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. 14, No. 6, 1980
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■ Biogenetic-type Synthesis of Clivimine from Clivacetine
Shigeru Kobayashi,* Yasuhiro Imakura, Hideki Ishikawa, and Etsuko Sasakawa
*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Abstract
The structures of clivacetine (1) and clivatine (4) were confirmed by the partial synthesis of clivacetine (1) from clivonine (2). Clivimine (3) was obtained by biogenetic-type synthesis from clivacetine (1), which seems to be a biosynthetic precursor of clivimine (3).
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■ Synthesis of 5-(Substituted alkyl)picolinic Acids, the Dopamine β-Hydroxylase Inhibitors. III
Koichi Miyano, Takeji Sakasai, and Hiroaki Hamano*
*Research Laboratories, Nippon-Kayaku Co. Ltd., 3-31-12, Shimo, Kita, Tokyo 115-0042, Japan
Abstract
Several 5-alkylpicolinic acids, dopamine β-hydroxylase inhibitors were synthesized from 2-cyclopropyl-5-cyclopropylcarbonylpyridine (I) as a suitable starting material.
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■ Synthesis of 4’-Phenylated Pyrimidine C-Nucleosides
T. Sato, M. Watanabe, and R. Noyori*
*Department of Chmistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan
Abstract
4’-Phenylated pyrimidine C-nucleosides have been prepared for the first time via the tetrabromoacetone/furan cyclocoupling approach.
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■ Alkaloid Production in Catharanthus roseus Cell Cultures. III. Catharanthine and Other Alkaloids from the 200GW Cell Line
James P. Kutney,* Lewis S. L. Choi, Pawel Kolodziejczyk, Stephen K. Sleigh, Keneeth L. Stuart, Brian R. Worth, W. G. W. Kurz,* K. B. Chatson, and F. Constabel
*Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada
Abstract
The production of catharanthine by suspension cultures of the “200GW” cell line from Catharanthus roseus is reported. Other alkaloids isolated are vallesiachotamine isomers, ajmalicine, hörhammerinine, hörhammericine, vindolinine, 19-epivindolinine and strictosidine lactam.
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■ Condensation with Tetrahydropyranylurea: Synthesis of 3-Tetrahydropyranyl Uracils
F. Gómez Contreras, T. Manzano, and P. Navarro*
*Instituto de Quimica Organica General, Consejo Superior Investigaciones Cientificas, Calle Juan de la Cierva, 3, E-28006 Madrid, Spain
Abstract
The 3-tetrahydropyranyl uracil derivatives 1 and 2 have been obtained by reaction of tetrahydropyranylurea (THPU) with diethyl ethoxymethylenemalonate. The sodium salt (monohydrate) of 1 was also isolated in the same reaction. In a similar way, THPU has been condensed with ethyl ethoxymethylenecyanoacetate to give the open chain compound 3, which was identified as a mixture of the E (3a) and Z (3b) isomers. Heating of THPU with triethyl orthoformate and ethyl cyanoacetate afforded an identical mixture of isomers. By using this last procedure, the ureidoethylene derivatives of diethyl malonate, malononitrile and malonic acid (4, 5 and 6, respectively) have also been isolated and identified.
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■ The Stereoselective Reduction of α-Aminopropiophenone Derivatives with Sodium Borohydride
Tetsuji Kametani,* Kazuo Kigasawa, Mineharu Hiiragi, Nagatoshi Wagatsuma, Toshitaka Kohagizawa, and Hitoshi Inoue
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
The ratio of erythro and threo products from the sodium borohydride reduction of the hydrochlorides, and other acid salts, of α-aminopropiophenone derivatives was determined. It was found that this procedure resulted in stereoselective formation of erythro-2-amino-1-phenylpropanols in contrast to sodium borohydride reduction of the corresponding free bases. The method was successfully applied to the synthesis of dl-erythro-2-(4-benzylpiperidino)-1-(4-hydroxyphenyl)propanol which has been used as a vasodilator.
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■ Photocyclization of N-3-Alkenylphthalimides. Effect of Alkyl Substitution on the Formation of Pyrroloisoindoles and Pyridoisoindoles
Minoru Machida, Kazuaki Oda, Kazuhiro Maruyama, Yasuo Kubo, and Yuichi Kanaoka*
*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan
Abstract
Photolysis of N-3-alkenylphthalimides 1 in methanol gave tetrahydro-5H-pyrrolo[2,1-a]isoindol-5-ones 2 and/or tetrahydropyrido[2,1-a]isoindol-6(2H)-ones 3 depending on the degree of substitution at the olefin carbons of 1. Electron transfer followed by the anti-Markownikoff addition of methanol is proposed as a possible mechanistic pathway.
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■ Formation of 1,1’-Bi-1H-pyrrolo[3,2-c]pyridines by the Deoxygenation of 4-Nitro-3-styrylpyridine 1-Oxides with Tervalent Phosphorus Compounds
Tarozaemon Nishiwaki,* Noritaka Abe, and Kenzo Moriyasu
*Department of Chemistry, Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan
Abstract
The deoxygenation reaction of 4-nitro-3-styrylpyridine 1-oxides with triethyl phosphite or, more favourably, with hexaalkylphosphorous triamide afforded 1,1’-bi-1H-pyrrolo[3,2-c]pyridines instead of a monomeric product.
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■ Studies on Heterocyclic Chemiatry. Part 22. Acylation of 4-Aryl-3-mercapto-3-isothiazoline-5-thiones with Aryl Isocyanate
Tarozaemon Nishiwaki,* Etsuko Kawamura, Noritaka Abe, and Mitsuo Iori
*Department of Chemistry, Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan
Abstract
The reaction of 4-aryl-3-mercapto-3-isothiazoline-5-thiones with aryl isocyanate result in exclusive formation of an N-acylated product, whose sulfur atom at C-5 undergoes a selective alkylation with diazomethane or alkyl iodide.
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■ Preparation of 1,4-Diphenyl-3-substituted Isoquinolines
Shuntaro Mataka, Kazufumi Takahashi, Yuhsuke Tsuda, and Masashi Tashiro*
*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan
Abstract
The reaction of o-dibenzoylbenzene (1) with benzylamine (2a), m-(2b) and p-xylylendiamine (2c), n-butylamine (2d), ethylglycinate (2f) and aminoacetonitrile (2g) in the presence of basic catalysts afforded the corresponding 3-substituted 1,4-diphenylisoquinolines (3a-d,f,g, and i), while the reaction of 1 with ethanolamine (2e) gave a trace amount of 3-hydroxymethylisoquinoline (3e) and 1,3-diphenylisobenzofuran (4) in 25% yield.
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■ Synthesis of Cycloheptadiimidazole Derivatives from a Reactive Troponoid
Hitoshi Takeshita,* Akira Mori, Tomoyoshi Minami, and Hirofumi Kondo
*Instituete of Advanced Material Study, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan
Abstract
The condensation of 2,4-dichloro-5-methoxytropone with guanidine or with amidines gave 1H-cyclohepta[1,2-d;3,4-d]diimidazoles and 1H-cyclohepta[1,2-d;4,5-d]diimidazoles, which possess the same heterocyclic skeletons with unique metabolites isolated from marine organisms. According to the NMR analysis, the condensations proceeded in the exclusive cine reaction.
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■ Synthesis of a Potential Intermediate to apo-Mitomycins
Tetsuji Kametani,* Yoshio Kigawa, Hideo Nemoto, Masataka Ihara, and Keiichiro Fukumoto
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Cyclisation of compound (8), which was obtained by condensation of benzyl α-bromo-α-(2-bromo-5-methoxy-4-methylphenyl)acetare (7) with trans-3-acetoxy-4-(N-ethoxycarbonyl-N-methylamino)-2-thiopyrrolidone (2), afforded pyrroloindoles (9) and (10), the former of which on hydrogenolysis gave carboxylic acid (11). Carboxaldehyde (13), which was synthesised from (11) via thioester (12) by successive treatment with oxalyl chloride and ethyl mercaptan, was converted into nitro compound (15). Finally reduction of (15) followed by oxidation of resulting amino compound (16) furnished (±)-1α-acetoxy-2β-[N-ethoxycarbonyl-N-methylamino]-2,3-dihydro-7-methoxy-6-methyl-5,8-dioxo-1H-pyrrolo[1,2-a]indole-9-carboxaldehyde (17).
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■ Reaction of Quinoline Methiodide with Bromo- or p-Toluenesulfonyloxy-acetonitrile Derivatives. Formation of a Novel Tricyclic Diazanonane System
Seitaro Saeki,* Yoshio Kaku, Masatomo Hamana,* and Hiroshi Noda
*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Abstract
Quinoline methiodide (1) reacts with ethyl bromocyanoacetate (2a) in the presence of triethylamine to afford ethyl 2-methyl-9-oxo-2,10-diazabenzo[c]tricyclo[4,2,1,07,11]nonane-8-carboxylate (3a) in 24.1% yield. The products of the same type (3b-d and 3f) are obtained from reactions of 1 with bromocyanoacetamide (2b), α-bromophenylacetonitrile (2c), α-bromo-p-nitrophenylacetonitrile (2d), and o-tosylates of benzaldehyde and p-chlorobenzaldehyde cyanohydrins (2e and 2f).
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■ Transformations in the Pyridine Series. A Simple Preparation of 3-Methyl-4-phenylpyridine and Corresponding 2-Carboxamides
Ernest A. Harrison, Jr., Kenner C. Rice,* and Michael E. Rogers
*Section of Medical Chemistry, Laboratory of Analytical Chemistry, NIDDK, National Institute of Health, Bethesda, MD 20982, U.S.A.
Abstract
A simple 3-step synthesis of 3-methyl-4-phenylpyridine (2), a key intermediate in the synthesis of several diverse types of potential pharmaceutical agents is reported. Conversion of this pyridine derivative, which is easily prepared on a large scale, to a number of the corresponding 2-carboxamides is described. Amide 5a of this series was active as a basic, nonsteroidal anti-inflammatory agent in the rat adjuvant arthritis test.
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■ Synthesis of (±)-Kreysiginone, a Homoaporphine and Homoprotoberberines via N-Oxide Intermediates
Tetsuji Kametani,* Masataka Ihara, Makoto Takemura, and Yoshinari Satoh
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Reaction of 1,2,3,4-tetrahydro-7-hydroxy-1-(3-hydroxy-4-methoxyphenethyl)-6-methoxy-2-methylisoquinoline N-oxide (2) with ferrous sulfate in methanol gave the 2,9-and 2,11-dihydroxyhomoprotoberberines (5 and 6). The 2,10-dihydroxy derivative (8) was obtained by the reaction of 1,2,3,4-tetrahydro-7-hydroxy-1-(4-hydroxy-3-methoxyphenethyl)-6-methoxy-2-methylisoquinoline N-oxide (4) with ferrous sulfate in hot acetic acid. Reaction of the N-oxides (2 and 4) with cuprous chloride in methanol afforded the phenol oxidative coupling products, the homoaporphine (12) and (±)-kreysiginones (13).
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■ A Short Route to the 8,13-Dioxo-14-methoxyberbines
G. Manikumar and M. Shamma*
*Department of Chemistry, The Pennsylvania State University, York Campus, P1031 Edgecomb Avenue, York, Pennsylvania 17403, U.S.A.
Abstract
Pyridinium chlorochromate oxidation of oxyprotoberberines, followed by methanol work-up, leads to 8,13-dioxo-14-methoxyberbines.
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■ Studies on Phenothiazines. Part 6. Synthesis of 3-Alkoxy-1-nitro-7-substituted Phenothiazines via Smiles Rearrangement
R. R. Gupta,* S. K. Jain, Naresh K. Goswami, and G. S. Kalwania
*Department of Chemistry, University of Rajasthan, Jaipur 302 004, India
Abstract
Synthesis of 3-alkoxy-1-nitro-7-substituted phenothiazines via Smiles rearrangement is reported. 5-Alkoxy-2-amino-3-nitro benzenethiols prepared by hydrolytic fission of 6-alkoxy-4-nitrobenzo-1,2,3-dithiazolium chloride (The Herz Compound) were condensed with substituted o-chloro-nitrobenzenes and the diaryl sulfides so obtained were converted into formyl derivatives by formic acid. The latter on treatment with alcoholic KOH underwent Smiles rearrangement yielding 3-alkoxy-1-nitro-7-substituted phenothiazines.
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■ 13C NMR Spectra of N-Substituted Aziridines
Kiyoshi Matsumoto,* Shun’kichi Nakamura, Takane Uchida, and Yoshinori Takemoto
*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
The 13C chemical shifts for the cis- and trans-N-substituted diphenyl, dibenzoyl, aroylaryl, and arylcyanoaziridines (1-8) have been reported (Table 1, 2, and 3). The differences of 13C chemical shifts between the cis and trans isomers and the effects of N- and ring C-substituents, and of the para-substituted groups of phenyl or benzoyl group upon the chemical shifts of the ring carbons are described. The chemical shifts of the ring carbons are qualitatively discussed in terms of steric compression effects.
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■ Mass Spectrometry of Oxazoles
Pietro Traldi,* Umberto Vettori, and Angelo Clerici
*Centro di Studio della Sintesi e Sterochimica di Speciali Sistemi Organici, C.N.R., Università degli Studi di Milano, Via C. Golgi, 19, 20133 Milano, Italy
Abstract
The mass spectral behaviour of oxazole and its derivatives represents quite a particular aspect of the chemistry of these heterocyclic compounds but is of paramount importance for the understanding of their structures. This review is an attempt to rationalize and discuss the major advances reported since pioneer studies.
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■ 3-Haloindolenines — Versatile Intermediates in the Indole Chemistry
Masazumi Ikeda* and Yasumitsu Tamura
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
This review summarized the preparation and synthetic use of 3-haloindolenines. Some of the factors which affect the reactivity of this interesting intermediates are also discussed.