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. 55, No. 11, 2001
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■ Javaberine A, New TNF-α and Nitric Oxide Production Inhibitor, from the Roots of Talinum paniculatum
Hiroshi Shimoda, Norihisa Nishida, Kiyofumi Ninomiya, Hisashi Matsuda, and Masayuki Yoshikawa*
*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan
Abstract
The methanolic (MeOH) extract from the roots of Talinum paniculatum was found to exhibit inhibitory activities on the lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and nitric oxide (NO) production from mouse peritoneal macrophages, and on the TNF-α production from rat epididymal adipose tissue. From the MeOH extract, two new 8-benzyltetrahydro-protoberberine–type alkaloids, named javaberines A and B, were isolated and their structures were elucidated on the basis of chemical and physicochemical evidence. The principal alkaloid, javaberine A, inhibited LPS-induced TNF-α and NO production from mouse peritoneal macrophages and TNF-α production from rat epididymal adipose tissue.
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■ Synthesis of 3,4-Dihydro-2H-benzopyrans from Phenols and α,β-Unsaturated Carbonyl Compounds
Hiroyuki Saimoto, Yoshie Ogo, Mie Komoto, Minoru Morimoto, and Yoshihiro Shigemasa*
*Tottori University, Faculty of Engineering, Department of Materials Science, 4-101 Koyama-minami, Tottori 680-8552, Japan
Abstract
The reaction between 2’,4’-dihydroxyacetophenone and methyl vinyl ketone catalyzed by CaCl2/KOH in aqueous methanol yielded a 1,4-adduct, which was cyclized to 3,4-dihydro-2H-benzopyran (4) by acidic treatment. Analogous reaction using α,β-unsaturated aldehydes afforded benzopyrans (4) or (5) in a one-pot reaction. This method was successfully applied to the synthesis of β-tubaic acid (6), an antimicrobial 2H-1-benzopyran-6-carboxylic acid.
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■ Simple Synthesis of 1,3,4,5a,6,10b,11,11a-Octahydro-2H-pyrazino[1’,2’:1,5]pyrrolo[2,3-b]indole Derivatives Based on 1-Hydroxyindole Chemistry
Yoshikazu Fukui and Masanori Somei*
*Kanazawa University, Faculty of Pharmaceutical Sciences, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
3-Substituted (3S,6S)-6-(1-hydroxyindol-3-ylmethyl)-2,5-piperazine- diones are prepared for the first time. They are shown to be suitable intermediates for the synthesis of 3,10b-disubstituted (3S,5aR,10bS,11aS)-1,3,4,5a,6,10b,11, 11a-octahydro-2H-pyrazino[1’,2’:1,5]pyrrolo[2,3-b]indole-1,4-dione derivatives.
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■ Stereoselective Syntheses of (E)- and (Z)-2,3-Dihydro-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-one Oxime Ethers
Saeed Emami and Abbas Shafiee*
*Department of Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Abstract
A synthesis of (E)- and (Z)-2,3-dihydro-3-(1H-1,2,4-triazol-1-yl)-4H-1-benzopyran-4-one oxime ethers [(E)- and (Z)-13] and (Z)-2,3-dihydro-3-(4H-1,2,4-triazol-4-yl)-4H-1-benzopyran-4-one oxime ethers [(Z)-17] are described. Ring closure of 2-(1,2,4-triazolyl)-2¢-hydroxyacetophenones (5 or 6) followed by reaction with HONH2.HCl gave the corresponding (Z)-oximes [(Z)-11 or (Z)-16]. O-Alkylation of (Z)-oximes afforded (Z)-oxime ethers [(Z)-13 or (Z)-17]. Reaction of (Z)-3-bromo-2,3-dihydro-4H-1-benzopyran-4-one oxime (18) with 1,2,4-triazole afforded (E)-oxime [(E)-11]. O-Alkylation of (E)-oxime gave the desired (E)-oxime ethers [(E)-13]. In addition, (Z)-oxime ethers [(Z)-13 or (Z)-17)] could also be obtained from the reaction of 2,3-dihydro-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-ones (2 or 14) with O-(arylmethyl)hydroxylamine hydrochloride (19).
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■ 3,5-Dichloro-4-pyridinecarbonitrile: A Multisite Substrate for Carbon Nucleophiles
Nevio Picci, Marco Pocci,* Annarosa Gugliuzza, Francesco Puoci, Angela De Munno, Francesca Iemma, and Vincenzo Bertini
*Dipartimento di Chimica e Tecnologie Farmaceutiche ed Alimentari, Università di Genova, Via Brigata Salerno, I-16147 Genova, Italy
Abstract
The reactivity of 3,5-dichloro-4-pyridinecarbonitrile (1) towards lithium or magnesium organo-metallic reagent is described. Conditions for substitution of cyano with alkyl or phenyl group, alkylation at the position 2 with removal of the 5-positioned chlorine, and formation of methyl or phenyl dichloro-pyridyl imines are reported. The obtained 4-alkyl-3,5-dichloropyridines can undergo a further alkylation at the position 2. The 3,5-dichloro-4-pyridyl residue is shown to be a good leaving group in form of anion yielding 3,5-dichloropyridine either from 1 or 3,5-dichloro-4-pyridinecarboxaldehyde.
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■ Synthesis of Bis-substituted Amidinobenzothiazoles as Potential Anti-HIV Agents
Livio Racane, Vesna Tralic-Kulenovic, Lelja Fiser-Jakic, David W. Boykin, and Grace Karminski-Zamola*
*Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulicev trg 20, P.O Box 177, HR-10000 Zagreb. Croatia
Abstract
In the multistep syntheses of the title compounds we obtained some new cyano-substituted heterocycles (1a, 1b, 2a, and 2b) as intermediates. Starting from dinitriles (2a and 2b) as well as from two formerly prepared dinitriles, substituted bisamidines (3a, 3b, 5a, 5b, 7a, and 7b) and amidino dihydrochlorides (4a, 4b, 6a, 6b, 8a, 8b, 9a, and 9b) have been synthesized.
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■ A Facile Entry to Bicyclic Systems from L-Glutamic Acid
Bryan A. Frieman, Charles W. Bock, and Krishna L. Bhat*
*Department of Chemistry, School of Science and Health, Philadelphia University, School House Lane & Henry Avenue,Philadelphia, PA 19144-5497, U.S.A.
Abstract
An efficient synthesis of bicyclic heterocycles has been realized from L-glutamic acid. The key step is the construction of the pyrrole ring in a single step, using tosylmethyl isocyanide (TosMIC) methodology. Structures of reaction intermediates and final products were investigated using density functional theory calculations.
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■ A Multinuclear NMR Spectral Study of Parent Azoles and Benzazoles: Experimental Results and GIAO Ab initio Calculations
Rosa M. Claramunt,* Concepción López, Dionisia Sanz, Ibon Alkorta, and José Elguero
*Departamento de Química Orgánica y Biologiá, Faclutade de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain
Abstract
The 13C and 15N chemical shifts of twelve azoles and benzazoles have been determined in the solid state at room temperature and in methanol solution at 178 K. The experimental values were compared with the absolute shieldings calculated at the GIAO/B3LYP/6-31G* level. These comparisons show that some signals, 13C NMR but especially 15N NMR, have to be corrected for hydrogen bonds present in certain solvents and in the solid state. The linear regressions are good enough to be used to predict some missing values.
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■ Four New Glucosides of Stilbene Oligomers from the Stem of Gnetum gnemonoides
Ibrahim Iliya, Toshiyuki Tanaka,* Miyuki Furasawa, Zulfiqar Ali, Ken-ichi Nakaya, Munekazu Iinuma, Yoshiaki Shirataki, Jin Murata, and Dedy Darnaedi
*Gifu Prefectrual Institute of Health and Environmental Sciences, 1-1 Nakafudogaoka, Kakamigahara, Gifu 504-0838, Japan
Abstract
Four new stilbene oligomeric glucosides, gnemonoside A, B, C and D, were isolated from the stem of Gnetum gnemonoides (BRONGN) along with four known stilbenoides, trans-resveratrol, gnetins C, D and E. The structures were elucidated on the basis of spectral evidence.
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■ Convenient Preparation of Heteroazulenes by the Reaction of 2-Aminotropone with Heterocumulenes in the Presence of a Base
Yuhki Mitsumoto and Makoto Nitta*
*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
Reactions of 2-aminotropone with heterocumulenes, N,N’-diphenylcarbodiimide, phenyl isothiocyanate, phenyl isocyanate, and carbon disulfide, in the presence of t-BuOK afforded 1-phenylcycloheptaimidazole-2(1H)-phenylimine, 1-phenylcyclohepataimidazole-2(1H)-thione, 1-phenylcycloheptaimidazol-2(1H)-one along with 2H-cycloheptaoxazol-2-one, and 2H-cycloheptathiazol-2-one along with 2H-cycloheptaoxazole-2-thione in good to moderate yields, respectively.
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■ Synthesis of a Thiino[2,3,4-d,e]phthalazine
Abdel Karim Karim, Montserrat Armengol, and John A. Joule*
*Department of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, U.K.
Abstract
The reaction of 5-(1,2-dibromo-2-phenylethenyl)phthalazine (16) with Na2CS3 gives 5-phenylthiino[2,3,4-d,e]phthalazine (17).
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■ Synthesis of Vinca Alkaloids and Related Compounds. Part 97. Epimerization with the Aid of Iodine
István Moldvai, Csaba Szántay Jr., and Csaba Szántay*
*Chemical Research Center, Institute of Chemistry, Hungarian Academy of Sciences, H-1525 Budapest, P.O.Box 17, Hungary
Abstract
(-)-15b-Hydroxy-14,15-dihydroeburnamenine (6) has been epimerized at the C(3) position with the aid of iodine. Octahydroindoloquinolizine derivatives containing hydroxyl group (11, 14, 17) gave the appropriate epimeric alcohols (13,16, 19) via pentacyclic intermediates (12, 15, 18).
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■ Copper(I) Iodide-promoted Hydroxylation onto the Lithium or Potassium Enolate of Lactones and Lactams
Norio Nakazawa, Keiko Tagami, Hitoshi Iimori, Shigeki Sano, Tsutomu Ishikawa, and Yoshimitsu Nagao*
*Sho-machi, Tokushima 770-8505, Japan
Abstract
After enolization of lactones (1a,b) and lactams (2a,b) with lithium or potassium hexamethyldisilazide in THF, each resultant enolate was treated with a solution prepared by mixing copper(I) iodide, pyridine, and tert-butyl hydroperoxide or N-methylmorpholine N-oxide in THF to give α-hydroxy lactones (3a,b) and α-hydroxy lactams (4a,b) in satisfied yields. This hydroxylation method was successfully applied to conversion of dl-desoxycamptothecin (dl-7) to dl-camptothecin (dl-5).
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■ 3-Hydroxy-4(1H)-pyridinone-containing Linear and Cyclic Hexapeptides and Their Iron(III) Complexes —Synthesis, Property, and the Growth-Promotion Activity —
Akira Katoh,* Yasushi Hikita, Manabu Harata, Junko Ohkanda, Taro Tsubomura, Akon Higuchi, Ryota Saito, and Kazuo Harada
*Faculty of Engineering, Seikei University, Musashino, Tokyo 180-8633, Japan
Abstract
Linear and cyclic hexapeptides composed of ε-(3-hydroxy-1,4-dihydro-2-methyl-4-oxo-1-pyridyl)-L-norleucine and glycine or β-alanine residue have been successfully synthesized. These hexapeptides formed 1:1 iron(III) complexes at neutral pH region. Glycine linear (8a)- and β-alanine cyclic hexa-peptide (10)-iron(III) complexes predominantly existed in Δ-configuration, while β-alanine linear hexapeptide (8b)-iron(III) complex existed in Λ-one. The relative stability constants of 8a, 8b, and 10-iron(III) complexes were estimated to be 31.6, 33.4, and 31.7, respectively. From iron(III) removal from human transferrin, linear hexapeptides (8a,b) were found to efficiently remove iron(III) compared with desferrioxamine B. The growth-promotion activity was also discussed.
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■ Reaction of N-Substituted 3,4-Dichloromaleimides with α-Mercaptoazaheterocycles
Galina G. Dubinina, Yulian M. Volovenko, Svetlana V. Shishkina, Oleg V. Shishkin, and Sergiy M. Yarmoluk*
*Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Zabolotnogo St., 03143 Kyiv, Ukraine
Abstract
Reaction of N-substituted 3,4-dichloromaleimides (1) with α-mer-captoazaheterocycles, 2-mercapto-1H-benzo[d]imidazole (2) and 3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-5-ones (4) in the presence of triethylamine, led to the formation of condensed thiazole ring resulting in 2,3-dihydro-1H-benzo[4,5]imidazo[2,1-b]pyrrolo[3,4-d][1,3]thiazole-1,3-diones (5) and 7,8-dihy-dro-2H,6H-pyrrolo[3’,4’:4,5][1,3]thiazolo[3,2-b][1,2,4]triazine-2,6,-8-triones (8), respectively. Refluxing of 8 in aqueous dioxane-triethylamine produced derivatives of 7-oxo-7H-[1,3]thiazolo[3,2-b][1,2,4]triazine-2-carboxamides (9) by destruction of maleimide ring with decarboxylation. The structure of 9i was confirmed by X-Ray analysis. 1 reacted with 2-thioxo-1,2,3,4-tetrahydro-4-quinazolinone (3) with cyclization at N-1 and N-3 positions.
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■ Synthesis of 3-Azabicyclo[3.3.1]nonane-6,9-diones
Brian D. Williams,* Birute Williams, Francis Bernardoni, Robert C. Finn, and Jon Zubieta
*Department of Chemistry, King's College, Wilkes-Barre, Pennsylvania 18711, U.S.A.
Abstract
A one pot synthesis of 3-azabicyclo[3.3.1]nonane-6,9-diones is described via the addition of acryloyl chloride to enamines of N-carboxy-4-piperidones. Yields of bicycle were highest when additions were made to vigorously boiling solutions of morpholine enamines. X-Ray analysis of an azabicyclic system revealed a chair-chair structure to be the preferred conformation. Hydrolysis of 3-azabicyclo[3.3.1]nonane-6,9-diones (IIa) and (IIb) yielded the monocyclic carboxylic acids (IIIa) and (IIIb).