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. 51, No. 2, 1999
Published online:
■ Late Stage of Biosynthesis of Intermolecular Diels-Alder Type Adducts in Morus alba L. Cell Cultures
Yoshio Hano, Taro Nomura,* and Shinichi Ueda
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
The 13C-enrichments of chalcone type Diels-Alder type adducts, kuwanons J (1), R (3), and V (4) resulting from administration experiment of [2-13C]acetate to Morus alba cell cultures as well as of 2-arylbenzofuran type adducts, chalcomoracin (5) and mulberrofuran E (6), revealed that major adducts (1) and (5) by the cell cultures are presumably derived from 4 and 6, respectively, through hydroxylation reaction. Kuwanon V (4) and mulberrofuran E (6) were found to be primary adducts in the M. alba cell cultures.
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■ Modified Uracils Convertible between Cations, Conjugated, and Cross-conjugated Mesomeric Betaines. Syntheses, Semiempirical Study, and X-Ray Analysis
Andreas Schmidt,* Markus Karl Kindermann, and Martin Nieger
*Laboratorium für Organische und Bioorganische, Institut für Chemie, Universität Osnabrück, Barbarastr. 7, D-4500 Osnabrück, Germany
Abstract
Nucleophilic substitution on the 6-chiorouracils (1) and (8) by heteroaromatics such as DMAP, 4-methylpyridine, and 3-hydroxypyridine yielded uracilylpyridinium salts (2, 3, 7, 10), mesomeric betaines (4, 5, 6), and a bis-betaine (9), respectively. A prototropic shift converts the CCMB (6A) into the CMB (6B), the dipole moments and most stable conformations of which were calculated. X-Ray crystallography was performed on the uracilylpyridinium salt (7).
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■ Time Dependent Interconversion of Diels-Alder Adducts into Michael Adducts
Kuniaki Itoh,* Kazue Kitoh, and Akira Sera
*Department of Chemistry, Faculty of Science, Kobe University, Nada-Ku, Kobe 6557-8501, Japan
Abstract
Furans react with methyl 3-nitroacrylate to concurrently give Diels-Alder adducts and Michael adducts, and the former turns into the latter. The orbital energy difference between a HOMOdiene and a LUMOdienophile seems to control the product distribution of the reaction.
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■ Unprecedented Cyanation and Cyanomethylation Following Ring Closure versus Dimer Formation during Anodic Oxidation of the Aspidofractinine Alkaloid Kopsamine
Toh-Seok Kam,* Tuck-Meng Lim, and Guan-Huat Tan
*Department of Chemistry, Unviersity of Malaya, Pantai Valley, 50603 Kuala Lumpur, Malaysia
Abstract
Anodic oxidation of the aspidofractinine-type indole alkaloid kopsamine on platinum in Et4NClO4/MeCN results in an unprecedented cyanation-cynomethylation reaction following ring closure while oxidation on vitreous carbon in LiClO4-MeOH yielded a dimerization product with a C2 element of symmetry.
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■ Heterocyclic Compounds from 3,4-Diaminodimethylamino-1-methylpyrazolo[3,4-d]pyrimidine: Approach to Novel ortho- and peri-Fused Heterocyclic Ring System
Zhijun Wang and Richard Neidlein*
*Departamento de Química Orgánica, Facultad de Ciencias Experimentales de Jaén, 23071 Jaén, Spain
Abstract
Treatment of 3,4-diamino-6-dimethylamino-1-methylpyrazolo[3,4-a]pyrimidine (4) with acid chlorides (5a-h) led to formatiom of 3-substituted carbonylamino-4-amino-6-dimethylamino-1-methylpyrazolo[3,4-d]pyrimidines (6a-h), which reacted with N,N-dirnethylformamide dimethyl acetal (7) to yield 4-dimethylaminoazomethinopyrazolo[3,4-d]pyrimidine derivatives (8a-c). Approach to novel ortho- and peri-fused tricyclic heterocyclic system, namely, 1,2,3,5,6,8-hexaazaacenaphthylene derivatives (11,12) is also reported.
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■ New Scaffolds for Peptidomimetics. Synthetic Approaches towards 2,4-Dioxooctahydropyrimido[1’,6’:1,2]pyrido[3,4-b]indole-6-carboxylic Acid Derivatives
Natalia De la Figuera, Ma Teresa García-López, Rosario Herranz, and Rosario González-Muñiz*
*Centro de Química Orgánica ’Manuel Lora-Tamayo’, Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, E-28006 Madrid, Spain
Abstract
The synthesis of 6-substituted 2,4-dioxooctahydropyrimido[1’,6’:1,2]pyrido[2,3-b]indole derivatives from 1-(alkyloxycarbonyl)methyltetrahydro-β-carboline-3-carboxylic acid derivatives is described. The construction of the pyrimidine ring competes with that of the imidazole, to provide imidazo[1’,5’:1,6]pyrido[2,3-b]indole derivatives, when an alkyloxycarbonyl group is placed in position 3 of the tetrahydro-β-carboline, but not when there is a carboxamide function in such position.
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■ Synthesis and Antitumor Activity of Javacarboline Derivatives
Hiroshi Yoshino, Kazuo Koike, and Tamotsu Nikaido*
*Department of Pharmacognosy, School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Syntheses of 12H-pyrido[2,1-a]-β-carbolin-5-ium bromides (15-27) and 11H-pyrrolo[2,l-a]-β-carbo1ines (32-35), structurally related to the tetracyclic alkaloid javacarboline (1) have been achieved via 2 steps routes starting from the respective β-carbolines. Their synthetic compounds showed potent antitumor activities against P-388 murine leukemia cells and PC-6 human lung carcinoma cells.
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■ Total Synthesis of (±)-Pedicularis-Lactone and (±)-Ningpogenin
An-Yang Lee, Meng-Yang Chang, and Nein-Chen Chang*
*Department of Chemistry, National Sun Yat Sen University, Kaohsiung, 804, Taiwan, R.O.C.
Abstract
A total synthesis of (±)-pedicularis-lactone (1) and (±)-ningpogenin (2) via a trisubstitued cyclopentenoid (5) is described. The key step is photolytic cleavage of the bicyclo[2.2.l]heptanone.
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■ Synthesis of an Antioxidant Having a Dibenz[b,f]oxepine Skeleton
Shuji Jinno and Takaaki Okita*
*Central Resarch Laboratory, Nippoon Suisan Kaisha, Ltd, 559-6 Kitanomatchi, Hachioji, Tokyo 192-0906, Japan
Abstract
Dibenz[b,f]oxepine derivative (1) isolated from a yeast as an antioxidant was synthesized via 17 reaction steps starting from methyl gallate. However, the physicochemical data of the synthetic compound (1) were different from the previously reported values. Moreover, the antioxidative activity of the synthetic 1 was slightly more active than that of the natural product.
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■ Synthesis and Antitumor Activity of Canthin-5,6-dione Derivatives
Kazuo Koike, Hiroshi Yoshino, and Tamotsu Nikaido*
*Department of Pharmacognosy, School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Syntheses of canthin-5,6-dione derivatives have been achieved via one step route starting from their respective β-carbolines. Their synthetic compounds showed antitumor activities against P-388 murine leukemia cells and PC-6 human lung carcinoma cells.
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■ Photocleavage of DNA by the Halo Benzamide Derivatives of Oligo-N-methylpyrrolecarboxamides
Masakazu Wakayama, Hiromi Iitsuka, Ichiro Suzuki, and Masayuki Shibuya*
*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi 1, Tokushima 770-8505, Japan
Abstract
The preparation of halo benzamide photonuclease containing DNA minor groove binding units of varying lengths is described. These molecules have been assayed for DNA-cleaving ability, and bromo and iodo derivatives were found to be very effective. The reaction mechanism was also investigated and a benzenoid carbon radical was shown to be responsible for the reaction.
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■ Synthesis of Novel Peptidomimetics, Cyclic Hexamers of Unnatural Amino Acids, 2,5-Disubstituted 3-Aminobenzoic Acids
Katsuya Endo* and Hiroyasu Takahashi
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
Coupling of 3-aminobenzoic acids and cyclization of their peptides have been accomplished, for the first time, using methanesulfonyl chloride. Cylindrical conformations for the 30-membered cyclic hexapeptides, with trans configuration at the amide bonds, are suggested by ROESY study as well as MM calculations.
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■ Dippinine C, a New Hexacyclic Chippiine Derivative from a Malayan Tabernaemontana
Toh-Seok Kam* and Kooi-Mow Sim
*Department of Chemistry, Unviersity of Malaya, Pantai Valley, 50603 Kuala Lumpur, Malaysia
Abstract
A new indole alkaloid, dippinine C, belonging to the chippiine group but with incorporation of an additional ring, was obtained from the stem-bark extract of Tabernaemontana coryinbosa and its structure established by spectral analysis.
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■ A Simple Synthesis of Benzocarbazolequinones via o-Nitroarylation of 2-Hydroxy-1,4-naphthoquinones
Kazuhiro Kobayashi,* Tetsuya Taki, Masataka Kawakita, Masaharu Uchida, Osamu Morikawa, and Hisatoshi Konishi
*Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Abstract
The reaction of 2-hydroxy-1,4-naphthoquinones (1a-c) with o-fluoronitrobenzenes (2a,b) in the presence of K2CO3 in DMSO at 100 °C gave 2-hydroxy-3-(2-nitroaryl)-1,4-naphthoquinones (3a-e) in moderate to fair yields, which in turn were transformed into the corresponding 11H-benzo[a]carbazole-5,6-dione (6a-e) and 5H-benzo[b]carbazole-6,11-dione (7a-e) derivatives in good yields by catalytic hydrogenation over PtO2 in AcOEt at room temperature and 1 atm, followed by exposure to air and then heating at reflux temperature.
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■ Fluoropyrazoles: An Ab initio Study
Rosa María Claramunt,* Ibon Alkorta, and José Elguero
*Centro de Química Orgánica ’Manuel Lora-Tamayo’, Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, E-28006 Madrid, Spain
Abstract
Quantum mechanic calculations have been done at the RHF and MP2 levels with the STO-3G, 6-31G**, 6-311G** basis sets on pyrazole itself and seven N-unsubstituted C-fluoropyrazoles. These calculations have been used to discuss the molecular structure of these compounds in relation to their aromaticity. The corresponding 1H, 13C, 15N and 19F chemical shifts were calculated using the GIAO perturbation method.
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■ Isoharmine Revisited: Thermal Rearrangement of a 3-Cyanomethyl-2-vinylindole
Janos Sapi,* Dominique Patigny, and Jean-Yves Laronze*
*Laboratoire de Chimie Thérapeutique, Laboratoire de Transformation et Synthèse de Substances Naturelles, Université de Reims-Champagne-Ardenne, 51, rue Cognacq-Jay, F-51096 Reims Cedex, France
Abstract
Thermolysis of 2-vinylindole derivative (1) led to indolylacrylonitrile (6) instead of β-carboline alkaloid isoharmine (4). Latter was prepared by following the conventional method and was fully characterized.
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■ Ex-Chiral Pool Synthesis of Aminooxazepinones as Conformationally Restricted β-Amino Acid Analogs
Dorothee Michel, Reiner Waibel, and Peter Gmeiner*
*Institut für Pharmazie und Lebensmittelchemie, Universität Erlangen-Nürnberg, Schuhstrasse 19, D-91052 Erlangen, Germany
Abstract
Starting from natural asparagine, an efficient synthesis of the dibenzyl protected 6-amino-1,3-oxazepin-4-one (7) is reported. According to NMR based conformational studies, the lactam-bridged β-amino acid analog (7) adopts preferentially a twisted boat structure. The incorporation of the described molecular scaffold to give a constrained β-analog of the dopamine receptor modulating peptide Pro-Leu-Gly-NH2 is described as an application in the field of medicinal chemistry.
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■ Synthesis of Optically Active 2-Chloromethyl-2-oxazolines by the Ortho-ester Codensation Method Using Triethyl Orthochloroacetate
Kazuyuki Kamata,* Hideki Sato, Emi Takagi, Isao Agata, and A. I. Meyers
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
A set of optically active 2-chloromethyl-2-oxazolines was synthesized by condensation of optically active 2-amino alcohols with triethyl orthochloroacetate which was prepared conveniently from triethyl orthoacetate by chlorination using tert-butyl hypochiorite.
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■ Syntheses of Various Imidazo[5,1-c][1,2,4]triazole Derivatives Having Potential Biological Activities
Mohamed Abdel Hamid Ismail
*Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassiya, Cairo, Egypt
Abstract
The title compounds (5a-f) and (6a-f) were synthesized from the corresponding 4-arylidene-hydrazonoimidazolidines (3a-f) and (4a-f) on treatment with acetic anhydride. The intermediates (3a-f) were obtained by reacting 4-hydrazono-2-thioxoimidazolidines (2a-b) with various aldehydes. The later (2a-b) were resulted by reacting 2,4-dithiohydantoins (1a-b) with N2H4. Methylation of 3a-f gave 4a-f.
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■ Studies of the Egyptian Traditional Folk Medicines. III. A New Diprenylated 3-Arylcoumarin from Egyptian Licorice
Masaki Baba, Ryoya Asano, Yoshihito Okada, Abdel-Nasser Singab, Shinji Fushiya, Makio Shibano, Genjiro Kusano, and Toru Okuyama*
*Meiji Pharmaceutical Uni1versity, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Abstract
A new diprenylated 3-arylcoumarin, named licocoumarin A, was isolated from Egyptian licorice together with two known compounds (kanzonol W, isoliquiritigenin), and the structure was confirmed to be 3’,8-diprenyl-7,2’,4’-trihydroxy-3-arylcoumarin.
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■ The 11 Positional Isomers of Nx, Ny-Dimethyladenine: Their Chemistry, Physicochemical Properties, and Biological Activities
Tozo Fujii* and Taisuke Itaya
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
Various Nx,Ny-disubstituted adenines are represented by the corresponding 11 possible positional isomers of Nx,Ny-dimethyl adenine, namely, N6,N6- (2), N6,1- (3), N6,3- (4), N6,7- (5), N6,9- (6), 1,3- (7), 1,7- (8), 1,9- (9), 3,7- (10), 3,9- (11), and 7,9-dimethyladenine (12). The chemistry, physicochemical properties, and biological activities of these Nx,Ny-dimethyladenines are reviewed with 513 reference citations.