Methyl 5a-acetoxymethyl-3-isopropyl-8-methyl-1,2,3,3a,4,5,5a,6,7,10,10a,10b-dodecahydro-7,10-endo-epidioxycylohepta[e]indene-3a-carboxylate

The molecule of the title compound, C23H34O6, is built up from three fused carbocycles, one five-membered, one six-membered and one seven-membered. The five-membered ring has an envelope conformation, whereas the six-membered ring has a perfect chair conformation and the seven-membered ring has a boat conformation. Intramolecular C—H⋯O hydrogen bonds together with van der Waals interactions stabilize the molecular conformation.

The molecule of the title compound, C 23 H 34 O 6 , is built up from three fused carbocycles, one five-membered, one sixmembered and one seven-membered. The five-membered ring has an envelope conformation, whereas the six-membered ring has a perfect chair conformation and the sevenmembered ring has a boat conformation. Intramolecular C-HÁ Á ÁO hydrogen bonds together with van der Waals interactions stabilize the molecular conformation.

Comment
The title compound was obtained from a methylation reaction over the acid group of 17-acetoxymulinic acid, which was previously isolated from Mulinum crassifolium (Apiaceae). Mulinum crassifolium is a 15 cm small shrub, which grows in the north of Chile at altitudes above 4000 m. This plant, commonly known as chuquican, susurco or espinilla is used in the folk medicine, principally against diabetes, and bronchial (caught) and intestinal disorders (Munizaga et al., 1958). Mulinane diterpenes exhibits antiplasmodial (Loyola et al., 2004) andanti-Tripanosomacruzi (Araya et al., 2003) activities.We have undertaken the X-ray crystal-structure determination of (I) in order to establish its molecular conformation and relative stereochemistry. We are not able to determine the absolute stereochemistry by X-ray methods and the configuration shown here was chosen to be in accord with that reported in previous chemical studies (Loyola et al., 1990). The structure consists of a mulinic acid skeleton and the isopropyl, acetyloxymethyl and carboxylate groups at C3, C5a and C3 are β-oriented respectively, whereas the endo-peroxide group is α-oriented. The cyclopentane (A), cyclohexane (B) and cycloheptene (C) rings are in an envelope, chair and boat conformation, respectively [Q 2 = 0.424 (3) Å, φ 2 = 107.2 (4)° for ring A; Q T = 0.553 (3) Å, θ = 159.6 (3)°, φ=189.2 (8)° for ring B; Q T = 1.123 (3) Å, φ 2 =179.9 (2)°, for ring C] (Cremer & Pople, 1975).
The A and B and B and C rings are trans and cis-fused respectively. The molecular conformation of the title compound, is stabilized by three strong intramolecular hydrogen bonds, Fig.2.

Experimental
Dried and finely powdered aerial parts of Mulinum crassifolium (1530 g) were extracted with petroleum ether at room temperature. The solvent was evaporated in vacuum yielding a gum (40 g). The concentrated petrol ether extract was fractionated on silica gel column with hexane-ethyl acetate mixtures of increasing polarity as elution solvents. The fraction (0.867 g) eluted was further separated and purified by silica gel chromatography to give 120.5 mg of 17-acetoxymulinic acid which was methylated with diazomethane using ethyl ether as solvent at room temperature to give 110 mg de (I). Recrystallization from hexane-ethyl acetate (7:3) at room temperature afforded colourless crystals suitable for X-ray diffraction analysis.

Refinement
H atoms bonded to C atoms were included in calculated positions and refined as riding atoms, with calculated C -H bond lengths in the range 0.96 -0.98 Å. For methyl atoms, U iso (H) = 1.5U eq (C), while for other H atoms, U iso (H) = 1.2U eq (C).
The data are 96% complete. Measurements were nor complete because the single-crystal used was extremely small and curved. The material was difficult to obtain in a suitable crystalline form and the best available specimen was lost late in the data collection. However, the reduced precision does not seriously affect the molecular skeleton and molecular arrangement.
We are not able to determine the absolute stereochemistry by X-ray methods and the configuration shown here was chosen to be in accord with that reported in previous chemical studies (Loyola et al., 1990). In the absence of significant anomalous supplementary materials sup-2 scattering effects, Friedel pairs were averaged. The highest electron-density peak is located 0.71 Å from atom C3a in the final difference Fourier and the deepest hole is located 0.81 Å from O4. Fig. 1. A view of the molecular structure of the title compound, showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii. Methyl 5a-acetoxymethyl-3-isopropyl-8-methyl-1,2,3,3a,4,5,5a,6,7,10,10a,10b-dodecahydro-7,10-endoepidioxycylohepta[e]indene-3a-carboxylate  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 Rfactors(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.