A Route to Potent, Selective, and Biased Salvinorin Chemical Space.
ACS central science August 23, 2023 Sarah J Hill, Nathan Dao, Vuong Q Dang et al.
A new chemical synthesis method produces salvinorin analogs that are more potent, selective, stable, and functionally biased than the natural compound salvinorin A. These analogs target the kappa-opioid receptor and could serve as templates for next-generation pain relievers, anti-itch treatments, and dissociative hallucinogens. The synthesis uses a special organocatalyst and a cobalt-catalyzed cycloaddition to efficiently create a library of these complex molecules, overcoming previous difficulties in modifying their structure.