Efficient Palladium-Catalyzed Synthesis of Unsymmetrical (Het)aryl­tetrazines

Leconte, Nicolas; Keromnes-Wuillaume, A.; Suzenet, Franck; Guillaumet, Gérald

doi:10.1055/s-2007-967991

Cited by 11 publications

(12 citation statements)

References 2 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10c and d). 89 Yields of 30-70% were achieved under microwave conditions for both reactions. This Pd-catalysed cross-coupling reaction represents the first of few methods to construct asymmetrical tetrazines using vinyl, aryl and heteroaryl substituents.…”

Section: Synthesis Of Tetrazine Derivativesmentioning

confidence: 98%

“…This Pd-catalysed cross-coupling reaction represents the first of few methods to construct asymmetrical tetrazines using vinyl, aryl and heteroaryl substituents. 89 Recently, Pd-catalysed Stille cross coupling reactions were developed for the derivatization of tetrazines at positions C3 and C6 with fluorescent probes (Fig. 10e).…”

Section: Synthesis Of Tetrazine Derivativesmentioning

confidence: 99%

“…44a). In vivo PET imaging and ex vivo biodistribution experiments revealed significant and specific uptake of the 64 Cu-DOTA and 89 Zr-DFO-trastuzumab bioconjugates in HER2positive BT-474 xenografts (Fig. 44a).…”

Section: ''Tetrazine Radiolabelling'' With Other Relevant Isotopesmentioning

confidence: 99%

“…284 Additionally the use of mild IEDDA conditions avoids the use of high temperatures that are usually required for labelling antibodies bearing coordinating agents. Recently, Weissleder et al developed a tetrazine conjugate that incorporated the DFO ligand for installation of 89 Zr and a BODIPY fluorophore for multimodal imaging. 89 Zr-DFO-BODIPYtrastuzumab was prepared within minutes by Tz/TCO ligation and PET imaging showed high tumour conspicuity.…”

Section: ''Tetrazine Radiolabelling'' With Other Relevant Isotopesmentioning

confidence: 99%

“…Recently, Weissleder et al developed a tetrazine conjugate that incorporated the DFO ligand for installation of 89 Zr and a BODIPY fluorophore for multimodal imaging. 89 Zr-DFO-BODIPYtrastuzumab was prepared within minutes by Tz/TCO ligation and PET imaging showed high tumour conspicuity. In addition, biodistribution studies confirmed high specific probe uptake in BT474 xenografts (HER2+) (237.3 AE 14.5% ID per g in BT474) compared to low, nonspecific probe uptake in BT20 xenografts (HER2À) (16.4 AE 5.6% ID per g) 96 h p.i.…”

Section: ''Tetrazine Radiolabelling'' With Other Relevant Isotopesmentioning

confidence: 99%

See 4 more Smart Citations

Inverse electron demand Diels–Alder reactions in chemical biology

2017

View full text Add to dashboard Cite

The emerging inverse electron demand Diels-Alder (IEDDA) reaction stands out from other bioorthogonal reactions by virtue of its unmatchable kinetics, excellent orthogonality and biocompatibility. With the recent discovery of novel dienophiles and optimal tetrazine coupling partners, attention has now been turned to the use of IEDDA approaches in basic biology, imaging and therapeutics. Here we review this bioorthogonal reaction and its promising applications for live cell and animal studies. We first discuss the key factors that contribute to the fast IEDDA kinetics and describe the most recent advances in the synthesis of tetrazine and dienophile coupling partners. Both coupling partners have been incorporated into proteins for tracking and imaging by use of fluorogenic tetrazines that become strongly fluorescent upon reaction. Selected notable examples of such applications are presented. The exceptional fast kinetics of this catalyst-free reaction, even using low concentrations of coupling partners, make it amenable for in vivo radiolabelling using pretargeting methodologies, which are also discussed. Finally, IEDDA reactions have recently found use in bioorthogonal decaging to activate proteins or drugs in gain-of-function strategies. We conclude by showing applications of the IEDDA reaction in the construction of biomaterials that are used for drug delivery and multimodal imaging, among others. The use and utility of the IEDDA reaction is interdisciplinary and promises to revolutionize chemical biology, radiochemistry and materials science.

show abstract

Section: Synthesis Of Tetrazine Derivativesmentioning

confidence: 98%

Section: Synthesis Of Tetrazine Derivativesmentioning

confidence: 99%

Section: ''Tetrazine Radiolabelling'' With Other Relevant Isotopesmentioning

confidence: 99%

Section: ''Tetrazine Radiolabelling'' With Other Relevant Isotopesmentioning

confidence: 99%

Section: ''Tetrazine Radiolabelling'' With Other Relevant Isotopesmentioning

confidence: 99%

See 3 more Smart Citations

Inverse electron demand Diels–Alder reactions in chemical biology

2017

View full text Add to dashboard Cite

show abstract

Accessing Functionalized Tetrazines as Click Chemistry Tools: A Synthesis Guide for Chemists and Chemical Biologists

Bickem,

Gavriel,

Neumann

2023

Eur J Org Chem

View full text Add to dashboard Cite

Since the first report that 1,2,4,5‐tetrazines undergo a bioorthogonal reaction with dienophiles in the form of an inverse electron‐demand Diels‐Alder reaction, the demand for high‐yielding synthetic approaches towards them grew steadily. Despite this significant interest, tetrazines were predominantly accessed via the Pinner synthesis or other Pinner‐like reactions, significantly limiting available substrates. In particular, the synthesis of unsymmetrically substituted s‐tetrazines for the selective conjugation to another species presented a major challenge. To tackle these challenges, new and innovative high‐yielding transformations have been developed to widen the scope of accessible symmetric and unsymmetric tetrazines. For instance, Ni(II), Zn(II), and sulphur‐catalysed reactions between two nitriles and hydrazine were developed, which provide access to a wide range of (un‐)symmetric aryl s‐tetrazines. Also, amidines and orthoesters give tetrazines with alkyl substituents, whereas the usage of CH2Cl2 yields valuable H‐monosubstituted tetrazines. Methods using thiocarbohydrazides, terminal fluoroolefins, oxetane esters, or tosyl hydrazones are among the recent additions. Due to the high interest in tetrazine click‐chemistry approaches, some of which reach beyond inverse electron‐demand Diels‐Alder reactions, we expect this overview of synthetic routes to aid the exploration for further applications of tetrazines. Ultimately, we hope to provide a guide for chemists and chemical biologists for accessing functional s‐tetrazines.

show abstract