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. 63, No. 6, 2004
Published online: 9th April, 2004
■ Studies of Isoindoles. 12. A Structural Revision of the 1:2 Mannich Type Condensation Reaction Product Formed from o-Phthalaldehyde and Substituted Aniline
Ichiro Takahashi,* Rika Miyamoto, Kenji Nishiuchi, Minoru Hatanaka, Akihito Yamano, Akiyo Sakushima, and Shinzo Hosoi*
*Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910-8507, Japan
Abstract
The structure of the double Mannich condensation product from o-phthalaldehyde and substituted aniline was proved to be iminoisoindoline, but not diimine, based on X-Ray analysis.
Published online: 16th April, 2004
■ A Novel Ring-opening Reaction of (Z)-2-Methyl-4-arylmethylene-5(4H)-oxazolone Derivatives with Acylhydrazines
Kei Maekawa, Yoshitaka Kanno, Kanji Kubo, Tetsutaro Igarashi, and Tadamitsu Sakurai*
*Departmnet of Applied Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan
Abstract
The ring-opening mode of the title oxazolones with acylhydrazines was investigated from both synthetic and mechanistic points of view. It was found that the novel ring-opening reaction proceeds to give 1,3,4-triazole-substituted (Z)-α-dehydroamino acids in high yields, irrespective of substituents and solvents examined. MM2 and PM5 calculations strongly suggested that the triazole ring is constructed via the preferential nucleophilic addition of the hydrazino nitrogen to the C–N double bond in the oxazolone ring.
Published online: 20th April, 2004
■ Chemistry of Polyhalogenated Nitrobutadienes, 1: A New Synthesis of Perfunctionalized 3-Amino-4-nitrothiophenes
Viktor A. Zapol′skii, Jan C. Namyslo, Arnold E. W. Adam, and Dieter E. Kaufmann*
*Institute of Organic Chemistry, Technical University of Clausthal, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany
Abstract
An efficient synthesis of perfunctionalized 3-amino-4-nitrothiophenes was developed starting from highly chlorinated 2-nitrobutadiene derivatives. The key step of this new approach is the cyclization reaction of highly nucleophilic, ω-chlorinated butadienyl thiolates generated from 2-(2-diorganylamino-3,3-dichloro-1-nitroallylidene)-[1,3]dithiolanes upon action of base.
Published online: 9th April, 2004
■ Functionalization of the Ring A in Some Benzo[g]pyridazino[1,2-b]phthalazine-6,13-dione Derivatives Related to Anthracyclinones
Rafael Jiménez, Ana M. Sanz, Fernando Gómez-Contreras,* M. Carmen Cano, María J. R. Yunta, Mercedes Pardo, and Lucrecia Campayo
*Departamento de Química Orgánica, Facultad de Ciencias Química, Universidad Complutense de Madrid, Ciudad Universitaria, E-28040 Madrid, Spain
Abstract
A synthesis of benzo[g]pyridazino[1,2-b]phthalazine-6,13-dione derivatives (2) and (3), respectively related to the feudomicinone B and daunomicinone skeletons, has been accomplished by [4+2] cycloaddition of benzo[g]phthalazine-1,4-dione with the adequate 1,3-diene. Functionalization of ring A with hydroxy substituents has been performed by reaction with N-bromosuccinimide in acid aqueous medium, sodium hydroxide, or hydrobromic acid via the corresponding epoxide, and the stereochemical features of electrophilic additions involved are commented in terms of steric and stereoelectronic factors. Easy isomerization of the C2-C3 double bond allows the introduction of hydroxy groups at the C1 or C4 positions, paving a way to further formation of the glycosides derivatives related to natural anthracyclines.
Published online: 9th April, 2004
■ Synthesis and NMR Spectroscopic Investigations with 3-Amino-, 3-Hydroxy-, and 3-Methoxy-4-acyl-1-phenyl-2-pyrazolin-5-ones
Wolfgang Holzer* and Linda Hallak
*Institute of Pharmaceutical Chemistry, University of Vienna, Pharmaziezentrum, Althanstraße 14, A-1090 Vienna, Austria
Abstract
Reaction of 3-amino-, 3-hydroxy- and 3-methoxy-1-phenyl-2-pyrazolin-5-one with carboxylic acid chlorides / calcium hydroxide in 1,4-dioxane mainly affords the corresponding 4-acyl-2-pyrazolin-5-ones. 3-Methoxy-1-phenyl-2-pyrazolin-5-one reacts with dimethylformamide diethyl acetal to give an (E)/(Z)-mixture of the 4-dimethylaminomethylene product, with tetracyanoethylene the 4-dicyanomethylene product is obtained, whereas with nitrous acid the 4-hydroximino derivative results. NMR-spectroscopic investigations (1H, 13C, 15N) with the obtained reaction products are presented.
Published online: 30th March, 2004
■ Regioselective Cleavage of Trisubstituted Epoxy-Linkage Using Lithium Trialkylborohydride Reagents: A New Route to the Key Intermediate of Maxacalcitol
Hitoshi Shimizu,* Kazuki Shimizu, Noboru Kubodera, Kenichi Yakushijin, and David A. Horne
*Chugai Pharmaceutical Company, Ltd., 5-5-1, Ukima, Kita-ku, Tokyo 115-8543, Japan
Abstract
Optimal conditions for the reductive cleavage of a trisubstituted epoxide leading regioselectively to the key intermediate tertiary alcohol of Maxacalcitol, used for the treatment of secondary hyperparathyroidism and psoriasis, have been established using lithium tri(sec-butyl)borohydride (L-Selectride) in THF.
Published online: 16th April, 2004
■ A Study of Structure and Dynamics of Prochiral N-C Axis for Asymmetric Transition Metal Catalysis, with Phosphorous-31 (V) by 3D NMR Spectroscopy Combined with MO Calculation
Yohko Sakamoto,* Kazuhiro Kondo, Maiko Tokunaga, Kumiko Kazuta, Hiroko Fujita, Yasuoki Murakami, and Toyohiko Aoyama
*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
We have synthesized five kinds of prochiral N-C axis for asymmetric transition metal catalysis with phosphorus-31 (V) and investigated their mobility in solution by measuring 31P NMR spin-lattice relaxation time (T1). 1-(S)-N-[2-(diphenylphosphinyl)naphthyl-2-(hydroxylmethyl)pyrrolidine; compound (1b), and 1-(S)-N-[2-(diphenylphosphinyl)naphthyl]-2-(pyrrolidinyl- methyl pyrroridine; compound (1e) was assigned on the basis of NMR spectral data. From the vicinal 31PÅ]1H and 1HÅ]13C coupling constants of J resolution spectra on the 3D NMR spectra, the dihedral angles of compounds (1b), and (1e) were determined. The optimum stable structures of these compounds were obtained on the basis of NMR spectral data combined with molecular orbital calculalations.
Published online: 9th April, 2004
■ Intramolecular Pauson-Khand Reaction of 3-Alkynyl-1-alkylidenecycles: A Convenient Synthesis of [5.n.1.01,5] Tricyclic Compounds
Miyuki Ishizaki,* Mina Masamoto, Osamu Hoshino, Kiyoshi Nishitani, and Hiroshi Hara*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
An intramolecular Pauson-Khand reaction of various 3-alkynyl-1-alkylidenecyclic compounds was performed to give the corresponding [5.n.1.01,5] tricyclic compounds (n = 2-4). A facile construction of the core structure in cedrene terpenoids was also investigated in detail and formal total synthesis of α- and β-cedrenes was accomplished.
Published online: 9th April, 2004
■ Kwakhurin, a Unique Isoflavone with Rejuvenating Activity from “Kwao Keur”: Further Characterization by 2D-NMR Spectrometry and Synthesis of Triisopropylkwakhurin
Misako Iwasaki, Toshiko Watanabe,* Tsutomu Ishikawa, Sunee Chansakaow, Yoshihiro Higuchi, and Satoshi Tahara
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Kwakhurin (5), a characteristic isoflavone component of Pueraria mirifica which has been used in folk medicine as “kwao keur” for rejuvenating purpose, was structurally approached by 2D-NMR experiments. Furthermore, the synthesis of kwakhurin (5) was attempted starting from the methyl ketone (12). Thus, deoxybenzoin derivative (22) was prepared by Friedel-Crafts acylation after protection of the phenolic function with a triisopropyl group. Modification of the substituents, O-prenylation, prenyl 1,3-rearrangement, and O-methylation afforded kwakhurin triisopropyl ether (38).
Published online: 16th April, 2004
■ Synthesis, Properties, and Redox Ability of Optically Active 3-Carbamoyl-1,6-dimethylpyrimido[4,5-c]pyridazine-5,7(1H,6H)-dione and Related Pyrimido-annulated Pyridine Analogues
Shin-ichi Naya, Kohtaro Shibayama, and Makoto Nitta*
*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
Optically active 3-carbamoyl-1,6-dimethylpyrimido[4,5-c]pyridazine-5,7(1H,6H)-dione (13a) and related pyrimido-annulated pyridine analogues (13b,c) were prepared via the corresponding 3-ethoxycarbonyl-1,6-dimethylpyrimido[4,5-c]pydazine-5,7(1H,6H)-dione (11a) and the related compounds (11b,c). The properties of 11a-c, 13a-c, and the related 1,3,6-trimethylpyrimido[4,5-c]pyridazine-5,7(1H,6H)-dione (18a) as well as 7-phenyl- and 3,7,8-trimethyl-pyrido[2,3-d]pyrimidine-2,4(3H,8H)-dione (18b,c) having no carbamoyl or ester function were studied by the UV-VIS spectra and redox potentials. Although pyridazine derivative (13a) was not reduced, pyridine derivatives (11b,c), (13b), and (18b) were reduced by Na2S2O4 to give dihydrogenated compounds (20b,c), (21b), and (22b), respectively. The photo-induced oxidation reactions of 13a,b and 18a-c toward some amines under aerobic conditions were studied to give the corresponding imines in more than 100% yields [based on compounds 13a,b and 18a-c], suggesting that the oxidation proceeds in an autorecycling process.
Published online: 9th April, 2004
■ Synthesis and Reactivity of a New Pyranoquinoxaline
Lamouri Hammal, Mokhtar Fodili, Mohamed Amari, Nawel Khier, Bellara Nedjar-Kolli,* Chantal André, Pascal Hoffmann, and Jacques Périé
*Department of Chemistry, Paul Sabatier University, Bat 2R1 - 118 route de Narbonne - 31062 Toulouse Cedex 4, France
Abstract
3-Methyl-3,4-dihydro-1H-pyrano[3,4-b]quinoxalin-1-one (2) was prepared from a series of 3-methyl-4,5,10,11-tetrahydropyrano[4,3-b][1,5]benzo- diazepin-1(3H)-one derivatives (1) bearing various substituents at position 11. The formation of this quinoxaline is initiated by oxidation of the diazepine-4’,11’-double bond to give an unstable epoxide intermediate, followed by a ring contraction which releases a carben species that has been trapped in the presence of cyclohexene. Reactivity of this new quinoxaline (2) with various primary and secondary amines was investigated.
Published online: 30th March, 2004
■ Microwave-assisted One-Pot Three Component Synthesis of Some New 4(3H)-Quinazolinone Derivatives
Minoo Dabiri,* Peyman Salehi, Mohammad S. Khajavi, and Ali A. Mohammadi
*Department of Chemistry, Faculty of Science, Shahid Beheshti University, Tehran 1983963113, Iran
Abstract
Efficient microwave-assisted synthesis of 4(3H)-quinazolinones by the one-pot three-component condensation of isatoic anhydride, primary amines and orthoesters in the presence of catalytic amounts of p-toluenesulfonic acid in high yields is reported.
Published online: 9th April, 2004
■ Synthesis of the New Pyrazolo[4,3-c]pyrrolizine Skeleton via Intramolecular Nitrilimine Cycloaddition
Giorgio Molteni*
*Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy
Abstract
Starting from the appropriate 1-substituted pyrrol-2-yl- (1) or indol-2-ylcarboxylic acid (6), the hydrazonyl chlorides (3) or (8) have been synthesised respectively. Their base treatment promoted the in situ generation of the corresponding nitrilimines (4) or (9), whose intramolecular 1,3-dipolar cycloaddition gave the title compounds in nearly quantitative yields.
Published online: 9th April, 2004
■ Two New Naphthalenyl Glucosides and a New Phenylbutyric Acid Glucoside from the Fruit of Juglans mandshurica
Lijuan Liu, Wei Li, Kazuo Koike, and Tamotsu Nikaido*
*Department of Pharmacognosy, School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Two new naphthalenyl glucosides, juglanosides F - G (1 - 2) and a new phenylbutyric acid glucoside, juglanoside H (3), along with three known naphthalenyl glucosides (4 - 6) were isolated from the fresh rejuvenated fruit of Juglans mandshurica. The structures of the new compounds were elucidated as 1,4,5-trihydroxynaphthalene 1,4-di-O-β-D-glucopyranoside (1), 1,4,5-trihydroxy- naphthalene 1,5-di-O-β-D-glucopyranoside (2), (R)-4-hydroxy-4-(3-hydroxy- phenyl)butyric acid 4-O-β-D-glucopyranoside (3), on the basis of spectroscopic analysis and chemical evidence.
Published online: 9th April, 2004
■ Two New Lignan Glycosides from Schisandra rubriflora
Ganpeng Li, Jingfeng Zhao, Yongqiang Tu, Xiaodong Yang, Hongbin Zhang, and Liang Li*
*School of Pharmacy, Yunnan University, Kunming 650091, China
Abstract
Two new lignan glycosides, rubriflosides A (1) and B (2), were isolated from the aerial parts of Schisandra rubriflora. Their structures were determined on the basis of spectroscopic evidences.
Published online: 9th April, 2004
■ A Bioactive Alkaloid from the Flowers of Trollius chinensis
Ru Feng Wang, Xiu Wei Yang, Chao Mei Ma, Shao Qing Cai,* Jian Nong Li, and Yukihiro Shoyama
*Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China
Abstract
A new compound, named as trolline was isolated from the ethanol extract of the flowers of Trollius chinensis Bunge. The chemical structure of this compound was elucidated by NMR, MS, IR, UV spectra and single-crystal X-Ray analysis. The in vitro antibacterial and antiviral experiments revealed that trolline exhibited appreciable antibacterial activity against respiratory bacteria such as Staphylococcus aureus, Streptococcus pneumoniae and Klebsiella pneumoniae. Trolline was also demonstrated to have moderate antiviral activity against influenza virus A and B.
Published online: 16th April, 2004
■ An Acylated Pelargonidin 3-Sophoroside from the Pale-brownish Red Flowers of Ipomoea nil
Kenjiro Toki, Norio Saito, Yasumasa Morita, Atsushi Hoshino, Shigeru Iida, Atsushi Shigihara, and Toshio Honda*
*Institute of Medical Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
A structurally new acylated anthocyanin was isolated from the pale-brownish red flowers of a duskish-2 mutant in the Japanese morning glory (Ipomoea nil or Pharbitis nil) as a major pigment together with a known anthocyanin. The new pigment was determined as pelargonidin 3-O-[2-O-(6-O- (trans-3-O-(β-glucopyranosyl)caffeoyl)-β-glucopyranosyl)-β-glucopyranoside], and the known anthocyanin was identified to be pelargonidin 3-sophoroside.
Published online: 12th March, 2004
■ Synthesis and Reactions of N-Ethynyl-heterocycles
Alan R. Katritzky,* Rong Jiang, and Sandeep K. Singh
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, U.S.A.
Abstract
Synthesis of N-ethynyl-heterocycles by elimination, nucleophilic substitution, isomerization, benzotriazole intermediates and other methods are reviewed. The reactions of N-ethynyl-heterocycles including additions, cycloadditions and polymerizations are discussed.