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.
Benzoheterocyclics
have been widely adopted as drug-like core scaffolds
that can be incorporated into DNA-encoded chemical library technology
for high-throughput hit discovery. Here, we present a visible light-promoted
divergent synthesis of on-DNA benzoheterocycles from aldehydes. Four
types of DNA-conjugated benzoheterocyclics were obtained under mild
conditions with a broad substrate scope. A cross substrate scope study,
together with enzymatic ligation and subsequent chemical diversifications,
were
conducted, demonstrating the feasibility of this approach in DNA-encoded
chemical library construction.
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