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. 75, No. 7, 2008
Published online: 22nd February, 2008
■ Pyrazolo[1,5-a][1,3,5]triazines(5-Aza-9-deazapurines): Synthesis and Biological Activity
Anton V. Dolzhenko, Anna V. Dolzhenko, and Wai-Keung Chui*
*Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore
Abstract
The present review gives an account on the synthetic routes to pyrazolo[1,5-a][1,3,5]triazine system, which is an isostere of purine, and polyfused systems bearing this heterocyclic core. Data concerning biological activity of compounds with pyrazolo[1,5-a][1,3,5]triazine skeleton are also discussed.
Published online: 14th March, 2008
■ Arylhydrazononitriles as Building Blocks in Heterocyclic Synthesis: Synthesis of New Benzothiazolyl-1,2,3-triazole Amines and -1,2,3-triazol-4-yl-1,3,4-thiadiazol-5-ylamines
Khadija Omar Badahdah
*Chemistry Department, Faculty of Science, King Abdul Aziz University, Jeddah, Saudi Arabia
Abstract
Benzothiazole-2-ylacetonitriles 6a-b and 5-benzoylamino-1,3,4-thiadiazol-2-ylacetonitrile 6c-d coupled with aromatic diazonium salts to yield arylhydrazones 7a-d. Compound 7a-d reacted with hydroxylamine hydrochloride in ethanolic sodium acetate to yield the corresponding amidoximes 8a-d. Compounds 8a-d cyclized readily into the 1,2,3-triazole derivatives 9a-d upon reflux in ethanolic DMF in the presence of anhydrous sodium acetate.
Published online: 29th February, 2008
■ Synthesis of Pyrrolo[2,3-d]pyrimidine Analogues of the Potent Antitumor Agent N-{4-[3-(2,4-Diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)propyl]benzoyl}-L- glutamic Acid (TNP-351)
Gaojun Zhu, Zenglu Liu, Yun Xu, and Zhenmin Mao*
*School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, PR China
Abstract
Two three-atom-bridged analogues of TNP-351, N-(4-{[(2-amino- 4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-ylmethyl)amino]methyl}- benzoyl)-L-glutamic acid (4) and N-(4-{[(2,4-diamino-7H-pyrrolo[2,3-d]- pyrimidin-5-ylmethyl)amino]methyl}benzoyl)-L-glutamic acid (5) were synthesized as anticancer agents, and their biological activities were evaluated.
Published online: 7th March, 2008
■ Medicinal Foodstuffs. XXXIII. Gastroprotective Principles from Boesenbergia rotunda (Zingiberaceae) - Absolute Stereostructures of Diels-Alder Type Addition Prenylchalcones
Masayuki Yoshikawa,* Toshio Morikawa, Kanako Funakoshi, Momotaro Ochi, Yutana Pongpiriyadacha, and Hisashi Matsuda
*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan
Abstract
The methanolic extract from the rhizomes of Boesenbergia rotunda (Zingiberaceae) was found to exhibit potent inhibitory activities on ethanol- or indomethacin-induced gastric mucosal lesions in rats. Through the bioassay-guided separation, six new optically active Diels-Alder type addition prenylcalcones, (+)-panduratin A (1a), (-)-panduratin A (1b), (+)-4-hydroxypanduratin A (2a), (-)-4-hydroxypanduratin A (2b), (+)-isopanduratin A (3a), and (-)-isopanduratin A (3b) were isolated together with 12 known compounds [(4-14) and geraniol]. The absolute stereostrucutures of six new compounds were elucidated on the basis of physicochemical evidence including CD spectra. Among them, the enantiomeric mixtures of panduratin A (1a, 1b) and 4-hydroxypanduratin A (2a, 2b), and pinocembrin (4) showed gastroprotective effects on ethanol- or indomethacin-induced gastric mucosal in rats.
Published online: 26th February, 2008
■ Solvent-Free Synthesis of 2-(1H-Benzimidazol-1-ylmethyl)-4-substituted 1-Hydroxyaryl by the Two Component Mannich Reaction between 6H,13H-5:12,7:14-Dimethanedibenzo-[d,i][1,3,6,8]tetraazecine (DMDBTA) and Phenols
Augusto Rivera,* Miguel Angel Navarro, and Jaime Ríos-Motta
*Departamento de Química, Universidad Nacional de Colombia, Ciudad Universitaria, Carrera. 30 # 45-03, Bogotá, D.C., Colombia
Abstract
A new series of Mannich bases (7a-e) were synthesized with good yields, in a single pot by a two component Mannich-type reaction under solvent-free conditions from 6H,13H-5:12,7:14-dimethanedibenzo[d,i][1,3,6,8]- tetraazecine (DMDBTA 1) and phenols (6a-e) at 150 °C. The mechanism of formation of those Mannich bases and their subsequent thermal decomposition into 1H-benzimidazole (8) and respective ortho-methylated phenols (9a-f) by an o-quinone-methide intermediate are also discussed.
Published online: 18th March, 2008
■ Enantioselective Synthesis of Piperidine Diamine Derivatives as Novel fXa Inhibitors
Akiyoshi Mochizuki,* Hiroyuki Naito, Yumi Nakamoto, Kouichi Uoto, and Toshiharu Ohta
*Medicinal Chemistry Research Laboratory I, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Abstract
Previously, we reported that racemic cis-piperidine diamine derivatives (±)-1 showed high anti-fXa, anticoagulation activity and oral activities. To confirm the active enantiomer, (3R,4S)-piperidine diamine derivatives (-)-1A and (-)-1B were synthesized enantioselectively from Boc-D-serine. These synthetic routes and intermediates could be utilized for the optimization of these derivatives. From the activities of (-)-1A and (-)-1B, (3R,4S)-isomer was confirmed to be the active enantiomer.
Published online: 11th March, 2008
■ Simple and Convenient Synthesis of 2,3,4,5-Tetrahydro-1,5-dioxopyrrolo[1,2-a]quinazoline- 3a(1H)-carboxylic Acids in Multi-Gram Scale
Rustam T. Iminov, Anton V. Tverdokhlebov,* Andrey A. Tolmachev, Yulian M. Volovenko, Alexander N. Kostyuk, Alexander N. Chernega, and Eduard B. Rusanov
*Enamine Ltd., Alexandra Matrosova str. 23, 01103, Kiev, Ukraine
Abstract
The title compounds were prepared in 70-100 grams scale by reaction of 2-amino-N-alkyl(aryl)benzamides with 2-oxoglutaric acid. Their structure was proved unambiguously by X-ray crystallographic study.
Published online: 4th March, 2008
■ A New Route for the Synthesis of Linezolid Mimetic 3,4-Disubstituted Oxazolidin-2-one Derivatives
Fumiko Fujisaki, Nobuhiro Abe, and Kunihiro Sumoto*
*Faculty of Pharmaceutical Sciences, Fukuoka University; Nanakuma, Jonan-Ku, Fukuoka 814-0180, Japan
Abstract
New oxazolidin-2-ones (3), which mimic the clinically useful antibacterial agent (1) (Linezolid) were prepared by using a cyclization procedure with diethyl carbonate from aminoalcohol (7) starting with DL-serine methyl ester hydrochloride (4) and aromatic carboxylic acid derivatives (5).
Published online: 14th March, 2008
■ Versatile Three Component Coupling for the Synthesis of Pyrazolopyridines and Other Pyrido Fused Systems
Carmen Almansa,* Marina Virgili, Elena Carceller, and Pedro Grima-Poveda
*Innovation and Drug Discovery, Palau Pharma S. A. (Grupo Uriach). Av. Camí Reial, 51-57, E-08184, Palau-Solità i Plegamans, Spain
Abstract
A new unexpected reaction of 1-(4-fluorophenyl)-2-(4-pyridyl)ethanone 2 with 3-aminopyrazole, involving loss of a 4-pyridylmethyl group, afforded 4,6-bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine 1 in good yields. Investigation of the features of this cyclization led to the development of a new three component coupling for the synthesis of pyrazolo[3,4-b]pyridines, from a ketone, an aldehyde and a 3-aminopyrazole in the presence of acid catalysis and a protic solvent. The study of the scope of this reaction showed its remarkable versatility and its usefulness in the preparation of other bicyclic systems, such as thieno[3,2-b]pyridines, pyrrolo[3,2-b]pyridines, imidazo[4,5-b]pyridines, furo[2,3-b]pyridines, isoxazolo[5,4-b]pyridines and, isothiazolo[5,4-b]pyridines. The three component nature of this reaction makes it suitable for the preparation of combinatorial libraries since scaffold decoration can be easily achieved in one step.
Published online: 14th March, 2008
■ Ring Current Models of Porphyrin and Conformational Analysis of the Dicarboxylate Complex of SNIV Porphyrin
Hajime Iwamoto* and Yoshimasa Fukazawa*
*Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan
Abstract
Several models for the porphyrin ring current effect are constructed based on a classical line current approximation and their performances in reproducing the observed induced shifts of ligand protons in SnIV(porphyrin) dicarboxylate complexes are compared. A new model is selected and it is found that the diamagnetic ring current running on the inner 16π-electron circuit of the porphyrin is the main contributor together with a minor paratropic ring current on the outer 20π-electron circuit. Conformational analyses of bis(biphenyl carboxylate) complexes of SnIV(tetraphenylporphyrin) in solution were carried out with this porphyrin ring current effect model.
Published online: 14th March, 2008
■ Synthesis of 5-(Adamantan-1-yl)-4,4-dimethyl-1-(3-oxyphenyl)-2,6,7-trioxabicyclo-[3.2.0]heptanes and Their Base-Induced Chemiluminescent Decomposition in Liquid/Solid Phase
Masakatsu Matsumoto,* Masatoshi Tanimura, Masahiko Tachi, and Nobuko Watanabe
*Department of Chemistry, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan
Abstract
Singlet oxygenation of 4-(adamantan-1-yl)-5-(3-hydroxy)phenyl-1,2-dihydrofuran 4a effectively gave bicyclic dioxetane 3a as crystals with a high melting point. Dioxetane 3a decomposed rapidly accompanied by the emission of blue light, when treated with tetrabutylammonium fluoride (TBAF) in DMSO or acetonitrile. The chemiluminescence efficiency for 3a was as high as those for tert-butyl-analog 2. In addition to chemiluminescent decomposition in a liquid phase, a finely powdered mixture of crystalline 3a and crystalline dimethylaminopyridine (DMAP) emitted blue light upon heating at 80-110 °C while maintaining a solid state.
Published online: 11th March, 2008
■ Synthesis of 6-Pyridylaminopurines
Luc Demange, Nassima Oumata, Julia Quinton, Serge Bouaziz, Olivier Lozach, Laurent Meijer, and Hervé Galons*
*INSERM U648, Université Paris Descartes, 4, avenue de l’Observatoire 75006 Paris, France
Abstract
An efficient synthesis of new 6-pyridinylaminopurines was developed based on Buchwald-Hartwig coupling reaction between aminopyridines and 2,6-dichloro-9-iso-propylpurine. The reaction was best carried out in the presence of a limited load of palladium acetate (4 %) as catalyst, racemic 2,2’-bis(diphenylphosphanyl)-1,1’-binaphtyl (8 %) as ligand and potassium tert-butoxide as base. Rising the load of catalyst, or using other catalysts and bases led to the development of side reactions.
Published online: 29th February, 2008
■ Facile Synthesis of 2-Anilinopyrimido[4,5-e]-[1,3,4]thiadiazines
Mehdi Bakavoli,* Mohammad Rahimizadeh, Ali Shiri, Hossein Eshghi, and Mohsen Nickpour
*Department of Chemistry, School of Sciences, Ferdowsi University, Mashhad 91775-1436, Iran
Abstract
One-pot synthesis of 2-anilino-pyrimido[4,5-e][1,3,4]thiadiazines through intermediates formed by reaction of 5-bromo-2-chloro-6-methyl-4- (1-methylhydrazino) pyrimidine with arylisothiocyanates is reported.
Published online: 26th February, 2008
■ Synthesis of Novel N-Substituted 6-Chlorothieno[2,3-e]-1,4,2-dithiazin-3-amine 1,1-Dioxides
Rajab Abu-El-Halawa,* Mahmoud H. Al-Refai, Mustafa M. El-Abadelah, and Hani D. Tabba
*Chemistry Department, Faculty of Science, Al al-Bayt University, Mafraq, Jordan
Abstract
A series of N-(substituted)-6-chlorothieno[2,3-e]-1,4,2-dithiazin-3- amine 1,1-dioxides (9a-g) were prepared via direct interaction of the appropriate isothiocyanate with 2,5-dichloro-3-thiophenesulphonamide 6 in THF in the presence of sodium hydride. The structures of these new bicyclic derivatives are based on microanalytical and spectral (IR, MS, and NMR) data.
Published online: 4th April, 2008
■ Thiophene Derivatives from the Aerial Part of Pluchea indica
Yun-Qi Qiu, Shu-Hua Qi, Si Zhang,* Xin-Peng Tian, Zhi-Hui Xiao, MIn-Yi Li, and Qing-Xin Li
*1Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, P. R. China
Abstract
Chemical investigation on the aerial part of Pluchea indica resulted in the isolation of two new thiophene derivatives, 2-(4-hydroxy-3- methoxybut- 1-yn-1-yl)-5-(penta-1,3-diyn-1-yl)thiophene (1) and 2-(4-O-β-glucopyranosyl- 3-hydroxybut-1-yn-1-yl)-5-(penta-1,3-diyn-1-yl)thiophene (2) along with three known thiophene derivatives 2-(3,4-dihydroxybut-1-yn-1-yl)-5-(penta-1,3-diyn-1-yl)thiophene (3), 2-(3-acetoxy-4-hydroxybut-1-yn-1-yl)-5-(penta-1,3-diyn-1-yl) thiophene (4) and 2-(prop-1-yn-1-yl)-5-(6-acetoxy-5-hydroxyhexa-1,3-diyn-1-yl) thiophene (5). The structures of 1 and 2 were determined on the bases of extensive spectroscopic analysis, including 1D and 2D NMR data. Antimicrobial activities of compounds 1-5 were tested.
Published online: 4th March, 2008
■ A Facile Synthesis of Imidazo[1,5-b]pyridazines from 3-Formylchromones
Andrey S. Plaskon, Sergey V. Ryabukhin,* Dmitriy M. Volochnyuk, Alexander N. Shivanyuk, and Andrey A. Tolmachev
*Enamine Ltd. 23 A. Matrosova st., 01103 Kyiv, Ukraine
Abstract
The recyclization of 3-formylchromones promoted by chlorotrimethylsilane with 1-amino-1H-imidazoles results in a set of imidazo[1,5-b]pyridazines is obtained in high preparative yields. It‘s found that the reaction is sensitive to the structure of NNC-binucleophiles.
Published online: 29th February, 2008
■ A Facile Synthesis of Novel Heteropolycyclic Pyrazines and Oxazoles Mechanistic Studies of 2,3-Dihydrobenzo[de]chromene-7,8-dione with Amines
Hua-pei Jian, Xing-yuan Wang, Zhi-shu Huang, Shi-liang Huang,* and Lian-quan Gu
*School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, P. R. China
Abstract
A series of novel heteropolycyclic pyrazines and oxazoles were synthesized by the reaction of 2,3-dihydrobenzo[de]chromene-7,8-dione (compound 1) with amines in mild reaction conditions. The mechanisms for these reactions were discussed.
Published online: 18th March, 2008
■ Synthesis of 1H-Isoindoles by Iodoamination of 2-Vinylbenzylidenamines
Kazuhiro Kobayashi,* Mai Horiuchi, Miyuki Tanmatsu, and Hisatoshi Konishi
*Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Abstract
An efficient method for the synthesis of 1H-isoindole derivatives is described. It is based on iodine mediated cyclization of aryl(or alkyl)(2-vinylbenzyliden)amine derivatives, which can be easily prepared from the reactions of 2-lithiostyrene derivatives with various nitriles, furnishing the corresponding iodoamination products, 3-aryl(or alkyl)-1-iodomethyl-1H-isoindole derivatives, in satisfactory overall yields.