Condensation of DNA-Conjugated Imines with Homophthalic Anhydride for the Synthesis of Isoquinolones on DNA.

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.