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. 1, 2004
Published online: 14th November, 2003
■ Benzodioxole Chemistry. 5. Dramatic Substituent Effect in the Reaction of Carbonyl-bridged Cyclic Carbonates with Methoxide Ion
William S. Grove and Ernest A. Harrison Jr.*
*Department of Chemistry, The Pennsylvania State University, York Campus, 1031 Edgecomb Avenue, York, Pennsylvania 17403, U.S.A.
Abstract
Benzodioxolediones (2c-e) undergo high-yield conversion to cyclopentenones (3c-e) in K2CO3/MeOH at room temperature, while analogs (2a) and (2b) yield exclusively cyclohexadiene carboxylates (1a and 1b) under these conditions. Isolation of intermediate 6(R,R’=Me R”=Ph) from the reaction of 2c with K2CO3/MeOH at 5-10 °C suggests that 3 is formed in a process triggered by attack of OMe(-) at the ester carbonyl of 2.
Published online: 14th November, 2003
■ Improvement in the Regioselectivity in the Ruthenium-catalyzed Metathesis Reaction of 2-Azabicyclo[2.2.1]hept-5-en-3-one (ABH) with Allyltrimethylsilane
Minoru Ishikura,* Miyako Hasunuma, and Makoto Saijo
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
2-Azabicyclo[2.2.1]hept-5-en-3-one (ABH) (1) with N-trialkylsilyl group was subjected to a ring-opening cross-metathesis reaction with allyl-trimethylsilane in the presence of a ruthenium catalyst, allowing the predominate formation of rel-(3R,5S)-3-(4,4,-dimethyl-4-silapentyl)-5-ethylpyrrolidin-2-one (5) over rel-(3R,5S)-5-(4,4,-dimethyl-4-silapentyl)-3-ethylpyrrolidin-2-one (6).
Published online: 10th November, 2003
■ New Synthesis and Biologically Active Molecular Design of Deazapteridine-Steroid Hybrid Compounds
Tomohisa Nagamatsu,* Hiroki Yamada, and Kazuyuki Shiromoto
*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
This paper describes a facile and general synthesis of a new class of the hybrid compounds (4, 5 and 16), possessing 5-deazapteridine and steroid in the same ring system, by condensation of 6-(monosubstituted amino)uracils (9) or 6-(monosubstituted amino)-2-phenylpyrimidin-4(3H)-ones (14) with 2-hydroxy-methyleneandrostanolone (10) or 2-hydroxymethylenetestosterone (15) under heating in the presence of p-toluenesulfonic acid monohydrate and their potential unti-coccidiosis activities.
Published online: 21st November, 2003
■ Synthesis of Optically Active Tetrahydro-3-benzazepine-2-carboxylic Acid Derivatives via the Ring Expansion Reaction of Isoquinolines and Enzymatic Resolution
Yuji Koseki, Hidefumi Ozawa, Katsuaki Kitahara, Ichiro Kato, Hiroto Sato, Haruhiko Fukaya, and Tatsuo Nagasaka*
*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
The facial approach to 3-benzazepine-2-carboxylic acid derivatives (1) via the ring expansion reactions of 10b-hydroxymethyloxazoloisoquinolines (3) to 3-benzazepines (2) is described. Utilizing enzymatic resolution, the synthesis of (-)-(S)-N-Cbz-3-benzazepine-2-carboxylic acid (1b) was achieved.
Published online: 31st October, 2003
■ Synthesis of N-Allyl and N-Propadienylacridones Using Phase-Transfer Catalysis
Lisbet Xuárez, Roland F. Pellón,* Norma D’Accorso, Verónica Montesano, and Mirtha Fasio
*Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina
Abstract
A convenient procedure for the synthesis of N-allyl substituted acridones under phase-transfer catalysis is reported using allyl bromide as alkylating agent. When propargyl bromide was used, in the same reaction conditions, no propynylacridone was detected in the reaction and only propadienylacridone was obtained in moderate yield.
Published online: 14th November, 2003
■ Bipyrrole Derivatives as New DNA-Minor Groove Binders
Mikimasa Tanada, Yoshihiro Shibata, Minoru Maeda, and Shigeki Sasaki*
*Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Abstract
Small molecules with capability of binding with DNA or RNA would have broad application as probes in genomic studies, and also as potential candidates for new therapeutic agents. In this study, we synthesized dithioamido-bipyrrole derivatives as new binding molecules to the duplex DNA. It has been revealed from the competitive binding experiments with the known intercalater, ethidum bromide, and the minor groove binder Hoechst 33258 that the dithioamido-bipyrrole derivatives with alkyl chains with medium length bind the duplex DNA in a similar manner with the minor groove binder. As ionic interactions are not included in the binding with the duplex DNA, the new dithioamido-bipyrrole skeleton may provide an interesting motif for DNA binding.
Published online: 4th November, 2003
■ Indium-mediated Reductive Inter-molecular Coupling Reaction of 2-Nitroaniline with Aromatic Aldehydes to Benzimidazoles
Byeong Hyo Kim,* Rongbi Han, Ji Sook Kim, Young Moo Jun, Woonphil Baik, and Byung Min Lee
*Department of Chemistry, Kwangwoon University, 447-1, Wolgye-Dong Nowon-ku, Seoul, 139-701, Korea
Abstract
2-Nitroaniline and aromatic aldehydes were coupled to give benzimidazoles in high yields in the presence of 2-bromo-2-nitropropane and indium at room temperature.
Published online: 14th November, 2003
■ Synthesis and Structural Studies of (2-Oxo-2,3-dihydroimidazo[1,2-a]pyridin-3-yl)acetic Acids
Anton V. Dolzhenko,* Nina V. Kolotova, Vladislav O. Kozminykh, Wai-Keung Chui,* Paul W. S. Heng, and Viktor N. Khrustalev
*Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore
Abstract
(2-Oxo-2,3-dihydroimidazo[1,2-a]pyridin-3-yl)acetic acids (4a-c, 9a-c) were prepared from 2-aminopyridines by acylation with maleic or citraconic anhydrides and followed by Michael addition. Formation of 3-methyl substituted derivatives (9a-c) from citraconic anhydride was found to be regioselective. The molecular conformations of the products in the solution and in the crystal form were discussed based on 1H NMR spectral and X-Ray data.
Published online: 10th November, 2003
■ Preparation and Structure of Diexo-Oxanorbornane-fused 1,3-Heterocycles
Ferenc Miklós, Iván Kanizsai, Steffen Thomas, Erich Kleinpeter, Reijo Sillanpää, and Géza Stájer*
*Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary
Abstract
Via the reaction of diexo-oxanorbornanedicarboxylic anhydride with toluene, the diexo-aroylcarboxylic acid (3a) was prepared, which exists partly as the tautomeric lactol (3b). With bifunctional reagents, 3a yields fused hetero-cycles containing three–six rings. Thus, alkylenediamines result in imidazole- and 1,3-diazepine-fused oxygen-bridged isoindolones (6a,b), alkanolamines form the oxazole- and 1,3-oxazine-fused oxanorbornene derivatives (7a-c), and o-phenylenediamine undergoes cyclization to furnish the condensed benzimidazole (8). The reaction of 3a with diexo-aminonorbornanecarbohydrazide yields a pyrimido-pyridazine containing six condensed rings (9). In a similar reaction with diendo-aminonorbornenecarbohydrazide, cyclopentadiene cleaves off to give the tricyclic retro Diels-Alder product (10). The structures, and particulary the configurations at the oxanorbornane ring systems and the position of the aryl substituent, were established by means of 1D- and 2D-NMR spectroscopy and, for 3b and 7c, also by X-Ray measurements.
Published online: 14th November, 2003
■ Synthetic Studies on Isoquinoline Derivatives with Multidrug Resistance (MDR) Modulating Activity
Chen Ma,* Su-Dong Cho, J. R. Falck, and Dong-Soo Shin
*School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China
Abstract
Tetrahydropyridazino-1,4-oxazinoisoquinoline derivatives with
multidrug resistance (MDR) modulating activity were designed and synthesized.
A key step for cyclization of 1,4-oxazine ring was developed using K2CO3 and
CH3CN in one-pot. Among prepared compounds, 2-(4-fluorobenzyl)-9,10-
dimethoxy-12-methyl-6,7,11b,12-tetrahydropyridazino[4’,5’,5,6][1,4]oxazine-
[3,4,-a]isoquinolin-1(2H)-one (1f) exhibited significant MDR reversing activity
and low toxicity, which might be as potential MDR agent.
Published online: 31st October, 2003
■ One-Pot Synthesis of Tetra-substituted Imidazoles on Silica Gel under Microwave Irradiation
Yu Xu, Yan-Zhi Liu, Lei Rui, Lei Liu, and Qing-Xiang Guo*
*Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei 230026, China
Abstract
A new procedure for synthesis of tetra-substituted imidazoles was developed. A series of imidazole derivatives including six new compounds were synthesized by this procedure via condensation of benzoin, aromatic aldehyde, amine and ammonium acetate in the presence of silica gel under solvent-free microwave irradiation.
Published online: 21st November, 2003
■ Synthesis of 2-Substituted 3,4-Dihydroquinazoline Derivatives via Regioselective Addition of a Carbon Nucleophile to a Carbodiimide
Bum Hoon Lee, Jae Yeol Lee,* Bong Young Chung, and Yong Sup Lee*
*Division of Life Sciences, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 131-650, Korea
Abstract
Synthesis of 2-alkyl or phenyl-substituted 3,4-dihydroquinazoline derivatives (6) is described via regioselective carbon nucleophilic addition (RMgBr and RM) to a carbodiimide (4) followed by intramolecular conjugate addition.
Published online: 4th November, 2003
■ Terpenoid Metabolites of the Marine Octocoral Eunicea laciniata
Kelly I. Marville, William F. Reynolds, R. Lynn Sealy, and 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
Abstract
A chemical investigation of the Caribbean marine octocoral Eunicea laciniata collected along the south coast of Barbados afforded a new cubitane diterpenoid (1), a new steroidal glycoside (3), along with two known diterpenes. Their structures were determined by 1D and 2D NMR spectral experiments.
Published online: 31st October, 2003
■ Two New Bicoumarins from Clausena excavata
Yuko Takemura, Kinuko Kanao, Asami Konoshima, Motoharu Ju-ichi,* Chihiro Ito, Hiroshi Furukawa, Harukuni Tokuda, and Hoyoku Nishino
*Faculty of Pharmacy, Meijo University, 150 Yagoto, Tempaku-ku, Nagoya, Aichi 468-8503, Japan
Abstract
Two novel type bicoumarins, named cladimarins A (1) and B (4), were isolated from the branch of Clausena excavata (Rutaceae) collected in Indonesia. The structures were elucidated on the basis of spectroscopical data especially by using HMBC method. Naturally occurring bicoumarin, connected two coumarin moieties by acetal ring as in 1 and by ester bond as in 4, is rare type. Inhibitory effects of new bicoumarins on EBV-EA activation induced by TPA in Raji cells were also demonstrated.
Published online: 21st November, 2003
■ Three New Lycoctonine-Type C19-Diterpenoid Alkaloids from Delphinium giraldii
Xian-Li Zhou, Qiao-Hong Chen, and Feng-Peng Wang*
*Department of Chemistry of Medicinal Natural Products, West China College of Pharmacy, Sichuan University, No. 17, Duan 3, Remin Nan Road, Chengdu 610041, China
Abstract
From the roots of Delphinium giraldii, three new lycoctonine-type C19-diterpenoid alkaloids, giraldine D (1), giraldine E (2) and giraldine F (3), have been isolated. The structures of 1~3 were established by spectroscopic evidence including 2D NMR spectroscopy.
Published online: 10th November, 2003
■ A New Resveratrol Hexamer from Upuna borneensis
Tetsuro Ito,* Toshiyuki Tanaka, Zulfiqar Ali, Yukihiro Akao, Yoshinori Nozawa, Yoshikazu Takahashi, Ryuichi Sawa, Ken-ichi Nakaya, Jin Murata, Dedy Darnaedi, and Munekazu Iinuma
*Gifu Prefectrual Institute of Health and Environmental Sciences, 1-1 Nakafudogaoka, Kakamigahara, Gifu 504-0838, Japan
Abstract
A new resveratrol hexamer, upunaphenol A, was isolated from an acetone soluble part of stem of Upuna borneensis (Dipterocarpaceae). The structure, which has twelve asymmetric carbon atoms on the partial structures of a dibenzobicyclo[3.2.1]octadiene ring and four dihydrobenzofuran rings, was determined by spectral analysis including 1D and 2D NMR spectral experiments. Resveratrol and four known resveratrol oligomers, ampelopsin F, isoampelopsin F, vaticanols C and B, were also isolated. Upunaphenol A was found to suppress cell growth in HL60 cells through induction of apoptosis with IC50 at 9.2 μM.
Published online: 31st October, 2003
■ Preparation and Optical Resolution of a New Helical Lactone Carrying the 2,8-Dioxabicyclo[3.3.0]octane Ring System
Makoto Yamaye,* Yusuke Ikeda, Namiko Cho(Toh), Yoshinori Miura, Tetsutaro Yoshinaga, Katsuya Mukae, and Toshiaki Tsuru
*Faculty of Engineering, Kyushu Kyoritsu University, 1-8 Jiyugaoka, Yahatanishiku, Kitakyushu 807-8585, Japan
Abstract
A new overcrowded lactone (3) carrying the 2,8-dioxabicyclo[3.3.0]octane ring system was prepared by a simple treatment of tetraol (1) (prepared from 2,7-dihydroxynaphthalene and glyoxal) with 3,5-xylenol, and readily resolved into its enantiomers having a specific rotation of >800° (absolute value). A preliminary experiment demonstrated that 3 would be a promising resolving agent.
Published online: 14th November, 2003
■ Structural Revision in Pyrazole Chemistry
Devinder Kumar* and Shiv P. Singh*
*Department of Applied Chemistry, Guru Jambheshwar University, Hisar-125001, Haryana, India
Abstract
Reaction of several heteroarylhydrazines with β-diketones has been incorrectly reported to generate triazepines or diazepines. It has now been firmly established that these reactions lead to the formation of pyrazoles. Further, many workers have reported the formation of pyrazoles in the reaction of heteroarylhydrazines with trifluoromethyl 1,3-diketones, whereas the actual products were found to be 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-pyrazoles. It was also established that with a trifluoromethyl β-diketone and hydrazines, the location of the CF3 group at position 3 or 5 of pyrazoles depends on the nature of the hydrazine. Erroneous reports concerning the structure of the products obtained by the reaction of dehydroacetic acid with hydrazines have also been revised.