86997-05-9

Upstream product

• 1558-23-2 3,6-dimethyl-1,2,4,5-tetrazine 
• 2645443-13-4 (E)-cyclooct-2-en-1-yl-(4-nitrophenyl)carbonate 
• 93301-76-9 axial-(E)-cyclooct-2-en-1-ol 
• 103-80-0 phenylacetyl chloride 
• 100-39-0 benzyl bromide 
• 93301-75-8 3-Hydroxy-trans-cycloocten 
• 122-04-3 4-nitro-benzoyl chloride 
• 3212-75-7 axial (E)-cyclooct-2-en-1-ol 
• 93-97-0 benzoic acid anhydride 
• 645-45-4 hydrocinnamic acid chloride 

Relevant academic research and scientific papers

A Cleavable C2-Symmetric trans-Cyclooctene Enables Fast and Complete Bioorthogonal Disassembly of Molecular Probes

Bioorthogonal chemistry is bridging the divide between static chemical connectivity and the dynamic physiologic regulation of molecular state, enabling in situ transformations that drive multiple technologies. In spite of maturing mechanistic understanding and new bioorthogonal bond-cleavage reactions, the broader goal of molecular ON/OFF control has been limited by the inability of existing systems to achieve both fast (i.e., seconds to minutes, not hours) and complete (i.e., >99%) cleavage. To attain the stringent performance characteristics needed for high fidelity molecular inactivation, we have designed and synthesized a new C2-symmetric trans-cyclooctene linker (C2TCO) that exhibits excellent biological stability and can be rapidly and completely cleaved with functionalized alkyl-, aryl-, and H-tetrazines, irrespective of click orientation. By incorporation of C2TCO into fluorescent molecular probes, we demonstrate highly efficient extracellular and intracellular bioorthogonal disassembly via omnidirectional tetrazine-triggered cleavage.

Click-to-Release from trans-Cyclooctenes: Mechanistic Insights and Expansion of Scope from Established Carbamate to Remarkable Ether Cleavage

The bioorthogonal cleavage of allylic carbamates from trans-cyclooctene (TCO) upon reaction with tetrazine is widely used to release amines. We disclose herein that this reaction can also cleave TCO esters, carbonates, and surprisingly, ethers. Mechanistic studies demonstrated that the elimination is mainly governed by the formation of the rapidly eliminating 1,4-dihydropyridazine tautomer, and less by the nature of the leaving group. In contrast to the widely used p-aminobenzyloxy linker, which affords cleavage of aromatic but not of aliphatic ethers, the aromatic, benzylic, and aliphatic TCO ethers were cleaved as efficiently as the carbamate, carbonate, and esters. Bioorthogonal ether release was demonstrated by the rapid uncaging of TCO-masked tyrosine in serum, followed by oxidation by tyrosinase. Finally, tyrosine uncaging was used to chemically control cell growth in tyrosine-free medium.

Unraveling Tetrazine-Triggered Bioorthogonal Elimination Enables Chemical Tools for Ultrafast Release and Universal Cleavage

Recent developments in bond cleavage reactions have expanded the scope of bioorthogonal chemistry beyond click ligation and enabled new strategies for probe activation and therapeutic delivery. These applications, however, remain in their infancy, with fu

CHEMICALLY CLEAVABLE GROUP

Disclosed is the use of the reactive components of the inverse electron-demand Diels Alder reaction for chemical masking and unmasking in vitro. This can be applied in complex chemical reactions and, particularly in the synthesis of biomolecules, e.g. on solid supports. The reactice components are a dienophile, particularly a trans-cyclooctene, and a diene, particularly a tetrazine.