HETEROCYCLES

■ Contents

■ Synthesis of Azaheterocycles and Related Molecules by Tf2NH-Catalyzed Cycloadditions

Naoya Shindo and Kiyosei Takasu*

*Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Acid-catalyzed cycloadditions utilizing nitrogen-containing building blocks are powerful tools for the synthesis of azaheterocyclic molecules. This review summarizes Tf2NH-catalyzed cycloadditions of imines and other related building blocks with electron-rich alkenes, alkynes, and 1,3-dienes, giving a various type of azaheterocycles and related nitrogen-containing compounds.

■ Highly Regioselective Ring Opening of a Common N,N-Dialkylaziridinium Ion by Carboxylic Acids

Ulises Hernández, Manuel Velasco, Jaime Vázquez, Joel L. Terán, Dino Gnecco, María L. Orea, David M. Aparicio, and Jorge R. Juárez*

*Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edif. IC8, Ciudad Universitaria 72570, Mexico

Abstract

A variety of optically active amino esters were synthesized via ring-opening reaction of (R)-1-phenyl-3-azaspiro[2.5]octan-3-ium ion derived from (R)-2-phenyl-2-(piperidin-1-yl)ethan-1-ol in a highly regioselective manner. Ring-opening reaction with carboxylates series generated in situ proceeded smoothly and with excellent yields (85-98%).

■ One-Pot Three-Component Synthesis of Novel Pyrazole-2,3-pyrroledicarboxylic Acid 2,3-Diesters

Emi Shirouzu, Eiichi Masumoto, Fumi Okabe-Nakahara, Kenji Yamagata, and Hiroshi Maruoka*

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

A facile synthesis of a series of pyrazol-3-one derivatives containing dihydropyrrole moiety using an efficient three-component reaction with 4-(dicyanomethylene)-3H-pyrazol-3-ones, acetylenic esters, and anilines is reported. The reaction is moderate to good yielding, tolerant towards a variety of amines, and provides access to novel pyrazole-2,3-pyrroledicarboxylic acid 2,3-diesters in a single step. All the synthesized compounds were characterized by spectroscopic analysis.

■ Syntheses of 4-Acetoxy- or Acetylthio-2-substituted Tetrahydrothiophene

Yaxi Li, Rui Ding, Yongguo Liu, Bianbian Ma, Baoguo Sun, and Hongyu Tian*

*Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Key Laboratory of Flavor Chemistry, Beijing Technology and Business University, Fucheng Road 11#, Haidian District 100048, China

Abstract

The generality of a three-step route for the preparation of 4-acetoxy-2-alkyltetrahydrothiophenes was investigated, which started from 1-alken-4-ols including epoxidation, mesylation and intramolecular nucleophilic substitution. 4-Acetoxy-2-alkyltetrahydrothiophenes could be produced in moderate to good yields by this method, even a bulky substituted group on the C-4 position of 1-alken-4-ol did not make significant effect on the reaction. In contrast, 1-alken-4-ols with an aryl group attached to the C-4 position gave acyclic products 1,4-diacetylthio-4-arylbutan-2-yl acetates when the reactions were carried out in acetonitrile under reflux. Whereas, 4-acetylthio-2-aryltetrahydrothiophenes were obtained in good yields when the reactions were carried out in toluene under reflux. A possible pathway for the latter involving an intermediate of episulfide was proposed.

■ Coumarins with Anti-Melanogenesis Activities from a Chemically Engineered Extract of a Marine-Derived Fungus

Hitoshi Kamauchi, Kaoru Kinoshita, and Kiyotaka Koyama*

*Department of Pharmacognosy and Phytochemistry, Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

Chemical investigation of new resources is critical for developing medicinal leads. Chemically engineered extracts, a technique for derivatization of natural extracts, was performed on crude extracts of marine-derived fungus Eurotium rubrum; the resulting reaction mixture exhibited enhanced tyrosinase inhibition. Coumarin derivatives (1-3) were isolated from this chemically engineered extract. The structures of 1-3 were established using NMR, MS, and IR methods, revealing coumarin structures with side chains biosynthesized by the acetate-malonate pathway. 1-3 showed tyrosinase inhibition (IC50 = 7.7, 13.3, and 9.5 μM, respectively) and anti-melanogenesis activity (IC50 = 6.6, 7.2, and 6.6 μM, respectively, against B16 melanoma cells).

■ Synthesis of 6,7-Dihydro-5H-thiopyrano[2,3-d]pyrimidin-5-one Derivatives Starting with 4,6-Dichloro-2-(methylsulfanyl)pyrimidine

Kazuhiro Kobayashi,* Ryoga Ono, Kouki Ishitobi, Ikuma Murayama, Hidetaka Hiyoshi, and Kazuto Umezu

*Applied Chemistry Field, Chemistry and Biotechnology Course, Department of Engineering, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

An efficient synthesis of 7-substituted 6,7-dihydro-5H-thiopyrano[2,3-d]pyrimidin-5-one derivatives from readily available 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP) has been developed. Thus, this starting material is converted to the corresponding 1-(4-chloro-6-methoxy(or dialkylamino)pyrimidin-5-yl)alk-2-en-1-ones by using easily operational sequences. These enones are then treated with sodium hydrogensulfide under mild conditions to afford the desired products in satisfactory yields.

■ Sulfanilic Acid-Catalyzed Green Synthesis of 4-Arylidene-2-phenyl-5(4H)-oxazolones

Hamzeh Kiyani* and Shiva Aslanpour

*School of Chemistry, Damghan University, 36719-41167 Damghan, Iran

Abstract

This study is focused on the catalytic activity of sulfanilic acid (SA) in the straightforward synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones via condensation of aromatic aldehydes, hippuric acid, and acetic anhydride under green experimental conditions (water solvent). The catalyst could be recovered easily from the filtrate via evaporation of the solvent and reused many times. It was found that the method is clean, relatively rapid, and environmentally friendliness alternative for the synthesis of Erlenmeyer-Plöchl azlactones as well as no needed for heating, microwave and ultrasound irradiations. Furthermore, all of the substrates and catalyst are easily accessible and inexpensive.

■ Three New C19-Diterpenoid Alkaloids from Aconitum apetalum

Jifa Zhang, Lin Chen, and Xianli Zhou*

*School of Life Science and Engineering, Southwest Jiaotong University, NO.111, North Second Ring Road Chengdu 610031, Sichuan, China

Abstract

Three new C19-diterpenoid alkaloids, named apetaldine H (1), apetaldine I (2) and apetaldine J (3), were isolated from the root of Aconitum apetalum. Their structures were elucidated by extensive spectroscopic analyses including 1D, 2D NMR, and HR-ESI-MS. Compounds (1–3) were evaluated for their cytotoxicity against the MCF-7, HepG2 and H460 human cancer cell lines.

■ An Efficient Solvent- and Catalyst-Free Synthesis of Bicyclic Pyridones with High Molecular Diversity via Cascade Reaction

Huang-Mei Fu, Hong-Bin Wang, Li-Juan Yang, Wen-Rong Yang,* and Chao Huang*

*Engineering Research Center of Biopolymer Functional Materials of Yunnan, School of Chemistry and Environment, Yunnan Minzu University, Kunming 650500, China

Abstract

Two efficient cascade routes for synthesis of substituted bicyclic pyridines under solvent- and catalyst-free conditions have been developed. One is conducted by refluxing the reaction mixture of heterocyclic ketene aminals (HKAs), triethoxymethane and dicarbonyl compounds. The other one is proceeded with HKAs and diethyl ethoxymethylenemalonate (EMME) under ultrasound irradiation. Both routes for preparation of bicyclic 2-pyridones carried out with low cost and easy available substrates and achieved diversity of target compounds in good yields efficiently and environmental-friendly.

■ Synthesis of 2,3-Disubstituted Indoles by Alkylative and Arylative Cyclization of 2-Alkenylphenylisocyanides with Grignard Reagents

Kazuo Yamazaki,* Yasutaka Tajima, Hitomi Tada, Yasuhito Kobayashi, Yutaro Miyamoto, Tomoko Ohkubo, and Masashi Ohba

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

Abstract

Alkylative cyclization of 3-(2-isocyanophenyl)propenoic acid tert-butyl ester with Grignard reagents proceeds smoothly to form 2-alkylindole-3-acetic acid derivatives in moderate-to-good yields. Substituted 3-(2-isocyanophenyl)propenoic acid tert-butyl esters undergo a similar reaction when phenylmagnesium bromide is used to render 2-phenylindole-3-acetic acid derivatives in moderate-to-good yields.

■ An Efficient Synthesis of 1-Hydroxy-5,8-dimethoxy-2-naphthaldehyde

Qijing Zhang, Jinyun Dong, Guang Huang, and Shaoshun Li*

*School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, China

Abstract

An efficient method for the preparation of 1-hydroxy-5, 8-dimethoxy-2-naphthaldehyde (1) was developed with a high overall yield (73.8%). Compared with the previously reported method, the reaction conditions are milder and the work-up of each step is much simpler. Moreover, the starting material considerably reduces the cost and is suitable for large-scale preparations.

■ Errata “Antiviral Activities of Some New 2,4,6-Trisubstituted 1,3,5-Triazines Having Alkoxy and/or Alkylamino Groups”: HETEROCYCLES, 2017, 94, 1653, DOI: 10.3987/COM-17-13735

Nobuko Mibu, Kazumi Yokomizo, Ai Yuzuriha, Marie Otsubo, Yuna Kawaguchi, Marina Sano, Izumi Sakai, Keita Nakayama, Jian-Rong Zhou, and Kunihiro Sumoto*

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan