DNA-Compatible ortho-Phthalaldehyde (OPA)-Mediated 2-Substituted Isoindole Core Formation and Applications

Authors：Nie, Qigui; Fang, Xianfu; Liu, Changyang; Zhang, Gong; Fan, Xiaohong; Li, Yangfeng^*; Li, Yizhou^*

Source：Journal of Organic Chemistry, 2022, 87(5): 2551-2558.

DOI：10.1021/acs.joc.1c02496

• LIBRARIES
• CHEMISTRY
• BIOCONJUGATION
• DESIGN

The incorporation of the isoindole core into the DNA-encoded chemical library is highly desirable for the great potential pharmacological characters exampled by molecules like lenalidomide. Herein, we reported a DNA-compatible protocol for the OPA-mediated transformation of amines into drug-like moieties represented by isoindolinone and thio-2-isoindole, respectively. The high conversion and wide substrate-scope property of our protocol render its feasibility in the manipulation of terminal amines on oligonucleotide conjugates, including "cap-and-catch" purification, sequential synthesis during DEL construction, and on-DNA macrocyclization.

• Institution
  重庆大学