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. 11, 1997
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■ A Novel Synthesis of 4-Perfluoroalkylquinolines and Related Substituted Quinolines
Agnieszka Czarny, Hyeran Lee, Martial Say, and Lucjan Strekowski*
*Department of Chemistry, Georgia State University, Atlanta, GA 30303, U.S.A.
Abstract
In spite of inefficient hydrolysis of 1-(2-aminophenyl)-2,2,3,3,4,4,4-heptafluorobutan-1-one diethyl acetal (2), this compound undergoes readily the acid-catalyzed Friedländer reaction with enolizable ketones to give the corresponding quinolines (4-6). The reaction of 2 with pentanal yields quinoline (12) as the major product.
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■ Formation and Trapping of 1,2-Dimethyleneazulene
Kunihide Fujimori,* Kameji Yamane, Masafumi Yasunami, and Kahei Takase
*Department of Chemistry, Faculty of Science, Shinshu University, Asahi, Matsumoto 390-8621, Japan
Abstract
1,2-Dimethyleneazulenes, an o-xylylene type reactive intermediate, have been generated by the heating of 1,3-dihydroazuleno[1,2-c]thiophene dioxides. The reactive intermediates were efficiently trapped by dienophiles, such as N-phenylmaleimide and diethyl azodicarboxylate, to form [4+2] cycloaddition products in high yields.
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■ Asymmetric Induction in Intramolecular [5+2] Cycloaddition of 2-(4-Alkenyl)-5-benzoyloxy(or 5-Silyloxy)-4-pyrones Involving Migration of the Pyrone O-5 Group to O-4
Naoki Ohmori, Miki Yoshimura, and Katsuo Ohkata*
*Department of Chemistry, Faculty of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526, Japan
Abstract
Heating of the title compounds (1a,b) at 130 °C in o-dichlorobenzene afforded [5+2] annulation products (2a,b) in 70% yield; 27-33% d.e. via 3-oxidopyrylium ylide. Reaction of the title compounds (1a,c) in the presence of ZnCl2 at 40 °C furnished [5+2] annulation products (2b,c) in 23-64% yield and 53-59% d.e. In the event, treatment of the 5-silyloxy derivatives (1d,e) with TBSOTf in the presence of 2,6-lutidine at even 20 °C for 16 h gave [5+2] annulation products (2d,e) with 75% d.e. and 78% d.e. in high yields, respectively
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■ Synthesis and Characterization of Fused Mesoionic 1,3,4-Oxadiazolium-2-thiolates from N-Amino-N,N’-dihydrodiazinediones
Dong Ju Jeon, Sung Chul Shin, and Youn Young Lee*
*Department of Chemistry, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, Korea
Abstract
The novel fused mesoionic 1,3,4-oxodiazolium-2-thiolates were synthesized from N-amino-N,N’-dihydrodiazinediones by treatment with carbon disulfide in the presence of 1,3-dicyclohexylcarbodiimide.
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■ Stereoselectivity in Addition of Phenylselenyl Chloride to Bicyclo[2.2.1]hept-2-ene Derivatives and Synthesis of 3'-Chloro Substituted Carbovir
Akemi Toyota,* Akiko Nishimura, and Chikara Kaneko
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Addition of phenylselenyl chloride to bicyclo[2.2.1]hept-2-enes was examined and the stereoselectivities have been clarified. The adducts derived from 2-azabicyclo[2.2.1]hept-5-en-3-ones having an electron-withdrawing group at 2-position were converted to 3’-chloro substituted carbovir.
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■ A Novel Abnormal Rearrangement in the Fischer Indole Synthesis
Hideaki Fujii, Akira Mizusuna, Ryuji Tanimura, and Hiroshi Nagase*
*Basic Research Laboratories, Toray Industries, Inc., 111, Tebiro, Kamakura, Kanagawa, 248, Japan
Abstract
In the Fischer indole synthesis of naltrexone N-methyl-N-(5,6,7,8-tetrahydro-1-naphthyl)hydrazone, an abnormal rearrangement of the fused 6-membered ring was observed. This abnormal rearrangement was not observed without the N-alkyl group of the hydrazone. The mechanism for the unexpected products was assumed to involve the [3,3] sigmatropic rearrangement at the substituted and more hindered ortho position and the subsequent rearrangement of the fused 6-membered ring via a spiro intermediate.
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■ Complex Base-induced Generation of 3,4-Didehydropyridine Derivatives : New Access to Aminopyridines or Pyridones
Karine Vinter-Pasquier, Brigitte Jamart-Grégoire, and Paul Caubère*
*INCMFU CNRS 0008, Faculte des Sciences-Campus Victor Grignard, Université Henri-Poincare, Bat. 2e cycle, Bld des Aiguillettes, BP 239 - 54506 Vandeceuvre Les Nancy Cedex, France
Abstract
The complex base, NaNH2-tert-BuONa, in THF easily transforms 3-bromopyridine and 2-pyridone derivatives into the corresponding hetarynes. The reaction of representative amines (dialkylamines, morpholine, piperidine) with these reactive intermediates leads to the preparation of aminopyridines in good yields and illustrates the synthetic usefulness of such reactions.
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■ Synthesis of 2H-1-Benzopyran-2,4(3H)-dione-3-carboxamide and 2H,3H-[1]Benzopyrano[4,3-b]pyrano-2-hydroxy-3-carboxamide-4,5-dione Derivatives via Carbon Suboxide
Leonardo Bonsignore* and Giuseppe Loy
*Dipartimento Farmaco Chimico Tecnologico, Universita di Cagliari, Via Ospedale 72, I-09124 Cagliari, Italy
Abstract
The reaction of substituted 2-hydroxybenzmides with carbon suboxide is described. By varying the weight ratio of the reagent, this reaction leads to the coumarin and/or pyranocoumarin derivatives in one step and with satisfactory yields.
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■ Synthesis and Conformational Analysis of Hexahydroisoquino[3,2-b][3]benzazepines (iso-B-Homoberbines)
Darius Paul Zlotos and Werner Meise*
*Pharmaceutical Institute Poppelsdorf, University of Bonn, Kreuzbergweg 26, D-53115 Bonn, Germany
Abstract
A new simple synthetic approach to the hexahydroisoquino[3,2-b][3]benzazepines has been developed. 3-Benzyl-2-tetralones (3a-c) were prepared in two different ways from 2-tetralone and 6-methoxy-2-tetralone. Regioselective methoxycarbonylation with dimethyl carbonate or with magnesium methyl carbonate gave the known β-keto esteres (1) or (1’), respectively, which could be alkylated to benzyl derivatives (2) and (2’), respectively. Demethoxycarbonylation using lithium iodide afforded the desired 3-benzyl-2-tetralones (3a-c), which furnished the lactams (4a-c) by submitting to the Schmidt reaction. Reduction usign borane and a final Pictet-Spengler cyclization gave the title compounds (6a-c). NMR measurements indicated that iso-B-homoberbines exist as equilibrium mixture of the cis and trans conformers in CDCl3 solution at room temperature, whereas the hydrochloride salt of 6b adopts a cis B-fused conformation.
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■ Aroylation of Fused Pyrimidines; Synthesis of 4-Aroylfuro[2,3-d]-, 4-Aroylthieno[2,3-d]-, and 4-Aroylisoxazolo[5,4-d]pyrimidines
Akira Miyashita,* Kazuhiro Obae, Yumiko Suzuki, Etsuo Oishi, Ken-ichi Iwamoto, and Takeo Higashino
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
4-Aroylfuro[2,3-d]- (4), 4-aroylthieno[2,3-d]- (7 and 8), and 4-aroylisoxazolo[5,4-d]pyrimidines (13) were synthesized by aroylation of the fused chloro- (3a and 12) or bromopyrimidines (3b, 5, and 6) with arenecarbaldehydes (2) catalyzed by an imidazolium salt (1a). The fused aroylpyrimidines (4 and 7) were also synthesized by oxidative decyanation of α-phenylheteroareneacetonitriles (10 and 11).
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■ Crystal and Molecular Structure of a Rimazolium®Decomposition Product.Calculation of Pyramidality of Analogous Cyclic Amides
Kálmán Simon,* Levente Pusztay, Miklós Hanusz, Zsolt Böcskei, Benjamin Podányi, Miklós Fehér, and István Hermecz
*CHINOIN Pharmaceutical and Chemical Works Ltd., P. O. Box 110, H-1325 Budapest, Hungary
Abstract
The solid state structure of 10 was determined by X-Ray investigations, and stereostructure of 1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a]pyrimidin-4-ones were studied by semiempirical quantum chemical calculations at the AM1 level. While 9a-unsubstituted 1-methyl-1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a]pyrimidin-4-ones adopt a cis-fused conformation, 9a-ethoxy-1-methyl derivative has a trans-fused conformation to avoid a serious non-bonding interaction between 9a-ethoxy and 1-methyl groups in cis-fused one.
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■ Novel Formation and Crystal Structure of 2-(2,2,2-Trifluoroethylidene)-6-trifluoro-methyl-2,3-dihydro-4H-1,4-oxazin-3-ones from N-Acetyl-N-alkyl-α-amino Acids
Masami Kawase,* Setsuo Saito, Hiroyuki Kikuchi, and Hiroshi Miyamae
*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japana
Abstract
The title compounds (2a-g) were formed from N-acetyl-N-alkyl-α-amino acids (1a-g) on treatment with trifluoroacetic anhydride in the presence of pyridine. The structure of the product (2a) was determined by single crystal X-Ray analysis.
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■ Synthesis of Mesomeric Betaines, Quinoliziniumides, via Back-donated 1,6-Cyclization
Yoshiro Matsuda,* Keisuke Katou, Takanobu Nishiyori, Takashi Uemura, and Maki Urakami
*Faculty of Environmental Studies, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
The reaction of 3-aminopyridinium salts (4) with polarized olefins (2a, b, 3) in the presence of triethylamine yielded the corresponding 3-aminopyridinium N-allylides (5a). Thermolysis of 3-aminopyridinium N-allylides (5a-c, h-j, l-n) in refluxing xylene afforded the 1,5-dipolar cyclization products, 8-aminoindolizines (6) togeher with the back-donated 1,6-cyclization products quinoliziniumides (7). In addition, thermolysis of N-allylides (5a-c, h-j, l-n) in refluxing AcOH gave quinoliziniumides (7).
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■ Synthesis of 6-, 7-, 8-, or 9-Substituted 1H-Pyrano[4,3-b]quinoline Derivatives by the Cyclization of 3-Acetyl-4-arylamino-2H-pyran-2-one Derivatives
Atsuko Sato, Mieko Morone, and Yutaka Azuma*
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
Heating of 3-acetyl-4-arylamino-6-methyl-2H-pyran-2-one derivatives in concd H2SO4 gave 6-, 7-, 8- or 9-substituted 6,10-dimethyl-1H-pyrano[4,3-b]quinoline derivatives.
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■ Suzuki Couplings with Phthalimidines - An Efficient Route to Staurosporinone Analogs
Kenneth C. Rupert, John H. Dodd, and James R. Henry*
*The R. W. Johnson Pharmaceutical Research Institute, Route 202, P.O. Box 300, Raritan, NJ 08869-0602, U.S.A
Abstract
Staurosporinone analogs have been prepared by an efficient process. The key step is a palladium mediated Suzuki coupling between a bromophthalimidine and an aromatic boronic acid.
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■ Synthesis of a New Annulenoannulene, Cycl[3.2.2]azino[1,2-a]cycl[3.2.2]azine
Yoshiro Matsuda,* Shinya Kohra, Keisuke Katou, Takahiro Itou, and Takashi Uemura
*Faculty of Environmental Studies, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
A new nitrogen-bridged annulenoannulene, cycl[3.2.2]azino[1,2-a]cycl[3.2.2]azine (8) was synthesized from the starting bispyridylmethane (1) via cycloaddition reaction of the indolizinocyclazine derivative (5) with diemthyl acetylenedicarboxylate (DMAD) as the key step.
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■ Synthesis of a Pyrido[2,3-d]pyrimidine Analogue of the Multitargeted Antifolate LY231514
Edward C. Taylor* and Koo Lee
*Department of Chemistry, Princeton University, Princeton, New Jersey 08544, U.S.A.
Abstract
Synthesis of pyrido[2,3-d]pyrimidines (9) and (21), ring-expanded analogues of the antitumor agent LY231514 (7), and its 4-amino analog, respectively, are described. Preliminary in vitro cell culture evaluation has shown that expansion of the pyrrole ring of the latter two pyrrolo[2,3-d]pyrimidines through introduction of a carbonyl group between positions 6 and 7 results in complete loss of cell growth inhibitory activity.
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■ Condensation of 2-Amino-5-chlorobenzoxazole with α-Bromoketones: A Mechanistic Study
Patrick J. Roy,* Kerri Landry, Yves Leblanc, Chun Li, and Nancy Tsou
*Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, Quebec, H9R 4P8, Canada
Abstract
The condensation of 2-aminobenzothiazoles with α-bromo ketones products the fused imidazothiazole (2) whereas the analogous reaction with 2-aminobenzoxazoles gives the unexpected carbamate (10) or the fused imidazooxazole (13), depending on the nature of the starting materials. Isotope labelling studies as well as a proposed mechanism will be discussed.
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■ A Neoclerodane Diterpenoid from Scutellaria guatemalensis (Labiatae)
Baldomero Esquivel,* Rosa María Domínguez, Miguel Angel Martínez, and Georgina Espinosa-Pérez
*Instituto de Química, Universidad Nacional Autónama de México, Circuito Exterior, Ciudad Universitaria, Coyoacán 04510 Mexico, D.F., Mexico
Abstract
A new neoclerodane diterpenoid, (13R)-6α,11β-diacetoxy-1β,12α-diisobutyryloxy-4α,18;18β,13-diepoxy-neo-clerodan-15,16-olide (Scuteguatemalin) has been isolated from the aerial parts of Scutellaria guatemalensis besides the known skullcapflavone II. The structure of the new diterpenoid was established by spectroscopic methods and confirmed by X-Ray analysis.
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■ Studies on Inhibitory Activity against Acetylcholinesterase of New Bisbenzylisoquinoline Alkaloid and Its Related Compounds
Tatsunori Ogino,* Takuji Yamaguchi, Toshitsugu Sato, Hiroshi Sasaki, Ko Sugama, Minoru Okada, and Masao Maruno
*Central Research Laboratory, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-11, Japan
Abstract
A new phenolic bisbenzylisoquinoline (BBI) alkaloids named 2’-N-norfangchinoline was isolated from the root of Stephania tetrandra S. MOORE along withfangchinoline (2) and atherospermoline (3). The chemical structure of 2’-N-norfangchinoline was proved to be 4 by spectral analyses and chemical methods. Moreover three phenolic BBI alkaloidal compounds, 2,2’-N,N-dinorfangchinoline (8), 2’-N-noratherospermoline (9), 2-N-norfangchinoline (10) were derived from tetradrine (1). And 12-O-acetyl antherospermoline (11) was obtained by partial acetylation of atherospermoline (3). Seven phenolic BBI compounds (2, 3, 4, 8, 9, 10, and 11) also have the inhibitory effect on acetylcholinesterase.
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■ Cesium Fluoride-mediated Claisen Rearrangements of Phenyl Propargyl Ethers: Substituent Effects of an ortho-Alkoxy Group on the Benzene Ring or Modified Propargyl Residues
Tsutomu Ishikawa,* Akiko Mizutani, Chizue Miwa, Yumie Oku, Naoko Komano (nee Ohkubo), Atsuya Takami, and Toshiko Watanabe
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
The expected 7-alkoxy-2-emthylbenzo[b]furans were effectively given in the CsF-mediated Claisen rearrangement of phenyl propargyl ethers with an o-alkoxy substituent on the benzene ring. On the other hand CsF did not affect the production of the corresponding benzo[b]furans when ethers, carrying a propargyl residue modified by either 1,1-dimethyl or 3-ethoxycarbonyl functions, were used as substrates in the rearrangement.
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■ Ring-Expansion of 2-Methylbenzo[b]furan to 3-Hydroxychromen-4-one: A Potential Approach to a Flavonol Skeleton
Tsutomu Ishikawa* and Chizue Miwa
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
A 2-methylbenzo[b]furan, prepared by the CsF-mediated Claisen rearrangement of a propargyl ether, could be smoothly transformed into a 3-hydroxychromen-4-one, a potential flavonol skeleton, by three successive treatment with NBS, OsO4, and Na2SO3.
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■ Design and Synthesis of Photoactivatable Coumarin-containing HIV-1 Integrase Inhibitors
He Zhao, Nouri Neamati, Yves Pommier, and Terrence R. Burke, Jr.*
*Laboratories of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, Building 37, Room 5C06, National Institute of Health, Bethesda, MD 20892, U.S.A.
Abstract
Three dimeric coumarin analogues (1 - 3) were prepared, each containing the photoactivatable benzophenone moiety. These compounds exhibited low micromolar IC50 values against HIV-1 integrase mediated 3’-processing and strand transfer, and may represent useful probes for elucidating enzyme-inhibitor interactions.