( )-1-Hydroxy-6 , 6-dimethyl-1 H , 6 H-naphtho-[ 1 , 2-c ] furan-3 , 9-trione

The 1-hydroxyphthalide unit in the title compound, (II), is present in several natural products which display biological activity. For example, madurahydroxylactone (Jutten et al., 2002) and its derivatives exhibit activity as esterone sulfatase inhibitors. 1-Hydroxyphthalides also have been used as precursors for the synthesis of inhibitors of platelet aggegation (Sugimoto et al., 1984) and GABAB receptor antagonists (Donati et al., 1989). 1-Hydroxyphthalides with a -ketone, as in compound (II), occur in natural product metabolites of aspergillus duricaulis (Achenbach et al., 1985) and the basidiomycete Hyphoderma radula (Henkel et al., 1997). We report here the structural elucidation of (II), prepared by regioselective reduction of anhydride (I) previously obtained from 4,4-dimethylcyclohexane-1,3-dione (Henderson et al., 2006).

The title compound, C 14 H 12 O 4 , crystallizes as discrete molecular species which form hydroxy-to-ketone hydrogenbonded dimers disposed about crystallographic centres of symmetry.

Comment
The 1-hydroxyphthalide unit in the title compound, (II), is present in several natural products which display biological activity. For example, madurahydroxylactone (Jutten et al., 2002) and its derivatives exhibit activity as esterone sulfatase inhibitors. 1-Hydroxyphthalides also have been used as precursors for the synthesis of inhibitors of platelet aggegation (Sugimoto et al., 1984) and GABA B receptor antagonists (Donati et al., 1989). 1-Hydroxyphthalides with a -ketone, as in compound (II), occur in natural product metabolites of aspergillus duricaulis (Achenbach et al., 1985) and the basidiomycete Hyphoderma radula (Henkel et al., 1997). We report here the structural elucidation of (II), prepared by regioselective reduction of anhydride (I) previously obtained from 4,4-dimethylcyclohexane-1,3-dione (Henderson et al., 2006).
Compound (II) crystallizes in the space group P2 1 /c as discrete molecular species and is isomorphous with 1-hydroxy-6,6-dimethyl-7,8-dihydronaphtho[1,2-c]furan-3,9(1H,6H)-dione (hyphodermin B) (Henderson et al., 2006). All three rings and carbonyl atom O3 are coplanar. In the structure of hyphodermin B, the cyclohexyl ring is disordered with C7 modelled as two C atoms with 50% occupancy above and below the plane. The methyl groups on C6 lie above and below this plane with the Fourier synthesis showing an eclipsed conformation for the H atoms on these two groups. Carbonyl atom O4 is twisted slightly out of the plane of the molecule, the pseudo-torsion angle O4-C9Á Á ÁC9b-C1 being 8.7 (3) . The geometry of the 1-hydroxyphthalimide ring is in good accord with that observed for other 1-hydroxyphthalide compounds (Valente et al., 1998;Khoo & Hazell, 1999;Paulus et al., 1994). In these two structures and in (II), the molecules form R 2 2 (14) (Bernstein et al., 1995) O-HÁ Á ÁO hydroxy-toketone hydrogen-bonded dimers about a crystallographic centre of symmetry (Table 2 and Fig. 1). This hydroxy-to-ketone dimerization mode is rare, with only six examples previously reported (Rath et al., 2005, and references therein).
Significant residual electron density in the vicinity of the H atom bonded to C1 suggested the presence of minor enantiomeric disorder of the hydroxy group in the crystal structure. This was modelled with occupancy factors of 0.9 for the major component and 0.  View of the major component of the molecule of (II), shown in its hydrogen-bonded dimer. The symmetry code of the primed atoms ( 0 ) is 2 À x, 2 À y, 1 À z). Displacement ellipsoids for non-H atoms are drawn at the 30% probability level and H atoms are shown as circles of arbitrary radii. Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (