Ibogaine and its main metabolite noribogaine provide important molecular prototypes for markedly different treatment of substance use disorders and co-morbid mental health illnesses. However, these compounds present a cardiac safety risk and a highly complex molecular mechanism. We introduce a class of iboga alkaloids - termed oxa-iboga - defined as benzofuran-containing iboga analogs and...
Abstract Substance use and related mental health epidemics are causing increasing suffering and death in diverse communities. 1,2 Despite extensive efforts focused on developing pharmacotherapies for treating substance use disorders, there is an urgent need for radically different therapeutic approaches. 3,4 Ibogaine provides an important drug prototype in this direction, as a psychoactive...
Salvinorin A (SalA) is a plant metabolite that agonizes the human kappa-opioid receptor (κ-OR) with high affinity and high selectivity over mu- and delta-opioid receptors. Its therapeutic potential has stimulated extensive semisynthetic studies and total synthesis campaigns. However, structural modification of SalA has been complicated by its instability, and efficient total synthesis has been...