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. 36, No. 3, 1993
Published online:
■ Synthetic Approaches to New Regioisomers of AZT and AZU
Vasu Nair* and David F. Purdy
*Department of Chemistry, The University of Iowa, Iowa City, Iowa 52242, U.S.A.
Abstract
Approaches to 1,4-anhydro-3-α-azido-2,3-dideoxy-2-β-[3,4-dihydro-2,4-dioxo-5-methyl-1(2H)-pyrimidinyl]-D-arabinitol and 1,4-anhydro-3-α-azido-2,3-dideoxy-2-β-[3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl]-D-arabinitol, conceptually new hydrolytically stable, optically active analogs of 3’-α-azido-3’-deoxythymidine (AZT) have been developed. These are among the first examples of regioisomeric analogs of AZT. The key synthetic steps and key intermediates are described. The generality aspects of the approaches are addressed.
Published online:
■ On the Regioselectivity in the Silyl Group Directed Baeyer-Villiger Reaction
Toshiaki Aida, Morio Asaoka,* Syuzo Sonoda, and Hisashi Takei
*Department of Life Chemistry, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan
Abstract
In the Baeyer-Villiger reaction of 3,5-bis-silylated cyclohexanones, preferential migration of the less substituted α-carbon was observed.
Published online:
■ Preparation of New 2-Chloro-5-fluoro-6-(4-phenylmethylpiperazinyl)-4-trifluoromethyl-3-nicotinic Acid
Philippe Remuzon,* Daniel Bouzard, and Jean-Pierre Jacquet
*Bristol-Myers Squibb Pharmaceutical Research Institute, Lognes, BP 62, 77422 Marne-La-Vallée Cedex 2, France
Abstract
The nicotinic acid (15), which could be a key intermediate for novel potential antibacterial 1,8-naphthyridine-3-carboxylic acid analogues, was prepared initiating with construction of the pyridine nucleus by ethyl 2-fluoroacetate and ethyl 2-trifluoroacetate.
Published online:
■ Synthesis of Functionalized Indolizino[8,7-b]indoles via 1,3-Dipolar Cycloaddition Reactions of 3,4-Dihydro-β-carboline Azomethine Ylides with Olefinic Derivatives
Guillaume Poissonnet, Marie-Héléne Théret, and Robert H. Dodd*
*Institut des Chimie des Substances Naturelles, C.N.R.S., Avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France
Abstract
The 1,3-dipolar cycloaddition reaction of 3,4-dihydro-β-carboline azomethine ylide (4) with dimethyl fumarate (5) and fumaronitrile (5’) is described. The resulting hexahydroindolizine products (6) and (6’) were dehydrogenated stepwise (- H2, - 2H2, - 3H2) using KMnO4, MnO2 and DDQ as oxidants.
Published online:
■ Porphyrins Coupled with Nucleoside Bases. Synthesis and Some Properties of Guanine, Cytosine and Adenine-Thymine Derivatives
Masao Hisatome,* Noriaki Maruyama, Koichi Ikeda, and Koji Yamakawa
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
Abstract
Synthesis of several porphyrin derivatives having a guanine, cytosine or adenine-thymine pair is described. Diamagnetic shift behaviors of the base proton signals in the 1H-nmr spectra of the derivatives and hypochromism of the Soret band in the electronic spectra are briefly discussed.
Published online:
■ Synthesis of Oxindoles by the Nafion-H Catalysed Decarboxylative Cyclization of α-Carbomethoxy-α-diazoacetanilides
Baosheng Liu and Andrew G. Wee*
*Department of Chemistry, University of Regina, Regina, Saskatchewan, S4S 0A2, Canada
Abstract
Diazoanilides (1), possessing electron-donating and electron-withdrawing groups in the aromatic ring, undergo Nafion-H catalysed decarboxylative cyclization to directly give highly functionalized oxindoles in moderate yields (39-79%).
Published online:
■ Annulation of Heterocycles via Ring Transformation of Isoxazoline-2-oxides by Lewis Acid
Kazuho Harada,* Kuniaki Sasaki, Eisuke Kaji, and Shonosuke Zen
*School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641, Japan
Abstract
Novel heterocyclic-annulated furo[3,3a-d]isoxazoles were synthesized through the ring transformation reaction of heterocyclic ring-substituted isoxazoline-2-oxides promoted by Lewis acid such as titanium tetrachloride. Structural determinations by single crystal X-ray and nmr analyses are reported.
Published online:
■ Ring Transformations of Heterocycles 2. Ring Contraction of 5,6-Dihydro-4H-1,2,4,5-oxatriazines into 1H-1,2,4-Triazoles
Mustafa M. El-Abadelah,* Ahmad Q. Hussein, Musa Z. Nazer, Osama M. Musa, Paul Rademacher,* and Heinz Bandmann
*Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan
Abstract
6-Monosubstituted 5,6-dihydro-4H-1,2,4,5-oxatriazines (3) undergo ring contraction, via elimination of H2O, to yield the respective 1H-1,2,4-triazoles (4). This transformation is envisaged to proceed via the ring-opened (E)-hydrazonoxime (5) which then suffers dehydrative cyclization. The process is acid-catalyzed and is thermally induced. Apparently, the driving force for this transformation is linked to the aromaticity of the triazole product.
Published online:
■ Lithiation of Δ2-Thiazolines: The C2-Anion Approach to 2-Substituted Derivatives and Their Reactivity
Giancarlo Fantin, Marco Fogagnolo, Alessandro Medici,* and Paola Pedrini
*Dipartimento di Chimica, Università degli Studi di Ferrara, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy
Abstract
Lithiation of 2-unsubstituted Δ2-thiazolines and quenching with various electrophiles to 2-functionalized derivatives is reported. In particular quenching of thiazolines (1a and 1b) with trimethylsilyl chloride affords the corresponding 2-trimethylsilyl-Δ2-thiazolines (7a and 7b). The reactivity of these masked C2-anions toward electrophiles is described. Similar approach is developped for chiral 4-[(tert-butyldimethylsilyloxy)methyl]-2-thiazoline (12). The synthesis of the chiral 2-formyl derivative, generated in situ from the C2-anion and N-formylmorpholine, and its reactivity toward phosphonium salt are also discussed.
Published online:
■ Anomalous ‘Lossen-Type’ Rearrangement Synthesis of Functionalized Imidazolinones
Dee Ann Casteel,* Rebecca S. Gephart, and Tracey Morgan
*Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, U.S.A.
Abstract
Reaction of an imidazolinone N-sulfonyloxyimide (3) with ammonia or methylamine provided carboxy-ureido compounds (4, 5, 6, and 7), products of a Lossen rearrangement in which the intermediate isocyanate is trapped by the amine. Possible mechanism(s) are discussed. Upon heating, the carboxy-ureido materials eliminate urea to form the carboxy substituted imidazolones (8, 9, 10).
Published online:
■ One-Pot Synthesis of 2,3-Dihydro-2,2-dimethylbenzofuran Derivatives
Kyoung Mahn Kim, Hyoung Rae Kim, and Eung K. Ryu*
*Korea Research Institute of Chemical Technology, P.O.Box 9, Daedeog Danji, Daejoen 305-606, Korea
Abstract
A tandem Claisen rearrangement-cyclization reaction of aryl methallyl ethers afforded the corresponding 2,3-dihydro-2,2-dimethylbenzofuran derivatives at -70 °C with aluminium chloride.
Published online:
■ Syntheses of 2-Azafluorenones from 3-Substituted 4-Arylpyridines
Min-Jen Shiao,* Kang-Hsiuan Liu, and Pen-Yuan Lin
*Institutue of Chemistry, Academia Sinica, 128, Yan-Chiu-Yuan Road, Sec II, Nankang, Taipei,11529, Taiwan, R.O.C.
Abstract
3-Substituted 4-arylpyridines (5a-i) were synthesized in good yields by reaction of mixed copper, zinc aryl organometallics (2a-e) with 1-ethoxycarbonylpyridinium chlorides (1a-d) followed by o-chloranil oxidation under reflux in toluene. The 4-arylpyridines (5a-i) are obtained predominantly. Having compounds (5a-i) in hand, a convenient method was developed for the synthesis of 2-azafluorenones (7a-f) by using cyclization of 4-arylpyridines (5a-i) with polyphosphoric acid.
Published online:
■ Selective and Simultaneous Deprotection of Amine and Lactam Functions in the Syntheses of Pyridazino[4,5-b]oxazinones and Pyridazino[4,5-b]thiazinones
Erzsébet Zára-Kaczián and Péter Mátyus*
*Institute for Drug Research Ltd., 47-49 Berlini st.1 H-1045 Budapest, Hungary
Abstract
Benzyloxymethyl (BOM) and benzyl (Bz) groups were employed for protection of the amide- and amino-nitrogens in the title compounds. The BOM protective group could be removed selectively or simultaneously with the Bz group depending on the reaction conditions. By catalytic hydrogenation of the fully protected pyridazinooxazinone (1b), unexpectedly the 4-methyl derivative (1e) could also be prepared. The mechanism for the formation of 1e is also discussed.
Published online:
■ A New Lignan, Formosalactone, from the Bark of Juniperus formosana Hay. var. concolor Hay.
Yueh-Hsiung Kuo* and Ming-Tsang Yu
*Department of Chemistry, National Taiwan University, Roosevelt Road Section 4, Taipei 106, Taiwan, R.O.C.
Abstract
The bark of Juniperus formosana Hay. var. concolor Hay. was found to contain a new lignan, formosalactone together with a known lignan, savinin. The structure has been elucidated by spectral evidence and chemical transformation.
Published online:
■ Synthesis of 1,1-Bis(3,5-dimethyl-2-furyl)ethene; The Chemo- and Site-selectivity of Its Cycloadditions
Jacek Ancerewicz and Pierre Vogel*
*Section de chimie, Université de Lausanne, 2, rue de la Barre, CH 1005 Lausanne, Switzerland
Abstract
The new polyene 1,1-bis(3,5-dimethyl-2-furyl)ethene (11) was derived from 2,4-dimethylfuran. Its reaction with dienophiles such as maleic anhydride, benzoquinone or 1-cyanovinyl acetate generated exclusively Diels-Alder adducts (9-oxabicyclo[4.3.0]nona-1,7-diene derivatives) involving the exocyclic double bond and one double bond of one furyl unit. The reaction of 11 with didehydrobenzene (benzyne) gave a 7-oxabicyclo[2.2.1]hepta-2,5-diene derivative resulting from the exclusive Diels-Alder addition of one furyl group, whereas dimethyl acetylenedicarboxylate added to 11 giving a mixture of the corresponding 7-oxabicyclo[2.2.1]hepta-2,5-diene and 9-oxabicyclo[4.3.0]nona-1,4,7-triene derivatives. With allenic acid, 11 added in a [2+2] fashion exclusively with its exocyclic double bond giving 2-[3,3-bis(3,5-dimethyl-2-furyl)cyclobutylidene]acetic acid with high selectivity.
Published online:
■ Wittig-Horner Reaction of Dimethyl Phthalide-3-phosphonates with Aldehydes: Synthesis of 3-Ylidenephthalides and Characterization of Their E- and Z-Isomers
Mitsuaki Watanabe,* Saori Ijichi, Hitoshi Morimoto, Kayoko Nogami, and Sunao Furukawa
*Center for Instrumental Analysis, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
Wittig-Horner reaction dimethyl phthalide-3-phosphonates with aldehydes in the presenece of lithium bis(trimethylsilyl)amide was investigated. Using their NOE experiments, both the E- and Z-isomers of 3-ylidenephthalides were clearly characterized.
Published online:
■ Synthesis of Halogenated Thiazole Derivatives of Oligo-N-methylpyrrolecarboxamide and Their Photochemical DNA Cleaving Activities
Yasuhiro Sakai, Toyomi Matsumoto, Akie Tanaka, and Masayuki Shibuya*
*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi 1, Tokushima 770-8505, Japan
Abstract
Synthesis of various halogenated thiazole derivatives of oligo-N-methylpyrrolecarboxamide and their DNA cleaving activities under UV-A irradiation were described.
Published online:
■ Artonins J, K, and L, Three New Isoprenylated Flavones from the Root Bark of Artocarpus heterophyllus Lamk.
Miwa Aida, Kazuki Shinomiya, Yoshio Hano, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Three new isoprenylated flavones, artonins J (1), K (2), and L (3) were isolated from the root bark of Artocarpus heterophyllus Lamk. (Moraceae). The structures of artonins J, K, and L were shown to be 1, 2, and 3, respectively, on the basis of spectroscopic data. The model compound (5) was derived from cycloartobiloxanthone (4) by treatment with alkaline solution.
Published online:
■ Ring-Opening of 4-Isoxazolines: Competitive Formation of Enamino Derivatives and α,β-Enones
Ugo Chiacchio, Franco Casuscelli, Angelo Liguori, Antonio Rescifina, Giovanni Romeo,* Giovanni Sindona, and Nicola Uccella*
*Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy
Abstract
Ring-opening 3-substituted 4-isoxazolines, proceeding through the intermediate isoxazolinium salts, follows two competing reaction pathways leading to α,β-enones and enamines respectvily. The rearrangement courses can be controlled as a function of substitution pattern and experimental conditions.
Published online:
■ Annelated 1,5-Benzodiazepines. Part 1. Three, Four, and Five Membered Rings
Alba Chimirri,* Rosaria Gitto, Silvana Grasso, Anna-Maria Monforte, Giovanni Romeo, and Maria Zappalà
*Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy
Abstract
This review describes the synthetic approaches to mono and diannelated 1,5-benzodiazepines with three, four, and five-membered rings fused to different positions of the 1,5-benzodiazepine skeleton.