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. 41, No. 4, 1995
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■ Exocyclization of Novel β,β-Difluoro-α-phenylvinyl Sulfide with Bidendate Heteroatom(N,O,S) Nucleophiles
Bum Tae Kim, Yong Ki Min, No Kyun Park, Kwang Yun Cho, and In Howa Jeong
*Korea Research Institute of Chemical Technology, Daejoen 305-606, Korea
Abstract
The exocyclization of novel β,β-difluoro-α-phenylvinyl sulfide with bidentate heteroatom (N, O, S) nucleophiles afforded various types of heterocyclic ketene acetals (O,O-, O,S-, S,S- N,N- N,O- N,S-). The ease of exocyclization depended on the ring size of heterocyclic ketene acetals.
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■ A Convenient Synthesis of Benzofuran-3-acetic Acids
Yagamare Fall, Lourdes Santana, Marta Teijeira, and Eugenio Uriarte
*Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15706 Santiago de Compostela, Spain
Abstract
We described a two-step synthesis of benzofuran-3-acetic acids (1) from phenols (2) involving alkali-mediated rearrangement of 4-halomethylcoumarins (3) via α,β-unsaturated acids (4). Electron-donating substituents at the meta position of the phenol favour high yields of the coumarin, which in all cases rearranges to afford benzofuran-3-acetic acids in near quantitative yields.
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■ Synthesis of Cribrostatins 1 and 2
Shinsuke Nakahara, Ryuichi Numata, Yoshihiro Tanaka, and Akinori Kubo
*Meiji College of Pharmacy, 1-35-23 Nozawa, Setagaya-ku, Tokyo 154, Japan
Abstract
Synthesis of the cytotoxic isoquinolinequinone cribrostatins 1 (1) and 2 (2), which were isolated from the blue marine sponge Cribrochalina sp., is described.
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■ Control of Highly Selective Ag+ Transport by Redox Reactions between Thiol and Disulfide Located inside a Cavity of Crown Ether
Tatsuya Nabeshima*, Hiroyuki Furusawa, Naoko Tsukada, Toshinobu Shinnai, Tsutomu Haruyama, and Yumihiko Yano
*Department of Chemistry, Faculty of Engineering, Gunma University, Kiryu, Gunma 376, Japan
Abstract
A novel crown ether containing a thiol group inside the ring has been prepared in good yield and exhibits Ag+ selectivity on transport of metal ions through a liquid membrane. However, the corresponding disulfide loses the affinity significantly.
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■ INOC Reaction in Alkaloid Synthesis –- Preparation of Potential Intermediate for the Synthesis of (-)-Reserpine –-
Masahiro Toyota, Masaki Matsuura, and Keiichiro Fukumoto
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-77, Japan
Abstract
Intramolecular nitrile oxide cycloaddition (INOC) reaction of the nitro olefin (10) furnished the isoxazoline (11), potential synthon for the E ring segment of (-)-reserpine (1), in quantitative yield.
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■ The Reaction of Quadricyclane with p-Anils
Fabrizio Fabris, Ottorino De Lucchi, Giovanni Valle, and Sergio Cossu
*Dipartimento di Chimica, Università di Venezia, Dorsoduro 2137, I-30123 Venezia, Italy
Abstract
The reaction of quadricyclane (Q) with p-anils has been generalized in order to define its scope. Tetrafluoro-, tetrachloro-, and tetrabromo-p-benzoquinones in dichloromethane or chloroform, at or below room temperature give predominant or exclusive formation of the adduct to the C=O bond of the quinone as confirmed by the X-ray structure of the adduct to chloranil. In the case of DDQ (dicyanodichloro-p-benzoquinone), the major product is the standard [4+2]-cycloadduct, while the adduct to the C=O bond is formed as minor product and adds to a second molecule of quadricyclane to form bis-adduct (4). The structure of the latter has also been defined by X-ray analysis.
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■ 3,5-Dichloro-4-pyridinecarbonitrile as a Key Reagent in a Synthesis of Copper Containing Amine Oxidase Inhibitors
Vincenzo Bertini, Francesco Lucchesini, Marco Pocci, and Angela De Munno
*Instituto di Analisi e Tecnologie Farmaceutiche ed Alimentari, Università di Genova, Via Brigata Salerno, I-16147 Genova, Italy
Abstract
Various synthetic approaches to 3,4,5-trifunctionalized pyridine derivatives useful as benzylamine oxidase inhibitors are extensively explored. Fully satisfactory preparations of the inhibitors 3,5-diethoxy-4-aminomethylpyridine (4), 3,5-bis(3-hydroxypropoxy)-4-aminomethylpyridine (11), 3,5-bis(4-hydroxybutoxy)-4-aminomethylpyridine (12) and 3-ethoxy-5-phenylmethoxy-4-aminomethylpyridine (16), all in the form of dihydrochloride salt, using 3,5-dichloro-4-pyridinecarbonitrile as key precursor, are reported.
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■ An Efficient Synthesis of Pyrrolo[1',2':2,3]pyridazino[6,1-a]isoindoles from 1-Phthalimidopyrrole
Stephan Marchalin and Bernard Decroix
*Laboratoire de Chimie, UER des Sciences et Techniques de l'Université du Havre, 30 rue Gabriel Péri, 76600 Le Havre, France
Abstract
A synthesis of pyrrolo[1’,2’:2,3]pyridazino[6,1-a]isoindole was developed. Reduction of 1-phthalimidopyrrole, followed by Wittig reaction using ethoxycarbonylmethylidenetriphenylphosphorane gave the carboxylic acid intermediate (3) which cyclized in the presence of boron trifluoride etherate to furnish the tricyclic ketone (4). Mannich reaction, Schmidt rearrangement, and reduction of the above ketone were studied.
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■ Synthesis and Characterization of 6-O-α- and 6-O-β-D-Glucopyranosylmorphine and 6-O-β-D-Glucopyranosylcodeine
Pavol Kovác and Kenner C. Rice
*Laboratory of Medicinal Chemistry, NIDDK, Bldg. 8, Rm. B1-23, National Institutes of Health, Bethesda, MD 20892-0815, U.S.A.
Abstract
6-O-α- and β-D-glucopyranosylmorphine and 6-O-β-D-glucopyranosylcodeine have been prepared by condensations of 2,3,4,6-tetra-O-acyl-α-D-glucopyranosyl bromides with 3-O-acetylmorphine and codeine, respectively, followed by deprotection. Depending upon the method of condensation, variable amounts of orthoesters were found among the final products of condensation together with the desired glycosides. Highest yields of glycosides were obtained when 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl bromide was the glycosyl donor, and when the condensation was promoted with silver triflate in the presence of a less than stoichiometric amount of 2,4,6-trimethylpyridine as the acid scavenger.
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■ Synthesis of Thieno-Diltiazem Analogues
Isolde Puschmann and Thomas Erker
*Institute for Pharmaceutical Chemistry, University of Vienna, A-1090 Vienna, Althanstr.14, Austria
Abstract
The replacement of benzene by thiophene in a molecule might result in an altered metabolism of the modified drug, a different biochemical profile and/or an elimination of side effects to a certain extent. Replacement of the fused aromatic moiety in diltiazem with thiophene provides cis-4-[(2-dimethylamino)-ethyl]-4,5,6,7-tetrahydro-7-(4-methoxyphenyl)-5-oxo-thieno[2,3-b][1,4]thiaz-epin-6-yl acetate (20). The synthsis starts with the reaction of 3-nitro-2-thiophenethiol and racemic trans-(4-methoxyphenyl)glycidate. The resulting threo and erythro products are reduced, cyclized, alkylated and acetylated to give the desired compounds (20) and (21).
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■ Synthesis and Reactions of Dialkyl (1-R-5-Amino-3-methylsulfanyl-1H-pyrazol-4-yl)-phosphonates
Harald G. Krug, Richard Neidlein, Roland Boese, and Walter Kramer
*Pharmazeutisch-Chemisches Institut, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany
Abstract
Dialkyl (1-cyano-2,2-bismethylsulfanylvinyl)phosphonates (2) react with hydrazines (4) to yield pyrazoles (5). The composition of one reaction product is examined by X-ray crystal structure analysis. N-Unsubstituted pyrazoles (5a) treated with 1,3-diketones (6) give pyrazolo[1,5-a]pyrimidines (7).
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■ Additional Bioactive Triterpenoids from Melia volkensii (Meliaceae)
Lu Zeng, Zhe-ming Gu, Phillip E. Fanwick, Ching-jer Chang, David L. Smith, and Jerry L. McLaughlin
*Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, U.S.A.
Abstract
Meliavolen (1) and melianinone (2), new triterpenes with an apotirucallane skeleton, together with two known compounds, 3-episapelin A (5) and nimbolin B (6), have been isolated from the root bark of Melia volkensii (Meliaceae) by using brine shrimp lethality for bioactivity-directed fractionation. The structures have been elucidated by spectral data. The relative and absolute stereochemistries of 2 were determined by correlating 2 with melianin A (3). The stereochemistry of 3 was determined by X-ray crystallographic analysis and Mosher methodology. The stereochemistry of 5 was also determined by Mosher methodology. The four isolated compounds, meliavolen (1), melianinone (2), 3-episapelin (5), and nimbolin B (6), were all moderately active in the brine shrimp lethality test and were significantly cytotoxic among human solid tumor cell lines with noted selectivities toward the colon cell line (HT-29).
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■ Synthesis of Tetracyclic Arylpyridodiazepines as Potential Anti HIV-1 Agents
Giovanni Viti, Danilo Giannotti, Rossano Nannicini, Giuseppe Balacco, Vittorio Pestellini, Paola Paoli, and Paolo Dapporto
*Chemical Research Department , A. Menarini Industrie Farmaceutiche Riunite s.r.l., V. Sette Santi 3, Firenze, Italy
Abstract
Some tetracyclic compounds containing the pyridodiazepine system condensed with the pyridofuro, pyridothieno, and indolo groups were synthesized. In the case of indole derivatives the outcome of the reaction is highly dependent by the nature of the substituents.
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■ 3-Methyl-1-phenacylbenzotriazolium Yilde : Cycloadditions with Acetylenic Esters and Aldehyde-mediated Dimerization
Alan R. Katritzky, Baozhen Yang, Jinlong Jiang, and Peter J. Steel
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, U.S.A.
Abstract
Stable 3-methyl-1-phenacylbenzotriazolium ylide (2) adds acetylenecarboxylic esters to form tricycles (3). Araldehydes react with two moles of 2 give poly-substituted 4,5-dihydrofurans (5). The pyrazoloquinoxaline structure of 3 was confirmed by X-ray analysis.
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■ Oxidation of 1,2,3,4-Tetrahydroisoquinolines to 3,4-Dihydroisoquinolines with Molecular Oxygen Catalyzed by Copper(Ö†) Chloride
Masao Shimizu, Hideo Orita, Takashi Hayakawa, Kunio Suzuki, and Katsuomi Takehira
*National Institute of Materials and Chemical Research, 1-1, Higashi, Tsukuba, Ibaraki 305, Japan
Abstract
A catalytic oxidation system, a CuCl2-O2 system, was efficient for dehydrogenation of 1,2,3,4-tetrahydroisoquinolines to 3,4-dihydroisoquinolines. Oxidation of 1,2,3,4-tetrahydroquinoline was also carried out.
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■ Pteridines, CIV. Regioselective Alkoxylation of Pteridines at the 6-Position by N-Bromo-succinimide and Alcohol
Takashi Sugimoto and Wolfgang Pfleiderer
*Department of Natural Science Informatics, School of Informatics and Sciences, Nagoya University, Chikusa-ku, Nagoya 464-01, Japan
Abstract
Reaction of 1,3-dimethyllumazine with N-bromosuccinimide or bromine in an appropriate alcohol afforded 6-alkoxy-1,3-dimethyllumazine. N-Iodosuccinimide or iodine also brought about the same reaction. This procedure was applicable to other pteridine compounds, such as 2-dimethylamino-4(3H)-oxopteridine. The mechanism of this alkoxylation reaction is discussed.
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■ 6-Acyllumazines from the Marine Polychaete, Odontosyllis undecimdonta
Hisae Kakoi*, Hideo Tanino, Kunisuke Okada, and Shoji Inoue
*Faculty of Pharmacy, Meijo University, Tenpaku, Nagoya 468, Japan
Abstract
Lumazine and its 3-methyl and 1,3-dimethyl derivatives having 6-acyl substituents such as acetyl, propionyl, β-methoxypropionyl, and β-hydroxypropionyl groups were isolated from the marine polychaete, Odontosyllis undecimdonta.
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■ Leptocarpine, a New Protopine Alkaloid
Eva Táborská, Hana Bochoráková, Petr Sedmera, Ivo Válka, and Vilim Simánek
*Institute of Medical Chemistry, Palacky University, 775 15 Olomouc, Czech Republic
Abstract
The structure of leptocarpine (1) a new protopine alkaloid isolated from the whole plant of Hypecoum leptocarpum was elucidated on the basis of spectral analysis, including 2D nmr spectroscopy and chemical transformation.
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■ Total Synthesis of Na,O-Di-Boc-5β-cyano-Z-geissoschizine and Na-Boc-21α-Cyanotetrahydroalstonine, the Latter a Synthetic Equivalent of Na-Boc-Cathenamine
Mauri Lounasmaa, Minna Halonen, and Reija Jokela
*Laboratory for Organic and Bioorganic Chemistry, Technical University of Helsinki, FIN-02150 Espoo, Finland
Abstract
Modified Polonovski reaction of the synthetically prepared Na,O-di-Boc-Z-geissoschizine cis-Nb-oxide (6), followed by cyano trapping of the formed iminium intermediates, led to four compounds (1), (5a), (7), and (8a) [and to two secondary products, (9) and (10)]. The most important of these compounds were Na,O-di-Boc-5β-cyano-Z-geissoschizine (5a) and Na-Boc-21α-cyanotetrahydroalstonine (8a) [synthetic equivalent of Na-Boc-cathenamine (8b)]. Change in the reaction temperature caused one (Δ4(21)) of the intermediate iminium ions to be strongly favoured, leading to the nearly exclusive formation of compound (8a) at the expense of compounds (5a), (7), (9), and (10).
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■ Carbon Functionalizations on Pyridine Ring via Trimethylstannyl Derivatives — An Example of Fusaric Acid Synthesis —
Yutaka Yamamoto, Takuo Tanaka, Hidekazu Ouchi, Masayo Miyakawa, and Yasuo Morita
*Tohoku College of Pharmacy, 4-1, Komatsushima 4 Chome, Aoba-ku, Sendai 981, Japan
Abstract
Method for introduction of two types of carbon functional groups, acyl and tert-butoxycarbonyl groups, in pyridine ring via bis(trimethylstannyl)pyridine (1) is explored. Application of this method to the synthesis of fusaric acid (11) is also described.