Current Organic Synthesis - Volume 21, Issue 4, 2024

Ketemines represent an interesting class of organic intermediates that has undergone a regrowth as a consequence of recent extensions of copper catalyzed azide alkyne cycloaddition (Cu- AAC) to other synthetic fields. This review summarizes the most recent generation methods of ketimines from CuAAC reaction, highlighting chemical properties focused on the synthesis of cyclic compounds, among others, affording a general outlook towards the development of new biologically active compounds.

Compounds containing triazole have many significant applications in the dye and ink industry, corrosion inhibitors, polymers, and pharmaceutical industries. These compounds possess many antimicrobial, antioxidant, anticancer, antiviral, anti-HIV, antitubercular, and anticancer activities. Several synthetic methods have been reported for reducing time, minimizing synthetic steps, and utilizing less hazardous and toxic solvents and reagents to improve the yield of triazoles and their analogues synthesis. Among the improvement in methods, green approaches towards triazole forming biologically active compounds, especially anticancer compounds, would be very important for pharmaceutical industries as well as global research community. In this article, we have reviewed the last five years of green chemistry approaches on click reaction between alkyl azide and alkynes to install 1,2,3-triazole moiety in natural products and synthetic drug-like molecules, such as in colchicine, flavanone cardanol, bisphosphonates, thiabendazoles, piperazine, prostanoid, flavonoid, quinoxalines, C-azanucleoside, dibenzylamine, and aryl-azotriazole. The cytotoxicity of triazole hybrid analogues was evaluated against a panel of cancer cell lines, including multidrug-resistant cell lines.

Over the last two decades, the design and development of fluorescent chemosensors for the targeted detection of Heavy Transition-metal (HTM) ions, anions, and biological analytes, have drawn much interest. Since the introduction of click chemistry in 2001, triazole moieties have become an increasingly prominent theme in chemosensors. Triazoles generated via click reactions are crucial for sensing various ions and biological analytes. Recently, the number of studies in the field of pyrene appendant triazole moieties has risen dramatically, with more sophisticated and reliable triazole-containing chemosensors for various analytes of interest described. This tutorial review provides a general overview of pyrene appendant-triazole-based chemosensors that can detect a variety of metal cations, anions, and neutral analytes by using modular click-derived triazoles.

This article covers the triazole-linked nucleic acids where the triazole linkage (TL) replaces the natural phosphate backbone. The replacement is done at either a few selected linkages or all the phosphate linkages. Two triazole linkages, the four-atom TL1 and the six-atom TL2, have been discussed in detail. These triazole-modified oligonucleotides have found a wide range of applications, from therapeutics to synthetic biology. For example, the triazole-linked oligonucleotides have been used in the antisense oligonucleotide (ASO), small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology as therapeutic agents. Due to the ease of the synthesis and a wide range of biocompatibility, the triazole linkage TL2 has been used to assemble a functional 300-mer DNA from alkyne- and azide-functionalized 100-mer oligonucleotides as well as an epigenetically modified variant of a 335 base-pair gene from ten short oligonucleotides. These outcomes highlight the potential of triazole-linked nucleic acids and open the doors for other TL designs and artificial backbones to fully exploit the vast potential of artificial nucleic acids in therapeutics, synthetic biology and biotechnology.

Cu(I)-catalyzed azide−alkyne 1,3-dipolar cycloaddition (CuAAC) - commonly known as the “click reaction” - serves as the most effective and highly reliable tool for facile construction of simple to complex designs at the molecular level. It relates to the formation of carbon heteroatomic systems by joining or clicking small molecular pieces together with the help of various organic reactions such as cycloaddition, conjugate addition, ring-opening, etc. Such dynamic strategy results in the generation of triazole and its derivatives from azides and alkynes with three nitrogen atoms in the five-membered aromatic azole ring that often forms gel-assembled structures having gelating properties. These scaffolds have led to prominent applications in designing advanced soft materials, 3D printing, ion sensing, drug delivery, photonics, separation, and purification. In this review, we mainly emphasize the different mechanistic aspects of triazole formation, which includes the synthesis of sugar-based and non-sugar-based triazoles, and their gel applications reported in the literature for the past ten years, as well as the upcoming scope in different branches of applied sciences.

Immediately after the invention of ‘Click Chemistry’ in 2002, the regioselective 1,2,3- triazole scaffolds resulted from respective organic azides and terminal alkynes under Cu(I) catalysis have been well recognized as the functional heterocyclic core at the centre of modern organic chemistry, medicinal chemistry, and material sciences. This CuAAC reaction has several notable features including excellent regioselectivity, high-to-excellent yields, easy to execute, short reaction time, modular in nature, mild condition, readily available starting materials, etc. Moreover, the resulting regioselective triazoles can serve as amide bond isosteres, a privileged functional group in drug discovery and development. More than hundreds of reviews had been devoted to the ‘Click Chemistry’ in special reference to 1,4-disubstituted triazoles, while only little efforts were made for an opposite regioisomer i.e., 1,5-disubstituted triazole. Herein, we have presented various classical approaches for an expeditious synthesis of a wide range of biologically relevant 1,5- disubstituted 1,2,3-triazole analogues. The syntheses of such a class of diversly functionalized triazoles have emerged as a crucial investigation in the domain of chemistry and biology. This tutorial review covers the literature assessment on the development of various synthetic protocols for the functionalized 1,5-disubstituted triazoles reported during the last 12 years.

Aims: Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells. Background: Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents. Objectives: Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their antiproliferative activity. Methods: First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells. Results: Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom. Conclusion: Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity.

Introduction: A novel series of chromen-3-yl-pyridine moieties were synthesized. IR, NMR, and MS spectroscopy were used to confirm the structure of these novel compounds and study antitumor activity of these compounds. The structure-activity relationship investigation demonstrated that 2,4-diamino- 5-(3-methoxyphenyl)-7-(2-oxo-2H-chromen-3-yl)-1,8-naphthyridine-3-carbonitrile (16), naphthyridine- 3-carbonitrile derivatives 17, 18 and pyrido[2,3-d]pyrimidine derivative 12 were found to be more effective, while compounds 5a,b, 9c, 11, 13 and 14 showed moderate activity for antitumor activities. Objectives: The objective was to design a series of new chromen-3-yl-pyridine and pyrido[2,3-d]pyrimidine derivatives and study the antitumor of these compounds. Materials and Methods: The condensation reaction of 3-acetyl-2H-chromen-2-one with 3-methoxy benzaldehyde and malononitrile or ethyl cyanoacetate in the presence of ammonium acetate and acetic acid under reflux to give the corresponding chromen-3-yl pyridine-3-carbonitrile derivatives. Results: In this study, the antitumor activity of the synthesized compounds chromen-3-yl-pyridine derivatives has been determined for the broad spectrum of cytotoxic activity toward the investigated three cell lines and 5-Fluorouracil, as reference drugs. Conclusion: A series of new chromen-3-yl-pyridine and pyrido[2,3-d]pyrimidine derivatives were synthesized in this work. All compounds were evaluated for cytotoxic activity.