HETEROCYCLES

■ Contents

■ Synthesis and Biological Evaluation of 3-((1-Methyl-1H-pyrrol-2-yl)methylene)indolin-2-one Derivatives as Potent Anticancer Active Agents

Jie Chen, Wei-nan Hu, Yang Xu, Wen Li, Ya-yun Qi, Yi-hong Fu, Jia-min Liu, Zhen-chao Wang,* and Gui-ping Ouyang*

*College of Pharmacy, Guizhou University, Huaxi St., Guiyang 550025, China

Abstract

A series of 3-((1-methyl-1H-pyrrol-2-yl)methylene)indolin-2-one derivatives were designed, synthesized, and evaluated for their inhibition activities against four tumor cells in vitro. These compounds were fully characterized by 1H NMR, 13C NMR, and HRMS. Antitumor experiments indicated that some compounds exhibited significant inhibition activities against SMMC-7721. Especially, the IC50 values of 7k and 7l (IC50 = 8.08 ± 0.95 µM, IC50 = 3.01 ± 0.61 µM) demonstrated the best antitumor activities against SMMC-7721 (human hepatoma cell lines) than the positive agents Sunitinib (IC50 = 8.27 ± 0.40 µM). Likewise, their structure activity relationship (SAR) was studied.

■ Synthesis of Optically Acitve γ-Lactams by Palladium Catalyzed Asymmetric Dicarbonylation Reaction of N-Arylsufonyl Homoallylic Amines

Ryosuke Takahashi, Nga Hang Thi Phan, Takuya Suga, Takahiro Soeta, and Yutaka Ukaji*

*Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

Optically active γ-lactams were prepared by asymmetric dicarbonylation reaction of N-arylsulfonyl homoallylic amines catalyzed by palladium in the presence of copper(I) triflate. By the use of benzyl-substituted bioxazoline ligand, the corresponding γ-lactams were obtained with enantioselectivities of up to 67% ee.

■ Synthesis of 8-Oxa-2-azabicyclo[3.2.1]octane Using a 1,3-Dipolar Cycloaddition Reaction

Kazuhiro Higuchi,* Yoshiki Matsubayashi, Takuma Sakurai, Motoki Ito, and Shigeo Sugiyama

*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

Herein, we report the application of 1,3-dipolar cycloaddition reaction toward the synthesis of a variety of 8-oxa-2-azabicyclo[3.2.1]octane compounds, the core structure of atkamine. The target compounds were obtained using a combination of a vinyl ether and carbonylylide, which was generated from a diazo compound and rhodium catalyst, in the presence of a Lewis acid.

■ Ruthenium-Catalyzed Hydroxyethylation of Cyclic Amines with Ethylene Glycol

Yushi Nakamura, Shuhei Tomioka, Yohei Oe,* and Tetsuo Ohta

*Department of Biomedical Information, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Tatara-miyakodani, Kyotanabe, Kyoto 610-0394, Japan

Abstract

It was found that a catalyst system RuCl2(PPh3)3/Xantphos is effective to install hydroxyethyl groups to the nitrogen atom of cyclic amines. Thus, the reactions of cyclic amines with ethylene glycol were performed in the presence of the RuCl2(PPh3)3/Xantphos catalyst in toluene at 120 °C for 22 h to provide the corresponding β-amino alcohols in up to 92% yield.

■ Synthesis and Antioxidant Activities of Some Novel Indane-Amide Substituted Pyrazole, Pyrimidine, Pyridine and 2-Pyrone Derivatives

Khaled S. Mohamed* and Elsherbiny H. El-Sayed

*Engineering Chemistry Department, Higher Institute for Engineering and Technology, New Damietta, New Damietta 34518, Egypt

Abstract

2-Cyano-N-(2,3-dihydro-1H-5-indenyl)-3-(dimethylamino)acrylamide (3) was used in synthetic paths to some novel indane-amide containing pyrazole, pyrimidine, fused pyrimidines, fused pyridines and 2-pyrone derivatives by reaction of 3 with various reagents. The newly synthesized compounds were investigated for their antioxidant activity. Some of the tested compounds exposed auspicious activities.

■ Synthesis of N-Substituted Pyrrole Derivatives via Indium-Assisted One-Pot Reduction/N-Annulation Sequence Reaction

Eungyung Kim, Mingyeong Jeong, Hyejeong Lee,* and Byeong Hyo Kim*

*Department of Chemistry, Kwangwoon University, Seoul 01897, Korea

Abstract

A synthesis strategy toward diverse pyrrole derivatives via an indium-mediated one-pot reductive N-annulation reaction has been developed. This protocol provides easy access to versatile N-substituted pyrroles in the presence of an indium/AcOH co-activation promotor, with excellent yields.

■ Environmentally Friendly Synthesis of N-Methylated Nitrogen Heterocycles from an Aqueous Solution of Methylamine and Diols

Akane Enomoto, Takuya Shimbayashi, and Ken-ichi Fujita*

*Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

N-Methylated nitrogen heterocycles are important compounds which are very common in organic, pharmaceutical, and material chemistry. Development of new environmentally friendly catalytic methods for the synthesis of N-methylated heterocycles using cost-effective and readily-available starting materials is strongly demanded. Herein, we report the efficient synthesis of N-methylated heterocycles using readily-available aqueous solution of methylamine and various diols catalyzed by iridium complexes. This catalytic system is attractive because of its high atom economy exhausting water as a sole by-product.

■ Synthesis and the First Structure–Activity Relationship Study of Imidazole Alkaloid from Red Ascidian as Aldose Reductase Inhibitors

Kenta Morikawa, Sota Uno, Shoko Higashi, Masaru Goto, and Ryota Saito*

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

Abstract

We synthesized a series of 2-aroyl-4-aryl-1H-imidazoles (2 and 3) and evaluated their in vitro AR inhibitory activity for the first time. We observed improved activities with derivatives having multiple catechol moieties.

■ An Ionic Liquid-Based Green Synthesis Strategy: Synthesis of Dihydropyrimidinones by Three-Component Biginelli-Type Reaction of Aliphatic Aldehydes, Aromatic Aldehydes and Urea

Lei-Han Fu, Zong-Bo Xie,* Guo-Qing Chen, Jin Lan, Zhi-Yu Hu, and Zhang-Gao Le*

*Department of Applied Chemistry, East China University of Technology, Guanglan Road 330013, China

Abstract

A Biginelli-type reaction involving aliphatic aldehydes, aromatic aldehydes, and urea was performed at high concentration with high regioselectivity to give a range of highly diverse 3,4-dihydropyrimidin-2-(1H)-one products in 58-88% yields, where a 30% aqueous solution of ionic liquid (1-ethyl-3-methylimidazolium tetrafluoroborate) was employed as a green reaction medium. The catalyst can be easily recycled and reused with similar efficacy for at least four cycles.