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. 10, 1998
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■ Synthesis of a Luminescent Compound: 8-Dimethylaminopyridazino[4,5-a][2.2.3]cyclazine-1,4(2H,3H)-diones
Yoshinori Tominaga,* Kaori Komiya, Seigo Kataoka, Yasuhiro Shigemitsu, Takashi Hirota, and Kenji Sasaki
*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
Some pyridazino[4,5-a][2.2.3]cyclazine-1,4(2H,3H)-diones (1a-d) as a luminescent compound were synthesized via several steps from indolizine derivatives. The key intermediates, dimethyl 6-dimethylamino[2.2.3]cyclazine-1,2-dicarboxylates (5,7) were synthesized by the [8+2] cycloaddition reaction of 7-dimethylaminoindolizines (4,6) with dimethyl acetylenedicarboxylate in the presence of Pd-C in refluxing toluene.
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■ Synthesis of Benzo[c]phenanthridine Alkaloids, Chelerythrine and Nitidine, Using a Novel Palladium-Phosphine Combination System - Pd(OAc)2, DPPP, and Bu3P -
Takashi Harayama,* Toshihiko Akiyama, Yuichiro Nakano, and Kentaro Shibaike
*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
Total synthesis of chelerythrine (1) and nitidine (4) was accomplished via the aryl-aryl cyclization reaction using a novel Pd reagent prepared from Pd(OAc)2, DPPP, and Bu3P. The present method was very versatile for coupling reaction not only between aromatic triflate and arene but also between aromatic halide and arene.
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■ Synthesis of Naphtho[2,3-b]indolizine-6,11-dione Derivatives by Iodine Oxidation of 2-Alkyl-1,4-naphthoquinones in the Presence of Substituted Pyridines
Attilio Citterio,* Mariacristina Fochi, Antonio Marion, Andrea Mele, Roberto Sebastiano, and Maurizio Delcanale
*Dipartimento di Chimica, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy
Abstract
Iodine oxidation of 2-alkyl-1,4-naphthoquinones (1) in the presence of substituted pyridines (2) afforded naphtho[2,3-b]indolizine-6,11-dione derivatives (3). Other oxidant systems (MnO2/I- or Fe(ClO4)3/I2) can be used and 2-alkylbenzoquinones reacted in lower yield. Iodination of 3 by I2 and dibenzoyl peroxide occurred seelctively at position 12.
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■ Free Radical Reaction of Diisopropyl Xanthogen Disulfide with Unsaturated Systems
Yves Gareau* and André Beauchemin
*Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, Quebec, H9R 4P8, Canada
Abstract
1,3-Dithiol-2-ones are prepared in one pot reaction from commercially available diisopropyl xanthogen disulfide (2) and alkynes under radical conditions. The 5-membered heterocycle is formed via a ring closure of vinyl radical (7) resulting from the thio radical addition of 5 to an alkyne. The reaction worked best for alkynes conjugated with a C=C double bond. The oxygen atoms of reagent (2) could be replaced by sulfur and this new reagent furnished 1,3-dithiol-2-thiones under radical conditions.
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■ Selective Thiophilic Addition of Alkyl- and Aryllithiums to Dithio Esters and a Sulfine in the Pyridine Series
Claude Lempereur, Nelly Plé, Alain Turck, Guy Quéguiner,* Florence Corbin, Carole Alayrac, and Patrick Metzner*
*Laboratoire de Chimie Moléculaire et Thio organique, UMR CNRS 6507, ISMRA-Université, 6 Boulevard du Maréchal Juin, 14050 Caen, France
Abstract
Reaction of two dithio esters and a new sulfine (S-thiocarbonyl oxide) with various aryl- and alkyllithiums at -78 °C afforded dithio acetals or their oxides, arising from a thiophilic addition. The intermediate carbanions can be trapped by alkyl halides or an aldehyde. This provides a new entry to pyridyl acyl anions, "Umpolung" synthons.
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■ Synthesis of Methyl 2-(1',1'-Dimethyl-2'-oxopropyl)thiazole-4-carboxylate and Related 2,4-Disubstituted Thiazoles. Key Intermediates in the Synthesis of Anthelmintic Agents Based on Marine Natural Product
Gloria Serra, Graciela Mahler, and Eduardo Manta*
*Cátedra de Química Orgánica, Facultad de Química, Universidad de la República, Avda. General Flores 2124, Casilla de Correo 1157, C. P. 1180 Montevideo, Uruguay
Abstract
Two methodologies, cyclodehydration of amides with TiCl4 and cyclodehydration of β-hydroxy thioamides with PEG linked Burgess reagent were used in order to obtain 2,4-disubstituted thiazole rings (2) and (3) respectively. The scope and limitations of both methods were compared and contrasted.
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■ Syntheses and Bioactivities of Acetophthalidin and Its Derivatives
Kanako Uchida, Hidenori Watanabe, Takeo Usui, Hiroyuki Osada, and Takeshi Kitahara*
*Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Abstract
Acetophthalidin is a potent cell cycle inhibitor which was isolated from a fungal strain. Both enantiomers of acetophthalidin and its derivatives were synthesized, and their bioactivities were examined.
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■ Unprecedented Base-promoted Oxidation of Imidazo[1',5':1,2]pyrido[3,4-b]indoles
Natalia De la Figuera, Ma Teresa García-López, Rosario Herranz, and Rosario González-Muñiz*
*Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, E-28006 Madrid, Spain
Abstract
1,3-Dioxotetrahydro-1H-imidazo[1’,5’:1,2]pyrido[3,4-b]indole derivatives show a high tendency towards the oxidation at the 11b-bridgehead position in basic media. This oxidation, affording the corresponding 11b-hydroxy derivatives, is produced by reaction between atmospheric oxygen and the imidazopyrido derivative under the enol form and can be suppressed by working in inert atmosphere. In marked contrast, these imidazo[1’,5’:1,2]pyrido derivatives are completely stable in acidic conditions.
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■ Radical Lactonizations at Anomalously High Concentrations
Jeffrey H. Byers,* Eileen A. Shaughnessy, and Trina N. Mackie
*Department of Chemistry and Biochemistry, Middlebury College, Middlebury, VT 05753, U.S.A.
Abstract
Photolyses of phenylseleno and iodo derivatives of allyl and propargyl malonate esters led to formation of phenylseleno and iodobutyrolactones, respectively, in synthetically useful yields. In contrast to allyl iodoacetate, which undergoes intermolecular cyclo-oligomerization at high concentration, malonate esters cyclize cleanly at concentrations as high as 0.78 M.
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■ Synthesis of 5-Substituted 3,4-Dihydro-3-amino-2H-1-benzopyran Derivatives via Palladium-catalysed Reactions
Robert Rezaie, Benoît Joseph, John B. Bremner, and Gérald Guillaumet*
*Institut de Chimie Organique et Analytique, UMR CNRS 6005, Université d'Orléans, BP 6759, Rue de Chartres, 45067 Orléans Cédex 2, France
Abstract
Syntheses of the previously unknown 5-substituted 3,4-dihydro-3-di-n-propylamino-2H-1-benzopyrans (2-12) from the triflate (1) via palladium-catalysed reactions are described.
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■ Aaptosamine, a New 5,8-Diazabenz[cd]azulene Alkaloid from the Caribbean Sponge Aaptos aaptos. An Unprecedented Base-catalyzed Rearrangement of 9-Demethyloxyaaptamine
Winston F. Tinto
*Laboratory of Bioorganic Chemistry, Department of Biological Chemical Sciences, University of the West Indies, Cave Hill Campus, P.O. Box 64, Bridgetown, Barbados, West Indies
Abstract
A new 5,8-diazabenz[cd]azulene alkaloid, aaptosamine, was isolated from the marine sponge Aaptos aaptos collected in the southern Caribbean. The structure was determined by 2D NMR spectroscopy using HMQC and HMBC experiments. The known alkaloid 9-demethyloxyaaptamine which was isolated from an earlier collection of A. aaptos, underwent an unprecedented base-catalyzed rearrangement to give a new furanonaphthyridine derivative.
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■ A Simple Synthesis of 1-Substituted 5-Aminopyrazoles and Pyrazolo[1,5-a]-s-triazine Derivative
Yoichi Yamada,* Heinosuke Yasuda, and Kazue Yoshizawa
*Department of Chemistry, Faculty of Education, Utsunomiya University, 350 Mine, Utsunomiya 321-8505, Japan
Abstract
Dialkyl 5-amino-1-carbamoylpyrazole-3,4-dicarboxylates (3) and the 1-aryl derivatives (5) are synthesized directly by the reaction of semicarbazide (2) or arylhydrazines (4) with dialkyl (E)-2,3-dicyanobutendioates (1) in the presence of organic salts, such as ammonium acetate or sodium acetate. Furthermore, the reaction of the 1,3-diamino compound (3; R=Et) with trimethyl orthoformate in acetic acid led to the formation of diethyl 7-hydroxypyrazolo[1,5-a]-s-triazine-2,3-dicarboxylate (6).
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■ Trifluoroacetylation of Methylpyridines and Other Methylazines: A Convenient Access to Trifluoroacetonylazines
Masami Kawase,* Mutsumi Teshima, Setsuo Saito, and Satoru Tani
*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japana
Abstract
Treatment of methyl substituted azines, such as pyridine, pyrimidine, quinoline, oxazole, benzoxazole, benzimidazole, and benzothiazole, with trifluoroacetic anhydride in the presence of pyridine at room temperature gave the corresponding trifluoroacetonyl substituted azines in good yields.
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■ The Formaiton of 3-Chloro-1,2,5-thiadiazoles from α-Oximidonitriles. Optimizaiton and Mechanistic Insights
John M. McGill* and Marybeth S. Miller
*Chemical Process Development, Tippecanoe Laboratories, Eli Lilly & Company, Lilly Corporate Center, Lafayette, Indiana 47902, U.S.A.
Abstract
The optimized formation of substituted 3-chloro-1,2,5-thiadiazoles (2) and (3) from the α-oximidonitrile (4) is described. New mechanistic insight into the formation of 3-chloro-1,2,5-thiadiazoles comes from the identification of a reaction intermediate in the thiadiazole ring-forming reaction.
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■ Studies on Nitrogen-containing Heterocyclic Compounds. Synthesis of Benzo[b][1,8]naphthyridine and Its Oxidation Reactions with Peroxy Acid
Isao Takeuchi, Noriko Naga, Tomomi Kariyama, Yoshiki Hamada,* and Hisao Matsuzaki
*Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan
Abstract
A new method for the synthesis of benzo[b][1,8]naphthyridine (4) was established through the dehydrogenation of 5,6,7,8-tetrahydro-1,9-diazaanthracene. Oxidation reactions of 4 with peroxy acid afforded seven-membered 1,4-oxazepine derivatives (5-8).
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■ Synthesis, Complexation and Fluorescence Behavior of Diaza-12-crown-4 Carrying Two Naphthyl Pendants
Kanji Kubo,* Emi Yamamoto, and Tadamitsu Sakurai
*Instituete of Advanced Material Study, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan
Abstract
N,N’-Bis(1-naphthylmethyl)-4,10-diaza-12-crown-4 (2) was found to display unique photophysical properties in the presence of the guest metal salts. The diazacrown (2) exhibited high Zn2+ enhancement selectivity and in the presence of this cation the host fluorescence intensities were increased by a factor of 43. The guest cation-induced fluorescence recovery of 2 was higher than N,N’-bis(1-naphthylmethyl)-4,13-diaza-18-crown-6 (1).
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■ Bipyridne Building Blocks for Self-Organization Systems: First Complete NMR-spectroscopic Investigation of 6,6'-Disubstituted 2,2'-Bipyridines Obtained via N-Oxidation Route and Related Reactions
Ulrich S. Schubert,* George R. Newkome,* Andreas Göldel, Alexander Pemp, Jörg L. Kersten, and Claus D. Eisenbach*
*Lehrstuhl für Makromolekulare Stoffe, Technische Universität München, Lichtenbergstrasse 4, D-85747 Garching, Germany
Abstract
One- and two-dimensional NMR-spectroscopic data of eight 6,6’-disubstituted 2,2’-bipyridines, prepared by the N-oxidation route, were used to confirm their structures. These key compounds in supramolecuar construction lead to the characterization of larger oligo(bipyridine) building blocks. Furthermore some related reactions are described which lead to unsymmetrically functionalized bipyridines or can be used for the purification of bishydroxy compounds.
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■ Synthesis of Protected 5-Formylpyrido[2,3-d]pyrimidine via a 2,3,4-Trisubstituted Pyridine Using an ortho-Lithiation Strategy; Application to the Synthesis of a Folate Derivative
Samuel E. Watson* and Anatoly Markovich
*Department of Chemistry, Long Island University, One University Plaza, Brooklyn, N.Y. 11201, U.S.A.
Abstract
A convenient route for the preparation of a protected 5-formylpyrido[2,3-d]pyrimidine from 2,3,4-trisubstituted pyridines has been developed. The readily available diethylacetal of pyridine 4-carboxaldehyde is chlorinated at the 2-position and then treated with LDA and methyl chloroformate to give a 2,3,4-trisubstituted pyridine (12). Treatment of 12 with guanidine hydrochloride gives the pyrido[2,3-d]pyrimidine in good yield. A 4-aminobenzoylglutamic acid side chain is installed by means of a reductive amination step to provide a 5-substituted derivative that is, after deprotection, a conformationally unrestricted analog of 5,10-methylenetetrahydrofolate (1), the natural co-factor for thymidylate synthase, an important chemotherapeutic target in the treatment of cancer.
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■ Unexpected Enolization of 2-Phenyl-3-piperidone Derivatives
Valérie Daley, Christian Cavé,* and Jean d'Angelo*
*Unité de Chimie Organique Associé au CNRS, Centre d'Etudes Pharmaceutiques, Université de Paris-Sud, 5, rue Jean-Baptiste Clément, 92296 Chatenay-Malabry Cedex, France
Abstract
Alkylation of 2-phenyl-3-piperidone (17) with methyl iodide or methyl acrylate furnished the 4,4-dialkylated derivatives (18) or (19), respectively. This unexpected enolization towards the less substituted form can be interpreted considering the appreciable steric strain which would exist in the more substituted enolate (21).
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■ Synthesis and Antiviral Evaluation of 3-Hydroxymethylpyrimido[1,6-c][1,3]oxazepine Derivatives
Ling-Yih Hsu,* Ya-Fun Kang, and John C. Drach
*School of Pharmacy, National Defense Medical Center, P.O. Box 90048-508, Neihu, Taipei, Taiwan, R.O.C.
Abstract
A number of pyrimido[1,6-c][1,3]oxazepin derivatives, the anti glycosidic constrained acyclic analogs of uridine and cytidine have been prepared. Compounds synthesized were evaluated for activity against herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). All of these compounds were inactive.
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■ The Thermal [3,3] Claisen Rearrangement of the 3-Substituted Phenyl Allyl and Propargyl Ethers. The Synthesis of 4-Halobenzo[b]furans
Vernon G. S. Box* and Panayiotis C. Meleties
*Department of Chemistry, The City College of the City University of New York, Convent Avenue @ 138th Street, New York, NY 10031, U.S.A.
Abstract
The thermal [3,3] Claisen rearrangement of the 3-substituted phenyl allyl and propargyl ethers is regioselective. The major product of the reaction incorporates a 1,2,3-trisubstituted benzene ring. The 2-allenylphenol intermediates can be manipulated into the preparation of 4-substituted benzo[b]furans. The observed regioselectivity supports the biradicaloid mechanism of the Claisen rearrangement.
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■ Further Furoclerodanes from Teucrium Genus
Franco Piozzi,* Maurizio Bruno, and Sergio Rosselli
*Dipartimento di Chimica Organica, Universita di Palermo, Via Archirafi 20 90123 Palermo, Italy
Abstract
The review updates the results reported during the last four years on the chemistry of these diterpenoids.