4-Hydr­oxy-3,4a,8-trimethyl-3,3a,4,4a,­7a,8,9,9a-octa­hydro­azuleno[6,5-b]furan-2,5-dione

The title compound, C₁₅H₂₀O₄, also known as dihydro­helenalin, is a drug obtained from a Chinese plant. It contains a seven-membered ring in a chair conformation and two five-membered rings in twist conformations. The crystal packing involves O—H...O hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 113 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.030
• wR factor = 0.077
• Data-to-parameter ratio = 9.0

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?

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           27.83
           From the CIF: _reflns_number_total               1605
           Count of symmetry unique reflns         1609
           Completeness (_total/calc)             99.75%
           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 C4     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C5     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C7     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C8     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C9     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C10    = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C13    = .          S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          1

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

   7 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 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
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Dihydrohelenalin is one of the active components isolated from the traditional Chinese medicinal herb, Centipeda minima (L.), which has been found in moisty places throughout China and India. It is used to treat rhinitis, sinusitis and nasopharyngal tumors (Bohlmann & Chen, 1980). We report here the crystal structure (Fig. 1).

The crystal structure of (I) illustrated in Fig. 1 shows that seven-ring is chair conformation. Intermolecular O—H···O hydrogen bonds stabilize the crysta structure.

Related literature

For background, see: Bohlmann & Chen (1980); for similar compounds, see: Giordano et al. (1992).

S2. Experimental

The air-dried plant of Centipeda minima (L.) was exacted with EtOH (95%) and the extract was concentrated in vacuo. The residue was subjected to silical-gel column chromatography. Elution with chloroform-methanol (95:5 v/v) yielded the title compound. The identity of the title compound was confirmed by NMR spectroscopy. ¹H NMR in CDCl₃ (500 MHz): 0.9(3H, 8, H-15), 1.22 (3H, d, J=7 Hz, H-14), 1.35 (3H, d, J=7 Hz, H-13), 1.75 (1H, ddd, H-9a), 2.18 (1H, m, H-10), 2.2 (1H, ddd, H-9 b), 4.36 (1H, s, H-6), 4.78 (1H, m, H-8), 6.1 (1H, dd, J=8, 4 Hz, H-3), 7.7 (1H, dd, J=8, 2 Hz, H-2).

S3. Refinement

In the absence ob anomalous scatterers Friedel pairs had been merged. The absolute configuration was set to be identical with the naturally occurring compound. All H atoms were positioned geometrically and refined using a riding model, with C—H in the range of 0.93 to 0.98 Å and with U_iso(H) = 1.2U_eq(C,O) or U_iso(H) = 1.5U_eq(methyl C). The coordinates of the hydroxyl H atom were refined.

Computing details

Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear (Rigaku/MSC, 2005); data reduction: CrystalClear (Rigaku/MSC, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL (Bruker, 1997).

Figures

Fig. 1. A view of the molecular structure of the title compound. Displacement ellipsoids are drawn at the 30% probability level.

4-Hydroxy-3,4a,8-trimethyl-3,3a,4,4a,7a,8,9,9a- octahydroazuleno[6,5-b]furan-2,5-dione

Crystal data

C15H20O4	Dx = 1.355 Mg m^−3
Mr = 264.31	Melting point = 222.0–224.0 K
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 6.3634 (13) Å	Cell parameters from 1887 reflections
b = 12.608 (3) Å	θ = 2.5–27.8°
c = 8.1146 (16) Å	µ = 0.10 mm^−1
β = 95.59 (3)°	T = 113 K
V = 647.9 (2) Å^3	Block, colorless
Z = 2	0.10 × 0.06 × 0.04 mm
F(000) = 284

Data collection

Rigaku Saturn diffractometer	1605 independent reflections
Radiation source: rotating anode	1508 reflections with I > 2σ(I)
Confocal monochromator	Rint = 0.033
Detector resolution: 7.31 pixels mm^-1	θmax = 27.8°, θmin = 2.5°
ω and ϕ scans	h = −8→8
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	k = −16→14
Tmin = 0.982, Tmax = 0.996	l = −10→9
4971 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.030	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.077	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0493P)^2 + 0.0251P] where P = (Fo^2 + 2Fc^2)/3
1605 reflections	(Δ/σ)max < 0.001
178 parameters	Δρmax = 0.22 e Å^−3
1 restraint	Δρmin = −0.18 e Å^−3

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 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	0.4530 (2)	0.75516 (10)	0.67372 (18)	0.0228 (3)
O2	0.11462 (19)	0.62013 (10)	0.85849 (17)	0.0172 (3)
H2	0.122 (4)	0.680 (2)	0.891 (3)	0.026*
O3	0.49752 (19)	0.31461 (9)	0.89731 (16)	0.0180 (3)
O4	0.8182 (2)	0.33531 (11)	1.02981 (18)	0.0222 (3)
C1	0.3892 (3)	0.67410 (14)	0.6056 (2)	0.0173 (4)
C2	0.3093 (3)	0.65984 (15)	0.4304 (2)	0.0219 (4)
H2A	0.3193	0.7104	0.3447	0.026*
C3	0.2207 (3)	0.56410 (15)	0.4119 (2)	0.0205 (4)
H3	0.1659	0.5361	0.3078	0.025*
C4	0.2164 (3)	0.50487 (13)	0.5728 (2)	0.0151 (3)
H4	0.0773	0.5224	0.6139	0.018*
C5	0.2305 (3)	0.38352 (14)	0.5744 (2)	0.0177 (4)
H5	0.3802	0.3617	0.5658	0.021*
C6	0.1580 (3)	0.34060 (14)	0.7367 (2)	0.0184 (4)
H6A	0.0139	0.3682	0.7455	0.022*
H6B	0.1454	0.2626	0.7250	0.022*
C7	0.2865 (3)	0.36248 (13)	0.9015 (2)	0.0167 (4)
H7	0.2163	0.3217	0.9864	0.020*
C8	0.3262 (3)	0.47520 (13)	0.9748 (2)	0.0146 (3)
H8	0.2140	0.4866	1.0511	0.018*
C9	0.3241 (3)	0.57586 (12)	0.8658 (2)	0.0137 (3)
H9	0.4232	0.6283	0.9241	0.016*
C10	0.3840 (3)	0.56456 (12)	0.6887 (2)	0.0137 (3)
C11	0.6100 (3)	0.52231 (14)	0.6802 (2)	0.0162 (3)
H11A	0.6195	0.4496	0.7228	0.024*
H11B	0.7102	0.5675	0.7475	0.024*
H11C	0.6441	0.5230	0.5650	0.024*
C12	0.0888 (3)	0.33500 (16)	0.4300 (3)	0.0244 (4)
H12A	0.1353	0.3597	0.3249	0.037*
H12B	−0.0578	0.3569	0.4373	0.037*
H12C	0.0984	0.2575	0.4355	0.037*
C13	0.5314 (3)	0.45433 (14)	1.0879 (2)	0.0194 (4)
H13	0.4850	0.4244	1.1926	0.023*
C14	0.6371 (3)	0.36407 (13)	1.0068 (2)	0.0170 (4)
C15	0.6810 (3)	0.54405 (15)	1.1414 (3)	0.0233 (4)
H15A	0.7498	0.5693	1.0459	0.035*
H15B	0.7883	0.5185	1.2271	0.035*
H15C	0.6016	0.6023	1.1859	0.035*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0248 (7)	0.0170 (6)	0.0273 (8)	−0.0031 (5)	0.0055 (6)	0.0005 (5)
O2	0.0140 (6)	0.0137 (5)	0.0239 (7)	0.0030 (5)	0.0020 (5)	−0.0020 (5)
O3	0.0169 (6)	0.0154 (6)	0.0218 (7)	0.0025 (4)	0.0023 (5)	0.0001 (5)
O4	0.0165 (6)	0.0228 (6)	0.0272 (8)	0.0035 (5)	0.0023 (5)	0.0071 (5)
C1	0.0142 (8)	0.0175 (8)	0.0207 (10)	0.0027 (6)	0.0041 (7)	0.0037 (7)
C2	0.0218 (9)	0.0265 (9)	0.0177 (10)	0.0051 (7)	0.0032 (7)	0.0060 (7)
C3	0.0174 (9)	0.0290 (9)	0.0150 (9)	0.0047 (7)	0.0003 (7)	0.0006 (7)
C4	0.0128 (8)	0.0187 (8)	0.0138 (9)	0.0000 (6)	0.0011 (6)	−0.0021 (7)
C5	0.0153 (8)	0.0185 (8)	0.0191 (10)	0.0001 (6)	0.0003 (7)	−0.0054 (7)
C6	0.0172 (8)	0.0153 (7)	0.0223 (10)	−0.0023 (6)	0.0007 (7)	−0.0003 (7)
C7	0.0157 (8)	0.0149 (8)	0.0196 (9)	0.0002 (6)	0.0020 (7)	0.0018 (7)
C8	0.0175 (8)	0.0141 (7)	0.0122 (8)	0.0007 (6)	0.0013 (6)	−0.0008 (6)
C9	0.0116 (8)	0.0124 (7)	0.0171 (9)	0.0011 (6)	0.0007 (6)	−0.0008 (6)
C10	0.0116 (8)	0.0148 (7)	0.0147 (9)	−0.0004 (6)	0.0013 (6)	0.0000 (6)
C11	0.0120 (8)	0.0191 (8)	0.0177 (9)	0.0004 (6)	0.0025 (6)	0.0004 (7)
C12	0.0240 (9)	0.0244 (9)	0.0243 (11)	−0.0057 (7)	−0.0001 (7)	−0.0078 (8)
C13	0.0191 (9)	0.0191 (8)	0.0192 (10)	0.0021 (7)	−0.0021 (7)	0.0007 (7)
C14	0.0170 (8)	0.0166 (8)	0.0176 (9)	0.0013 (6)	0.0023 (7)	0.0056 (7)
C15	0.0200 (9)	0.0255 (9)	0.0228 (11)	−0.0001 (7)	−0.0058 (7)	−0.0026 (8)

Geometric parameters (Å, º)

O1—C1	1.213 (2)	C7—C8	1.552 (2)
O2—C9	1.441 (2)	C7—H7	1.0000
O2—H2	0.80 (3)	C8—C13	1.544 (2)
O3—C14	1.347 (2)	C8—C9	1.546 (2)
O3—C7	1.475 (2)	C8—H8	1.0000
O4—C14	1.205 (2)	C9—C10	1.529 (2)
C1—C2	1.473 (3)	C9—H9	1.0000
C1—C10	1.539 (2)	C10—C11	1.541 (2)
C2—C3	1.335 (3)	C11—H11A	0.9800
C2—H2A	0.9500	C11—H11B	0.9800
C3—C4	1.507 (3)	C11—H11C	0.9800
C3—H3	0.9500	C12—H12A	0.9800
C4—C5	1.533 (2)	C12—H12B	0.9800
C4—C10	1.547 (2)	C12—H12C	0.9800
C4—H4	1.0000	C13—C14	1.506 (3)
C5—C12	1.535 (3)	C13—C15	1.515 (3)
C5—C6	1.536 (3)	C13—H13	1.0000
C5—H5	1.0000	C15—H15A	0.9800
C6—C7	1.523 (3)	C15—H15B	0.9800
C6—H6A	0.9900	C15—H15C	0.9800
C6—H6B	0.9900
C9—O2—H2	109.2 (17)	C7—C8—H8	105.6
C14—O3—C7	109.80 (13)	O2—C9—C10	108.17 (14)
O1—C1—C2	127.68 (17)	O2—C9—C8	107.35 (13)
O1—C1—C10	125.24 (17)	C10—C9—C8	118.16 (13)
C2—C1—C10	107.06 (15)	O2—C9—H9	107.6
C3—C2—C1	108.70 (17)	C10—C9—H9	107.6
C3—C2—H2A	125.6	C8—C9—H9	107.6
C1—C2—H2A	125.6	C9—C10—C1	110.26 (13)
C2—C3—C4	113.23 (17)	C9—C10—C11	113.15 (14)
C2—C3—H3	123.4	C1—C10—C11	103.35 (13)
C4—C3—H3	123.4	C9—C10—C4	113.33 (14)
C3—C4—C5	119.72 (16)	C1—C10—C4	102.31 (14)
C3—C4—C10	102.46 (14)	C11—C10—C4	113.33 (14)
C5—C4—C10	116.38 (14)	C10—C11—H11A	109.5
C3—C4—H4	105.7	C10—C11—H11B	109.5
C5—C4—H4	105.7	H11A—C11—H11B	109.5
C10—C4—H4	105.7	C10—C11—H11C	109.5
C4—C5—C12	111.23 (16)	H11A—C11—H11C	109.5
C4—C5—C6	109.65 (15)	H11B—C11—H11C	109.5
C12—C5—C6	108.12 (15)	C5—C12—H12A	109.5
C4—C5—H5	109.3	C5—C12—H12B	109.5
C12—C5—H5	109.3	H12A—C12—H12B	109.5
C6—C5—H5	109.3	C5—C12—H12C	109.5
C7—C6—C5	120.55 (15)	H12A—C12—H12C	109.5
C7—C6—H6A	107.2	H12B—C12—H12C	109.5
C5—C6—H6A	107.2	C14—C13—C15	113.24 (16)
C7—C6—H6B	107.2	C14—C13—C8	104.89 (15)
C5—C6—H6B	107.2	C15—C13—C8	120.98 (15)
H6A—C6—H6B	106.8	C14—C13—H13	105.5
O3—C7—C6	108.55 (14)	C15—C13—H13	105.5
O3—C7—C8	105.59 (13)	C8—C13—H13	105.5
C6—C7—C8	123.76 (14)	O4—C14—O3	121.47 (16)
O3—C7—H7	105.9	O4—C14—C13	128.40 (17)
C6—C7—H7	105.9	O3—C14—C13	110.13 (15)
C8—C7—H7	105.9	C13—C15—H15A	109.5
C13—C8—C9	116.10 (14)	C13—C15—H15B	109.5
C13—C8—C7	99.70 (13)	H15A—C15—H15B	109.5
C9—C8—C7	122.73 (15)	C13—C15—H15C	109.5
C13—C8—H8	105.6	H15A—C15—H15C	109.5
C9—C8—H8	105.6	H15B—C15—H15C	109.5
O1—C1—C2—C3	−169.13 (19)	C8—C9—C10—C11	−60.42 (18)
C10—C1—C2—C3	12.6 (2)	O2—C9—C10—C4	−51.72 (17)
C1—C2—C3—C4	3.8 (2)	C8—C9—C10—C4	70.39 (18)
C2—C3—C4—C5	−148.81 (17)	O1—C1—C10—C9	38.0 (2)
C2—C3—C4—C10	−18.3 (2)	C2—C1—C10—C9	−143.68 (14)
C3—C4—C5—C12	−43.8 (2)	O1—C1—C10—C11	−83.2 (2)
C10—C4—C5—C12	−167.85 (15)	C2—C1—C10—C11	95.10 (16)
C3—C4—C5—C6	−163.30 (15)	O1—C1—C10—C4	158.87 (18)
C10—C4—C5—C6	72.62 (18)	C2—C1—C10—C4	−22.84 (17)
C4—C5—C6—C7	−66.9 (2)	C3—C4—C10—C9	142.38 (14)
C12—C5—C6—C7	171.70 (15)	C5—C4—C10—C9	−85.06 (18)
C14—O3—C7—C6	156.60 (14)	C3—C4—C10—C1	23.69 (16)
C14—O3—C7—C8	21.99 (17)	C5—C4—C10—C1	156.25 (15)
C5—C6—C7—O3	−61.67 (19)	C3—C4—C10—C11	−86.89 (17)
C5—C6—C7—C8	62.8 (2)	C5—C4—C10—C11	45.7 (2)
O3—C7—C8—C13	−30.25 (17)	C9—C8—C13—C14	−105.84 (17)
C6—C7—C8—C13	−155.97 (17)	C7—C8—C13—C14	28.15 (18)
O3—C7—C8—C9	99.57 (17)	C9—C8—C13—C15	23.6 (2)
C6—C7—C8—C9	−26.2 (3)	C7—C8—C13—C15	157.62 (18)
C13—C8—C9—O2	−143.00 (15)	C7—O3—C14—O4	176.85 (16)
C7—C8—C9—O2	94.45 (18)	C7—O3—C14—C13	−3.05 (19)
C13—C8—C9—C10	94.47 (18)	C15—C13—C14—O4	29.1 (3)
C7—C8—C9—C10	−28.1 (2)	C8—C13—C14—O4	162.99 (18)
O2—C9—C10—C1	62.28 (16)	C15—C13—C14—O3	−151.05 (15)
C8—C9—C10—C1	−175.61 (14)	C8—C13—C14—O3	−17.1 (2)
O2—C9—C10—C11	177.47 (13)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O4^i	0.80 (3)	2.09 (3)	2.8792 (19)	173 (2)

Symmetry code: (i) −x+1, y+1/2, −z+2.