Alternariol 9-O-methyl ether

Sreekanth Dasari; Mohan Bhadbhade; Brett A Neilan

doi:10.1107/S1600536812015000

. 2012 Apr 21;68(Pt 5):o1471. doi: 10.1107/S1600536812015000

Alternariol 9-O-methyl ether

Sreekanth Dasari ^a, Mohan Bhadbhade ^b, Brett A Neilan ^a,^*

PMCID: PMC3344582 PMID: 22590344

Abstract

The title compound (AME; systematic name: 3,7-dihydroxy-9-methoxy-1-methyl-6H-benzo[c]chromen-6-one), C₁₅H₁₂O₅, was isolated from an endophytic fungi Alternaria sp., from Catharanthus roseus (common name: Madagascar periwinkle). There is an intramolecular O—H⋯O hydrogen bond in the essentially planar molecule (r.m.s. deviation 0.02 Å). In the crystal, the molecule forms an O—H⋯O hydrogen bond with its centrosymmetric counterpart with four bridging interactions (two O—H⋯O and two C—H⋯O). The almost planar sheets of the dimeric units thus formed are stacked along b axis via C—H⋯π and π–π contacts [with C⋯C short contacts between aromatic moieties of 3.324 (3), 3.296 (3) and 3.374 (3) Å].

Related literature

Species of the fungal genus Alternaria are known producers of mycotoxins and have previously been described as plant endophytes. For the isolation of Alternariol (AOH) and Alternariol 9-O-methyl ether (AME) see: An et al. (1989 ▶); Wen (2009 ▶); Ashour et al. (2011 ▶). For ¹H, ¹³C and two-dimensional experimental data analysis see: Koch et al. (2005 ▶); Siegel et al. (2010 ▶). For the biological activity see: Aly et al. (2008 ▶).

Experimental

Crystal data

C₁₅H₁₂O₅
M _r = 272.25
Triclinic,
a = 7.1819 (7) Å
b = 8.9393 (8) Å
c = 10.2511 (10) Å
α = 105.296 (5)°
β = 105.174 (4)°
γ = 101.430 (4)°
V = 586.90 (10) Å³
Z = 2
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 160 K
0.29 × 0.13 × 0.06 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ▶) T _min = 0.967, T _max = 0.993
7824 measured reflections
2062 independent reflections
1718 reflections with I > 2σ(I)
R _int = 0.020

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.096
S = 1.05
2062 reflections
184 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; 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: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812015000/hg5207sup1.cif

e-68-o1471-sup1.cif^{(21.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812015000/hg5207Isup2.hkl

e-68-o1471-Isup2.hkl^{(101.4KB, 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
O4—H4⋯O4ⁱ	0.82	2.47	2.9371 (19)	117
C9—H9⋯O1ⁱⁱ	0.93	2.64	3.4645 (16)	148
C4—H4A⋯O2ⁱⁱⁱ	0.93	2.32	3.2511 (16)	174
O4—H4⋯O3	0.82	1.84	2.5692 (13)	148
O1—H1⋯O3ⁱⁱⁱ	0.82	2.14	2.9619 (13)	176

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

This work was supported by the Australian Endeavour Fellowship Scheme (SD) and the Australian Research Council (BAN).

supplementary crystallographic information

Comment

The title compound was isolated from an endophytic Alternaria sp. from the host plant Catharanthus roseus. Alternariol 9-O-methyl ether is a mycotoxin often isolated from Alternaria sp.. It has been reported to exhibit mild antimicrobial activity (An et al., 1989; Wen 2009; Ashour et al., 2011), cytotoxicity and protein kinase inhibitory activity (Aly et al., 2008). ¹H, ¹³C and two-dimensional NMR spectral data was reported previously (Koch et al., 2005; Siegel et al., 2010). Although mycotoxins have been studied extensively, the single-crystal structure of alternariol 9-O-methy ether is reported here for the first time.

An ORTEP view of the title compound (Fig. 1) shows an intramolecular O4—H4···O3 hydrogen bond. The two centrosymmetric partners make a total of four interactions - the two hydrogen bonds O1—H1···O3⁽ⁱⁱⁱ⁾ and C4—H4A···O2⁽ⁱⁱⁱ⁾ , ((iii) -x + 2, -y, -z + 1) are duplicated across the inversion centre. The hydrogen H4 also makes a short contact with O4 of another centrosymmetrically related molecule (O4—H4···O4⁽ⁱ⁾, (i) -x + 2, -y + 1, -z + 2). The bridged centrosymmetric dimers translated along c axis make C9—H9···O1⁽ⁱⁱ⁾, (ii) x, y + 1, z + 1 and O4—H4···O4⁽ⁱ⁾ contacts (Table. 1 and Fig. 2). These almost planar sheets thus formed in ac plane are stacked along b axis; these make C—H···π contacts with the edge of the ring in one direction (C14—H14B···C9^(iv) = 2.88 Å and C15—H15C···C1^(iv) = 2.85 Å, (iv) 1 - x, 1 - y, 1 - z) and π–π contacts in the opposite direction with considerable overlap of aromatic moieties with values of short contact between C3···C8^(v) = 3.324 (3) Å, C1···C6^(v) = 3.296 (3) Å and C5···C12^(v) = 3.374 (3) Å with (v) 1 - x, -y, 1 - z (Fig. 3).

Experimental

Alternaria sp. was isolated from Catharanthus roseus and cultured in malt extract media for production of secondary metabolites. The crude ethyl acetate extract was fractionated on silica gel with a stepwise gradient of hexane to ethyl acetate and to methanol to yield 12 fractions. Fractions 6 and 7, which were eluted with 2:1 and 1:1 hexane, ethyl acetate showed fine needle like crystals on slow evaporation. These fine needles were recrystallized using dichloromethane to yield plate like crystals for crystallographic analysis. The positive and negative ESI-MS analysis of the title compound exhibited molecular ion peak at m/z 273, attributing to [M+H]⁺ and at m/z 271, attributing to [M—H]^- , respectively, infereing its molecular weight to be 272 g/mol which is in agreement with the previously reported values (Ashour et al., 2011).