12α-Hy­droxy-3,27-dioxooleanano-28,13-lactone

Jun-yi Hu; Gang-gang Wu; Ying-qian Xu; Guo-yong Xiao; Peng Lei

doi:10.1107/S1600536812017783

. 2012 May 2;68(Pt 6):o1586. doi: 10.1107/S1600536812017783

12α-Hydroxy-3,27-dioxooleanano-28,13-lactone

Jun-yi Hu ^a,^*, Gang-gang Wu ^a, Ying-qian Xu ^a, Guo-yong Xiao ^a, Peng Lei ^a

PMCID: PMC3379199 PMID: 22719397

Abstract

There are two independent molecules in the asymmetric unit of the title compound, C₃₀H₄₄O₅. They comprise a triterpenoid skeleton of five six-membered rings and a five-membered lactone ring. The five six-membered rings are all trans-fused. In both independent molecules the D rings adopt a slightly distorted half-chair conformation due the presence of the lactone ring while the other four six-membered rings all adopt chair conformations. The characteristic carbon–carbon double bond of the oleanoic skeleton is absent. Intermolecular O—H⋯O hydrogen bonds between the hydroxy and carbonyl groups occur in the crystal structure.

Related literature

For the pharmacological properties of pentacyclic triterpene acids, see: Gene et al. (1996 ▶); Hu et al. (2009 ▶); Xu et al. (2007 ▶).

Experimental

Crystal data

C₃₀H₄₄O₅
M _r = 484.65
Orthorhombic,
a = 12.4457 (3) Å
b = 15.5804 (4) Å
c = 27.1710 (8) Å
V = 5268.7 (2) Å³
Z = 8
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 113 K
0.32 × 0.30 × 0.26 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2007 ▶) T _min = 0.975, T _max = 0.979
46805 measured reflections
6391 independent reflections
6106 reflections with I > 2σ(I)
R _int = 0.054

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.095
S = 1.10
6391 reflections
649 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: CrystalClear (Rigaku, 2007 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: CrystalStructure (Rigaku, 2007 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812017783/kp2404sup1.cif

e-68-o1586-sup1.cif^{(48.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812017783/kp2404Isup2.hkl

e-68-o1586-Isup2.hkl^{(312.8KB, 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
O2—H2⋯O4ⁱ	0.86 (3)	1.94 (3)	2.782 (2)	167 (3)
O7—H7⋯O6ⁱⁱ	0.90 (3)	1.91 (3)	2.803 (2)	172 (2)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This project was granted financial support from the Science and Technology Department of Liaoning Province Science Foundation (2010226003), the Higher Education Department of Liaoning Province Research Foundation (LS2020089) and the Graduate Education Innovation Program 2010.

supplementary crystallographic information

Comment

Pentacyclic triterpene acids such as oleanolic acid, crataegolic acid and ursolic acid and their glycosides are widely distributed in the plant kingdom. They exhibit a variety of pharmacological properties such as analgesic (Gene et al., 1996), cytotoxic (Hu et al., 2009), and immunosuppressive activities (Xu et al., 2007). Recently, our laboratories have disclosed the design and synthesis of a novel series of oleanolic acid derivatives. Herewith, we report the synthesis and crystal structure of the title compound. The title compound crystallizes with two molecules per asymmetric unit (Fig. 1). Each molecule contains a five-membered lactone ring and five trans-fused cyclohexane rings via A(C1—C5, C10), B(C5—C10), C(C8, C9, C11—C14), D(C13—C18) and E(C17—C22) in the molecule A, respectively, and A'(C31—C35, C40), B'(C35—C40), C'(C38, C39, C41—C44), D'(C43—C48) and E'(C47—C52) in the molecule B, respectively. The characteristical carbon double bond of oleanoic skeleton is absent in the title compound. Ring A(A'), B(B'), C(C') and E(E') adopt chair conformations, while ring D(D') adopts a slightly distorted half-chair conformation as a result of the formation of the lactone ring. The hydroxy groups attached to atom C12 and C42 are equatorial. The intermolecular O—H···O hydrogen bonds were observed between the hydroxy groups and carbonyl groups (Table 1) which stablize the crystal structure.

Experimental

Commercially available oleanolic acid and Jones reagent in dry CH₂Cl₂/acetone (1/1) was stirred at 278 K for 1 h to give 3-oxoolean-12-en-28-oic acid. Reaction of 3-oxoolean-12-en-28-oic acid with O₃ in CH₂Cl₂/MeOH (1:1) at 223 K gave 12-hydroxy-3-oxooleanano -28,13-lactone. A stream of NOCl was introduced to an ice-cold solution of 12-hydroxy-3-oxooleanano-28,13-lactone in pyridine at 233 K over 30 min to give lactone nitrite. A solution of lactone nitrite in acetone was irradiated by high pressure Hg lamp through a Pyrex filter under nitrogen atmosphere for 1 h to give oxime. To a solution of oxime in dioxane and AcOH, aqueous TiCl₃ was added under ice, keeping temperature of 299 K by cooling, for 4 h to give imine. To imine in dioxane and AcOH, an aqueous solution of NaNO₂ was added for 1 h to obtain the title compound. Crystals suitable for X-ray structure analysis were obtained by slow evaporation of a solution in methanol at room temperature.