HETEROCYCLES

■ Contents

■ Advances on Catalytic Approaches towards the Synthesis of Quinoline Derivatives Using Povarov Reaction

Kamal Kant, Sourav Banerjee, Chandresh K. Patel, Sangita Kalita, Reetu Reetu, Priyadarshini Naik, Nayyef Aljaar, and Chandi C. Malakar*

*Department of Chemistry, National Institute of Technology Manipur, Imphal-795004, India

Abstract

The aza-Diels-Alder reaction is a [4+2] cycloaddition, involving the insertion of nitrogen atom into dienes or dienophiles. A series of biologically and pharmaceutically active essential heterocycles have been developed as a result of this approach. This method witnessed as a powerful tool for the construction of a diverse range of biological active quinoline scaffolds and other nitrogen containing heterocyclic compounds due to its operational modesty, high atom economy, regio- and stereoselectivity. The present report focuses on the advancement of aza-Diels-Alder reaction for the synthesis of optically active and inactive quinoline derivatives.

■ New C19-Diterpeniod Alkaloids from Aconitum novoluridum

Peixin Deng, Yan Xiao, Mengyi Deng, Shuai Huang, Lin Chen, Jiang Xie, and Xianli Zhou*

*School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, P.R. China

Abstract

Four new C19-diterpenoid alkaloids novolunines D–F (1–3) and 8-O-ethylbrevicanine C (4), were isolated from the root of Aconitum novoluridum. The structures of four new alkaloids were established on the basis of spectra data (HR-ESI-MS, 1D- and 2D-NMR). The anti-inflammatory activity of isolated alkaloids was also carried out.

■ Synthesis and Biological Assessment of Novel Heterocyclic Nucleoside Analogues Using Microwave-Assisted Hantzsch Reaction

Abdelaaziz Ouahrouch,* Jamal Krim, and Moha Taourirte

*Laboratory of Biotechnology, Materials and Environment, Faculty of Sciences, Ibn Zohr University, Agadir 80000, Morocco

Abstract

This paper reports a one-pot synthesis of 5-(1,4-dihydropyridyl) derivatives of 2’-deoxyuridines using Hantzsch condensation of 5-formyl-2’-deoxyuridine and NH4OAc with diverse β-dicarbonyl compounds under solvent-free microwave irradiation conditions. The synthesized compounds were evaluated for their antiviral activities against human rhinovirus (HRV) and hepatitis C virus (HCV), as well as antibacterial activities against a series of Gram-positive and Gram-negative bacteria. The products carrying an unsymmetrical 1,4-dihydropyridyl moiety showed excellent antiviral activity against HCV.

■ An Efficient Ton Scale Process of Chlorfluazuron

Kai Yin,* Xin Yin, Hao Wu, Jiang Yu, Youlan He, Xin Yang, Minmin Gu, Wenliang Wu, Jiangyu Yang, and Yiwei Zhang*

*School of Chemistry and Chemical Engineering, Southeast University, SuYuan road No.79 in Nanjing 211189, China

Abstract

An efficient and novel synthetic route of chlorfluazuron (1) on a ton scale has been developed, from the commercially available chemicals 3,5-dichloronitrobenzene, 2,3-dichloro-5-(trifluoromethyl)pyridine, and 2,6-difluorobenzamide. The key intermediate, 4-amino-2,6-dichlorophenol (2), was synthesized in one step by 3,5-dichloronitrobenzene with 78.1% yield and 99.5% purity. At the same time, 3,5-dichloroaniline (15), a co-product with great market demand, was also obtained with 20.9% yield and 99.2% purity. Chlorfluazuron (1) was obtained from 4-amino-2,6-dichlorophenol (2) in 91.9% yield over two steps and 99.2% purity. Compared with the original process route, the new synthetic route has the advantages of fewer reaction steps, higher overall yield, less process safety hazard and environmental impact.

■ Functionalization of Phenothiazine Derivatives by Ammonium Bridge

Hideki Hayashi,* Tadashi Ogawa, Hiroshi Seno, and Take-aki Koizumi

*Nagoya Municipal Industrial Research Institute, 3-4-41, Rokuban, Atsuta-ku, Nagoya 456-0058

Abstract

Ammonium-bridged bis(promazine) type compounds (BA-PF6: [Y-N+Me2-CH2-R-CH2-N+Me2-Y]2+[PF6-]2, Y = 3-(phenothiazin-10-yl)propyl, 3-(5-oxophenothiazin-10-yl)propyl, 3-(2-chlorophenothiazin-10-yl)propyl, and 3-(5-oxo-2-chlorophenothiazin-10-yl)propyl; R = octane-1,8-diyl, 1,4-phenylene, biphenylene-4,4’-diyl, and 2,2'-bipyridine-4,4’-diyl) were prepared and the effects of the central R unit and side Y unit were investigated. The products’ optical and electrochemical properties showed the effect of the central and side unit, suggesting that the products had two independent functional groups in one molecule. X-Ray crystallographic analyses indicated that the spatial placement of the compounds was controlled by the central R unit, which behaves as a spacer without changing the properties of the molecules.

■ N-Alkylation of Azoles with Enones Assisted by P(III) or Fe2O3-Nanoparticles as Recyclable Catalyst

Elangbam Pinky Devi, Saibabu Polina, Kamal Kant, Arup K. Kabi, Nabil Al-Zaqri, Nayyef Aljaar, and Chandi C. Malakar*

*Department of Chemistry, National Institute of Technology Manipur, Langol, Imphal-795004, Manipur, India

Abstract

Hexamethylphosphorous triamide (HMPT)-assisted and Fe2O3-nanoparticles (NPs) catalysed approaches towards the formation of C-N bond is described by the reaction between azoles and enone-compounds. The transformations were accomplished under mild conditions at temperatures 25 °C and 50 °C respectively. The efficacy and robustness of the reaction conditions can be envisioned by regioselective construction of N-heterocyclic scaffolds embedded with cycloalkyl residue. The established reaction conditions were found competent over a series of enones and azole derivatives to furnish the desired molecules in high yields ranging from 52-86% under P(III)-mediated conditions and 67-86% under the influences of Fe2O3-NPs as recyclable catalyst. It was observed that the catalyst can be recycled up to six times with good yields of the product.

■ Synthesis of 2-Anilino-2,4,4,6,6-pentachlorocyclotriphosphazenes (N3P3Cl5(NAr(R)))

Manabu Kuroboshi,* Ryota Takahashi, and Hideo Tanaka

*Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka 3-1-1, Kita-ku, Okayama, Japan

Abstract

Hexachlorocyclotriphosphazene (HCCP, N3P3Cl6, 1) was treated with anilines in THF at 0 ºC to give a corresponding mono-substituted 2-anilino-2,4,4,6,6-pentachlorocyclotriphosphazenes (N3P3Cl5(NAr(R)), 2) in good to moderate yield. Multi-substituted products N3P3Cl6-n(NAr(R))n (n ≥ 2)) were not detected in 31P NMR spectra of the reaction mixture.

■ Design, Synthesis, and Molecular Docking Studies of Chroman-4-one Linked Thiosemicarbazide Derivatives as Inhibitors of KatG and Anti-Mycobacterium tuberculosis Agents

Lei Wang, Hong-Mei Dong, Xin Zhao, and Zai-Chang Yang*

*College of Pharmacy, Guizhou University, Guiyang 550025, PR China

Abstract

Twenty compounds were designed as ligands for molecular docking with Mtb KatG, and 13 compounds with high scoring values were selected for synthesis. In vitro antimicrobial susceptibility tests have shown that all the 13 compounds have anti-Mtb activity (MIC = 1-32 μg/mL). Among the 13 compounds, compound 4g showed the strongest anti-Mtb activity with an MIC of 1 μg/mL. Therefore, the mechanism of action of compound 4g was preliminarily investigated by molecular docking, enzyme inhibition test, ROS assay, and time-killing curve. The results indicated that the anti-Mycobacterium tuberculosis effect of compound 4g may be related to its inhibition of KatG enzyme. In summary, this study provides a new idea for the development of novel anti-Mtb drugs.