Planta Med 2013; 79 - P43
DOI: 10.1055/s-0033-1336485

Convenient Synthesis and In Vitro Pharmacological Activity of Thioesters of Salvinorin B

PR Polepally 1, K White 2, BL Roth 2, JK Zjawiony 1
  • 1Department of Pharmacognosy, and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677 – 1848, USA
  • 2Department of Pharmacology, School of Medicine and Division of Medicinal Chemistry and Natural Products, School of Pharmacy, NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, NC 27599, USA

Salvia divinorum is a plant from the mint family that has been used in traditional spiritual practices by the Mazatec Indians of Oaxaca, Mexico. Chewing fresh leaves or smoking dried leaves will produce hallucinogenic-like experiences [1]. These experiences last for an hour and are reported to be potent and intense [2]. The psychoactive component of this plant, the neoclerodane diterpenoid salvinorin A, has been studied intensively as a potent and selective κ-opioid receptor (KOR) agonist [3]. Since its discovery, a large number of analogues have been synthesized [4]. Among these analogs RB-64 (22-thiocyanatosalvinorin A) has high affinity to KOR and is also an irreversible ligand [5]. As part of our continuing efforts to understand ligand-receptor interactions, we designed and synthesized a new series of thioester salvinorin B derivatives and evaluated for their in vitro binding affinity to kappa, mu and delta-opioid receptors.

Acknowledgements: This work was supported by the NIH Grant R01 DA017204 and the NIMH Psychoactive Drug Screening Program (PDSP), UNC at Chapel Hill, NC 27599. References: [1] Valdes LJ, et al. (1983)J Ethanopharmacol, 7: 287 – 312. [2] Sheffler DJ, et al. (2003) Trends Pharmacol Sci, 24: 107 – 109. [3] Roth BL, et al. (2002) Proceedings of the National Academy of Sciences, 99: 11934 – 11939. [4] Cunningham CW, et al. (2011) Pharmacol Rev, 63: 316 – 347. [5] Yan F, et al. (2009) Biochem, 48: 6898 – 6908.