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Acta Crystallogr Sect E Struct Rep Online. 2010 September 1; 66(Pt 9): o2263.
Published online 2010 August 11. doi:  10.1107/S1600536810030850
PMCID: PMC3008014

(4S,5S,6S)-4-Hy­droxy-3-meth­oxy-5-methyl-5,6-ep­oxy­cyclo­hex-2-en-1-one

Abstract

The title compound, C8H10O4, was isolated from culture extracts of the endophytic fungus Xylaria sp. (PB-30). The cyclo­hexenone ring exhibits a flattened boat conformation. In the crystal structure, mol­ecules related by translation along the b axis are linked into chains through O—H(...)O hydrogen bonds. Weak non-classical C—H(...)O contacts are also observed in the structure.

Related literature

For background to the structures of bioactive secondary metabolites from endophytic fungus and their activities, see: Tansuwan et al. (2007 [triangle]); Shiono et al. (2005 [triangle]); Mitsui et al. (2004 [triangle]). For related structures and the assignment of the absolute configuration, see: Mitsui et al. (2004 [triangle]); Shiono et al. (2005 [triangle]). For puckering parameters, see: Cremer & Pople (1975 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2263-scheme1.jpg

Experimental

Crystal data

  • C8H10O4
  • M r = 170.16
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2263-efi1.jpg
  • a = 4.2208 (1) Å
  • b = 7.5459 (3) Å
  • c = 25.0802 (8) Å
  • V = 798.80 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.11 mm−1
  • T = 293 K
  • 0.42 × 0.40 × 0.30 mm

Data collection

  • Bruker SMART APEXII CCD area-detector diffractometer
  • 6038 measured reflections
  • 1768 independent reflections
  • 1551 reflections with I > 2σ(I)
  • R int = 0.021

Refinement

  • R[F 2 > 2σ(F 2)] = 0.041
  • wR(F 2) = 0.116
  • S = 1.07
  • 1768 reflections
  • 112 parameters
  • H-atom parameters constrained
  • Δρmax = 0.32 e Å−3
  • Δρmin = −0.24 e Å−3

Data collection: APEX2 (Bruker, 2008 [triangle]); cell refinement: SAINT (Bruker, 2008 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]); software used to prepare material for publication: publCIF (Westrip, 2010 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810030850/cv2746sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810030850/cv2746Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

Financial support from the Department of Chemistry, Faculty of Science, Chulalongkorn University, the Rachadapiseksompoj Endowment, Chulalongkorn University, the Thailand research fund (grant No. MRG5280213), the National Center of Excellence for Petroleum, Petrochemicals and Advanced Materials, and the A1–B1 project, Faculty of Science, Chulalongkorn University, is gratefully acknowledged. The Thai Government Stimulus Package 2 (TKK2555), under the Project for Establishment of a Comprehensive Center for Innovative Food, Health Products and Agriculture, is acknowledged for support of the X-ray Crystallographic analysis.

supplementary crystallographic information

Comment

Endophytic fungi have been proven to be a rich source of novel structural compounds with interesting biological activities and a high level of biodiversity. In the previous investigations of bioactive compounds produced by an endophytic fungus, Xylaria sp (strain PB-30), two antimalarial benzoquinones were isolated (Tansuwan et al., 2007). As a part of our continuing search for anticancer metabolites of this fungus, we found that the title compound is one of major metabolite showing cytotoxicity against various human cell lines, for example breast ductal carcinoma (BT474), human undifferentiated lung carcinoma (CHAGO), human liver hepatoblastoma (HEP-G2), human gastric carcinoma (KATO-3), and human colon adenocarcinoma (SW620) at IC50 values of 10.51, 11.11, 6.25, 5.61 and 5.31 µg/ml, respectively.

The title compound was previously isolated from the organic extracts of the fungus xylariaceous endophytic fungus (strain YUA-026), and elucidated on the basis of spectroscopic analysis (Shiono et al., 2005). Herein we present the crystal structure of the title compound, which was isolated from the fermentation culture of the endophytic fungus Xylaria sp (strain PB-30) at room temperature under a static condition.

The cyclohexenone ring exhibits a flattened boat conformation with puckering amplitudes Q = 0.232 (1), [var phi] = 176.5 (3)° and θ = 81.8°. The 3-methoxy substitutent is in the plane of the cyclohexenone ring to which it is attached [dihedral angle = 7.4 (2)°]. Epoxide ring makes dihedral angles of 87.23 (6)° with the cyclohexenone rings C1—C6. The hydroxyl group locates on the same side of the epoxide ring. In the crystal, the molecules are linked to each other through O—H···O hydrogen bonds, building a polymeric chain parallel to the b-axis. Weak non-classical C—H···O contacts are also observed in the structure. The absolute configuration could not be determined therefore it was assigned on the basis of literature data (Shiono et al., 2005).

Experimental

The endophytic fungus Xylaria sp. PB-30 was cultivated in 100 ml of malt extract broth (MEB) in a 250 ml flask (x 300) under static condition at room temperature for 35 days. The culture was filtered through filter paper (Whatman No.1). The culture broth (23 L) was concentrated by rotary evaporator in vacuo to give the concentrated broth (1.5 L) and then extracted with EtOAc (x5), CH2Cl2: MeOH (1:1) (x5) and MeOH (x5), respectively. The solvents were evaporated under reduced pressure at 30°C to give EtOAc crude as yellow viscous liquid (29.61 g), CH2Cl2: MeOH crude as brown viscous liquid (21.45 g) and MeOH crude as brown viscous liquid (4.74 g).

The EtOAc crude extract (29.61 g) was subjected to a column chromatography [SephadexTM LH-20 (400 g), column diameter 3.6 cm] using 5% dichloromethane in MeOH as eluent. 10 ml of each fraction was collected. The similar fractions were combined on the basis of TLC profile and monitored by UV, iodine vapor and vanillin/H2SO4 reagent to give 14 combined fractions.

The fractions EB-5 and EB-6 were combined and purified by crystallization from a 1:1 mixture of CH2Cl2 and acetone to obtain the title compound as colorless crystals (25.8 mg).

m.p. 153–155¯C; [α]D 20 -100 o (c = 0.1, MeOH); λmax (MeOH) (log ε) 260 nm (3.75); HRESIMS m/z 363.0579 [2M+Na]+calc. for (C8H10O4)2 Na 363.1055 FT—IR (KBr) vmax (cm-1): 3445, 3070, 3033, 2987, 2940, 2917, 2857, 1642, 1605, 1386, 1300, 1253, 1213, 1070, and 1014; 1H-NMR δ (CDCl3, 400 MHz) 1.64 (3H, s, Me), 2.58 (1H, d, J=6.0 Hz, 4-OH), 3.32 (1H, d, J=2.0 Hz, 6-H), 3.76 (3H, s, OMe), 4.48 (1H, d, J=6.0 Hz, 4-H) and 5.25 (1H, d, J= 2.0 Hz, 2-H) p.p.m.; 13C-NMR δ (CDCl3, 100 MHz) 18.9 (Me), 56.6 (OMe), 59.4 (C-5), 60.5 (C-6), 69.1 (C-4), 98.2 (C-2), 171.3 (C-3) and 193.4 (C-1) p.p.m.

Refinement

All H atoms were positioned geometrically and treated as riding, with C—H bonding lengths constrained to 0.93 Å (aromatic CH), 0.96 Å (methyl CH3), 0.97 Å (methylene CH2), and O—H = 0.84 Å, and with Uiso(H) = 1.2Ueq(CH) or Uiso(H) = 1.5Ueq(CH3, methylene C or OH). 1159 Friedel pair were merged before the final refinement. The absolute configuration was assigned on the basis of the known configuration of the starting material as R, S and S for C4, C5 and C6-positions, respectively.

Figures

Fig. 1.
The molecular structure of the title compound, showing 50% probability displacement ellipsoids and the atom numbering scheme. Hydrogen atoms are shown as spheres of arbitrary radius.

Crystal data

C8H10O4F(000) = 360
Mr = 170.16Dx = 1.415 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 2855 reflections
a = 4.2208 (1) Åθ = 2.8–32.8°
b = 7.5459 (3) ŵ = 0.11 mm1
c = 25.0802 (8) ÅT = 293 K
V = 798.80 (4) Å3Prism, colourless
Z = 40.42 × 0.40 × 0.30 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer1551 reflections with I > 2σ(I)
Radiation source: MoRint = 0.021
graphiteθmax = 33.1°, θmin = 2.8°
[var phi] and ω scansh = −6→6
6038 measured reflectionsk = −11→7
1768 independent reflectionsl = −37→32

Refinement

Refinement on F20 restraints
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.041w = 1/[σ2(Fo2) + (0.0798P)2 + 0.0232P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.116(Δ/σ)max = 0.001
S = 1.07Δρmax = 0.32 e Å3
1768 reflectionsΔρmin = −0.24 e Å3
112 parameters

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
C10.6030 (4)0.12154 (17)0.88766 (6)0.0349 (3)
C20.6543 (4)0.19049 (16)0.83465 (5)0.0337 (3)
H20.67780.11210.80630.04*
C30.6687 (3)0.36664 (16)0.82548 (5)0.0268 (2)
C40.6073 (3)0.50632 (15)0.86741 (5)0.0248 (2)
H40.38940.54890.86320.03*
C50.6459 (3)0.43752 (15)0.92384 (5)0.0242 (2)
C60.6377 (4)0.24623 (17)0.93348 (5)0.0293 (3)
H60.55860.20640.96820.035*
C70.5554 (5)0.56563 (19)0.96737 (5)0.0372 (3)
H7A0.6780.67210.96380.056*
H7B0.59640.51281.00150.056*
H7C0.33420.59360.96450.056*
C80.7980 (6)0.3240 (2)0.73390 (6)0.0452 (4)
H8A0.62170.24770.72640.068*
H8B0.97910.25370.74330.068*
H8C0.84610.39380.70290.068*
O10.5405 (5)−0.03468 (14)0.89674 (5)0.0594 (5)
O20.8156 (3)0.65036 (13)0.85837 (4)0.0392 (3)
H2A0.7350.74190.86960.059*
O30.7187 (4)0.43952 (13)0.77758 (4)0.0379 (3)
O40.9367 (3)0.34098 (15)0.93283 (4)0.0350 (2)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0486 (8)0.0182 (5)0.0379 (6)0.0011 (5)0.0071 (7)−0.0006 (4)
C20.0484 (8)0.0210 (5)0.0318 (6)−0.0004 (5)0.0055 (6)−0.0066 (4)
C30.0325 (6)0.0226 (5)0.0253 (5)0.0013 (5)0.0029 (5)−0.0029 (4)
C40.0297 (5)0.0174 (4)0.0272 (5)0.0020 (4)0.0042 (4)−0.0011 (4)
C50.0254 (5)0.0211 (5)0.0261 (5)−0.0009 (4)0.0018 (4)−0.0029 (4)
C60.0360 (6)0.0231 (5)0.0289 (5)0.0008 (5)0.0029 (5)0.0024 (4)
C70.0521 (9)0.0286 (6)0.0310 (6)−0.0041 (6)0.0082 (6)−0.0093 (5)
C80.0645 (11)0.0422 (8)0.0290 (6)0.0011 (9)0.0103 (7)−0.0080 (6)
O10.1057 (14)0.0182 (4)0.0545 (7)−0.0065 (6)0.0200 (9)0.0002 (4)
O20.0545 (7)0.0199 (4)0.0431 (5)−0.0081 (4)0.0158 (5)−0.0024 (4)
O30.0593 (7)0.0294 (4)0.0250 (4)0.0029 (5)0.0074 (5)−0.0019 (3)
O40.0280 (5)0.0368 (5)0.0400 (5)0.0022 (4)−0.0047 (4)0.0019 (4)

Geometric parameters (Å, °)

C1—O11.2292 (17)C5—C71.5074 (17)
C1—C21.444 (2)C6—O41.4506 (18)
C1—C61.4924 (19)C6—H60.98
C2—C31.3503 (17)C7—H7A0.96
C2—H20.93C7—H7B0.96
C3—O31.3379 (15)C7—H7C0.96
C3—C41.5113 (16)C8—O31.4393 (17)
C4—O21.4162 (17)C8—H8A0.96
C4—C51.5162 (17)C8—H8B0.96
C4—H40.98C8—H8C0.96
C5—O41.4448 (16)O2—H2A0.82
C5—C61.4640 (18)
O1—C1—C2123.24 (14)O4—C6—C559.43 (9)
O1—C1—C6118.88 (14)O4—C6—C1112.79 (12)
C2—C1—C6117.85 (12)C5—C6—C1119.79 (11)
C3—C2—C1121.21 (11)O4—C6—H6117.2
C3—C2—H2119.4C5—C6—H6117.2
C1—C2—H2119.4C1—C6—H6117.2
O3—C3—C2124.38 (11)C5—C7—H7A109.5
O3—C3—C4111.41 (10)C5—C7—H7B109.5
C2—C3—C4124.08 (11)H7A—C7—H7B109.5
O2—C4—C3108.50 (10)C5—C7—H7C109.5
O2—C4—C5110.21 (11)H7A—C7—H7C109.5
C3—C4—C5113.09 (10)H7B—C7—H7C109.5
O2—C4—H4108.3O3—C8—H8A109.5
C3—C4—H4108.3O3—C8—H8B109.5
C5—C4—H4108.3H8A—C8—H8B109.5
O4—C5—C659.82 (9)O3—C8—H8C109.5
O4—C5—C7115.19 (12)H8A—C8—H8C109.5
C6—C5—C7120.44 (11)H8B—C8—H8C109.5
O4—C5—C4114.18 (10)C4—O2—H2A109.5
C6—C5—C4119.29 (10)C3—O3—C8118.11 (11)
C7—C5—C4115.41 (11)C5—O4—C660.75 (8)
O1—C1—C2—C3168.6 (2)C7—C5—C6—O4−103.26 (15)
C6—C1—C2—C3−13.3 (3)C4—C5—C6—O4102.54 (13)
C1—C2—C3—O3179.30 (16)O4—C5—C6—C1−100.39 (15)
C1—C2—C3—C4−5.2 (3)C7—C5—C6—C1156.36 (15)
O3—C3—C4—O2−40.34 (16)C4—C5—C6—C12.2 (2)
C2—C3—C4—O2143.68 (16)O1—C1—C6—O4125.98 (19)
O3—C3—C4—C5−162.94 (13)C2—C1—C6—O4−52.22 (19)
C2—C3—C4—C521.1 (2)O1—C1—C6—C5−167.29 (19)
O2—C4—C5—O4−72.54 (13)C2—C1—C6—C514.5 (2)
C3—C4—C5—O449.10 (15)C2—C3—O3—C8−7.4 (3)
O2—C4—C5—C6−140.21 (13)C4—C3—O3—C8176.65 (16)
C3—C4—C5—C6−18.57 (18)C7—C5—O4—C6111.98 (13)
O2—C4—C5—C764.33 (16)C4—C5—O4—C6−111.05 (12)
C3—C4—C5—C7−174.03 (13)C1—C6—O4—C5112.19 (13)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H2A···O1i0.821.992.8148 (17)180.
C4—H4···O2ii0.982.543.521 (2)176.
C6—H6···O4iii0.982.563.5208 (17)167.

Symmetry codes: (i) x, y+1, z; (ii) x−1, y, z; (iii) x−1/2, −y+1/2, −z+2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CV2746).

References

  • Bruker (2008). APEX2 and SAINT Bruker AXS Inc., Madison, Wiscosin, USA.
  • Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc.97, 1354–1358.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Mitsui, T., Miyake, Y., Kakeya, H., Osada, H. & Kataoka, T. (2004). J. Immunol.172, 3428–3436. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Shiono, Y., Murayama, T., Takahashi, K., Okada, K., Katohda, S. & Ikeda, M. (2005). Biosci. Biotechnol. Biochem.69, 287–292. [PubMed]
  • Tansuwan, S., Pornpakakul, S., Roengsumran, S., Petsom, A., Muangsin, N., Sihanonta, P. & Chaichit, N. (2007). J. Nat. Prod.70, 1620–1623. [PubMed]
  • Westrip, S. P. (2010). J. Appl. Cryst.43, 920–925.

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