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. 12, 1998
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■ Stereoselective Intermolecular Hydride Shift Mechanism of the New Reduction of Benzylic Alcohols with Acid
Masaru Kihara,* Junichi Andoh, and Chiaki Yoshida
*Pharmaceutical Sciences, Graduate of School, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Abstract
A stereoselective intermolecular hydride shift mechanism of the new reduction reaction of the benzylic hydroxy group of 4-hydroxy-4-phenyl-1,2,3,4-tetrahydroisoquinoline (1) to the corresponding alkane (2) with acid was proved by reaction of the deuterated derivatives (5 and 6) of 1.
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■ Synthesis of β-Carboline Derivatives and Their Interaction with Duplex-DNA
Sanae Tamura, Takeo Konakahara,* Harunobu Komatsu, Tomokazu Ozaki, Yuichi Ohta, and Hiroki Takeuchi
*Department of Industrial Chemistry, Faculty of Science and Technology, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
3-Amino-9-N-(2-aminoethyl)carbamoylethyl-β-carboline (3) was synthesized from 3-methoxycarbonyl-β-carboline through successive cyanoethylation, Curtius rearrangement, and addition reaction of ethylenediamine in 45% overall yield. The terminal aliphatic amino group of 3 was transformed to a N’-methylureido group with succinimidyl N-methylcarbamate to afford a compound 4 in 80% yield. Affinity of 3, 4, β-carboline (1), and 3-amino-β-carboline (2) to a DNA oligomer or calf thymus DNA was spectrophotometrically studied. Optical spectroscopy of these β-carbolines showed 25 ~ 65 nm bathochromic shifts of the light absorption bands upon binding to the nucleic acids, which suggests binding by intercalation. Scatchard plots, obtained by fluorescence titration, gave the corresponding binding constants KD to the DNA oligomer; 7.45 x 103, 5.13 x 105, 7.34 x 105, and 7.01x 105, respcetively. The terminal aliphatic amino group considerably decreases the intercalating ability of 3 to DNA.
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■ Photo-induced Rearrangement of 1-Ethoxy-2-phenylindole
Koji Yamada and Masanori Somei*
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
Photoirradiation of 1-ethoxy-2-phenylindole in methanol afforded 3- and 6-ethoxy-2-phenylindoles. The structural determination of the latter is carried out by direct comparison of its spectral data with those of the authentic 4-, 5-, 6-, and 7-ethoxy-2-phenylindoles, whose syntheses are also included.
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■ Substitutions at the Thiazole Moiety of Epothilone
Michael Sefkow* and Gerhard Höfle
*Gesellschaft fur Biotechnologische Forschung mbH, Mascheroder Weg 1, D-38124 Braunschweig, Germany
Abstract
Epothilone A is metalated at low temperature with an excess of butyllithium preferentially at C19 of the thiazole moiety. After addition of various carbon and heteroatom electrophiles the corresponding substitution products were obtained. Some of them have similar cytotoxic activity than the starting material.
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■ Solution- and Solid-Phase Synthesis of Combinatorial Libraries of Trisubstituted 1,3,5-Triazines
Thierry Masquelin,* Nathalie Meunier, Fernand Gerber, and Gérard Rossé
*F.Hoffmann-La Roche Ltd., Pharma Research, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
Abstract
A general synthesis of trisubstituted 1,3,5-triazines of types (4) and (5) by condensation of amidines (2) and thiouronium salts (3) with dimethyl cyanoiminodithiocarbonate (1) was first established in solution (Scheme 1). Further investigations were directed toward a multidirectional cleavage procedure of the 2-alkylsulfinyl intermediates with different nucleophiles to form highly substituted 1,3,5-triazines of type (8) and (9). This methodology was successfully transferred onto solid support taking advantages of a sulfur-based safety catch linkage, using the polymer-bound thiouronium salt (11) (Scheme 3). In addition, other compounds libraries were chemoselectively generated on solid support in good to excellent yields combining both solution- and solid-phase synthesis, sarting from a resin-bound thiol (15) and cyanuric chloride (16) (Scheme 4).
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■ Synthesis of Vinca Alkaloids and Related Compounds XCII. Umpolung Reactions of Enamines through Enammonium Salts
András Lukács, Lajos Szabó, Eszter Baitz-Gács, Petra Bombicz, András Dobó, György Kalaus, and Csaba Szántay*
*Institute of Inorganic Chemistry, Technical University of Budapest, Gellért tér 4, H-1521 Budapest, Hungary
Abstract
Preparation of enammonium salt from enamine causes Umpolung, i.e. reverses the reactivity of the original compound. Consequently salt (1) or (9) can be reacted with cyanide anion which attacks C1 resulting either in unsaturated cyanide (11) or rearranged products like 5, 12, 13.
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■ Synthesis of Pyrido[2,3-d]pyrimidines via Palladium-catalyzed Coupling Reaction Followed by Electrocyclic Reaction
Kee Yoon Rho, Joong Hyup Kim, Sung Hoon Kim, and Cheol Min Yoon*
*Department of Chemistry, College of Science and Technology, Korea University, Jochiwon, Choong-nam, 339-700, Korea
Abstract
Pyrido[2,3-d]pyrimidines (5a-h) were regioselectively synthesized by the reaction of 5-iodo-6-(dimethylaminomethylene)amino-1,3-dimethyluracil (3), which was prepared from the reaction of 6-amino-1,3-dimethyluracil with dimethylformamide dimethyl acetal followed by iodination, with various olefins (4a-h) in the presence of a catalytic amount of Pd(OAc)2, Cul, and K2CO3 in DMF at 100 °C.
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■ Synthesis of Furo[3,2-b]pyridine Analogue of Efaroxan
Patrice Mayer,* Chantal Loubat, and Thierry Imbert
*Division of Medicinal Chemistry, Centre de Recherche Pierre Fabre, 17, avenue Jean Moulin, 81100 Castres, France
Abstract
2-(4,5-Dihydro-1H-imidazol-2-yl)-2-ethyl-2,3-dihydrofuro[3,2-b]pyridine was synthesized in eight steps starting from 3-hydroxy-2-methylpyridine. The key step was a cyclization of a 2-chloromethyl-3-butyroxypyridine derivative. The target molecule is an aza analogue of efaroxan, a potent and selective antagonist of α2-adrenoceptors.
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■ Synthesis of 3-Arylpyrrolidines by Cycloadditions of N,N-Bis(benzotriazolylmethyl)amines to Styrenes
Alan R. Katritzky,* Yunfeng Fang, Ming Qi, and Daming Feng
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.
Abstract
A novel synthesis of 3-arylpyrrolidines (3a-m) via the cycloaddition of bis-benzotriazole derivatives to styrenes is described.
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■ Introduction of Alkenyl Group Bearing an Electron-withdrawing Group to the 5-Position of Imidazole Ring by Heck Reaction
Masayuki Yamashita, Miho Oda, Kayo Hayashi, Ikuo Kawasaki, and Shunsaku Ohta*
*Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
Abstract
A DMF solution of 5-iodo-1-methyl-2-phenylthio-1H-imidazole (7) and a large excess of acrylic esters, acrylonitrile, or methyl vinyl ketone was heated in a sealed tube in the presence of Pd(PPh3)4 to give the Heck reaction products, 5-alkenyl-1-methyl-2-phenylthio-1H-imidazoles, in 10 - 84 % yields.
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■ Novel Pyridine-Formation Reactions of 2-(Phosphoranylideneamino)-acrylaldehydes with Acetylenic Esters. Synthesis of 2-Mono- and 2,5-Disubstituted Nicotinates
Nobuhiro Kanomata* and Tadashi Nakata
*The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan
Abstract
Preparation of 2-(phosphoranylideneamino)acrylaldehydes, novel formyl-substituted (vinylimino)phosphoranes, was accomplished by the reaction of formyl-2H-azirines with triphenylphosphine. Their novel pyridine-formation reactions with acetylenic esters achieved the preferential formation of 2-mono- and 2,5-disubstituted nicotinate derivatives.
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■ Regioselective Protection of 11-Hydroxy Group and Inversion of Configuration at C-15 in m-Phenylene PGI2 Derivatives
Hisanori Wakita, Yutaka Hosono, and Hiroshi Nagase*
*Basic Research Laboratories, Toray Industries, Inc., 111, Tebiro, Kamakura, Kanagawa, 248, Japan
Abstract
The 15β-hydroxy isomer of a m-phenylene PGl2 derivative was converted to its 15α-hydroxy isomer by regioselective protection of 11-hydroxyl group by acylation using 3,5-dinitrobenzoyl chloride followed by inversion of configuration at C-15. A possibility of the presence of π-π interaction between the benzene ring (electron donor) in m-phenylene PGl2 derivative and that (electron acceptor) in the acid chloride is discussed.
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■ Synthesis of a New Annulenoannulenone, 3H-Cycl[3.2.2]azino[2,1-e]cycl[3.3.2]azin-3-one
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 annulenoannulenone, 3H-cycl[3.2.2]azino[2,1-e]cycl[3.3.2]azin-3-one (10) was synthesized from bispyridylmethane (1) via cycloaddition reaction of indolizinoquinolizinium salt (6) with methyl acetylene-carboxylate (MAC) as the key step.
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■ 2-Bromo-2-nitropropane/Zn Promoted Reductive Cyclizations of ortho-Carbonyl, Imino, or Azo Substituted Nitrobenzenes
Byeong Hyo Kim,* Yoon Seok Lee, Woong Kwon, Youngoo Jin, Jung Ae Tak, Young Moo Jun, Woonphil Baik, and Byung Min Lee
*Department of Chemistry, Kwangwoon University, 447-1, Wolgye-Dong Nowon-ku, Seoul, 139-701, Korea
Abstract
Under the mild conditions, reductive cyclizations of 2-nitrobenzaldehydes, 2’-nitroacetophenone, and N-(2-nitrobenzylidene)anilines were accomplished in the presence of 2-bromo-2-nitropropane/Zn in methanolic solution. Under the similar conditions in MeOH/CH2Cl2, o-nitro-substituted phenylazobenzenes have been converted into 2-aryl-2H-benzotriazoles via reductive cyclizations that are widely used as UV absorbers. Synthesis and mechanistic details are discussed.
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■ Reaction of N-Phenoxyphthalimide Derivatives with Aluminum Chloride in Benzene
Kensaku Uto, Etsuko Miyazawa, Katsuhiro Ito, Takeshi Sakamoto, and Yasuo Kikugawa*
*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japana
Abstract
N-Phenoxyphthalimides react with AlCl3 in benzene to form products of intramolecular N-C and intramolecular C-C bond formation via aryloxenium ion intermediates. N-Phenoxy derivatives having an electron-withdrawing substituent on the para position react with solvent benzene on the imide carbonyl, assisted by the neighboring oxygen atom, to produce N-(4-substituted phenoxy)-3,3-diphenyl-2,3-dihydroisoindol-1-ones.
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■ Reactivity of Dimethylphenylsilyllithium toward 5- and 6-Substituted 1,3-Dimethyluracil Derivatives
Raffaele Saladino,* Luigi Stasi, Gabriele Volpe, Rosario Nicoletti, and Maurizio Botta*
*Dipartimento Agrochimico, Universita degli studi di Viterbo "La Tuscia", Via San Camillo de Lellis, 01100 Viterbo, Italy
Abstract
Dimethylphenylsilyllithium (PhMe2SiLi) reacts with 5-substituted 1,3-dimethyluracils by selective addition at the electrophilic C-6 position of the uracil ring to give the corresponding 6-dimethylphenylsilyl-5,6-dihydrouracil derivatives. The reaction of PhMe2SiLi with 6-substituted 1,3-dimethyluracils showed a different selectivity, and an unusual addition at the C-5 position was observed. This synthetic procedure appears to be an efficient entry to a new class of highly functionalized 5,6-dihydro-1,3-dimethyluracils characterized by the presence of a silicon substituent selectively introduced at the C-5 and C-6 positions of the uracil ring.
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■ A Facile Synthesis of Methyl 5-Amino-6-chloro-2H-1-benzopyran-8-carboxylate Derivatives
Takuji Kakigami,* Kunihisa Baba, and Toshinao Usui
*General Research Park, Sanwa Kagaku Kenkyusho Co., Ltd., 363, Shiosaki, Hokusei-cho, Inabe-gunn, Mie 511-0406, Japan
Abstract
Methyl 6-chloro-5-pivaloylamino-2H-1-benzopyran-8-carboxylate (4d) was prepared in good yield as a result of the thermal cyclization of methyl 5-chloro-4-pivaloylamino-2-propargyloxybenzoate (3d) using N,N-diethylaniline as a solvent.
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■ Studies on Diastereoselective Synthesis of 3-Vinyl-5-carbomethoxy-2-oxabicyclo[3.3.0]octane Derivatives Employing Palladium(II) Oxidative Cyclization
Emerson Poley Peçanha, Carlos Alberto Manssour Fraga, and Eliezer Jesus Barreiro*
*Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, P.O.Box 68006, Rio de Janeiro RJ 21944-970, Brazil
Abstract
3-α,β-Vinyl-5-carbomethoxy-2-oxabicyclo[3.3.0]octane derivatives (7a,b) were synthesized through heterocyclization of alcohols trans- and cis-2-[(E)-buten-2-yl-1-]-2-carbomethoxycyclopentanols (5a,b) employing a palladium acetate / cupric acetate catalytic system. This cyclization process was diastereoselective, favoring the formation of 3β-vinyl (exo) diastereomer (7b). In addition, the employ of adequate solvent system, i.e. isopropanol/water, could prevent a ketalization side reaction verified in methanol/water.
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■ Formation of Highly Substituted Pyrrole Derivatives: An Unexpected Domino Reaction
Claudia Wittland and Nikolaus Risch*
*Universität-GH Paderborn, Fachbereich für Chemie und Chemietechnik, Warburger Str. 100, D-33098 Paderborn, Germany
Abstract
An unexpected multistep domino reaction for the preparation of highly substituted pyrrole derivatives is described. During this reaction, which uses a secondary benzylic amine (e.g. N-benzyl-(1-phenylethyl)amine) and benzaldehyde as starting materials, a methyl group is transformed into a quaternary sp2-carbon atom and three equivalents of benzaldehyde are reduced.
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■ A New Efficient Synthesis of 6-Nitroquipazine
Byoung Se Lee, Byung Chul Lee, Jong-Gab Jun, and Dae Yoon Chi*
*Department of Chemistry and Chemical Dynamic Center, Inha University, 253, Yonghyundong Namgu, Inchon 402-751, Korea
Abstract
A convenient and regioselective synthesis of 6-nitroquipazine from hydrocarbostyril in three steps is described. This synthetic route involved a nitration, a chlorination followed by aromatization, and an aromatic substitution reaction.
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■ Nitration of 6-Hydroxy-1-methylpyridin-2-one
Edith Bouey-Bencteux, Raymond Houssin, Charles Dogimont, and Jean-Pierre Hénichart*
*Institut de Chimie Pharmaceutique Albert Lespagnol, Université de Lille 2, 3, rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France
Abstract
Classical conditions of nitration applied to the 6-hydroxy-1-methylpyridine-2-one lead to the dimerisation of the compound following a Michael addition-type mechanism. This paper deals with the structure of this product determined by NMR studies.
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■ New Efficient Syntheses of 6,7-Dibromoquinoline-5,8-diones
Han Young Choi, Byoung Se Lee, Dae Yoon Chi,* and Dong Jin Kim*
*Department of Chemistry and Chemical Dynamic Center, Inha University, 253, Yonghyundong Namgu, Inchon 402-751, Korea
Abstract
Key intermediates for potential antitumor or antifungal agents, 2- and 3-methyl-6,7-dibromoquinoline-5,8-diones have been synthesized from 2,5-dimethoxyaniline and acrolein derivatives in three-step-one-pot with 38-41% isolation yields using Skraup reaction. The three steps are ring formation of quinoline, didemethylation, and oxidation of hydroquinone including dibromination on C6 and C7 positions.
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■ Synthesis of 4-Silyl-substituted Methyl Nicotinates via Silylcupration of N-Acylpyridinium Salts
Cornelia E. Hösl and Klaus Th. Wanner*
*Institut für Pharmazie, Universität M&uuuml;nchen, Sophienstrasse 10, D-80333 München, Germany
Abstract
A general synthetic method for the preparation of 4-silyl-substituted methyl nicotinates (5) is described. The reaction sequence includes a silylcupration of the N-acylated 3-methoxypyridinium salts (2) followed by oxidation of the resulting dihydropyridines (3) to give 5.
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■ Two New Isoflavones from Erythrina suberosa var. glabrescences
Hitoshi Tanaka,* Toshihiro Tanaka, Hideo Etoh, Naoharu Watanabe, Mansoor Ahmad, Imran Qurashi, and Mohammad Rehan Khan
*Faculty of Pharmacy, Meijo University, 150 Yagoto, Tempaku-ku, Nagoya, Aichi 468-8503, Japan
Abstract
Two new isoflavones, erysubins A and B, were isolated from the wood of Erythrina suberosa var. glabrescences (Leguminosae) and their structures were elucidated on the basis of spectroscopic evidence.
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■ A Convenient Synthesis of 2-Phenylbenzofuran Derivatives with Potent Testosterone 5α-Reductase Inhibitory Activities
Koki Ishibashi, Katsuyoshi Nakajima, and Takahide Nishi*
*Medicinal Chemistry Research Laboratories, Sankyo Co. Ltd., 5-14-21 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Abstract
A convenient method for the synthesis of 4-[2-(benzo[b]furan-2-yl)phenyloxy]butyric acid derivatives with a carbamoyl group at the 5 or 6 position of the benzofuran ring showing potent 5α-reductase inhibitory activities was developed. Oxazolin-2-ylbenzofuran derivatives were treated with tert-BuLi followed by tri(n-butyl)tin chloride, to give 2-tri(1-butyl)stannylbenzofuran derivatives. A palladium-catalyzed cross-coupling reaction of these benzofuran derivatives with tert-butyl 4-(2-iodophenyloxy)butyrate afforded the 2-phenyl benzofuran compounds in good yields.
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■ Ring Opening Reactions of Succinimides
Alan R. Katritzky,* Jiangchao Yao, Ming Qi, Yueting Chou, David J. Sikora, and Shannon Davis
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.
Abstract
This review describes recent examples of inter- and intra-molecular nucleophilic ring opening of succinimides, including aminolysis, alcoholysis, and reactions with carbon nucleophiles.