Download PDF
Synfacts 2007(12): 1225-1225  
DOI: 10.1055/s-2007-991305
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Salvinorin A

Contributor(s):Philip Kocienski, Stewart Eccles
J. R. Scheerer, J. F. Lawrence, G. C. Wang, D. A. Evans*
Harvard University, Cambridge, USA
Asymmetric Synthesis of Salvinorin A, A Potent κ Opioid Receptor Agonist
J. Am. Chem. Soc.  2007,  129:  8968-8969  
CrossrefGoogle Scholar
Further Information

Publication History

Publication Date:
22 November 2007 (online)

 PDF Download Permissions and Reprints

Key words

bis-Michael addition - macrolactonization -

Significance

Salvinorin A is a neoclerodane diterpene isolated from Salvia divinorum. As a potent agonist of the κ opioid receptor, it is the only non-alkaloid psychoactive substance and the most potent naturally occuring hallucinogen. The synthesis of salvinorin exploits a bis-Michael addition of macrocylce E to create the tricyclic core. A rich array of innovative chemistry was used to synthesise fragment B.

Comment

The 14-membered macrolactone E was produced at very low concentrations (0.0015 M) using MNBA to produce a mixed an­hydride which cyclized in very good yield (96%). The transannular bis-Michael addition of E promoted by TBAF was proposed to go via the transition state F to give the correct stereochemistry in G. It was also suggested that a concerted exo-selective Diels-Alder reaction would result in the correct product.

   Permissions and Reprints