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. 2007 Jan 9:3:1.
doi: 10.1186/1860-5397-3-1.

8-epi-Salvinorin B: crystal structure and affinity at the kappa opioid receptor

Thomas A Munro  1 , Katharine K Duncan, Richard J Staples, Wei Xu, Lee-Yuan Liu-Chen, Cécile Béguin, William A Carlezon Jr, Bruce M Cohen
Affiliations

8-epi-Salvinorin B: crystal structure and affinity at the kappa opioid receptor

Thomas A Munro et al. Beilstein J Org Chem. .

Abstract

There have been many reports of epimerization of salvinorins at C-8 under basic conditions, but little evidence has been presented to establish the structure of these compounds. We report here the first crystal structure of an 8-epi-salvinorin or derivative: the title compound, 2b. The lactone adopts a boat conformation with the furan equatorial. Several lines of evidence suggest that epimerization proceeds via enolization of the lactone rather than a previously proposed indirect mechanism. Consistent with the general trend in related compounds, the title compound showed lower affinity at the kappa opioid receptor than the natural epimer salvinorin B (2a). The related 8-epi-acid 4b showed no affinity.

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Figures

Figure 1
Figure 1
Stereoview of the molecular structure of 2b, showing 50% probability displacement ellipsoids and the atom-numbering scheme. Only one of the two molecules in the asymmetric unit is shown.
Figure 2
Figure 2
Stereoview of the packing of 2b. H atoms are not shown.
Scheme 1
Scheme 1
Koreeda et al's proposed mechanism for the epimerization.
See this image and copyright information in PMC

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