6β,10β-Cadinene-6,10-diol: a sesquiterpenoid from the rhizome of Acorus calamus L.

The title compound [systematic name: (1S,6R,7S,10S)-7-isopropyl-10-methyl-4-methyl­enedeca­hydro­naphthalene-6,10-diol], C₁₅H₂₆O₂, was isolated from the rhizome of Acorus calamus L. The mol­ecule contains two fused six-membered rings, each in a chair conformation. The mol­ecules are linked together by inter­molecular O—H...O hydrogen bonding.

Key indicators

• Single-crystal X-ray study
• T = 153 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.031
• wR factor = 0.090
• Data-to-parameter ratio = 10.7

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       2.78 Ratio
PLAT222_ALERT_3_C Large Non-Solvent    H     Ueq(max)/Ueq(min) ...       3.10 Ratio

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.50
           From the CIF: _reflns_number_total               1860
           Count of symmetry unique reflns         1868
           Completeness (_total/calc)             99.57%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C1     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C6     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C7     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C10    = .          S

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   5 ALERT level G = General alerts; check

   4 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

S1. Comment

Acorus calamus L. is a traditional Chinese herb distributed widely in China. It is well known for its medicinal properties such as emetic stomach in dyspepsy, remittet fever, nerve tonic and expectorant (Robert & Henrey, 1983). As part of our investigation of the bioactive constituents of the rhizome of A. calamus, we recently isolated the title compound. Its structure was elucidated by spectroscopic analysis including two-dimensional NMR, and was confirmed by single-crystal X-ray diffraction analysis.

The molecule contains two trans fused six-membered rings (Fig. 1). In the crystal structure, the molecules are combined by intermolecular hydrogen bonding.

Related literature

For general background, see: Robert & Henrey (1983). For a related structure, see: Yamamura et al. (1971).

S2. Experimental

The rhizome of Acorus calamus L. (15 kg) were collected in the Tibet Autonomous area of China. The ethanol extract (2 kg) was suspended in water (2 l) and partitioned successively with petroleum ether, EtOAc and n-butanol. The EtOAc extract (1 kg) was chromatographed over silica gel (160–200 mesh, 2.3 kg) column with eluents of increasing polarity [petroleum ether-acetone (20:1, 15:1, 10:1, 5:1, 2:1, 1:1)] to afford Fr. 1–7 according to TLC analysis. Fr.5 (200 g) was applied to a silica gel (200–300 mesh, 1.6 kg) column and eluted with petroleum ether-acetone (10:1, 5:1, 2:1, 1:1) to obtain the title compound. The isolated product was recrystallized from a methanol solution to afford single crystals (30 mg).

S3. Refinement

Hydroxy H atoms were located in a difference Fourier map and refined isotropically. Other H atoms were placed in calculated positions with C—H = 0.94–1.00 Å, and refined in riding mode with U_iso(H) = 1.2U_eq(C). As no significant anomalous scatters the absolute configuration could not be determined from the X-ray analysis, Friedel pairs were merged. We assigned the conformation by reference to the chiral molecule of known absolute configuration (Yamamura et al., 1971).

Computing details

Data collection: RAPID-AUTO (Rigaku, 2004); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Siemens, 1997); software used to prepare material for publication: SHELXTL.

Figures

Fig. 1. View of the molecule of (1) showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

(1S,6R,7S,10S)-7-isopropyl-10-methyl-4-methylenedecahydronaphthalene-6,10-diol

Crystal data

C15H26O2	Dx = 1.127 Mg m^−3
Mr = 238.36	Melting point = 443–444 K
Orthorhombic, P21212	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2 2ab	Cell parameters from 13629 reflections
a = 9.8941 (4) Å	θ = 3.0–27.5°
b = 15.7201 (7) Å	µ = 0.07 mm^−1
c = 9.0288 (4) Å	T = 153 K
V = 1404.3 (1) Å^3	Block, colourless
Z = 4	0.36 × 0.36 × 0.36 mm
F(000) = 528

Data collection

Rigaku R-AXIS RAPID IP diffractometer	1823 reflections with I > 2σ(I)
Radiation source: Rotating Anode	Rint = 0.021
Graphite monochromator	θmax = 27.5°, θmin = 3.0°
ω scans	h = −12→12
13880 measured reflections	k = −20→20
1860 independent reflections	l = −11→11

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.031	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.090	w = 1/[σ^2(Fo^2) + (0.0656P)^2 + 0.1876P] where P = (Fo^2 + 2Fc^2)/3
S = 1.00	(Δ/σ)max = 0.001
1860 reflections	Δρmax = 0.31 e Å^−3
174 parameters	Δρmin = −0.15 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.033 (5)

Special details

Experimental. ¹³C NMR (600 MHz, CDCl₃, δ, p.p.m.): 50.3(C1), 22.8(C2), 34.3(C3), 145.9(C4), 45.6(C5), 76.4(C6), 51.5(C7), 16.5(C8), 41.3(C9), 71.8(C10), 25.5(C11), 18.0(C12), 23.6(C13), 28.1(C14), 111.5(C15).

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 matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² 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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.61793 (9)	0.70501 (6)	0.40440 (9)	0.0191 (2)
O2	0.84327 (9)	0.79719 (6)	0.46991 (9)	0.0219 (2)
C1	0.74027 (12)	0.79747 (8)	0.22996 (13)	0.0169 (2)
H1	0.7625	0.8010	0.1221	0.020*
C2	0.64773 (13)	0.87333 (8)	0.26421 (16)	0.0238 (3)
H2A	0.6980	0.9270	0.2480	0.029*
H2B	0.6201	0.8712	0.3695	0.029*
C3	0.52124 (14)	0.87232 (9)	0.16545 (18)	0.0288 (3)
H3A	0.4599	0.9190	0.1955	0.035*
H3B	0.5479	0.8820	0.0611	0.035*
C4	0.44852 (13)	0.78906 (9)	0.17762 (14)	0.0238 (3)
C5	0.53566 (12)	0.71155 (8)	0.15681 (14)	0.0222 (3)
H5A	0.5623	0.7076	0.0513	0.027*
H5B	0.4818	0.6603	0.1809	0.027*
C6	0.66413 (11)	0.71181 (7)	0.25289 (12)	0.0156 (2)
C7	0.75716 (12)	0.63626 (7)	0.21106 (14)	0.0183 (2)
H7	0.7832	0.6457	0.1053	0.022*
C8	0.88917 (13)	0.63991 (8)	0.29947 (14)	0.0211 (3)
H8A	0.8690	0.6338	0.4063	0.025*
H8B	0.9482	0.5920	0.2697	0.025*
C9	0.96268 (12)	0.72341 (8)	0.27323 (15)	0.0213 (3)
H9A	0.9885	0.7273	0.1675	0.026*
H9B	1.0467	0.7242	0.3328	0.026*
C10	0.87654 (12)	0.80067 (8)	0.31411 (13)	0.0187 (2)
C11	0.69087 (14)	0.54676 (8)	0.21637 (16)	0.0251 (3)
H11	0.5945	0.5535	0.1852	0.030*
C12	0.6908 (2)	0.50475 (10)	0.36807 (18)	0.0434 (4)
H12A	0.6393	0.4516	0.3636	0.052*
H12B	0.6491	0.5431	0.4404	0.052*
H12C	0.7840	0.4925	0.3980	0.052*
C13	0.75947 (19)	0.48835 (9)	0.1035 (2)	0.0398 (4)
H13A	0.8562	0.4845	0.1258	0.048*
H13B	0.7472	0.5116	0.0037	0.048*
H13C	0.7190	0.4315	0.1087	0.048*
C14	0.95452 (14)	0.88257 (9)	0.28216 (18)	0.0277 (3)
H14A	0.9036	0.9314	0.3203	0.033*
H14B	0.9669	0.8888	0.1750	0.033*
H14C	1.0430	0.8801	0.3307	0.033*
C15	0.31656 (14)	0.78297 (11)	0.20471 (19)	0.0336 (3)
H15A	0.274 (2)	0.7267 (13)	0.214 (2)	0.040 (5)*
H15B	0.263 (2)	0.8316 (14)	0.223 (2)	0.046 (6)*
H1O	0.688 (3)	0.7229 (15)	0.460 (3)	0.062 (7)*
H2O	0.918 (2)	0.7915 (13)	0.518 (2)	0.045 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0174 (4)	0.0239 (4)	0.0159 (4)	0.0001 (4)	0.0043 (3)	0.0028 (4)
O2	0.0207 (4)	0.0292 (4)	0.0160 (4)	0.0001 (4)	−0.0021 (3)	−0.0034 (4)
C1	0.0172 (5)	0.0171 (5)	0.0165 (5)	−0.0021 (4)	0.0004 (4)	0.0021 (4)
C2	0.0238 (6)	0.0174 (5)	0.0301 (7)	0.0009 (5)	−0.0020 (5)	0.0013 (5)
C3	0.0242 (6)	0.0253 (6)	0.0370 (7)	0.0027 (5)	−0.0041 (6)	0.0092 (6)
C4	0.0201 (6)	0.0293 (6)	0.0220 (6)	0.0001 (5)	−0.0051 (5)	0.0077 (5)
C5	0.0181 (5)	0.0253 (6)	0.0231 (6)	−0.0038 (5)	−0.0047 (5)	0.0024 (5)
C6	0.0152 (5)	0.0173 (5)	0.0144 (5)	−0.0020 (4)	0.0009 (4)	0.0021 (4)
C7	0.0187 (5)	0.0174 (5)	0.0186 (5)	−0.0020 (4)	0.0032 (5)	−0.0007 (4)
C8	0.0194 (5)	0.0208 (5)	0.0232 (6)	0.0036 (5)	0.0015 (5)	−0.0012 (5)
C9	0.0144 (5)	0.0267 (6)	0.0228 (6)	−0.0008 (4)	0.0013 (4)	−0.0032 (5)
C10	0.0173 (5)	0.0214 (5)	0.0173 (5)	−0.0026 (5)	0.0003 (4)	−0.0013 (5)
C11	0.0251 (6)	0.0180 (5)	0.0322 (7)	−0.0036 (5)	0.0052 (6)	−0.0010 (5)
C12	0.0644 (11)	0.0240 (6)	0.0417 (8)	−0.0068 (7)	0.0146 (9)	0.0073 (7)
C13	0.0463 (9)	0.0239 (7)	0.0491 (9)	−0.0067 (6)	0.0125 (8)	−0.0134 (7)
C14	0.0237 (6)	0.0261 (6)	0.0332 (7)	−0.0090 (5)	−0.0006 (6)	−0.0006 (6)
C15	0.0211 (6)	0.0432 (8)	0.0367 (8)	0.0028 (6)	−0.0012 (6)	0.0089 (7)

Geometric parameters (Å, º)

O1—C6	1.4462 (13)	C7—H7	1.0000
O1—H1O	0.90 (3)	C8—C9	1.5193 (16)
O2—C10	1.4457 (14)	C8—H8A	0.9900
O2—H2O	0.86 (2)	C8—H8B	0.9900
C1—C2	1.5350 (17)	C9—C10	1.5290 (17)
C1—C10	1.5484 (16)	C9—H9A	0.9900
C1—C6	1.5568 (15)	C9—H9B	0.9900
C1—H1	1.0000	C10—C14	1.5284 (17)
C2—C3	1.5367 (19)	C11—C12	1.521 (2)
C2—H2A	0.9900	C11—C13	1.530 (2)
C2—H2B	0.9900	C11—H11	1.0000
C3—C4	1.4976 (19)	C12—H12A	0.9800
C3—H3A	0.9900	C12—H12B	0.9800
C3—H3B	0.9900	C12—H12C	0.9800
C4—C15	1.332 (2)	C13—H13A	0.9800
C4—C5	1.5044 (18)	C13—H13B	0.9800
C5—C6	1.5389 (16)	C13—H13C	0.9800
C5—H5A	0.9900	C14—H14A	0.9800
C5—H5B	0.9900	C14—H14B	0.9800
C6—C7	1.5493 (16)	C14—H14C	0.9800
C7—C8	1.5318 (17)	C15—H15A	0.98 (2)
C7—C11	1.5531 (16)	C15—H15B	0.94 (2)
C6—O1—H1O	105.3 (17)	C7—C8—H8A	109.4
C10—O2—H2O	107.7 (14)	C9—C8—H8B	109.4
C2—C1—C10	113.29 (10)	C7—C8—H8B	109.4
C2—C1—C6	110.89 (9)	H8A—C8—H8B	108.0
C10—C1—C6	112.60 (9)	C8—C9—C10	112.45 (9)
C2—C1—H1	106.5	C8—C9—H9A	109.1
C10—C1—H1	106.5	C10—C9—H9A	109.1
C6—C1—H1	106.5	C8—C9—H9B	109.1
C1—C2—C3	111.16 (11)	C10—C9—H9B	109.1
C1—C2—H2A	109.4	H9A—C9—H9B	107.8
C3—C2—H2A	109.4	O2—C10—C14	109.30 (11)
C1—C2—H2B	109.4	O2—C10—C9	109.37 (10)
C3—C2—H2B	109.4	C14—C10—C9	110.01 (10)
H2A—C2—H2B	108.0	O2—C10—C1	106.14 (9)
C4—C3—C2	110.96 (10)	C14—C10—C1	111.99 (10)
C4—C3—H3A	109.4	C9—C10—C1	109.94 (10)
C2—C3—H3A	109.4	C12—C11—C13	109.84 (12)
C4—C3—H3B	109.4	C12—C11—C7	114.92 (12)
C2—C3—H3B	109.4	C13—C11—C7	109.61 (11)
H3A—C3—H3B	108.0	C12—C11—H11	107.4
C15—C4—C3	123.18 (14)	C13—C11—H11	107.4
C15—C4—C5	121.77 (13)	C7—C11—H11	107.4
C3—C4—C5	115.05 (11)	C11—C12—H12A	109.5
C4—C5—C6	113.62 (10)	C11—C12—H12B	109.5
C4—C5—H5A	108.8	H12A—C12—H12B	109.5
C6—C5—H5A	108.8	C11—C12—H12C	109.5
C4—C5—H5B	108.8	H12A—C12—H12C	109.5
C6—C5—H5B	108.8	H12B—C12—H12C	109.5
H5A—C5—H5B	107.7	C11—C13—H13A	109.5
O1—C6—C5	105.78 (9)	C11—C13—H13B	109.5
O1—C6—C7	111.20 (9)	H13A—C13—H13B	109.5
C5—C6—C7	110.57 (9)	C11—C13—H13C	109.5
O1—C6—C1	110.04 (9)	H13A—C13—H13C	109.5
C5—C6—C1	109.09 (9)	H13B—C13—H13C	109.5
C7—C6—C1	110.07 (9)	C10—C14—H14A	109.5
C8—C7—C6	110.54 (9)	C10—C14—H14B	109.5
C8—C7—C11	112.21 (10)	H14A—C14—H14B	109.5
C6—C7—C11	115.85 (9)	C10—C14—H14C	109.5
C8—C7—H7	105.8	H14A—C14—H14C	109.5
C6—C7—H7	105.8	H14B—C14—H14C	109.5
C11—C7—H7	105.8	C4—C15—H15A	119.8 (12)
C9—C8—C7	111.05 (10)	C4—C15—H15B	121.4 (14)
C9—C8—H8A	109.4	H15A—C15—H15B	118.7 (18)
C10—C1—C2—C3	173.71 (10)	O1—C6—C7—C11	62.51 (13)
C6—C1—C2—C3	−58.55 (13)	C5—C6—C7—C11	−54.69 (13)
C1—C2—C3—C4	54.42 (15)	C1—C6—C7—C11	−175.28 (11)
C2—C3—C4—C15	129.47 (15)	C6—C7—C8—C9	−57.77 (13)
C2—C3—C4—C5	−50.57 (16)	C11—C7—C8—C9	171.24 (10)
C15—C4—C5—C6	−129.50 (14)	C7—C8—C9—C10	58.00 (13)
C3—C4—C5—C6	50.54 (15)	C8—C9—C10—O2	61.20 (13)
C4—C5—C6—O1	66.73 (12)	C8—C9—C10—C14	−178.75 (12)
C4—C5—C6—C7	−172.78 (10)	C8—C9—C10—C1	−54.97 (13)
C4—C5—C6—C1	−51.61 (13)	C2—C1—C10—O2	62.15 (13)
C2—C1—C6—O1	−59.63 (12)	C6—C1—C10—O2	−64.69 (12)
C10—C1—C6—O1	68.48 (12)	C2—C1—C10—C14	−57.05 (14)
C2—C1—C6—C5	56.00 (12)	C6—C1—C10—C14	176.11 (10)
C10—C1—C6—C5	−175.89 (9)	C2—C1—C10—C9	−179.67 (10)
C2—C1—C6—C7	177.48 (10)	C6—C1—C10—C9	53.49 (12)
C10—C1—C6—C7	−54.41 (12)	C8—C7—C11—C12	43.20 (16)
O1—C6—C7—C8	−66.54 (12)	C6—C7—C11—C12	−85.04 (15)
C5—C6—C7—C8	176.26 (9)	C8—C7—C11—C13	−81.05 (14)
C1—C6—C7—C8	55.66 (12)	C6—C7—C11—C13	150.71 (12)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O2	0.90 (3)	1.94 (3)	2.7240 (13)	146 (2)
O2—H2O···O1^i	0.86 (2)	2.10 (2)	2.9452 (13)	167 (2)

Symmetry code: (i) x+1/2, −y+3/2, −z+1.