HETEROCYCLES

■ Contents

■ Recent Achievements in the Synthesis of Heterocyclic Compounds by Phthalhydrazide-Based Multicomponent Reactions

Ghodsi Mohammadi Ziarani,* Negar Jamasbi, and Fatemeh Mohajer

*Department of Chemistry, Faculty of Physic and Chemistry, Alzahra University, Tehran, Iran. P. O. Box 1993893973

Abstract

Phthalhydrazide is one of the useful starting material toward the synthesis of heterocyclic compounds, and considered as a valuable structural unit in organic synthesis due to its significant pharmacological and biological activities. There are many multicomponent reactions using phthalhydrazide under different conditions. This review article aims to give an overview of recent applications of phthalhydrazide in the multicomponent reactions during the period of 2006 to 2021.

■ Synthesis and Structure−Activity Relationship Study of Intervenolin, an Antitumor and Anti-Helicobacter pylori Quinolone Natural Product

Takumi Watanabe*

*Institute of Microbial Chemistry, Tokyo (BIKAKEN), 3-14-23 Kamiosaki Shinagawa-ku, Tokyo 141-0021, Japan

Abstract

This review article overviews the chemistry and biology of intervenolin, a quinolone natural product bearing unusual substituents. Intervenolin was isolated as a modulator of tumor–stroma interactions, communication between tumor cells and surrounding normal cells to regulate tumor-associated events including proliferation. The synthesis of intervenolin by the author employs thiocyanate–isothiocyanate rearrangement and Suzuki–Miyaura cross coupling as key reactions, which was utilized in structure–activity relationship studies. The SAR studies generated analogs that are effective in vivo. Moreover, several intervenolin and analogs also showed anti-Helicobacter pylori activity. Mechanistic aspects of these biological activities, and synthetic study on structurally related natural products by Spring and co-workers are also discussed.

■ A Long-Wavelength Emission Fiuorescent Probe Based on TCF Derivatives for High-Sensitivity Detection of Hg2+

Yuan Sun, Keli Zhong, Lijun Tang,* and Xiaomei Yan*

*College of Chemistry and Materials Engineering, Bohai University, Jinzhou, 121013, China

Abstract

A new fluorescent probe 1 that derived from 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) has been developed. Probe 1 displays selective recognition toward Hg2+ in MeOH/Tris (1:1, v/v, Tris 20 mM, pH = 7.4) solution through fluorescence turn on behavior. The Hg2+ sensing mechanism underwent Hg2+-triggered removal of thiocarbonyl moiety of probe 1, which resulting in releasing of the highly emissive compound 2. The Hg2+ recognition process holds some advantages including rapid response (<3 min), low detection limit (1.06 nM), and a large Stokes shift (160 nm). Cell imaging studies showed that probe 1 has membrane permeability and low toxicity to cells, and can be used to detect Hg2+ in living cells.

■ Design and One-Pot Synthesis of Some New [3,5-Di(4’,5’-diphenyl-2’-substituted)-1H-imidazol-1-yl)]-1H-1,2,4-triazole Derivatives: in silico ADMET and Docking Study, Antibacterial and Antifungal Activities Evaluation

Nadia Hadhoum,* Fatima Zohra Hadjadj-Aoul, Smain Hocine, Souhila Bouaziz-Terrachet, Amar Abdoun, Nacera Seklaoui, Fella Boubrit, Wissem Abderrahim, and Lamine Redouane Mekacher

*Department of Pharmacie, University Mouloud mammeri, Tizi Ouzou, Algeria

Abstract

In this paper, a new series of some [3,5-di(4’,5’-diphenyl-2’- substituted)-1H-imidazol-1-yl)]-1H-1,2,4-triazole derivatives (C1-C9) were efficiently synthesized by a one-pot three component reaction via a coupling of benzil, aldehydes and 3,5-diamino-1,2,4-triazole and using ceric ammonium nitrate as a catalyst. The structures of the newly compounds were investigated by IR, 1H NMR, 13C NMR and UV-visible spectroscopy. The in vitro antibacterial and antifungal activities showed that the C9 is the most active compound. The C9 docking study revealed the best mode of binding in the active site of the cytochrome P450 lanosterol 14α-demethylase. All the synthesized compounds were predicted as non-carcinogens and demonstrated acceptable pharmacokinetic profile in blood brain barrier (BBB) and human intestinal absorption (HIA).

■ Four-Component Synthesis of Functionalized 1,3,4-Oxadiazole Derivatives Bearing the 2-Amino benzothiazole Moiety

Milad Bazaz Rastkar, Bita Mohtat,* Gholam Bagheri Marandi, and Hoorieh Djahaniani

*Department of Chemistry, School of Sciences, Islamic Azad University Karaj Branch, Moazen St., Karaj 31485-313, Iran

Abstract

A one-pot sixteen derivatives of N-((5-(aryl)-4H-pyrazol-3-yl)(aryl)methyl)benzo[d]thiazol-2-amine (5a–p) were synthesized from 2-aminobezothiazole, aromatic aldehyde, N-isocyaniminotriphenylphosphorane on reaction with aryl carboxylic acid derivatives under a catalyst-free condition in CH2Cl2 by a Ugi-4CR/aza-Wittig cyclization at room temperature in fairly good yields. The newly synthesized compounds were confirmed and deduced based on IR, 1H NMR, 13C NMR, and mass spectroscopy, and elemental analysis.

■ A Facile, Efficient and Catalyst Free Synthesis of Imidazole, Tetrazole and Pyrimidine Combined Moiety as Potential Antimicrobial and Antitubercular Agents

Nayankumar M. Panchani and Hitendrakumar S. Joshi*

*Department of Chemistry, Saurashtra University, Saurashtra University, Rajkot-360 005, India

Abstract

The tetrazole fused pyrimidine system possesses a broad spectrum of biological activities. So, we have synthesized 5-(substitutedphenyl)-7-(1H- imidazol-4-yl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine derivatives (5a-n) by reaction of chalcones with 5-aminotetrazole without catalyst in appropriate solvent. The structural elucidation of these compounds is based on MS, IR, 1H-NMR and 13C-NMR spectral data. The in vitro anti-microbial activity was investigated against Gram-positive and Gram-negative bacterial and fungal strains. It was found that the compounds 5a, 5b, 5c, 5d, 5e showed significant activities against tested organisms as compared to standard drugs (Ampicillin and Griseofulvin) while compounds 5a, 5c, 5i, and 5k showed good percentage of average inhibition in the dormant and active stage of tuberculosis.

■ When Hydrazonoyl Chlorides Meet Allenes: a Site- and Regio-Selective Copper(I)-Catalysed Approach to 5-Substituted Pyrazoles

Giorgio Molteni,* Stefano Baroni, Marco Manenti, and Alessandra Silvani

*Department of Chemistry, University of Milano, Via Golgi 19, 20133 Milano, Italy

Abstract

The reaction between hydrazonoyl chlorides and monosubstituted allenes in the presence of catalytic amounts of copper(I) chloride gives 1,3,5-substituted pyrazoles under mild conditions and very short reaction times. This site- and regioselective process involves first the complexation of copper(I) on the external double bond of the allene moiety, followed by nucleophilic attack on the central carbon atom of the so-formed copper(I)-complexed allene by the terminal nitrogen of the hydrazonoyl chloride. Subsequent ring closure to thetarget pyrazole ring is possible in the presence of electron-attracting groups on theallene moiety. A catalytic cycle has been proposed on the basis of the experimental results.

■ Microwave-Assisted Synthesis of 2-Aminothiophene Derivatives via Improved Gewald Reactions

Bankang Ruan, Zhiyan Zhang, Lei Huang, Chao Xu, and Luolan Li*

*Shizhen College of Guizhou University of Traditional Chinese Medicine, Shizhen College, Guiyang, China

Abstract

In this paper, a new and efficient method was developed to prepare 2-aminothiophene derivatives through improved Gewald reaction. Thirty-one final products were synthesized under microwave radiation for 30 min with 57%-95% isolated yield. All the products were could be used as building blocks in drug discovery.

■ A Convenient Synthesis of Novel 6-Aryl-5-phenyl-5-oxido-6,7-dihydro[1,3,4,2]thiadiazaphospholo[5,4-c][1,2,4,5]triazaphosphinines

Tarik E. Ali,* Mohammed A. Assiri, Abdullah Y. Alzahrani, and Mohamed A. Salem

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

Abstract

A convenient method for design of novel 6-aryl-5-phenyl-5-oxido-6,7- dihydro[1,3,4,2]thiadiazaphospholo[5,4-c][1,2,4,5]triazaphosphinines was achieved. This method depended on three-component reaction of 5-hydrazino-1,3,4,2-thiadiaza- phosphole with aromatic aldehydes and phenyldichlorophosphine in dry THF. The methodology was easy, efficient, catalyst-free and good synthetic procedure.