An ent-kaurane diterpenoid from Isodon japonica var. glaucocalyx

Su-Ping Bai; Guo-Sheng Luo; Xiao-Yi Zhang; Wei Liu

doi:10.1107/S1600536809027159

. 2009 Jul 18;65(Pt 8):o1898. doi: 10.1107/S1600536809027159

An ent-kaurane diterpenoid from Isodon japonica var. glaucocalyx

Su-Ping Bai ^a,^*, Guo-Sheng Luo ^b, Xiao-Yi Zhang ^a, Wei Liu ^a

PMCID: PMC2977125 PMID: 21583588

Abstract

The title compound, 14β-acetoxy-7α-hydroxy-ent-kaur-16-ene-3,15-dione or glaucocalyxin B, C₂₂H₃₀O₅, a natural ent-kaurane diterpenoid, is composed of four rings with the expected cis and trans ring junctions. In the crystal structure, there are two molecules in the asymmetric unit related by a noncrystallographic twofold screw axis, and ring A is disordered [ratio occupancies 0.829 (19):0.171 (19)], such that both chair and boat conformations are present, but with the boat conformation as the major component. In the crystal, molecules are linked by intermolecular O—H⋯O hydrogen bonds.

Related literature

For related literature on the genus Isodon and diterpenoids therefrom, see: Liu et al. (1988 ▶); Kim et al. (1992 ▶); Sun et al. (2001 ▶); Bai et al. (2005 ▶). For expected bond-length ranges, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₂₂H₃₀O₅
M _r = 374.46
Monoclinic,
a = 8.485 (4) Å
b = 23.786 (10) Å
c = 9.930 (4) Å
β = 91.039 (17)°
V = 2003.8 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.36 × 0.34 × 0.32 mm

Data collection

Rigaku R-AXIS RAPID diffractometer
Absorption correction: none
19620 measured reflections
4669 independent reflections
2856 reflections with I > 2σ(I)
R _int = 0.070

Refinement

R[F ² > 2σ(F ²)] = 0.063
wR(F ²) = 0.164
S = 1.00
4669 reflections
524 parameters
14 restraints
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: RAPID-AUTO (Rigaku, 2004 ▶); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; 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 global, I. DOI: 10.1107/S1600536809027159/ez2171sup1.cif

e-65-o1898-sup1.cif^{(41.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809027159/ez2171Isup2.hkl

e-65-o1898-Isup2.hkl^{(228.7KB, 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
O2—H2O⋯O1ⁱ	0.82	2.09	2.747 (6)	137
O2—H2O⋯O1ⁱ	0.82	2.09	2.747 (6)	137
O2′—H2O′⋯O1′ⁱ	0.82	2.05	2.764 (5)	146
O2′—H2O′⋯O1*ⁱ	0.82	2.24	2.89 (3)	136

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported by the Henan Province Science and Technology Foundation (grant No. 082300450440)

supplementary crystallographic information

Comment

The title compound (I) is a natural ent-kaurane diterpenoid isolated from the medicinal plant Isodon japonica var. glaucocalyx. This plant has been used in antibacterial, inflammation-diminishing and stomachic agents. The structure has been postulated previously based on spectroscopic methods (Liu et al., 1988; Kim et al.,1992; Bai et al., 2005). In order to further confirm the structure and conformation of (I), a crystal structure analysis, reported here, was undertaken.

The X-ray crystallographic analysis of (I) confirms the previously proposed molecular structure of (I). Fig. 1 shows its conformation: two carbonyl groups located at C3 and C15, while a hydroxyl group and an acetoxyl group adopt α and β-orientations at C7 and C14 respectively. There is a trans junction between ring A (C1–C5/C10) and ring B (C5–C10); cis junctions are present between ring B and ring C (C8/C9/C11–C14), and ring C and ring D (C8/C13–C16).

The crystal structure analysis shows that there are two molecules in the asymmetric unit, each with different bond lengths and angles, but which are within expected ranges (Allen et al., 1987). In both molecules ring B adopts a chair conformation and ring C has a slight-twist chair conformation. Ring A is disordered, such that both chair and boat conformations are present, but with the boat conformation as the major component. The ratios of boat to chair conformations are 66.7%:32.3% for C1–C5/C10, and 82.9%:17.1% for C1'–C5'/C10'. Ring D shows an envelope conformation; the flap atom, C14, lies 0.660 (6) Å from the plane defined by atoms C8, C15, C16 and C13 [0.665 (7) Å for atom C14'].

Compound (I) contains seven chiral centers at C5(S), C7(R), C8(R), C9(S), C10(R), C13(R) and C14(R). Although the absolute configuration could not be reliably determined from anomalous dispersion effects, the negative optical rotation showed this compound to be in the ent-kaurane seuies as reported in genus Isodon (Sun et al., 2001), rather than in the kaurane series, and so allowed us to assign the correct configuration. In the crystal structure, the molecules are linked by O—H···O hydrogen bonds into chains parallel to the c axis (Table 1 and Fig. 2).

Experimental

The dried and crushed leaves of Isodon japonica var. glaucocalyx (10 kg, collected from Hui Prefecture, Henan Province, China) were extracted four times with Me₂CO/H₂O (7:3, v/v) at room temperature over a period of seven days. The extract was filtered and the solvent was removed under reduced pressure. The residue was then partitioned between water and AcOEt. After removal of the solvent, the AcOEt residue was separated by repeated silica gel (200–300 mesh) column chromatography and recrystallization from CHCl₃/Me₂CO(20:1), giving 700 mg of compound (I) (m.p. 463–465 K. Optical rotation: [α]_D²⁰ -130 ° (c 0.95, CHCl₃). Crystals suitable for X-ray analysis were obtained by slow evaporation of a solution of the compound (I) in Me₂CO at room temperature.