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. 31, No. 7, 1990
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■ Synthesis of Vinca Alkaloids and Related Compounds LIII. A Simple Synthesis of (±)-3-Oxovincadifformine and (±)-3-Oxominovine
György Kalaus, Chau Phan Dinh, Mária Kajtár-Peredy, János Brlid, Lajos Szabó, and Csaba Szántay*
*Central Research Institute for Chemistry, Hungarian Academy of Sciences, H-1525 Budapest, Pusztaszeri ut 59-67, P.O.Box 17, Hungary
Abstract
Starting from compound 1 syntheses of th title compounds were achieved via linear reaction sequences.
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■ Synthesis of Benzodioxane Prostacyclin Analogue
Sachio Mori* and Shozo Takechi
*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan
Abstract
Benzodiaoxane prostacyclic analogue ((±)-1) was synthesized via stereocontrolled construction of cyclopentanobezodioxane (17) (7, R2 = MOM) utilizing the Mitsunobu reaction, and subsequent introduction of the propenyl group into 17 by radical C-C coupling leading to 19 (8, R2 = MOM).
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■ Synthesis of Benzoxolane Prostacyclin Analogue
Sachio Mori* and Shozo Takechi
*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan
Abstract
Benzoxolane prostacyclin analogue ((±)-1) was synthesized with key step involving regio- and stereocontrolled carbon-carbon bond formation using allylic phosphate (17) and stabilized copper reagent derived from 15, followed by intramolecular selenoetherification leading to cylopentanobenzoxolane (19).
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■ Application of TiCl4 Induced Iminium Ion Cyclizations to the Preparations of Piperidine Alkaloids: Total Syntheses of (±)-Coniine
Tsung-Fan Teng, Jyh-Hwa Lin, and Teng-Kuei Yang*
*Department of Chemistry, National Chung-Hsing University, Taichung, 40227, Taiwan, R.O.C.
Abstract
Syntheses of (±)-coniine via TiCl4 induced iminium ion cyclizations of α-cyanoamines are described. Moreover, (α-cyanoalkyl)amine could lead to the cyclic piperidine system in good yield.
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■ Stereocontrolled Iodolactonization of erythro and threo Tertiary Amides
David P. Rotella* and Xun Li
*Department of Pharmacology, School of Pharmacy, University of Mississippi, University, Mississippi 38677, U.S.A.
Abstract
A series of α-amino and dialkyl-β-oxygenated (hydroxyl and alkyl ester) tertiary amides were subjected to iodolactonization and it was observed that with only 1 exception, (threo 11b), all of the compounds cyclized with useful levels of stereoselection (at least 3:1). While the origin of this effect is obscure, these results suggest that in such amide substrates with at least one substituent larger than methyl a to the amide, iodolactonization is a viable strategy for the stereocontrolled preparation of highly substituted γ-butyrolactones.
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■ 2-(Trimethylsilyl)- and 2-(Trimethylstannyl)-Δ2-thiazolines: Synthetic Aspects and Reactivity
Olga Bortolini, Giancarlo Fantin, Marco Foganolo, Alessandro Medici,* and Paolo Pedrini
*Dipartimento di Chimica, Università di Ferrara, 44100 Ferrara, Italy
Abstract
The synthesis of 2-(trimethylsilyl)- and 2-(trimethylstannyl)-Δ2-thiazolines is reported. The reactivity of the title compounds toward various electrophiles is also discussed.
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■ Synthesis of Double-armed Azaoligocycles Based upon High Pressure Aromatic Nucleophilic Substitution Reactions
Kiyoshi Matsumoto,* Hiroyuki Minatogawa, Mitsuo Toda, and Megumu Munakata
*College of Liberal Arts and Sciences, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
A variety of double-armed azaoligocycles were prepared through high pressure SNAr reactions (0.8 GPa, 100 °C) of homo-piperazine with five- and six-membered heteroaromatic halides, the yields being good to excellent when the halides are activated by electronic effects.
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■ Hydrolyzable Tannins having a Depsidone-forming Valoneoyl Group
Tsutomu Hatano, Osamu Namba, Ling Chen, Taeko Yasuhara, Kazufumi Yazaki, Takashi Yoshida, and Takuo Okuda*
*Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
Prostrain C (1) isolated from Euphorbia prostrata, and proecoxims C (2) and D (3) isolated from Stachyurus praecox, were found to be hydrolyzable tannins having a depsidone-forming valoneoyl group as a constituent unit. The orientation of the valoneoyl group in praecoxins C and D as in the structures 2 and 3 was unequivocally proved by the 1H-13C long-range shift correlation spectrum of rugosin C (5) which was chemically correlated with praecoxin C.
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■ An Enantioselective Synthesis of the Key Intermediate for the Preparation of 1β-Methylcarbapenem Antibiotics
Toshio Honda,* Hiroyuki Ishizone, Koichi Naito, and Yukio Suzuki
*Institute of Medical Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
An enantioselective synthesis of the key intermediate for the preparation of 1β-methylcarbapenem has been achieved by employing the cyclopentane derivative (8), as a chiral source, readily derived from (-)-carvone.
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■ Use of 1,3-Dioxin-4-ones and Their Related Compounds in Synthesis. 27. Novel Asymmetric Hetero-Diels-Alder Reaction Using Chiral Spiro 5-Methylene-1,3-dioxane-4,6-diones Having 1-Methone at the 2-Position
Masayuki Sato,* Kazuya Kano, Noritaka Kitazawa, Hiroyuki Hisamichi, and Chikara Kaneko*
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Diastereofacially selective heter-Diels-Alder reaction of spiro (E or Z)-5-arylidene-1,3-dioxane-4,6-diones and 2-methoxypropene was studied. The dihydropyrans thus obtained were converted to optically active β-arylated δ-oxohexanoic acids. The diastereofacil selectivity fo the hetero-Diels-Alder reactions is explained by the sofa-conformation of the heterodienes which accepts the dienophile at the convex α-side preferentially.
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■ Further Norditerpenoid Alkaloids from Delphinium nuttallianum
Yili Bai, Michael Benn,* and Walter Majak
*Department of Chemistry, The University of Calgary, Alberta, T2N 1N4, Canada
Abstract
A study of the minor bases of D. nuttallianum resulted in the isolation and identification of eight known and five new diterpenoid alkaloids.
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■ A Novel Appraoch to Chiral Cyclobutanes — An Enantioselective Total Synthesis of (+)-(S,Z)-5-(1-Decenyl)dihydro-2(3H)-furanone and (-)-(R,Z)-5-(1-Decenyl)dihydro-2(3H)-furanone
Hideo Nemoto, Hiroki Ishibashi, Masahiko Mori, Shigekazu Fujita, and Keiichiro Fukumoto*
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
An enantioselective synthesis of (+)-(S,Z)-5-(1-decenyl)dihydro-2(3H)-furanone (25) and (-)-(R,Z)-5-(1-decenyl)dihydro-2(3H)-furanone (26) was achieved starting with either (10) or (11) prepared by reduction of the chiral cyclobutanone (8) which was derived stereospecifically from the cyclopropyl carbinol (6) by ring expansion reaction.
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■ The Synthesis of Thienotriazolothiazepines
Hitoshi Nagaoka, Hiromu Hara, and Toshiyasu Mase*
*Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., 21, Miyukigaoka, Ibaraki 305, Japan
Abstract
Some derivatives of thienotriazolothiazepine, a novel heteroazepine, were synthesized. These compounds showed anti-PAF activity.
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■ Studies on Intramolecular Mannich Reaction of (S)-2-(α-Hydroxyethyl)benzimidazole. Synthesis of (1S)-4-Aryl-4,5-dihydro-1-methyl-1H,3H-[1,3,5]oxadiazepino[5,6-a]benzimidazoles — A New Class of Heterocyclic Compounds
Shaheen A. Hussain,* Tahira B. Sarfaraz, Naheed Sultana, Najma Murtaza, and Izhar H. Qureshi
*Pharmaceutical and Fine Chemical Research Centre, P.C.S.I.R. Laboratories, Karachi-75280, Pakistan
Abstract
The intramolecular Mannich reaction of (S)-2-(α-hydroxyethyl)benzimidazole with primary aromatic amines IIa-g and formaldehyde has been shown to furnish a new class of heterocyclic compounds: (1S)-4-aryl-4,5-dihydro-1-methyl-1H,3H-[1,3,5]oxadiazepino[5,6-a]benzimidazoles IIIa-g. the antibacetrial activity of these compounds has also been evaluated.
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■ New Synthetic Approach to 1-Azabicyclo[x.y.0]alkalne Skeletons from β-Enamino Diesters Derived from Meldrum’s Acid
Mansour Haddad, Jean Pierre Célérier, Gjergj Haviari, Gérard Lhommet,* Hamid Dhimane, Jean Claude Pommelet, and Josselin Chuche
*Laboratoire de Chimie des Hétérocycles URA 455, Université P. et M. Curie, 4, Place Jussieu - case 43 F-75252 Paris Cedex 05, France
Abstract
Two complementary methods for the synthesis of title compounds (4 and 6), namely, monodecarboxylating transesterification of β-enamino esters 2 followed by intramolecular cyclization of 3, and direct cyclization of 2 under flash vaccum thermolysis conditions, have been elaborated. Further investigations allowed the identification of β-enamino acid chloride 5 as a stable intermediate in the direct cyclization of 2 into 6. Azabicyclic compounds 4 were stereospecifically converted to bicyclic β-amino alcohols 9 by means of stereocontrolled carbon-carbon double bond catalytic hydrogenation followed by ester moiety reduction.
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■ The Selective Benzylic Bromination of o-Xylenes. A Useful Synthesis of Phthalides
Vernon G. S. Box* and George P. Yiannikouros
*Department of Chemistry, The City College of the City University of New York, Convent Avenue @ 138th Street, New York, NY 10031, U.S.A.
Abstract
The free radical bromination of aryl methyl groups can be controlled by the strategic positioning of a remote stereo-electroni blocking group on the aryl ring. This tactic leads to the efficient synthesis of selectively benzylically brominated molecules whichare useful synthetic intermediates. This methodology has been applied to the synthesis of some phthalides.
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■ Reactivity of Heteroaromatic Aldehydes with Low Valent Titanium
Luis Castedo,* M. Magdalena Cid, Rosa Domíngues, Julio A. Seijas, and M. Carmen Villaverde
*Departamento de Química Orgánica, Universidad de Santiago de Compostela, E-15706, Santiago de Compostela, Spain
Abstract
Behaviour of various aromatic heterocycles under dicarbonylic coupling with low valent titanium was studied. The results showed that the electron donating properties of the ring affect the degree of oxidation of the coupled compound.
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■ Structure and Oxidation of 2-Hydroxy-3,6-diisobutylpyrazines
Akihiro Ohta,* Akihiko Kojima, Chiseko Sakuma, Teruo Kurihara, and Shigeru Ogasawara
*Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Tautomeric structures of 2-hydroxy-3,6-diisobutylpyrazine (1), 5-chloro-2-hydroxy-3,6-diisobutylpyrazine (2) and 2-hydroxy-3,6-diisobutyl-5-methoxypyrazine (3) are discussed. The oxidation of 1, 2, and 3 with permaleic acid gave the corresponding monoxides 2-hydroxy-3,6-diisobutylpyrazine (12), 5-chloro-2-hydroxy-3,6-diisobutylpyrazine 1-oxide (13), and 2-hydroxy-3,6-diisobutyl-5-methoxypyrazine 1-oxide (14), respectively.
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■ A Facile Synthesis of 1-Aryl-2-arylthio-1H-imidazoles
Ricardo Bossio, Stefano Marcaccini,* Roberto Pepino, Cecilia Polo, and Tomás Torroba
*CNR, Centro di Studio Sulla Chimica e la Struttura dei Composti Eterociclici e lolo Applicazioni, c/o Dipartimento di Chimica Organica "Ugo Schiff", Università di Firenze, Via Gino Capponi 9, I-50121 Firenze, Italy
Abstract
The reaction between the hitherto unknown 2,2-diethoxy-1-isocyanoethane (1) with sulfenyl chlorides (2) and arylamines afforded isothioureas (4) which were cyclized to give the title compounds.
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■ Polycondensed Heterocycles. V. Synthesis of 5H,11H-Pyrrolo[2,1-c][1,4]benzothiazepine
Antonio Garofalo, Vito Nacci,* Federico Corelli, and Giuseppe Campiani
*Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Banchi di Sotto 55, 53100 Siena, Italy
Abstract
The 5H,11H-pyrrolo[2,1-c][1,4]benzothiazepine ring system has been prepared by two synthetic pathways, involving the intramolecular nucleophilic displacement on 1-(2-fluoreobenzyl)-2-mercaptomethylpyrrole or the Pummerer rearrangement of 1-(2-ethoxycarbonylmethylsulfinylbenzyl)pyrrole followed by in situ cyclization, respectively.
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■ Reaction of β-Bromo-N-heteroaromatics with Phenylacetonitrile
Setsuya Ohba, Takao Sakamoto, and Hiroshi Yamanaka*
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
The reaction of 3-bromopyridine with phenylacetonitrile in the presence of NaH in THF gave a simple substitution product, α-phenyl-3-pyridineacetonitrile, whereas the reaction of 5-bromopyrimidine with phenylacetonitrile under similar conditions gave a ring-transformation product, 2-amino-5-bromo-3-phenylpyridine. 3-Bromoquinoline and 4-bromoisoquinoline underwent the former type reaction, while 3-bromo- and 3-chloroisoquinolines were converted into 2-amino-3-phenyl-1-naphthalenecarbonitrile according to the latter type reaction.
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■ Studies on Pyrazolo[3,4-d]pyrimidine Derivatives. XVIII. Facile Preparation of 1H-Pyrazolo[3,4-d]pyrimidin-4(5H)-ones
Akira Miyashita,* Chihoko Iijima, Takao Higashino, and Hideaki Matsuda
*Schol of Pharmaceutical Sciences, University of Shizuoka, 395 Yada, Shizuoka 422, Japan
Abstract
Reaction of 5-amino-1-phenyl-1H-pyrazole-4-carboxamide (4) with the esters (3a-h) in the presence of sodium ethoxide in ethanol gave 1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (1a) and its 6-substitued derivatives (1b-h). Simlar treatment of 5-amino-1-methyl-1H-pyrazole-4-carboxamide (5) with 3a-h gave the 1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones (2a-h).
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■ Seven Prenylphenols, Antiarones C, D, E, F, G, H, and I from the Root Bark of Antiaris toxicaria Lesch.
Yoshio Hano, Pedro Mitsui, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Three new prenylchalcones, antiarones C, D, and E along with four new prenylflavonones, antiarones F, G, H, and I were isolated from the root bark of Antiaris toxicaria Lesch. On the basis of spectral evidence, the structures of antiarones C - I were shown to be 2 - 8, respectively. A known compound, (±)-sigmoidin A (1) was also isolated.
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■ Deoxygenative 2-Alkoxylation of Quinoline 1-Oxide
Mitsuo Hayashida, Haruyoshi Honda, and Masatomo Hamana*
*Faculty of Pharmaceutical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812, Japan
Abstract
Treatment of quinoline 1-oxide (1) with ethyl chloroformate or tosyl chloride and triethylamine in some lower alcohols affords the corresponding 2-alkoxyquinolines (2a-f) in generally satisfactory yields. Reactions of 2-methylpyridine and 2-methylquinoline 1-oxides lead to the corresponding 2-ethoxycarbonyloxymethyl (3 and 5) and 2-ethoxymethyl derivatives (4 and 6).
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■ Isolation, Structure Elucidation, and Synthesis of the Major Anaerobic Bacterial Metabolite of the Dietary Carcinogen 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)
Mohammad Bashir, David G. I. Kingston,* Robert J. Carman, Roger L. Van Tassell,and Tracy D. Wilkins*
*Department of Chemisry, Virginia Polytecnic Institute and State University, Blacksburg, Virginia 24061-0212, U.S.A.
Abstract
Incubation of the heterocyclic cooked food mutagen 2-amino-3,8-dimethyl-3H-imidazo[4,5-f]quinoxaline (MeIQx, 1) with mixed human fecal microflora under anaerobic conditions yielded 2-amino-3,6-dihydro-3,8-dimethylimidazo[4,5-f]quinoxalin-7-one (7-HOMeIQx, 2), as the major metablite, but with low overall conversion. The metabolite 2 and its isomer 7 have been synthesized. The metabolite 2 is a direct-acting mutagen, but its isomer 7 is non-mutagenic in the absence of metabolic activation.
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■ Cudraflavones C and D, Two New Prenylflavones from the Root Bark of Cudrania ricuspidata (Carr.) Bur.
Yoshio Hano, Yutaka Matsumoto, Kazuko Shinohara, Jin-Yun Sun, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Two new prenylflavones, cudraflavones C (1) and D (2), along with six known compounds were isolated from the root bark of Cudrania tricuspidata (Carr.) Bur. (Moraceae), collected in China. The structures of cudraflavones C and D were shown to be 1 and 2, respectively, on the basis of spectroscopic data.
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■ Components of the Root Bark of Morus insignis Bur. 1. Structures of Four New Isoprenylated Xathones, Morusignins A, B, C, and D
Yoshio Hano,Tsuyoshi Okamoto, Taro Nomura,* and Yasunori Momose
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Four new isoprenylated xanthones, morusignins A (1), B (2), C (3), and D (4) were isolated from the root bark of Morus insignis Bur. (Moraceae), colleced in paraguay, along with three known isoprenylated xanthones, gartanin (5), garcinone B (6), and toxyloxanthone B (7). The Structures of morusignins A - D were shown to be 1 - 4, respectively on the bais of spectroscopic data.
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■ Short Synthesis of (±)-Corynantheidol and (±)-3-Epicorynantheidol
Mauri Lounasmaa* and Reija Jokela
*Laboratory for Organic and Bioorganic Chemistry, Technical University of Helsinki, P.O. Box 6100, FIN-02150 HUT, Espoo 15, Finland
Abstract
A short synthesis for (±)-corynantheidol and (±)-3-epicorynantheidol is described.
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■ Synthesis of 4-Methyl-2-benzazepin-3-one Analogs of Diltiazem
John T. Hunt,* Mary F. Malley, and Jack Z. Gougoutas
*The Squibb Institute for Medical Research, P. O. Box 4000, Princeton, N.J. 08540-4000, U.S.A.
Abstract
An efficient method for the preparation of an alternative benzazepinone ring fusion, the cis and trans isomers of 4-methyl-5-(4-methoxyphenyl)-1,2,4,5-tetrahydro-3H-2-benzazepin-3-one (3), is described. The key reaction involved the ZnCl2-catalyzed alkylation of 3-(4-methoxyphenyl)phthalide (4) with the trimethylsilylketene acetal of ethyl propionate to form 5 as a mixture of diastereomers. Selective reductionof the carboxylic acid, conversion of the primary alcohol to the primary amine and cyclization produced the isomers of 3, which were separated by crystallization. The solid state conformation of the cis isomer (10) and a related 1-benzazepin-2-one were compared.
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■ Withangulatin A, a New Withanolide from Physalis angulata
Chiu-Ming Chen,* Zong-Tsi Chen, Chiu-Hsiang Hsieh, Wen-Sen Li, and Say-Yee Wen
*Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, Taiwan, R.O.C.
Abstract
A new withanolide as a topoisomerase II inhibitor, withangulatin A was isolated from the whole herb of Physalis angulata L. (Solanaceae). The structure of withangulatin A was established as (20S,22R)-15α-acetoxy-5β,6β-epoxy-4β,14α-dihydroxy-1-oxowitha-2,16,24-trienolide (I) on the basis of spectroscopic and chemical evidence.