supporting information


Acta Cryst. (2013). E69, o938-o939    [ doi:10.1107/S1600536813013524 ]

(1R,2S,4S,4aS,8S,8aS)-4-Hy­droxy-8,8a-dimethyl-10-oxo-2,3,4,7,8,8a-hexa­hydro-1H-4a,1-(ep­oxy­methano)­naphthalen-2-yl acetate

O. Selaïmia-Ferdjani, C. Bidjou-Haiour, A. Planchat and M. Pipelier

Abstract top

The title compound, C15H20O5, presents a bis­norsesquiterpene skeleton, with a trans-deca­line backbone constrained by the lactone bridge. The [alpha]-hy­droxy substituent and the methyl group belonging to the two deca­line rings are in axial positions, whereas the other methyl group and the acyl group occupy the sterically preferred equatorial positions. The mol­ecular structure is stabilized by an intra­molecular C-H...O hydrogen bond. In the crystal, mol­ecules are linked into chains along [010] by O-H...O hydrogen bonds

Comment top

Several nardosinane sesquiterpene derivatives, extracted from different soft corals (Lemnalia, Paralemnalia, Rhytisma and others), have already expressed promising biological properties (Bishara et al. 2008; Huang et al. 2011; Lu et al. 2011; Petit et al. 2004; Wang et al. 2012) while the potential of others remains to be explored (El-Gamal et al. 2005; Huang et al. 2006; Wang and Duh 2007; Wang et al. 2010). In our continuing interest in the total synthesis of biologically active compounds, we have recently proposed a synthetic strategy to access such sesquiterpene derivatives. In the course of the synthesis, the title compound appeared as an analogue structurally close to the natural lactone Paralemnolide A (Wang et al. 2012) which possesses cytotoxic activity. We report herein on the crystal structure of a new nardosinane sesquiterpene analogue.

The title compound presents a bisnorsesquiterpene skeleton, with a trans-decaline backbone constrained by the lactone bridge. The α-hydroxy substituent and the methyl group belonging to the two decaline rings are in an axial position, whereas the other methyl group and the acyl group occupy the sterically preferred equatorial position. In the crystal, the molecules form chains connected by O-H···O hydrogen bonds. The crystal structure is further stabilized by C-H···O contacts.

Related literature top

For the synthesis of the title compound, see: Selaimia-Ferdjani et al. (2013). For the biological activity of the natural lactone Paralemnolide A analogue of the title compound, see: Wang et al. (2012) and of related nardosinane sesquiterpene derivatives, see: Bishara et al. (2008); Huang et al. (2011); Petit et al. (2004); Lu et al. (2011). For related nardosinane sesquiterpenes whose biological activity has not yet been investigated, see: El-Gamal et al. (2005); Huang et al. (2006); Wang & Duh (2007); Wang et al. (2010).

Experimental top

Title compound was synthesized according to the reported method (Selaimia-Ferdjani et al., 2013): To a solution of diene 1 (100 mg, 0.38 mmol) in CH2Cl2 (2.5 ml) at 0°C was added via cannula a solution of mCPBA (350 mg, 0.38 mmol) in CH2Cl2 (5.0 ml). After 20 min, the reaction mixture was quenched with saturated NaHCO3 solution (10 ml). The aqueous layer was extracted with CH2Cl2 (3 x 25 ml) then the combined organic layers were washed with brine (50 ml), dried over MgSO4, filtered and concentrated under vacuum. The residue was purified by flash chromatography (eluant Petroleum Ether-EtOAc 100/0 to 7/3) to afford lactone 2 (title compound) (63 mg, 60%) as a solide. Crystals suitable for X-ray structure analysis (colorless crystals) were obtained by slow evaporation of a solution of the title compound in ethyl acetate/hexane (1:1, v/v) at room temperature. mp = 434 K; [α]20D= - 17 (c = 0.29 in CH2Cl2); 1H NMR (400 MHz, CDCl3) d 6.28 (ddd, J6–5 = 10.1 Hz, J6–7 = 4.7 Hz, J6–7 = 1.5 Hz, 1H, H6), 5.69 (d, J6–5 = 10.1 Hz, 1H, H5), 5.45 (ddd, J2–1 = 3.1 Hz, J3–2 = 7.2 Hz, J3–2 = 10.4 Hz, 1H, H2), 4.27 (d, J4–3 = 6.6 Hz, 1H, H4), 2.82 (d, J2–1 = 3.1 Hz, 1H, H1), 2.39 (m, 1H, H3), 2.15 (s, 3H, H13), 1.91–2.35 (m, 4H, H3, H7, H7, H8), 1.27 (s, 3H, H10), 0.90 (d, J8–11 = 6.5 Hz, 3H, H11). MS (EI): m/z (%) = 220 (28), 124 (96), 109 (72), 95 (29), 43 (100) HRMS (ESI+): calcd. for [M+Na]+ (C15H20O5Na) 303.12029, found 303.12015; elemental analysis calcd (%) C15H20O5: C 64.27, H 7.19, found: C 64.24, H 7.16.

Refinement top

H atoms bonded to C atoms were positioned with idealized geometry and were refined with Uiso(H) = 1.2× Ueq(C)) using a riding model with C—H = 0.96 Å. The H atom bonded to the O atom was located from a difference Fourier syntheses and it was freely refined.

Computing details top

Data collection: COLLECT (Nonius, 1998); cell refinement: EVALCCD (Duisenberg et al., 2003); data reduction: COLLECT (Nonius, 1998); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: JANA2006 (Petříček et al., 2006); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: JANA2006 (Petříček et al., 2006).

Figures top
[Figure 1] Fig. 1. Synthetic scheme to prepare title compound.
[Figure 2] Fig. 2. ORTEP drawing of the X-Ray crystallographic structure of the title molecule, with atom labeling. The displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as small spheres of arbitrary radius
[Figure 3] Fig. 3. Portion of the crystal structure showing the packing of the H–bonded infinite chains of the title compound. The intermolecular O-H···O bonds are depicted by blue lines.
(1R,2S,4S,4aS,8S,8aS)-4-Hydroxy-8,8a-dimethyl-10-oxo-2,3,4,7,8,8a-hexahydro-1H- 4a,1-(epoxymethano)naphthalen-2-yl acetate top
Crystal data top
C15H20O5Z = 2
Mr = 280.3F(000) = 300
Monoclinic, P21Dx = 1.288 Mg m3
Hall symbol: P 2ybMo Kα radiation, λ = 0.71069 Å
a = 10.3312 (10) ŵ = 0.10 mm1
b = 7.1692 (8) ÅT = 293 K
c = 10.8502 (6) ÅBlock, colourless
β = 115.958 (5)°0.48 × 0.42 × 0.30 mm
V = 722.56 (12) Å3
Data collection top
Nonius KappaCCD
diffractometer
3328 independent reflections
Radiation source: X-ray tube2774 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.049
CCD, ϕ and ω frames scansθmax = 28.1°, θmin = 6.5°
Absorption correction: gaussian
(JANA2006; Petříček et al., 2006)
h = 1313
Tmin = 0.967, Tmax = 0.972k = 99
12282 measured reflectionsl = 1414
Refinement top
Refinement on F277 constraints
R[F2 > 2σ(F2)] = 0.050H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.138Weighting scheme based on measured s.u.'s w = 1/(σ2(I) + 0.0025000002I2)
S = 1.84(Δ/σ)max = 0.013
3328 reflectionsΔρmax = 0.15 e Å3
185 parametersΔρmin = 0.12 e Å3
0 restraints
Crystal data top
C15H20O5V = 722.56 (12) Å3
Mr = 280.3Z = 2
Monoclinic, P21Mo Kα radiation
a = 10.3312 (10) ŵ = 0.10 mm1
b = 7.1692 (8) ÅT = 293 K
c = 10.8502 (6) Å0.48 × 0.42 × 0.30 mm
β = 115.958 (5)°
Data collection top
Nonius KappaCCD
diffractometer
3328 independent reflections
Absorption correction: gaussian
(JANA2006; Petříček et al., 2006)
2774 reflections with I > 2σ(I)
Tmin = 0.967, Tmax = 0.972Rint = 0.049
12282 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0500 restraints
wR(F2) = 0.138H atoms treated by a mixture of independent and constrained refinement
S = 1.84Δρmax = 0.15 e Å3
3328 reflectionsΔρmin = 0.12 e Å3
185 parameters
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O4a0.24245 (17)0.3248 (2)0.96277 (13)0.0469 (6)
O20.13229 (15)0.5347 (2)0.74186 (16)0.0540 (6)
O90.1870 (2)0.6248 (2)0.95660 (17)0.0580 (7)
O40.0236 (2)0.0757 (2)0.7741 (2)0.0747 (9)
O120.3391 (2)0.4418 (4)0.5763 (2)0.0969 (10)
C10.0910 (2)0.4390 (3)0.74640 (18)0.0373 (6)
C20.0592 (2)0.3717 (3)0.7223 (2)0.0452 (8)
C30.0495 (3)0.2237 (3)0.8268 (3)0.0614 (11)
C40.0719 (3)0.0820 (3)0.8628 (3)0.0554 (10)
C50.3316 (3)0.0382 (3)0.9057 (3)0.0649 (10)
C60.4264 (3)0.0442 (5)0.8551 (3)0.0789 (12)
C70.4257 (3)0.1856 (5)0.7544 (3)0.0787 (13)
C80.3245 (2)0.3495 (4)0.7387 (2)0.0565 (9)
C90.1760 (2)0.4802 (3)0.8969 (2)0.0409 (7)
C100.0991 (3)0.1656 (4)0.5957 (2)0.0558 (9)
C110.3100 (3)0.4779 (6)0.6212 (3)0.0855 (15)
C120.2732 (2)0.5534 (3)0.6613 (2)0.0504 (8)
C130.3297 (3)0.7288 (4)0.6924 (3)0.0661 (11)
C8a0.1778 (2)0.2776 (3)0.72788 (18)0.0400 (7)
C4a0.2064 (2)0.1689 (3)0.8603 (2)0.0446 (7)
H1c50.3433450.0534190.974280.0778*
H1c60.5007690.0487190.8851260.0947*
H1c70.5216580.2315280.7819060.0945*
H2c70.3983310.1271840.6669530.0945*
H1c80.3659310.425450.8196370.0678*
H1c110.2622030.5909010.6254420.1026*
H2c110.2546860.4165460.5353490.1026*
H3c110.4038840.5071080.6288330.1026*
H1c100.1620910.0709560.5900840.0669*
H2c100.0706510.2474850.5181770.0669*
H3c100.0152590.1080380.5957740.0669*
H1c10.0782380.5419240.685550.0448*
H1c20.1088520.3179460.6326280.0543*
H1c130.2665440.8302370.6983420.0793*
H2c130.3350070.7159160.7781330.0793*
H3c130.423990.7535810.6208270.0793*
H1c30.0417670.2832270.9089810.0736*
H2c30.1398070.1593920.7954060.0736*
H1c40.0991310.0408570.9550870.0665*
H10.056 (5)0.173 (7)0.818 (4)0.107 (13)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O4a0.0587 (9)0.0363 (7)0.0343 (7)0.0011 (7)0.0100 (6)0.0009 (5)
O20.0389 (8)0.0493 (8)0.0649 (9)0.0047 (7)0.0145 (7)0.0114 (8)
O90.0699 (11)0.0392 (7)0.0577 (9)0.0061 (8)0.0212 (8)0.0126 (7)
O40.0777 (13)0.0319 (8)0.0961 (15)0.0112 (8)0.0212 (11)0.0057 (9)
O120.0516 (11)0.1034 (17)0.1043 (16)0.0019 (11)0.0053 (10)0.0446 (15)
C10.0363 (9)0.0341 (8)0.0368 (9)0.0012 (8)0.0116 (7)0.0027 (8)
C20.0379 (10)0.0385 (9)0.0574 (12)0.0036 (8)0.0191 (9)0.0110 (9)
C30.0679 (15)0.0409 (10)0.0914 (18)0.0106 (11)0.0498 (14)0.0025 (12)
C40.0704 (16)0.0313 (10)0.0618 (14)0.0047 (10)0.0264 (12)0.0031 (9)
C50.0615 (15)0.0462 (11)0.0603 (14)0.0115 (12)0.0022 (12)0.0025 (11)
C60.0530 (15)0.0752 (17)0.0814 (18)0.0256 (15)0.0043 (13)0.0116 (16)
C70.0430 (13)0.105 (2)0.0816 (18)0.0144 (15)0.0214 (12)0.0156 (17)
C80.0391 (11)0.0744 (15)0.0528 (12)0.0025 (11)0.0171 (9)0.0064 (12)
C90.0448 (10)0.0342 (9)0.0414 (9)0.0066 (8)0.0168 (8)0.0016 (8)
C100.0477 (12)0.0648 (14)0.0440 (11)0.0048 (11)0.0100 (9)0.0161 (11)
C110.0634 (18)0.123 (3)0.0822 (18)0.0143 (19)0.0428 (15)0.011 (2)
C120.0388 (10)0.0562 (12)0.0541 (12)0.0009 (10)0.0183 (9)0.0023 (11)
C130.0491 (13)0.0702 (15)0.0796 (16)0.0127 (12)0.0289 (12)0.0025 (14)
C8a0.0353 (9)0.0430 (9)0.0351 (9)0.0008 (8)0.0091 (7)0.0031 (8)
C4a0.0498 (11)0.0325 (8)0.0406 (10)0.0004 (8)0.0097 (8)0.0019 (8)
Geometric parameters (Å, º) top
O4a—C91.340 (2)C5—H1c50.96
O4a—C4a1.504 (2)C6—C71.488 (5)
O2—C21.456 (3)C6—H1c60.96
O2—C121.337 (2)C7—C81.532 (4)
O9—C91.201 (3)C7—H1c70.96
O4—C41.426 (3)C7—H2c70.96
O4—H10.83 (5)C8—C111.526 (5)
O12—C121.185 (3)C8—C8a1.556 (3)
C1—C21.535 (3)C8—H1c80.96
C1—C91.507 (3)C10—C8a1.531 (3)
C1—C8a1.530 (3)C10—H1c100.96
C1—H1c10.96C10—H2c100.96
C2—C31.524 (4)C10—H3c100.96
C2—H1c20.96C11—H1c110.96
C3—C41.526 (4)C11—H2c110.96
C3—H1c30.96C11—H3c110.96
C3—H2c30.96C12—C131.486 (4)
C4—C4a1.534 (4)C13—H1c130.96
C4—H1c40.96C13—H2c130.96
C5—C61.316 (5)C13—H3c130.96
C5—C4a1.495 (3)C8a—C4a1.545 (3)
C9—O4a—C4a108.72 (13)C7—C8—H1c8108.87
C2—O2—C12118.11 (17)C11—C8—C8a113.63 (18)
C4—O4—H1111 (3)C11—C8—H1c8105.3
C2—C1—C9108.2 (2)C8a—C8—H1c8106.65
C2—C1—C8a110.30 (16)O4a—C9—O9121.67 (17)
C2—C1—H1c1107.44O4a—C9—C1109.53 (16)
C9—C1—C8a101.19 (14)O9—C9—C1128.80 (17)
C9—C1—H1c1115.73C8a—C10—H1c10109.47
C8a—C1—H1c1113.8C8a—C10—H2c10109.47
O2—C2—C1105.87 (16)C8a—C10—H3c10109.47
O2—C2—C3108.7 (2)H1c10—C10—H2c10109.47
O2—C2—H1c2112.88H1c10—C10—H3c10109.47
C1—C2—C3111.08 (17)H2c10—C10—H3c10109.47
C1—C2—H1c2110.54C8—C11—H1c11109.47
C3—C2—H1c2107.84C8—C11—H2c11109.47
C2—C3—C4115.7 (3)C8—C11—H3c11109.47
C2—C3—H1c3109.47H1c11—C11—H2c11109.47
C2—C3—H2c3109.47H1c11—C11—H3c11109.47
C4—C3—H1c3109.47H2c11—C11—H3c11109.47
C4—C3—H2c3109.47O2—C12—O12122.1 (2)
H1c3—C3—H2c3102.43O2—C12—C13111.11 (19)
O4—C4—C3110.43 (19)O12—C12—C13126.8 (2)
O4—C4—C4a111.3 (3)C12—C13—H1c13109.47
O4—C4—H1c4108.45C12—C13—H2c13109.47
C3—C4—C4a111.97 (19)C12—C13—H3c13109.47
C3—C4—H1c4107.71H1c13—C13—H2c13109.47
C4a—C4—H1c4106.8H1c13—C13—H3c13109.47
C6—C5—C4a122.5 (3)H2c13—C13—H3c13109.47
C6—C5—H1c5118.76C1—C8a—C8110.28 (18)
C4a—C5—H1c5118.76C1—C8a—C10114.76 (15)
C5—C6—C7124.3 (3)C1—C8a—C4a98.29 (18)
C5—C6—H1c6117.87C8—C8a—C10110.2 (2)
C7—C6—H1c6117.87C8—C8a—C4a108.26 (15)
C6—C7—C8112.8 (3)C10—C8a—C4a114.46 (17)
C6—C7—H1c7109.47O4a—C4a—C4102.8 (2)
C6—C7—H2c7109.47O4a—C4a—C5108.89 (15)
C8—C7—H1c7109.47O4a—C4a—C8a101.37 (14)
C8—C7—H2c7109.47C4—C4a—C5113.57 (19)
H1c7—C7—H2c7105.88C4—C4a—C8a114.52 (16)
C7—C8—C11111.6 (3)C5—C4a—C8a114.1 (2)
C7—C8—C8a110.4 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C8—H1c8···C90.962.482.913 (4)107.28
C10—H3c10···O40.962.312.946 (4)122.91
C2—H1c2···O120.962.362.668 (3)98.20
O4—H1···O9i0.83 (5)2.10 (4)2.907 (2)165 (4)
Symmetry code: (i) x, y+1, z.

Experimental details

Crystal data
Chemical formulaC15H20O5
Mr280.3
Crystal system, space groupMonoclinic, P21
Temperature (K)293
a, b, c (Å)10.3312 (10), 7.1692 (8), 10.8502 (6)
β (°) 115.958 (5)
V3)722.56 (12)
Z2
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.48 × 0.42 × 0.30
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correctionGaussian
(JANA2006; Petříček et al., 2006)
Tmin, Tmax0.967, 0.972
No. of measured, independent and
observed [I > 2σ(I)] reflections
12282, 3328, 2774
Rint0.049
(sin θ/λ)max1)0.663
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.050, 0.138, 1.84
No. of reflections3328
No. of parameters185
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.15, 0.12

Computer programs: COLLECT (Nonius, 1998), EVALCCD (Duisenberg et al., 2003), SIR2004 (Burla et al., 2005), JANA2006 (Petříček et al., 2006), Mercury (Macrae et al., 2006).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C10—H3c10···O40.962.312.946 (4)122.91
O4—H1···O9i0.83 (5)2.10 (4)2.907 (2)165 (4)
Symmetry code: (i) x, y+1, z.
 
Acknowledgements top

The authors thank the Profas Programme for a 18 month PhD felloship for OS-F in the CEISAM laboratory at Nantes University.