HETEROCYCLES

■ Contents

■ The Fascinating Chemistry of Mesoionic 4-Trifluoroacetyl-1,3-oxazolium-5-olates and Related Compounds

Ryosuke Saijo and Masami Kawase*

*Faculty of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan

Abstract

This review illustrates the unexpected and unique transformation of mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates (4-TFMK-münchnones) on treatment with different nucleophiles. A trifluoromethyl group that cannot be synthesized by the usual methods is incorporated in the products. The research discussed in this review is focused on the rich chemistry of 4-TFMK-münchnones. In particular, we highlight the recent advances in their use in contemporary organic synthesis, primarily of trifluoromethyl-substituted heterocycles. The chemistry of related mesoionic compounds is also discussed.

■ Synthetic Approaches toward Certain Structurally Related Antimicrobial Thiazole Derivatives (2010-2020)

Abdelfattah Hassan, Heba A. Hassan, Dalia Abdelhamid, and Gamal El-Din A. Abuo-Rahma*

*Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia, Egypt & Pharmaceutical Chemistry Department, Faculty of Pharmacy, Deraya University, New Minia, Minia, Egypt

Abstract

In the present literature review, we comprehensively discuss different methods of synthesis of published antimicrobial thiazole derivatives in the last decade mainly those which showed antibacterial, antimycobacterial and/or antifungal activity. Owing to the great diversity of thiazole-derived antimicrobial agents, we organized most of them chemically in stipulated classes. In each class, we mentioned common methods of thiazole ring closure and indicated antimicrobial activity of the most active derivatives in clear and simple way.

■ Synthesis, Antimicrobial and Antitumor Study of New Pyrido[2,1-a]isoquinolines via Isoquinoline-1-acetonitrile

Mohamed A. M. Teleb, Hamdi M. Hassaneen,* Hyam A. Abdelhadi, Yara N. Laboud, and Fatma M. Saleh

*Department of chemistry, Faculty of science, University of Cairo, Giza 12613, Egypt

Abstract

Refluxing of enaminonitrile 3 with arylacetonitriles 2 in ethanol in the presence of piperidine afforded 4H-pyrido[2,1-a]isoquinoline-1-carbonitriles 6. Refluxing of 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile 1 with ethyl 3-aryl-2-cyanoacrylates 9 in acetonitrile in the presence of piperidine gave the corresponding 4H-pyrido[2,1-a]isoquinoline-1,3-dicarbonitriles 13. All the new synthesized compounds were identified by elemental analysis and spectral data. Cytotoxic assay was investigated for in vitro antitumor screening against MCF7, HepG2 and HCT-116 cell lines. Molecular docking using Mcule.com. software was carried out for the most potent compound 6b. The results are compared with doxorubicin standard anticancer drug. Antimicrobial activities were investigated, and all compounds revealed no antimicrobial activities against all tested strains except compounds 13b and 13e.

■ Natural Osthole-Based Ester Derivatives as Potential Fungicidal Agents: Design, Synthesis and Quantitative Structure-Activity Relationship (QSAR)

Yong-Ling Wu,* Yong Yan, Tin-Tin Pan, and Dou-dou Wang

*College of Biology Pharmacy and Food Engineering, Shangluo University, Shangluo 726000, Shaanxi, China

Abstract

Turning potential natural products into value-added fungicides is a bioactivity-guided mixed synthesis method. Thirty-two derivatives were designed and synthesized to improve the potential use of the osthole, a natural coumarin pharmacophore. Compound Os14 with 3-ClPh showed a high in vitro and in vivo antifungal activity than other derivatives. The preliminary structure-activity relationships (SARs) demonstrated that compounds with a short aliphatic chain or electron-withdrawing groups on phenyl ring would have more desirable potency. Meanwhile, the quantitative structure-activity relationship (QSAR) model (R2 = 0.928, F = 83.54, S2 = 0.0042) were performed using Gaussian and CODESSA software with optimal conformers and heuristic regression analysis, which revealed a correlation of antifungal activity and molecular structures. Thus, these results laid the foundation for further design of improved crop-protection agents based on osthole scaffold.

■ Application of a New 4'‎‎‒‎‎‎Functionalized 2,2': 6',2''‎‎‒‎‎‎Terpyridine Ruthenium(II) Complex as a Sensitizer in Dye Sensitized Solar Cells

Azam Nasirian,* Valiollah Mirkhani,* Majid Moghadam,* Shahram Tangestaninejad, and Iraj Mohammadpoor-Baltork

*Department of Chemistry, Catalysis Division, University of Isfahan, 81746‎‎‒‎‎‎73441, Isfahan, Iran

Abstract

In this work, the synthesis of a Ru(II) complex derived from 4'‎‎‒‎‎‎functionalized‎‎‒‎‎‎2,2':6',2''‎‎‒‎‎‎terpyridine ligand was described and the its spectral property of this complex was investigated. We synthesized this ligand and used that for the synthesis of Ru(II) complex. Ligand and complex were characterized by UV–vis, FT‎‎‒‎‎‎IR, ESI-MS, CHN analysis and NMR methods. After synthesis and characterization of this complex, we investigated the application of this complex as a photosensitizer in manufacturing of dye-sensitized solar cells. A sandwich cell was prepared using the dye anchored TiO2 film as a working electrode and a second conducting glass coated with chemically deposited platinum as a counter electrode. The application of this complex in a dye-sensitized nanocrystalline TiO2 solar cell has demonstrated a short-circuit current density of 12.84 mA, with an open circuit potential of 0.69 V. The total efficiency of this dye-sensitized solar cell with this complex was 4.97%.

■ Organocatalyzed Three-Component Synthesis of Isoxazol-5(4H)-ones under Aqueous Conditions

Zeinab Faramarzi and Hamzeh Kiyani*

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

Abstract

The three-component cyclocondensation was performed using various frequently available aryl/heteroaryl aldehydes, hydroxylamine hydrochloride, and β-ketoesters in water as a green reaction medium at 80 °C. In this reaction, isoxazol-5(4H)-ones were obtained in the presence of 2-aminopyridine as an efficient and low-cost organocatalyst. The present methodology offers sustainable approach with appreciable yields of the desired heterocycles. This procedure has expectant features, including shorter reaction times, easy separation of pure products, avoiding the hazardous organic solvents, simplicity experimental procedure, operationally simple, and eco-friendly. The heterocyclic structures were characterized using physical properties and analysis of spectral data.

■ Concise Synthesis of Eutigoside C

Shiqiang Yan, Yueyue Zhu, Lisha Wu, Liqun Chi,* and Wei Zhang*

*School of Pharmacy, Fudan University, Shanghai, 201203, China

Abstract

Eutigoside C, a new glucoside with a variety of biological activities, was synthesized via regioselective Me2SnCl2-catalyzed O-6 acylation and mild oxidation strategy. Through this route, eutigoside C was obtained from inexpensive starting materials in a linear 5-step sequence with an overall yield of 35.2%.

■ New and Practical Synthesis of GS-441524, the Key Intermediate of Remdesivir

Bo Li, Han Wang,* Cong Sun, Sheng Lu, LinLin Kang, and Shun Jiang

*College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China

Abstract

A new and practical synthesis of GS-441524, the key intermediate for remdesivir, is developed. 4-Amino-7-iodopyrrolo[2,1-f][1,2,4]triazine is protected by DMF-DMA, and reacted with 2,3,5-tri-O-benzyl-D-ribonolactone to give the product in 61% isolated yield. The next cyanation and debenzylation are carried out at −30 °C successively in 67% yield over two steps with >99% purity (HPLC). Purification methods of the intermediates and the final product involved in the route are developed.

■ New Synthesis of Abexinostat

Xiaolei Zhu, Han Wang,* Sheng Lu, Cong Sun, Zhiyong Xu, and Jingli Xu

*College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China

Abstract

A practical and convergent synthetic route of abexinostat was developed successfully. The key intermediate 3-((dimethylamino)methyl)- benzofuran-2-carboxylic acid (16) was prepared from 1-(2-hydroxyphenyl)ethan-1-one in 76.6% yield over 4 steps. Methyl 4-(2-aminoethoxy)benzoate hydrochloride (20) was synthesized from methyl 4-hydroxybenzoate in 97.0% yield over 2 steps. Abexinostat was obtained from 16 and 20 in 72.4% yield over 2 steps and 98.7% purity. Purification methods of the intermediates and the final product involved in the route were developed.

■ Three New Anti-Rotavirus Chromeno[3,2-c]pyridines from the Whole Plant of Thalictrum scabrifolium

Qiu-Fen Hu, Fan Wu, Tao Zhou, Min Zhou, Ya-Ning Zhu, Bing-Biao Cai, Ming-Xin Liu, Man-Fei Li, Guang-Yu Yang,* and Yin-Ke Li*

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, Yunnan Minzu University, Kunming 60500, P. R. China

Abstract

Three new chromeno[3,2-c]pyridines (1-3) were isolated from the whole plants of Thalictrum scabrifolium. Their structures were elucidated by spectroscopic methods, including extensive 1H, 13C, and 2D-NMR techniques. Compounds 1-3 were also tested for their anti-rotavirus activity, and they exhibited potent anti-rotavirus activity with therapeutic index (TI) valves of 23.7, 18.3, and 19.2 respectively.