DNA-Compatible ortho-Phthalaldehyde (OPA)-Mediated 2-Substituted Isoindole Core Formation and Applications
Qigui Nie1, Xianfu Fang1, Changyang Liu1
1Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People's Republic of China.
Abstract:
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.
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