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Acta Cryst. (2013). E69, o872-o873    [ doi:10.1107/S1600536813012294 ]

Alternariol 9-O-methyl ether dimethyl sulfoxide monosolvate

S. Dasari, K. I. Miller, J. A. Kalaitzis, M. Bhadbhade and B. A. Neilan

Abstract top

The title compound (systematic name: 3,7-dihydroxy-9-methoxy-1-methyl-6H-benzo[c]chromen-6-one dimethyl sulfoxide monosolvate), C15H12O5·C2H6OS, was isolated from an unidentified endophytic fungus (belonging to class Ascomycetes) of Taxus sp. In the crystal, both the alternariol 9-O-methyl ether (AME) and the dimethyl sulfoxide (DMSO) molecules exhibit crystallographic mirror symmetry. One of the hydroxy groups makes bifurcated hydrogen bonds, viz. an intramolecular bond with the carbonyl group and an intermolecular bond with the carbonyl group in an inversion-related AME molecule. In the crystal, the AME molecules are organized into stacks parallel with the b axis by [pi]-[pi] interactions between centrosymmetrically related molecules [the distance between the centroid of the central ring and the centroid of the methoxy-substituted benzene ring in the next molecule of the stack is 3.6184 (5) Å]. Pairs of DMSO molecules, linked via centrosymmetric C-H...O contacts, are inserted into the voids created by the AME molecules, making O-H...O and C-H...O contacts with the hosts.

Comment top

Extracts of the fungal endophyte Ascomycete F53 have previously demonstrated promising anti-proliferative activity against multiple myeloma RPMI-8226 cells, and mild growth inhibitory activities against Staphylococcus aureus, Escherichia coli and Cryptococcus albidus (Miller et al., 2012). The mycotoxin alternariol 9-O-methyl ether (AME) was previously thought to be produced soley by the fungal genus Alternaria however, its production has recently been reported from other fungal genera including Phoma sp.. Chemical profiling and genetic analysis of the fungus demonstrated the potential of the fungus to biosynthesize the mycotoxins, AOH, AME and other related derivatized secondary metabolites (data not shown).

Alternariol 9-O-methyl ether (AME; C15H12O5) and its precursor alternariol (AOH) are well known for their mammalian toxicity, mutagenic properties and mild antimicrobial properties.

Although AME has been well studied as a mycotoxin, the crystal structure was only recently reported by us (Dasari et al., 2012). Due to the title compound's demonstrated varied biological activities it is a suitable candidate molecule to study its molecular arrangement in different crystalline environments. In this report, we present the DMSO solvated form of this compound.

An ORTEP view of the molecule and the solvent, DMSO, (Fig. 1) shows two O—H···O hydrogen bonds; one within the AME molecule (O4—H1O4···O3) and the other one between AME and DMSO (O1—H1O1···O1d). The molecular association involving significant interactions (Fig. 2) shows that the two DMSO molecules are held between two pairs of AME molecules making a network of C—H···O hydrogen bonds (Table 1). The two DMSO molecules are associated via centrosymmetric C1D—H3···O1D contacts. Each of these is attached through their methyl groups to two AME molecules via C—H···O contacts (Fig. 2 and Table 1). The two views of molecular packing looking down b axis (Fig. 3) and down an arbitrary direction (Fig. 4) show stacking of molecules with the DMSO molecules inserted into the crystal lattice without disturbing the parallel layer arrangement that was observed in the unsolvated form.

Related literature top

For the bioactivity of AME and its precursor alternariol, see: Aly et al. (2008); Brugger et al. (2006); Pfeiffer et al. (2007); Miller et al. (2012). For their occurrence as contaminants in food and beverages, see: Lau et al. (2003). For the related crystal strucutre of alternariol, see: Dasari et al. (2012).

Experimental top

The fungal endophyte Ascomycete F53 was isolated from the Chinese medicinal plant Taxus yunnanensis, which was collected from mountainious area of Yunnan province in the Peoples Republic of China. A seed culture of Ascomycete F53 was used to innoculate 1L malt extract broth which was incubated for 21 days for the production of fungal secondary metabolites. The culture broth and mycelium were extracted with ethyl acetate (1L) to yield crude extract which was then fractionated on silica gel using a stepwise gradient of hexane to ethyl acetate and then with methanol to yield 12 fractions. The ethyl acetate fraction was further separated using C18 Sep-pak soild phase extraction column and eluted with a stepwise gradient of water to methanol. The fraction which eluted with 2:1 water/methanol yielded the title compound. The compound was dissolved in DMSO, and on slow evaporation of the solvent, formed plate like crystals.

Refinement top

All H-atoms (except for the two hydroxy H atoms) were positioned geometrically [C—H = 0.95 to 0.99 Å] and were refined using a riding-model approximation, with Uiso(H) = 1.2 Ueq(C) or 1.5 Ueq(C-methyl). The torsional freedom of one of the methyl groups in the AME molecule was restricted by using DFIX restraints for intramolecular H···H distances [H14A···H11 and H14B···H11: 2.043 (1); H14C···H2: 2.190 (1)]. The hydroxyl oxygen peaks were located in the difference Fourier map and were refined in riding mode with their isotropic displacement parameters Uiso(H) = 1.5 Ueq(O).

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL-Plus (Sheldrick, 2008); software used to prepare material for publication: SHELXTL-Plus (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. ORTEP view of the title compound showing the intramolecular and intermolecular AME···DMSO hydrogen bonds. Thermal ellipsoids are drawn at 40% probability level.
[Figure 2] Fig. 2. Molecular association between AME molecules and solvent DMSO molecules depicting a network of interactions.
[Figure 3] Fig. 3. Packing of molecules viewed down the crystallographic b axis.
[Figure 4] Fig. 4. Packing of molecules along an arbitrary direction.
3,7-Dihydroxy-9-methoxy-1-methyl-6H-benzo[c]chromen-6-one dimethylsulfoxide monosolvate top
Crystal data top
C15H12O5·C2H6OSF(000) = 736
Mr = 350.37Dx = 1.465 Mg m3
Monoclinic, C2/mMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yCell parameters from 4872 reflections
a = 18.8906 (8) Åθ = 2.7–30.6°
b = 6.8391 (3) ŵ = 0.24 mm1
c = 15.3542 (8) ÅT = 150 K
β = 126.815 (3)°Plate, colourless
V = 1588.08 (13) Å30.38 × 0.09 × 0.05 mm
Z = 4
Data collection top
Bruker Kappa APEXII CCD
1524 independent reflections
Radiation source: fine-focus sealed tube1382 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.029
φ scans, and ω scans with κ offsetsθmax = 25.0°, θmin = 1.7°
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
h = 2122
Tmin = 0.916, Tmax = 0.988k = 88
7177 measured reflectionsl = 1818
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.032Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.093H-atom parameters constrained
S = 1.10 w = 1/[σ2(Fo2) + (0.055P)2 + 0.9734P]
where P = (Fo2 + 2Fc2)/3
1524 reflections(Δ/σ)max < 0.001
144 parametersΔρmax = 0.27 e Å3
3 restraintsΔρmin = 0.32 e Å3
Crystal data top
C15H12O5·C2H6OSV = 1588.08 (13) Å3
Mr = 350.37Z = 4
Monoclinic, C2/mMo Kα radiation
a = 18.8906 (8) ŵ = 0.24 mm1
b = 6.8391 (3) ÅT = 150 K
c = 15.3542 (8) Å0.38 × 0.09 × 0.05 mm
β = 126.815 (3)°
Data collection top
Bruker Kappa APEXII CCD
1524 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
1382 reflections with I > 2σ(I)
Tmin = 0.916, Tmax = 0.988Rint = 0.029
7177 measured reflectionsθmax = 25.0°
Refinement top
R[F2 > 2σ(F2)] = 0.032H-atom parameters constrained
wR(F2) = 0.093Δρmax = 0.27 e Å3
S = 1.10Δρmin = 0.32 e Å3
1524 reflectionsAbsolute structure: ?
144 parametersFlack parameter: ?
3 restraintsRogers parameter: ?
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
O10.39016 (10)0.00000.94667 (11)0.0391 (4)
O20.42281 (8)0.00000.67046 (11)0.0206 (3)
O30.45897 (9)0.00000.55957 (11)0.0265 (4)
O40.34069 (9)0.00000.35176 (11)0.0237 (3)
O50.04062 (9)0.00000.22240 (11)0.0268 (4)
C10.21796 (12)0.00000.64985 (15)0.0174 (4)
C20.25831 (11)0.00000.76077 (13)0.0205 (4)
C30.34992 (13)0.00000.83847 (15)0.0227 (5)
C40.40259 (13)0.00000.80403 (15)0.0209 (4)
C50.36216 (13)0.00000.69341 (16)0.0173 (4)
C60.39827 (13)0.00000.56791 (16)0.0190 (4)
C70.30546 (12)0.00000.47951 (15)0.0172 (4)
C80.28052 (13)0.00000.37232 (16)0.0185 (4)
C90.19222 (13)0.00000.28315 (15)0.0202 (4)
C100.12935 (13)0.00000.30239 (16)0.0192 (4)
C110.15201 (12)0.00000.40773 (13)0.0194 (4)
C120.24039 (13)0.00000.49846 (16)0.0161 (4)
C130.27066 (12)0.00000.61190 (15)0.0162 (4)
C140.11825 (10)0.00000.57677 (11)0.0218 (4)
C150.01044 (14)0.00000.11184 (16)0.0292 (5)
S1D0.30260 (3)0.00000.10913 (4)0.02538 (19)
O1D0.27939 (9)0.00000.00407 (11)0.0298 (4)
C1D0.37818 (10)0.1967 (2)0.17933 (12)0.0285 (4)
Atomic displacement parameters (Å2) top
O10.0209 (8)0.0812 (13)0.0132 (7)0.0000.0091 (7)0.000
O20.0136 (7)0.0319 (7)0.0157 (7)0.0000.0084 (6)0.000
O30.0170 (7)0.0435 (9)0.0217 (8)0.0000.0131 (6)0.000
O40.0209 (7)0.0340 (8)0.0190 (7)0.0000.0134 (6)0.000
O50.0173 (7)0.0422 (9)0.0130 (7)0.0000.0048 (6)0.000
C10.0179 (10)0.0161 (9)0.0162 (9)0.0000.0092 (8)0.000
C20.0195 (10)0.0265 (10)0.0188 (10)0.0000.0132 (9)0.000
C30.0221 (10)0.0303 (11)0.0142 (10)0.0000.0100 (9)0.000
C40.0135 (9)0.0284 (10)0.0151 (10)0.0000.0054 (8)0.000
C50.0166 (9)0.0180 (9)0.0180 (10)0.0000.0108 (8)0.000
C60.0189 (10)0.0190 (9)0.0184 (10)0.0000.0108 (8)0.000
C70.0181 (10)0.0152 (9)0.0176 (10)0.0000.0103 (9)0.000
C80.0236 (10)0.0152 (9)0.0200 (10)0.0000.0150 (9)0.000
C90.0257 (11)0.0198 (9)0.0140 (9)0.0000.0113 (9)0.000
C100.0165 (9)0.0190 (9)0.0157 (10)0.0000.0062 (8)0.000
C110.0164 (10)0.0226 (9)0.0176 (10)0.0000.0094 (9)0.000
C120.0188 (9)0.0118 (8)0.0161 (9)0.0000.0097 (8)0.000
C130.0163 (9)0.0145 (9)0.0165 (10)0.0000.0092 (8)0.000
C140.0174 (10)0.0307 (10)0.0190 (10)0.0000.0119 (9)0.000
C150.0266 (12)0.0389 (12)0.0132 (10)0.0000.0072 (9)0.000
S1D0.0166 (3)0.0424 (3)0.0167 (3)0.0000.0097 (2)0.000
O1D0.0221 (8)0.0481 (9)0.0152 (7)0.0000.0090 (6)0.000
C1D0.0306 (8)0.0267 (8)0.0234 (8)0.0054 (6)0.0136 (7)0.0019 (6)
Geometric parameters (Å, º) top
O1—C31.351 (2)C7—C121.423 (3)
O1—H1O10.8003C8—C91.386 (3)
O2—C61.349 (2)C9—C101.385 (3)
O2—C51.386 (2)C9—H90.9300
O3—C61.228 (2)C10—C111.403 (2)
O4—C81.350 (2)C11—C121.393 (3)
O5—C101.360 (2)C12—C131.472 (3)
O5—C151.431 (2)C14—H14A0.9600
C1—C21.388 (2)C14—H14B0.9600
C1—C131.423 (3)C14—H14C0.9600
C1—C141.508 (2)C15—H15A0.9600
C2—C31.394 (3)C15—H15B0.9600
C3—C41.378 (3)S1D—O1D1.5166 (15)
C4—C51.383 (3)S1D—C1D1.7790 (15)
C4—H4C0.9300S1D—C1Di1.7790 (15)
C5—C131.401 (3)C1D—H40.9600
C6—C71.437 (3)C1D—H30.9600
C7—C81.415 (3)C1D—H50.9600
C3—O1—H1O1109.6O5—C10—C11113.60 (17)
C6—O2—C5122.59 (15)C9—C10—C11122.51 (17)
C8—O4—H1O4105.8C12—C11—C10120.51 (16)
C10—O5—C15118.07 (16)C12—C11—H11119.7
C2—C1—C13119.87 (17)C10—C11—H11119.7
C2—C1—C14115.84 (16)C11—C12—C7117.39 (17)
C13—C1—C14124.30 (16)C11—C12—C13124.49 (17)
C1—C2—C3122.50 (18)C7—C12—C13118.13 (17)
C1—C2—H2118.7C5—C13—C1115.19 (17)
C3—C2—H2118.7C5—C13—C12116.97 (17)
O1—C3—C4117.92 (18)C1—C13—C12127.83 (17)
O1—C3—C2123.20 (18)C1—C14—H14A109.5
C4—C3—C2118.88 (18)C1—C14—H14B109.5
C3—C4—C5118.47 (18)H14A—C14—H14B109.5
C4—C5—O2112.33 (16)H14B—C14—H14C109.5
C4—C5—C13125.09 (18)O5—C15—H15A109.5
O2—C5—C13122.58 (17)O5—C15—H15B109.5
O3—C6—O2115.63 (17)H15A—C15—H15B109.5
O3—C6—C7126.07 (18)O5—C15—H15C109.5
O2—C6—C7118.30 (17)H15A—C15—H15C109.5
C8—C7—C12120.78 (17)H15B—C15—H15C109.5
C8—C7—C6117.79 (17)O1D—S1D—C1D105.68 (6)
C12—C7—C6121.43 (18)O1D—S1D—C1Di105.68 (6)
O4—C8—C9116.93 (17)C1D—S1D—C1Di98.23 (10)
O4—C8—C7122.14 (17)S1D—C1D—H4109.5
C9—C8—C7120.93 (18)S1D—C1D—H3109.5
C10—C9—C8117.89 (18)H4—C1D—H3109.5
O5—C10—C9123.89 (18)H3—C1D—H5109.5
C13—C1—C2—C30.000 (1)C15—O5—C10—C11180.0
C1—C2—C3—C40.000 (1)O5—C10—C11—C12180.0
O1—C3—C4—C5180.000 (1)C9—C10—C11—C120.0
C2—C3—C4—C50.000 (1)C10—C11—C12—C70.0
O3—C6—C7—C12180.0O2—C5—C13—C120.000 (1)
O2—C6—C7—C120.0C2—C1—C13—C50.000 (1)
Symmetry code: (i) x, y, z.
Hydrogen-bond geometry (Å, º) top
O1—H1O1···O1Dii0.801.822.617 (2)175
O4—H1O4···O30.891.762.575 (2)151
O4—H1O4···O3iii0.892.593.162 (2)123
C4—H4C···O1iv0.932.623.467 (2)152
C1D—H4···O40.962.703.401 (2)130
C1D—H5···O2iii0.962.663.2970 (19)124
Symmetry codes: (ii) x, y, z+1; (iii) x+1, y, z+1; (iv) x+1, y, z+2.
Hydrogen-bond geometry (Å, º) top
O1—H1O1···O1Di0.801.822.617 (2)174.6
O4—H1O4···O30.891.762.575 (2)151.0
O4—H1O4···O3ii0.892.593.162 (2)123.2
C4—H4C···O1iii0.932.623.467 (2)152.0
C1D—H4···O40.962.703.401 (2)130.3
C1D—H5···O2ii0.962.663.2970 (19)123.9
Symmetry codes: (i) x, y, z+1; (ii) x+1, y, z+1; (iii) x+1, y, z+2.
Acknowledgements top

Funding from the Australian Endeavour Fellowship Scheme (SD) and and the Australian Research Council (BAN) is gratefully acknowledged.

References top

Aly, A. H., Edrada-Ebel, R., Indrani, I. D., Wray, V., Muller, W. E. G., Totzke, F., Zirrgiebel, U., Schachtele, C., Kubbutat, M. H. G., Lin, W. H., Proksch, P. & Ebel, R. (2008). J. Nat. Prod. 71, 972–980.

Brugger, E.-M., Wagner, J., Schumacher, D. M., Koch, K., Podlech, J., Metzler, M. & Lehmann, L. (2006). Toxicol. Lett. 164, 221–230.

Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.

Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

Dasari, S., Bhadbhade, M. & Neilan, B. A. (2012). Acta Cryst. E68, o1471.

Lau, B. P.-Y., Scott, P. M., Lewis, D. A., Kanhere, S. R., Cleroux, C. & Roscoe, V. A. (2003). J. Chromatogr. A, 998, 119–131.

Miller, K. I., Qing, C., Sze, D. M.-Y., Roufogalis, B. D. & Neilan, B. A. (2012). Microb. Ecol. 64, 431–449.

Pfeiffer, E., Schebb, N. H., Podlech, J. & Metzler, M. (2007). Mol. Nutr. Food Res. 51, 307–316.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.