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

Josephine Yuen, Jing Chai, Yun Ding

2020Bioconjugate Chemistry29 citationsDOI

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.

Topics & Concepts

ChemistryConjugated systemAldehydeDNAImineCondensation reactionAmideDNA condensationCombinatorial chemistryCondensationOrganic chemistryCatalysisBiochemistryPolymerPhysicsTransfectionGeneThermodynamicsSynthesis and Biological ActivityChemical Synthesis and AnalysisCancer therapeutics and mechanisms
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