(1S,2R,3R,6R,7S,8R,10S,11S)-13-{[4-(4-Chloro-phen-yl)piperazin-1-yl]meth-yl}-10-hy-droxy-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(33)ClN(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 is built up from fused five- and ten-membered rings with two additional ep-oxy ring systems and a chloro-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 shows an envelope conformation with the C atom closest to the hy-droxy group forming the flap. The mol-ecular conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond between the hy-droxy group and a piperazine N atom. The crystal structure is stabilized by weak C-H⋯O inter-actions.

Related literature

For background to the medicinal uses of the plant Anvillea adiata, see: El Hassany et al. (2004 ▶); Qureshi et al. (1990 ▶). For the reactivity of this n class="Chemical">sesquiterpene, see: Hwang et al. (2006 ▶); Neukirch et al. (2003 ▶); Neelakantan et al. (2009 ▶); Castaneda-Acosta et al. (1997 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶). For the synthetic procedure, see: Moumou et al. (2010 ▶).

Experimental

Crystal data

C25H33ClN2O5

M = 476.98

Orthorhombic,

a = 8.0138 (3) Å

b = 10.7218 (5) Å

c = 28.0174 (13) Å

V = 2407.32 (18) Å3

Z = 4

Mo Kα radiation

μ = 0.20 mm−1

T = 296 K

0.33 × 0.17 × 0.04 mm

Data collection

Agilent Xcalibur Sapphire1 long nozzle diffractometer

13518 measured reflections

4328 independent reflections

3315 reflections with I > 2σ(I)

R int = 0.030

Refinement

R[F 2 > 2σ(F 2)] = 0.041

wR(F 2) = 0.102

S = 1.03

4328 reflections

301 parameters

H-atom parameters constrained

Δρmax = 0.22 e Å−3

Δρmin = −0.21 e Å−3

Absolute structure: Flack (1983 ▶), 1836 Friedel pairs

Flack parameter: 0.03 (13)

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/S1600536812011816/bt5834sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812011816/bt5834Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812011816/bt5834Isup3.cml

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

C25H33ClN2O5	F(000) = 1016
Mr = 476.98	Dx = 1.316 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 13518 reflections
a = 8.0138 (3) Å	θ = 2.4–25.2°
b = 10.7218 (5) Å	µ = 0.20 mm−1
c = 28.0174 (13) Å	T = 296 K
V = 2407.32 (18) Å3	Patelet, colourless
Z = 4	0.33 × 0.17 × 0.04 mm

Agilent Xcalibur Sapphire1 long nozzle diffractometer	3315 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.030
Graphite monochromator	θmax = 25.2°, θmin = 2.4°
Detector resolution: 8.2632 pixels mm-1	h = −9→7
ω scans	k = −12→12
13518 measured reflections	l = −31→33
4328 independent 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)] = 0.041	H-atom parameters constrained
wR(F2) = 0.102	w = 1/[σ2(Fo2) + (0.0489P)2 + 0.3159P] where P = (Fo2 + 2Fc2)/3
S = 1.03	(Δ/σ)max = 0.001
4328 reflections	Δρmax = 0.22 e Å−3
301 parameters	Δρmin = −0.21 e Å−3
0 restraints	Absolute structure: Flack (1983), 1836 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.03 (13)

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	0.5658 (3)	0.08524 (19)	1.03681 (8)	0.0420 (6)
H1	0.5100	0.1552	1.0527	0.050*
C2	0.5983 (3)	−0.0172 (2)	1.07076 (8)	0.0417 (5)
H2	0.6496	−0.0907	1.0561	0.050*
C3	0.4995 (3)	−0.0452 (2)	1.11324 (8)	0.0486 (6)
C4	0.4939 (3)	−0.1805 (2)	1.12703 (9)	0.0570 (7)
H4A	0.4843	−0.1867	1.1615	0.068*
H4B	0.5981	−0.2197	1.1178	0.068*
C5	0.3493 (3)	−0.2521 (2)	1.10412 (9)	0.0578 (7)
H5A	0.3715	−0.3408	1.1065	0.069*
H5B	0.2480	−0.2349	1.1219	0.069*
C6	0.3212 (3)	−0.2194 (2)	1.05269 (8)	0.0451 (5)
H6	0.4234	−0.2069	1.0341	0.054*
C7	0.1731 (3)	−0.1534 (2)	1.03400 (8)	0.0435 (5)
C8	0.1828 (3)	−0.0735 (2)	0.98945 (8)	0.0436 (5)
H8	0.0683	−0.0523	0.9803	0.052*
C9	0.2755 (2)	0.04992 (19)	0.99890 (8)	0.0394 (5)
H9A	0.2505	0.0772	1.0311	0.047*
H9B	0.2329	0.1128	0.9772	0.047*
C10	0.4669 (2)	0.04236 (19)	0.99307 (7)	0.0387 (5)
H10	0.4957	−0.0450	0.9870	0.046*
C11	0.5445 (3)	0.1206 (2)	0.95335 (9)	0.0466 (6)
H11	0.4888	0.2019	0.9524	0.056*
C12	0.7203 (3)	0.1384 (2)	0.97059 (10)	0.0530 (6)
C13	0.5433 (3)	0.0646 (3)	0.90349 (9)	0.0570 (6)
H13A	0.6072	0.1181	0.8824	0.068*
H13B	0.5983	−0.0160	0.9044	0.068*
C14	0.3600 (3)	0.0359 (3)	1.13124 (9)	0.0605 (7)
H14A	0.3633	0.0388	1.1655	0.091*
H14B	0.2550	0.0020	1.1211	0.091*
H14C	0.3727	0.1187	1.1187	0.091*
C15	0.0266 (3)	−0.1177 (3)	1.06488 (10)	0.0604 (7)
H15A	−0.0753	−0.1407	1.0492	0.091*
H15B	0.0276	−0.0292	1.0702	0.091*
H15C	0.0341	−0.1603	1.0949	0.091*
C16	0.2978 (4)	0.1685 (2)	0.87270 (10)	0.0625 (7)
H16A	0.3649	0.2123	0.8493	0.075*
H16B	0.2932	0.2192	0.9013	0.075*
C17	0.1245 (4)	0.1503 (3)	0.85354 (10)	0.0708 (8)
H17A	0.0556	0.1119	0.8779	0.085*
H17B	0.0765	0.2309	0.8459	0.085*
C18	0.2143 (4)	−0.0440 (3)	0.81888 (10)	0.0701 (8)
H18A	0.2250	−0.0878	0.7887	0.084*
H18B	0.1511	−0.0966	0.8405	0.084*
C19	0.3848 (4)	−0.0219 (3)	0.83936 (9)	0.0638 (7)
H19A	0.4387	−0.1014	0.8453	0.077*
H19B	0.4520	0.0237	0.8165	0.077*
C20	−0.0295 (4)	0.0626 (3)	0.78687 (10)	0.0725 (8)
C21	−0.1371 (5)	0.1627 (4)	0.78375 (14)	0.1020 (12)
H21	−0.1106	0.2367	0.7993	0.122*
C22	−0.2840 (5)	0.1548 (5)	0.75781 (18)	0.1239 (17)
H22	−0.3552	0.2232	0.7564	0.149*
C23	−0.3247 (5)	0.0485 (8)	0.73460 (13)	0.1231 (19)
C24	−0.2246 (7)	−0.0525 (8)	0.73785 (16)	0.157 (2)
H24	−0.2548	−0.1264	0.7228	0.188*
C25	−0.0770 (5)	−0.0464 (5)	0.76352 (14)	0.1235 (16)
H25	−0.0085	−0.1163	0.7652	0.148*
N1	0.3753 (2)	0.04868 (18)	0.88377 (6)	0.0494 (5)
N2	0.1238 (3)	0.0725 (2)	0.81120 (7)	0.0628 (6)
O1	0.1903 (2)	−0.28639 (14)	1.02786 (6)	0.0532 (4)
O2	0.2538 (2)	−0.14084 (14)	0.95132 (6)	0.0524 (4)
H2A	0.2752	−0.0930	0.9293	0.079*
O3	0.72935 (19)	0.12359 (15)	1.01782 (6)	0.0526 (4)
O4	0.8427 (2)	0.16250 (18)	0.94779 (8)	0.0750 (6)
O5	0.6623 (2)	0.01156 (16)	1.11736 (6)	0.0582 (5)
Cl	−0.51185 (15)	0.0396 (2)	0.70351 (4)	0.1995 (9)

	U11	U22	U33	U12	U13	U23
C1	0.0249 (11)	0.0402 (12)	0.0608 (15)	−0.0039 (9)	0.0027 (10)	−0.0073 (10)
C2	0.0270 (11)	0.0431 (12)	0.0550 (13)	−0.0006 (10)	−0.0066 (10)	−0.0054 (10)
C3	0.0383 (13)	0.0548 (14)	0.0526 (13)	−0.0048 (12)	−0.0054 (11)	−0.0063 (12)
C4	0.0538 (16)	0.0640 (17)	0.0531 (15)	−0.0004 (13)	−0.0068 (12)	0.0055 (12)
C5	0.0558 (17)	0.0509 (15)	0.0668 (17)	−0.0033 (12)	−0.0025 (13)	0.0080 (12)
C6	0.0370 (13)	0.0395 (11)	0.0587 (15)	−0.0069 (11)	0.0010 (11)	−0.0022 (11)
C7	0.0276 (12)	0.0436 (12)	0.0592 (14)	−0.0060 (10)	−0.0002 (10)	−0.0094 (11)
C8	0.0262 (11)	0.0475 (12)	0.0571 (14)	0.0011 (10)	−0.0054 (10)	−0.0073 (11)
C9	0.0287 (11)	0.0375 (10)	0.0519 (12)	0.0045 (10)	−0.0023 (9)	−0.0048 (10)
C10	0.0321 (11)	0.0312 (10)	0.0529 (13)	0.0003 (9)	0.0017 (10)	−0.0025 (10)
C11	0.0407 (13)	0.0394 (11)	0.0596 (14)	0.0009 (11)	0.0045 (11)	0.0011 (11)
C12	0.0449 (15)	0.0371 (12)	0.0769 (19)	−0.0073 (11)	0.0137 (14)	−0.0016 (12)
C13	0.0545 (16)	0.0561 (15)	0.0603 (15)	0.0075 (13)	0.0122 (12)	0.0010 (13)
C14	0.0567 (16)	0.0644 (16)	0.0605 (15)	−0.0039 (15)	0.0105 (13)	−0.0146 (13)
C15	0.0323 (13)	0.0733 (17)	0.0756 (18)	−0.0046 (13)	0.0082 (13)	−0.0063 (14)
C16	0.074 (2)	0.0525 (15)	0.0609 (16)	0.0130 (14)	−0.0042 (14)	−0.0013 (12)
C17	0.0699 (19)	0.0800 (19)	0.0627 (17)	0.0234 (17)	−0.0014 (15)	−0.0092 (15)
C18	0.091 (2)	0.0634 (16)	0.0558 (16)	0.0037 (17)	0.0012 (15)	−0.0100 (14)
C19	0.078 (2)	0.0597 (16)	0.0538 (15)	0.0120 (15)	0.0097 (14)	−0.0076 (13)
C20	0.070 (2)	0.107 (2)	0.0399 (14)	−0.011 (2)	0.0070 (14)	0.0107 (16)
C21	0.078 (3)	0.103 (3)	0.125 (3)	−0.015 (2)	−0.027 (2)	0.042 (2)
C22	0.078 (3)	0.161 (4)	0.132 (4)	−0.029 (3)	−0.026 (3)	0.074 (3)
C23	0.072 (3)	0.246 (6)	0.051 (2)	−0.036 (4)	−0.0035 (18)	0.020 (3)
C24	0.107 (4)	0.273 (8)	0.090 (3)	−0.009 (5)	−0.012 (3)	−0.086 (4)
C25	0.095 (3)	0.184 (4)	0.091 (3)	0.010 (3)	−0.011 (2)	−0.073 (3)
N1	0.0549 (13)	0.0464 (10)	0.0470 (11)	0.0071 (10)	0.0056 (10)	−0.0016 (9)
N2	0.0683 (16)	0.0730 (15)	0.0470 (12)	0.0009 (12)	0.0021 (11)	0.0035 (11)
O1	0.0456 (10)	0.0396 (8)	0.0743 (11)	−0.0113 (7)	−0.0040 (8)	−0.0042 (8)
O2	0.0547 (10)	0.0493 (9)	0.0533 (10)	−0.0031 (8)	0.0010 (8)	−0.0097 (8)
O3	0.0334 (9)	0.0503 (9)	0.0741 (12)	−0.0118 (7)	0.0018 (8)	−0.0018 (8)
O4	0.0548 (12)	0.0705 (12)	0.0998 (15)	−0.0224 (10)	0.0286 (11)	−0.0036 (11)
O5	0.0424 (10)	0.0716 (11)	0.0606 (10)	−0.0096 (9)	−0.0145 (8)	−0.0055 (9)
Cl	0.0911 (8)	0.430 (3)	0.0770 (6)	−0.0500 (13)	−0.0245 (6)	0.0210 (12)

C1—O3	1.473 (3)	C13—H13A	0.9700
C1—C2	1.476 (3)	C13—H13B	0.9700
C1—C10	1.531 (3)	C14—H14A	0.9600
C1—H1	0.9800	C14—H14B	0.9600
C2—O5	1.436 (3)	C14—H14C	0.9600
C2—C3	1.461 (3)	C15—H15A	0.9600
C2—H2	0.9800	C15—H15B	0.9600
C3—O5	1.444 (3)	C15—H15C	0.9600
C3—C4	1.502 (4)	C16—N1	1.461 (3)
C3—C14	1.503 (3)	C16—C17	1.502 (4)
C4—C5	1.530 (3)	C16—H16A	0.9700
C4—H4A	0.9700	C16—H16B	0.9700
C4—H4B	0.9700	C17—N2	1.450 (3)
C5—C6	1.500 (3)	C17—H17A	0.9700
C5—H5A	0.9700	C17—H17B	0.9700
C5—H5B	0.9700	C18—N2	1.460 (4)
C6—O1	1.449 (3)	C18—C19	1.500 (4)
C6—C7	1.478 (3)	C18—H18A	0.9700
C6—H6	0.9800	C18—H18B	0.9700
C7—O1	1.443 (3)	C19—N1	1.458 (3)
C7—C15	1.508 (3)	C19—H19A	0.9700
C7—C8	1.516 (3)	C19—H19B	0.9700
C8—O2	1.409 (3)	C20—C21	1.379 (5)
C8—C9	1.540 (3)	C20—C25	1.393 (5)
C8—H8	0.9800	C20—N2	1.409 (4)
C9—C10	1.545 (3)	C21—C22	1.386 (5)
C9—H9A	0.9700	C21—H21	0.9300
C9—H9B	0.9700	C22—C23	1.353 (7)
C10—C11	1.526 (3)	C22—H22	0.9300
C10—H10	0.9800	C23—C24	1.350 (8)
C11—C12	1.501 (4)	C23—Cl	1.737 (4)
C11—C13	1.520 (3)	C24—C25	1.386 (6)
C11—H11	0.9800	C24—H24	0.9300
C12—O4	1.199 (3)	C25—H25	0.9300
C12—O3	1.335 (3)	O2—H2A	0.8200
C13—N1	1.465 (3)
O3—C1—C2	106.49 (17)	N1—C13—H13A	108.9
O3—C1—C10	104.81 (17)	C11—C13—H13A	108.9
C2—C1—C10	112.58 (17)	N1—C13—H13B	108.9
O3—C1—H1	110.9	C11—C13—H13B	108.9
C2—C1—H1	110.9	H13A—C13—H13B	107.7
C10—C1—H1	110.9	C3—C14—H14A	109.5
O5—C2—C3	59.81 (14)	C3—C14—H14B	109.5
O5—C2—C1	119.30 (18)	H14A—C14—H14B	109.5
C3—C2—C1	125.7 (2)	C3—C14—H14C	109.5
O5—C2—H2	113.8	H14A—C14—H14C	109.5
C3—C2—H2	113.8	H14B—C14—H14C	109.5
C1—C2—H2	113.8	C7—C15—H15A	109.5
O5—C3—C2	59.26 (14)	C7—C15—H15B	109.5
O5—C3—C4	114.4 (2)	H15A—C15—H15B	109.5
C2—C3—C4	115.1 (2)	C7—C15—H15C	109.5
O5—C3—C14	113.6 (2)	H15A—C15—H15C	109.5
C2—C3—C14	123.9 (2)	H15B—C15—H15C	109.5
C4—C3—C14	116.8 (2)	N1—C16—C17	110.8 (2)
C3—C4—C5	113.5 (2)	N1—C16—H16A	109.5
C3—C4—H4A	108.9	C17—C16—H16A	109.5
C5—C4—H4A	108.9	N1—C16—H16B	109.5
C3—C4—H4B	108.9	C17—C16—H16B	109.5
C5—C4—H4B	108.9	H16A—C16—H16B	108.1
H4A—C4—H4B	107.7	N2—C17—C16	111.8 (2)
C6—C5—C4	113.5 (2)	N2—C17—H17A	109.3
C6—C5—H5A	108.9	C16—C17—H17A	109.3
C4—C5—H5A	108.9	N2—C17—H17B	109.3
C6—C5—H5B	108.9	C16—C17—H17B	109.3
C4—C5—H5B	108.9	H17A—C17—H17B	107.9
H5A—C5—H5B	107.7	N2—C18—C19	111.9 (2)
O1—C6—C7	59.07 (14)	N2—C18—H18A	109.2
O1—C6—C5	117.00 (19)	C19—C18—H18A	109.2
C7—C6—C5	124.9 (2)	N2—C18—H18B	109.2
O1—C6—H6	114.7	C19—C18—H18B	109.2
C7—C6—H6	114.7	H18A—C18—H18B	107.9
C5—C6—H6	114.7	N1—C19—C18	111.2 (2)
O1—C7—C6	59.48 (13)	N1—C19—H19A	109.4
O1—C7—C15	113.19 (19)	C18—C19—H19A	109.4
C6—C7—C15	122.9 (2)	N1—C19—H19B	109.4
O1—C7—C8	117.09 (19)	C18—C19—H19B	109.4
C6—C7—C8	121.41 (19)	H19A—C19—H19B	108.0
C15—C7—C8	111.7 (2)	C21—C20—C25	116.9 (3)
O2—C8—C7	110.80 (18)	C21—C20—N2	121.2 (3)
O2—C8—C9	112.11 (18)	C25—C20—N2	121.9 (3)
C7—C8—C9	111.63 (18)	C20—C21—C22	121.1 (4)
O2—C8—H8	107.3	C20—C21—H21	119.4
C7—C8—H8	107.3	C22—C21—H21	119.4
C9—C8—H8	107.3	C23—C22—C21	120.6 (5)
C8—C9—C10	114.54 (17)	C23—C22—H22	119.7
C8—C9—H9A	108.6	C21—C22—H22	119.7
C10—C9—H9A	108.6	C24—C23—C22	120.0 (4)
C8—C9—H9B	108.6	C24—C23—Cl	120.2 (5)
C10—C9—H9B	108.6	C22—C23—Cl	119.7 (6)
H9A—C9—H9B	107.6	C23—C24—C25	120.3 (5)
C11—C10—C1	101.98 (17)	C23—C24—H24	119.8
C11—C10—C9	116.96 (19)	C25—C24—H24	119.8
C1—C10—C9	114.46 (18)	C24—C25—C20	121.1 (5)
C11—C10—H10	107.6	C24—C25—H25	119.5
C1—C10—H10	107.6	C20—C25—H25	119.5
C9—C10—H10	107.6	C19—N1—C16	107.29 (19)
C12—C11—C13	110.6 (2)	C19—N1—C13	109.5 (2)
C12—C11—C10	102.57 (19)	C16—N1—C13	111.6 (2)
C13—C11—C10	116.78 (19)	C20—N2—C17	116.2 (2)
C12—C11—H11	108.9	C20—N2—C18	116.1 (2)
C13—C11—H11	108.9	C17—N2—C18	111.7 (2)
C10—C11—H11	108.9	C7—O1—C6	61.45 (14)
O4—C12—O3	120.6 (2)	C8—O2—H2A	109.5
O4—C12—C11	128.6 (3)	C12—O3—C1	110.04 (18)
O3—C12—C11	110.8 (2)	C2—O5—C3	60.93 (14)
N1—C13—C11	113.45 (19)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2A···N1	0.82	2.14	2.943 (2)	166
C1—H1···O4i	0.98	2.37	3.271 (3)	152
C10—H10···O1ii	0.98	2.41	3.329 (3)	153

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2A⋯N1	0.82	2.14	2.943 (2)	166
C1—H1⋯O4i	0.98	2.37	3.271 (3)	152
C10—H10⋯O1ii	0.98	2.41	3.329 (3)	153

Symmetry codes: (i) ; (ii) .