Macrocyclizing DNA-Linked Peptides via Three-Component Cyclization and Photoinduced Chemistry

While DNA-encoded macrocyclic libraries have gained substantialattention and several hit compounds have been identified from DNA-encodedlibrary technology, efficient on-DNA macrocyclic methods are alsorequired to construct DNA-linked libraries with a high degree of cyclizationand DNA integrity. In this paper, we reported a set of on-DNA methodologies,including the use of an OPA-mediated three-component cyclization withnative handles of amino acids and photoredox chemistries. These chemistriesproceed smoothly under mild conditions in good to excellent conversions,successfully generating novel isoindole, isoindoline, indazolone,and bicyclic scaffolds.

Automated summary

This paper presents a set of on-DNA methodologies for constructing DNA-linked libraries with high cyclization and DNA integrity. These methodologies include OPA-mediated three-component cyclization and photoredox chemistries, which can generate novel isoindole, isoindoline, indazolone, and bicyclic scaffolds in good to excellent conversions.