10α-Hy-droxy-4,9-dimethyl-13-[(4-phenyl-piperazin-1-yl)meth-yl]-3,8,15-trioxatetra-cyclo-[10.3.0.0.0]tetra-decan-14-one.

The title compound, C(25)H(34)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), which was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The mol-ecule contains a fused five- and ten-membered ring system. The ten-membered ring adopts an approximate chair-chair conformation, while the five-membered ring is in an envelope conformation, with the C atom closest to the hy-droxy group forming the flap. The piperazine ring is in a chair conformation. In the crystal, O-H⋯O hydrogen bonds connect mol-ecules into chains along [100]. Weak inter-molecular C-H⋯O hydrogen bonds are also present.

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 ▶). For the reactivity of this sesquiterpene, see: Hwang et al. (2006 ▶); Neukirch et al. (2003 ▶); Neelakantan et al. (2009 ▶). For the synthesis, see: Moumou et al. (2010 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C25H34N2O5

M = 442.54

Orthorhombic,

a = 7.7666 (5) Å

b = 9.6059 (8) Å

c = 31.181 (2) Å

V = 2326.2 (3) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 298 K

0.45 × 0.36 × 0.28 mm

Data collection

Bruker X8 APEX CCD area-detector diffractometer

10922 measured reflections

2723 independent reflections

2362 reflections with I > 2σ(I)

R int = 0.024

Refinement

R[F 2 > 2σ(F 2)] = 0.040

wR(F 2) = 0.104

S = 1.06

2723 reflections

293 parameters

H-atom parameters constrained

Δρmax = 0.17 e Å−3

Δρmin = −0.18 e Å−3

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXS97 (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/S1600536811042012/lh5350sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811042012/lh5350Isup2.hkl

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

C25H34N2O5	F(000) = 952
Mr = 442.54	Dx = 1.264 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 10922 reflections
a = 7.7666 (5) Å	θ = 2.7–26.4°
b = 9.6059 (8) Å	µ = 0.09 mm−1
c = 31.181 (2) Å	T = 298 K
V = 2326.2 (3) Å3	Prism, colourless
Z = 4	0.45 × 0.36 × 0.28 mm

Bruker X8 APEX CCD area-detector diffractometer	2362 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.024
graphite	θmax = 26.4°, θmin = 2.7°
φ and ω scans	h = −9→9
10922 measured reflections	k = −11→7
2723 independent reflections	l = −38→34

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.104	H-atom parameters constrained
S = 1.06	w = 1/[σ2(Fo2) + (0.0537P)2 + 0.4378P] where P = (Fo2 + 2Fc2)/3
2723 reflections	(Δ/σ)max < 0.001
293 parameters	Δρmax = 0.17 e Å−3
0 restraints	Δρmin = −0.18 e Å−3

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.

	x	y	z	Uiso*/Ueq
C1	0.5441 (3)	0.2316 (2)	0.91768 (7)	0.0347 (5)
H1	0.4879	0.1665	0.8979	0.042*
C2	0.5370 (3)	0.1777 (2)	0.96267 (7)	0.0327 (5)
H2	0.6143	0.2252	0.9827	0.039*
C3	0.4930 (3)	0.0341 (3)	0.97477 (7)	0.0349 (5)
C4	0.5705 (3)	−0.0184 (3)	1.01607 (8)	0.0415 (6)
H4A	0.4920	−0.0840	1.0293	0.050*
H4B	0.5859	0.0591	1.0356	0.050*
C5	0.7438 (3)	−0.0892 (3)	1.00857 (8)	0.0435 (6)
H5A	0.7981	−0.1076	1.0360	0.052*
H5B	0.7252	−0.1777	0.9943	0.052*
C6	0.8616 (3)	−0.0009 (3)	0.98170 (8)	0.0383 (6)
H6	0.8588	0.0985	0.9888	0.046*
C7	0.9154 (3)	−0.0312 (3)	0.93753 (8)	0.0383 (6)
C8	0.9740 (3)	0.0848 (3)	0.90772 (8)	0.0404 (6)
H8	1.0567	0.0437	0.8876	0.048*
C9	0.8307 (4)	0.1514 (3)	0.88067 (8)	0.0416 (6)
H9A	0.7518	0.0783	0.8720	0.050*
H9B	0.8825	0.1885	0.8548	0.050*
C10	0.7253 (3)	0.2680 (2)	0.90184 (7)	0.0311 (5)
H10	0.7914	0.3042	0.9262	0.037*
C11	0.5317 (3)	0.4573 (3)	0.89329 (8)	0.0414 (6)
C12	0.6839 (3)	0.3904 (3)	0.87154 (7)	0.0376 (6)
H12	0.6455	0.3523	0.8440	0.045*
C13	0.8251 (4)	0.4953 (3)	0.86298 (8)	0.0431 (6)
H13A	0.7729	0.5793	0.8516	0.052*
H13B	0.8786	0.5194	0.8901	0.052*
C14	0.4374 (4)	−0.0747 (3)	0.94329 (9)	0.0473 (6)
H14A	0.3988	−0.0306	0.9174	0.071*
H14B	0.3451	−0.1284	0.9554	0.071*
H14C	0.5328	−0.1349	0.9369	0.071*
C15	1.1040 (4)	0.5453 (3)	0.83687 (8)	0.0519 (7)
H15A	1.1452	0.5467	0.8662	0.062*
H15B	1.0668	0.6387	0.8295	0.062*
C16	0.9013 (3)	0.4473 (3)	0.78904 (8)	0.0490 (7)
H16A	0.8618	0.5393	0.7808	0.059*
H16B	0.8051	0.3836	0.7864	0.059*
C17	1.0437 (4)	0.4021 (3)	0.75924 (8)	0.0509 (7)
H17A	1.0794	0.3082	0.7664	0.061*
H17B	1.0018	0.4018	0.7299	0.061*
C18	1.2483 (4)	0.5027 (4)	0.80761 (8)	0.0542 (8)
H18A	1.3418	0.5691	0.8100	0.065*
H18B	1.2915	0.4122	0.8163	0.065*
C19	1.3260 (4)	0.4797 (3)	0.73301 (8)	0.0448 (6)
C20	1.3357 (4)	0.3688 (3)	0.70444 (8)	0.0473 (6)
H20	1.2490	0.3020	0.7040	0.057*
C21	1.4749 (4)	0.3575 (4)	0.67644 (8)	0.0571 (8)
H21	1.4797	0.2835	0.6573	0.069*
C22	1.6044 (4)	0.4538 (4)	0.67685 (9)	0.0645 (9)
H22	1.6992	0.4434	0.6589	0.077*
C23	1.5932 (4)	0.5657 (4)	0.70384 (10)	0.0714 (10)
H23	1.6792	0.6331	0.7035	0.086*
C24	1.4562 (4)	0.5797 (4)	0.73158 (9)	0.0615 (8)
H24	1.4503	0.6568	0.7496	0.074*
C26	0.8708 (4)	−0.1630 (3)	0.91409 (9)	0.0535 (7)
H26A	0.8222	−0.2288	0.9338	0.080*
H26B	0.9730	−0.2015	0.9015	0.080*
H26C	0.7886	−0.1428	0.8919	0.080*
N1	0.9589 (3)	0.4506 (2)	0.83356 (6)	0.0398 (5)
N2	1.1901 (3)	0.4959 (2)	0.76275 (6)	0.0461 (6)
O1	0.4819 (3)	0.5750 (2)	0.89055 (6)	0.0565 (5)
O2	0.3686 (2)	0.14622 (18)	0.97984 (5)	0.0400 (4)
O3	0.4524 (2)	0.36458 (19)	0.91853 (5)	0.0447 (4)
O5	1.0321 (2)	−0.0547 (2)	0.97319 (6)	0.0543 (5)
O4	1.0600 (2)	0.19268 (19)	0.92937 (7)	0.0538 (5)
H4	1.1392	0.1600	0.9436	0.081*

	U11	U22	U33	U12	U13	U23
C1	0.0319 (12)	0.0320 (12)	0.0403 (12)	−0.0020 (11)	−0.0021 (11)	0.0019 (10)
C2	0.0281 (11)	0.0336 (12)	0.0364 (11)	−0.0008 (11)	0.0030 (10)	0.0008 (9)
C3	0.0274 (11)	0.0351 (12)	0.0421 (12)	−0.0020 (10)	0.0068 (10)	0.0002 (10)
C4	0.0464 (14)	0.0380 (13)	0.0402 (12)	−0.0040 (12)	0.0048 (11)	0.0072 (11)
C5	0.0486 (14)	0.0374 (14)	0.0446 (13)	0.0030 (12)	−0.0051 (12)	0.0065 (11)
C6	0.0304 (12)	0.0343 (13)	0.0502 (13)	0.0040 (11)	−0.0070 (11)	−0.0018 (11)
C7	0.0330 (12)	0.0338 (13)	0.0479 (13)	0.0062 (11)	−0.0035 (11)	−0.0007 (11)
C8	0.0326 (12)	0.0363 (13)	0.0522 (14)	0.0066 (11)	0.0058 (11)	−0.0029 (11)
C9	0.0485 (15)	0.0362 (13)	0.0401 (12)	0.0049 (13)	0.0062 (12)	0.0012 (11)
C10	0.0303 (12)	0.0302 (12)	0.0328 (11)	−0.0005 (10)	−0.0014 (9)	0.0020 (9)
C11	0.0404 (13)	0.0420 (14)	0.0417 (13)	0.0051 (13)	−0.0057 (11)	0.0079 (11)
C12	0.0414 (13)	0.0336 (13)	0.0377 (12)	0.0019 (11)	−0.0008 (11)	0.0024 (10)
C13	0.0503 (14)	0.0352 (13)	0.0438 (13)	−0.0031 (13)	0.0073 (12)	0.0012 (11)
C14	0.0444 (14)	0.0394 (15)	0.0582 (15)	−0.0041 (13)	0.0002 (13)	−0.0033 (12)
C15	0.0527 (16)	0.0597 (18)	0.0434 (13)	−0.0120 (16)	0.0041 (12)	−0.0116 (13)
C16	0.0419 (14)	0.0639 (18)	0.0413 (13)	−0.0058 (15)	−0.0014 (11)	0.0009 (13)
C17	0.0485 (15)	0.0646 (18)	0.0396 (13)	−0.0098 (16)	−0.0015 (12)	−0.0086 (13)
C18	0.0467 (14)	0.073 (2)	0.0431 (13)	−0.0101 (15)	0.0003 (12)	−0.0112 (15)
C19	0.0479 (14)	0.0498 (15)	0.0368 (12)	−0.0031 (14)	0.0010 (11)	0.0005 (12)
C20	0.0538 (16)	0.0476 (15)	0.0403 (13)	−0.0030 (15)	0.0013 (13)	0.0019 (12)
C21	0.069 (2)	0.0614 (18)	0.0413 (14)	0.0143 (19)	0.0050 (14)	0.0000 (14)
C22	0.0538 (18)	0.098 (3)	0.0419 (15)	0.003 (2)	0.0075 (13)	0.0051 (17)
C23	0.0574 (19)	0.099 (3)	0.0578 (18)	−0.030 (2)	0.0051 (16)	0.0013 (19)
C24	0.0633 (18)	0.068 (2)	0.0528 (16)	−0.0199 (19)	0.0080 (15)	−0.0106 (15)
C26	0.0663 (19)	0.0335 (14)	0.0608 (16)	0.0041 (14)	0.0044 (15)	−0.0079 (13)
N1	0.0409 (11)	0.0424 (12)	0.0362 (10)	−0.0028 (11)	0.0019 (9)	−0.0001 (9)
N2	0.0454 (12)	0.0543 (14)	0.0386 (10)	−0.0091 (12)	0.0029 (10)	−0.0090 (10)
O1	0.0590 (12)	0.0477 (11)	0.0627 (11)	0.0188 (11)	0.0078 (10)	0.0146 (9)
O2	0.0310 (8)	0.0414 (9)	0.0477 (9)	0.0018 (8)	0.0081 (7)	0.0000 (8)
O3	0.0333 (9)	0.0458 (10)	0.0548 (10)	0.0089 (9)	0.0045 (8)	0.0136 (9)
O5	0.0371 (10)	0.0594 (12)	0.0662 (12)	0.0123 (10)	−0.0069 (9)	0.0060 (10)
O4	0.0350 (10)	0.0429 (11)	0.0834 (14)	−0.0036 (9)	−0.0090 (10)	0.0003 (10)

C1—O3	1.463 (3)	C13—H13A	0.9700
C1—C2	1.496 (3)	C13—H13B	0.9700
C1—C10	1.532 (3)	C14—H14A	0.9600
C1—H1	0.9800	C14—H14B	0.9600
C2—O2	1.445 (3)	C14—H14C	0.9600
C2—C3	1.471 (3)	C15—N1	1.452 (3)
C2—H2	0.9800	C15—C18	1.502 (4)
C3—O2	1.456 (3)	C15—H15A	0.9700
C3—C14	1.497 (4)	C15—H15B	0.9700
C3—C4	1.508 (3)	C16—N1	1.459 (3)
C4—C5	1.526 (4)	C16—C17	1.508 (4)
C4—H4A	0.9700	C16—H16A	0.9700
C4—H4B	0.9700	C16—H16B	0.9700
C5—C6	1.503 (4)	C17—N2	1.455 (3)
C5—H5A	0.9700	C17—H17A	0.9700
C5—H5B	0.9700	C17—H17B	0.9700
C6—O5	1.446 (3)	C18—N2	1.471 (3)
C6—C7	1.468 (3)	C18—H18A	0.9700
C6—H6	0.9800	C18—H18B	0.9700
C7—O5	1.452 (3)	C19—C20	1.390 (4)
C7—C26	1.502 (4)	C19—C24	1.395 (4)
C7—C8	1.521 (4)	C19—N2	1.414 (3)
C8—O4	1.406 (3)	C20—C21	1.394 (4)
C8—C9	1.536 (3)	C20—H20	0.9300
C8—H8	0.9800	C21—C22	1.367 (5)
C9—C10	1.537 (3)	C21—H21	0.9300
C9—H9A	0.9700	C22—C23	1.368 (5)
C9—H9B	0.9700	C22—H22	0.9300
C10—C12	1.542 (3)	C23—C24	1.378 (4)
C10—H10	0.9800	C23—H23	0.9300
C11—O1	1.198 (3)	C24—H24	0.9300
C11—O3	1.339 (3)	C26—H26A	0.9600
C11—C12	1.507 (3)	C26—H26B	0.9600
C12—C13	1.513 (4)	C26—H26C	0.9600
C12—H12	0.9800	O4—H4	0.8200
C13—N1	1.451 (3)
O3—C1—C2	105.50 (18)	N1—C13—H13A	108.4
O3—C1—C10	104.70 (18)	C12—C13—H13A	108.4
C2—C1—C10	114.50 (19)	N1—C13—H13B	108.4
O3—C1—H1	110.6	C12—C13—H13B	108.4
C2—C1—H1	110.6	H13A—C13—H13B	107.4
C10—C1—H1	110.6	C3—C14—H14A	109.5
O2—C2—C3	59.88 (14)	C3—C14—H14B	109.5
O2—C2—C1	116.93 (19)	H14A—C14—H14B	109.5
C3—C2—C1	125.0 (2)	C3—C14—H14C	109.5
O2—C2—H2	114.5	H14A—C14—H14C	109.5
C3—C2—H2	114.5	H14B—C14—H14C	109.5
C1—C2—H2	114.5	N1—C15—C18	111.4 (2)
O2—C3—C2	59.19 (15)	N1—C15—H15A	109.3
O2—C3—C14	113.4 (2)	C18—C15—H15A	109.3
C2—C3—C14	123.6 (2)	N1—C15—H15B	109.3
O2—C3—C4	114.79 (19)	C18—C15—H15B	109.3
C2—C3—C4	116.1 (2)	H15A—C15—H15B	108.0
C14—C3—C4	116.2 (2)	N1—C16—C17	111.6 (2)
C3—C4—C5	111.7 (2)	N1—C16—H16A	109.3
C3—C4—H4A	109.3	C17—C16—H16A	109.3
C5—C4—H4A	109.3	N1—C16—H16B	109.3
C3—C4—H4B	109.3	C17—C16—H16B	109.3
C5—C4—H4B	109.3	H16A—C16—H16B	108.0
H4A—C4—H4B	107.9	N2—C17—C16	110.4 (2)
C6—C5—C4	111.8 (2)	N2—C17—H17A	109.6
C6—C5—H5A	109.3	C16—C17—H17A	109.6
C4—C5—H5A	109.3	N2—C17—H17B	109.6
C6—C5—H5B	109.3	C16—C17—H17B	109.6
C4—C5—H5B	109.3	H17A—C17—H17B	108.1
H5A—C5—H5B	107.9	N2—C18—C15	111.1 (2)
O5—C6—C7	59.77 (15)	N2—C18—H18A	109.4
O5—C6—C5	117.3 (2)	C15—C18—H18A	109.4
C7—C6—C5	125.7 (2)	N2—C18—H18B	109.4
O5—C6—H6	114.2	C15—C18—H18B	109.4
C7—C6—H6	114.2	H18A—C18—H18B	108.0
C5—C6—H6	114.2	C20—C19—C24	117.9 (3)
O5—C7—C6	59.36 (15)	C20—C19—N2	123.0 (2)
O5—C7—C26	112.7 (2)	C24—C19—N2	119.1 (2)
C6—C7—C26	123.9 (2)	C19—C20—C21	120.2 (3)
O5—C7—C8	113.3 (2)	C19—C20—H20	119.9
C6—C7—C8	120.8 (2)	C21—C20—H20	119.9
C26—C7—C8	112.9 (2)	C22—C21—C20	120.8 (3)
O4—C8—C7	112.9 (2)	C22—C21—H21	119.6
O4—C8—C9	107.5 (2)	C20—C21—H21	119.6
C7—C8—C9	115.1 (2)	C21—C22—C23	119.4 (3)
O4—C8—H8	107.0	C21—C22—H22	120.3
C7—C8—H8	107.0	C23—C22—H22	120.3
C9—C8—H8	107.0	C22—C23—C24	120.8 (3)
C8—C9—C10	117.0 (2)	C22—C23—H23	119.6
C8—C9—H9A	108.0	C24—C23—H23	119.6
C10—C9—H9A	108.0	C23—C24—C19	120.8 (3)
C8—C9—H9B	108.0	C23—C24—H24	119.6
C10—C9—H9B	108.0	C19—C24—H24	119.6
H9A—C9—H9B	107.3	C7—C26—H26A	109.5
C1—C10—C9	117.5 (2)	C7—C26—H26B	109.5
C1—C10—C12	100.36 (18)	H26A—C26—H26B	109.5
C9—C10—C12	113.83 (19)	C7—C26—H26C	109.5
C1—C10—H10	108.2	H26A—C26—H26C	109.5
C9—C10—H10	108.2	H26B—C26—H26C	109.5
C12—C10—H10	108.2	C13—N1—C15	108.97 (19)
O1—C11—O3	121.5 (2)	C13—N1—C16	112.8 (2)
O1—C11—C12	128.6 (2)	C15—N1—C16	108.6 (2)
O3—C11—C12	109.9 (2)	C19—N2—C17	117.8 (2)
C11—C12—C13	111.3 (2)	C19—N2—C18	113.5 (2)
C11—C12—C10	102.31 (19)	C17—N2—C18	109.8 (2)
C13—C12—C10	117.7 (2)	C2—O2—C3	60.93 (15)
C11—C12—H12	108.4	C11—O3—C1	110.30 (18)
C13—C12—H12	108.4	C6—O5—C7	60.87 (15)
C10—C12—H12	108.4	C8—O4—H4	109.5
N1—C13—C12	115.7 (2)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O2i	0.82	2.11	2.902 (3)	161
C14—H14B···O5ii	0.96	2.59	3.289 (3)	129
C21—H21···O1iii	0.93	2.51	3.441 (4)	174

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯O2i	0.82	2.11	2.902 (3)	161
C14—H14B⋯O5ii	0.96	2.59	3.289 (3)	129
C21—H21⋯O1iii	0.93	2.51	3.441 (4)	174

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