Dearomative intermolecular [2 + 2] photocycloaddition for construction of C(sp³)-rich heterospirocycles on-DNA.

ABSTRACT: DNA-encoded library (DEL) screens have significantly impacted new lead compound identification efforts within drug discovery. An advantage of DELs compared to traditional screening methods is that an exponentially broader chemical space can be effectively screened using only nmol quantities of billions of DNA-tagged, drug-like molecules. The synthesis of DELs containing diverse, sp³-rich spirocycles, an important class of molecules in drug discovery, has not been previously reported. Herein, we demonstrate the synthesis of complex and novel spirocyclic cores via an on-DNA, visible light-mediated intermolecular [2 + 2] cycloaddition of olefins with heterocycles, including indoles, azaindoles, benzofurans, and coumarins. The DNA-tagged exo-methylenecyclobutane substr

SUBMITTER: Li L 

PROVIDER: S-EPMC9993886 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature