Synthesis of Substituted 1,2,3‐Triazoles through Organocatalysis

Anebouselvy, Kengadarane; Ramachary, Dhevalapally B.

doi:10.1002/9783527694174.ch4

Cited by 18 publications

(6 citation statements)

References 90 publications

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“…The second set of precursors includes readily available aromatic azides differently functionalized at the aryl ring, prepared via known procedures from commercially available aromatic amines, using NaNO 2 and NaN 3 , or from aryl chlorides using NaN 3 (see the Supporting Information). Subsequently, the azide and aldehyde precursors were combined via a Ramachary-Bressy-Wang organocatalyzed azide-carbonyl [3 + 2] cycloaddition (organo-click) reaction to form a 1,2,3-triazole ring, which is a major pharmacophore system among nitrogen-containing heterocycles. − 1,2,3-Triazoles have been found to have a broad spectrum of applications, such as antiviral, antituberculosis, antibacterial, anticancer, antimalarial agents, and more . In this work, we planned to vary the substituents on the 1,2,3-triazole pharmacophore to achieve the chemical diversity of artemisinin–triazole antimalarial hybrid compounds for structure–activity relationship studies (see compounds 1 – 18 , Figure ).…”

Section: Results and Discussionmentioning

confidence: 99%

Access to Artemisinin–Triazole Antimalarials via Organo-Click Reaction: High In Vitro/In Vivo Activity against Multi-Drug-Resistant Malaria Parasites

Herrmann,

Leidenberger,

Quadros

et al. 2024

JACS Au

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Malaria is one of the most widespread diseases worldwide. Besides a growing number of people potentially threatened by malaria, the consistent emergence of resistance against established antimalarial pharmaceuticals leads to an urge toward new antimalarial drugs. Hybridization of two chemically diverse compounds into a new bioactive product is a successful concept to improve the properties of a hybrid drug relative to the parent compounds and also to overcome multidrug resistance. 1,2,3-Triazoles are a significant pharmacophore system among nitrogen-containing heterocycles with various applications, such as antiviral, antimalarial, antibacterial, and anticancer agents. Several marketed drugs possess these versatile moieties, which are used in a wide range of medical indications. While the synthesis of hybrid compounds containing a 1,2,3-triazole unit was described using Cu-and Ru-catalyzed azide−alkyne cycloaddition, an alternative metal-free pathway has never been reported for the synthesis of antimalarial hybrids. However, a metal-free pathway is a green method that allows toxic and expensive metals to be replaced with an organocatalyst. Herein, we present the synthesis of new artemisinin−triazole antimalarial hybrids via a facile Ramachary-Bressy-Wang organocatalyzed azide-carbonyl [3 + 2] cycloaddition (organo-click) reaction. The prepared new hybrid compounds are highly potent in vitro against chloroquine (CQ)-resistant and multi-drug-resistant Plasmodium falciparum strains (IC 50 (Dd2) down to 2.1 nM; IC 50 (K1) down to 1.8 nM) compared to CQ (IC 50 (Dd2) = 165.3 nM; IC 50 (K1) = 302.8 nM). Moreover, the most potent hybrid drug was more efficacious in suppressing parasitemia and extending animal survival in Plasmodium berghei-infected mice (up to 100% animal survival and up to 40 days of survival time) than the reference drug artemisinin, illustrating the potential of the hybridization concept as an alternative and powerful drug-discovery approach.

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Section: Results and Discussionmentioning

confidence: 99%

Access to Artemisinin–Triazole Antimalarials via Organo-Click Reaction: High In Vitro/In Vivo Activity against Multi-Drug-Resistant Malaria Parasites

Herrmann,

Leidenberger,

Quadros

et al. 2024

JACS Au

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“…Copper-catalyzed azide–alkyne [3 + 2]-cycloaddition of 6aa with PhN 3 7 in water and tert -BuOH at 25 °C for 24 h furnished the click product 8aa in 75% yield (Scheme , eq 2). It is a popular fact that 1,2,3-triazoles are biologically and medicinally important compounds, and 1,2,3-triazoles containing cyclic-1,3-diketones will be interesting intermediates for medicinal and material chemistry . Subsequently, we thought of executing an intramolecular cyclization of coupling products 5 under the Lewis acid catalysis, as compounds 5 contain the requisite active functional groups .…”

Section: Applications Of C-propargylation Productsmentioning

confidence: 94%

Organocatalytic Reductive Propargylation: Scope and Applications

et al. 2019

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An amino acid-catalyzed three-component reductive coupling protocol has been developed for the selective high-yielding synthesis of nearly fifty examples of propargylated cyclic/acyclic systems from the various propargyl aldehydes, cyclic/acyclic CH acids, and Hantzsch ester under ambient conditions. It is an economical, efficient, catalytic, metal-free protocol for the quick gram-scale synthesis of propargylated cyclic/acyclic compounds, and many of these coupling compounds were purified by a simple precipitation–filtration technique instead of column chromatography. Functionally rich propargylated cyclic-1,3-diketones were specifically transformed into dihydropyrans found in natural products and drugs through an annulative etherification reaction by using Lewis-acid (AgOTf) catalysis. Further, we developed the C-methylation reactions on propargylated cyclic-1,3-diketones, which are prolific synthons in natural products and medicinal chemistry.

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“…In recent years, chemists employed various strategies for the synthesis of functionalized 1,2,3-triazoles, as functionalized 1,2,3-triazoles found a wide range of applications in biological studies, therapeutic drug discovery, material chemistry, and agrochemical industry. − The thermally induced nonselective Huisgen azide–alkyne [3 + 2]-cycloaddition was transformed into the highly regiospecific 1,4-disubstituted-1,2,3-triazoles with high yields through the copper(I)-catalyzed azide–alkyne [3 + 2]-cycloaddition as click reaction by Sharpless and Meldal independently. − Apart from Cu-catalysis, azide–alkyne [3 + 2]-cycloadditions were also developed with ruthenium, − iridium, − nickel, − magnesium, and also using strain-promoted − manner for the construction of functionalized 1,2,3-triazoles. Besides the transition metal-mediated azide–alkyne [3 + 2]-cycloaddition reaction for 1,2,3-triazoles synthesis, Ramachary, Bressy, Wang, Dehaen, Paixao, and other groups developed alternative green synthetic methods of azide-carbonyl [3 + 2]-cycloadditions employing a variety of amines as organocatalysts. − …”

Section: Introductionmentioning

confidence: 99%

Direct Organocatalytic Chemoselective Synthesis of Pharmaceutically Active 1,2,3-Triazoles and 4,5′-Bitriazoles

Gorachand,

Surendra Reddy,

Ramachary

2024

ACS Org. Inorg. Au

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Carbonyl-containing 1,4,5-trisubstituted-and 1,4-disubstituted-1,2,3triazoles are well-known for their wide range of applications in pharmaceutical and medicinal chemistry, but their high-yielding metal-free synthesis has always remained challenging, as no comprehensive protocol has been outlined to date. Owing to their structural and medicinal importance, herein, we synthesized various carbonyl-containing 1,4,5-trisubstituted-and 1,4-disubstituted-1,2,3-triazoles and unsymmetrical 4,5′bitriazoles with high yields and chemo-/regioselectivity from the library of 2,4diketoesters and azides in a sequential one-pot manner through the combination of organocatalytic enolization, in situ [3 + 2]-cycloaddition, and hydrolysis reactions. The commercial availability of the starting materials/catalysts, diverse substrate scope, performance in a one-pot manner, chemo-/regioselectivity of organo-click reaction, quick synthesis of unsymmetrical 4,5′-bitriazoles, a large number of synthetic applications, and numerous medicinal applications of carbonyl-containing 1,2,3-triazoles are the key attractions of this metal-free organo-click work.

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Synthesis of Substituted 1,2,3‐Triazoles through Organocatalysis

Cited by 18 publications

References 90 publications

Access to Artemisinin–Triazole Antimalarials via Organo-Click Reaction: High In Vitro/In Vivo Activity against Multi-Drug-Resistant Malaria Parasites

Access to Artemisinin–Triazole Antimalarials via Organo-Click Reaction: High In Vitro/In Vivo Activity against Multi-Drug-Resistant Malaria Parasites

Organocatalytic Reductive Propargylation: Scope and Applications

Direct Organocatalytic Chemoselective Synthesis of Pharmaceutically Active 1,2,3-Triazoles and 4,5′-Bitriazoles

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