HETEROCYCLES

■ Contents

■ Development of Samarium Diiodide-Promoted Regioselective Carbon-Carbon Bond Cleavage Reaction of γ-Halo- and ε-Halo-α,β-unsaturated Carbonyl Compounds: Application to the Synthesis of Biologically Active Natural Products

Toshio Honda*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Samarium diiodide (SmI2), a mild and selective one electron transfer reagent, has been utilized in a wide range of synthetic transformations. Among the various reactions developed for SmI2, we focused on its use for fragmentation reactions, and established a regioselective carbon-carbon bond cleavage reaction of γ-halo carbonyl compounds. Utilization of this strategy in the synthesis of various types of biologically active natural products is discussed in this review article.

■ Regio- and Stereoselective 1,3-Dipolar Cycloaddition of C-Aryl-N-phenylnitrones over (E)-Arylidene-(2H)-indan-1-ones: Synthesis of Highly Substituted Novel Spiro-isoxazolidines

Nadia Wannassi, Mohamed Mehdi Rammah, Sarra Boudriga, Mohamed El Baker Rammah,* Karin Monnier-Jobé,* Kabula Ciamala, Michael Knorr, Mironel Enescu, Yoann Rousselin, and Marek M. Kubicki

*Department of Chemistry, Laboratory of Heterocyclic Organic Chemistry, Faculty of Sciences, University of Monastir, Avenue Ali Bourguiba, Skanès
5000 Monastir, Tunisia

Abstract

Synthesis of a series of novel spiro-isoxazolidines has been accomplished in good yields by regio- and diastereoselective 1,3-dipolar cycloaddition of (E)-2-arylidene-(2H)-indan-1-ones 1a-d to C-aryl-N-phenylnitrones 2e-h. The structure of the spiro-adducts 3ae-dh was elucidated by 1H and 13C NMR spectroscopy. The proposed regio- and stereochemistry of spiranic compounds 3ae and 3be has been corroborated by two single crystal X-ray crystallographic analyses and by means of DFT calculations.

■ Isolation and Identification of a Gravity-Induced Growth Inhibitor in Etiolated Radish Hypocotyls

Tsuyoshi Hasegawa, Wai Wai Thet Tin,* Hideyuki Shigemori, Toshihiko Otomatsu, Katsutoshi Hirose, Kensuke Miyamoto, Junichi Ueda, and Koji Hasegawa

*Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

Abstract

A growth inhibitor of which content in etiolated radish hypocotyls was increased under 500 g gravity conditions produced by centrifugation, but decreased under simulated microgravity conditions on a 3-dimensional clinostat, comparing to 1 g conditions, was isolated from etiolated radish hypocotyls grown under 1 g conditions. It was determined to be 3,6’-disinapoylsucrose by its 1H and 13C NMR and MS spectral data. When etiolated radish seedlings were placed horizontally, the gravitropic curvature took about 30 min to start. The distribution of endogenous 3,6’-disinapoylsucrose between the peripheral cell layers of the upper and lower flank of radish hypocotyls during gravitropic curvature was analyzed using a physicochemical assay. Its content rapidly increased in the peripheral cell layers of the upper halves, peaking at 30 min after the onset of gravitropic stimulation, then gradually decreased. On the other hand, the content in the peripheral cell layers of the lower halves was almost equal to that in the vertical control during gravitropic curvature. Its unilateral application caused the hypocotyls to bend toward the site of application. These results suggest that gravitropic stimulation suppresses the growth rate of the upper side of radish hypocotyls by increasing the content of the growth inhibitor 3,6’-disinapoylsucrose in the peripheral cell layers of the upper halves, causing a gravitropic response.

■ Voltammetric Behavior of Mediator-Modified Electrode by Electrochemical Polymerization of Nitroxyl Radical Precursor Containing Pyrrole Side Chain

Tetsuya Ono, Makiko Tsunoda, Shigehiro Takahashi, Toshio Obata, Takanori Sone, and Yoshitomo Kashiwagi*

*School of Pharmaceutical Sciences, Ohu University, 31-1 Misumido, Tomita-machi, Koriyama, Fukushima 963-8611, Japan

Abstract

This paper describes the voltammetric behavior of TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-modified electrode prepared by the electrochemical polymerization of TEMPO-modified pyrrole. The modified electrode exhibits a symmetrical reversible redox wave at +0.7 V versus Ag/AgCl, which originates from the electron transfer between the pyrrole-polymerized layer and the electrode. The properties of the polymers on the electrode surface can be modulated by varying the applied polymerization potential. The TEMPO-modified electrode exhibits electrocatalytic activity for the oxidation of geraniol.

■ Asymmetric Acyl-Strecker Reaction Promoted by Novel Thiourea Organocatalyst

Takuya Kanemitsu, Eisuke Toyoshima, Michiko Miyazaki, Kazuhiro Nagata, and Takashi Itoh*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

Asymmetric acyl-Strecker reaction using novel thiourea organocatalyst is described. Screening experiments of the catalysts revealed that a bifunctional organocatalyst afforded an enantio-enriched product via an unique mechanism. That is, dihydroisoquinoline derivatives were converted to a corresponding 1-cyano-1,2,3,4-tetrahydroisoquinolines using the bifunctional thiourea catalyst derived from Betti base in moderate yield and enantioselectivity.

■ Eight New Oleanane-Type Triterpenoid Saponins from Platycodon Root

Motonori Fukumura, Daigo Iwasaki, Yasuaki Hirai, Yumiko Hori, Kazuo Toriizuka, Peter T. M. Kenny, Yoshiyuki Kuchino, and Yoshiteru Ida*

*Yokohama College of Pharmacy, 601, Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan

Abstract

Eight new triterpenoid saponins, platyconic acids B (1), C (2), D (3), E (4), platycodins J (5), K (6), L (7) and platycosaponin A (8), were isolated from Platycodon Root, together with twelve known compounds, and they were characterized on the basis of their spectroscopic and chemical data.

■ Synthesis and Spectroscopic Characterization Study of Some Cyclic-Azodioxides

Mohammad A. Naser Al-Magmoy,* Zeki A. Nasir Al-Shamkhani, and Ali Hashem Essa

*Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq

Abstract

New compounds of cyclic-azodioxides have been prepared by oxidation of the corresponding diamines with sodium tungstate and hydrogen peroxide in a mixed ethanol/water solvent. Spectroscopic techniques, including IR, UV, 1H NMR, and 13C NMR, and CHN analysis were used to identify the products. In solution, the azodioxides were found to be in equilibrium with the corresponding dinitroso compounds. The IR values of the synthesised compounds are in agreement with the theoretical IR spectra.

■ Synthesis of Two Estradiol-Imidazole C-Ribonucleoside Hybrid Compounds Exhibiting Inhibitory Effects against Type 1 17β-Hydroxysteroid Dehydrogenase

Shinya Harusawa,* Chihiro Kojima, Kensuke Fujii, Yuusaku Yamashita, Tomoya Tanaka, Lisa Araki, Toshinobu Yoshimura, Minoru Sakaguchi, Yoshihide Usami, and Masanori Takaoka

*Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

Novel estradiol-imidazole C-nucleoside hybrid compounds 4a and 4b, which have C4-linked C0- and C2-imidazole ribonucleosides as adenosine mimics and amide bond linkers, were designed and synthesized based on EM-1745, an inhibitor of type 1 17β-hydroxysteroid dehydrogenase (17β-HSD1). Compounds 4a and 4b were also tested as enzyme inhibitors.

■ Non-CRET-Based Green Chemiluminescence of Imidazopyrazinone Modified by 2,3,6,7-Tetrahydro-1H,5H-benzo[i,j]quinolizine as a Strong Electron-Donating Unit

Ryota Saito*

*Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

A new imidazopyrazinone derivative, 1, having a 2,3,6,7-tetrahydro-1H,5H-benzo[i,j]quinolizin-9-yl (julolidin-9-yl) group at the 6-position, was synthesized and exhibited a largely red-shifted chemiluminescence in diglyme containing acetate buffer caused by a strong electron donation from the julolidin-9-yl group. The maximum wavelength was observed at 523 nm, which represents the most red-shifted light achieved only by the electron-donating effect from the 6-position of the imidazopyrazinone skeleton without any aids of extended π-conjugation systems or longer-wavelength-light emitting fluorophores.

■ Iron-Catalyzed One-Pot Synthesis of 2-Aminobenzothiazoles from 2-Aminobenzenethiols and Isothiocyanates under Ligand-Free Conditions in Water

Wenying Wang, Wenying Zhong, Runxia Zhou, Jinsheng Yu, Juan Dai, Qiuping Ding,* and Yiyuan Peng*

*College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China

Abstract

A practical and efficient method for the synthesis of 2-aminobenzothiazoles has been developed via an iron-catalyzed one-pot tandem reaction. Various 2-aminobenzothiazoles were conveniently synthesized in moderate to excellent yields. It is highlighted that the reaction is conducted under ligand-free conditions in water.

■ A Rapid and High-Yielding Synthesis of Thiazoles and Aminothiazoles Using Tetrabutylammonium Salts

Erdal Kocabas,* Ahmet Burak Sarıguney, and Ahmet Coskun

*Department of ChemistryM, Selcuk University, Meram 42009, Konya, Turkey

Abstract

A convenient method for the synthesis of thiazoles and aminothiazoles by treatment of phenacyl bromides with thioamides/thiourea in the presence of tetrabutylammonium hexafluorophosphate (Bu4NPF6) at room temperature was developed. The products having high yields were formed rapidly (within 15 min). The method is simple, rapid and practical, generating thiazole derivatives in excellent isolated yields. The structures of the newly synthesized products were identified by FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis data.

■ Synthesis of 1,2-Disubstituted Benzimidazoles and 2-Substituted Benzothiazoles Catalyzed by HCl-Treated trans-3,5-Dihydroperoxy-3,5-dimethyl-1,2-dioxolane

Davood Azarifar,* Kaveh Khosravi, Zohreh Najminejad, and Khadijeh Soleimani

*Faculty of Chemistry, Bu-Ali Sina University, P.O. Box 4135, Hamedan 6517838683, Iran

Abstract

The catalytic effect of trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane in the presence of HCl has been explored in one-pot condensation reaction of o-phenylenediamines and o-aminobenzenethiol with a variety of aldehydes into their corresponding 2-aryl-1-arylmethylimidazoles and 2-arylbenzothiazoles respectively. The reactions were conducted under mild conditions in MeCN at room temperature to afford the products in excellent yields.

■ Convenient Synthesis of Some 3-Phenyl-1-benzofuran-2-carboxylic Acid Derivatives as New Potential Inhibitors of CLC-Kb Channels

Luca Piemontese, Giuseppe Carbonara, Giuseppe Fracchiolla, Antonio Laghezza, Paolo Tortorella, and Fulvio Loiodice*

*Medicinal Chemistry Department, University of Bari “Aldo Moro”, via E. Orabona, 4, 70126, Bari, Italy

Abstract

Improved experimental conditions were carried out for the preparation in high yields of some 3-phenyl-1-benzofuran-2-carboxylic acids, potent inhibitors of ClC-K chloride channels. A one-pot condensation-cyclization was set up starting from different 2-hydroxybenzophenones whose reactivity was significantly affected from the electronic properties of their substituents.