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. 8, 1996
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■ Conversion of Artemisinic Acid into (-)-Fabianane
Mankil Jung* and Byoung Hee Youn
*Department of Chemistry, Yonsei University, Seoul 120-749, Korea
Abstract
The conversation of (-)-fabianane from atemisinic acid was achieved in seven steps via photooxidative cyclization as a key step.
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■ The Palladium Catalysed Cross-coupling Reaction of Triethyl (1-Methylindol-2-yl)borate with Propargyl Carbonate
Minoru Ishikura* and Isao Agata
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
The palladium catalysed cross-coupling reaction of triethyl (1-methyindole-2-yl)borate with propargy carbobates could be used for a simple formation of 2-allenylindoles.
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■ Synthesis of Aminopyrimidopyidazines as Chemiluminescent Compounds by Reaction of Functionalized Maleimide with Various Amine Derivatives
Yoshinori Tominaga,* Noriko Yoshioka, and Seigo Kataoka
*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
The reaction of ketene dithipacetal, bis(methylthio)methylenepropanedinitrile, with nitromethane gave 2-hydroxyimino-4-cyano-3-methylthiomaleimide (3) which was readily derived to the ncorresponding 4-cyano-3-methylthiomalemide (5) by methylation with dimethyl sulfate followed by hydrolysis with hydrochloric acid. Compound 5 smoothly reacted with various amine compounds to give the corresponding amino-polycyclic pyrimidines containing a pyrroline ring, which were redily converted to the desired polycyclic pyridazine derivatives in good yields.
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■ Preparation of p-Benzoquinono[b]oxepines and Their Aromatic Ring Annulated Derivatives
Naoki Kakusawa, Kiyohiro Inui, Jyoji Kurita, and Takashi Tsuchiya*
*School of Pharmacy, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan
Abstract
Reaction of pyridazine N-oxides with 2,3-didehydrobenzoquinone resulted in the formation of the novel p-benzoquinono[b]oxepines, from which their aromatic ring annulated derivatives such as naphthoquinono-, anthraquinono-, 1-azanaphthoquinini-oxepines were prepared by Diels-Alder reactions.
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■ A Convenient Synthesis of Diastereomeric Synthons: Ethyl 3-Methyl-1,2,3,4-tetrahydroisoquinoline-1-acetates by Direct and Reverse Substituent Introduction
Ferenc Fülöp,* János Tari, Gábor Bernáth,* and Pál Sohár
*Institute of Pharmaceutical Chemistry, Albert Szent-Györgyi Medical University, POB 121, H-6701 Szeged, Eötvös u. 6, Hungary
Abstract
The two diastereomers of ethyl 3-methyl-1,2,3,4-tetrahydroisoquinoline-1-acetate (4 and 5) were synthesized from 1-(3’,4’-dimethoxyphenyl)isopropylamine (1) by direct and reverse substituent introductions. The cause of the diastereo-stereoselectivity is rationalized.
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■ Absolute Stereochemistries of Giganin and Longanin, Bioactive Non-tetrahydrofuran Ring Annonaceous Acetogenins from Asimina longifolia
Qing Ye, Jerry L. McLaughlin,* and Dean Evert
*Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, 1333 Robert E. Heine Pharmacy Building West Lafayette IN 47907, Indiana 47907, U.S.A.
Abstract
Two cytotoxic Annonaceous aetogenins, giganin (1) and longanin (2), were isolated from the leaves and twings of Asimina longifolis (Annonaceae). These compounds represented the type of Annonaceous astogenin lacking either tetrahydrofuran or epoxide rings along the aliphatic chain. Compound (2) is novel and giganin is previously known. The planar structures and absolute configurations of both were elucidated by 1H and 13C nmr and ms before and after certain chemical derivatizations. Compound (2) gave cytotoxic ED50 values comparable to those of adriamycin in a panel of human solid tumor cell lines.
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■ One-Pot Synthesis of New Spiro- and Tricyclic Pyridazino[4,5-c]pyridazinones
Tetsuo Yamasaki, Yuji Yoshihara, Yoshinari Okamoto, Tadashi Okawara, and Mitsuru Furukawa*
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
New 1,4-dihydropyridazino[4,5-c]pyridazine-4-spiro-3’-lactones (3) were prepared by one-pot cyclization from 5-hydrazinopyridazinones (1), 4-bromo-5-hydrazinopyridazinones (5) and a-ethoxyalyllactones (2). The reaction of 5 with 2-hydroxy-3,5-diethoxycarbonylcyclopent-2-en-1-one (6) afforded cyclopenteno[c]pyridazino[4,5-c]pyridazinone (7) and 12a,13a-diethoxycarbonyl-5,8-dimethyl-1,2,5,8,11,12,12b,13a-octahydro-2,3,5,6,7,8,10,11-octaazadibenzo[a,i]fluorene(8).
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■ Synthesis and Antimalarial Activity of New 4,6-Dialkoxy- and 4,6-Bis(alkylthio)pyrido[3,2-g]quinoline Derivatives
Carole Matias, Abdallah Mahamoud, Jacques Barbe, Bruno Pradines, and Jean-Claude Doury
*Faculte de Pharmacie, 27, Bd Jean-Moulin 13385 Marseille Cedex 5, France
Abstract
A set of 4,6-dialkoxy- and 4,6-bis(alkylthio)pyrido[3,2-g]quinoline derivatives was prepared from 2,8,10-trimethylpyrido[3,2-g]quinoline-4,6-dione as starting material. The latter was synthesized in a simple and convenient two step procedure. These compounds were tested in vitro on chloroquinosusceptible and chloroquinoresistant strains of Plasmodium falciparum. Two of them possess a 50% inhibitory concentration (IC50) lower than 100nM against both strains.
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■ Synthesis of 2,12-Dithia[3](2,6)pyridino[3](1,4)cycl[3.2.2]azinophane and It's Barrier to Methylene Twist
Yoshiro Matsuda,* Keisuke Katou, Hiroshi Matsumoto, Takanobu Nishiyori, Takashi Uemura, and Maki Urakami
*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
A synthesis of the title compound (11) is completed starting from indolizine (3). Key intermediate, bis(mercaptomethyl)cycl[3.2.2]azine (9) has been synthesized by reduction of bis(acetylthiomethyl)cycl[3.3.2]azine (8) with LiAlH4. 2,12-Dithia[3](2,6)pyridino[3](1,4)cycl[3.2.2]azinophanes (11a,b) have been synthesized by the reaction of 9 with 2,6-bis(bromomethyl)pyridine (10) in the presence of Cs2CO3 by the high dilution method. In the 1H-nmr spectrum of 11a,b, these exist in the syn conformation in their 1H-nmr spectra. With regard to 2,12-dithia[3](2,6)pyridino[3](1,4)cycl[3.2.2]azinophane (11a), the coalescence temperature for the methylene twist yields an activation barrier, δ G‡, of 79.5 kJ mol-1 for variable temperature (VT) nmr method.
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■ Synthesis of 3-Alkylfuropyridines via Palladium-catalyzed Cyclization of Iodopyridinyl Allyl Ethers
Sung Yun Cho, Sung Soo Kim, Kyung-Ho Park, Seung Kyu Kang, Joong-Kwon Choi, Ki-Jun Hwang, and Eul Kgun Yum
*Korea Research Institute of Chemical Technology, P. O. Box 107, Yusong, Taejon 305-606, Korea
Abstract
The palladium-catalyzed cyclization of iodopyridinyl allyl ethers derived from dihalopyridines and sodium allyl alkoxide provides from [2,3-b]pyridines, furo[3,2-c]pyridines, and furo[2,3-c]pyridines.
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■ Synthesis of Homohydantoin-Thiazolidine Bicyclic Compounds
Mostafa Hatam, Sabine Köpper, and Jurgen Martens*
*Fachbereich Chemie, Universitat Oldenbrug, P. O. Box 2503 D-26111 Oldenburg, Germany
Abstract
Preparation of various homohydrantoin-thiazolidine bicyclic compounds from 3-thiazolines is described. The reaction of C2-mono-substituted 3-thiazolines proceeds with considerable diastereoselectivity. The assignment for relative configuration of the prepared compounds was carried unequivocally by nmr spectroscopical analysis.
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■ Formation of Spiro-Lactols upon Reaction of Ninhydrin with Methyldiazines
Gottfried Heinisch, Wolfgang Holzer,* Kurt Mereiter, Barbara Strobl, and Changtu Zheng
*Institute of Pharmaceutical Chemistry, University of Vienna, Althanstrasse14, A-1090 Vienna, Austria
Abstract
Reaction of ninhydrin (4) with 4-methylpyridazine or 4-methylquinoline leads to 2-hydroxy-2-heteroarylmethyl-1,3-indandiones (5), which resist dehydration to the corresponding 2-heteroarylmethylene-1,3-indandiones (2). In contrast, employing methyl(di)azines with a methyl group in α-position to a ring nitrogen atom (3-methylpyridazine, 4-methylpyrimidine, 2-methylpyrazine, 2-methylquinoline, 2-methylquinoxaline) results in the exclusive formation of novel 3a’,8b’-dihydroxy-3’-heterozryl-3a’,8b’-dihydrospiro[indane-2,2’(3’H)-4’H-indeno[1,2-b]furan]-1,3,4’-triones (7) which might result from cyclisation of initially formed 2,2’-dihydroxy-2,2’-(heteroarylmethylene)bis-1,3-indandiones (6).
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■ Asymmetric Synthesis of (R)-(+)-Noranicanine
Keiko Komori, Keiko Takaba, and Jun-ichi Kunitomo
*Faculty of Pharmaceutical Science, Mukogawa-Women's University, 11-68 Koushien Kyuban-Cho, Nishinomiya, Hyogo 663-8179, Japan
Abstract
Optically active (R)-(+)-noranicanine (1) was synthesized via stereoselective reduction of the corresponding iminium ion possessing a chiral auxiliary by polniaszek’s method.
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■ Research on Antiviral Agents. 5. Lithiation of 6-Methyluracil as a New and Efficient Entry to C(6)-Substituted Uracils
Maurizio Botta,* Raffaele Saladino, Giuliano delle Monache, Gabriella Gentile, and Rosario Nicoletti*
*Dipartimento Agrochimico, Universita degli studi di Viterbo "La Tuscia", Via San Camillo de Lellis, 01100 Viterbo, Italy
Abstract
Synthesis of numerous C(6)-substituted uracils can be effected by lithiation of N(1),N(3)-substituted 6-methyluracils (1) and (4) with LiHMDS, followed by the reaction of the resulting lithio derivatives with carbon, sulfur, and selenium electrophiles. The unexpected migration of the N(1)-benzoyl group in the metalation-alkylation and the high stereoselectivity obtained in the reaction with substituted cyclohexanones are also reported.
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■ Preparation and Conformational Study of Deformyl-Z- and Deformyl-E-geissoschizine Epimers and Na-Boc Derivatives, and Their Nb-Oxides
Mauri Lounasmaa,* Reija Jokela,* Pirjo Hanhinen, Christiane Laine, and Ulla Anttila
*Laboratory of Organic Chemistry, Helsinki University of Technology, P.O. Box 6100,FIN-02015 HUT, Espoo, Finland
Abstract
Syntheses are reported for deformylgeissoschizine isomers (1-4) and their Na-Boc derivatives (5-8), as well as for their Nb-oxides (cis and trans) (9-13) and (16-20). Predominant conformations of the compounds were determined by nmr measurements.
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■ 3-Lithio-1-(triisopropylsilyl)indole. Preparation and Reactions with Electrophilic Reagents
Mercedes Amat, Swargam Sathyanarayana, Sabine Hadida, and Joan Bosch*
*Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Av. de Joan XXIII, s/n, 08028 Barcelona, Spain
Abstract
3-Lithio-1-(triisopropylsilyl)indole (2) is prepared by halogen-metal exchange from the corresponding 3-bromoindole and regioselectively reacts with a variety of electrophilic reagents to give 3-substituted indoles.
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■ A Convenient Synthesis of N-Substituted 2,3-Dihydro-3-oxoisothiazolo[5,4-b]pyridines in Acidic Condition
Hideo Terauchi,* Akihiko Tanitame, Keiko Tada, and Yoshinori Nishikawa
*Discovery Research Laboratories Ö†, Dainippon Pharmaceutical Co., Ltd., Enoki 33-94, Suita, Osaka 564, Japan
Abstract
A novel and convenient synthesis of N-substituted 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridines which possess potent in vitro inhibitory activity against gastric (H+/K+)-ATPase is reported. Compared with the methods reported previously, the compounds were syntehsized more readily in relatively high yields by conversion of N-substituted 2-(benzyl-, 1-phenylethyl-, and benzhydrylsulfinyl)nictinamides (17d-l) in a diluted hydrochloricccc acid-methanol solution at room tempeature.
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■ Asymmetric Synthesis of Key Synthetic Intermediates of Aspidosperma and Hunteria Type Indole Alkaloids
Kunisuke Okada,* Kazumasa Murakami, Hideo Tanino, Hisae Kakoi, and Shoji Inoue
*Faculty of Pharmacy, Meijo University, 150 Yagoto, Tempaku-ku, Nagoya, Aichi 468-8503, Japan
Abstract
Chiral synthon (6), prepared from α,β-epoxy-ketone (4) via 1,2-acyl migration reaction as a key step, was converted to lactones (7) and (8), the key intermediates for Aspidosperma and hunteria type indole alkaloids.
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■ Synthesis of Yuehchukene Analogues, Murrapanine and Normurrapanine Utylizing Thermal Reaction of β-(1-Hydroxybutenyl)indoles under Neutral Reaction Conditions
Jyh-Horng Sheu,* Yua-Kuang Chen, Huey-Fen Chung, Ping-Jyun Sung, and Song-Fong Lin
*Institute of Marine Resources, National Sun Yat Sen University, 70 Lien-Hai Rd., Kaohsiung, 80424, Taiwan, R.O.C.
Abstract
β-(1-Hydroxybutenyl)indoles, which were prepared in high yields from indole-3-carboxaldehyde, could be converted into yuehchukene analogues (8a,b), murrapanine (9a) and normurrapanine (9b) in one step under thermal-induced reaction conditions in neutral solution of ethylene glycol and water. β-(1-Hydroxybutenyl)indoles are supposed to be dehydrated to 1-(β-indolyl)-1,3-nutadienes which react further to yuehchukene analogues via a Diels-Alder pathway. Murrapanine and normurrapanine showed a cytotoxicity toward KB cells.
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■ Anomalous Bamford-Stevens Reaction of cis-N-Alkyl-3-phenylaziridin-2-yl Phenyl Ketones. Preparation of 1,6-Dihydro-1, 2,3-triazine Derivatives
Motonobu Morioka,* Masahiko Kato, Hiroshi Yoshida, and Tsuyoshi Ogata
*Department of Applied Chemistry, Faculty of Engineering, Shizuoka University, 3-5-1 Johoku, Hamamatsu 432-8561, Shizuoka, Japan
Abstract
The Bamford-Stevens reaction of cis-aziridinyl ketone tosylhydrazones (1a-k) yielded 1,6-dihydro-1,2,3-triazine derivatives (3a-k) without eliminating the nitrogen molecule. The reaction was induced using a slight excess of sodium hydride (2) or sodium ethoxide. When a large amout of sodium ethoxide was used, 1-isopropylamino-3,5-dephenylpyrazole (4a) was formed from the corresponding substrate (1a).
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■ A New Route for the Synthesis of 3-Methoxythiophenes
Jaime Lissavetzky* and Ignacio Manzanares
*Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, 28006 Madrid, Spain
Abstract
A new synthesis of 4-substituted, 5-substituted and 4,5-disubstituted 3-methoxythiophenes is reported. The reaction takes place in three steps in nearly quantitative yields starting from methyl 3-hydroxythiophene-2-carboxylates.
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■ Silver(I) Salt Promoted Generation of Nitrile Oxides from Hydroxymoyl Chlorides
Yuji Tokunaga, Masataka Ihara, and Keiichiro Fukumoto*
*Pharnaceutical Institute, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan
Abstract
Treatment of hydroximoyl chlorides with silver(I) salt in the presence of olefins as dipolarophiles caused the formation of nitrile oxides and the subsequent intermolecular 1,3-dipolar cycloaddition forming corresponding isoxazoline derivatives in high yields.
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■ Asymmetric Synthesis of (R)-1-(2-Methoxy-3,4-methylenedioxybenzyl)-2-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoqunoline (So-called "Fumarizine")
Keiko Takaba, Keiko Komori, Jun-ichi Kunitomo,* and Toshimasa Ishida
*Faculty of Pharmaceutical Science, Mukogawa-Women's University, 11-68 Koushien Kyuban-Cho, Nishinomiya, Hyogo 663-8179, Japan
Abstract
(R)-1-(2-Methoxy-3,4-methylenedioxybenzyl)-2-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline (so-called "fumarizine") (1) was synthesized via the stereoselective reduction of the corresponding chiral iminium ion (11), which was obtained by the Bischler-Napieralski cyclization of N-[(R)-1-phenylethyl]-N-2-(3,4-methylenedioxyphentlethyl]-2-(2-methoxy-3,4-methylenedioxyphenyl)acetamide (10). The synthetic compound (1) was shown to difffer from natural fumarizine, the structure of which is not formula (1).