Improved Diazo-Transfer Reaction for DNA-Encoded Chemistry and Its Potential Application for Macrocyclic DEL-Libraries

DNA-encoded libraries (DEL) are increasingly being used to identify new starting points for medicinal chemistry in drug discovery. Herein, we discuss the development of methods that allow the conversion of both primary amines and anilines, attached to DNA, to their corresponding azides in excellent yields. The scope of these diazo-transfer reactions was investigated, and a proof-of-concept has been devised to allow for the synthesis of macrocycles on DNA.

Automated summary

In this paper, the development of methods converting primary amines and anilines attached to DNA to their corresponding azides with high yields is discussed. The scope of these reactions was studied and a proof-of-concept for the synthesis of macrocycles on DNA has been devised.