8 Sydnone-Based Cycloadditions in Click Chemistry

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).

2.5 CuAAC and Metal-Free 1,3-Dipolar Huisgen Cycloadditions in Drug Discovery

2022 ◽  
Author(s):  
K. M. Kacprzak ◽  
I. Skiera ◽  
J. Rutkowski
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Click Chemistry ◽  
Combinatorial Chemistry ◽  
High Throughput Screening ◽  
Dipolar Cycloaddition ◽  
Discovery Process ◽  
Metal Free ◽  
The Stability

AbstractProclaimed by Sharpless in 2001, the manifesto of click chemistry philosophy shifted the focus from target-oriented to drug-like-oriented synthesis, and has enormously accelerated the drug-discovery process over the last two decades. Copper(I)-catalyzed and metal-free versions of the Huisgen 1,3-dipolar cycloaddition of azides and alkynes have become the reference click chemistry synthetic tools. These processes are adaptable to various drug-design modes such as kinetic target guided synthesis (in situ click chemistry assembling; KTGS), combinatorial chemistry/high-throughput-screening approaches, or structure-based rational projecting. Moreover, the facile click chemistry derivatization of natural or synthetic products, linking molecules or improving the stability of leads by installation of 1,2,3-triazoles, is another important stream of bioactivities. This review is intended to provide a general overview of click-chemistry-powered drug design, with dozens of successful examples resulting in the discovery of nanomolar-active 1,2,3-triazoles in every stage of drug development.

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

2009 ◽  
Vol 13 (03) ◽  
pp. 336-345 ◽  
Author(s):  
Mikhail A. Grin ◽  
Ivan S. Lonin ◽  
Anna A. Lakhina ◽  
Elena S. Ol'shanskaya ◽  
Alexey I. Makarov ◽  
...  
Keyword(s):  
Triple Bond ◽  
Tautomeric Form ◽  
Click Reaction ◽  
Copper Cation ◽  
Water Soluble ◽  
Dipolar Cycloaddition ◽  
Nmr Studies ◽  
Metal Free ◽  
Cu Complex ◽  
Derivatives Of

Glucose-, galactose- and lactose-containing photosensitizers based on derivatives of chlorophyll a and bacteriochlorophyll a were synthesized with the use of [3+2] cycloaddition between sugar azides and triple bond derivatives of chlorins and bacteriochlorins. Unlike bacteriochlorin cycloimide, chlorin was detected to form a Cu -complex during the click reaction. An approach to the synthesis of metal-free glycosylated chlorins was developed with the use of "protection" by Zn 2+ cation and subsequent demetalation. It is based on the action of alkynyl chlorin e6 derivative Zn -complex, which is resistant to the substitution by copper cation. Bacteriochlorin p cycloimide conjugate with per-acetylated β-D-lactose was obtained and shown to become water-soluble after unblocking of the lactose hydroxy functions. NMR studies allowed for the elucidation of structure, tautomeric form and conformation of the obtained compounds.

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

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.

scholarly journals "Click" chemistry as a tool to create novel biomaterials: a short review

2017 ◽  
Vol 1 (1) ◽  
pp. 22-34
Author(s):  
Mariana Barbosa ◽  
Cristina Martins ◽  
Paula Gomes
Keyword(s):  
Click Chemistry ◽  
Biomedical Applications ◽  
Recent Literature ◽  
Click Reaction ◽  
Cycloaddition Reaction ◽  
Polymeric Materials ◽  
Short Review ◽  
Dipolar Cycloaddition ◽  
Functionalization Of Polymers ◽  
Grafting Modification

In recent years, there has been a growing demand for novel strategies for biomedical applications. Chitosan is a typical cationic amino-containing polysaccharide that has been widely used due to its unique properties. The grafting modification of chitosan has been explored as an interesting method to develop multifunctional novel chitosan hybrid materials for drug delivery, tissue engineering, and other biomedical applications. Recently, “click” chemistry has been introduced into the synthesis of polymeric materials with well-defined and complex chain architectures. The Huisgen’s 1,3-dipolar cycloaddition reaction between alkynes and azides yielding triazoles is the principal example of a “click” reaction. Bioconjugation, surface modification, and orthogonal functionalization of polymers were successfully performed through this chemoselective reaction. In recent literature interest has been shown in this cycloaddition for the modification of polysaccharides, however, only a few chitosan graft copolymers have been synthesized by this technique.

The application of click chemistry for targeting quadruplex nucleic acids

2019 ◽  
Vol 55 (6) ◽  
pp. 731-750 ◽  
Author(s):  
Puja Saha ◽  
Deepanjan Panda ◽  
Jyotirmayee Dash
Keyword(s):  
Nucleic Acids ◽  
Click Chemistry ◽  
Click Reaction ◽  
Dipolar Cycloaddition

The Cu(i)-catalyzed azide and alkyne 1,3-dipolar cycloaddition (CuAAC), commonly known as the “click reaction”, has emerged as a versatile synthetic tool for targeting quadruplex nucleic acids.

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

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.

Fluorogenic probes for mitochondria and lysosomes via intramolecular photoclick reaction

The Analyst ◽  
2021 ◽  
Author(s):  
Song Liu ◽  
Han Su ◽  
Lingli Bu ◽  
Jiangyu Yan ◽  
Guorui Li ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Click Reaction ◽  
Living Cells ◽  
Fluorogenic Probes

Probes based on the intramolecular tetrazole-ene photo-click reaction were developed for the in situ fluorescence imaging of mitochondria and lysosomes in living cells.

scholarly journals "Click" chemistry as a tool to create novel biomaterials: a short review

2015 ◽  
Vol 1 (1) ◽  
pp. 22-34 ◽  
Author(s):  
Mariana Barbosa ◽  
Cristina Martins ◽  
Paula Gomes
Keyword(s):  
Click Chemistry ◽  
Biomedical Applications ◽  
Recent Literature ◽  
Click Reaction ◽  
Cycloaddition Reaction ◽  
Polymeric Materials ◽  
Short Review ◽  
Dipolar Cycloaddition ◽  
Functionalization Of Polymers ◽  
Grafting Modification

In recent years, there has been a growing demand for novel strategies for biomedical applications. Chitosan is a typical cationic amino-containing polysaccharide that has been widely used due to its unique properties. The grafting modification of chitosan has been explored as an interesting method to develop multifunctional novel chitosan hybrid materials for drug delivery, tissue engineering, and other biomedical applications. Recently, “click” chemistry has been introduced into the synthesis of polymeric materials with well-defined and complex chain architectures. The Huisgen’s 1,3-dipolar cycloaddition reaction between alkynes and azides yielding triazoles is the principal example of a “click” reaction. Bioconjugation, surface modification, and orthogonal functionalization of polymers were successfully performed through this chemoselective reaction. In recent literature interest has been shown in this cycloaddition for the modification of polysaccharides, however, only a few chitosan graft copolymers have been synthesized by this technique.

scholarly journals Metal-Free “Click” Chemistry: Efficient Polymer Modification via 1,3-Dipolar Cycloaddition of Nitrile Oxides and Alkynes

2009 ◽  
Vol 42 (15) ◽  
pp. 5411-5413 ◽  
Author(s):  
Ishwar Singh ◽  
Zoya Zarafshani ◽  
Jean-François Lutz ◽  
Frances Heaney
Keyword(s):  
Click Chemistry ◽  
Dipolar Cycloaddition ◽  
Polymer Modification ◽  
Metal Free ◽  
Nitrile Oxides
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