From the Huisgen cycloaddition to bioorthogonal chemistry. A commentary on the 2022 Nobel Prize in Chemistry

Abstract

The first achievement of the 2022 Chemistry Nobel Prize awardees, Sharpless in particular, was of a conceptual nature and consisted in the proposal of the click chemistry concept, together with its placement in a broader theoretical frame. In a second phase, both Sharpless and Meldal established the copper(I)-catalyzed conditions that allowed the Huisgen 1,3-dipolar cycloaddition to be recognized as the first click reaction, which was broadly employed in all fields of chemistry. These discoveries laid the ground for the development by Bertozzi of bioorthogonal chemistry on the basis of the increased reactivity associated to ring strain in cyclooctyne derivatives. The influence of these ideas and discoveries has been widespread and has led to innumerable advances in many fields of Chemistry and Biology. Keywords: Click chemistry; cycloadditions; drug synthesis; biological chemistry; drug discovery