(3R,4S,5S,8S,10R,13R)-3-Hydroxykaura-9(11),16-dien-18-oic acid

The title compound, C20H28O3, was isolated during our investigation into the chemical composition and pharmacological activity of Centipeda cunninghamii (DC.) A. Braun & Asch. (Asteraceae). The enantiopure compound, a diterpene with a carbon skeleton, is composed of three six- and one five-membered rings in chair, twist-boat, half-chair and envelope conformations, respectively. Each molecule makes one intra- and one intermolecular O—H⋯O hydrogen bond in the crystal lattice, forming hydrogen-bonded chains along [010]. The absolute configuration of the compound was assigned on the basis of optical rotation measurements.

The title compound, C 20 H 28 O 3 , was isolated during our investigation into the chemical composition and pharmacological activity of Centipeda cunninghamii (DC.) A. Braun & Asch. (Asteraceae). The enantiopure compound, a diterpene with a carbon skeleton, is composed of three six-and one fivemembered rings in chair, twist-boat, half-chair and envelope conformations, respectively. Each molecule makes one intraand one intermolecular O-HÁ Á ÁO hydrogen bond in the crystal lattice, forming hydrogen-bonded chains along [010]. The absolute configuration of the compound was assigned on the basis of optical rotation measurements.
The majority of the ent-kaurane diterpenes characteristically exhibit negative values for optical rotation with the exception of those that feature a double bond between C9 and C11. Piozzi and co-workers (Piozzi et al., 1972) have demonstrated that sequential catalytic hydrogenation of the exocyclic C16-C17 and the endocyclic C9-C11 double bonds in grandiflorenic acid [(4α)-kaura-9(11),16-dien-18-oic acid] transforms the optical rotation from +38 to +43° and subsequently to -80° in the saturated product. More recently Reynolds and co-workers (Reynolds et al., 1991) have analysed the solid state and solution characteristics of grandiflorenic acid, and have determined that the introduction of the C9-C11 double bond in grandiflorenic acid has a drastic effect on the molecular conformation and consequently on optical rotation, whereby the B ring adopts a boat conformation compared to the regular chair conformation in kaurenoic acid. In the case of compound (I) the observed rotation is [α] D 22 + 30.8° (c 0.12, MeOH), which is in agreement with values for the methyl ester derivative of the 3S isomer, +15° (Bohlmann et al., 1982) and the closely related grandiflorenic acid +32.1° (Brieskorn & Pöhlmann, 1968) and + 46° (Reynolds et al., 1991) and establishes the 3R,4S,5S,8S,10R,13R absolute stereochemistry of compound (I). The 3S isomer of compound (I) has been obtained previously from Ichthyothere terminalis (Bohlmann et al., 1982) and Pseudognaphalium cheiranthifolium (Mendoza & Urzúa, 1998). The antibacterial activity of the 3S isomer has also been evaluated and is described in Mendoza et al. (1997).
The column was eluted using a stepwise gradient of H 2 O/CH 3 CN containing 0.05% CF 3 COOH (3:2 to 1:3 over 16.4 min; 1:3 isocratic for 3.6 min; then 1:3 to 1:9 over 1.0 min; then 1:9 isocratic for 7 minutes) at a flow rate of 15 ml/min. Crystals suitable for X-ray diffraction were obtained by slow evaporation of the H 2 O/CH 3 CN HPLC eluent of (I).

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance mat- 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 Rfactors(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.  (4) 169 (5) O1-H1O1···O2 0.96 (7) 1.94 (6) 2.651 (4) 129 (5) Symmetry codes: (i) −x+1, y−1/2, −z+2.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
supplementary materials sup-9