Neoaustin: a meroterpene produced by Penicillium sp.

The title meroterpene neoaustin {systematic name: (1'S,2'R,3S,7'R,9'S,11'S,12'R)-11'-hydr-oxy-2,2,2',9',12'-penta-methyl-6',15'-dimethyl-ene-2,6-dihydro-13'-oxaspiro-[pyran-3,5'-tetra-cyclo-[7.5.1.0(1,11).0(2,7)]penta-deca-ne]-6,10',14'-trione}, C(25)H(30)O(6), comprises five rings, three six-membered and two five-membered. The absolute configuration was established based on [α(D)] = +166.91° (c 1.21, CH(2)Cl(2)). In the crystal, the mol-ecules are connected into a supra-molecular helical chain via O-H⋯O hydrogen bonds reinforced by C-H⋯O contacts.


S1. Comment
Endophytic fungi live in very intimate association with plant tissue and can produce compounds similar and sometimes identical to those produced by the host plant. Thus, fungi have been a rich source of important biologically active secondary metabolites, such as meroterpenoids, a class of complex metabolites derived from a mixed terpenoidpolyketide biosynthetic pathway. During an on-going study of substances produced by endophytic fungi, the title compound (I) was isolated and its structure postulated based on APCIMS (Atmospheric Pressure Chemical Ionization Mass Spectrometry) and a variety of NMR studies (dos Santos and Rodrigues-Fo, 2003). As suitable crystals were subsequently obtained, a crystal structure determination of (I) was undertaken, Fig. 1. The three six-membered rings are in different distorted conformations. Referring to the labels in Scheme 1, ring A is in a highly distorted half-boat conformation, ring B in a slightly distorted chair, and ring C is in a chair distorted towards a half-chair conformation. The five membered rings, D and E, are in a highly distorted envelope and a distorted twist conformation, respectively. The ring-puckering parameters (Cremer & Pople, 1975;Iulek & Zukerman-Schpector, 1997) (Table 1).

S2. Experimental
Compound (I), Neoaustin, was produced during cultivation of the fungus Penicillum sp over sterilized rice, and isolated from the methanol extract of the culture. Suitable crystals were obtained, by slow evaporation, from a mixture of dichloromethane, methanol and water.

S3. Refinement
The H atoms were refined in the riding-model approximation with C-H = 0.93 -0.98 Å and (0.82 Å for O-H), and with U iso (H) = 1.5U eq (methyl-C) or 1.2U eq (remaining-C and O). In the absence of significant anomalous scattering effects, 1008 Friedel pairs were averaged in the final refinement.  The molecular structure of (I) showing atom labelling scheme and displacement ellipsoids at the 30% probability level (arbitrary spheres for the H atoms).

Figure 2
Detail of the hydrogen bonding in (I). Hydrogen bonds are shown as hollow dashed bonds. See Table 1

Data collection
Bruker APEXII CCD area-detector diffractometer Radiation source: fine-focus sealed tube Graphite monochromator φ and ω scans 18157 measured reflections 2622 independent reflections 2453 reflections with I > 2σ(I) where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.17 e Å −3 Δρ min = −0.13 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 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.