10α-Hy-droxy-13-{[4-(2-hy-droxy-phen-yl)piperazin-1-yl]meth-yl}-4,9-dimethyl-3,8,15-trioxatetra-cyclo-[10.3.0.0(2,4).0(7,9)]penta-decan-14-one.

The title compound, C(25)H(34)N(2)O(6), 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 ten-membered ring adopts an approximate chair-chair conformation, while the piperazine ring displays a near regular chair conformation and the five-membered ring an envelope conformation with the C atom closest to the hy-droxy group forming the flap. The mol-ecular conformation is stabilized by an O-H⋯N hydrogen bond, which generates an S(7) loop, and the crystal structure features weak C-H⋯O inter-actions.

Related literature

For background to the medicinal uses of the plant Anvillea adiata, see: Abdel Sattar et al. (1996 ▶); El Hassany et al. (2004 ▶); Qureshi et al.(1990 ▶). For the reactivity of this sesquiterpene, see: Hwang et al. (2006 ▶); Neukirch et al. (2003 ▶); Neelakantan et al. (2009 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶). For the synthesis, see: Moumou et al. (2010 ▶).

Experimental

Crystal data

C25H34N2O6

M = 458.54

Orthorhombic,

a = 8.0978 (2) Å

b = 10.3660 (3) Å

c = 28.8194 (8) Å

V = 2419.15 (11) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 180 K

0.27 × 0.21 × 0.06 mm

Data collection

Agilent Xcalibur Sapphire1 long-nozzle diffractometer

27441 measured reflections

2829 independent reflections

2540 reflections with I > 2σ(I)

R int = 0.034

Refinement

R[F 2 > 2σ(F 2)] = 0.034

wR(F 2) = 0.093

S = 1.05

2829 reflections

302 parameters

H-atom parameters constrained

Δρmax = 0.19 e Å−3

Δρmin = −0.18 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/S1600536812013876/bt5864sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812013876/bt5864Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812013876/bt5864Isup3.cml

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

C25H34N2O6	F(000) = 984
Mr = 458.54	Dx = 1.259 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 4934 reflections
a = 8.0978 (2) Å	θ = 2.4–26.4°
b = 10.3660 (3) Å	µ = 0.09 mm−1
c = 28.8194 (8) Å	T = 180 K
V = 2419.15 (11) Å3	Platelet, colourless
Z = 4	0.27 × 0.21 × 0.06 mm

Agilent Xcalibur Sapphire1 long-nozzle diffractometer	2540 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.034
Graphite monochromator	θmax = 26.4°, θmin = 2.4°
Detector resolution: 8.2632 pixels mm-1	h = −10→10
ω scan	k = −12→12
27441 measured reflections	l = −35→36
2829 independent reflections

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)] = 0.034	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.093	H-atom parameters constrained
S = 1.05	w = 1/[σ2(Fo2) + (0.0508P)2 + 0.396P] where P = (Fo2 + 2Fc2)/3
2829 reflections	(Δ/σ)max = 0.002
302 parameters	Δρmax = 0.19 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.

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	0.9344 (2)	0.90928 (19)	−0.02860 (7)	0.0367 (4)
H1	0.8850	0.8325	−0.0428	0.044*
C2	0.9628 (2)	1.01210 (18)	−0.06365 (7)	0.0365 (4)
H2	1.0098	1.0913	−0.0506	0.044*
C3	0.8665 (2)	1.0334 (2)	−0.10613 (7)	0.0396 (4)
C4	0.8570 (3)	1.1717 (2)	−0.12197 (7)	0.0445 (5)
H4A	0.8464	1.1734	−0.1555	0.053*
H4B	0.9593	1.2150	−0.1139	0.053*
C5	0.7118 (3)	1.2463 (2)	−0.10047 (8)	0.0462 (5)
H5A	0.7327	1.3380	−0.1037	0.055*
H5B	0.6123	1.2265	−0.1178	0.055*
C6	0.6825 (2)	1.21618 (18)	−0.05000 (7)	0.0379 (4)
H6	0.7828	1.2067	−0.0313	0.045*
C7	0.5359 (2)	1.1463 (2)	−0.03197 (7)	0.0396 (4)
C8	0.5440 (2)	1.06794 (19)	0.01276 (7)	0.0394 (4)
H8	0.4306	1.0443	0.0211	0.047*
C9	0.6417 (2)	0.94191 (19)	0.00614 (7)	0.0372 (4)
H9A	0.6198	0.9086	−0.0247	0.045*
H9B	0.6022	0.8787	0.0283	0.045*
C10	0.8304 (2)	0.95749 (18)	0.01223 (7)	0.0335 (4)
H10	0.8530	1.0498	0.0158	0.040*
C11	1.0873 (3)	0.8737 (2)	0.03774 (8)	0.0446 (5)
C12	0.9101 (3)	0.8883 (2)	0.05318 (7)	0.0412 (5)
H12	0.8608	0.8024	0.0561	0.049*
C13	0.9013 (3)	0.9554 (3)	0.10023 (7)	0.0496 (5)
H13A	0.9726	0.9101	0.1218	0.060*
H13B	0.9435	1.0425	0.0970	0.060*
C14	0.7331 (3)	0.9440 (2)	−0.12263 (8)	0.0483 (5)
H14A	0.7379	0.9369	−0.1558	0.073*
H14B	0.6273	0.9775	−0.1136	0.073*
H14C	0.7486	0.8604	−0.1090	0.073*
C15	0.3946 (3)	1.1047 (3)	−0.06229 (9)	0.0563 (6)
H15A	0.2926	1.1346	−0.0492	0.084*
H15B	0.3928	1.0123	−0.0643	0.084*
H15C	0.4082	1.1407	−0.0927	0.084*
C16	0.6773 (3)	0.8326 (2)	0.13338 (8)	0.0527 (6)
H16A	0.7548	0.7954	0.1553	0.063*
H16B	0.6741	0.7773	0.1062	0.063*
C17	0.5082 (3)	0.8371 (2)	0.15515 (8)	0.0536 (6)
H17A	0.4288	0.8697	0.1328	0.064*
H17B	0.4746	0.7508	0.1641	0.064*
C18	0.5649 (4)	1.0502 (2)	0.18283 (8)	0.0589 (6)
H18A	0.5678	1.1051	0.2101	0.071*
H18B	0.4873	1.0870	0.1609	0.071*
C19	0.7342 (4)	1.0444 (2)	0.16120 (8)	0.0562 (6)
H19A	0.7689	1.1308	0.1526	0.067*
H19B	0.8125	1.0112	0.1837	0.067*
C20	0.3698 (3)	0.9137 (3)	0.22451 (7)	0.0543 (6)
C21	0.2250 (4)	0.8504 (4)	0.21250 (9)	0.0761 (9)
H21	0.2159	0.8136	0.1832	0.091*
C22	0.3734 (4)	0.9667 (3)	0.26908 (8)	0.0709 (8)
C23	0.0932 (4)	0.8409 (5)	0.24322 (11)	0.0987 (13)
H23	−0.0019	0.7968	0.2345	0.118*
C24	0.1028 (5)	0.8958 (5)	0.28612 (11)	0.1027 (14)
H24	0.0137	0.8906	0.3064	0.123*
C25	0.2443 (5)	0.9589 (4)	0.29923 (10)	0.0941 (12)
H25	0.2519	0.9960	0.3285	0.113*
N1	0.7348 (2)	0.96134 (17)	0.11978 (6)	0.0455 (4)
N2	0.5106 (3)	0.92072 (19)	0.19603 (6)	0.0495 (5)
O1	0.5493 (2)	1.28526 (14)	−0.02754 (5)	0.0491 (4)
O2	1.03111 (18)	0.97758 (15)	−0.10802 (5)	0.0469 (4)
O3	1.09685 (17)	0.88006 (14)	−0.00863 (5)	0.0451 (4)
O4	1.2079 (2)	0.85660 (19)	0.06106 (7)	0.0647 (5)
O5	0.6083 (2)	1.14333 (15)	0.04947 (5)	0.0477 (4)
H5	0.6267	1.0969	0.0719	0.071*
O6	0.5154 (3)	1.0222 (2)	0.28351 (6)	0.0802 (7)
H6A	0.5209	1.0960	0.2733	0.120*

	U11	U22	U33	U12	U13	U23
C1	0.0321 (9)	0.0299 (9)	0.0479 (11)	0.0032 (8)	−0.0011 (8)	−0.0058 (8)
C2	0.0312 (9)	0.0324 (9)	0.0459 (11)	0.0008 (8)	0.0036 (8)	−0.0072 (8)
C3	0.0390 (10)	0.0366 (10)	0.0432 (10)	0.0039 (9)	0.0050 (9)	−0.0047 (9)
C4	0.0502 (12)	0.0408 (11)	0.0424 (11)	−0.0014 (10)	0.0038 (10)	0.0026 (9)
C5	0.0512 (12)	0.0354 (10)	0.0520 (12)	0.0050 (10)	−0.0030 (10)	0.0036 (9)
C6	0.0368 (9)	0.0273 (9)	0.0495 (11)	0.0038 (8)	−0.0024 (9)	−0.0031 (8)
C7	0.0292 (9)	0.0368 (10)	0.0528 (11)	0.0055 (8)	0.0020 (9)	−0.0069 (9)
C8	0.0286 (9)	0.0387 (11)	0.0510 (11)	−0.0012 (8)	0.0058 (9)	−0.0084 (9)
C9	0.0334 (9)	0.0302 (9)	0.0481 (11)	−0.0046 (8)	0.0032 (8)	−0.0024 (9)
C10	0.0338 (9)	0.0247 (8)	0.0422 (10)	−0.0027 (8)	0.0003 (8)	−0.0024 (8)
C11	0.0449 (11)	0.0295 (10)	0.0595 (14)	0.0035 (9)	−0.0052 (10)	0.0031 (9)
C12	0.0423 (11)	0.0317 (10)	0.0497 (12)	−0.0038 (9)	−0.0032 (9)	0.0042 (9)
C13	0.0526 (12)	0.0487 (12)	0.0476 (12)	−0.0130 (11)	−0.0063 (10)	0.0030 (10)
C14	0.0514 (12)	0.0449 (12)	0.0486 (12)	0.0008 (11)	−0.0045 (10)	−0.0093 (10)
C15	0.0347 (10)	0.0661 (15)	0.0681 (15)	0.0008 (11)	−0.0093 (11)	−0.0049 (13)
C16	0.0673 (15)	0.0400 (11)	0.0507 (13)	−0.0082 (11)	0.0034 (11)	−0.0016 (10)
C17	0.0652 (15)	0.0479 (12)	0.0477 (12)	−0.0124 (12)	0.0016 (11)	−0.0064 (10)
C18	0.0862 (18)	0.0468 (13)	0.0437 (12)	−0.0020 (14)	0.0024 (12)	−0.0055 (10)
C19	0.0812 (17)	0.0421 (12)	0.0453 (12)	−0.0141 (13)	−0.0024 (12)	−0.0038 (10)
C20	0.0631 (14)	0.0615 (15)	0.0383 (11)	0.0001 (12)	−0.0038 (10)	0.0010 (10)
C21	0.0652 (17)	0.109 (2)	0.0540 (15)	−0.0100 (18)	0.0020 (13)	−0.0159 (16)
C22	0.0793 (18)	0.093 (2)	0.0400 (12)	−0.0080 (18)	−0.0029 (13)	−0.0030 (14)
C23	0.0665 (18)	0.152 (4)	0.077 (2)	−0.017 (2)	0.0028 (16)	−0.017 (2)
C24	0.080 (2)	0.166 (4)	0.0622 (18)	−0.005 (3)	0.0191 (17)	−0.009 (2)
C25	0.099 (2)	0.136 (3)	0.0474 (15)	−0.010 (3)	0.0122 (16)	−0.0135 (19)
N1	0.0591 (11)	0.0380 (9)	0.0395 (9)	−0.0088 (9)	−0.0025 (8)	−0.0001 (8)
N2	0.0633 (12)	0.0474 (10)	0.0377 (9)	−0.0045 (9)	−0.0025 (9)	−0.0010 (8)
O1	0.0493 (8)	0.0347 (7)	0.0632 (9)	0.0146 (7)	0.0045 (8)	−0.0050 (7)
O2	0.0422 (8)	0.0502 (9)	0.0483 (8)	0.0074 (7)	0.0107 (7)	−0.0054 (7)
O3	0.0345 (7)	0.0412 (8)	0.0595 (9)	0.0091 (6)	0.0002 (7)	0.0014 (7)
O4	0.0506 (10)	0.0639 (11)	0.0795 (12)	0.0140 (9)	−0.0195 (9)	0.0087 (10)
O5	0.0556 (9)	0.0409 (8)	0.0464 (8)	0.0056 (7)	0.0029 (7)	−0.0096 (7)
O6	0.0937 (15)	0.1145 (18)	0.0323 (8)	−0.0403 (14)	−0.0040 (9)	−0.0159 (10)

C1—O3	1.468 (2)	C13—H13A	0.9700
C1—C2	1.486 (3)	C13—H13B	0.9700
C1—C10	1.531 (3)	C14—H14A	0.9600
C1—H1	0.9800	C14—H14B	0.9600
C2—O2	1.438 (2)	C14—H14C	0.9600
C2—C3	1.468 (3)	C15—H15A	0.9600
C2—H2	0.9800	C15—H15B	0.9600
C3—O2	1.454 (2)	C15—H15C	0.9600
C3—C14	1.501 (3)	C16—N1	1.467 (3)
C3—C4	1.507 (3)	C16—C17	1.507 (4)
C4—C5	1.538 (3)	C16—H16A	0.9700
C4—H4A	0.9700	C16—H16B	0.9700
C4—H4B	0.9700	C17—N2	1.463 (3)
C5—C6	1.507 (3)	C17—H17A	0.9700
C5—H5A	0.9700	C17—H17B	0.9700
C5—H5B	0.9700	C18—N2	1.462 (3)
C6—O1	1.447 (2)	C18—C19	1.507 (4)
C6—C7	1.484 (3)	C18—H18A	0.9700
C6—H6	0.9800	C18—H18B	0.9700
C7—O1	1.450 (3)	C19—N1	1.472 (3)
C7—C15	1.503 (3)	C19—H19A	0.9700
C7—C8	1.525 (3)	C19—H19B	0.9700
C8—O5	1.415 (2)	C20—C21	1.387 (4)
C8—C9	1.539 (3)	C20—C22	1.397 (3)
C8—H8	0.9800	C20—N2	1.407 (3)
C9—C10	1.546 (3)	C21—C23	1.390 (4)
C9—H9A	0.9700	C21—H21	0.9300
C9—H9B	0.9700	C22—O6	1.352 (4)
C10—C12	1.524 (3)	C22—C25	1.362 (4)
C10—H10	0.9800	C23—C24	1.363 (5)
C11—O4	1.198 (3)	C23—H23	0.9300
C11—O3	1.340 (3)	C24—C25	1.372 (5)
C11—C12	1.510 (3)	C24—H24	0.9300
C12—C13	1.525 (3)	C25—H25	0.9300
C12—H12	0.9800	O5—H5	0.8200
C13—N1	1.463 (3)	O6—H6A	0.8200
O3—C1—C2	106.00 (15)	N1—C13—H13A	108.8
O3—C1—C10	105.01 (15)	C12—C13—H13A	108.8
C2—C1—C10	111.93 (16)	N1—C13—H13B	108.8
O3—C1—H1	111.2	C12—C13—H13B	108.8
C2—C1—H1	111.2	H13A—C13—H13B	107.7
C10—C1—H1	111.2	C3—C14—H14A	109.5
O2—C2—C3	60.01 (12)	C3—C14—H14B	109.5
O2—C2—C1	119.04 (16)	H14A—C14—H14B	109.5
C3—C2—C1	126.31 (18)	C3—C14—H14C	109.5
O2—C2—H2	113.6	H14A—C14—H14C	109.5
C3—C2—H2	113.6	H14B—C14—H14C	109.5
C1—C2—H2	113.6	C7—C15—H15A	109.5
O2—C3—C2	58.99 (12)	C7—C15—H15B	109.5
O2—C3—C14	113.75 (17)	H15A—C15—H15B	109.5
C2—C3—C14	123.63 (19)	C7—C15—H15C	109.5
O2—C3—C4	114.47 (17)	H15A—C15—H15C	109.5
C2—C3—C4	115.01 (18)	H15B—C15—H15C	109.5
C14—C3—C4	117.03 (19)	N1—C16—C17	111.8 (2)
C3—C4—C5	113.32 (18)	N1—C16—H16A	109.3
C3—C4—H4A	108.9	C17—C16—H16A	109.3
C5—C4—H4A	108.9	N1—C16—H16B	109.3
C3—C4—H4B	108.9	C17—C16—H16B	109.3
C5—C4—H4B	108.9	H16A—C16—H16B	107.9
H4A—C4—H4B	107.7	N2—C17—C16	110.0 (2)
C6—C5—C4	113.91 (18)	N2—C17—H17A	109.7
C6—C5—H5A	108.8	C16—C17—H17A	109.7
C4—C5—H5A	108.8	N2—C17—H17B	109.7
C6—C5—H5B	108.8	C16—C17—H17B	109.7
C4—C5—H5B	108.8	H17A—C17—H17B	108.2
H5A—C5—H5B	107.7	N2—C18—C19	110.2 (2)
O1—C6—C7	59.28 (12)	N2—C18—H18A	109.6
O1—C6—C5	116.54 (17)	C19—C18—H18A	109.6
C7—C6—C5	124.42 (19)	N2—C18—H18B	109.6
O1—C6—H6	114.9	C19—C18—H18B	109.6
C7—C6—H6	114.9	H18A—C18—H18B	108.1
C5—C6—H6	114.9	N1—C19—C18	111.2 (2)
O1—C7—C6	59.10 (13)	N1—C19—H19A	109.4
O1—C7—C15	113.14 (19)	C18—C19—H19A	109.4
C6—C7—C15	123.0 (2)	N1—C19—H19B	109.4
O1—C7—C8	116.85 (17)	C18—C19—H19B	109.4
C6—C7—C8	121.45 (17)	H19A—C19—H19B	108.0
C15—C7—C8	111.79 (19)	C21—C20—C22	115.7 (3)
O5—C8—C7	110.71 (17)	C21—C20—N2	124.3 (2)
O5—C8—C9	111.84 (17)	C22—C20—N2	119.9 (3)
C7—C8—C9	111.69 (16)	C20—C21—C23	121.6 (3)
O5—C8—H8	107.5	C20—C21—H21	119.2
C7—C8—H8	107.5	C23—C21—H21	119.2
C9—C8—H8	107.5	O6—C22—C25	118.8 (3)
C8—C9—C10	113.91 (16)	O6—C22—C20	117.9 (3)
C8—C9—H9A	108.8	C25—C22—C20	123.1 (3)
C10—C9—H9A	108.8	C24—C23—C21	120.3 (3)
C8—C9—H9B	108.8	C24—C23—H23	119.9
C10—C9—H9B	108.8	C21—C23—H23	119.9
H9A—C9—H9B	107.7	C23—C24—C25	119.7 (3)
C12—C10—C1	102.06 (15)	C23—C24—H24	120.1
C12—C10—C9	117.19 (17)	C25—C24—H24	120.1
C1—C10—C9	114.97 (16)	C22—C25—C24	119.6 (3)
C12—C10—H10	107.3	C22—C25—H25	120.2
C1—C10—H10	107.3	C24—C25—H25	120.2
C9—C10—H10	107.3	C13—N1—C16	110.91 (19)
O4—C11—O3	121.3 (2)	C13—N1—C19	109.86 (18)
O4—C11—C12	128.6 (2)	C16—N1—C19	108.35 (16)
O3—C11—C12	110.09 (18)	C20—N2—C18	116.3 (2)
C11—C12—C10	102.80 (17)	C20—N2—C17	115.4 (2)
C11—C12—C13	110.61 (18)	C18—N2—C17	109.78 (17)
C10—C12—C13	117.03 (17)	C6—O1—C7	61.63 (12)
C11—C12—H12	108.7	C2—O2—C3	61.00 (13)
C10—C12—H12	108.7	C11—O3—C1	110.46 (16)
C13—C12—H12	108.7	C8—O5—H5	109.5
N1—C13—C12	113.86 (18)	C22—O6—H6A	109.5

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···N1	0.82	2.15	2.952 (2)	164
C1—H1···O4i	0.98	2.49	3.440 (3)	165
C10—H10···O1ii	0.98	2.36	3.232 (2)	148
C18—H18A···O6	0.97	2.32	2.943 (3)	121
C25—H25···O2iii	0.93	2.55	3.299 (4)	138

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O5—H5⋯N1	0.82	2.15	2.952 (2)	164
C1—H1⋯O4i	0.98	2.49	3.440 (3)	165
C10—H10⋯O1ii	0.98	2.36	3.232 (2)	148
C18—H18A⋯O6	0.97	2.32	2.943 (3)	121
C25—H25⋯O2iii	0.93	2.55	3.299 (4)	138

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