9α-Hy-droxy-12-{[4-(4-meth-oxy-phen-yl)piperazin-1-yl]meth-yl}-4,8-dimethyl-3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.

The title compound, C(26)H(36)N(2)O(5), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.0(2,4)]tetra-dec-7-en-13-one), wich was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The mol-ecule is built up from fused five- and ten-membered rings with the meth-oxy-phenyl-piperazine group as a substituent. The ten-membered ring adopts an approximate chair-chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring a flattened envelope conformation; the C(H)-C-C(H) atoms representing the flap lie out of the mean plane through the remaining four atoms by 0.343 (3) Å. The dihedral angle between the mean planes of the ten-membered ring and the lactone ring is 18.12 (14)°. An intra-molecular O-H⋯N hydrogen bond occurs. The crystal structure features weak C-H⋯O inter-actions.

Related literature

For background to the medicinal uses of the plant Anvillea radiata, see: Abdel Sattar et al. (1996 ▶); Bellakhdar (1997 ▶); El Hassany et al. (2004 ▶); Qureshi et al. (1990 ▶). For ring-puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C26H36N2O5

M = 456.57

Orthorhombic,

a = 6.7066 (7) Å

b = 11.9033 (11) Å

c = 30.322 (4) Å

V = 2420.6 (4) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 180 K

0.33 × 0.17 × 0.04 mm

Data collection

Agilent Xcalibur Sapphire1 (long nozzle) diffractometer

Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ▶) T min = 0.732, T max = 1.000

14543 measured reflections

4925 independent reflections

3663 reflections with I > 2σ(I)

R int = 0.055

Refinement

R[F 2 > 2σ(F 2)] = 0.055

wR(F 2) = 0.130

S = 1.04

4925 reflections

303 parameters

H-atom parameters constrained

Δρmax = 0.25 e Å−3

Δρmin = −0.23 e Å−3

Data collection: CrysAlis PRO (Agilent, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶)and PLATON (Spek, 2009 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812003662/ds2172sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812003662/ds2172Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812003662/ds2172Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C26H36N2O5	F(000) = 984
Mr = 456.57	Dx = 1.253 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 14543 reflections
a = 6.7066 (7) Å	θ = 3.1–26.4°
b = 11.9033 (11) Å	µ = 0.09 mm−1
c = 30.322 (4) Å	T = 180 K
V = 2420.6 (4) Å3	Platelet, colourless
Z = 4	0.33 × 0.17 × 0.04 mm

Agilent Xcalibur Sapphire1 (long nozzle) diffractometer	4925 independent reflections
Radiation source: fine-focus sealed tube	3663 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.055
Detector resolution: 8.2632 pixels mm-1	θmax = 26.4°, θmin = 3.1°
ω scans	h = −8→8
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010)	k = −14→14
Tmin = 0.732, Tmax = 1.000	l = −37→37
14543 measured reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.055	H-atom parameters constrained
wR(F2) = 0.130	w = 1/[σ2(Fo2) + (0.0567P)2] where P = (Fo2 + 2Fc2)/3
S = 1.04	(Δ/σ)max = 0.001
4925 reflections	Δρmax = 0.25 e Å−3
303 parameters	Δρmin = −0.23 e Å−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0073 (12)

Experimental. Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. CrysAlisPro (Agilent Technologies)

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
C1	0.4429 (4)	0.9320 (2)	0.06430 (8)	0.0236 (6)
H1	0.5156	0.9747	0.0877	0.028*
C2	0.3207 (4)	1.0088 (2)	0.03673 (9)	0.0276 (6)
H2	0.2198	0.9692	0.0181	0.033*
C4	0.2646 (4)	1.1235 (2)	0.04810 (10)	0.0328 (7)
C5	0.0642 (5)	1.1608 (2)	0.03175 (11)	0.0440 (8)
H5A	0.0334	1.1215	0.0038	0.053*
H5B	0.0681	1.2425	0.0256	0.053*
C6	−0.1006 (5)	1.1365 (3)	0.06533 (12)	0.0500 (9)
H6A	−0.0928	1.1917	0.0897	0.060*
H6B	−0.2323	1.1447	0.0510	0.060*
C7	−0.0803 (4)	1.0198 (2)	0.08363 (11)	0.0377 (7)
H7	−0.1012	0.9598	0.0635	0.045*
C8	−0.0368 (5)	0.9912 (3)	0.12466 (10)	0.0396 (8)
C9	0.0201 (4)	0.8728 (3)	0.13688 (10)	0.0382 (7)
H9	−0.0145	0.8614	0.1686	0.046*
C10	0.2457 (4)	0.8572 (2)	0.13205 (9)	0.0306 (6)
H10A	0.2871	0.7920	0.1502	0.037*
H10B	0.3133	0.9245	0.1440	0.037*
C11	0.3171 (4)	0.8384 (2)	0.08456 (8)	0.0227 (6)
H11	0.1959	0.8291	0.0657	0.027*
C12	0.4457 (4)	0.7345 (2)	0.07835 (8)	0.0243 (6)
H12	0.5218	0.7194	0.1061	0.029*
C13	0.5872 (4)	0.7650 (2)	0.04265 (9)	0.0266 (6)
C15	0.3307 (4)	0.6301 (2)	0.06537 (9)	0.0288 (6)
H15A	0.2635	0.6437	0.0368	0.035*
H15B	0.4256	0.5673	0.0612	0.035*
C16	0.2748 (4)	0.5460 (2)	0.13653 (9)	0.0309 (7)
H16A	0.3659	0.6011	0.1504	0.037*
H16B	0.3552	0.4806	0.1271	0.037*
C17	0.1246 (4)	0.5089 (3)	0.16934 (9)	0.0358 (7)
H17A	0.1933	0.4746	0.1949	0.043*
H17B	0.0488	0.5749	0.1800	0.043*
C18	−0.1058 (4)	0.4730 (2)	0.11077 (9)	0.0327 (7)
H18A	−0.1952	0.5357	0.1190	0.039*
H18B	−0.1878	0.4138	0.0967	0.039*
C19	0.0472 (4)	0.5141 (2)	0.07857 (9)	0.0328 (7)
H19A	0.1264	0.4495	0.0678	0.039*
H19B	−0.0213	0.5480	0.0529	0.039*
C20	−0.1351 (4)	0.3686 (2)	0.18020 (9)	0.0271 (6)
C21	−0.0596 (5)	0.3360 (2)	0.22117 (9)	0.0383 (7)
H21	0.0699	0.3598	0.2297	0.046*
C22	−0.1693 (5)	0.2703 (3)	0.24923 (10)	0.0429 (8)
H22	−0.1147	0.2493	0.2769	0.051*
C23	−0.3549 (5)	0.2348 (3)	0.23802 (10)	0.0413 (8)
C24	−0.4336 (5)	0.2676 (3)	0.19821 (11)	0.0467 (8)
H24	−0.5644	0.2447	0.1902	0.056*
C25	−0.3234 (4)	0.3338 (3)	0.16971 (10)	0.0387 (7)
H25	−0.3798	0.3555	0.1423	0.046*
C26	0.3438 (5)	1.1828 (3)	0.08780 (12)	0.0526 (10)
H26A	0.4715	1.1494	0.0964	0.079*
H26B	0.2485	1.1756	0.1121	0.079*
H26C	0.3634	1.2625	0.0809	0.079*
C27	−0.0231 (7)	1.0695 (3)	0.16314 (13)	0.0744 (13)
H27A	−0.0360	1.1472	0.1528	0.112*
H27B	0.1062	1.0598	0.1777	0.112*
H27C	−0.1304	1.0527	0.1841	0.112*
C28	−0.6231 (7)	0.1128 (6)	0.2554 (2)	0.134 (3)
H28A	−0.7310	0.1678	0.2527	0.201*
H28B	−0.6591	0.0564	0.2776	0.201*
H28C	−0.6019	0.0758	0.2269	0.201*
N1	0.1814 (3)	0.59719 (17)	0.09797 (7)	0.0254 (5)
N2	−0.0123 (3)	0.42794 (18)	0.15021 (7)	0.0286 (5)
O3	0.4135 (3)	1.10270 (15)	0.01501 (7)	0.0388 (5)
O4	−0.0873 (3)	0.79295 (17)	0.11206 (8)	0.0440 (6)
H4	−0.0112	0.7400	0.1049	0.066*
O5	−0.4482 (4)	0.1672 (2)	0.26829 (8)	0.0655 (8)
O12	0.6957 (3)	0.70592 (16)	0.02200 (7)	0.0392 (5)
O14	0.5817 (3)	0.87658 (14)	0.03489 (6)	0.0277 (4)

	U11	U22	U33	U12	U13	U23
C1	0.0273 (14)	0.0170 (13)	0.0264 (13)	0.0045 (11)	0.0020 (12)	−0.0043 (11)
C2	0.0301 (14)	0.0167 (12)	0.0360 (15)	−0.0029 (12)	−0.0034 (13)	0.0024 (13)
C4	0.0362 (15)	0.0138 (13)	0.0484 (18)	0.0002 (12)	−0.0031 (14)	−0.0001 (13)
C5	0.0467 (18)	0.0231 (15)	0.062 (2)	0.0085 (14)	−0.0062 (17)	0.0091 (15)
C6	0.0412 (18)	0.0364 (18)	0.072 (2)	0.0170 (16)	−0.0093 (18)	0.0051 (18)
C7	0.0255 (14)	0.0313 (16)	0.056 (2)	0.0021 (14)	−0.0035 (15)	−0.0011 (15)
C8	0.0371 (17)	0.0342 (17)	0.0476 (19)	0.0160 (15)	0.0053 (15)	−0.0058 (15)
C9	0.0415 (17)	0.0354 (16)	0.0377 (16)	0.0084 (14)	0.0085 (15)	−0.0036 (15)
C10	0.0373 (15)	0.0254 (15)	0.0292 (15)	0.0072 (13)	0.0056 (13)	0.0000 (13)
C11	0.0273 (13)	0.0154 (12)	0.0254 (13)	0.0033 (11)	−0.0001 (11)	−0.0005 (11)
C12	0.0321 (14)	0.0164 (13)	0.0243 (13)	0.0055 (11)	0.0037 (12)	−0.0002 (11)
C13	0.0318 (14)	0.0178 (13)	0.0301 (15)	0.0059 (12)	0.0005 (13)	−0.0005 (12)
C15	0.0411 (15)	0.0178 (13)	0.0275 (14)	0.0053 (13)	0.0049 (13)	0.0000 (12)
C16	0.0339 (16)	0.0270 (15)	0.0319 (15)	−0.0020 (12)	−0.0040 (13)	0.0092 (13)
C17	0.0423 (17)	0.0355 (16)	0.0294 (15)	−0.0113 (14)	−0.0069 (14)	0.0075 (13)
C18	0.0419 (17)	0.0257 (14)	0.0304 (15)	−0.0056 (13)	−0.0096 (14)	0.0057 (12)
C19	0.0479 (17)	0.0237 (14)	0.0269 (14)	−0.0051 (14)	−0.0052 (14)	0.0025 (12)
C20	0.0375 (15)	0.0154 (12)	0.0283 (14)	0.0028 (11)	−0.0006 (12)	−0.0014 (11)
C21	0.0473 (18)	0.0352 (17)	0.0325 (15)	−0.0144 (15)	−0.0045 (15)	0.0053 (14)
C22	0.059 (2)	0.0404 (18)	0.0295 (15)	−0.0120 (17)	−0.0055 (16)	0.0058 (15)
C23	0.0438 (18)	0.0407 (18)	0.0395 (18)	−0.0049 (15)	0.0043 (15)	0.0094 (15)
C24	0.0338 (16)	0.048 (2)	0.058 (2)	−0.0046 (16)	−0.0044 (16)	0.0198 (17)
C25	0.0367 (16)	0.0369 (17)	0.0425 (17)	0.0059 (15)	−0.0034 (14)	0.0138 (15)
C26	0.056 (2)	0.0249 (16)	0.077 (3)	0.0041 (16)	−0.0127 (19)	−0.0184 (17)
C27	0.103 (3)	0.056 (2)	0.064 (2)	0.039 (2)	−0.001 (2)	−0.022 (2)
C28	0.076 (3)	0.183 (6)	0.143 (5)	−0.071 (4)	−0.035 (3)	0.119 (5)
N1	0.0358 (13)	0.0180 (11)	0.0223 (11)	−0.0021 (10)	−0.0044 (10)	0.0038 (9)
N2	0.0372 (13)	0.0231 (11)	0.0255 (12)	−0.0044 (10)	−0.0039 (11)	0.0039 (10)
O3	0.0443 (11)	0.0162 (9)	0.0558 (13)	−0.0018 (9)	0.0035 (11)	0.0104 (9)
O4	0.0342 (12)	0.0337 (12)	0.0640 (14)	−0.0016 (10)	0.0071 (11)	0.0012 (11)
O5	0.0575 (15)	0.0798 (19)	0.0593 (15)	−0.0293 (15)	−0.0015 (13)	0.0339 (15)
O12	0.0498 (13)	0.0286 (10)	0.0390 (12)	0.0102 (10)	0.0163 (10)	−0.0017 (9)
O14	0.0314 (10)	0.0177 (9)	0.0341 (10)	0.0027 (8)	0.0081 (9)	0.0003 (8)

C1—O14	1.448 (3)	C16—C17	1.483 (4)
C1—C2	1.485 (4)	C16—H16A	0.9900
C1—C11	1.526 (3)	C16—H16B	0.9900
C1—H1	1.0000	C17—N2	1.452 (3)
C2—O3	1.439 (3)	C17—H17A	0.9900
C2—C4	1.457 (4)	C17—H17B	0.9900
C2—H2	1.0000	C18—N2	1.453 (3)
C4—O3	1.437 (4)	C18—C19	1.499 (4)
C4—C26	1.494 (4)	C18—H18A	0.9900
C4—C5	1.500 (4)	C18—H18B	0.9900
C5—C6	1.530 (4)	C19—N1	1.460 (3)
C5—H5A	0.9900	C19—H19A	0.9900
C5—H5B	0.9900	C19—H19B	0.9900
C6—C7	1.502 (4)	C20—C25	1.367 (4)
C6—H6A	0.9900	C20—C21	1.396 (4)
C6—H6B	0.9900	C20—N2	1.416 (3)
C7—C8	1.323 (4)	C21—C22	1.370 (4)
C7—H7	0.9500	C21—H21	0.9500
C8—C27	1.496 (5)	C22—C23	1.358 (4)
C8—C9	1.507 (4)	C22—H22	0.9500
C9—O4	1.410 (4)	C23—O5	1.371 (4)
C9—C10	1.532 (4)	C23—C24	1.374 (4)
C9—H9	1.0000	C24—C25	1.384 (4)
C10—C11	1.534 (4)	C24—H24	0.9500
C10—H10A	0.9900	C25—H25	0.9500
C10—H10B	0.9900	C26—H26A	0.9800
C11—C12	1.520 (3)	C26—H26B	0.9800
C11—H11	1.0000	C26—H26C	0.9800
C12—C13	1.484 (4)	C27—H27A	0.9800
C12—C15	1.515 (4)	C27—H27B	0.9800
C12—H12	1.0000	C27—H27C	0.9800
C13—O12	1.190 (3)	C28—O5	1.396 (5)
C13—O14	1.350 (3)	C28—H28A	0.9800
C15—N1	1.460 (3)	C28—H28B	0.9800
C15—H15A	0.9900	C28—H28C	0.9800
C15—H15B	0.9900	O4—H4	0.8400
C16—N1	1.460 (3)
O14—C1—C2	106.8 (2)	N1—C16—H16A	109.3
O14—C1—C11	105.74 (18)	C17—C16—H16A	109.3
C2—C1—C11	111.8 (2)	N1—C16—H16B	109.3
O14—C1—H1	110.8	C17—C16—H16B	109.3
C2—C1—H1	110.8	H16A—C16—H16B	107.9
C11—C1—H1	110.8	N2—C17—C16	111.0 (2)
O3—C2—C4	59.49 (17)	N2—C17—H17A	109.4
O3—C2—C1	119.8 (2)	C16—C17—H17A	109.4
C4—C2—C1	125.9 (2)	N2—C17—H17B	109.4
O3—C2—H2	113.6	C16—C17—H17B	109.4
C4—C2—H2	113.6	H17A—C17—H17B	108.0
C1—C2—H2	113.6	N2—C18—C19	111.2 (2)
O3—C4—C2	59.63 (17)	N2—C18—H18A	109.4
O3—C4—C26	113.4 (3)	C19—C18—H18A	109.4
C2—C4—C26	122.8 (3)	N2—C18—H18B	109.4
O3—C4—C5	116.3 (2)	C19—C18—H18B	109.4
C2—C4—C5	115.5 (3)	H18A—C18—H18B	108.0
C26—C4—C5	116.4 (3)	N1—C19—C18	112.4 (2)
C4—C5—C6	111.8 (3)	N1—C19—H19A	109.1
C4—C5—H5A	109.3	C18—C19—H19A	109.1
C6—C5—H5A	109.3	N1—C19—H19B	109.1
C4—C5—H5B	109.3	C18—C19—H19B	109.1
C6—C5—H5B	109.3	H19A—C19—H19B	107.9
H5A—C5—H5B	107.9	C25—C20—C21	117.2 (3)
C7—C6—C5	110.8 (3)	C25—C20—N2	122.6 (2)
C7—C6—H6A	109.5	C21—C20—N2	119.9 (2)
C5—C6—H6A	109.5	C22—C21—C20	121.1 (3)
C7—C6—H6B	109.5	C22—C21—H21	119.5
C5—C6—H6B	109.5	C20—C21—H21	119.5
H6A—C6—H6B	108.1	C23—C22—C21	121.0 (3)
C8—C7—C6	127.2 (3)	C23—C22—H22	119.5
C8—C7—H7	116.4	C21—C22—H22	119.5
C6—C7—H7	116.4	C22—C23—O5	115.7 (3)
C7—C8—C27	126.0 (3)	C22—C23—C24	118.9 (3)
C7—C8—C9	121.9 (3)	O5—C23—C24	125.4 (3)
C27—C8—C9	112.0 (3)	C23—C24—C25	120.3 (3)
O4—C9—C8	111.7 (3)	C23—C24—H24	119.8
O4—C9—C10	111.8 (2)	C25—C24—H24	119.8
C8—C9—C10	109.9 (3)	C20—C25—C24	121.4 (3)
O4—C9—H9	107.7	C20—C25—H25	119.3
C8—C9—H9	107.7	C24—C25—H25	119.3
C10—C9—H9	107.7	C4—C26—H26A	109.5
C9—C10—C11	114.6 (2)	C4—C26—H26B	109.5
C9—C10—H10A	108.6	H26A—C26—H26B	109.5
C11—C10—H10A	108.6	C4—C26—H26C	109.5
C9—C10—H10B	108.6	H26A—C26—H26C	109.5
C11—C10—H10B	108.6	H26B—C26—H26C	109.5
H10A—C10—H10B	107.6	C8—C27—H27A	109.5
C12—C11—C1	103.3 (2)	C8—C27—H27B	109.5
C12—C11—C10	114.3 (2)	H27A—C27—H27B	109.5
C1—C11—C10	116.4 (2)	C8—C27—H27C	109.5
C12—C11—H11	107.5	H27A—C27—H27C	109.5
C1—C11—H11	107.5	H27B—C27—H27C	109.5
C10—C11—H11	107.5	O5—C28—H28A	109.5
C13—C12—C15	109.7 (2)	O5—C28—H28B	109.5
C13—C12—C11	104.7 (2)	H28A—C28—H28B	109.5
C15—C12—C11	114.2 (2)	O5—C28—H28C	109.5
C13—C12—H12	109.4	H28A—C28—H28C	109.5
C15—C12—H12	109.4	H28B—C28—H28C	109.5
C11—C12—H12	109.4	C16—N1—C15	111.1 (2)
O12—C13—O14	120.4 (2)	C16—N1—C19	107.7 (2)
O12—C13—C12	129.1 (2)	C15—N1—C19	109.4 (2)
O14—C13—C12	110.5 (2)	C20—N2—C17	116.3 (2)
N1—C15—C12	113.2 (2)	C20—N2—C18	117.5 (2)
N1—C15—H15A	108.9	C17—N2—C18	110.9 (2)
C12—C15—H15A	108.9	C4—O3—C2	60.88 (17)
N1—C15—H15B	108.9	C9—O4—H4	109.5
C12—C15—H15B	108.9	C23—O5—C28	117.9 (3)
H15A—C15—H15B	107.8	C13—O14—C1	111.0 (2)
N1—C16—C17	111.7 (2)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N1	0.84	2.14	2.977 (4)	170
C2—H2···O12i	1.00	2.42	3.225 (4)	137
C5—H5B···O3ii	0.99	2.45	3.310 (4)	145
C7—H7···O14iii	0.95	2.50	3.198 (4)	130
C15—H15A···O12i	0.99	2.57	3.413 (4)	143
C15—H15A···O14i	0.99	2.50	3.469 (4)	165

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯N1	0.84	2.14	2.977 (4)	170
C2—H2⋯O12i	1.00	2.42	3.225 (4)	137
C5—H5B⋯O3ii	0.99	2.45	3.310 (4)	145
C7—H7⋯O14iii	0.95	2.50	3.198 (4)	130
C15—H15A⋯O12i	0.99	2.57	3.413 (4)	143
C15—H15A⋯O14i	0.99	2.50	3.469 (4)	165

Symmetry codes: (i) ; (ii) ; (iii) .