HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Masatomo Hamana's Special Issues, Vol. 33, No. 1, 1992
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■ A Novel syntjesis of 4-Methyl-, 4-Oxo-, and 4-Amino-3-(3-methyl-5-isoxazolyl)pyridine Derivatives via N-Silyl-1-aza-allyl-Anion
Takeo Konakahara,* Naoki Sugama, and Kenji Sato
*Department of Industrial and Engineering Chemistry, Faculty of Science and Technology, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
An N -silyl-1-aza-ally1 anion (1) reacted with alkoxyalkenes (3a) - (3e) to afford the corresponding 4-methylpyridines (4a) and (4b), 4-pyridones (5c) and (5d), and 4-aminopyridine (4e) , possessing a 3-methyl-5-isoxazolyl group on C-3 atom, in 91, 90, 62, 27, and 68% yields, respectively, whereas alkoxyalkenes (3f ) and (3g) gave the corresponding N-adduct intermediates (6f ) and (6g) in 46 and 60% yields.
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■ Synthetic Approaches to Phorbols via the Intramolevular Nitrile Oxide Cycloaddition: Stereocontrol of the B-C Ring Junction
Kazuhiko Shigeno, Kazuhiko Ohne, Tetsuo Yamaguchi, Hiroaki Sasai, and Masakatsu Sibasaki*
*Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Abstract
The intramolecular cycloaddition of the nitrile oxide, synthesized from (+)-3-carene via 9 , provided the tetracyclic isoxazoline (10) stereospecifically. The isoxazoline (10) was converted to the carbotetracycle (17) via 15 utilizing the intramolecular McMurry coupling as a key step.
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■ 1-(2-Oxazolinyl)indoles
Yohko Takeda, Hironobu Nishiyama, Minoru Ishikawa, Kazuyuki Kamata, and Masanao Terashima*
*Faculty of Pharmaceutical Scicences, Higashinihonngakuen University, 1757 Kanazawa, Toubetu-cho, Ishikari-gun, Hokkaodo 061-0212, Japan
Abstract
Utilization of 1-(2-oxazolinyl)indoles, prepared from 1-cyano compounds, to the synthesis of 2-substituted indoles was investigated.
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■ Reaction of Aromatic N-Oxides with Dipolarophiles. XVII. Cycloaddition Behavior of Allenes toward Pyridine N-Oxides and Formation of Azetidine-type Cycloadduct
Toshikazu Matsuoka, Tomoaki Hasegawa, Kazunobu Harao, and Takuzo Hisano*
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
3,5-Dimethylpyridine N-oxide was allowed to react with phenylsulfonylpropadiene in CHCl3 at room temperature to give a mixture of the 1:1 [1,5] sigmatropic rearrangement product and the 1:2 azetidine-type cycloadduct. The structure of the azetidine-type cycloadduct was determined by single crystal X-ray analysis. The reaction behavior and the regioselectivity are discussed in terms of the frontier molecular orbital considerations.
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■ Oxidation of Amines with 4a-FIEt-OOH: An Enzyme Model of FAD-Containing Monooxygenase
Shigeru Oae,* Kaoru Ogawa Asada, Toshiaki Yoshimura,and Ken Fujimori
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
Unlike the real enzyme, FAD-containing monooxygenase, 4a-FlEt-OOH, oxidizes most of common primary, secondary and tertiary water-soluble amines, such as N -methylmorpholine and n-octylamine. Both kinetic rates and products of the oxidation were obtained. The plots of the rates vs. pKa values gave three different correlations lines depending upon the types of amines.
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■ A Synthesis of a New Type Heterocyclic Compound Using Deils-Alder Cycloaddition of 2-Methylene-1,2-dihydropyridines
Hiroto Nakano, Hiroshi Tomisawa, and Hiroshi Hongo*
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
Diels-Alder cycloaddition of 2-methylene-1,2-dihydropyridines having an active methylene group at the 1-position with N-phenylmaleimide gave isoquinuclidines, and cyclization of the adducts obtained afforded a new type of heterocyclic ring system, 2-azatricyclo[5.2.2.02,6]undecanes.
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■ Triazolopyridines. Part 12: A New Synthesis of Indolizines from Triazolopyridine Ylides
Belen Abarca, Rafael Ballesteros, Mohamed R. Metni, and Gurnos Jones*
*Department of Chemistry, University of Keele, Keele, staffordshire, ST5 5BG, U.K.
Abstract
Treatment of 2-acylmethyl-1,2,3-triazolo[1,5-a]pyridinium ylides (1) with methyl propiolate in non-polar solvent gives good yiedes of 1,2,3-trisubstituted indolizines (5). A mechanism for the transformation is suggested.
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■ Preparation of Heteroarenecarbonitriles by Reaction of Heteroarene N-Oxides with Trimethylsilyl Cyanide in the Presence of DBU
Akira Miyashita,* Touru Kawashima, Chihoko Iijima, and Takeo Higashino
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
Several heteroarenecarbonitriles were prepared from the corresponding heteroarene N-oxides by treatment with trimethylsilyl cyanide (TMSCN) in the presence of a base in tetrahydrofuran (THF). 1,8-Diazabicyclo[5.4.0]-7-undecene (DBU) was found to be an effective base for the cyanation.
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■ A Synthetic Approache to (±)-O-Methylclavizepine: An Alternative Synthesis of C-Norcularine
Hiroshi Hara, Masanori Kishigami, Masaki Endoh, Ken-ichi Kaneko, and Osamu Hoshino*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
Abstract
C-Norcularine (2) was synthesized stepwise via the xanthone (3) or by intramolecular Pictet-Spengler reaction directly from the amino aldehyde (10).
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■ Two Complex Flavonoids in the Farinose Exudate of Pityrogramma calomelanos
Fujio Asai, Munekazu Iinuma,* Toshiyuki Tanaka, and Mizuo Mizuno
*Department of Pharmacognosy, Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
From the farinose exudate of Pityrogramma calomelanos, two new complex flavonoids named calomelanols D and E were isolated. Their structures were determined by spectroscopic analysis.
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■ Synthesis of 2-Indolyl-1,4-benzodiazepin-5-ones Utilizing a mannich Type Cyclization
Nobuyuki Matsunaga, Hiroshi Harada, Toyohiko Aoyama, and Takayuki Shioiri*
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
2-Indolyl-1,4-benzodiazepin-5-ones (3) have been efficiently synthesized from Boc-α-amino acids (4), 3-hydroxyanthranilic acid (8), and indole; the key step is a Mannich type cyclization accompanied with introduction of indole.
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■ Palladium-catalyzed Cross-coupling Ractions of Chloropyrazines with Aromatic Heterocycles
Yutaka Aoyagi, Akira Inoue, Isamu Koizumi, Rie Hashimoto, Kazuko Tokunaga, Kaori Gohma, Junko Komatsu, Kumiko Sekine, Ayako Miyafuji, Jun Kunoh, Rieko Honma, (the late) Yasuo Akita, and Akihiro Ohta*
*Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
In the presence of tetrakis(triphenylphosphine)palladium, chloropyrazines were treated with aromatic heterocycles such as furan, thiophene, pyrrole, N-substituted pyrroles, benzo[b]furan, benzo[b]thiophene, oxazole, thiazole, N-methylimidazoles, benz[b]oxazole and benzo[b]thiazole. The corresponding coupling products were obtained in moderate to good yields. The structures of the coupling products were determined.
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■ Formation of 2,5-Dihydro-3H-pyrazolo[4,3-c]quinolin-3-ones from Ethyl 3-Amilino-2-(2-tert-butyl-2H-tetrazol-5-yl)acrylates
Sumiro Isoda* and Hideyuki Kanno
*Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd., 16-13, Kitakasai 1-chome, Edsogawa-ku, Tokyo 134, Japan
Abstract
Thermal cyclization of ethyl 2-(2-tert -butyl-2H-tetrazol-5-yl)-3-(4-chloroanilino)acrylate (5) did not afford the intended 4-quinolinone derivative (6) , but yielded 2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (7) . The reaction mechanism is thought to have been double cyclization of the nitrile imine intermediate (C).
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■ Syntheses and Absolute Configurations of Optically Pure 4-Isopropyl-N-tosyl-1,3-oxazolidines
Hiroshi Takahashi,* Takeshi Tubuki, and Kimio Higashiyama
*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
(2S,4S)-4-Isopropyl-N-tosyl-1,3-oxazolidines (3a-e)having methyl, cyclohexyl, phenyl, o-bromophenyl, or o-formylphenyl group at the 2-position of the ring were synthesized, and these products were confirmed to consist of one isomer by 1H-nmr spectral analyses in spite of a newly created asymmetric center at the 2-position. The absolute configurations of 3a-e were determined by difference nuclear Overhauser effect studies.
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■ Synthesis of a Naturally Occurring Benzocyclobutene, Muscomosin
Toshio Honda* and Tetsuya Toya
*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
A naturally occuning benzocyclobutene, muscomosin (2) was synthesized from 1-cyanobenzocyclobutene derivative.
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■ Thermal Reaction of Benzimidazolium N-Allylides
Yoshiro Matsuda,* Makoto Yamashita, Kimitoshi Takahashi, Shizuki Ide, Katsura Torisu, and Kazuki Furuno
*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
The reaction of benzimidazolium salt (3) and polarized olefins (1a,b,d and 2c) with K2CO3 in CHCl3 gave the corresponding benzimidazolium N -allylides (4a-d). Thermolyses of N-allylides (4a,b) in refluxing xylene afforded the 1,5-dipolar
cyclization product, benzopyrroloimidazole (5a), whereas heating of N-allylides (4c,d) resulted in back-donated 1,6-cyclization to give the mesomeric betaines, benzimidazopyridiniumides (7a,b). Treatment of 3 and 2a with K2CO3 in CHCl3 yielded directly benzopyrroloimidazole (5b), while similar treatment of 3 with
1c or 2b gave benzopyrrolopyrazines (6a,b).
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■ Synthesis and Neuroexcitatory Activity of Some Acromelic Acid Analogs
Katsuhiro Konno, Kimiko Hashimoto, and Haruhisa Shirahama*
*Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
Abstract
The pyridine derivatives (6~9), analogs of acromelic acid A (1) which were potent excitatory amino acids, were synthesized. In the crayfish neuromuscular junction, depolarizing activity of these derivatives was comparable to those of acromelic acid A and domoic acid. At the isolated rat spinal motoneurons, compounds (6), (7) and (8) were found to be powerful excitants as potent as kainic acid, while 9 was inactive.
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■ Synthesis and Biological Evalution of Functionalized Epoxides Structurally Related to the Carbapenem Family
Jacqueline Marchand-Brynaert, John Davies, and Léon Ghosez*
*Laboratoire de Chimie Organique de Synthèse, Université Catholique de Louvain, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium
Abstract
Epoxides (6) and (7), topologically related to the carbapenem antibiotics,
were designed as potential alkylating inhibitors of the bacterial D,D-peptidases. The
olefinic precursors (8-9) were readily prepared, in three steps, by coupling the Wittig
reagent (13) with the aldehyde synthons (10) or (11) resulting from diastereoselective aldol condensations. Epoxide (7) showed a weak anti-β-lactamase activity.
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■ Elucidation of the Reaction Path for the Nitrosation of 2- and 4-Methylpyridine 1-Oxides with Alkyl Nitrite in Liquid Ammonia
Yoshinobu Tagawa, Hideo Togashi, and Yoshinobu Goto*
*Faculty of Pharmaceutical Sciences, Fukuoka University, Nakamura, Jonan-ku, Fukuoka, 814-0180, Japan
Abstract
The reaction path for the nitrosation of 2- and 4-methylpyridine 1-oxides with alkyl nitrite in the presence of NaNH2 in liquid NH3 was elucidated experimentally, and theoretically by the use of a semiempirical molecular orbital method (PM3 method). In the case of the nitrosation of 4-methylpyridine 1-oxide at room temperature, only 4-pyridinecarboxamide 1-oxide was obtained, while at -33°C a thermodynamically unstable aldoxime, (Z )-4-pyridinecarbaldehyde 1-oxide oxime, which was easily transformed into E-form by heating, was obtained. On the other hand, the nitrosation of 2-methylpyridine 1-oxide gave only a thermodynamically stable aldoxime, (E)-2-pyridinecarbaldehyde 1-oxide oxime, both at room temperature and at -33°C. These results were reasonably explained by PM3 method.
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■ Tetracyanoquinodimethanes Fused with 1,2,5-Thiadiazole and Pyrazine Units
Yoshiaki Tsubota, Takanori Suzuki, Yoshiro Yamashita, Toshio Mukai, and Tsutomu Miyashi＊
*Department of Chemistry, Faculty of Science, Tohoku University
Abstract
1,2,5-Thiadiazolopyrazino-TCNQs underwent reversible four-stage one-electron reduction and gave conductive CT complexes with some donors. The X-ray structural analysis of the unsubstituted derivative revealed that the coplanar “sheet”- like network was formed by interatomic contacts of S--N≡C and H--N≡C in crystal.
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■ Synthesis of (±)-Tetrahydropseudodistomin, a Hydrogenation Product of Antineoplastic Alkaloids, Pseudodistomins A and B
Iwao Utsunomiya, Masashi Ogawa, and Mitsutaka Natsume＊
*Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158, Japan
Abstract
2-Alkyl-1,2,3,6-tetrahydro-3-pyridinols (6, R2 = H) with trans arrangement of the side chains were prepared by sodium cyanoborohydride reduction of the singlet oxygen adducts (5) of 1,2-dihydropyridine derivatives (4) in the presence of tin (II) chloride. Stereoselective synthesis of (±)-tetrahydropseudodistomin (3) was achieved starting from one of such reaction products (10) by way of 12 and 14.
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■ Synthesis of (+)- and (-)-Mellein Utilkizing an Annelation Reaction of Isoxazoles with Dimethyl 3-Oxoglutarate
Naoki Takeuchi,＊ Kaori Goto, Yuki sasaki, Takashi Fujita, Kohsuke Okazaki, Kohji Kamata, and Seisho Tobinaga
*Showa College of Pharmaceutical Sciences, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Abstract
Naturally occurring dihydroisocoumarins, (+) - and (-) -mellein (2 and 3), metabolites of fungals, Cercospora sp. and Aspergillus sp., etc., were synthesized from the isoxazoles (32) and (33) by the annelation reactions with dimethyl 3-oxoglutarate.
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■ Reaction of Dehydroellagitannins with L-Cysteine Methyl Ester
Takashi Tanaka, Hiroshi Fujisaki, Gen-ichiro Nonaka,＊ and Itsuo Nishioka
*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Abstract
Reaction of dehydroellagitannins (e.g . 1 ) with L-cysteine methyl ester (5) at room temperature yielded the condensation products (e.g. 3 and 4), together with a partial hydrolysate (e.g. 2), while heating the mixture at 80ÅãC afforded 4 and the hydrolysate(2) in fairly good yields. In addition, reduction of a dehydrohexahydroxydiphenoyl ester group to a hexahydroxy-diphenoyl group with thiols is also described.
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■ Ozonolysis of 1-Substituted Imidazoles
Choji Kashima,＊ Kaori Harada, and Akira Hosomi
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
1-Substituted imidazoles was ozonolyzed cleanly without any complicated procedures into the corresponding N-acylamides, which were regarded to be much useful derivatives of either amines or acyl compounds.
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■ A Synthesis and an X-Ray Analysis of 2'-C-, 3'-C- and 5'-C-Methylsangivamycins
Yasushi Murai, Hironori Shiroto, Tatsuya Ishizaki. Takamasa Iimori,＊ Yoshio Kodama, Yasuo Ohtsuka, and Takeshi Oishi
*Faculty of Engineering, Yokohama National University, Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan
Abstract
3’-C, 5’(R)-C - and 5’(S)-C-Methylsangivamycins (3-5) were synthesized by
the trimethylsilyl triflate mediated coupling reaction of the methyl substituted ribose
derivatives (7), (9) and (1 0) with me base moiety (1 1) and the successive functional
group manipulation. 2’-C -Methylsangivamycin (2) was synthesized by the condensation of the sodium salt of 23 with the chlorosugar (28) as me key step. The crystalline structures of C -methyisangivamycins (2-4) were determined by X-ray studies.
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■ Mass Spectrometry of Prenylated Flavonoids
Mitsuo Takayama, Toshio Fukai, Yoshio Hano, and Taro Nomura＊
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
The fragmentation patterns originating from the degradation of prenyl group(s) in positive ion electron ionization (EI), fast-atom bombardment (FAB) and chemical ionization (CI) mass spectrometry (MS) of prenylated flavonoids were reviewed. The EI spectra showed the characteristic fragmentation patterns reflecting the location of prenyl group in the flavonoid compounds, whereas the FAB and CI spectra showed relatively monotonous patterns. It was described how the El and FAB fragmentation patterns are useful for the identification of prenylated flavonoids.
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■ Development of Modified Chiral Dioxolane Bisphosphine Ligands and Their Use in Efficient Asymmetric Synthesis of Naturally Occurring Lignans
Toshiaki Morimoto, Mitsuo Chiba, and Kazuo Achiwa＊
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
This review deals with our recent works on the development of efficient chiral bisphisphine ligands, modified DIOPs, bearing a dioxolane framework and their application to the asymmetric total synthesis of naturally occurring lignans such as (+)-collinusin, (-)-deoxypodophyllotoxin, and (+)-neoisostegane using rhodium(I)-catalyzed asymmetric hydrogenation of itaconic acid derivatives as a key step. Related asymmetric total syntheses of lignans using an equimolar amount of chiral sources are also reviewed.
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■ Oligomeric Hydrolyzable Tannins — Their 1H NMR Spectra and Partial Degradation
Takashi Yoshida, Tsutomu Hatano, Takako Kuwajima, and Takuo Okuda＊
*Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
The 1H nmr spectroscopy provides a convenient method of assigning the orientation of the valoneoyl group in the oligomeric hydrolyzable tannins, which is the unit most frequently joining the monomeric constituents in the molecules. The behavior of oligomers upon partial degradation has been found to be dependent on the location of valoneoyl group on the glucose core.