Self-Immolative Arylcarbonates for Nucleic Acid Templated Reactions

Nucleic acid templated reactions are of particular interest for the development of diagnostic tools or the generation of libraries of molecules. Amine/carbonate oligonucleotide templated reactions that release a colored reporter are known, but improvements of performance, in terms of speed, sensitivity, and selectivity, remain necessary. We report here on the synthesis of halogenated arylcarbonates with self-immolative properties that can be readily connected under mild conditions to commercially available alkyne functionalized oligonucleotides using click chemistry. Those carbonate oligonucleotides can then be reacted in a templated fashion with commercially available amine bearing oligonucleotides and release a compound of interest. The reactivity of the carbonate oligonucleotide can be tuned to better suit a particular application by changing the electronic properties of the aromatic linker, the steric hindrance at the reactive carbonate site, and/or the pH of the medium. A detailed kinetic analysis of various substrates reacting in such templated reactions is also presented.