Click Chemistry: The Triazole Ring as a Privileged Peptidomimetic Scaffold

2014 ◽  
pp. 99-121 ◽  
Keyword(s):  
Click Chemistry ◽  
Triazole Ring

scholarly journals SYNTHESIS OF A 1,2,3-TRIAZOLE-CONTAINING MACROCYCLE BASED ON THE "CLICK CHEMISTRY" REACTION AND ANALYSIS OF ITS PLANAR CHIRALITY USING NMR AND DFT CALCULATIONS

2020 ◽  
pp. 55-61
Author(s):  
H. Yampolska ◽  
S. Kharchenko ◽  
A. Kozytskyi ◽  
A. Kyrylchuk ◽  
Z. Voitenko ◽  
...  
Keyword(s):  
Dft Calculations ◽  
Click Chemistry ◽  
Protein Interactions ◽  
Variable Temperature ◽  
Triazole Ring ◽  
Building Blocks ◽  
Ring Closure ◽  
Amide Bond ◽  
High Yield ◽  
Planar Chirality

Macrocycles represent previously unexplored promising drug candidates, that can be useful for treating protein-protein interactions. Atropoisomerism is an inherent feature of the natural macrocyclic peptides that is significant for their activity and selectivity, and, therefore, should be introduced into newly synthesized macrocycles. Synthesis of the libraries of artificial macrocycles faces many challenges due to their structure and size. Herein we report on the preparation of a 16-membered macrocycle containing 1,2,3-triazole ring, spiro-piperidine, and phenyl moieties, as well as a chiral carbon atom. Our approach to the macrocycle was inspired by the "build/couple/pair" (B/C/P) strategy, a part of diversity-oriented synthesis methodology. We have employed readily accessible starting materials and robust synthetic procedures which allowed us to obtain the target macrocycle in a high yield. Standard methods of amide bond formation were used for the coupling of macrocycle building blocks. Click chemistry azide-alkyne cycloaddition was exploited at the final ring closure step. The assignment of signals in 1H and 13C NMR spectra of the macrocycle was performed using a series of 2D NMR techniques. The macrocycle displayed planar chirality, which, in a combination with a stereocenter with the known configuration, was sufficient to propose possible structures of diastereomers. The diastereomers could differ by the relative position of triazole ring. Their racemization could occur through a "rope skipping" motion involving the cyclic chain crossing the plane of 1,2,3-triazole ring. The supposed structures of diastereomers were corroborated by means of a various NMR spectroscopy techniques and DFT calculations. Analysis of the amide NH chemical shift temperature coefficients coupled with the data on optimized geometries obtained by DFT convincingly demonstrated that the intramolecular hydrogen bonds play a major role in stabilization of the diastereomer structures. According to the variable temperature NMR experiment, the interconversion of two diastereomers did not occur even at heating up to 70 °C.

scholarly journals Microwave-Assisted Synthesis of Novel Bis-Flavone Dimers as New Anticancer Agents

2018 ◽  
Vol 16 (1) ◽  
pp. 66-75 ◽  
Author(s):  
Andrew McGown ◽  
Abby Ragazzon-Smith ◽  
John A. Hadfield ◽  
Herman Potgetier ◽  
Patricia A. Ragazzon
Keyword(s):  
Anticancer Activity ◽  
Click Chemistry ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Triazole Ring ◽  
Microwave Assisted Synthesis ◽  
Anticancer Properties ◽  
Microwave Assisted ◽  
Ic50 Values ◽  
High Yields

In this study, we describe a microwave-based click chemistry method used to prepare a family of novel bis-flavone dimers. The substituted 7-hydroxy and 4’-hydroxy flavonoids were linked through a triazole ring. The compounds were easily synthesized and purified in high yields. The bisflavonoids were tested on different cell lines including HCT116, HepG2, MCF7 and MOLT-4. Several analogues showed to have anticancer activity with IC50 values in the range of 20-60 μM. Flavonoids are known for their anticancer properties and this method provides the basis for new medicinal structures.

Using Sodium Hydride and Potassium Carbonate as Bases in Synthesis of Substituted 2-Amino-4-aryl-7-propargyloxy-4H-chromene-3-carbonitriles

2019 ◽  
Vol 16 (3) ◽  
pp. 423-430
Author(s):  
Nguyen D. Thanh ◽  
Do S. Hai ◽  
Vu T.N. Bich ◽  
Pham T.T. Hien ◽  
Nguyen T.K. Duyen ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Potassium Carbonate ◽  
Sodium Hydride ◽  
Triazole Ring ◽  
Biological Properties ◽  
Alkylation Reaction ◽  
Propargyl Bromide ◽  
Propargyl Ether ◽  
Ether Synthesis ◽  
Chromene Ring

Aims and Objective: 1-Alkynes are the important precursors for the CuAAC click chemistry. The hybrid of 1,2,3-triazole ring to the chromene ring and sugar moiety could bring some remarkable biological properties. Propargyl derivatives are usually used in the click chemistry. This article reported the synthesis of 2-amino-4-aryl-7-propargyloxy-4-aryl-4H-chromene-3-carbonitriles using propargyl bromide as alkylation agent and the use of potassium carbonate and sodium hydride as bases in the conversion of 2-amino-4-aryl-7- hydroxy-4-aryl-4H-chromene-3-carbonitriles into corresponding propargyl ethers in Williamson’s ether synthesis. Materials and Methods: The use of CTAB for the synthesis of benzylidene malononitriles and anhydrous potassium carbonate as a catalyst in absolute ethanol in the synthesis of 2-amino-7-hydroxy-4H-chromene-3- carbonitriles is an efficient and simple synthetic method. Propargyl ether compounds of these 4H-chromene-3- carbonitriles were obtained from the alkylation reaction by propargyl bromide. Two procedures were applied: K2CO3 as a base in acetone solvent (Procedure A) and NaH as a base in DMF solvent (Procedure B). The single-crystal X-ray structure of propargyl ether 5e has been studied. Results: The use of K2CO3 and NaH as bases in the Williamson’s ether synthesis from 2-amino-7-hydroxy-4Hchromene- 3-carbonitriles showed that Procedure B was the better route and gave ethers in the higher yields. 2- Amino-4-aryl-7-propargyloxy-4-aryl-4H-chromene-3-carbonitriles were obtained from corresponding 7- hydroxy-4H-chromene-3-carbonitriles. Yields of ethers 5a-i were 70−89% and 80−96%, respectively depending on the used procedures. Conclusion: The described methods are simple, clean and environmentally friendly alternatives for the preparation of 2-amino-4-aryl-7-hydroxy-4H-chromene-3-carbonitriles. The conditions for the transformation of these compounds into propargyl ethers include dried DMF as a solvent, NaH as a base and reaction time of 2 h at the room temperature. A series of 2-amino-4-aryl-7-hydroxy-4-aryl-4H-chromene-3-carbonitriles were obtained based on investigated reaction condition.

Phosphorescent Pt(ii) complexes bearing a monoanionic C^N^N luminophore and tunable ancillary ligands

2017 ◽  
Vol 46 (10) ◽  
pp. 3160-3169 ◽  
Author(s):  
Marian Hebenbrock ◽  
Linda Stegemann ◽  
Jutta Kösters ◽  
Nikos L. Doltsinis ◽  
Jens Müller ◽  
...  
Keyword(s):  
Excited State ◽  
Click Chemistry ◽  
Intermolecular Interactions ◽  
Triazole Ring ◽  
Ancillary Ligands

A new monoanionic pincer luminophore is presented, yielding phosphorescent Pt(ii) complexes bearing a neutral 1,2,3-triazole ring introduced via click chemistry. The overall charge, intermolecular interactions and excited state properties can be manipulated and controlled.

scholarly journals Recent Advances in Bioactive Flavonoid Hybrids Linked by 1,2,3-Triazole Ring Obtained by Click Chemistry

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 230
Author(s):  
Daniela Pereira ◽  
Madalena Pinto ◽  
Marta Correia-da-Silva ◽  
Honorina Cidade
Keyword(s):  
Click Chemistry ◽  
Mechanism Of Action ◽  
Biological Activities ◽  
Triazole Ring ◽  
Pharmacokinetic Profile ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Antifouling Activity ◽  
Sar Studies ◽  
Structure Activity

As a result of the biological activities of natural flavonoids, several synthetic strategies aiming to obtain analogues with improved potency and/or pharmacokinetic profile have been developed. Since the triazole ring has been associated with several biological activities and metabolic stability, hybridization with a 1,2,3-triazole ring has been increasingly reported over the last years. The feasible synthesis through copper (I) catalyzed azide-alkyne cycloaddition (CuAAC) has allowed the accomplishment of several hybrids. Since 2017, almost 700 flavonoid hybrids conjugated with 1,2,3-triazole, including chalcones, flavones, flavanones and flavonols, among others, with antitumor, antimicrobial, antidiabetic, neuroprotective, anti-inflammatory, antioxidant, and antifouling activity have been reported. This review compiles the biological activities recently described for these hybrids, highlighting the mechanism of action and structure–activity relationship (SAR) studies.

scholarly journals A novel route for preparing 5′ cap mimics and capped RNAs: phosphate-modified cap analogues obtained via click chemistry

2017 ◽  
Vol 8 (1) ◽  
pp. 260-267 ◽  
Author(s):  
Sylwia Walczak ◽  
Anna Nowicka ◽  
Dorota Kubacka ◽  
Kaja Fac ◽  
Przemyslaw Wanat ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Triazole Ring

A different approach for synthesizing 5′ cap mimics to yield a novel class of dinucleotide cap analogues containing a triazole ring within the oligophosphate chain.

Brownian motion retarded polymer-encapsulated liquid crystal droplets anchored over a patterned substrate via click chemistry

RSC Advances ◽  
2014 ◽  
Vol 4 (52) ◽  
pp. 27135-27139 ◽  
Author(s):  
Arun Prakash Upadhyay ◽  
Prasenjit Sadhukhan ◽  
Sudeshna Roy ◽  
Raj Ganesh S Pala ◽  
Sri Sivakumar
Keyword(s):  
Brownian Motion ◽  
Liquid Crystal ◽  
Click Chemistry ◽  
Triazole Ring ◽  
Patterned Substrate

Formation of a five-membered strong triazole ring to facilitate the highly stable anchoring of LC droplet encapsulated polymer capsules over a patterned substrate.

Click Chemistry Expedited Radiosynthesis: Sulfur [18F]fluoride Exchange of Aryl Fluorosulfates

2019 ◽  
Author(s):  
Qinheng Zheng ◽  
Hongtao Xu ◽  
Hua Wang ◽  
Wen-Ge Han Du ◽  
Nan Wang ◽  
...  
Keyword(s):  
Click Chemistry ◽  
High Performance ◽  
Isotopic Exchange ◽  
Tumor Imaging ◽  
Radiochemical Yield ◽  
Exchange Method ◽  
Molar Activity ◽  
Positron Emission ◽  
Sulfur Fluoride

The lack of simple, efficient [<sup>18</sup>F]fluorination processes and new target-specific organofluorine probes remains the major challenge of fluorine-18-based positron emission tomography (PET). We report here a fast isotopic exchange method for the radiosynthesis of aryl [<sup>18</sup>F]fluorosulfate based PET agents enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully-automated <sup>18</sup>F-radiolabeling of twenty-five structurally diverse aryl fluorosulfates with excellent radiochemical yield (83–100%) and high molar activity (up to 281 GBq µmol<sup>–1</sup>) at room temperature in 30 seconds. The purification of radiotracers requires no time-consuming high-performance liquid chromatography (HPLC), but rather a simple cartridge filtration. The utility of aryl [<sup>18</sup>F]fluorosulfate is demonstrated by the <i>in vivo</i> tumor imaging by targeting poly(ADP-ribose) polymerase 1 (PARP1).

Solubilization of Itraconazole by Surfactants and Phospholipid-Surfactant Mixtures: Interplay of Amphiphile Structure, pH and Electrostatic Interactions

2020 ◽  
Author(s):  
Zahari Vinarov ◽  
Gabriela Gancheva ◽  
Nikola Burdzhiev ◽  
Slavka S. Tcholakova
Keyword(s):  
Nmr Spectroscopy ◽  
Electrostatic Interactions ◽  
Triazole Ring ◽  
Water Soluble ◽  
Single Chain ◽  
Surfactant Mixtures ◽  
Solubilization Capacity ◽  
Water Soluble Drugs ◽  
Hydrophobic Chain ◽  
Brick Dust

Although surfactants are frequently used in enabling formulations of poorly water-soluble drugs, the link between their structure and drug solubilization capacity is still unclear. We studied the solubilization of the “brick-dust” molecule itraconazole by 16 surfactants and 3 phospholipid:surfactant mixtures. NMR spectroscopy was used to study in more details the drug-surfactant interactions. Very high solubility of itraconazole (up to 3.6 g/L) was measured in anionic surfactant micelles at pH = 3, due to electrostatic attraction between the oppositely charged (at this pH) drug and surfactant molecules. <sup>1</sup>H NMR spectroscopy showed that itraconazole is ionized at two sites (2+ charge) at these conditions: in the phenoxy-linked piperazine nitrogen and in the dioxolane-linked triazole ring. The increase of amphiphile hydrophobic chain length had a markedly different effect, depending on the amphiphile type: the solubilization capacity of single-chain surfactants increased, whereas a decrease was observed for double-chained surfactants (phosphatidylglycerols). The excellent correlation between the chain melting temperatures of phosphatidylglycerols and itraconazole solubilization illustrated the importance of hydrophobic chain mobility. This study provides rules for selection of itraconazole solubilizers among classical single-chain surfactants and phospholipids. The basic physics underpinning the described effects suggests that these rules should be transferrable to other “brick-dust” molecules.

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