Xiaojie Lu; Lijun Fan; Christopher B. Phelps; Christopher P. Davie; Christine P. Donahue
Bioconjugate Chem., 2017, 28, 6, 1625-1629
https://doi.org/10.1021/acs.bioconjchem.7b00292

Abstract

DNA-encoded library technology (ELT) is now widely used in pharmaceutical, biotech and academic research for hit identification and target validation. New on-DNA reactions are keys to exploring greater chemical space and accessing challenging chemotypes such as configurationally constrained macrocycles. Herein, we describe the first on-DNA ring-closing metathesis (RCM) and cross-metathesis (CM) reactions promoted by fast initiating Grubbs Ru reagents. Under the optimized conditions, MgCl2 was used to protect the DNA from Ru-induced decomposition. The substrate scope for on-DNA RCM was established and the same conditions were applied to a CM reaction with good conversions.