HETEROCYCLES

■ Contents

■ Transition Metal-Catalyzed Synthesis of π-Conjugated Cyclic Esters and Amides from Alkynes and Carbonyl Reagents

Tetsuaki Fujihara and Yasushi Tsuji*

*Deparment of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoudai-katsura, Nishikyo, Kyoto 615-8510, Japan

Abstract

The transition metal-catalyzed intermolecular reaction of carbonyl precursors with alkynes is a simple method for constructing various carbonyl compounds. We review the syntheses of π-conjugated cyclic carbonyl compounds from the reaction of alkynes with suitable carbonyl precursors in the presence of transition metal catalysts. These methods afford isocoumarins, chromones, 2-quinolones, 4-quinolones, and isoquinolones, and the reaction of diynes with carbon dioxide produces pyrones.

■ Reductive Cyclization Reactions to Bicyclic Compounds Using Samarium Diiodide

Motoo Tori* and Masakazu Sono

*Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-machi, Tokushima, 770-8514, Japan

Abstract

This review covers reports on the one-electron reductive cyclization reactions affording bicyclic compounds, such as hydrindans, perhydronaphthalenes, perhydroguaianes, and other systems including five-, six-, seven-, and eight-membered carbocycles using SmI2. The substrate is aldehyde, ketone, or ester. The effect of additives, such as H2O, MeOH, HMPA, and NiI2, was studied. The mechanistic aspects recently investigated are also introduced.

■ Synthesis and Antimicrobial Evaluation of Some Isoxazole Based Heterocycles

Elham S. Darwish, Khalid A. Atia, and Ahmad M. Farag*

*Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Abstract

The versatile hitherto unreported 2-cyano-N-(4-{[(5-methylisoxazol-3-yl)amino]sulfonyl}phenyl)acetamide (3) was utilized for the synthesis of a variety of heterocycles incorporating sulfamoyl moiety. The 2-pyridone derivatives were obtained via reaction of cyanoacetamide with pentane-2,4-dione, arylidenes malononitrile, or terephthalaldehyde and malononitrile upon heating under reflux in the presence of a catalyst. Condensation of the cyanoacetamide 3 with salicylaldehyde furnished the corresponding chromene derivatives. Coupling of 3 with arene diazonium chlorides gave the hydrazone derivatives 13a-c, which upon treatment with hydrazine hydrate and ethyl chloroformate furnished the corresponding pyrazole and triazine derivatives, respectively. Reaction of 3 with carbon disulfide and 1,2-dibromoethane, 1,3-dibromopropane or dimethyl sulfate afforded 2-cyano-2-(1,3-dithiolan-2-ylidene)-N-(4-{[(5-methylisoxazol-3-yl)amino]sulfonyl}phenyl)acetamide (18), 2-cyano-2-(1,3-dithian-2-ylidene)-N-4-{[(5-methylisoxazol-3-yl)amino]sulfonyl}phenyl)acetamide (19), and 2-cyano-N-(4-{[(5-methylisoxazol-3-yl)amino]sulfonyl}phenyl)-3,3-bis(methylthio)acrylamide (20). The newly synthesized compounds were evaluated for their in vitro antibacterial and antifungal activities, and showed promising results.

■ An Efficient Synthesis of (3S,5S)-5-[3,3-Dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]piperidine-3-carboxamide as Potent Renin Inhibitor

Yutaka Mori,* Mitsuhiro Iwamoto, Kazuki Mori, Masao Yoshida, Takeshi Honda, Takahiro Nagayama, and Takahide Nishi

*New Modality Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

Abstract

We report synthesis and biological evaluation of (3S,5S)-5-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]piperidine-3-carboxamide as renin inhibitor. This effective synthetic route involves a zinc mediated Barbier reaction and an intramolecular Horner-Wadsworth-Emmons reaction of sterically hindered ketone as key reactions. The prepared compound 4 exhibited both potent renin inhibitory activity and significant in vivo efficacy in furosemide pretreated cynomolgus monkeys.

■ Synthetic Access to Poly-Substituted 11H-Pyrido[3,2-a]carbazoles, a DNA-Intercalating Ellipticine Related Structure, and Their Antiproliferative Activity

Ming-Yu Wu, Elkhabiry Shaban, Marta Świtalska, Ning Wang, Miho Shimoda, Yusuke Mizutani, Megumi Yoshida, Zhen-Wu Mei, Hiroyuki Kawafuchi, Junzo Nokami, Joanna Wietrzyk,* Xiao-Qi Yu, and Tsutomu Inokuchi*

*Division of Chemsitry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

The facile procedure for the synthesis of the 11H-pyrido[3,2-a]carbazole structure involving the Fischer indole cyclization on tetrahydroquinolinones, available from enaminones and methyl 2-formyl-3-oxopropanoate, followed by the aromatization of the resulting 5,6-dihydro derivatives is described. This method allows for the introduction of substituents at C2, C6, and C8 to the scaffold by choice of the starting materials. In the biological testing, introduction of the phenyl group at C6 is significantly effective to improve the antiproliferative activity.

■ Nickel-Catalyzed Ligand-Free Systhesis of Benzoxazoles and Oxazolines via Isocyanide Insertion

Jin-Mei Wang, Xiao Jiang, Ting Tang, Yong-Ming Zhu,* and Jing-Kang Shen*

*School of Pharmaceutical Science, Soochow University, #199, Renai Road, Suzhou City 215123, China

Abstract

A novel and efficient route to benzoxazoles and oxazolines involving a nickel-catalyzed three-component coupling reaction of iodobenzene, an amino alcohol and tert-butyl isocyanide has been developed. A wide array of products have been prepared in good to excellent yields in the absence of ligand.

■ A New Flavonoid Glycoside and Four Other Chemical Constituents from Viscum coloratum and Their Antioxidant Activity

Ronghua Fan, Yuying Ma, Hongxia Yuan, Yongzhi Zhang, Binbin Wei, Yunli Zhao,* and Zhiguo Yu*

*School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China

Abstract

A new flavonoid glycoside, identified as rhamnazin-3-Ο-β-D-(6′′-β-hydroxy-β-methylglutaryl)-β-D-glucoside-4′-Ο-β-D-glucoside (1), along with four known compounds, shikimic acid (2), quebrachitol (3), abscisic acid (4), 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (5), were isolated from the branches and leaves of Viscum coloratum. Their structures were elucidated on the basis of MS, 1D NMR, and 2D NMR techniques. All compounds were isolated in the family Loranthaceae for the first time. This paper describes the isolation, structural elucidation as well as in vitro antioxidant activity of these isolates.

■ A Facile Synthesis and Ring-Opening Reactions of Novel 2-Ferrocenyl-3,4-dihydropyrans

Yuying Du, Hui Qiao, Limin Han,* Ning Zhu, and Quanling Suo

*Chemical Engineering College, Inner Mongolia University of Technology, Hohhot 010051, China

Abstract

A series of novel 2-ferrocenyl-3,4-dihydropyrans were synthesized in good to excellent yields through three-component reaction of vinylferrocene, 1,3-dicarbonyl compound and formaldehyde near room temperature under catalyst-free conditions. The obtained ferrocenyl dihydropyrans can also react readily with indole in the presence of alum, providing a ring-opening product in high yield, and this result opens an effective way to access a new class of complex ferrocenyl derivatives.

■ A Convenient Synthetic Method of Isoxazole Derivatives Using Copper(II) Nitrate

Ken-ichi Itoh,* Tadashi Aoyama, Hiroaki Satoh, Kenta Hasegawa, Natsumi Meguro, Akira C. Horiuchi, Toshio Takido, and Mitsuo Kodomari

*Department of Liberal Arts and Science, College of Science and Technology, Nihon University, 7-24-1 Narashinodai, Funabashi-shi, Chiba 274-8501, Japan

Abstract

3-Acetylisoxazoles were synthesized by the reaction of alkenes or alkynes in acetone as solvent with copper(II) nitrate and formic acid. In the case of ethyl acetate as solvent, 3-benzoylisoxazoles were yielded by the reaction of alkynes and acetophenone with copper(II) nitrate and nitric acid. This synthetic method provides a convenient production of isoxazole derivatives.

■ An Efficient One-Pot Synthesis of Some New Substituted 1,2,3,5-Thiatriazolidin-4-one 1,1-Dioxides

Monaem Balti,* Khaireddine Dridi, and Mohamed Lotfi El Efrit

*Department of Chemistry, Faculty of Sciences of Tunis-Tunisia, El Manar-B.P. 94 Poste Romena, 1068, Tunisia

Abstract

A series of some new 1,2,3,5-thiatriazolidin-4-one 1,1-dioxides derivatives were synthesized by reacting respectively β-cyanohydrazines and phosphorylated hydrazine with chlorosulfonyl isocyanate in good yields. The structures of all the newly prepared compounds were confirmed by IR, 1H, 13C, 31P-NMR spectral data and elemental analysis.

■ An Efficient Method for the Preparation of 4-Alkoxy-substituted Thieno[2,3-b]pyridines

Keiji Saito, Satoru Naito, and Tsuyoshi Shinozuka*

*Department of Chemistry, Daiichi Sankyo India Pharma Private Limited, Village Sehroul, Sector-18, Udyog Vihar Industrial Area, Gurugaon, 122 015, India

Abstract

An efficient method for the preparation of 4-alkoxy-substituted thieno[2,3-b]pyridines is described. The key intermediates, 4-alkoxy-2-chloro-3-cyanopyridines, were synthesized from a variety of alcohols by nucleophilic substitution with 3-cyano-2,4-dichloropyridine or by Mitsunobu reaction with 2-chloro-4-hydroxynicotinonitrile. Subsequent reaction of 4-alkoxy-2-chloro-3-cyanopyridines with 2-(acetylthio)acetamide under basic conditions provided 4-alkoxy-substituted thieno[2,3-b]pyridines in fair to good yields.

■ Photocyclization Reactions of N-Substituted 3-(2-Hydroxynaphthalen-1-yl)propenamide Derivatives Accompanied by Liberation of Aliphatic and Aromatic Primary Amines

Koh Watanabe, Shun Takahashi, Takuya Yoshizawa, Tetsutaro Igarashi, and Tadamitsu Sakurai*

*Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

(E)-3-(2-Hydroxynaphthalen-1-yl)propenoyl- and (E)-3-(2-hydroxynaphthalen-1-yl)-2-methylpropenoyl-protected aliphatic and aromatic primary amines were synthesized and their photolytic behavior in methanol was explored. The results showed that irradiation of the hydroxynaphthyl-propenamide derivatives in a protic polar solvent at wavelengths greater than 280 nm or 340 nm causes rather efficient deprotection reactions to afford the desired amines quantitatively along with fluorescent benzocoumarins.