Hoodigogenin A from Hoodia gordonii

The title molecule (systematic name: 12-O-β-tigloyl-3β,14β-dihydroxypregn-5-en-20-one), C26H38O5, isolated from aerial parts of Hoodia gordonii, has its steroid A and C rings in chair conformations, its B ring in a half-chair conformation, and its five-membered ring in an envelope conformation. The OH group at the C/D ring junction forms an intramolecular hydrogen bond with the keto substituent. The OH group on the A ring forms an intermolecular hydrogen bond with the tiglate C=O group, propagating [010] chains in the crystal structure.

The title molecule (systematic name: 12-O--tigloyl-3,14dihydroxypregn-5-en-20-one), C 26 H 38 O 5 , isolated from aerial parts of Hoodia gordonii, has its steroid A and C rings in chair conformations, its B ring in a half-chair conformation, and its five-membered ring in an envelope conformation. The OH group at the C/D ring junction forms an intramolecular hydrogen bond with the keto substituent. The OH group on the A ring forms an intermolecular hydrogen bond with the tiglate C O group, propagating [010] chains in the crystal structure.  Table 1 Hydrogen-bond geometry (Å , ).  , 2006;Nutrition Business Journal, 2007;MacLean & Luo, 2004). As a part of our ongoing studies on Hoodia, we recently described isolation and characterization of 11 new oxypregnane glycosides (Hoodigosides A-K) along with P57AS3, the reported active oxypregnane glycoside from H. gordonii (Pawar et al., 2007). These glycosides consist of the title compound, hoodigogenin A, (I) as the aglycone. (I) is an unique pregnane derivative, owing to the cis-fusion of rings C and D of the steroid skeleton and the tiglic ester functionality at C12, and is only reported so far from H. gordonii.

Reports
The preliminary structure of (I) was elucidated with the help of one-dimensional and two-dimensional NMR, and HRESI-MS methods. The relative configurations were established using the NOESY correlations, in which (I) was characterized as having β-OH groups at C3, and C14. The tiglic ester substitution at C12 and the acetyl side chain at C17 were assigned a β orientation as well (Pawar et al., 2007). Here we report the crystal structure of (I) (Fig. 1), which confirms the relative configurations ascribed by the NMR studies.
The The O2-H group forms an intramolecular hydrogen bond with C(O)Me carbonyl O3, making a discrete seven-membered ring, graph set S(7) (Etter, 1990 The sub-fraction 2 was repeatedly chromatographed on a silica gel column using isocratic solvent systems of hexane: CHCl 3 (2:98) and CH 2 Cl 2 (100%) that led to isolation of the title compound as an amorphous solid. Compound (I) displayed a prominent blue spot on TLC upon spraying with anisaldehyde-H 2 SO 4 reagent, followed by heating at 100 °C for 1-2 minutes. Further, (I) was dissolved in acetone:hexane (70:30 v/v), which upon standing at room temperature for 24 h yielded 150 mg of colorless crystals. Colorless plates of (I) suitable for X-ray diffraction were obtained by recrystallization in hexane with few drops of acetone. The specific rotation of hoodigogenin A [α] 25 D is +1.33 (c0.3, CHCl 3 ). Detailed HRESI-MS and NMR data for (1) were described previously (Pawar et al., 2007).

Refinement
The absolute configuration of (I) could not be determined, and was chosen to agree with the accepted configuration of pregnane steroids (C3 S, C8 R, C9 S, C10 R, C12 R, C13 S, C14 S, C17 S): Friedel pairs were averaged before refinement.
The H atoms were placed in idealized positions (C-H = 0.95-0.99Å, O-H = 0.84Å) and thereafter treated as riding with U iso (H) = 1.2U eq (C) or 1.5U eq (methyl C, O). Fig. 1. View of the molecular structure of (I), with displacement ellipsoids at the 50% level (spheres of arbitrary radius for the H atoms).