HETEROCYCLES

■ Contents

■ A Review on Indole[2,3-a]quinolizidine: The Synthetic Approaches to the Development of Bioactive Indolo[2,3-a]quinolizidine Scaffolds

Shivangi Sharma, Yukti Monga, Ashu Gupta, and Shivendra Singh*

*Applied Chemistry, Amity University Madhya Pradesh, A-Block, ASET, India

Abstract

Tetracyclic indolo[2,3-a]quinolizidine motifs are an important class of molecules in research and development due to their wide spectrum of biological activities, which include anti-allergic, antibacterial, antiviral, and other bioactive qualities. To develop the indolo[2,3-a]quinolizidine system, innovative synthetic methods have thus attracted tremendous attention during the past decades. This article describes the synthetic approaches developed to target the most important alkaloids of this family, with an emphasis on the possible use of these alkaloids or their analogues to treat a variety of illnesses, ranging from cancer to neurological disorders. In this review article, we have described several crucial synthetic methodologies leading to the indolo[2,3-a]quinolizidine scaffolds. Further, the biological activities and the structure-activity relationships (SAR) of such derivatives towards various disease gives a better understanding of the significance of this moiety in medicinal chemistry.

■ Asymmetric Inverse-Electron-Demand 1,3-Dipolar Cycloadditions Using Organocatalysts

Hiroyuki Suga* and Yasunori Toda

*Department of Materials Chemistry, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan

Abstract

1,3-Dipolar cycloaddition reactions have been utilized as a powerful tool for the construction of five-membered heterocyclic rings in organic synthesis because of their stereospecificity and regioselectivity. A large number of chiral Lewis acid-catalyzed asymmetric 1,3-dipolar cycloadditions for both normal- and inverse-electron-demand types have already been reported. Asymmetric normal-electron-demand 1,3-dipolar cycloadditions have also been well studied in organocatalysis, and a significant number of examples have been reported. In contrast, successful examples of asymmetric inverse-electron-demand 1,3-dipolar cycloadditions using organocatalysts are currently limited. This review focuses on chiral organic molecule-mediated enantioselective inverse-electron-demand 1,3-dipolar cycloaddition reactions. For 1,3-dipoles, we mainly cover nitrones, C,N-cyclic azomethine imines, N,N-cyclic azomethine imines, and nitrile oxides. Similar types of inverse-electron-demand [3+2] cycloadditions are described, employing hydrazones, oxaziridines, and azo compounds. Among the organocatalyst-mediated asymmetric inverse-electron-demand cycloadditions, more examples were found for using azomethine imines than for other 1,3-dipoles. N-Triflylphosphoramides, phosphoric acids, amines, N-heterocyclic carbenes, amine-thioureas, and amine-ureas, depending on which 1,3-dipoles or dipolarophiles are used, would be the chiral catalyst of choice for achieving asymmetric inverse-electron-demand 1,3-dipolar cycloadditions.

■ Highly Diastereoselective Self-1,3-Dipolar [3+3] Cycloaddition of Azomethine Ylides Promoted by Cesium Catalyst

Hai Ren,* Xiong-Jiang Li, Wei Wu, Jun Shi, and Jun-Rong Song*

*The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guizhou Medical University, 3491 Baijin Road, Guiyang 550014, China

Abstract

A highly diastereoselective self-1,3-dipolar [3+3] cycloaddition reaction catalyzed by cesium carbonate has been established for the synthesis of 2,5-dispirooxindole-piperazines. This reaction involves the reaction of azomethine ylides derived from unprotected isatins with tetrahydroisoquinolines. The method is characterized by its simplicity, avoidance of excess external acids and high diastereoselectivity.

■ A Series of Novel Coumarin Derivatives: Design, Synthesis and Evaluation of Anti-Tumor Activity

Zhuo Zhang, Bing He, Fei-Yang Shang, and Li-Qin He*

*School of Pharmacy, Anhui University of Chinese Medicine, Yaohai District of Hefei City, Anhui Province, Mo Dian Xiang Anhui University of Chinese medicine shaoquan Lake Campus, 230012, China

Abstract

A series of novel coumarin derivatives were synthesized and evaluated for their solubility and in vitro anti-proliferative activities against seven different tumor cell lines. As a result, most of the target compounds exhibited prominent inhibitory activities. Especially, compound 12c exhibited the most potent inhibitory activity with IC50 values of 0.29-0.84 μM for both six tumor cell lines and one drug-resistant tumor cell line Bel-7402/5-FU, which are 5.45 - 22.55-fold better than 5-FU. Mechanism research revealed that compound 12c blocked the cancer cell cycle at the G2/M phase and induced apoptosis of tumor cells. Our results indicate that compound 12c is worth further investigating as an effective anti-cancer candidate.

■ Efficient Synthesis of Quinazoline-2,4(1H,3H)-Diones from 2-Aminobenzonitriles and Co2 Catalyzed by 2-Hydroxypyridine Anion-Based Ionic Liquid at Atmospheric Pressure

Lele Li, Jiayi Jin, Wanyao Hu, Jiayi Huang, and Qi Feng*

*Department of Science Education, Zhejiang International Studies University, No. 299, Liuhe Road, Zhejiang International Studies University, Hangzhou, Zhejiang, China

Abstract

Ionic liquids are widely used in the capture and utilization of CO2, and achieving efficient chemical conversion of CO2 under atmospheric pressure remains a challenging research topic. In this paper, 2-hydroxypyridine anion-based ionic liquids, which were easy to prepare, were used to synthesize quinazoline-2,4(1H,3H)-diones from 2-aminobenzonitriles and CO2 at atmospheric pressure. The reaction sequence worked well for 4-substituted substrates, but the effect was poor for 3-substituted substrates, possibly due to steric hindrance. The CO2 absorption experiment and 13C NMR analysis show that [Ch][2-OP]-CO2 complex is the actual catalyst for this reaction. This method has moderate to excellent yields for catalytic conversion of various 4-substituted 2-aminobenzonitriles with electron withdrawing and electron donating groups, providing a new way for chemical conversion and utilization of CO2.

■ An Efficient Route for the Synthesis of 2-Arylbenzothiazoles in an Ionic Liquid, Using Ultrasound Irradiation

Xiaofeng Yu,* Xiaorui Duan, Tao Wang, and Feng Wang

*School of Materials and Chemical Engineering, Bengbu University, 1866 Caoshan road Bengbu city, 233000, China

Abstract

The condensation of 2-aminothiophenol and aromatic aldehydes promoted by an ionic liquid of [n-HexylNEt3][HSO4] results 2-arylbenzothiazoles in high yields under ultrasound irradiation.

■ A Convenient One-Pot Synthesis of Novel 1,4-Dihydro-1,2-Benzoxaphosphinino[4,3-C]Pyrazoles

Tarik E. Ali* and Mohammed A. Assiri

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo, Egypt

Abstract

We have synthesized novel examples of 1,2-benzoxaphosphinino- [4,3-c]pyrazoles in one-pot. The methodology depends on the cyclization of 5-(2-hydroxyphenyl)-1-phenyl-1H-pyrazole with different examples of phosphorus halides and sulfides. The possible reaction mechanisms of the formation of these products were displayed and discussed. The isolated products were established by elemental analyses and spectral tools.

■ Large-Scale Synthesis of the Key Intermediates of Tetrahydropyran Derivatives under Flow Conditions

Keitaro Umeno, Hiroshi Yamaguchi, Tatsuya Teshigawara, Yoko Yasuno, and Tohru Oishi*

*Department of Chemistry, Faculty of Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan

Abstract

An efficient method under continuous flow conditions was developed for successive methylation and DIBALH reduction of a ketoester giving a key intermediate for synthesizing a tetrahydropyran derivative. This method enabled large-scale synthesis of the intermediate at room temperature with safety quenching of the reaction mixture.