Redetermination and absolute configuration of (+)-7-epiclusianone

Omar E Christian; Frank R Fronczek; Khoa Ky; Shreedu Pradhan; Anjela Manandhar; Cecilia Richmond

doi:10.1107/S1600536812043784

. 2012 Oct 27;68(Pt 11):o3222–o3223. doi: 10.1107/S1600536812043784

Redetermination and absolute configuration of (+)-7-epiclusianone

Omar E Christian ^a,^*, Frank R Fronczek ^b, Khoa Ky ^a, Shreedu Pradhan ^a, Anjela Manandhar ^a, Cecilia Richmond ^c

PMCID: PMC3515307 PMID: 23284527

Abstract

The absolute configuration of 3-benzoyl-4-hydroxy-6,6-dimethyl-1,5,7-tris(3-methylbut-2-enyl)bicyclo[3.3.1]non-3-ene-2,9-dione, C₃₃H₄₂O₄, isolated from Hypericum hypericoides, has been determined. The previous study [Xiao et al. (2007 ▶). J. Nat. Prod. 70, 1779–1782] gave only the established relative configuration. The three stereogenic centers are now established as 1R, 5R and 7S on the basis of the refinement of the Flack absolute structure parameter against Cu Kα data and correspond to a specific rotation of [α]_D ²⁰ = +66°. The enol–hydroxy group forms an intramolecular O—H⋯O hydrogen bond to close an S(6) ring.

Related literature

For a review of polycyclic polyprenylated acylphloroglucinols, see: Ciochina & Grossman (2006 ▶). For background to Clusiaceae metabolites, see: Garnsey et al. (2011 ▶); Zhang et al. (2010 ▶); Christian et al. (2008 ▶); Wu et al. (2008 ▶). For relative-configuration structure determinatons, see: Santos et al. (1998 ▶); Xiao et al. (2007 ▶); Martins et al. (2009 ▶). For related structures, see: McCandlish et al. (1976 ▶); Fronczek et al. (2012 ▶). For optical rotation results for the title compound, see: Piccinelli et al. (2005 ▶) and for related compounds, see: Tanaka et al. (2004 ▶). For keto–enol tautomerism in related compounds, see: Martins et al. (2007 ▶). For absolute configuration based on resonant scattering from light atoms, see: Hooft et al. (2008 ▶)

Experimental

Crystal data

C₃₃H₄₂O₄
M _r = 502.67
Orthorhombic,
a = 8.6177 (4) Å
b = 12.4157 (6) Å
c = 26.8632 (13) Å
V = 2874.2 (2) Å³
Z = 4
Cu Kα radiation
μ = 0.59 mm⁻¹
T = 90 K
0.25 × 0.24 × 0.16 mm

Data collection

Bruker Kappa APEXII CCD DUO diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2004 ▶) T _min = 0.824, T _max = 0.889
17192 measured reflections
5171 independent reflections
5131 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.028
wR(F ²) = 0.074
S = 1.03
5171 reflections
345 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.14 e Å⁻³
Absolute structure: Flack (1983 ▶), 2200 Friedel pairs
Flack parameter: 0.04 (12)

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶).

Supplementary Material

Click here for additional data file.^{(27.3KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812043784/hb6978sup1.cif

e-68-o3222-sup1.cif^{(27.3KB, cif)}

Click here for additional data file.^{(253.3KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812043784/hb6978Isup2.hkl

e-68-o3222-Isup2.hkl^{(253.3KB, hkl)}

Click here for additional data file.^{(11.1KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812043784/hb6978Isup3.cml

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
O2—H2O⋯O4	1.014 (16)	1.477 (16)	2.4368 (12)	155.7 (15)

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Acknowledgments

Financial support provided by the Louisiana Environmental Research Center (LERC), Chenier Plain Sustainability Initiative Collaboration Award # 687217–10-006. Upgrade of the diffractometer was made possible by grant No. LEQSF(2011–12)-ENH-TR-01, administered by the Louisiana Board of Regents.

supplementary crystallographic information

Comment

Recently, there has been a resurgence of interest in the Clusiaceae family due mainly to the significant synthetic challenge presented by several compound classes isolated from this family, in particular the benzophenone-type metabolites which contain the bridged bicyclics (Garnsey et al., 2011) and tricyclic cores (Zhang et al., 2010). The simpler and stereochemically less dense bicyclononanes occur frequently in the genus Hypericum (Christian et al., 2008), plants related to St. John's Wort (Ciochina & Grossman, 2006). The Hypericum genus is one of largest in the Clusiaceae family of plants and is distributed worldwide. The phloroglucinol derived metabolites from various species within this genus have shown good potential as antioxidants (Wu et al., 2008). The hexane extract of Hypericum hypericoides collected in Lake Charles, Louisiana, yielded the title compound (I). 7-Epiclusianone (I) has previously been isolated from Rheedia gardneriana (Santos et al., 1998), H. sampsonii (Xiao et al., 2007) and from a Jamaican collection of H. hypericoides (Christian et al., 2008). The gross structure was confirmed by ¹H NMR, ¹³C NMR and DEPT analysis displaying the diagnostic resonances for the bicyclononane core, in addition to the requisite ³J_HH coupling to establish the C-7 prenyl group as axial (Piccinelli et al., 2005, Christian et al., 2008). The melting point (365–366 K) and specific rotation (+66°) of (I) was similar to that of Santos et al., (1998) (+77°), Piccinelli et al., (2005) (+62.3°) and Christian et al., (2008) (+67.5°). However, these values are in stark contrast to the H. sampsonii collection isolated by Xiao and coworkers, which gave a specific rotation of -9.65° (Xiao et al., 2007). This ambiguity in the stereochemistry and a lack of absolute structural data prompted this investigation to unequivocally determine the absolute configuration of (I) and correlate it with chiroptical data.

The structure of (I) has been reported several times, all at room temperature and yielding only relative configuration (Santos et al., 1998; Xiao et al., 2007; Martins et al., 2009). Our low-temperature Cu Kα data with 2200 Bijvoet pairs allowed unambiguous determination of the absolute configuration from the Flack (1983) parameter x=0.04 (12). The Hooft et al., (2008) analysis yielded y=0.02 (4) and P2(true)=1.000. This configuration is depicted in Fig. 1, and has the R configuration at C1 and C5, and the S configuration at C7.

Keto-enol tautomerism is a common feature in natural polyprenylated benzophenones (Martins et al., 2007), and also exists in (I). In the solid, the C═C double bond is between C3 and C4, with distance 1.3932 (16) Å, and C2═O1 is a ketone, with distance 1.2169 (13) Å. Hydroxy group O2 forms an intramolecular hydrogen bond to the benzophenone O4, as shown in Fig. 2.

The quite different [α]_D²⁰ value of -9.65° for 7-epiclusianone from H. sampsonii reported by Xiao et al., (2007) is of considerable interest, particularly since that structure was confirmed by crystal structure determination. It seems likely that their sample was a partial racemate. Closely related polyprenylated phloroglucinols have been found to be racemic by crystal structure determination. Clusianone from Clusia congestiflora crystallizes in racemic Pna2₁ (McCandlish et al., 1976). Hyperibone L from H. dolabriforme differs from (I) only by having a methyl group instead of an prenyl group at C5, and crystallizes in racemic P-1 (Fronczek et al., 2012), while it has been reported with an optical rotation of +69.5° from H. scabrum (Tanaka et al., 2004). Since no obvious means of racemization of these compounds during isolation and crystallization is apparent, the plants appear to commonly produce both enantiomers, and in unequal amounts.

Experimental

Hypericum hypericoides was collected from Sam Houston Jones State Park, Calcasieu Parish, LA, (N 30 18.1246, W 93 15.5163) in June 2011. Voucher specimens are preserved in the Herbarium, Department of Biological Sciences, McNeese State University. The dried and pulverized roots of H. hypericoides (204 g) were extracted with hexane (3 x 1.5 L). The evaporation of the hexanes yielded a yellowish gum (4.3 g). The hexane extract was chromatographed over silica gel and eluted with 0 – 100% hexane/ethyl acetate mixtures to yield fifteen fractions (B1 – B15). Fraction B2 yielded 7-epiclusianone (I), and slow evaporation from methanol yielded suitable crystals. The crystals were colorless and cube-like (m.p. 365 - 366 K). The HREIMS, ¹H and ¹³C NMR were the same as indicated in the literature (Christian et al., 2008).