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
Alan R. Katritzky's Special Issues, Vol. 37, No. 2, 1994
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■ The Three-Component Condensation of Monoterpenes with Formaldehyde and Cyclohexane-1,3-dione. A Simple Route to Polyketide Terpenes
Stefan Koser and H. M. R. Hoffmann*
*Institut fur Organische Chemie, Universität Hannover, Schneiderberg 1 B 3000 Hannover, Germany
Abstract
The framework of polyketide terpenes was obtained by the title tandem reaction which was carried out in one-pot under optimized conditions. Even tetrasubstituted olefins react, sterically hindered octahydronaphthalene (6) giving tetracyclic propellane (7).
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■ Reaction of Pyrylium Salts with Amino Acid Derivatives Part 3. Ribonuclease A Inactivation by Trisubstituted Pyrylium Salts
Claudiu T. Supuran, Emil Pop, and Antonie Dinculescu*
*Pharmos Corporation, 2 Innovation Drive, Alachua, FL32615, U.S.A.
Abstract
Treatment of ribonuclease A with 2,4,6-trisubstituted pyrylium salts completely inhibits the activity of this enzyme. The inactivation is probably due to the reaction of the ε-amino group of the active site Lys 41 residue with the pyrylium cation, leading to pyridinium derivatives which hinder the access of substrates to the active site of the enzyme
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■ Preparation of a Deoxynojirimycin Analog Containing an Imidazole Ring
Kevin Burgess,* David A. Chaplin, Alan D. Elbein, and Yucheng Zeng
*Department of Chemistry, Texas A & M University, College Station, Texas 77843-3255, U.S.A
Abstract
The deoxynojirimycin analogs (4) and (5) were prepared via addition of a metallated imidazole to an aldehyde; these compounds were screened for inhibition of glycosidase enzymes and anti-HIV activities.
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■ Total Synthesis of (±)-cis-, trans-Cembranolides (±)-Sarcophytonin B from Geranylgeraniol
Kiyoshi Nishitani, Toshihiko Konomi, Kiyonobu Okada, and Koji Yamakawa*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
Abstract
(±)-cis-Cembranolide (I) was synthesized via Cr(II) mediated intramolecular macrocyclization of ω-formyl-β-methoxycarbonylallyl halides (6a and b), which were prepared starting from geranylgeraniol. The stereoselective synthesis of (±)-trans-cembranolide (II) was achieved by lactonization of 14-membered cis-intermediate (7) with inversion of the stereochemistry at C-2. (±)-Sarcophytonin B (III) was also synthesized from (±)-cis-cembranolide (I) via isomerization of the exo-cyclic double bond.
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■ Pyrrole Ring Opening in 5-Nitroso- and 5-Phenylazo-1H-pyrrolotetrazoles — An Unexpected Valence Isomerism
Dietrich Moderhack* and Dirk Decker
*Institut für Phaemazeutische Chemie, Technische Universität, D-38106 Brauschweig, Germany
Abstract
1,6-Disubstituted 5-nitroso-1H-pyrrolotetrazoles ring open below 20°C to give the isomeric acrylonitrile oxides. The 5-phenylazo analogs as well as 5-nitroso derivatives havingin addition an acceptor group at C-7 are stable at 20°C, but heating with the dipolarophile DMAD leads to pyrazoles and isoxazoles.
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■ Reactions of Some 1-(4,5-Dihydroimidazol-2-yl)azoles with Aroyl and Ethoxycarbonyl Isothiocyanates
Franciszek Saczewski*
*Department of Organic Chemistry, Medical Academy, 80-416 Gdansk, Poland
Abstract
Three components cyclocondensations of the imidazole derivative (1c) with aroyl isothiocyanates afforded 6,7,8,8a-tetrahydro-3-aroylimidazo[1,2-a][1,3,5]triazine-2,4(3H,8H)dithiones (5a-e), while similar reaction with ethoxycarbonyl isothiocyanate led to the formation of ethyl 5-thioxo-2,3,8,9-tetrahydro-5H-diimidazo[1,2-a:1’,2;-c]-[1,3,5]triazine-6-carboxylate (10).
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■ Synthesis and Characterization of Thieno[3,4-c][1,2,5]thiadiazoles
Shoji Tanaka, Masaaki Tomura, and Yoshiro Yamashita*
*Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan
Abstract
Thieno[3,4-c][1,2,5]thiadiazoles (1a-b) were synthesized and characterized based on the spectral and structural data. The most notable smctural feature of this “nonclassical” condensed thiophene is the small HOMO-LUMO separation leading to the highly amphoteric redox properties compared with the related “classical” thiophenes. The X-ray structure analysis suggested that this heterocycle has the character of a thiocarbonyl ylide. Short intermolecular S---N contacts were found in the crystal.
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■ Electrocyclic Ring Closure of 1-Azatrienes as a Route to the Indolo[3,2,1-ij][1,6]naphthyridine Ring System
Andrew L. Germain, Thomas L. Gilchrist,* and Paul D. Kemmitt
*Department of Chemistry, University of Liverpool, Liverpool, L69 3BX, U.K.
Abstract
t- Methods of annelation of indole across the 1- and 2-positions have been explored using both the intramolecular Heck reaction and Dieckmann cyclisation. Two examples 5 and 7 of the title ring system have been produced by the thermal cyclisation of indole-3-carboxaldehyde oximes with an akenyl substituent at C-2.
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■ Lithiation Routes to Oxindoles and 2-indolinethiones: Precursors to 2,2'-Dithiobisindoles with Tyrosine Kinase Inhibitory Properties
Gordon W. Rewcastle* and William A. Denny
*Cancer Reserach Laboratory, Univerity of Auckland, School of Medicine, Private Bag 92019, Auckland, New Zealand
Abstract
N-Substituted oxindoles and 2-indolinethiones can be prepared by lithiation of carboxyl protected N,2-dimethylanilines followed by quenching with CO2 or CS2 respectively. 2-Indolinethione derivatives are also available via demethylation of 2-methylthioindoles, which are prepared by lithiation of N-substituted indoles and treatment with dimethyl disulfide.
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■ The Reaction of Diazines with Allyltributyltin via N-Alkoxycarbonyldiazinium Salts
Takashi Itoh, Hiroshi Hasegawa, Kazuhiro Nagata, Yuji Matsuya, and Akio Ohsawa*
*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Abstract
Pyridazines were allowed to react with allyltributyltin in the presence of chloroformate to give 1-alkoxycarbonyl-6-allyl- and 1-alkoxycarbonyl-4-allyldihydro-pyridazines as major and minor products, respectively. The reaction was applied to other diazines, and tetrahydro-adducts were obtained in the case of pyrimidine and pyrazine. Benzo-fused diazines also reacted in the same manner to afford the allyl-adducts in good yields.
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■ Diastereoselective [2+3] Cycloadditions of Nitrones to 2-Oxazolone Heterocycles
Tadao Ishizuka, Hirofumi Matsunaga, Junji Iwashita, Takenori Arai, and Takehisa Kunieda*
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
Highly diastereoselective [2+3]cycloadditions of N-benzyl- and N-tert-butyl-α-phenylnitrones to 3-(2-substituted 7,7-dimethylbicyclo[2.2.1]heptane-1-carbonyl)-2-oxazolones are described.
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■ Synthesis of (±)-Clavicipitic Acid and Its Derivatives
Masanori Somei,* Shoichi Hamamoto, Kyoko Nakagawa, Fumio Yamada, and Toshiharu Ohta
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
A formal total synthesis of (±)-clavicipitic acid was achieved in five steps from indole-3-carboxaldehyde. Syntheses of (±)-4-cyano-, (±)-4-methyl-, and (±)-4-hydroxymethyl-6-(2-methyl-1-propen-1-yl)-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indoles are also reported.
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■ Synthesis of Thiapyrano[4,3-b]indoles by the Hetero Diels-Alder Reaction Using 3-Thioacetylindoles as a Diene
Masayuki Murase, Noriaki Nishino, Norichika Nara, Yoshimi Nakanishi, and Seisho Tobinaga*
*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Abstract
A new synthesis of thiapyrano[4,3-b]indoles by the hetero Diels-Alder reactions of 3-thioacetylindoles (1) with dienophiles is described.
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■ Kinetic Study of the Reduction of Methemoglobin with Ascorbate Using a COBAS-FARA Centrifugal Analyzer
Kilian Dill* and Evelyn L. McGown
*Molecular Device Corporation, 4700 Bohannon Drive, Menlo Park, CA, 94025, U. S. A.
Abstract
The reduction-kinetics of methemoglobin with ascorbic acid were monitored using a COBAS-FARA centrifugal analyzer. The data from the initial rates for the reduction of hemoglobin were monitored as a function of the ascorbate concentration. The results show a first order dependence of the reaction rates on the ascorbate concentration and the rate constant was found to be 1.34 x 10-2 s-1 M-1. Ascorbic acid is a one electron donor in this process and consequently forms a stable radical. The presence of oxyhemoglobin interferes with the reduction of methemoglobin by ascorbate.
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■ Alkylation of 4(5)-Substituted Imidazoles
Paul Benjes and Ross Grimmett*
*Chemistry Department, University of Otago, P. O. box 56, Dunedin, New Zealand
Abstract
4(5)-Substituted imidazoles were alkylated under “neutral” and alkaline conditions to give mixtures of isomers in ratios which depended on the reaction conditions, and the nature of the substituent and alkylating agents.
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■ The First Total Synthesis of γ-Schizandrin and Gomisin N Having Natural Configurations
Masahide Tanaka, Toshihiro Ohshima, Hiroshi Mitsuhashi, Masao Maruno, and Takeshi Wakamatsu*
*Central Research Laboratory, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-11, Japan
Abstract
The total syntheses of γ-schizandrin and gomisin N were achieved in a stereoselective manner. The success of these synthesis heavily depends on the stereoselective reduction of tetracyclic lactones with magnesium in methanol.
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■ Direct Regioselective Formation of Polysubstituted Tetrahydrofurans from Unprotected Polyols
Hiromichi Fujioka, Hidetoshi Kitagawa, Michinori Kondo, and Yasuyuki Kita*
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
The reaction of unprotected polyols (tetraols, pentitol and hexitol) with trimethyl orthobenzoate in CH2Cl2-MeOH afforded polysubstituted tetrahydrofurans in a one-pot synthesis.
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■ A Straightforward Synthesis of (±)-4-Amino-4-deoxyerythrose via Its Bisulfite Anomer
Jean-Bernard Behr, Albert Defoin, and Jacques Streith*
*Ecole Nationale Supérieure de Chimie de Mulhouse, Université de Haute Alsace, 3, Rue Alfred Werner 68093 Mulhouse Cedez, France
Abstract
Hetero-Diels-Alder reaction of N-butadienyl-2-pyrrolidone (1a) with acylnitroso dienophile (3) led with very high regioselectivity to the racemic cycloadduct (6). A sequence of stereospecific reactions, as well as some protection/deprotection steps, gave the bisulfite derivative (2b) of (±)-4-amino-4-deoxyerythrose (2a) as a single and crystalline anomer. Asymmetric induction as applied to the Diels-Alder cycloaddition step with various N-butadienylpyroglutamate esters (1b-e) permitted to work out optimal experimental conditions, the best d.e. value being 76%.
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■ Chiral Nucleofugals: Synthesis and Structure of Functionalised Acetals Derived from D-(+)-Glucose
Pierre Duhamel,* Gerard Plé, and Jean-Yves Valnot
*Université de Rouen, Faculté des Sciences, URA CNRS DO 464et IRCOF, F-76821 Mont saint Aignan, France
Abstract
D-(+)-Glucose derived iodoacetals (1) (Y= I) of known absolute configuration have been synthesized and their behaviour towards nucleophilic substitution was studied as a model for the synthesis of precursors of chiral nucleofugals with a pendant ligand.
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■ Synthesis of 2H-1-Benzopyrans from Aryllithium and α,β-Unsaturated Aldehydes
Raymundo Cruz-Almanza,* Francisco Pérez-Flores, and Cristina Lemini
*Instituto de Química, Universidad Nacional Autónama de México, Circuito Exterior, Ciudad Universitaria, Coyoacán 04510 Mexico, D.F., Mexico
Abstract
The synthesis of 2,2-dialkyl-2H-1-benzopyrans (23), (25), (27), (30), (31) and (29) was performed employing the 1,2-addition reaction of aryllithium salts to cyclocitral, 3-methyl-2-butenal, citral and farnesal respectively. Subsequent deprotection with a Mexican bentonitic earth (Tonsil) in wet acetone was followed by ring closure reaction as the key step. Interesting intermediate products were isolated in the formation of benzopyrans (30) and (31).
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■ An Activated Trifluoromethyl Group as a Synthon for 2-Substituted Benzothiazole and Benzoxazole
Alexander S. Kiselyov, Maryam Hojjat, Koen Van Aken and Lucjan Strekowski*
*Department of Chemistry, Georgia State University, Atlanta, GA 30303, U.S.A.
Abstract
Dianions derived from 2-mercaptoaniline and 2-hydroxyaniline are cyclized to 2-substituted benzothiazole and benzoxazole, respectively, in the reaction with ortho or para trifluommethyl-substituted anilines and quinolinamines that involves the CF3 group. The carbon atom of the CF3 group becomes C-2 of the five-membered ring system. Synthesis of 3-trifluoromethylquinoline-4-amine and 5-trifluoromethylquinoline-6-amine is also reported.
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■ Synthesis of Desmethyl Tiagabine
Mukund S. Chorghade,* Peter Ellegaard, Elaine C. Lee, Hans Petersen, and Per Olaf Sørensen
*Department 54P, Abbott Laboratories, Abbott Park, N. Chicago, IL60064, U.S.A.
Abstract
The title compound has been investigated as one in a series of novel and selective GABA uptake inhibitors that exhibit potent anti-convulsant effects. Versatile syntheses have been developed for the preparation of this compound in excellent yields. Key steps are a Grignard reaction followed by ring opening with simultaneous dehydration and bromination of a hydroxymethyl cyclopropane with bromotrimethylsilane; displacement of bromine with ethyl R-(-)-piperidine-3-carboxylate and an acid or base catalyzed hydrolysis of the ester moiety.
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■ Preparation of New Thiohydroxamic Acid Derivatives: Synthesis of Substituted 1-Hydroxy-1,2-dihydoroimidazole-2-thiones
Derek H. R. Barton, Ching-Yu Chern, and Catherine Tachdjan*
*Department of Chemistry, Texas A & M University, College Station, Texas 77843-3255, U.S.A
Abstract
A general method for the synthesis of the title compounds is reported. The N-phenacylarylamines (11), prepared from the corresponding phenacyl bromides (9) and arylamines (10), give the thiono (or dithio) carbamates (12) on treatment with phenoxythionocarbonyl or thiophenoxythionocarbonyl chlorides and potassium carbonate in dichloromethane. The desired thiohydroxamic acids (13) are obtained by heating compounds (12) with hydroxylamine hydrochloride in pyridine/ethanol.
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■ A Synthetic Bilirubin in a Porphyrin-like Conformation
Ki-Oh Hwang and David A. Lightner*
*Department of Chemistry, University of Nevada, Reno, Nevada 89557-0020, USA
Abstract
An analog of bilirubin is held in a porphyrin-like shape by an N21,N24-methanobridge. In this conformation, the two propionic acid groups cannot participate in intramolecular hydrogen bonding, and the pigment is thus much more polar and hydrophilic than bilirubin. The uv-visible spectra (εmax 20,400, λmax 381 nm in benzene and εmax 23,800, λmax 385 nm) are nearly invariant over the solvent polarity range. Circular dichroism of the pigment complex with human serum albumin gives a weak bisignate Cotton effect: δεmax422 = -4.7, δεmax366 = +3.7 in pH 7.4 buffer.
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■ An Unusual Aromatization of Hantzsch-Type 4-Antipyryl-1,4-dihydropyridines
Jean-Jacques Vanden Eynde,* Annie Mayence, André Maquestiau, and Ernst Anders
*Organic Chemistry Laboratory, University of Mons-Hainaut, Place du Parc 20, B-7000 Mons, Belgium
Abstract
Under acidic conditions, Hantzsch-type 4-antipyryl-1,4-dihydropyridines undergo an elimination of the 4-substituent to yield 4-unsubstituted pyridines and antipyrine. The mechanism and the scope of the reaction are discussed.
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■ Ring Opening of 4-Chloroquinazoline into 2-Arylmethyleneaminobenzonitrile by Grignard Reaction
Akira Miyashita,* Takami Sasaki, Etsuo Oishi, and Takeo Higashino
*School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
The treatment of 4-chloroquinazoline (1) with arylmagnesium bromide (3) in tetrahydrofuran (THF) resulted in the formation of 2-arylmethyleneaminobenzonitrile (2). Continued reaction of ring opening of 1 and subsequent hydrolysis of the products (2) afforded the corresponding arenecarbaldehydes (4).
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■ Two New Xanthones in the Underground Part of Calophyllum inophyllum
Munekazu Iinuma,* Hideki Tosa, Toshiyuki Tanaka, and Shigetomo Yonemori
*Department of Pharmacognosy, Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
From the root bark of Calophyllum inophyllum L. (Guttiferae), a new xanthone named caloxanthone C (1) and 4-hydroxyxanthone (2), and from the heartwood of root, a new xanthone 1-hydroxy-2-methoxyxanthone (3) in addition to three known xanthones [1,2-dimethoxy- (4), 2-hydroxy-1-methoxy- (5)], and 6-deoxyjacareubin (6) were isolated. The structures were characterized by means of a spectroscopic analysis.
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■ A Synthesis of (±)-Pinoresinol and Its Related Compound Using Potassium Persulfate (K2S2O8) Oxidation of Benzoylacetates
Jun Maruyama, Miho Kobayashi, Masaaki Miyashita, Isao Kouno, and Hiroshi Irie*
*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
A synthesis of (±)-pinoresinol has been accomplished by application of the oxidative coupling reaction of benzoylacetate with potassium persulfate as a key step.
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■ A Synthesis of 2-Oxo-2H-pyrano-[2,3-f]quinoline Derivatives
Simona Fajgelj, Ljubo Golic, Branko Stanovnik,* and Miha Tisler
*Department of Chemistry, University of Ljubljana, Murnikova 6, P. O. Box537 61000 Ljubljana, Slovenia
Abstract
A synthesis of some derivatives of 2-oxo-2H-pyrano[2,3-f]quinoline from 5,8-quinolinequinone and dialkyl 2-aminofumarate is described.
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■ Chlorination of 5-[2-(N-Silylamino)vinyl]isothiazole and Related Derivatives with N-Chlorosuccinimide. Inhibition of Ring-Transformation (Bond Switch) by Steric Hindrance
Katsuo Ohkata, Yoshihiko Ohyama, and Kin-ya Akiba*
*Department of Chemistry, Faculty of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526, Japan
Abstract
The selective monochlorination of 5-[2-(N-silylamino)vinyl]isothiazoles (1a,b) and their related compounds (1c,d, 2a-g, 3a-c, and 4a,b) with N-chlorosuccinimide is described. Chlorination of 1a,b occurred at vinyl carbon to give 5a,b and the geometry was determined to be Z-isomer according to spectral data. It is noteworthy that 1d smoothly occurred bond switch at room temperature but 5d did not ring-transform under the same conditions.