Four new 1,2,3-triazole phthalimide derivatives with a potent anti-inflammatory activity have been synthesized in the good yields by the 1,3-dipolar cycloaddition reaction from N-(azido-alkyl)phthalimides and terminal alkynes. The anti-inflammatory activity was determined by injecting carrageenan through the plantar tissue of the right hind paw of Swiss white mice to produce inflammation. All the compounds 3a–c and 5a–c exhibited an important anti-inflammatory activity; the best activity was found for the compounds 3b and 5c, which showed to be able to decrease by 69% and 56.2% carrageenan-induced edema in mice. These compounds may also offer a future promise as a new anti-inflammatory agent.
Click chemistry-based strategies for the synthesis of 2-amino-alkyl-1,2,3-triazole-1,4-naphthoquinone derivatives make it possible to obtain desired products from 1,4-naphthoquinone (1,4-NQ), and bio-based lawsone, nor-lapachol and lapachol. The first route (Strategy A) starting from 1,4-NQ and amino alcohols, then 2-amino-alkyl-1,4-NQ alcohols, were tosylated. The azide ion displaced the tosylate group to afford 2-azide-alkyl-1,4-NQ, which was submitted to a copper-catalyzed azide alkyne cycloaddition (CuAAC) condition. The triazole-naphthoquinones were obtained in an overall yield of roughly 47%. Another pathway (Strategy B) substituted bromo-alkyl-phthalimides using NaN 3 as the nucleophile, sequential CuAAC and deprotection of phthalimide group with hydrazine producing amino-triazoles. The subsequent reaction with 1,4-NQ produced 2-amino-alkyl-1,2,3-triazole-1,4-NQ derivatives in an overall yield of 45-76% in four steps. After we developed these two strategies, linear synthesis (Strategy A) was chosen to prepare 2-[(2-(1H-1,2,3-triazol-1-yl)ethylamino)]-3-(3-methylpropenyl)-1,4-naphthoquinones from lawsone with an overall yield of approximately 27% in six steps. On the other hand, convergent synthesis (Strategy B) was employed for the synthesis of 2-[(4-phenyl-1H-1,2,3-triazol-1-yl)alkylamino)]-3-(3-methylbut-2-en-1-yl)-1,4-naphthoquinones from the reaction between 2-methoxylapachol with amino-triazoles with a global yield of about 21%. These synthetic strategies might lead us to new opportunities to build small-molecule libraries for future biological exploration.Keywords: click chemistry, amino-naphthoquinone, lapachol, nor-lapachol, 1,2,3-triazole IntroductionThe synthesis of New Chemical Entities (NCE) remains unaffected by changes in the focus of chemical science. 1A number of synthetic strategies have been developed recently to allow organic chemists to create a great variety of molecules. In order to access novel and diverse chemical libraries of compounds with potential biological activity the use of catalytic methods is prominent.From a synthetic point of view, the Huisgen 1,3-dipolar cycloaddition reaction between organic azides and terminal alkynes has been a straightforward method to assemble a large number of molecules, especially since Sharpless and co-workers 2 and Meldal and co-workers 3 proposed the copper-catalyzed azide-alkyne cycloaddition (CuAAC). This protocol has permitted easy access to molecular diversity of 1,2,3-triazoles and encouraged synthetic chemists to design projects based on this scaffold. [4][5][6][7][8][9][10][11] This reaction has provided the opportunity to synthesize molecules having new properties or biological activities, 12,13 including anti-tuberculosis, 14 antiviral, 15 antitumoral, [16][17][18] antifungal, 19 antibiotic (e.g., tazobactam, see Figure 1a), 20 among others, as can be found in the literature. 21 Moreover, naphthoquinones moieties such as potent trypanocidal and leishmanicidal activities have been synthesized (Figure 1a). [22][23][24] S i n c e m o l ...
This works evaluates the catalytic capacity of metalorganic materials synthesized, based on Cu+ and ambidentade ligand in Huisgen cycloaddition reaction. The synthesis of 1,2,3-triazole was made using CuCl and CuI salts, and the [Cu(4,4’-dipy)]Cl and [Cu(4,4’-dipy)]I compounds as catalysts, with or without base catalysis by triethylamine. The copper salts and compounds lead to formation of the desired triazole product; however, in the synthesis mediated by [Cu(4,4’-dipy)]I does not generate the product, even after 48 h of reaction. The reaction with [Cu(4,4’-dipy)]Cl mediated or not by triethylamine showed high yields of 88 % and 70 %, respectively. The [Cu(4,4’-dipy)]Cl compounds was reused five times, and regenerated by ascorbic acid, maintaining thus, the same reaction yield.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.