Josephine Yuen; Jing Chai; Yun Ding
Bioconjugate Chem., 2020, 31(12), 2712-2718
https://doi.org/10.1021/acs.bioconjchem.0c00508

Abstract

Condensation of imines with anhydrides have been proven to be a valuable method for the synthesis of tetrahydroisoquinolones. Herein, we report the application of this chemistry with DNA-conjugated imines. Condensation of DNA-conjugated imine (which can be formed in situ from DNA-conjugated amines and aldehydes or DNA-conjugated aldehyde and primary amines) with homophthalic anhydride produces isoquinolones in moderate to excellent yields. The formed isoquinolone can be further derivatized with a variety of amines through amide bond formation. Development of this chemistry on-DNA enables the synthesis of an isoquinolone core-focused DNA-encoded library.