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. 45, No. 1, 1997
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■ Carbon-Carbon Bond Cleavage of α-Hydroxybenzylheteroarenes to Ketones and Heteroarenes by Catalytic Action of Cyanide Ion Based on Retro-Benzoin Condensation
Akira Miyashita,* Yumiko Suzuki, Yuki Takemura, Ken-ichi Iwamoto, and Takeo Higashino
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
Treatment of 4-(α-benzyl-α-hydroxybenzyl)quinazoline (2a) with potassium cyanide in DMF resulted in carbon-carbon bond cleavage to give benzyl phenyl ketone (3a) and quinazoline (4). Similar results were obtained with other 4-(α-hydroxybenzyl)quinalozines (2b-f and 7a). This reactioin proceeds through retrobenzoin condensation. This condensation also proceeded in pyrazolopyrimidine (9a) triazolopyrimidine (10a), quinoxaline (11a), and benzimidazole (12a), and the imidazolium salt (16) was an effective catalyst.
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■ A Stereocontrolled Synthesis of Pironetin
Mukund K. Gurjar,* Anjan Chakrabarti, and A. V. Rama Rao
*Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Abstract
The total synthesis of potent immunosuppressive agent - pironetin (PA-48153c) was achieved using highly stereocontrolled reactions.
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■ Synthesis of 2,4-Dimethylthiobenzo[c][2,7]naphthyridin-5(6H)-one: A Potentially Useful Intermediate for the Synthesis of Pyridoacridine Alkaloids
Kenneth L. Smith and Partha S. Ray*
*Department of Chemistry, The University of Memphis, Memphis, Tennessee 38152, U.S.A.
Abstract
Synthesis of the titled benzo[c][2,7]naphthyridinone (1) is described using intramolecular inverse electron demand Diels-Alder chemistry of 1,2,4-triazines (10) and (11).
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■ High Pressure Diels-Alder Reactions of Pyridones with Cyclooctyne
Kiyoshi Matsumoto,* Mona Ciobanu, Maki Yoshida, and Takane Uchida
*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
The high-pressure (0.8 GPa) Diels-Alder reactions of N-methyl-2(1H)-pyridones with cyclooctyne have afforded the corresponding stable bridged tricyclic 1:1 cycloadducts in moderate to good yields.
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■ Synthesis and Reactions of 4H-Imidazo[4,5-e][2,1,3]benzothiadiazol-5(6H)-one
Dodda Mohan Rao, Thota Giridhar, Gunapati Venkateswara Prasad, Reguru Buchi Reddy,* and Garimella Venkata Padmanabha Chandra Mouli
*Research and Development Center, Cheminor Drugs Limited, I.D.A.., Jeedimetla, Hyderabad-500055, India
Abstract
4H-Imidazo[4,5-e][2,1,3]benzothiadiazol-5(6H)-one (3) has been prepared by the condensation of 4,5-diamino-2,1,3-benzothiadiazol (1) with urea. 4,5-Diamino-2,1,3-benzothiadiazole (1) was also fused with thiourea to get the 5-mercapto-4H-imidazo[4,5-e][2,1,3]benzothiadiazole (2). Reactions on the compound (3) have been investigated.
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■ A Synthesis and Properties of 1-Substituted 1,4,5,6-Tetrahydro-pyrimidines
Bülent Alici, Engin Çetinkaya,* and Bekir Çetinkaya
*Fen-Edebiyat Fakultesi, Inönü University, 44069 Malatya, Turkey
Abstract
The condensation of 1-substituted 1,3-diaminopropane with N,N-dimethylformamide dimethylacetal gives 1-alkyl- or aryl-1,4,5,6-tetrahydropyrimidines (2) and (3). Alkylation of the tetrahydropyrimidine derivatives with alkyl halides produces the 1,3-dialkyltetrahydropyrimidinium salts (4 and 5). The attempted dehydrogeneration of 2 with sulfur leads to insertion of sulfur on the molecule.
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■ Reactions of 1-Substituted 2,2-Difluorostyrenes with Dianions of 1,3-Diketones: Novel Synthesis of 4H-Pyran-4-one Derivatives
Bum Tae Kim, No Kyun Park, Chwang Siek Pak, Myong Sang Kim, and In Howa Jeong*
*Pharmaceutical Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yusung, Daejeon 305-606, Korea
Abstract
Treatment of 1-substituted 2,2-difluorostyrenes with dianions of 1,3-diketones, which are generated via the reaction of 1,3-diketones with 4 equiv. of LDA in THF at -78 °C, resulted in the formation of 4H-pyran-4-one derivatives in moderated yields by warming to 25 °C.
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■ An Approach towards Fused Thieno[3,2-b]pyridines
Hamad Z. Alkhathlan*
*Chemistry Department, King Saud University, P.O. Box2455, Riyadh-11451, Saudi Arabia
Abstract
A series of fused thieno[3,2-b]pyridines was prepared via the condensation of substituted 2-acetyl-3-aminothiophenes and acid anhydrides. In addition, selected examples of these compounds were prepared via an intramolecular Wittig reaction.
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■ Application of the Mercuric Acetate-Edetic Acid Oxidation Method to the Synthesis of 11-Aza-1,2,3,4,5,6,7,12b-octahydroindolo[2,3-a]quinolizines
Yves Blache,* Mohammed Hichour, Olivier Chavignon, Alain Gueiffier, Jean-Claude Teulade, Gerard Dauphin, and Jean-Pierre Chapat
*E. A. 2414 Pharmacochimie et Biomolécules, Laboratoire de Chimie Organique Pharmaceutique, Université Montpellier I, 15 Avenue Charles Flahault, 34060 Montpellier, France
Abstract
The synthesis of 11-azaindolo[2,3-a]quinolizidines such as 2 is reported by cyclisation of lactams (1a) or piperidines (1b).
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■ Synthesis of Hydroxyflavanones from Substituted Acetophenones and Benzaldehydes in the Presence of Silica Gel, Boric Acid and Piperidine
Wei Han Zhang, Wing Lai Chan,* Yuan Hua Lin, Yau Shan Szeto, Yong Cheng Lin, and Chi Hung Yeung
*Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom Kowloon, China
Abstract
Direct synthesis of hydroxyflavanones from appropriately substituted acetophenones and benzaldehydes was achieved in the presence of boric acid, silica gel and piperidine. The formation of flavanones presumably involved the reaction between the acetophenone-boric acid complex (1) and the piperidinoaldehyde adduct (2) to yield the piperidino ketone (3). Elimination of piperidine from 3 gave the chalcone (4), which cyclized to flavanone (5).
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■ Synthesis of 2-Hydroxymethyl-3,5-dimethyl-4-methoxypyridine : A Key Intermediate for Omeprazole
Shan-Yen Chou* and Shyh-Fong Chen
*Deparatment of Medicinal Chemistry, Development Center for Biotechnology, Hsi-Chih Research Park 102, Lane 169, Kang Ning St, Hsi Chih 221, Taipei Hsien, Taiwan, R.O.C.
Abstract
A synthesis of 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine, a key intermediate for the preparation of gastric acid inhibiting compound omeprazole, is described. The procedure consists of preparation of pyrone, pyridone and pyridine derivatives sequentially.
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■ Synthesis of (Z)-3-Benzylidene-3,4-dihydro-2-oxo-2H-1,4-benzoxazine-5-carboxylic Acid, a Naturally Occurring Inhibitor of Glutathione S-Transferase
T. Ross Kelly,* Carmen Martinez, and Richard J. Mears
*E. F. Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02167, U.S.A.
Abstract
Preparation of a number of 2H-1,4-benzoxazine-2-ones has been effected by reaction of substituted 2-aminophenols with methyl 3-phenylpyruvate. This methodology has been applied to afford a rapid and efficient synthesis of the naturally occuring glutathione S-transferase inhibitor (Z)-3-benzylidene-3,4-dihydro-2-oxo-2H-1,4-benzoxazine-5-carboxylic acid.
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■ Synthesis and Conformational Behaviour of 2-Phenylperhydropyrrolo[1,2-d]-[1,3,4]oxadiazine and 2-Phenylper-hydropyrido[1,2-d][1,3,4]oxadiazine; New Heterocyclic Ring Systems
Ari Rosling, Ferenc Fülöp, Reijo Sillanpää, and Jorma Mattinen*
*Department of Organic Chemistry, Åbo Akademi University, Biskopsgatan 8, FIN-20500 Åbo, Finland
Abstract
Hydrazino alcohols, 1-amino-2-hydroxymethylpyrrolidine (1) and 1-amino-2-hydroxymethylpiperidine (2), were synthesized and subsequently ring closured with ethyl benzimidate to the title compounds (7) and (8), which have new ring system. Variable-temperature 1H nmr measurements, supported by X-ray analysis, indicated that pyrrolo[1,2-d][1,3,4]oxadiazine (7) exists exclusively in a cis-fused conformation (in CDCl3 at room temperature), whereas pyrido[1,2-d][1,3,4]oxadiazine (8) adopts a trans-fused conformation.
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■ Synthesis of Pyrido[2,3-b]pyrazines from Pyrido[2,3-c]furoxan
Tohru Takabatake, Tomoyuki Miyazawa, and Minoru Hasegawa*
*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan
Abstract
The synthesis of substituted pyrido[2,3-b]pyrazines was carried out. Pyrido[2,3-b]pyrazine 1,4-dioxides (3) and pyrido[2,3-b]pyrazine 1-oxides (4) were obtained from pyrido[2,3-c]furoxan (1) and 1,3-diketones or β-keto esters catalyzed by silica gel, alumina, or molecular sieves.
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■ Synthesis and the Skraup Reaction of Amino-5H-benzothiopyrano[2,3-b]pyridin-5-ones
Hidetoshi Fujiwara*
*Niigata College of Pharmacy, 5-13-2 Kamishin'ei-cho, Niigata 950-2081, Japan
Abstract
The New amino derivatives of 5H-[1] benzothiopyrano [2,3-b] pyridin-5-one were synthesized. The Skraup reaction of these amino-5H- [1] benzothiopyrano [2,3-b] pyridin-5-ones was conducted in the presence of grycerol, fuming sulfuric acid, nitrobenzene, iron (II) sulfate and boric acid. 6-Amino-, 7-amino-, 8-amino- and 9-Amino-5H-[1] benzothiopyrano [2,3-b] pyridin-5-ones gave 12H-pyrido [3’,2’:5,6]thiopyrano [2,3-h] quinolin-12-one, 12H-pyrido [3’,2’:5,6] thiopyrano [3,2-f] quinolin-12-one, 7H-pyrido [3’,2’:5,6] thiopyrano [3,2-h] quinolin-7-one, respeectively.
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■ Selective Synthesis of 2-Substituted Indazolin-3-ones without N-1 Protection
Vicente J. Arán, Enrique Díez-Barra,* Antonio de la Hoz, and Prado Sánchez-Verdú
*Facultad de Quimica, Universidad de Castilla-La Mancha, Campus Universitario, 13071 Ciudad Real, Spain
Abstract
N-2-Alkylation of indazolin-3-ones was performed in neutral conditions. This method represents a direct and efficient entry to a class of compounds having interesting biological activities, avoiding the generally required N-1 protection.
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■ An Improved Synthesis of Levofloxacin
Soon Bang Kang, Seonhee Park, Yong Hae Kim, and Youseung Kim*
*Division of Applied Science, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Korea
Abstract
The benzoxazinecarboxylic acid (8), a precursor of levofloxacin (1), was prepared from (S)-2-amino-1-propanol (2) in 4 steps in good overall yield. The synthesis is characterized by one pot construction of 8 from the useful benzoylacrylates (7) which are effectively prepared in three steps. The key intermediates (7)were obtained from 2-nitrobenzoyl derivative (6a) and 2-fluorobenzoyl derivative (6b) through acylation of the acrylates (5), respectively.
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■ INOC Reaction in Alkaloid Synthesis — Stereocontrolled Formal Total Synthesis of (+)-Pumiliotoxin C
Masahiro Toyota,* Takanobu Asoh, and Keiichiro Fukumoto
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
A formal total synthesis of (+)-pumiliotoxin C (1), the antipode of the arrow poison frog toxin, starting from the chirally homogeneous (1’S, 6’S)-2-(6’-benzyloxymethyl-2’-cyclohexyl)ethanol (2) is described. The synthesis features the intramolecular nitrile oxide cycloaddition (INOC) reaction of the nitro olefin (5) to furnish the isoxazoline (6).
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■ Substituent Effect of an N-Amino Group on the H-D Exchange of Ring Hydrogens of Adenines Compared with an N-Methyl Group
Wei Wu, Tetsuya Saga, Isamu Terashima, Ken-ichi Saeki, Kohfuku Kohda,* and Yutaka Kawazoe
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
Substituent effects of an N-amino group on the H-D exchange of ring hydrogens of adenines were compared with those of N-methyl group by treating N3-, N7-, and N9-substituted adenines in phosphate buffered D2O media at 70 °C. N-Aminoadenines underwent H-D exchange in position 8 faster than the corresponding N-methyladenines. Rates of the exchange of C8-hydrogen of N9-substituted adenines were independent of pD of the medium in an ordinary pD range above their pKa. In strongly alkaline media, N9-aminoadenine underwent H-D exchange at position 2, but N9-methyladenine did not.
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■ Artonols A, B, C, D, and E, Five New Isoprenylated Phenols from the Bark of Artocarpus communis Forst.
Miwa Aida, Norihisa Yamaguchi, Yoshio Hano, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Five new isoprenylated phenols, artonols A (1), B (2), C (3), D (4), and E (5) were isolated from the bark of Artocarpus communis Forst. (Moraceae), along with four known compounds, artonin E (6), cycloartobiloxanthone (7), artonin K (8), and artobiloxanthone (9). The structures of artonols A, B, C, D, and E were shown to be 1 - 5, respectively, on the basis of spectroscopic data. Artonols A (1) and B (2) have unique structures. These compounds are biogenetically assumed to be derivatives from the flavone derivatives having the dihydrobenzoxanthone skeleton, such as artobiloxanthone (9).
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■ Synthesis and the Absolute Configuration of PQ-8, a C14-Polyacetylene Compound Isolated from Panax quinquefolium
Mitsuru Satoh, Naoki Takeuchi, and Yasuo Fujimoto*
*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Abstract
PQ-8 (5), a C14-polyacetylene compound isolated from Panax quinquefolium, was synthesized starting from L-(+)-diethyl tartrate. The absolute stereostructure of PQ-8 was confirmed as (6R,7S)-6,7-epoxytetradeca-1,3-diyne.