Synthetic Work Towards Salvinorin A


Salvinorin A is the active compound in the plant Salvia divinorum, commonly known as salvia. It is a highly selective kappa opioid agonist, which gives it potent hallucinogenic and potent analgesic properties. The natural compound was isolated and characterized in 1982, and a multitude of pharmacological and derivatization studies have been performed to highlight its importance and efficacy. The first total synthesis was performed in 2007 by the David Evans group utilizing a transannular bis-Michael reaction to create the tricyclic skeleton in one step from a 14-member macrocycle. A second total synthesis was achieved by the Hagiwara group in 2008 via simple step-wise transformations. While these syntheses are useful, they are not effective for more extensive study of the target compound due to the large number of steps and low total yields. The work described herein set out to develop a shorter, simpler, and ideally more economical synthesis in order to enable broader studies of the target compound. The more focused goal of this work is to develop a library of compounds with derivatization of the furanyl group at C12. Though a total synthesis was not achieved, the work contained within has set up future work in order to complete this goal and facilitate the development of libraries of derivatives that can further elucidate desired pharmacological effects.



Salvinorin A, Salvia divinorum, Synthesis, Organic chemistry, Hagiwara, Opioid agonist