Alternariol 9-O-methyl ether dimethyl sulfoxide monosolvate

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 π–π 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.

The title compound (systematic name: 3,7-dihydroxy-9-methoxy-1-methyl-6H-benzo[c]chromen-6-one dimethyl sulfoxide monosolvate), C 15 H 12 O 5 ÁC 2 H 6 OS, was isolated from an unidentified endophytic fungus (belonging to class Ascomycetes) of Taxus sp. In the crystal, both the alternariol 9-Omethyl 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 inversionrelated AME molecule. In the crystal, the AME molecules are organized into stacks parallel with the b axis byinteractions 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-HÁ Á ÁO contacts, are inserted into the voids created by the AME molecules, making O-HÁ Á ÁO and C-HÁ Á ÁO contacts with the hosts.

Experimental
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: SHELXTL-Plus.   (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; C 15 H 12 O 5 ) 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.

Experimental
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
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 U iso (H) = 1.2 U eq (C) or 1.5 U eq (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 U iso (H) = 1.5 U eq (O).

Computing details
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).    Packing of molecules along an arbitrary direction. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.