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. 24, No. 5, 1986
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■ 1,2,5-Thiadiazole-1-oxides. V. Ring Transformations to Pyrazine, 1,2,4-Thiadiazole and Pyrrole
Sandor Karady,* Joseph S. Amato, Robert A. Reamer, and Lonard M. Weinstock
*Division of Merck & Co., Inc., Merck Research Laboratories, P.O.Box 2000, Rahway, NJ 07065, U.S.A.
Abstract
Rearrangement of 2-alkyl-1,2,5-thiadiazole-3-on-1-oxides to pyrazine, 1,2,4-thiadiazole and pyrrole derivatives is described. Ring opening to a sufinylamine and cyclization by cycloaddition or nucleophilic addition is the postulated mechanism.
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■ Asimicin, a New Cytotoxic and Pesticidal Acetogenin from the Pawpaw, Asimina triloba (Annonaceae)
J. Kent Rupprecht, Ching-jer Chang, John M. Cassady, Jerry L. McLaughlin,* Kenneth L. Mikolkajczak, and David Weisleder
*Department of Medicinal Chemistry and Molecular Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, 1333 Robert E. Heine Pharmacy Building, West Lafayette IN 47907, U.S.A.
Abstract
Asimicin, a new trihydroxy-bistetrahydrofuran fatty acid γ-lactone has been isolated, using brine shrimp lethality for activity-directed fractionation, from extracts of the bark and the seeds of the pawpaw tree, Asimina triloba Dunal. (Annonaceae). This compound is extremely cytotoxic and shows promising pesticidal activities.
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■ Synthesis of Cryptands under High Pressure. The Role of Solvent and Leaving Group in Double Quaternization Reactions
Marek Pietraszkiewicz, Piotr Salanski, Ryszard Ostaszewski, and Janusz Jurczak*
*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland
Abstract
The rate of double quaternization reaction of N,N’-dimethyldiazacoronand (1) with bis(2-iodoethyl) ether (2a) under high pressure strongly depends on solvent polarity. The nature of the leaving group in bis(2-halogenoethyl) ethers (2a-c) or in bis(2-tosyloxyethyl) ether (2d) influences the rate of double quaternization reaction.
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■ High-pressure Synthesis of 5,6-Dihydro-2H-pyran System. Eu(fod)3 Mediated (4+2)Cycloaddition of 1-Methoxybuta-1,3-diene to N-Protected α-Amino Aldehydes
Adam Golebiowski, Jan Izdebski, Ulla Jacobsson, and Janusz Jurczak*
*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland
Abstract
High-pressure [4+2]cycloaddition of 1-methoxybuta-1,3-diene (1) to N-protected α-amino aldehydes (2) is described. The use of a lanthanide catalyst permits reduction of the required pressure to 10 kbar.
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■ Reaction of the 2-Nitroenamine in Acid
Adam Krówczynski and Lech Kozerski*
*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland
Abstract
2-Nitroenamines bearing heteroaryl substituents on enamine nitrogen rearrange in acids to amidooxime of the pyruvic acid or give the products of the intramolecular cyclization, di- and triaza-indenes, whereas N-aryl substituted substrates yield quinoxaline oxides. Nitronic acid of the 2-nitroenamine is suggested as a primary reactive species in acid solution. 13C and 15N NMR data are discussed which provide the evidence for this intermediate.
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■ Structure Determination of the Ochrosia Alkaloid Ochropposinine: Syntheses of (±)- and (-)-Ochropposinine
Tozo Fujii,* Masashi Ohba, Yakeshi Tachinami, Hisae Miyajima, Michel Koch, and Elisabeth Seguin
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
The tetracyclic alcohols (±)-I and (-)-I have been synthesized from the lactim ethers (±)-III and (+)-III via the intermediates (±)-VII and (+)-VII, (±)-IX and (+)-IX, (±)-X and (+)-X, XI, and (±)-XlI and (-)-XII. The identity of the synthetic (-)-I with natural ochropposinine unequivocally established the structure and absolute stereochemistry of this Ochrosia alkaloid.
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■ Nitriles in Heterocyclic Synthesis: Novel Synthesis of Pyridazine Derivatives
Nadia S. Ibrahim,* Fathy M. Abdel Galil, Ramadan M. Abdel-Motaleb, and Mohamed H. Elnagdi
*Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
Abstract
The crotononitriles 1a-c coupled with aryldiazonium salts to yield either the acyclic hydrazones or azahydrazones depending on coupling reaction conditions. Both hydrazones and azodrazones could be cyclized to the corresponding pyridazine derivatives. Direct formation of pyridazines on coupling 1b and 1c with aryldiazonium salts was observed. Structures of reaction products are confirmed by spectral and analytical data.
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■ A Novel Reductive Amino Cyclization Method and Its Application for the Syntheses of Pyrrolidine and Piperidine Nucleus
Fumio Yamada, Toshifumi Hasegawa, Masayuki Wakita, Mitsuru Sugiyama, and Masanori Somei*
*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
A novel synthetic method for pyrrolidine and piperidine derivatives is developed. Its versatility is proved by the syntheses of 6a,9a-cis-6,6a,7,8,9,9a-hexahydro-2H-isoindolo[4,5,6-cd]indole and cactus alkaloid, (±)-lophocerine.
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■ (+)-Roemearine, a C-4 Hydroxylated Tetrahydrobenzylisoquinoline Alkaloid
Tekant Gözler,* Belkis Gözler, Nevin Tanker, Alan J. Freyer, Hélène Guinaudeau, and Maurice Shamma
*Department of Chemistry, The Pennsylvania State University, York Campus, P1031 Edgecomb Avenue, York, Pennsylvania 17403, U.S.A.
Abstract
Roemeria carica A. Baytop (Papaveraceae) of Turkish origin has supplied (+)-roemecarine (1), which is the first C-4 hydroxylated tetrahydrobenzylisoquinoline alkaloid. Species 1 is accompanied in the plant extract by its N-oxide, (+)-roemecarine 2-α-N-oxide (4).
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■ Reduction of N-Alkoxycarbonyllactams with NaBH4/EtOh-H+: A Facile Synthesis of α-Ethoxyurethanes
Tatsuo Nagasaka,* Hirohisa Tamano, and Fumiko Hamaguchi
*School of Pharmacy, Tokyo University of Pharmacy and Life Science,1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Reduction of N-alkoxycarbonyllactams with NaBH4/H+ in ethanol (Speckamp’s condition) afforded α-ethoxyurethanes (Shono’s compounds) in good yields.
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■ Preparation of Naphthalene Derivatives by Reaction of Benzynes with Thiophene-1,1-dioxides
Juzo Nakayama,* Masami Kuroda, and Masamatsu Hoshino
*Department of Chemistry, Faculty of Science, Saitama University, Saitama, Saitama 338-8570, Japan
Abstract
The reaction of benzynes with thiophene 1,1-dioxides affords the Diels-Alder cycloadducts which spontaneously lose sulfur dioxide to give the corresponding naphthalene derivatives in moderate yields. Further reaction of benzyne with naphthalenes yielding dibenzobarrelenes is observed in a few cases.
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■ 1,3-Anionic Cycloaddition of 1,3-Diphenyl-2-azaallyl Lithium to Thioketenes and Thioketene S-Oxides
Ernst Schaumann,* Helmut Behr, and Gunadi Adiwidjaja
*Institut für Organische Chemie, Universität Hamburg, Martin-Luther-King-Platz 6, D-20416 Hamburg, Germany
Abstract
Cycloaddition of 1,3-diphenyl-2-azaallyl lithium (4) to the thioketenes 5a,b leads to thiazolidines 7a,b. Evidence for an open-chain anionic intermediate 8 is obtained by trapping with methyl iodide and through the stereochemistry of 7a as revealed in an X-ray crystallographic study. With thioketene S-oxides 10a,b, 4 yields thiazoles 15 via a ‘second-generation’ Pummerer reaction.
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■ Studies on as-Triazine Derivatives. VII. Resemblance between as-Triazines and Quinazolines in Nucleophilic Addition-elimination Reactions
Shoetsu Konno, Setsuya Ohba, Mataichi Sagi, and Hiroshi Yamanaka*
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Alike 4-chloroquinazoline, 5-chloro-1,2,4-triazines (as-triazines) reacted with aromatic aldehydes in the presence of 1,3-dimethylbenzimidazolium iodide under basic conditions to give 5-aroyl-as-triazines. The Grignard reaction of 5-cyano-as-triazine with arylmagnesium bromides failed to give any significant product. Some analogy of as-triazines with quinazolines, in their chemical properties, was additionally investigated.
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■ Metallo-ketene-S,N-acetals. New Synthesis of Azacycloalka[3,2-c]pyridin-2-ones
Hiroki Takahata, Toshiaki Suzuki, and Takao Yamazaki*
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
S-Lithio-ketene-S,N-actals (3 and 4), generated from N-methylthiolactams (1 and 2) with n-buthyllithium (n-BuLi), react with aryl isocyanates (5) to give 3-(N-arylcarbamoyl)thiolactams (6 and 7), which are transformed into azacycloalka[3,2-c]pyridine-2-ones (12 and 13), respectively, using sulfide extrusion of thioiminium salts (8 and 9) with malononitrile followed by cyclization.
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■ Structure of Mulberrofuran M, a Novel 2-Arylbenzofuran Derivative from the Cultivated Mulberry Tree (Morus alba L).
Yoshio Hano, Kazuhiro Hirakura, Takehisa Someya, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
A novel 2-arylbenzofuran derivative named mulberrofuran M (1) was isolated from an acetone extract of the reddish violet powder obtained from the surface of the root bark of cultivated mulberry tree (Ichinose, a cultivated variety of Morus alba L.). The structure was shown to be 1 on the basis of spectral evidence.
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■ Structure and Syntheses of SEN-125 and Oxotomaymycin
Miwako Mori,* Yasuhiro Uozumi, and Yoshio Ban
*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan
Abstract
The structure of SEN-215 was determined as (11aS)(E)-2-ethylidene-2,3,5,10,11,11a-hexahydro-8-hydroxy-7-methoxy-5-oxo-1H-pyrrolo[2,1-c][1,4]benzodiazepine by conversion of (E)- and (Z)-pretomaymycin into (E)- and (Z)-SEN-215.
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■ A Novel Skeletal Rearrangement of an Indolizidine Alkaloid, Swainsonine via an Aziridinium Intermediate
Hiroyuki Setoi, Hidekazu Takeno, and Masashi Hashimoto*
*Fujisawa Pharmaceutical Co. Ltd., 5-2-3 Tokodai, Tsukuba, Ibaragi 300-2635, Japan
Abstract
Nucleophilic displacement reactions of mesylate 3, derived from swainsonine (1), gave the rearranged products 5 along with the swainsonine-type products 6 via an aziridinium intermediate 4.
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■ Lincomycin Analogues. II. Chain-extension of Methyl-6-aldehydo-3,4-O-isopropylidene-1-thio-β-D-galcto-1,5-pyranoside
Jean M. J. Tronchet and Mohamed A. M. Massoud*
*Pharmaceutical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
Abstract
Synthesis of methyl 2,3,4,6-tetra-O-acetyl-1-thio-α-D-galactopyranoside and its β-anomer (3 and 4) from the 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl brormide via the isothiauronium salt in HMPT involved a considerable increase in the proportion of the α-anomer. Deacetylation of (3 and 4) with sodium methoxide yielded 5 and 6 respectively. Conversion of (6) into the corresponding 3,4-isopropylidene derivative (7) followed by oxidation with Collin reagent gave the aldehydo-sugar (8) which when reacted with a stabilised phosphorane led in excellent yield to the Z-unsaturated bromo-sugar (9).
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■ Sensitized Photooxidation of 2,5-Furanyldimethyl Dibenzoate
Yueh-Hsiung Kuo* and Chir-Jeng Shieh
*Department of Chemistry, National Taiwan University, Roosevelt Road Section 4, Taipei 106, Taiwan, R.O.C.
Abstract
Sensitized photooxidation of 2,5-furanyldimethyl dibenzoate was carried out in acetonitrile and methanol respectively. Two products, 3 and 6, were obtained via O,O-diradical intermediate 15 which was discovered from ozonide for the first time.
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■ The Structure of Heterophylloidine and Panicutine
S. William Pelletier,* Balawant S. Joshi, Haridutt K. Desai, Al Panu, and Alfred Katz
*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.
Abstract
Heterophylloidine (Aconitum heterophylloides Stapf) and panicutine (A. paniculatum Lam.) have been shown to be identical. CD measurements on derivatives of heterophylloidine and hetisine indicate that the keto groups in panicutine must be located at C(6), C(13) and not at C(6), C(11) as previously reported. The structure of panicutine is therefore 1, as proposed earlier for heterophylloidine.
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■ Nitrogen Assisted Acetal Ring Clevage. Part II. Preparation of Synthons for Eburnamine-vincamine Alkaloids
Mauri Lounasmaa* and Arto Tolvanen
*Laboratory of Organic Chemistry, Helsinki University of Technology, P.O. Box 6100,FIN-02015 HUT, Espoo, Finland
Abstract
The cleavage of cyclic 3-substituted tetrahydropyridine acetals under the modified Polonovski reaction conditions is described. The method was applied to the preparation of a 1-formylindolo[2,3-a]quinolizidine derivative.
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■ Synthesis of Novel Methyl (2-Oxo-3-morpholinylodene)acetates
George B. Mullen, Vassil St. Georgiev,* and Chiristopher G. Acker
*Department of Organic Chemistry, Pharmaceutical Division, Pennwalt Corporation, Rochester, New York 14623, U.S.A.
Abstract
The synthesis of a series of novel (2-oxo-3-morpholinylidene)acetic acid methyl esters is described.
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■ Synthesis of (2S,5S)-2,5-Bis(phenylmethyl)piperazine by the Reduction with Sodium Borohydride Using Titanium Tetrachloride
Kenso Soai,* Hiroshi Hayashi, and Hitoshi Hasegawa
*Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan
Abstract
Optically active piperazine 1 is synthesized in relatively high yield by the reduction of cyclo-L-Phe-L-Phe with sodium borohydride-titanium tetrachloride.
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■ Termolysis of Sodium Salt of Furfural Tosylhydrazone in the Presence of Silver Chromate: Formation of 2-Furyl(p-toluenesulfonyl)methane via 1,3-N→C Migration of Tosyl Group
Katsuhiro Saito* and Hiraku Ishihara
*Faculty of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Abstract
The thermal decomposition of sodium salt of furfural tosylhydrazone in diglyme in the presence of silver chromate afforded trans-1,2-di(2-furyl)ethylene and 2-furyl(p-toluenesulfonyl)methane. The former product is formed via (2-furyl)methylene, while the latter product is considered to be derived via 1,3 N→C migration of tosyl group in furfural tosylhydrazyl radical, which is generated by one electron oxidation of furfural tosylhydrazone by silver chromate.
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■ Horridine, a New Isoeuonyminol Skeleton Alkaloid
Antonio G. González,* Esteban A. Ferro, and Angel G. Ravelo
*Instituto Universitario de Química Orgánica, Universidad de La Laguna, Tenerife, Canary Islands, Spain
Abstract
The structure of a new alkaloid, horridine, isolated from the ethanol extract of the root bark of Maytenus horrida Reiss (Celastraceae) was established from spectral and degradation data.
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■ A Carbon-13 and Proton Nuclear Magnetic Resonance Study of Hydroxy- and Mercapto-nitropyridines and Their N-, O-, and S-Methyl Derivatives and Analogous Compounds in Dimethyl Sulfoxide
Gordon B. Barlin* and M. David Fenn
*Department of Pharmacology, John Curtin School of Medical Research, Australian National University, GPOBox 334, Canberra, ACT 2601, Australia
Abstract
Carbon-13 and proton n.m.r. spectra of hydroxy- and mercapto-nitropyridines and their N-, O- and S-methyl derivatives and analogous compounds have been measured in (D6)dimethyl sulfoxide. Carbon-13 n.m.r. spectroscopy, in contrast to 1H n.m.r. spectroscopy, has bean shown to provide a clear distinction between O-methyl and nuclear N-methyl groups. Methoxy groups were found to occur in the range δ 52.80 to 57.18, nuclear N-methyl groups at 33.59-43.56, and methylthio groups at 12.00-14.65 for the compounds examined in (D6)dimethyl sulfoxide. 3-Nitropyridine-4-thiol† unlike its oxygen analogue, 3-nitropyridin-4-ol† appears to exist in the thiol form.
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■ A New Mechanism (SEi) for Electrophilic Substitution in Indoles. Chlorination of Indoles with Sodium Hypochlorite by Competitive SE2 and SEi Mechanisms
Michael De Rosa,* Angela Cuenca, and Maria Raquel Fernandez
*Departamento de Quimica, Universidad Simon Bolivar, Apartado 80659, Caracas 1080-A, Venezuela
Abstract
The chlorination of 5-substituted indoles (OCH 3, CH3, Br, CN, NO2) with NaOCl was studied. Mixtures of N-chloro- and N-chloro-3-chloro-indoles were formed. Indoles reacted with OCl- in a SEi process to give N-chloroindoles. This reaction was favored by substituents which increased the acidity of the indolic N-H. Indoles or their conjugate bases also reacted with HOCl in a SE2 reaction to give 3-chloroindoles which were then converted to their N-chloro derivatives with excess NaOCl.
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■ Isolation of a New Tetranortrietrpenoid from Azadirachta indica A, Juss (Meliaceae)
Salimuzzaman Siddiqui,* Shaheen Faizi, Tariq Mahmood, and Bina Shaheen Siddiqui
*H. E. J. Postgraduate Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
A new γ-hydroxybutenolide tetranortriterpenoid named as isonimbocinolide has been isolated from the acidic fraction of the fresh, undried leaves of Azadirachta indica A. Juss (neem) and its structure established through chemical and spectral studies. This fraction showed insect growth regulating properties against mosquitoes (Aedes aegypti).
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■ One-flask Synthesis of 4-[Bis(methylthio)]methylene-2-phenyl-5-oxo-4,5-dihydro-1,3-oxazole and Its Aminolyses
Ram Ashare, Jalpana Roy, and Arya K. Mukerjee*
*Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi - 221005, India
Abstract
Cyclisation of hippuric acid with ethyl chloroformate and triethylamine in benzene and subsequent triethylaminemediated condensation with carbon disulphide and S-methylation afford the title compound which undergoes 1,5-bond cleavage on heating with molar proportion of a primary amine in the presence of glacial acetic acid, the ketenethioacetal moiety remaining intact. On increasing the proportion of the amine and heating the mixture for a longer period, the corresponding N,N’-disubstituted benzoylaminomalondiamides are obtained.
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■ Synthesis of Optically Active 3-Mercaptopyrrolidine Derivatives. Synthetic Intermediates of Carbapenem RS-533 and Its Isomer
Tomoyuki Shibata, Kimio Iino, and Yukio Sugimura*
*Chemical Research Laboratories and Analytical & Metabolic Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Abstract
The optically active 3-mercaptopyrrolidine derivatives(3a, 3b, 4a and 4b), which are synthetic intermediates of the carbapenem RS-533 (2a) and its isomer (2b), were synthesized by convenient and practical methods.