Hoodigogenin A from Hoodia gordonii

Yatin J Shukla; Frank R Fronczek; Rahul S Pawar; Ikhlas A Khan

doi:10.1107/S1600536808022368

. 2008 Jul 31;64(Pt 8):o1643–o1644. doi: 10.1107/S1600536808022368

Hoodigogenin A from Hoodia gordonii

Yatin J Shukla ^a, Frank R Fronczek ^b,^*, Rahul S Pawar ^c, Ikhlas A Khan ^a,^c

PMCID: PMC2962224 PMID: 21203331

Abstract

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.

Related literature

For related literature, see: Allen (2002 ▶); Consumer Reports (2006 ▶); Etter (1990 ▶); MacLean & Luo (2004 ▶); Muller & Albers (2002 ▶); Nutrition Business Journal (2007 ▶); Pawar et al. (2007 ▶); Shin et al. (1990 ▶); Van Heerden et al. (1998 ▶).

Experimental

Crystal data

C₂₆H₃₈O₅
M _r = 430.56
Orthorhombic,
a = 7.6523 (9) Å
b = 10.6885 (12) Å
c = 27.705 (3) Å
V = 2266.0 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 100 K
0.30 × 0.27 × 0.05 mm

Data collection

Nonius KappaCCD (with an Oxford Cryosystems Cryostream cooler) diffractometer
Absorption correction: none
9377 measured reflections
2677 independent reflections
2156 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.100
S = 1.02
2677 reflections
287 parameters
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: COLLECT (Nonius, 2000 ▶); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: SCALEPACK and DENZO (Otwinowski & Minor, 1997 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808022368/hb2752sup1.cif

e-64-o1643-sup1.cif^{(25.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808022368/hb2752Isup2.hkl

e-64-o1643-Isup2.hkl^{(131.5KB, 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
O1—H10H⋯O5ⁱ	0.84	2.11	2.941 (3)	173
O2—H20H⋯O3	0.84	2.10	2.886 (2)	156

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Symmetry code: (i) Inline graphic .

Acknowledgments

The purchase of the diffractometer was made possible by grant No. LEQSF (1999–2000)-ENH-TR-13, administered by the Louisiana Board of Regents. Phytochemical research on H. gordonii was funded by USFDA ‘Botanical Dietary Supplements: Science-Base for Authentication’ grant No. FD-U-002071-07. The authors thank Missouri Botanical Garden, USA for authentic plant material. YJS is thankful to the NCNPR for a graduate research assistantship.

supplementary crystallographic information

Comment

Hoodia gordonii, a succulent plant, is one of the 18 species of Hoodia (Fam. Asclepiadaceae) that are indigenous to the summer rainfall regions of the Kalahari Desert in South Africa, Botswana and Namibia (Muller & Albers, 2002). In past few years, Hoodia gordonii has gained popularity as a weight-loss dietary supplement (Van Heerden et al., 1998; Consumer Reports, 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.

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 A and C rings (C1—C5, C10; C8, C9, C11—C14 respectively) have chair conformations, with endocyclic torsion-angle magnitudes in the range 42.2 (3) to 60.1 (2)°. The unsaturated B ring (C5—C10) has a half-chair conformation, with C8 displaced by 0.431 (2) Å and C9 by -0.373 (2) Å from the best plane of the other four C atoms. The five-membered D ring has an envelope conformation, with C14 at the flap position, displaced by 0.625 (2) Å from the best plane of the other four C atoms. The conformation of the C(O)Me group with respect to the main skeleton is defined by the torsion angle C16—C17—C20—O3, -37.5 (3)°, and the conformation of the tiglate substituent with respect to the skeleton by C11—C12—O4—C22, -102.8 (2)°. The tiglate is approximately planar, having a slight twist of -5.2 (3)° about its central bond (O4—C22—C23—C25).

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 O1—H group forms an intermolecular hydrogen bond with tiglate O5 (at 2-x, y-1/2, 3/2-z), thus making chains in the [0 1 0] direction (Table 1).

The Cambridge Structural Database (version 5.29, Nov. 2007; Allen, 2002) contains only one Δ⁵-pregnane steroid having O-substituents at C3, C12, and C14, refcode SENKUR (Shin et al., 1990). SENKUR, like (I) has OH groups at C3 and C14, a benzoate at C12, and also OH groups at C8 and C17. The conformations of the A, B, and C rings in (I) and SENKUR are similar, with 18 endocyclic torsion angles differing by a mean value of 5.7°. The five-membered ring of SENKUR, however, has an envelope conformation with a different atom, C13 at the flap position. This may be a result of the fact that SENKUR has the opposite configuration at C17, with the C(O)Me substituent α oriented (Shin et al., 1990).

Experimental

Powdered aerial parts of H. gordonii were purchased from a commercial supplier. The plant material was authenticated by Vaishali Joshi by comparing with authentic sample of H. gordonii obtained from Missouri Botanical Garden Missouri, USA. A voucher specimen (Voucher No. 2799) has been deposited in the repository of The National Center for Natural Product Research. 4.75 kg of coarsely powdered H. gordonii was extracted by percolation with CHCl₃ (4 × 4 L). These extracts were combined and concentrated to obtain a thick mass (402.1 g). The extract was dissolved in MeOH/H₂O (95:5 v/v) and partitioned with hexane. The polar fraction (136 g) was subjected to VLC on silica gel (1500 g) by eluting with gradients of CHCl₃/MeOH/H₂O from 100:4:0.5 (3L), up to 90:12:0.5 (by increasing MeOH and reducing CHCl₃, each by 1% increments), to generate eight sub-fractions.

The sub-fraction 2 was repeatedly chromatographed on a silica gel column using isocratic solvent systems of hexane: CHCl₃ (2:98) and CH₂Cl₂ (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-H₂SO₄ 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, CHCl₃). Detailed HRESI-MS and NMR data for (1) were described previously (Pawar et al., 2007).