(2S,4aR,6aR,7R,9S,10aS,10bR)-7-Carb­oxy-2-(3-fur­yl)-6a,10b-dimethyl-4,10-dioxoperhydro­benzo[f]isochromen-9-yl acetate

Paulo Carvalho; Lukasz M Kutrzeba; Jordan K Zjawiony; Mitchell A Avery

doi:10.1107/S1600536809002074

. 2009 Feb 6;65(Pt 3):o471–o472. doi: 10.1107/S1600536809002074

(2S,4aR,6aR,7R,9S,10aS,10bR)-7-Carboxy-2-(3-furyl)-6a,10b-dimethyl-4,10-dioxoperhydrobenzo[f]isochromen-9-yl acetate

Paulo Carvalho ^a, Lukasz M Kutrzeba ^b, Jordan K Zjawiony ^b,^c, Mitchell A Avery ^a,^c,^d,^*

PMCID: PMC2968482 PMID: 21582142

Abstract

The asymmetric unit of the title compound, C₂₂H₂₆O₈, contains two crystallographically independent molecules with closely comparable conformations (r.m.s. overlay = 0.54 Å for 30 non-H atoms). All six-membered rings display chair conformations, with a slight distortion for the lactone ring. The molecules are connected by O—H⋯O hydrogen bonds into chains along [010], with the independent molecules segregated into separate chains. The two molecules in the asymmetric unit face each other in a head-to-tail fashion, with the furan ring of one molecule turned towards the carboxylic acid terminal of the other molecule.

Related literature

For the biosynthesis of Salvinorin A, see: Kutrzeba et al. (2007 ▶). For the isolation of Salvinorin A and further synthesis details, see: Lee, Karnati et al. (2005 ▶); Lee, He et al. (2005 ▶); Stewart (2005 ▶). For details on epimerization at the C-8 stereogenic center, see: Harding et al. (2005 ▶).

Experimental

Crystal data

C₂₂H₂₆O₈
M _r = 418.43
Monoclinic,
a = 11.2735 (6) Å
b = 16.8015 (9) Å
c = 11.3765 (6) Å
β = 111.934 (3)°
V = 1998.86 (18) Å³
Z = 4
Cu Kα radiation
μ = 0.89 mm⁻¹
T = 100 (2) K
0.19 × 0.12 × 0.09 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: none
33644 measured reflections
7269 independent reflections
6962 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.074
S = 1.10
7269 reflections
549 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.18 e Å⁻³
Absolute structure: Flack (1983 ▶), 3360 Friedel pairs
Flack parameter: −0.09 (13)

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL .

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809002074/bi2338sup1.cif

e-65-0o471-sup1.cif^{(31.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809002074/bi2338Isup2.hkl

e-65-0o471-Isup2.hkl^{(355.7KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O8—H8A⋯O6ⁱ	0.82	1.92	2.7264 (18)	168
O8′—H8′⋯O3′ⁱⁱ	0.82	1.92	2.7308 (17)	172

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Symmetry code: (i) Inline graphic ; (ii) .

Acknowledgments

The authors thank the Center for Disease Control and Prevention, USA, for providing financial assistance (CDC cooperative agreements 1UO1CI000211–03 and1UO1 CI000362–01). This Investigation was conducted in a facility constructed with support from Research Facilities Improvement Program grant No. C06 RR-14503–01 from the National Center for Research Resources, National Institutes of Health.

supplementary crystallographic information

Comment

Diterpenoid salvinorin A is a potent kappa opioid agonist isolated from Mexican mint Salvia divinorum. The biosynthesis of this natural product was studied using synthetic analogues of salvinorin A modified at C-2 and C-18 as chemical probes for in vitro enzymatic reactions. Salvinorin A and its C-8 epimeric counterpart revealed low affinity to the kappa-opioid receptor.

Experimental

The starting material for synthesis, salvinorin A, was isolated from dry plant material, and purified according to a previously published procedure (Stewart, 2005). Salvinorin A acid was synthesized following Lee, He et al. (2005), by using LiI in pyridine as a selective hydrolyzing agent of C-4 methyl ester.