1,3-dipolar cycloaddition in the synthesis of glycoconjugates of natural chlorins and bacteriochlorins

The 1,2,3-triazole group is one of the most important connective linkers and functional aromatic heterocycles in modern chemistry. The boom in growth of, in particular, 1,4-disubstituted triazole products since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1-substituted-1,2,3-triazoles, has been surprisingly more challenging. We report a straightforward and scalable click-protocol for the synthesis of 1-substituted-1,2,3-triazoles from organic azides and the bench stable acetylene-surrogate, ethenesulfonyl fluoride (ESF). The transformation proceeds through a thermal 1,3-dipolar cycloaddition of the azide and ESF to give a sulfonyl fluoride substituted triazoline, that itself spontaneously aromatizes through formal loss of HF/SO<sub>2 </sub>to give the stable triazole products with excellent fidelity. The new click reaction tolerates a wide selection of substrates and proceeds smoothly under metal-free conditions to give the products in excellent yield, and without need for additives or chromatographic purification. Further, under controlled conditions, the 1-substituted-1,2,3-triazole products undergo Michael reaction with a second equivalent of ESF to give the unprecedented 1-substituted triazolium sulfonyl fluoride salts, demonstrating the versatility and orthogonal reactivity of ESF. The importance of this novel method is evidenced through the late-stage modification of several drugs and drug fragments, including the synthesis of a new improved derivative of the famous antibiotic, chloramphenicol.

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Metal-Free Click Synthesis of Functional 1-Substituted-1,2,3-Triazoles

10.26434/chemrxiv.9937754 ◽

2019 ◽

Author(s):

Marie-Claire Giel ◽

Christopher J. Smedley ◽

Emily R. R. Mackie ◽

Taijie Guo ◽

Jiajia Dong ◽

...

Keyword(s):

Click Reaction ◽

Dipolar Cycloaddition ◽

Chromatographic Purification ◽

Metal Free ◽

Organic Azides ◽

Novel Method ◽

Fluoride Salts ◽

Sulfonyl Fluoride ◽

Click Synthesis ◽

Selection Of

The 1,2,3-triazole group is one of the most important connective linkers and functional aromatic heterocycles in modern chemistry. The boom in growth of, in particular, 1,4-disubstituted triazole products since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1-substituted-1,2,3-triazoles, has been surprisingly more challenging. We report a straightforward and scalable click-protocol for the synthesis of 1-substituted-1,2,3-triazoles from organic azides and the bench stable acetylene-surrogate, ethenesulfonyl fluoride (ESF). The transformation proceeds through a thermal 1,3-dipolar cycloaddition of the azide and ESF to give a sulfonyl fluoride substituted triazoline, that itself spontaneously aromatizes through formal loss of HF/SO<sub>2 </sub>to give the stable triazole products with excellent fidelity. The new click reaction tolerates a wide selection of substrates and proceeds smoothly under metal-free conditions to give the products in excellent yield, and without need for additives or chromatographic purification. Further, under controlled conditions, the 1-substituted-1,2,3-triazole products undergo Michael reaction with a second equivalent of ESF to give the unprecedented 1-substituted triazolium sulfonyl fluoride salts, demonstrating the versatility and orthogonal reactivity of ESF. The importance of this novel method is evidenced through the late-stage modification of several drugs and drug fragments, including the synthesis of a new improved derivative of the famous antibiotic, chloramphenicol.

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8 Sydnone-Based Cycloadditions in Click Chemistry

10.1055/sos-sd-235-00329 ◽

2022 ◽

Author(s):

F. Friscourt

Keyword(s):

Drug Discovery ◽

Click Chemistry ◽

Click Reaction ◽

Living Cells ◽

Dipolar Cycloaddition ◽

Metal Catalysis ◽

Metal Free ◽

Fluorogenic Probes ◽

Release Strategy

AbstractThe 1,3-dipolar cycloaddition of sydnones (1,2,3-oxadiazolium-5-olates) with dipolarophiles, such as alkynes, has recently emerged as a versatile click reaction, with applications ranging from the mild and regioselective preparation of polysubstituted pyrazoles for drug discovery to the metal-free bioorthogonal ligation of biomacromolecules in living cells. This chapter reviews the importance of metal catalysis for controlling the regioselectivity of the copper-mediated reaction (CuSAC), as well as the development of fluorogenic probes, the click and release strategy, and photo-triggered ligations based on strain-promoted sydnone–alkyne cycloadditions (SPSAC).

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Recent Advances in the Synthesis of Bioactive Quinoline-Based 1,2,3-Triazoles via Cu-Catalyzed Huisgen 1,3-Dipolar Cycloaddition (“Click Reaction”)

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x13666161102150625 ◽

2017 ◽

Vol 13 (6) ◽

pp. 488-503 ◽

Cited By ~ 6

Author(s):

Vladimir V. Kouznetsov ◽

Leonor Y. Vargas-Mendez ◽

Fedor I. Zubkov

Keyword(s):

Click Reaction ◽

Dipolar Cycloaddition ◽

Recent Advances

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Synthesis of Novel 1,2,3-Triazole Derivatives of Isocoumarins and 3,4-Dihydroisocoumarin with Potential Antiplasmodial Activity In Vitro

Medicinal Chemistry ◽

10.2174/1573406416666200602161047 ◽

2020 ◽

Vol 16 ◽

Author(s):

Lucas da Silva Santos ◽

Matheus Fillipe Langanke de Carvalho ◽

Ana Claudia de Souza Pinto ◽

Amanda Luisa da Fonseca ◽

Julio César Dias Lopes ◽

...

Keyword(s):

Triazole Ring ◽

Antiplasmodial Activity ◽

World Health ◽

Dipolar Cycloaddition ◽

Terminal Alkynes ◽

The World ◽

Ic50 Values ◽

Derivatives Of ◽

Active Substances

Background: Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the urge for the development of new antimalarial drugs. Objective: Synthesis and in vitro antiplasmodial evaluation of triazole compounds derived from isocoumarins and a 3,4- dihydroisocoumarin. Method: The compounds were synthesized in 4 to 6-step reactions with the formation of the triazole ring via the Copper(I)-catalyzed 1,3-dipolar cycloaddition between isocoumarin or 3,4-dihydroisocoumarin azides and terminal alkynes. This key reaction provided compounds with an unprecedented connection of isocoumarin or 3,4-dihydroisocoumarin and the 1,2,3-triazole ring. The products were tested for their antiplasmodial activity against a Plasmodium falciparum chloroquine resistant and sensitive strains (W2 and 3D7, respectively). Results: Thirty-one substances were efficiently obtained by the proposed routes with an overall yield of 25-53%. The active substances in the antiplasmodial test displayed IC50 values ranging from 0.68-2.89 μM and 0.85-2.07 μM against W2 and 3D7 strains, respectively.

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Potential anticonvulsants: Substituted N-benzylidene derivatives of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19831173 ◽

1983 ◽

Vol 48 (4) ◽

pp. 1173-1186 ◽

Cited By ~ 2

Author(s):

Václav Bártl ◽

Jiří Holubek ◽

Emil Svátek ◽

Marie Bartošová ◽

Miroslav Protiva

Keyword(s):

Acute Toxicity ◽

Water Soluble ◽

Hypotensive Activity ◽

Anticonvulsant Effect ◽

Maximal Electroshock ◽

Soluble Salts ◽

Sleeping Time ◽

Central Depression ◽

Derivatives Of ◽

Electroshock Seizures

Reactions of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins XIVa-XIVd with benzaldehyde, 3,4-dimethoxybenzaldehyde, 4-dimethylaminobenzaldehyde, salicylaldehyde, 3-ethoxy-4-hydroxybenzaldehyde, 2-(2-dimethylaminoethoxy)benzaldehyde, 3-(2-dimethylaminoethoxy)benzaldehyde and 3-ethoxy-4-(2-dimethylaminoethoxy)benzaldehyde afforded a series of 19 hydrazones IIIa-Xc. Some of them showed the expected anticonvulsant effect but only towards pentetrazole; antagonism of maximal electroshock seizures was not observed. In general, the products have a character of tranquillizers: in higher does they produce central depression, potentiate the thiopental sleeping time, have hypothermic action; in single cases antiamphetamine, antireserpine, antihistamine and cataleptic effects were observed. The water-soluble salts of the basic hydrazones VIIIa, VIIIc, IXc and Xc, administered parenterally, showed a rather high acute toxicity and revealed also adrenolytic and hypotensive activity.

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Antioxidant Network Based on Sulfonated Polyhydroxyalkanoate and Tannic Acid Derivative

Bioengineering ◽

10.3390/bioengineering8010009 ◽

2021 ◽

Vol 8 (1) ◽

pp. 9

Author(s):

Laura Brelle ◽

Estelle Renard ◽

Valerie Langlois

Keyword(s):

Gallic Acid ◽

Tannic Acid ◽

Water Soluble ◽

Gel Formation ◽

Ene Reaction ◽

Inorganic Cations ◽

Medium Chain Length ◽

Physically Crosslinked ◽

The Stability ◽

Derivatives Of

A novel generation of gels based on medium chain length poly(3-hydroxyalkanoate)s, mcl-PHAs, were developed by using ionic interactions. First, water soluble mcl-PHAs containing sulfonate groups were obtained by thiol-ene reaction in the presence of sodium-3-mercapto-1-ethanesulfonate. Anionic PHAs were physically crosslinked by divalent inorganic cations Ca2+, Ba2+, Mg2+ or by ammonium derivatives of gallic acid GA-N(CH3)3+ or tannic acid TA-N(CH3)3+. The ammonium derivatives were designed through the chemical modification of gallic acid GA or tannic acid TA with glycidyl trimethyl ammonium chloride (GTMA). The results clearly demonstrated that the formation of the networks depends on the nature of the cations. A low viscoelastic network having an elastic around 40 Pa is formed in the presence of Ca2+. Although the gel formation is not possible in the presence of GA-N(CH3)3+, the mechanical properties increased in the presence of TA-N(CH3)3+ with an elastic modulus G’ around 4200 Pa. The PHOSO3−/TA-N(CH3)3+ gels having antioxidant activity, due to the presence of tannic acid, remained stable for at least 5 months. Thus, the stability of these novel networks based on PHA encourage their use in the development of active biomaterials.

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Dissociation of imino proton(s) of a highly water-soluble metal-free phthalocyanine and determination of its pKa value in water

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424613500235 ◽

2013 ◽

Vol 17 (06n07) ◽

pp. 447-453 ◽

Cited By ~ 2

Author(s):

Hiroaki Isago ◽

Harumi Fujita

Keyword(s):

Aqueous Media ◽

Thermal Reaction ◽

Water Soluble ◽

Acid Dissociation ◽

Acid Dissociation Constant ◽

Metal Free ◽

Imino Proton ◽

Pka Value ◽

Triton X

Dissociation of imino proton(s) in the cavity of the macrocycle of a highly water-soluble, metal-free phthalocyanine ( H 2( H 4 tsppc ); where H 4 tsppc denotes tetrakis{(2′,6′-dimethyl-4′-sulfonic acid)phenoxy}phthalocyaninate) in ethanolic and aqueous solutions has spectrophotometrically been investigated. The spectral changes associated with reaction with NaOH have been found to involve one-proton transfer process in aqueous media while two-protons process in ethanolic media. The acid-dissociation constant of the first imino proton in water (in the presence of Triton X-100) has been determined to be 12.5 ± 0.2 (as pKa) at 25 °C. The doubly deprotonated species in EtOH has been easily converted to its corresponding cobalt(II) derivative by thermal reaction with anhydrous CoCl 2.

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