Visible-Light-Driven C-H Oxidation of Cyclic Tertiary Amines: Access to Synthetic Strychnos Alkaloids with Antiviral Activity

Abstract

Air and visible light have been used in facile direct C-H oxidation of cyclic tertiary amines at ambient conditions, employing organic dyes as photocatalysts and LED. Tolerance of this new environmentally compatible protocol to various side-chain derivatizations of tryptoline and tetrahydroisoquinoline substrates was demonstrated. The developed method provides a straightforward and sustainable route towards δ-lactams, which feature strong antiviral properties (EC₅₀ down to 4.6±1.8 μm) against human cytomegalovirus (HCMV). The clear advantages, which are easily available and inexpensive reagents, organic dyes, visible light, air/O₂ and atom efficiency, make this system highly appealing for synthesis of versatile Strychnocarpine alkaloid derivatives with antiviral activity.

Keywords: aerobic photooxidation; antiviral alkaloids; cyclic amines; lactams; metal-free C−H oxidation; organic dyes.