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. 53, No. 1, 2000
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■ X-Ray Structures of a Pair of Atropisomers of 1-(3’-Substituted Benzoyl)-2-naphthylindolines and Some Comments
Akiko Watanabe, Tetsuya Moriguchi, Fumikazu Ito, Yasuyuki Yoshitake, Masashi Eto, and Kazunobu Harano*
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
A pair of atropisomers due to restricted rotation about Csp3—Csp2 bond for 1-(3’-nitrobenzoyl)-2-(2”-hydroxynaphthyl)-3,3-dimethylindoline was isolated. The conformational analysis of both isomers was performed based on the crystallographic and 1 H-NMR spectral data.
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■ Preparation and a Novel Rearrangement Reaction of 1,2,3,4-Tetrahydro-9-hydroxy-β-carboline, and Their Applications for the Total Synthesis of (±)-Coerulescine
Masanori Somei,* Koichi Noguchi, Ryutaro Yamagami, Yumiko Kawada, Koji Yamada, and Fumio Yamada
*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
Novel 9-hydroxy-β-carboline derivatives were produced for the first time. A novel rearrangement reaction of 1,2,3,4-tetrahydro-9-hydroxy-β-carbolines was discovered to give 3,3-disubstituted oxindoles, which was successfully applied to the total synthesis of (±)-coerulescine.
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■ An Efficient Total Synthesis of Ellipticine
Minoru Ishikura,* Ayako Hino, and Nobuya Katagiri
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
A total synthesis of ellipticine could be attained through the palladium catalyzed tandem cyclization-cross-coupling reaction of indolylborate (2b) with vinyl bromide (3) as a key reaction.
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■ Cathylation of 4,6-Dimethyl-2-oxopyridine-3-carbonitrile Derivatives Leading to the Synthesis of Furo[2,3-b;4,5-b’]dipyridines and Novel Tricyclic Furo[2,3,4-ij][2,7]naphthyridine
Chyun-Feng Lin, Yi-Feng Lin, Yan-Chung Lo, Kuo-Tung Chen, and Tsann-Long Su*
*Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan, R.O.C.
Abstract
Cathylation of ethyl 2-(3-cyano-4,6-dimethylpyridine-2-yloxy)acetate afforded a trace amount of new tricyclic furo[2,3,4-ij][2,7]naphthyridine derivative. An attempt was made for an alternate method for the synthesis this new tricyclic ring system. Treatment of 4,6-dimethyl-2-oxopyridine-3-carbonitrile (1) with various α-halocarbonyl compounds (such as chloropropanone or substituted 2-bromoacetophenones) gave a mixture of N- and O-alkylated compounds, which were readily converted into indolizines and 2-acetyl-3-amino- or 3-amino-2-benzoylfuro[2,3-b]pyridines. The 3-aminofuro[2,3-b]pyridine derivatives were further converted into furo[2,3-b;4,5-b’]dipyridines, but not the expected tricyclic furonaphthyridines, via N,O-acetylation and cyclization.
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■ [N](3,5)Isoxazolophanes: Dynamic Behavior and Reaction with Electron-deficient Acetylene Leading to [N](2,6)Pyridinophanes
Hiroyuki Yamamoto and Makoto Nitta*
*Department of Chemistry, School of Science and Engineering, Materials Research Laboratory for Bioscience and Photonics, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
1H NMR spectroscopy at various temperatures clarified the dynamic behavior of the oligomethylene chains for [8](3,5)isoxazolophane (1) and unsubstituted and 4-methyl-substituted [9](3,5)isoxazolophanes (2a,b). The energy barriers (ΔGc‡) for the bridge flipping are 18.6 kcalmol-1 (Tc 100 °C) for 1 and 11.5 kcalmol-1 (Tc-10 °C) for 2a. Compound (2b) does not undergo bridge flipping in temperatures ranging from 25 °C to 150 °C. The energy barriers for the pseudorotation are 11.1-11.2 kcalmol-1 (Tc -10 °C), 9.1 kcalmol-1 (Tc-70 °C), and 8.6 kcalmol-1 (Tc-80 °C) for 1, 2a, and 2b, respectively. The Mo(CO)6-induced reaction of 2a,b with dimethyl acetylenedicarboxylate afforded [9](2,6)pyridinophane derivatives, albeit in low yields.
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■ Preparation of Lavendamycin Analogues
Christine Barbier, Arnaud Joissains, Alain Commerçon, Jean-François Riou, and François Huet*
*Laboratoire de Synthèse Organique, UPRESA CNRS 6011, Faculté des Sciences, Université du Maine, Avenue Olivier Messiaen, F-72085 Le Mans Cedex 9, France
Abstract
A Pictet-Spengler type reaction conducted under modified conditions using a catalytic amount of pyridinium p - toluenesulfonate was used to prepare several lavendamycin (1) analogues.
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■ An Alternative Route for the Preparation of 1-Benzostannepines, 1-Benzostibepines and 1-Benzosilepines via Te-Li Exchange of 1-Benzotellurepines
Haruki Sashida*
*Faculty of Pharmaceutical Science, Hokuriku University, School of Pharmacy, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan
Abstract
Treatment of 1-benzotellurepines (1) with t-BuLi in the presence of TMEDA in ether followed by addition of a metal reagent (Cl2SnBu2, Cl2SbPh and Cl2SiMe2) afforded the corresponding 1-benzostannepines (4), 1-benzostibepines (5) and 1-benzosilepines (6), respectively, in one pot via the tellurium - lithium exchange.
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■ Photochemical Dimerization of Styrylnaphthofurans-II
Irena Skoric, Zeljko Marinic, and Marija Sindler-Kulyk*
*Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulicev trg 19, HR-10000 Zagreb, Croatia
Abstract
Irradiation of styrylnaphthofurans (3a, 3b) [10-1 M] (benzene) under anaerobic conditions gives mainly dimeric products (65-70%): [2+2] ethene-ethene cycloaddition products (9a, 9b, 10a, 10b and 11a, 11b) (40-44%) and [2+2] ethene-furan cycloaddition products (12a, 12b) (20-22%). Minor quantities of electrocyclization products (7a, 7b) (3.5-4.5%) and dihydrocyclization products (8a, 8b) (3-4.5%) are also isolated. The structures of the products are based on 1H and 13C NMR spectra, applying COSY, LR COSY, APT, HETCOR and NOESY techniques.
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■ 1,3-Dipolar Cycloaddition Reactions of Benzonitrile Oxide to 2(1H )-Pyrazinone and Its N - and O - Methyl Derivatives
Antonino Corsaro,* Ugo Chiacchio, Venerando Pistarà, and Giancarlo Perrini
*Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy
Abstract
2(1H)-Pyrazinone, which is in equilibrium with 2-pyrazinol, reacts with benzonitrile oxide (BNO) affording the N1-adduct with a 67% yield, while 2-methoxypyrazine gives two methoxypyrazinones (ca. 3%) and a biscycloadduct together with its degradation product, which derive from the two unisolable monocycloadducts to the C=N4 double bond. N-Methylpyrazinone gives only the degradation product (3.4%) of the initial monocycloadduct of BNO to C=N4 double bond.
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■ Synthesis of Polycylic Systems via Diels-Alder Reactions of Sugar Derived Dienes
P. Areces Bravo,* M. C. Pozo Carrero, E. Román Galán, and J. A. Serrano Blázquez
*Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain
Abstract
Several Diels-Alder reactions of sugar derived dienes (2Z, 4E)-1,3,6-triacetoxyhexa-2,4-diene (2) and (2Z, 4E)-1,3-diacetoxy-6-cyclohexylamino-hexa-2,4-diene (3) with a number of electron-deficient dienophiles were carried out in a completely stereoselective manner to give the corresponding cycloadducts or cascade reaction products. Subsequent chemical transformations yielded highly functionalized polycyclic systems having a controlled stereochemistry. The new compounds described in here keep the all-cis configuration at their centers.
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■ Synthesis and Conformational Analysis of Some New Pyrano[2,3-c]xanthen-7-one and Pyrano[3,2-b]xanthen-6-one Derivatives with Cytotoxic Activity
Konstantinos Ghirtis, Nicole Pouli, Panagiotis Marakos,* Alexios-Leandros Skaltsounis, Stephane Leonce, Daniel H. Caignard, and Ghanem Atassi
*Department of Pharmacy, Division of Pharmaceutical Chemistry, University of Athens, Panepistimiopolis-Zografou, Athens GR-15771, Greece
Abstract
The synthesis, conformational analysis and preliminary biological evaluation of some new pyrano[2,3-c]xanthen-7-ones and pyrano[3,2-b]xanthen-6-ones is described. Certain compounds possess interesting cytotoxic activity against murine leukemia L1210 cells.
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■ A Convenient Synthesis of 4-Trifluoromethylimidazol-1-ols
Yasuhiro Kamitori*
*Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University, Kobe 657-8501, Japan
Abstract
1,1,1-Trifluoroalkane-2,3-dione 3-oximes easily obtainable from aldehyde dialkylhydrazones were reacted with aldehydes in the presence of ammonium acetate followed by treatment with 1N HCl affording 4-trifluoromethylimidazol-1-ols in good yields.
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■ GABA-analogous Spirocyclic Amino Acid Esters, 5. N-Benzyl-7-azaspiro[4.5]decane-1-carboxylates
Markus Bendl, Michael Eder, Ingo Langhammer, and Ernst Urban*
*Institute of Pharmaceutical Chemistry, University of Vienna , Pharmaziezentrum, Althanstraße 14, A-1090 Vienna, Austria
Abstract
N-Benzyl-7-azaspiro[4.5]decane-1-carboxylates (4a and 4b) were prepared in a seven step synthesis starting from ethyl cyclopentanonecarboxylate (5). Aminolysis of the β-keto ester (5) with benzylamine led to the β-keto amide (9) which gave the α-substituted β-keto amide (10) by addition of acrolein. Reduction of 10 with LiAlH4 resulted in a reductive cyclization yielding a mixture of the epimeric spirocyclic alcohols (12a and 12b, 3:1). Oxidation of the alcohols (12a and 12b) was archieved with (COCl)2/DMSO giving the spirocyclic ketone (14). Treatment of 14 with tosylmethyl isocyanide and tert-BuOK yielded a mixture of diastereomeric nitriles (15a and 15b, 6:4) which was separated by chromatography. Hydrolysis and esterification of 15a and 15b led to the diastereomerically pure amino acid esters (4a and 4b) which represent novel analogs of GABA with restricted conformational flexibility.
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■ A Facile and Convenient Synthetic Method for Fluorine-containing 1H-Pyrrolo[3,2-h]quinolines
Etsuji Okada* and Norikado Tsukushi
*Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Abstract
Aromatic nucleophilic nitrogen-nitrogen exchange reaction of N,N dimethyl-5,7-bis(trifluoroacetyl)-8-quinolylamine (1) with some amino acid derivatives gave the corresponding N-[5,7-bis(trifluoroacetyl)-8-quinolyl]amino acid derivatives (2) in excellent yields. Base-catalyzed cyclization of 2 afforded fluorine-containing 1H-pyrrolo[3,2-h]quinolines (3, 4) in high yields.
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■ Preparation and Spectral Properties of the Nitrogen Analogs of (E)-5,5’-Diaryl- 3,3’-bifuranylidene-2,2’-diones and Their Derivatives
Hajime Irikawa* and Norihide Adachi
*Department of Chemistry, Faculty of Science, Shizuoka University, Ohya, Shizuoka 422-8529, Japan
Abstract
(E)-5,5’-bis(2-methylphenyl)- and (E)-5,5’-bis(2,4,6-trimethyl-phenyl)-3,3’-bifuranylidene-2,2’-diones and their isomeric pyrano[4,3-c]pyran-1,5-diones were converted into the nitrogen analogs, in which the aryl groups were twisted relative to the parent skeletons, and had small conjugation effect. Another nitrogen analogs bearing coplanar aryl rings were prepared, and their UV-VIS and NMR spectral data were compared with those of the analogs having twisted aryl groups. Conjugation effect of the 2-alkylphenyl group is bathochromic shift by 24 nm. Steric compression due to coplanarity of the aryl rings causes a deshielding of a 1H NMR signal by Å` 0.6 ppm, and a shielding of a 13C NMR signal by Å` 5 ppm.
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■ Total Synthesis of a Novel Cytotoxic Metabolite Gymnastatin A
Mukund K. Gurjar* and Pushpal Bhaket
*National Chemical Laboratory, Pune 411 008, India
Abstract
The first total synthesis of a novel, potent cytotoxic metabolite gymnastatin A is described.
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■ Anionic [3,3] Rearrangements of Cyclic Hydrazine Diacylates to Medium-Size Cyclic Diamides and Their Structures
Yasuyuki Endo,* Takuya Uchida, and Kentaro Yamaguchi
*Graduate School of Pharmaceutical Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Abstract
The anionic rearrangement of N,N’-dimethyl-N,N’-diacylhydrazines to 1,2-disubstituted succinamides proceeds in the presence of a ajacent enolate- stabilizing substituent such as a phenyl group. However, a substituent that poorly stabilizes the α-carbanion results in an extremely low yield of the products. The [3,3] sigmatropic rearrangement generally requires a chair form for the cyclic six-centered transition state. When the dienolates of N,N’-diacylhydrazines have favorable steric factors for the cyclic transition state, the rearrangement seems to proceed smoothly. The diacylates of 5- to 8-membered cyclic hydrazine which readily adopt a favorable conformation for the [3,3] rearrangement readily rearrange to 9- to 12-membered cyclic diamides.
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■ Reactions of Tetrasulfur Tetranitride Antimony Pentachloride Complex (S4N4·SbCl5) with Primary β-Enaminones and β-Enamino Esters: Synthesis of 4-Substituted 3-Aroyl- and 3-Ethoxycarbonyl-1,2,5-thiadiazoles
Su-Hak Bae, Kyongtae Kim,* and Young Ja Park
*Department of Chemistry, Seoul National University, Seoul 151-742, Korea
Abstract
The reaction of tetrasulfur tetranitride antimony pentachloride complex (S4N4·SbCl5) with 3-amino-3-alkyl-1-aryl-2-propenones and 3-amino-1,3-diaryl-2-propenones in toluene at 100°C produced 4-substitued 3-aroyl-1,2,5-thiadiazoles (3a-p) in 12 to 57% yields. Similarly treatment of β-enamino esters with S4N4.SbCl5 complex under the same conditions as for the reaction with β-enaminones gave ethyl 3-aryl-1,2,5-thiadizole-4-carboxylates (3q-x) in 41 to 54% yields. The formation of the products may be explained by the same mechanism as that proposed for the formation of 1,2,5-thiadizoles from 5-substitued 3-alkyl- and 3-aryl-isoxazoles and S4N4.SbCl5 complex.
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■ Efficient Syntheses of (S)-4-Hydroxy-2-pyrrolidinone Derivatives
Osamu Kanno, Masao Miyauchi, and Isao Kawamoto*
*Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Abstract
Efficient syntheses of (S)-4-hydroxy-2-pyrrolidinone ((S)-2) and (R)-4-acetylthio-2-pyrrolidinone (5), which are key intermediates of oral carbapenem CS-834, were studied. The most efficient route to (S)-2 from (S)-3-hydroxybutyrolactone (8) was accomplished in high yield via (S)-N-allyl-3-(1-ethoxy)ethoxy-4-hydroxybutyramide (14).
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■ Sensitized Photoreduction of Nitrosoazoles on Titanium Dioxide
Andrea Pace, Silvestre Buscemi, Nicolò Vivona,* and Tullio Caronna
*Dipartimento di Chimica Organica “E. Paternò”, Università di Palermo , Viale delle Scienze-Parco D’Orleans II, 90128 Palermo, Italy
Abstract
The photosensitized reduction of some 4-nitrosopyrazoles and 4-nitrosoimidazoles using titanium dioxide as a photocatalyst has been investigated. The photoreaction produces the corresponding 4-aminoazoles and assumes an initial electron transfer from the conduction band of the excited titanium dioxide to the nitroso compound, followed by hydrogen transfer from the solvent. The photoreduction reaction takes also place by irradiating nitrosoazoles in the presence of triethylamine in acetonitrile, pointing out the electron transfer also to occur from a ground state donor to the excited nitrosoazole.
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■ 5-Butyl-3,5-diaryl-4,5-dihydro-1,2,4-oxadiazoles, and a One-Step Synthesis of 4,4-Dibutyl-2-phenylbenzo-1,3-oxazine
Rajendra M. Srivastava,* Maurício F. Rosa, Carlos Eduardo M. Carvalho, Samira da G. M. Portugal, Ira M. Brinn, Maria da Conceição Pereira, and Octávio A. C. Antunes
*Departamento de Química Fundamental, Universidade Federal de Pernambuco, Cidade Universitária, 50.740-540 Recife, PE, Brazil
Abstract
The synthesis of 5-butyl-3,5-diaryl-4,5-dihydro-1,2,4-oxadiazoles is described. The present work also describes the discovery of a reaction leading to the conversion of 5-butyl-5-(2-hydroxyphenyl)-3-phenyl-4,5-dihydro-1,2,4-oxadiazole (1d) to 4,4-dibutyl-2-phenylbenzo-1,3-oxazine (3).
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■ Regioselective Aminomethylations of Bicyclic Phenols
Jos Lange,* Sonja Hoogeveen, Willem Veerman, and Henri Wals
*Solvay Pharmaceuticals Research Laboratpries, Medicinal Chemistry Department, P. O. Box 900, 1380 DA Weesp, The Netherlands
Abstract
The regioselectivity in the aminomethylations (the Mannich reaction) of bicyclic phenols has been studied. Highly regioselective Mannich reactions enable easy synthetic access to novel bicyclic dialkylaminomethylphenols under very mild reaction conditions.
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■ An Expeditious Synthesis of Pyrrolo[3,4-d]pyrimidine-2,4-dione from Uracil
Michael N. Zimmerman, Norman H. Nemeroff, Charles W. Bock, and Krishna L. Bhat*
*Department of Chemistry, School of Science and Health, Philadelphia University,
Philadelphia, PA 19144, U.S.A.
Abstract
An efficient, practical and cost effective synthesis of the title compound has been realized from uracil. The key step is the construction of the pyrrole ring using tosylmethylisocyanide (TosMIC) methodology. The structure of uracil, reaction intermediates and the final product were investigated using density functional calculations.
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■ Synthesis of Mesomeric Betaines, [1,2,4]Triazolo[2,3-a]pyridiniumides, via Back-donated 1,6-Cyclization
Yoshiro Matsuda,* Keisuke Katou, Chieko Motokawa, and Takashi Uemura
*Faculty of Environmental Studies, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
The reaction of [1,2,4]triazolium salts (4a,b) with polarized alkenes (1a,b, 2a) in the presence of K2CO3 in CHCl3-EtOH gave the corresponding triazolium N-allylides (5a-c). Thermolyses of the N-allylides (5a-c) afforded the 7-imino[1,2,4]triazolo[2,3-a]pyridiniumide derivatives (6a,b) and the 7-oxo-[1,2,4]triazolo[2,3-a]pyridiniumide derivative (7a). Similar treatment of the salts (4a,b) with alkenes (1c, 2b) directly yielded mesomeric betaines (7b,c), while the reaction of the salt (4b) with alkene (2c) gave the pyrrolo[2,1-f][1,2,4]triazine derivative (8).
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■ An Efficient Synthesis of (±)-cis-2-Amino-6-hydroxy-9-[4’-hydroxyethyl-2’-cyclopenten-1’-yl]purine
Won Kim, Hyangdug Kim, and Hakjune Rhee*
*Department of Chemistry, Hanyang University, Ansan, Kyunggi-do 425-791, Korea
Abstract
The synthesis of a carbovir analogue, (±)-cis-2-amino-6-hydroxy-9-[4’-hydroxyethyl-2’-cyclopenten-1’-yl]purine (2) was achieved from 2,5-norbornadiene (3) in six steps and 31 % overall yield. This route involves a Meinwald rearrangement, one-pot operation (acid-hydrolysis and subsequent sodium borohydride reduction), and a Pd(0)-catalyzed coupling reaction.