8-epi-Salvinorin B: crystal structure and affinity at the kappa opioid receptor.
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.
Munro
Thomas A
TA
Mailman Research Center, McLean Hospital, 115 Mill St, Belmont, MA 02478-9106, USA. tmunro@mclean.harvard.edu
Duncan
Katharine K
KK
Staples
Richard J
RJ
Xu
Wei
W
Liu-Chen
Lee-Yuan
LY
Béguin
Cécile
C
Carlezon
William A
WA
Cohen
Bruce M
BM