Rapid Access to a Broad Range of 6′-Substituted Firefly Luciferin Analogues Reveals Surprising Emitters and Inhibitors

Light-emitting firefly luciferin analogues contain electron-donating groups in the 6′-position, but the scope of known 6′-substitution remains narrow. A two-step route to a broad range of 6′-substituted luciferin analogues was developed to fill this void and enable more extensive study of the 6′-functionality. This chemistry allowed direct access to “caged” amide and bright azetidine analogues, but also revealed thioether inhibitors and unexpectedly luminogenic aryl amine derivatives.