivity of the product.
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■ A Facile and Convenient Synthesis of 1,2,3,6-Tetrahydropyridazines Using Azodicarboxylates under Lanthanum Triflate Catalysis
Massimo Curini,* Francesco Epifano, Maria Carla Marcotullio, and Ornelio Rosati
*Dipartimento di Chimica e Tecnologia del Farmaco, Facoltà di Farmacia, Università di Perugia , Via del Liceo, 1, 06123 Perugia, Italy
Abstract
The hetero-Diels-Alder reaction catalyzed by lanthanum triflate hydrate using diethyl azodicarboxylate as dienophile, yielding differently substituted 1,2,3,6-tetrahydropyridazines, is described.