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. 10, 2000
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■ New Synthesis of KT5823 Indolocarbazole Aglycone
Guillaume E. Burtin,* Daivd J. Madge,* and David L. Selwood
*The Wolfson Institute for Biomedicinal Reseach, Biological and Medicinal Chemsitry, University College London, Cruciform Building, Gower Street, London, WC1E 6AU, U.K.
Abstract
The indolo[2,3-a]pyrrolo[3,4-c]carbazole aglycone of the selective protein kinase G inhibitor KT5823 has been synthesised in four steps and 36% overall yield from 2,3-dichloro-N-methylmaleimide by utilising an efficient new two step reduction sequence for the key imide to amide transformation.
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■ Reaction of 3-Ethoxycarbonylindolizine-1,2-dicarboxylic Anhydride with (3-Bromo-4-pyridyl)triisopropoxytitanium: Synthesis of 5,12-Dimethylindolizino[2,1-g]isoquinoline (Ellipticine Analogue)
Yasuyoshi Miki,* Noriko Nakamura, Ryota Yamakawa, Hajime Hibino, Hiroko Hachiken, and Ko-ichi Matsushita
*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan
Abstract
Reaction of indolizine-1,2-dicarboxylic anhydride with (3-bromo-4-pyridyl)triisopropoxy-titanium gave 2-(3-bromoisonicotinoyl)-3-ethoxycarbonyl--indolizine-1-carboxylic acid as the sole product. The indolizine-1-carboxylic acid could be converted to 5,12-dimethyl-indolizine-[2,1-g]isoquinoline in six steps.
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■ Total Synthesis and Conformational Analysis of Monophenyl Substituted Protoporphyrins. IX
Adriana E. Robinsohn, Marta S. Maier, and Graciela Y. Buldain*
*Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, (1113) Buenos Aires, Argentina
Abstract
The total synthesis of meso-monoaryl protoporphyrins (1) and (2) using a MacDonald type [2+2] condensation is described. In this method a bisformyl dipyrrylmethane is treated with a biscarboxydipyrrylmethane. Attempts to obtain the δ-meso-monoaryl protoporphyrin (7) by the a,c-biladiene method failed as it could not be prepared starting from its tripyrrene precursor. The synthesis of the latter compound is described. Molecular modeling studies allowed us to find the most favorable conformations for compounds (1) and (2). In both porphyrins, the exocyclic phenyl group adopts a noncoplanar disposition relative to the plane of the macrocycle. In porphyrin (2) the macrocycle is nearly planar while nonplanar saddle conformation was obtained for porphyrin (1).
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■ Reaction of 3-Ethoxycarbonylindolizine-1,2-dicarboxylic Anhydride: Synthesis of 2-Acylindolizines and Quinones
Yasuyoshi Miki,* Noriko Nakamura, Ryota Yamakawa, Hiroko Hachiken, and Ko-ichi Matsushita
*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan
Abstract
Reaction of indolizine-1,2-dicarboxylic anhydride with Grignard reagents gave 2-acylindolizine-1-carboxylic acids, which were converted to 2-acylindolizines. The anhydride reacted with anisole in the presence of titanium chloride(IV) to afford 2-(4-methoxybenzoyl)indolizine-1-carboxylic acid, which was also led to 2-(4-methoxybenzoyl)indolizine. Successive treatment of the 2-acylindolizine-1-carboxylic acids with phosphorus pentachloride and aluminum(III) chloride provided the corresponding quinones.
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■ Synthesis of Phenazine 5,10-Dioxides from Benzofuroxan Catalyzed by Molecular Sieves
Tohru Takabatake, Tomoyuki Miyazawa, Mahiro Kojo, and Minoru Hasegawa*
*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan
Abstract
The synthesis of substituted phenazines was carried out. Phenazine 5,10-dioxides (3) were obtained from benzofuroxan (1) with dihydroxybenzene derivatives (2) catalyzed by molecular sieves at room temperature.
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■ Reductive Smiles Rearrangement of 1-[(5-Chloro-2-nitrophenyl)sulfonyl]-1H-pyrrole-2-carbohydrazide to 1-Amino-6-chloro-2-(1H-pyrrol-2-yl)benzimidazole
Romano Silvestri, Augusto Pifferi, Gabriella De Martino, Silvio Massa, Carmela Saturnino and Marino Artico*
*Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università di Roma “La Sapienza”, BOX 36 - ROMA 62, Piazzale Aldo Moro 5, 00185 Roma, Italy
Abstract
Treatment of 1-[(5-chloro-2-nitrophenyl)sulfonyl]-1H-pyrrole-2-carbohydrazide with powdered iron in glacial acetic acid afforded 1-amino-6-chloro-2-(1H-pyrrol-2-yl)benzimidazole as the sole product. This compound was also obtained by iron-acetic acid reduction of 1-(5-chloro-2-nitrophenyl)-1H-pyrrole-2-carbohydrazide. Splitting of the sulfone group occurred only in the presence of the carbohydrazide group. In fact, iron-acetic acid reduction of 5-chloro-2-nitrophenyl 2-ethoxycarbonyl-1H-pyrrol-1-yl sulfone gave the expected 2-amino-5-chlorophenyl 2-ethoxycarbonyl-1H-pyrrol-1-yl sulfone. Treatment of this compound with hydrazine yielded the corresponding carbohydrazide, which failed cyclization when reacted with phosphorus pentoxide. Formation of 7-chloropyrrolo[1,2-b] [1,2,5]benzothiadiazepin-11(10H)-one 5,5-dioxide with loss of hydrazine was observed when the above amino hydrazide was reacted with 2-hydroxypyridine or with glacial acetic acid.
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■ A New Synthesis of Pyrazolo[4,3-e][1,2,4]triazines via Acid Promoted Ring Closure of the Phenylhydrazones of 5-Acyl-1,2,4-triazines
Andrzej Rykowski,* Mariusz Mojzych, and Zbigniew Karczmarzyk
*Institute of Chemistry, University of Podlasie, 08-110 Siedlce, Poland
Abstract
The reaction of various substituted phenylhydrazones of 5-acyl-1,2,4-triazines in the presence of 1.1 equivalent of HCl in boiling ethanol-dioxane mixture has been studied. In all reactions the formation of the corresponding pyrazolo[4,3-e][1,2,4]triazines (3a-r) takes place in good yield. The structures of 3a-r were unequivocally established by spectroscopic methods as well as by X-Ray analysis of selected 5-methyl-3-phenyl-7-(p-tolyl)pyrazolo[4,3-e][1,2,4]triazine (3a).
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■ Catalytic Asymmetric Synthesis and Asymmetric Autocatalysis of Chiral 5,5’-(3,3’-Bipyridyl)dialkanediol
Shigehisa Tanji, Tomohiko Nakao, Itaru Sato, and Kenso Soai*
*Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601 Japan
Abstract
(S,S)-(-)-5,5′-(3,3′-Bipyridyl)dialkanediols (5a, b) with up to 98.6% e.e. was synthesized by the enantioselective addition of dialkylzincs to 3,3′-bipyridine-5,5′-dicarbaldehyde (4) using N,N-dipropylnorephedrine as a chiral catalyst. Chiral diol (5a) was found to work as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to aldehyde (4).
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■ Reaction of 3-Iodochromone with Nucleophiles. 2. Reaction with Mercaptoazoles
Yoshiaki Sugita,* Shengzhen Yin, and Ichiro Yokoe*
*Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan
Abstract
3-Iodochromone (1a) easily reacted with mercaptoazoles in the presence of potassium carbonate to give 3-azolylthiochromones in good yields. In the case of 2-mercaptobenzimidazole (2a) as a nucleophile, the benzimidazo[2,1-b]thiazole derivative (4a) was obtained as the major product along with 3-(1H-benzimidazol-2-ylthio)chromone (3a). The ratio of the two products was found to be affected by the electron density on the nitrogen atom in the benzimidazole ring.
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■ A Concise Preparation of Yuehchukene and Its Analogues
Minoru Ishikura,* Katsuaki Imaizumi, and Nobuya Katagiri
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
The palladium catalyzed carbonylative cross-coupling reaction of indolylborates (2) with vinyl triflates (3) afforded indol-2-yl ketones (4), which were subsequently converted to hexahydroindeno[2,1-b]indoles (5) with the aid of an acid. This protocol was well adapted for the total synthesis of yuehchukene.
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■ A Tetracycloundecane Derivative of Pyrrolidinobenzoxazinone
Makhluf J. Haddadin and Musa Z. Nazer*
*Department of Chemistry, American University of Beirut, Beirut, Lebanon
Abstract
Conversion of 2-nitrobenzaldehyde by DBU to anthranilic acid (AA,II) and the reaction of the latter with tetracyclo[6.3.0.04,11.05,9]undecane-3,6-dione (TCUD,I) to produce a heterocyclic tetracycloundecane derivative of pyrrolidinobenzoxazinone (TCUPB,III) are reported.
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■ Prieurianin-Type Tetranortriterpenoids from the Bark of Dysoxylum hainanense
Xiao-Dong Luo, Shao-Hua Wu. Xiao-Sheng Yang, Rong-Wei Teng, Yun-Bao Ma, Da-Gang Wu,* Xiao-Jiang Hao, Yang Lu, Xu-Ying Liu, and Qi-Tai Zheng
*Laboratory of Phytochemistry, Kunming Institute of Botany, The Chinese Academy of Sciences, Kunming, Yunnan 650204, China
Abstract
From the ethanolic extract of the bark of Dysoxylum hainanense Merr., three new seco-tetranortriterpenoids structurally related to prieurianin, dysoxylumins A (1), B (2) and C (3) were isolated. Their structures were elucidated on the basis of 1D and 2D NMR techniques. The structure and stereochemistry of compound 1 were demonstrated by X-Ray crystallography.
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■ Novel Rings B,D-Secolimonoids from the Stem Bark of Khaya senegalensis
Samir A. M. Abdelgaleil, Hiroaki Okamura, Tetsuo Iwagawa, Matsumi Doe, and Munehiro Nakatani*
*Department of Chemistry and Bioscience, Faculty of Science, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan
Abstract
Two new rings B,D-secolimonoids, named khayalactol and 1-O-acetylkhayanolide B, were isolated together with three known rings B,D-secolimonoids, methyl angolensate and its 6-hydroxy and 6-acetoxy derivatives, from the ether extract of the stem bark of a meliaceous plant Khaya senegalensis. The structure of these new compounds was elucidated by spectrospcopic means. The antifeedant property of the isolated compounds is also described.
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■ A Synthesis of (±)-Dihydronitraraine
Emmi Päiviö, Mathias Berner, Arto Tolvanen, and Reija Jokela*
*Laboratory of Organic Chemistry, Helsinki University of Technology, P.O. Box 6100, FIN-02015 HUT Espoo, Finland
Abstract
A short synthesis of (±)-dihydronitraraine (1) from an unknown 5,6,7,8-tetrahydroisoquinoline ester (3) is presented. The Fry reaction of tetrahydroisoquinolinium salt (4), followed by cyclization and hydrogenation, gave an alloyohimbane derivative (6), which was reduced to yield dihydronitraraine (1). Complete 1H NMR and 13C NMR data of dihydronitraraine (1) and intermediate (6) are reported.
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■ Reaction of N-Acylated Isofebrifugine with Acid
Yasuo Takeuchi,* Kumiko Azuma, Hitoshi Abe, and Takashi Harayama
*Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
The reaction of N-acylated isofebrifugine with hydrochloric acid is discussed. Although the corresponding deprotected compound was not isolated, three new heterocyclic compounds were obtained. Based on these findings, new furan and pyrrole derivatives were prepared.
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■ First Total Syntheses of (+)-Polyoxin B and (+)-Polyoxin D
Kimio Uchida, Keisuke Kato, Kentaro Yamaguchi, and Hiroyuki Akita*
*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
First total syntheses of the peptidyl nucleoside antibiotics, polyoxins B (1) and D (2), are achieved based on the coupling reactions of the N-protected L-carbamoyl-polyoxamic acid derivative (6) with polyoxin C (8), 6 with polyoxin C acid (9), respectively.
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■ Formation of Isoquinoline Derivatives by the Irradiation of N-Acetyl-α-dehydrophenylalanine Ethyl Ester and Its Derivatives
Hideki Hoshina, Hitoshi Tsuru, Kanji Kubo, Tetsutaro Igarashi, and Tadamitsu Sakurai*
*Departmnet of Applied Chemistry, Faculty of Engineering, Kanagawa University, Kanagawa-ku, Yokohama 221-8686, Japan
Abstract
The irradiation of a nitrogen-purged acetonitrile solution of the title compounds (1) with Pyrex filtered light was found to give isoquinoline derivatives (2) via the excited state (Z)-isomers, whereas in methanol 1-azetine derivative was also detected along with 2 but side reactions occurred appreciably on prolonged irradiation. An examination of substituent effects on the reactivities of the excited state (Z)-isomers shows that the efficiency for formation of 2 undergoes great steric and electronic effects of the substituent introduced into the benzene ring of 1, though the bulkiness of the alkoxycarbonyl group in 1 affected this efficiency to only a slight extent. On the other hand, in the presence of benzophenone as a triplet sensitizer, the starting (Z)-isomer underwent an exclusive isomerization into the corresponding (E)-isomer without yielding any isoquinoline derivative, being consistent with the occurrence of the photocyclization reaction from the excited singlet state (Z)-isomer.
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■ Solvent-free Synthesis of Thio-alkylxanthines from Alkylxanthines Using Microwave Irradiation
Rodrigo Rico-Gómez,* Francisco Nájera, Juan Manuel López-Romero, and Pedro Cañada-Rudner
*Departamento de Química Orgánica, Universidad de Malága, E-29071 Malága, Spain
Abstract
An expeditious, solvent-free procedure for the conversion of the xanthine bases theophylline, 8-methyltheophylline, caffeine, and theobromine to the corresponding 6-thio and 2,6-dithio derivatives using Lawesson’s reagent under microwave irradiation is proposed.
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■ Royleinine, a New Norditerpenoid Alkaloid from Delphinium roylei
Ayhan Ulubelen,* Ali H. Meriçli, Filiz Meriçli, Ufuk Kolak, Muhammed Arfan, Manzoor Ahmad, and Habib Ahmad
*Faculty of Pharmacy, University of Istanbul, 34452 Istanbul, Turkey
Abstract
A new norditerpenoid alkaloid, royleinine (1) has been isolated from the aerial parts of Delphinium roylei Munz, along with three more norditerpenoid alkaloids, isotalitazidine, condelphine and senbusine-C. The structure of 1 has been established on the basis of its spectroscopic data (IR, HRMS, 1H, 13C, 1H - 1H and 1H - 13C COSY and NOESY spectra).
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■ Recent Advances in the Synthesis of Heterocycles from Oximes
Edgars Abele and Edmunds Lukevics*
*Latvian Institute of Organic Synthesis, 21 Aizkraukles Street, Riga, LV-1006, Latvia
Abstract
Modern methodologies of preparation of three-, five-, six- and seven-membered heterocyclic compounds from oximes and their derivatives have been reviewed. Syntheses of bicyclic and tricyclic ring systems from oximes are included.