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