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. 48, No. 9, 1998
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■ Synthesis of Tetrapyrrole Nitrogen Mustards with Potential Anti-tumor Activities
Zhi-Long Chen,* Wei-Qin Wan, Jing-Rong Chen, Fang Zhao, and De-Yu Xu
*Institute of Pharmaceutical Chemistry, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China
Abstract
Eight porphyrin nitrogen mustards and six meso-tetraphenylporphin nitrogen mustards were synthesized. Most of the compounds possess both the chemotherapeutic and photochemotherapeutic effects on tumor.
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■ Epoxidation of Four Possible Conformers of Humulene 9,10-Epoxide: First Isolation of 2R*, 3R*, 6S*, 7S*, 9S*, 10S*-Humulene 2,3;6,7;9,10-Triepoxide
Kiyoharu Hayano,* Nobue Ito, Makoto Sato, Masayuki Takishima, and Katsura Mochizuki
*Chemistry Laboratory, Hokkaido College of Education, Ainosato, Sapporo, Hokkaido 002-8502, Japan
Abstract
The complete reaction of humulene 9,10-epoxide {(2E, 6E)-9,10-epoxy-3,7,11,11-tetramethylcycloundeca-2,6-diene, (1)} with m-CPBA produced a hitherto unknown 2R*, 3R*, 6S*, 7S*, 9S*, 10S*-2,3;6,7;9,10-triepoxy-3,7,11,11-tetramethylcycloundecane (6) together with three known humulene triepoxides (7, 8 and 9), in the ratio of 6 : 7 : 8 : 9 = 1.3 :11.5 : 22.6 : 64.6. The configuration of 6 was determined X-Ray crystallography (C15H24O3: space group p21/n with a = 14.147 (4) Å, b = 8.419 (3) Å, c = 12.238 (4) Å, β = 102.10 (3)°, Z = 4). The new triepoxide (6) maintained configuration corresponding to the TT conformer, one of the four possible conformers of 1.
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■ Regioselective Ring-Opening of 2,3-Epoxy Alcohols with Tetramethylammonium Triacetoxyborohydride
Toshio Honda* and Hirotake Mizutani
*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
Treatment of 2,3-epoxy alcohols with tetramethylammonium triacetoxyborohydride afforded the ring-opening products at the C-3 position, regioselectively, where the presence of Me4NBH(OAc)3 increased the reaction rate and regioselectivity by forming the chelation intermediate between the metal center and the epoxy alcohol oxygens.
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■ Regiospecific Demethylation-Sulfonation of 2',3'-Dimethoxyflavones
Amar Habsaoui, José Luis Franquet Cami, Jean Claude Wallet,* and Emile M. Gaydou
*Laboratorie de Phytochimie, Case 412, Faculté del Sciences de St-Jérome, Avenue Escadrille Normandie-Niemen 13397 Marseille Cedex 20, France
Abstract
By a careful control of the temperature at 85 °C, the selective demethylation of 2’,3’-dimethoxyflavones with sulfuric acid occurs at the 2’-hindered methoxy group followed by para sulfonation. At higher temperature, demethylation is complete.
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■ [4π+2σ]-Type Cycloaddition Reactions of Naphtho[b]cyclopropene with C,N-Diphenylnitrones to Form Dihydronaphthoxazines
Shinichi Ando, Junichi Imamura, Atsushi Hattori, Makiko Tajitsu, and Katsuhiro Saito*
*Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Abstract
Reactions of naphtho[b]cyclopropene with C,N-diphenylnitrone derivatives afforded dihydronaphthoxazine derivatives. The reaction is considered to proceed through a [4π + 2σ]-type cycloaddition process via a zwitter ionic intermediate generated by a rupture of the C-C σ-Bond of the three-membered ring of naphtho[b]cyclopropene caused by a nucleophilic attack of tne nitrone.
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■ The Gracilines: A Novel Subgroup of the Amaryllidaceae Alkaloids
Seda Noyan, Gudrun Hopp Rentsch, Mustafa Ali Önür, Tekant Gözler, Belkis Gözler, and Manfred Hesse*
*Organisch-chemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
Abstract
A new subgroup of the Amaryllidaceae alkaloids having a 10b,4a-ethanoiminodibenzo[b,d]pyrane (2-benzopyrano[3,4-d]indole) uncleus is isolated from two different Galanthus species as three novel monomeric alkaloids, (+)-graciline (1), (+)-11-acetoxygraciline (2) and (+)-3,4-dihydro-3-hydroxygraciline (3). The fourth new compound, (-)-digracine (4) is a dimer of two such moieties.
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■ Synthesis of 2-Substituted 3-Alkenyl-indoles by the Palladium-catalyzed Cyclization Followed by Alkenylation (Heck Reaction)
Akito Yasuhara,* Masashi Kaneko, and Takao Sakamoto*
*Faculty of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan
Abstract
The reaction of N-protected 2-alkynylanilines with electron-deficient alkenes in the presence of a palladium (II) catalyst and copper dichloride in acetonitrile gave 2-substituted 3-alkenylindoles.
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■ Five New Withanolides from Withania coagulans
Atta-ur-Rahman,* Muhammad Yousaf, Waseem Gul, Samina Qureshi, M. Iqbal Choudhary, Wolfgang Voelter, Antje Hoff, Fricke Jens, and Aniqa Naz
*International Centre for Chemical Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
Phytochemical studies on the whole plant of Withania coagulans have resulted in the isolation of five new withanolides, namely coagulins H, I, J, K and L (1-5). Their structures have been established as (17S,20S,22R)-5α,6β,14α,15α,17,20-hexahydroxy-1-oxowitha-2,24-dienolide (1), (14R,17S,20S,22R)-5α,6β,17-trihydroxy-14,20-epoxy-1-oxowitha-2,24-dienolide (2), (14R,17R,20R,22R)-3β,27-dihydroxy-14,20-epoxy-1-oxowitha-5,24-dienolide (3), (14R,17R,20R,22R)-14,20-epoxy-3β-(O-β-D-glucopyranosyl)-1-oxowitha-5,24-dienolide (4) and (14R,17R,20R,22R)-14,17,20-trihydroxy-3β-(O-β-D-glucopyranosyl)-1-oxowitha-5,24-dienolide (5), respectively on the basis of spectroscopic techniques.
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■ Stereocontrolled Addition of Grignard Reagents to Chiral 1,3-Oxazolidines Having N-Methoxybenzyl Groups: Effect of N-Substituent in Diastereoselectivity
Takayasu Yamauchi, Hiroshi Takahashi, and Kimio Higashiyama*
*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
Chiral 1,3-oxazolidines having various N-methoxybenzyl groups were synthesized from (R)-phenylglycinol in three steps. The reactions of chiral 1,3-oxazolidines with Grignard reagents proceeded gently to give the corresponding chiral amines in quantitative yield and high diastereoselectivity. The best results regarding diastereoselectivity were achieved using a chiral 1,3-oxazolidine having N-2,4,6-trimethoxybenzyl moiety. These nitrogen functional groups could be easily removed from the chiral amines using TFA.
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■ The X-Ray Molecular Structure of (Z)-1-(4,5-Diphenyl-1,2,3-triazol-2-yl)-1,2-diphenylethylene at 200 K
Concepción Foces-Foces,* Rostislav E. Trifonov, Vladimir A. Ostrovski,* Michail B. Shcherbinin, and José Elguero
*Departamento de Cristalografía, Instituto de Química-Físca 'Rocasolano', C. S. I. C., Serrano, 119, E-28006 Madrid, Spain
Abstract
The molecular and crystal structure of (Z)-1-(4,5-diphenyl-1,2,3-triazol-2-yl)-1,2-diphenylethylene has been determined by X-Ray analysis at 200K. The above (Z)-isomer was crystallized from the mixture of two 2H-triazole stereoisomers.
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■ A Novel Tetracyclic System Containing the 1,2,6-Thiadiazine Ring: Synthesis, Structural Assignment and Tautomeric Studies
Nuria Campillo, Angeles de la Cruz, Pilar Goya, and Juan A. Páez*
*Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, E-28006 Madrid, Spain
Abstract
Condensation of 3,4,5-triamino-2H-1,2,6-thiadiazine 1,1-dioxide with phthalaldehyde afforded a tetracyclic system of thiadiazino[3’,4’:4,5]imidazo[2,1-a]isoindole 2,2-dioxide. In order to establish the correct structure it was necessary to use an 15N-labelled thiadiazine derivative as starting material. Ab initio theoretical calculations and the Onsager model have been used to study annular tautomerism in this novel structure.
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■ On the Reaction of Dipivaloylketene Dimer with Oximes and Hydrazines — Synthesis of Tetraoxaadamantanes
Turkaram S. Dalvi, C. Oliver Kappe, Curt Wentrup, and Gert Kollenz*
*Institut fur Organische Chemie, Karl-Franzens-Universitat Graz, Heinrichstr. 28, A-8010 Graz, Austria
Abstract
Synthesis of mono-functionalized trioxabicyclo[3.3.1]nona-3,7-dienes ("bridged bisdioxines") (3) as well as (7), and their transformation into the corresponding 2,4,6,8-tetraoxadamantanes (5) and (8), respectively, by proton-catalyzed hydrolysis, is described.
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■ Nitrogen Bridgehead Compounds Part 90. An Efficient Versatile Synthesis of 1-Methyl-2-substituted 1,2,3,4-Tetrahydro-6H-pyrazino[2,1-b]quinazoline-3,6-diones
József Kökösi,* János Almási, Benjamin Podányi, Miklós Fehér, Zsolt Böcskei, Kálmán Simon, and István Hermecz*
*Institute for Pharmaceutical, Chemistry Semmelweis, University of Medicine, Högyes E. u. 9. 1092 Budapest, Hungary
Abstract
A versatile synthesis of 2-substituted 1-methyl- and 1,4-dimethyl-1,2,3,4-tetrahydro-6H-pyrazino[2,1-b]quinazoline-3,6-diones is presented, starting from 2-(1-bromoethyl)quinazolin-4(3H)-one. The key step of the reaction sequence is the diastereoselective cyclization of 2-{[1-(N-2-haloacyl-N-substituted amino]ethyl}quinazolin-4(3H)-ones. Usually 1,4-dimethyl derivatives are obtained as pure racemic cis-compounds (2-alkyl and 2-benzyl derivatives), or a mixture of diastereomers, containing the 4-methyl group in quasiaxial position.
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■ Diels-Alder Cycloaddition of Methacrolein N,N-Dimethylhydrazone to 1,4-Naphthoquinone Derivatives
Alma M. Jiménez, M. Victoria Martín, and M. Carmen Paredes*
*Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, E-28006 Madrid, Spain
Abstract
Diels-Alder cycloadditions of naphthoquinone derivatives (3-8) with methacrolein N,N-dimethylhydrazone (9) have been investigated. In the reaction with the quinones (3-4) and (8) the initial cycloadducts (10, 11 and 17a,b) were isolated in good yields. However, the cycloaddition with quinones (5-7) affords directly the corresponding aromatized azaanthraquinones (12, 15a and 16a,b) in good yields.
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■ Synthesis and Transformations of 2-Amino-1-(4,5-Dihydro-1H-imidazol-2-yl)benzimidazoles. A Route to 2,3-Dihydrobenzo[4,5]imidazo[1,2-c]imidazo[1,2-a][1,3,5]triazine Ring System
Franciszek Saczewski,* Tomasz Debowski, and Jacek Szmigiel
*Department of Organic Chemistry, Medical University of Gdansk, Al. Gen. Hallera 107, 80-416 Gdansk, Poland
Abstract
Starting from 3-(4,5-dihydro-1H-imidazol-2-yl)-2-oxo-2,3-dihydrobenzimidazole-1-carbonitriles (1a-e) and the 2-amino-1-(4,5-dihydro-1H-imidazol-2-yl)benzimidazoles (2a-e) and 1-(4,5-dihydro-1H-imidazol-2-yl)-2-oxo-2,3-dihydrobenzimidazoles (3a-e) have been synthesized. Cyclocondensation of 2a with acetic anhydride or acyl chlorides gave novel functionalized 2,3-dihydrobenzo[4,5]imidazo[1,2-c]imidazo[1,2-a]triazines (4a-d).
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■ Total Synthesis of Topsentin, Antiviral and Antitumor Bis(indolyl)imidazole
Ikuo Kawasaki, Hideo Katsuma, Yohko Nakayama, Masayuki Yamashita, and Shunsaku Ohta*
*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan
Abstract
Topsentin (1), which was isolated from marine sponges and has antiviral and antitumor activities, was synthesized via a cross coupling reaction in the presence of palladium catalyst at th 5-position and an acylation at the 2-position of imidazole ring.
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■ Reaction of (Vinylimino)phosphoranes with Electron-deficient Acetylenes: Synthesis and Reactivity of 1,2λ5-Azaphosphinines
Hiroyuki Yamamoto, Tomoshige Kobayashi, and Makoto Nitta*
*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
The reactions of trimethoxy(1-Phenylvinylimino)phosphorane and methoxydiphenyl(1-phenylvinylimino)phosphorane with electrone-deficient acetylenes results in the formation of 1,2-λ5-azaphosphinines (7a,b) and (9a,b), while those of triphenyl(1-phenylvinylimino)phosphorane and trimethoxy(vinylimino)phosphorane with dimethyl acetylenedicarboxylate (DMAD) proceeds via formal [2+2] cycloadducts to give functionalized butadienes. Thermal rearrangement of 7a,b and the preparation of HBF4 salts of 9a,b are studied. Reactions of compounds 7a,b and 9a with DMAD leading to λ5-phosphinine derivatives are studied as well.
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■ Preparation of Both (D)- and (L)-Serinol Derivatives from N-[(S)-α-Methylbenzyl]-aziridine-2(S)-methanol
Soo-Kyung Choi and Won-Koo Lee*
*Department of Chemistry, Sogang University, Seoul 121-742, Korea
Abstract
Both (D)- and (L)-serinol derivatives were prepared efficiently from enantiomerically pure N-[(S)-α-methylbenzyl]aziridine-2(S)-methanol. Each of those serinols was transformed to the corresponding aldehyde and reacted with an ylide to give a coupling product.
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■ Pyrimidine Derivatives Starting from Dicyanoketene Ethylene Acetal
Zhijun Wang and Richard Neidlein*
*Pharmazeutisch-Chemishces Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany
Abstract
Dicyanoketene ethylene acetal (1) reacted with substituted guanidines to yield o-aminocyanopyrimidines, which reacted with N,N-dimethylformamide dimethyl acetal to afford N,N-dimethylaminomethyleneaminopyrimidine derivatives. A new approach to pyrimido[4,5-d]pyrimidines from o-aminocyanopyrimidine and N-dichloromethylenedialkyliminium chlorides followed by cyclization with ammonium hydroxide was reported.
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■ Studies on the Metabolites of Penicillium vulpinum
Mitsuko Makino, Toshinari Endoh, Yoshio Ogawa, Kazuko Watanabe, and Yasuo Fujimoto*
*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan
Abstract
Two new metabolites, 2-methoxymethyl-3-pentylphenol (1) and 3-butyl-7-hydroxyphthalide (2), were isolated from the culture broth of Penicillium vulpinum along with four knwon phenols, gentisyl alcohol (3), 2-methylhydroquinone (4), 3-hydroxybenzyl alcohol (5), 6-methylsalicyclic acid (6), and epoformin (7). The structures of new metabolites were determined by analyses of their MS and NMR spectra. It was found that the cytotoxic activity of the culture broth of P. vulpinum was mainly due to epoformin (7) and 2-methylhydroquinone (4).
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■ Reactions of 2-tert-Butyl-3-phenyl-oxaziridine with Alkyl Isothiocyanates and Its Application to Glucosyl-aminoheterocycle Synthesis
Masao Shimizu,* Yasuo Gama, and Isao Shibuya
*National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
Abstract
2-tert-Butyl-3-phenyloxaziridine was heated with alkyl isothiocyanates to afford 4-alkyl-2-tert-butyl-3-phenyl-1,2,4-oxadiazolidine-5-thiones. The reaction mechanism of the ring formation was discussed. This reaction was applicable to synthesis of glucosylaminoheterocycles.
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■ Use of Enzymes in Preparation of Enantiopure 1,4-Dihydropyridines
Stefan Marchalín, Miloslav Chudík, Vladimír Mastihuba, and Bernard Decroix*
*Laboratoire de Chimie, Faculté des Sciences et Techniques, Université du Havre, 25, rue Philippe Lebon, BP 540, 76058 Le Havre Cedex, France
Abstract
Various chemoenzymatic routes to optically pure biologically active dihydropyridines are reviewed. The review is focused on influence on the biotransformation of the main in vivo enzymatic activity of the hydrolase (lipase, esterase, protease), the microorganism source of the lipase and the substituents of the 1,4-dihydropyridine ring, as well as the physicochemical properties of the solvent and the nature of the nucleophile. The influence of these variables in the desymmetrisation of prochiral diesters or in the resolution of racemic compounds is analyzed.