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

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.

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] D 20 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 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. 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 7epiclusianone (I), and slow evaporation from methanol yielded suitable crystals. The crystals were colorless and cubelike (m.p. 365 -366 K). The HREIMS, 1 H and 13 C NMR were the same as indicated in the literature (Christian et al., 2008).

Refinement
H atoms on C were placed in idealized positions with C-H distances 0.95 -1.00 Å and thereafter treated as riding.
Coordinates of the OH hydrogen atom were refined. A torional parameter was refined for each methyl group. U iso for H were assigned as 1.2 times U eq of the attached atoms (1.5 for methyl and OH).

Computing details
Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); 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).    Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.