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HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
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Special Issue
Pierre Potier's Special Issues, Vol. 64, No. 1, 2004
Published online: 17th August, 2004
■ Preparation of 2’,3’-Oxorane-fused Carbocyclic Nucleosides Based on N-Substituted 2-Azabicyclo[2.2.1]hept-5-en-3-ones
Minoru Ishikura,* Kota Matsumoto, and Atsushi Murakami
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
The epoxidation of N-substituted 2-azabicyclo[2.2.1]hept-5-en-3-ones (1) led to the exo-selective formation of epoxides (2), and the use of 2 for the preparation of 2’,3’-oxirane-fused carbocyclic nucleosides (10) was attempted.
Published online: 19th October, 2004
■ A Short Synthesis of (-)-Deoxoprosophylline
Angélique Jourdant and Jieping Zhu*
*Institut de Chimie des Substances Naturelles, C.N.R.S., 1 avenue de la Terrasse, Bat. 27, 91198 Gif sur Yvette, France
Abstract
Syntheses of (-)-deoxoprosophylline from chiral L-N,N-dibenzylserine (TBDMS) aldehyde is reported. A highly diastereoselective nucleophilic addition of Büchi’s Grignard reagent to chiral serinal followed by an intramolecular reductive amination of ω-oxo amino diol are two key steps of the present synthesis.
Published online: 3rd September, 2004
■ Synthesis of 2,3-Dihydrofuro[3,2-c]pyridine-3,4-dicarboxylic Acid, a Conformationally Constrained Analogue of the Subtype Selective NMDA Receptor Agonist Homoquinolinic Acid
Marcus Vinicius Nora de Souza, Zhaohua Yan, and Robert H. Dodd*
*Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France
Abstract
4-Allyloxy- and 4-prop-2-ynyloxy-3-iodopicolinic acid derivatives, obtained by reaction of 4-chloro-2-iodopicolinanilides (11,14) with the sodium salts of allyl alcohol and propargyl alcohol, respectively, were subjected to tri-n-butyltin hydride/AIBN free radical cyclization conditions. While the propargylic compound (15) did not cyclize, the allylic compounds (8, 28) cyclized in the presence of diphenyl diselenide, TEMPO or oxygen as radical trapping agents to give the corresponding 2,3-dihydrofuro[3,2-c]pyridine-4-carboxylic acid derivatives substituted at C-3 by a phenylselenylmethyl (20), 2,2,6,6-tetramethylpiperidin-1-yloxymethyl (22) or hydroxymethyl group (29), respectively. The latter was oxidized to the 3-carboxylic acid using ruthenium chloride /sodium periodate and the C-4 benzyl ester was hydrogenolyzed to afford the title compound (5), a conformationally constrained analogue of the subtype selective NMDA receptor agonist, homoquinolinic acid.
Published online: 22nd October, 2004
■ Studies on the Condensation Products from N-Primary 1,2-Amino Alcohols and Formaldehyde
David J. Aitken,* Laure Besson, Françoise Fournier, Henri-Philippe Husson, Pascale Lemoine, Denis Lesage, Francine Libot, Pierre-Guy Martin, Christelle Mellin-Morlière, Valérie Monnier, Jean-Claude Tabet, and Bernard Viossat
*Department of Chemistry, SEESIB Laboratory, Clermont-Ferrand 2, University of Blaise Pascal, 24 avenue des Landais, 93117 Aubiere, France
Abstract
The products of the condensation reactions of twenty-six different 1,2-amino alcohols with excess aqueous formaldehyde were identified, with the help of a simple and effective analytical technique based on mass spectroscopy. With a few exceptions, which arise from steric or solubility effects, most amino alcohols form bis(oxazolidine)methane adducts preferentially.
Published online: 3rd September, 2004
■ Reactions of 3-Phenyl-8-triphenylphosphoimino-1-azaazulene with Aryl Isocyanate, Aryl Isothiocyanate, and Carbondisulfide
Kentaro Nagamatsu, Hiroyuki Fujii, Noritaka Abe,* and Akikazu Kakehi
*Department of Chemistry, Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan
Abstract
Reaction of 3-phenyl-8-triphenylphosphoimino-1-azaazulene (1) with some aryl isocyanates gave 2-arylimino-4-phenyl-2,2a-dihydro-1,2a-diazacyclopent[cd]azulenes (2) and 8-arylimino-1,8-dihydro-1-azaazulenes (3). Reaction of 1 with p-toluenesulfonyl isocyanate gave 2-imino-3-(p-methylphenyl)-4-phenyl-2,2a-dihydro-1,2a-diazacyclopent[cd]azulene as cyclization-rearrangement product. Reaction of phenyl isothiocyanate gave 2. Tautomerization of between 8-imino-1,8-dihydro-1-azaazulenes (3) and 8-amino-1-azaazulenes was discussed on the basis of X-Ray structure analysis and molecular orbital calculation.
Published online: 3rd September, 2004
■ Synthesis of Azulen-3-ylheterocyclic Using 2-(1-Methoxycarbonylazulen-3-yl)ethynyltriphenylphosphonium Bromide
Noboru Morita,* Shiro Moriyama, Taku Shoji, Masashi Nakashima, Masataka Watanabe, Shigeru Kikuchi, Shunji Ito, and Kunihide Fujimori
*Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan
Abstract
3-(3-methoxycarbonylazulen-1-yl)ethynyltriphenylphosphonium bromide was prepared from methyl 3-formylazulenecarboxylate. Its resonance structures were discussed on the basis of the 1H and 13C NMR spectroscopy. Furthermore, its reactivity with o-substituted aniline was examined. We found that 2-(1-methoxycarbonyl-azulen-3-yl)ethynyltri-phenylphosphonium bromide reacted with o-substituted aniline except 2-aminophenol to give corresponding methyl 3-(benzazol-2-yl)azulene-1-carboxylate.†
Published online: 5th October, 2004
■ Alternative Access to Lactosamine-derived Oxazoline via 2-Ulose Oxime as a Key Intermediate
Eisuke Kaji,* Yumiko Osa, Naomi Shinohara, Chiho Yanagi, Masae Sekine, and Kakashi Nishino
*School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641, Japan
Abstract
Lactosamine-derived oxazoline was synthesized via 2-ulose oxime as a key intermediate, in which substituent effects of the acyloxyimino group were investigated. On reduction of the oxime to amino group, p-chlorobenzoyloxime provided a good gluco : manno selectivity of 13 : 1. N-Acetyllactosaminyl chloride derived therefrom was readily converted into the oxazoline by AgOTf-promoted cyclization with an 84% yield.
Published online: 20th August, 2004
■ Design and Synthesis of 16-Membered Hybrid Macrolide Having a Thiazole Side Chain on the Carbonolide Skeleton
Noriyuki Nakajima* and Makoto Ubukata
*Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398
Abstract
Design and synthesis of a 16-membered hybrid macrolide, which contained a 16-membered carbonolide-type lactone framework with a thiazole sidechain, were described.
Published online: 10th December, 2004
■ Synthesis and Reactions of N-o-Anisylsulfonylmethyl- and N-o-sec-Butoxysulfonylmethylcarbodiimides with Aldehydes
Vishnu K. Tandon,* Kunwar A. Singh, Sanjay Rai, and Albert M. van Leusen
*Chemistry Department, Lucknow University, Lucknow 226007, India
Abstract
N-o-Anisylsulfonylmethyl- and N-o-sec-butoxysulfonylmethyl- carbodiimides (2) and (3) have been synthesized from the corresponding sulfinic acids by Mannich reaction. 2 and 3 are useful synthons in two step synthesis of 2-amino-1,3-oxazoles(4).
Published online: 19th October, 2004
■ Optically Active Tropocoronands Having Amino Acid Residues in Linker Chains: Syntheses, Metal Coordination Properties, and Their Abilities as an Asymmetric Catalyst
Ohki Sato* and Akira Tanbo
*Department of Chemistry, Faculty of Science, Saitama University, Urawa, Saitama 338-8570, Japan
Abstract
Optically active tropocoronands (7) having L-amino acid moieties were synthesized by stepwise and one-pot reactions of tropolone derivatives with amino acid linker chains. The coordination styles of their Ni(Ö†) and Pd(Ö†) complexes and the abilities as an asymmetric catalyst were investigated.
Published online: 19th November, 2004
■ Schiff Base Formation between 5-Formyl-2’-deoxyuridine and Lysine ε-Amino Group at Monomer and Oligomer Levels
Atsushi Kittaka,* Chikafumi Horii, Hiromichi Tanaka, Tadashi Miyasaka, Kazuo T. Nakamura, Reiko Kuroda, and Toru Sugiyama*
*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan
Abstract
Schiff base formation between the 5-formyl group of 5-formyl-2’-deoxyuridine, which is an oxidative thymidine lesion, and the ε-amino group of lysine at both monomer and oligomer levels is reported.
Published online: 10th December, 2004
■ New [2+2] and [4+4] Photodimerizations of 2-Pyridones in an Inclusion Complex with a Simple Carboxylic Acid Host: A Model of DNA Damage by Photodimerization of Its Thymine Component
Shinya Hirano, Shinji Toyota, and Fumio Toda*
*Department of Chemistry, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Okayama 700-0005, Japan
Abstract
A new [2+2] photodimerization of 5-chloro- and 5-methyl-2- pyridones to the corresponding cis-anti-dimer in an inclusion complex with 1,1’-biphenyl-2,2’-dicarboxylic acid was found. This reaction is a good model of thymine dimerization in a nucleotide which causes damage to DNA. A new [4+4] photodimerization of 5-chloro-2-pyridone to the cis-syn-dimer in the inclusion complex with 1,2,4,5-benzenetetracarboxylic acid was also found. The mechanism of these stereoselective photoreactions in the solid state was studied by X-Ray analysis.
Published online: 9th November, 2004
■ Synthesis of Orthogonally Protected Enantiopure 2,9-Diaminodecanedioic Acid: A Model for a New General Method for the Synthesis of Orthogonally Protected α,α’-Diaminodicarboxylic Acids
Cyrille Truchot and N. André Sasaki*
*Institut de Chimie des Substances Naturelles, C.N.R.S., 1 avenue de la Terrasse, Bat. 27, 91198 Gif sur Yvette, France
Abstract
A new method for the synthesis of orthogonally protected enantiopure α,α’-diaminodicarboxylic acids is described. A key step involves the Julia olefination of an aldehyde and a sulfone, both of which are derived from an optically pure dicarboxylic amino acid such as aspartic and glutamic acid. Straightforward synthesis of orthogonally protected 2,9-diaminodecanedioic acid is chosen to demonstrate the conciseness of this new versatile approach.
Published online: 9th November, 2004
■ Polymer-supported Phosphinooxathiane as Ligands for Palladium-catalyzed Asymmetric Allylations
Hiroto Nakano,* Kouichi Takahashi, and Reiko Fujita
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
New polymer-supported chiral ligands, PS-DES, PS-Et, and TentaGel supporting phosphinooxathianes were prepared and used in palladium-catalyzed asymmetric allylic alkylation and amination.
Published online: 9th November, 2004
■ Synthesis of Perhydropyrrolo[1,2-a]pyrazine-1,4-diones and Their Sulfur-Analogues by Ring-Enlargement of N-(2H-Azirin-3-yl)-L-prolinates
Artur Budzowski, Anthony Linden, and Heinz Heimgartner*
*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Abstract
The hydrolysis of methyl N-(2,2-dimethyl-2H-azirin-3-yl)-L-prolinate (1c) at 50°C in the presence of silica gel afforded (S)-perhydro-3,3-dimethylpyrrolo[1,2-a]pyrazine-1,4-dione ((S)-4a), which was thionated chemoselectively to give the corresponding 1-thioxo derivative ((RS)-5a) as a racemic mixture. On the other hand, treatment of 1c with hydrogen sulfide led to the 4-thioxo isomer ((S)-6a). Thionation with Lawesson reagent yielded the bisthioxo compound ((RS)-7a), again as a racemate. Analogous reactions were carried out with the heterospirocyclic N-(2H-azirin-3-yl)-L-prolinates (1d) and (1e). The structures of (RS)-5a, (S)-6a-c, and (RS)-7a have been established by X-Ray crystallography.
Published online: 3rd December, 2004
■ Discovery and Synthesis of a Potent, Selective and Orally Bioavailble EP4 Receptor Agonist
Robert N. Young,* Xavier Billot, Yongxin Han, Deborah A. Slipetz, Nathalie Chauret, Michel Belley, Kathleen Metters, Marie-Claude Mathieu, Gillan M. Greig, Danielle Denis, and Mario Girard
*Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, Quebec, H9R 4P8, Canada
Abstract
An optimized analog of prostaglandin E2 which incorporates a γ-lactam in place of the cyclopentanone ring and which incorporates metabolically stabilized side chains, has been identified and shown to exhibit potent and selective EP4 receptor agonism. The compound (2) (L-000902688) is also well absorbed on oral dosing and exhibits a long half-life making it an excellent tool for the study of the role of EP4 receptor in physiology and disease. An efficient synthesis of 2 from a chiral synthon is described.
Published online: 29th November, 2004
■ A Facile Formation of Anti-Bredt’s Compounds from the Reaction of 1-Aroyl-2-aryl-3a,6a-diazapentalenes with Acetylenedicarboxylates
Hirokazu Iida, Hidehiro Uekusa, Yuji Ohashi, Hiroshi Hamana, Takahisa Machiguchi,* and Kiyoshi Matsumoto*
*Faculty of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, 3 Shiomi-cho, Choshi, Chiba 288-0025, Japan
Abstract
The reaction of 1-aroyl-2-aryl-3a,6a-diazapentalenes with acetylene-di-carboxylates affords surprisingly unusual anti-Bredt’s adducts having 4,10-diazabicyclo-[5.2.1]-deca-1,3,5,8-tetraene structure. The structure was elucidated by making full uses of new MMR spectroscopies and finally an X-Ray crystallo-graphic analysis. The plausible mechanism for the formation of the present compounds is described.
Published online: 27th April, 2004
■ Intramolecular Pd-catalyzed Biaryl Coupling Reaction of N-Aryl-2-triflyloxybenzamides Using Pd(OAc)2, 1,3-Bis[diphenylphosphino]propane, Bu3P, and DBU
Hiromi Nishioka, Yoshimi Shoujiguchi, Hitoshi Abe, Yasuo Takeuchi, and Takashi Harayama*
*Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
Intramolecular Pd-catalyzed coupling reactions of N-aryl-2-triflyloxybenzamides were examined. The procedure using DBU as a base was effective for even in the reaction of oxygen-substituted benzamides.
Published online: 30th July, 2004
■ Organolanthanide Catalyzed Intramolecular 5-endo-dig Hydroamination: An Unusual Anti-Markovnikov Cyclization
Gary A. Molander* and Hikaru Hasegawa
*Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323, U.S.A.
Abstract
Intramolecular 5-endo-dig hydroaminations of homopropargylamine derivatives were efficiently catalyzed by the organolanthanide precatalyst, Cp*2YbCH(TMS)2 (Cp* = C5Me5), to give the endocyclic enamine products. The 5-endo-dig hydroamination was also preferred in the presence of another olefin that would afford a 6-exo cyclization.
Published online: 2nd November, 2004
■ 2-(o-Aminoaryl)indole Derivatives via the Coupling-Cyclization of o-Alkynylanilines with o-Halotrifluoroacetanilides in the Presence of a Palladium Catalyst
Antonio Arcadi, Sandro Cacchi,* Giancarlo Fabrizi, Fabio Marinelli, and Luca M. Parisi
*Department of Studies of Chemistry and Technology of Biologically Active Substances, University “La Sapienza”, P. le A. Moro 5, 00185 Rome, Italy
Abstract
The reaction of o-ethynylanilines with o-halotrifluoroacetanilides in the presence of PdCl2(PPh3)2 and Et3N in DMF at 90 °C affords 2-(o-trifluoroacetamidoaryl)indoles. The presence of the free amino group was found to play a crucial role in favoring the cyclization step.
Published online: 22nd September, 2004
■ Short Step Synthesis of an Antibiotic, 6-Cyano-5-methoxy-12-methylindolo[2,3-a]carbazole
Masanori Somei,* Fumio Yamada, Yoshiaki Suzuki, Shinobu Ohmoto, and Hiroyuki Hayashi
*Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan
Abstract
For evaluating the effectiveness of organic synthesis, both intellectual property factor (IPF) and application potential factor (APF) are proposed. As a representative example, a highly effective synthetic method with IPF value of 53.8 and APF value of 100 has been established starting from indigo directing toward an antibiotic, 6-cyano-5-methoxy-12-methylindolo[2,3-a]carbazole, using only conventional reagents without using any protecting groups.
Published online: 21st September, 2004
■ Combinatorial Chemical Synthesis of 4-Heteroaryl-3-substituted Pyrroles from Nitroalkenes
Clara Baldoli, Giuseppe Cremonesi, Piero Dalla Croce, Concetta La Rosa,* and Emanuela Licandro
*Dipartimento di Chimica Organica e Industriale, Centro C. N. R., Università degli Studi di Milano, V. Venezian 21, I-20133 Milano, Italy
Abstract
A small library of 4-(2-furyl)- or 4-(2-thienyl)-3-substituted pyrroles has been prepared by reaction of 2-(2-furyl or 2-thienyl)-1-nitro-1-alkenes (1) with secondary enamines (2). The reaction gives pyrrole derivatives by means of a Michael-type addition intermediate. Cyclization is influenced by the nature of the solvent and the substituent in the enamine β position, and by enamine-nitrogen nucleophilicity.
Published online: 5th October, 2004
■ Direct Synthesis of Heterobiaryls by Radical Addition to Pyridine: Epeditious Synthesis of Chelating Ligands
David Crich* and Mitesh Petel
*Department of Chemistry, University of Illinois at Chicago, 845 West Taylor St., Chicago, IL 60607-7061, U.S.A.
Abstract
The addition of aryl radicals to pyridine may be affected in moderate yield on exposure of aryl iodides to tributyltin hydride, AIBN, and diphenyl diselenide in hot pyridine. Mixtures of ortho-, meta-, and para-aryl substituted pyridines are typically obtained. When the iodide is ortho-substituted with a hydrogen bond donor, such as o-iodophenol, significantly improved selectivity for ortho-substituted pyridines, with potential as bidentate chelating ligands, is obtained.
Published online: 12th November, 2004
■ Asymmetric Synthesis of All Six Regioisomers of N-Boc-dimethylphenylalanines
Hidekazu Ouchi, Midori Kumagai, Shinobu Sakurada, and Hiroki Takahata*
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
All possible regioisomers of dimethyl-substituted (S)-phenylalanine were efficiently synthesized by reacting the Ni(II)-complex of the chiral Schiff base of glycine with (S)-2-N-(N-benzylprolyl)aminobenzophenone.
Published online: 9th November, 2004
■ Senepodine F, a New C22N2 Alkaloid from Lycopodium chinense
Yusuke Hirasawa, Hiroshi Morita, and Jun’ichi Kobayashi*
*Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan
Abstract
A new C22N2 Lycopodium alkaloid, senepodine F (1), consisting of a decahydroquinoline and a quinolizidine ring has been isolated together with senepodines A (2) and E (3) from the club moss Lycopodium chinense. The relative stereochemistry of 1 was determined by NOESY correlations for a deacetylated derivative.
Published online: 17th September, 2004
■ Metabolites from Marine Sponges of the Genus Plakortis
Fredirik Rahm, Patricia Y. Hayes, and William Kitching*
*Department of Chemistry, The University of Queensland, St. Lucia, Brisbane, Queensland Q1d 4072, Australia
Abstract
Metabolites from the Plakortis genus of sponges are reviewed, with major focus on P. halichondrioides, P.simplex, P. angulospiculatus, P. lita, P. nigra, P. quasiamphiaster, P. zygompha, and the closely related Plakinastrella onkodes. The structures, stereochemistry, pharmacological activity and selected syntheses of these metabolites are discussed. Peroxy containing, polyketide derived metabolites constitute a prevalent class of biologically potent metabolites from Plakortis species.
Published online: 7th September, 2004
■ 2-Azabicyclo[2.2.0]hex-5-enes and 2-Azabicyclo[2.2.0]hexanes. A Review
Grant R. Krow* and Kevin C. Cannon
*Department of Chemistry, Temple University, Philadelphia, PA 19122, U.S.A.
Abstract
The synthesis and reactions of 2-azabicyclo[2.2.0]hex-5-enes and 2-azabicyclo[2.2.0]hexanes are reviewed.
Published online: 26th October, 2004
■ β-Lactones as Intermediates for Natural Product Total Synthesis and New Transformations
Yingcai Wang, Reginald L. Tennyson, Daniel Romo*
*Department of Chemistry, Texas A & M University, College Station, Texas 77843-3255, U.S.A.
Abstract
The exploration of β-lactone reactivity and transformations has continued since the first synthesis of these strained heterocycles by Einhorn in 1883. The principal reactivity modes of β-lactones include nucleophilic addition resulting in either acyl C2-O1 or alkyl C4-O1 cleavage, rearrangement leading to ring expansion, decarboxylation, and electrophilic reactions of β-lactone enolates. Recent advances in asymmetric β-lactone synthesis has led to further developments in the area of novel transformations of β-lactones and significantly increased applications in natural product total synthesis. The latter topic is the focus of this review and covers the period inclusive to the end of 2003.