Synthesis and Biological Evaluation of O6C-Salvinorin Alkyne Probes
Etienne Cotter, Giovanni Leoni, Nathan Dao et al.
The authors report an optimized, scalable synthetic route for salvinorin-based probes that target the kappa-opioid receptor. Methodological improvements include substituting a Grignard reagent with an organozinc protocol and enhancing a samarium-mediated reaction with LiBr. These advances enabled the synthesis of two active positive-control probes and three negative-control probes. A screen of over 300 GPCRs confirmed the exceptional KOR selectivity of a novel alkyne probe, establishing it as a tool for validating target-specific engagement in situ.