9-Hy-droxy-4,8-dimethyl-12-(piperidin-1-ylmeth-yl)-3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.

The title compound, C(20)H(31)NO(4), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo-[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 the pipyridin-1-yl-methyl group as a substituent. The ten-membered ring adopts an approximate chair-chair conformation, while the six-membered ring display a chair conformation and the five-membered ring an envelope conformation with the C(H)-C-C(H) atom at the flap. The dihedral angle between the ten-membered ring and the lactone ring is 21.7 (4)°. The mol-ecular conformation is stabilized by an O-H⋯N hydrogen bond and the crystal structure is stabilized by weak inter-molecular 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 the typical conformation of sesquiterpene lactones, see: Watson & Zabel (1982 ▶). For reactivity of this sesquiterpene, see: Hwang et al. (2006 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C20H31NO4

M = 349.46

Monoclinic,

a = 11.8390 (6) Å

b = 6.7053 (3) Å

c = 12.0875 (6) Å

β = 101.399 (5)°

V = 940.63 (8) Å3

Z = 2

Mo Kα radiation

μ = 0.09 mm−1

T = 180 K

0.44 × 0.13 × 0.11 mm

Data collection

Agilent Xcalibur Sapphire1 long nozzle diffractometer

Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ▶) T min = 0.858, T max = 1.000

10503 measured reflections

2096 independent reflections

1996 reflections with I > 2σ(I)

R int = 0.024

Refinement

R[F 2 > 2σ(F 2)] = 0.028

wR(F 2) = 0.071

S = 1.05

2096 reflections

229 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.16 e Å−3

Δρmin = −0.16 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 publication routines (Farrugia, 1999 ▶).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811038803/bt5649sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811038803/bt5649Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536811038803/bt5649Isup3.cml

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

C20H31NO4	F(000) = 380
Mr = 349.46	Dx = 1.234 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 10503 reflections
a = 11.8390 (6) Å	θ = 3.4–26.4°
b = 6.7053 (3) Å	µ = 0.09 mm−1
c = 12.0875 (6) Å	T = 180 K
β = 101.399 (5)°	Box, colorless
V = 940.63 (8) Å3	0.44 × 0.13 × 0.11 mm
Z = 2

Agilent Xcalibur Sapphire1 long nozzle diffractometer	2096 independent reflections
Radiation source: fine-focus sealed tube	1996 reflections with I > 2σ(I)
graphite	Rint = 0.024
Detector resolution: 8.2632 pixels mm-1	θmax = 26.4°, θmin = 3.4°
ω scan	h = −14→14
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010)	k = −8→8
Tmin = 0.858, Tmax = 1.000	l = −15→15
10503 measured 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)] = 0.028	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.071	H-atom parameters constrained
S = 1.05	w = 1/[σ2(Fo2) + (0.0473P)2 + 0.0809P] where P = (Fo2 + 2Fc2)/3
2096 reflections	(Δ/σ)max < 0.001
229 parameters	Δρmax = 0.16 e Å−3
1 restraint	Δρmin = −0.16 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 > σ(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	0.71467 (12)	0.2598 (2)	0.66934 (12)	0.0185 (3)
H1	0.7678	0.1867	0.7306	0.022*
C2	0.78094 (12)	0.3815 (2)	0.60123 (12)	0.0204 (3)
H2	0.7329	0.4808	0.5510	0.024*
C3	0.90205 (13)	0.4403 (3)	0.63599 (14)	0.0242 (3)
C4	0.93406 (14)	0.6394 (3)	0.59414 (15)	0.0320 (4)
H4A	0.8832	0.6688	0.5206	0.038*
H4B	1.0144	0.6341	0.5823	0.038*
C5	0.92313 (15)	0.8072 (3)	0.67800 (17)	0.0341 (4)
H5A	0.9905	0.8040	0.7413	0.041*
H5B	0.9226	0.9379	0.6397	0.041*
C6	0.81409 (13)	0.7844 (2)	0.72347 (14)	0.0265 (3)
H6	0.7440	0.7997	0.6703	0.032*
C7	0.80412 (13)	0.7456 (3)	0.82848 (14)	0.0264 (3)
C8	0.68939 (14)	0.6851 (2)	0.85621 (13)	0.0237 (3)
H8	0.6920	0.7171	0.9375	0.028*
C9	0.67106 (13)	0.4587 (2)	0.84106 (12)	0.0202 (3)
H9A	0.7448	0.3906	0.8720	0.024*
H9B	0.6143	0.4157	0.8864	0.024*
C10	0.62893 (11)	0.3886 (2)	0.71874 (11)	0.0172 (3)
H10	0.6103	0.5093	0.6700	0.021*
C11	0.52119 (12)	0.2569 (2)	0.70277 (11)	0.0186 (3)
H11	0.5205	0.1808	0.7738	0.022*
C12	0.53608 (12)	0.1144 (2)	0.61067 (12)	0.0207 (3)
C13	0.40794 (12)	0.3691 (3)	0.66791 (12)	0.0216 (3)
H13A	0.4040	0.4256	0.5916	0.026*
H13B	0.3434	0.2737	0.6636	0.026*
C14	0.90140 (16)	0.7399 (4)	0.93004 (17)	0.0431 (5)
H14A	0.9745	0.7663	0.9063	0.065*
H14B	0.9044	0.6079	0.9654	0.065*
H14C	0.8886	0.8417	0.9844	0.065*
C15	0.97876 (14)	0.3631 (3)	0.74176 (16)	0.0336 (4)
H15A	1.0573	0.3466	0.7286	0.050*
H15B	0.9497	0.2342	0.7621	0.050*
H15C	0.9793	0.4583	0.8034	0.050*
C16	0.36161 (14)	0.4537 (3)	0.84869 (13)	0.0241 (3)
H16A	0.4219	0.3604	0.8864	0.029*
H16B	0.2882	0.3791	0.8291	0.029*
C17	0.30269 (13)	0.6655 (3)	0.68699 (13)	0.0258 (3)
H17A	0.2298	0.5903	0.6649	0.031*
H17B	0.3248	0.7164	0.6174	0.031*
C18	0.28408 (15)	0.8390 (3)	0.76082 (15)	0.0316 (4)
H18A	0.2196	0.9219	0.7207	0.038*
H18B	0.3543	0.9228	0.7760	0.038*
C19	0.34845 (15)	0.6219 (3)	0.92854 (13)	0.0315 (4)
H19A	0.4229	0.6924	0.9513	0.038*
H19B	0.3266	0.5668	0.9974	0.038*
C20	0.25678 (15)	0.7677 (3)	0.87217 (14)	0.0341 (4)
H20A	0.2539	0.8833	0.9225	0.041*
H20B	0.1804	0.7019	0.8583	0.041*
N	0.39312 (10)	0.5309 (2)	0.74545 (10)	0.0202 (3)
O1	0.46527 (10)	0.00689 (19)	0.55635 (10)	0.0299 (3)
O2	0.64460 (9)	0.12085 (16)	0.59253 (9)	0.0211 (2)
O3	0.86868 (9)	0.2885 (2)	0.55096 (10)	0.0295 (3)
O4	0.59735 (10)	0.79420 (18)	0.79140 (10)	0.0297 (3)
H4	0.5376	0.7235	0.7795	0.045*

	U11	U22	U33	U12	U13	U23
C1	0.0182 (6)	0.0179 (7)	0.0187 (6)	−0.0003 (6)	0.0017 (5)	−0.0029 (6)
C2	0.0194 (7)	0.0215 (7)	0.0212 (7)	0.0018 (6)	0.0065 (6)	−0.0019 (6)
C3	0.0180 (7)	0.0247 (8)	0.0314 (8)	−0.0006 (6)	0.0081 (6)	−0.0036 (7)
C4	0.0246 (8)	0.0331 (10)	0.0415 (9)	−0.0051 (7)	0.0143 (7)	0.0047 (8)
C5	0.0301 (8)	0.0225 (8)	0.0514 (11)	−0.0055 (7)	0.0119 (8)	0.0035 (8)
C6	0.0237 (7)	0.0155 (7)	0.0401 (9)	0.0000 (6)	0.0060 (6)	0.0004 (7)
C7	0.0242 (7)	0.0188 (7)	0.0344 (8)	−0.0023 (6)	0.0015 (6)	−0.0065 (6)
C8	0.0251 (7)	0.0208 (7)	0.0240 (7)	0.0002 (6)	0.0022 (6)	−0.0054 (6)
C9	0.0217 (7)	0.0215 (7)	0.0169 (7)	−0.0015 (6)	0.0024 (5)	−0.0015 (6)
C10	0.0171 (6)	0.0175 (7)	0.0169 (7)	−0.0008 (5)	0.0033 (5)	−0.0007 (5)
C11	0.0192 (6)	0.0200 (7)	0.0167 (6)	−0.0033 (6)	0.0041 (5)	0.0000 (6)
C12	0.0211 (7)	0.0215 (7)	0.0198 (6)	−0.0024 (6)	0.0047 (5)	−0.0004 (6)
C13	0.0188 (7)	0.0284 (8)	0.0178 (7)	−0.0012 (6)	0.0041 (5)	−0.0021 (6)
C14	0.0302 (9)	0.0549 (13)	0.0404 (10)	−0.0072 (9)	−0.0021 (7)	−0.0102 (10)
C15	0.0217 (7)	0.0288 (9)	0.0470 (10)	0.0011 (7)	−0.0012 (7)	−0.0003 (8)
C16	0.0269 (7)	0.0272 (8)	0.0199 (7)	0.0002 (7)	0.0089 (6)	0.0032 (6)
C17	0.0235 (7)	0.0325 (9)	0.0221 (7)	0.0055 (7)	0.0057 (6)	0.0052 (7)
C18	0.0319 (8)	0.0283 (9)	0.0342 (9)	0.0086 (7)	0.0058 (7)	0.0037 (7)
C19	0.0377 (9)	0.0373 (10)	0.0202 (7)	0.0049 (8)	0.0078 (6)	−0.0008 (7)
C20	0.0344 (9)	0.0408 (10)	0.0290 (8)	0.0092 (9)	0.0108 (7)	−0.0049 (8)
N	0.0188 (6)	0.0247 (6)	0.0178 (6)	0.0011 (5)	0.0057 (4)	0.0031 (5)
O1	0.0277 (6)	0.0321 (7)	0.0293 (6)	−0.0091 (5)	0.0041 (5)	−0.0100 (5)
O2	0.0207 (5)	0.0207 (5)	0.0226 (5)	−0.0025 (4)	0.0058 (4)	−0.0058 (4)
O3	0.0236 (5)	0.0338 (6)	0.0346 (6)	−0.0012 (5)	0.0145 (5)	−0.0100 (6)
O4	0.0244 (5)	0.0211 (6)	0.0431 (6)	0.0033 (5)	0.0051 (5)	−0.0017 (6)

C1—O2	1.4541 (17)	C11—H11	1.0000
C1—C2	1.488 (2)	C12—O1	1.1982 (19)
C1—C10	1.5401 (19)	C12—O2	1.3461 (17)
C1—H1	1.0000	C13—N	1.466 (2)
C2—O3	1.4444 (17)	C13—H13A	0.9900
C2—C3	1.466 (2)	C13—H13B	0.9900
C2—H2	1.0000	C14—H14A	0.9800
C3—O3	1.445 (2)	C14—H14B	0.9800
C3—C4	1.503 (2)	C14—H14C	0.9800
C3—C15	1.506 (2)	C15—H15A	0.9800
C4—C5	1.537 (3)	C15—H15B	0.9800
C4—H4A	0.9900	C15—H15C	0.9800
C4—H4B	0.9900	C16—N	1.4658 (19)
C5—C6	1.508 (2)	C16—C19	1.512 (2)
C5—H5A	0.9900	C16—H16A	0.9900
C5—H5B	0.9900	C16—H16B	0.9900
C6—C7	1.324 (2)	C17—N	1.4699 (19)
C6—H6	0.9500	C17—C18	1.509 (2)
C7—C14	1.509 (2)	C17—H17A	0.9900
C7—C8	1.517 (2)	C17—H17B	0.9900
C8—O4	1.4136 (19)	C18—C20	1.522 (2)
C8—C9	1.540 (2)	C18—H18A	0.9900
C8—H8	1.0000	C18—H18B	0.9900
C9—C10	1.5375 (19)	C19—C20	1.518 (3)
C9—H9A	0.9900	C19—H19A	0.9900
C9—H9B	0.9900	C19—H19B	0.9900
C10—C11	1.5320 (19)	C20—H20A	0.9900
C10—H10	1.0000	C20—H20B	0.9900
C11—C12	1.504 (2)	O4—H4	0.8400
C11—C13	1.523 (2)
O2—C1—C2	107.15 (11)	C10—C11—H11	109.5
O2—C1—C10	105.68 (10)	O1—C12—O2	121.14 (14)
C2—C1—C10	111.55 (12)	O1—C12—C11	128.04 (14)
O2—C1—H1	110.8	O2—C12—C11	110.82 (12)
C2—C1—H1	110.8	N—C13—C11	113.50 (11)
C10—C1—H1	110.8	N—C13—H13A	108.9
O3—C2—C3	59.52 (9)	C11—C13—H13A	108.9
O3—C2—C1	119.86 (13)	N—C13—H13B	108.9
C3—C2—C1	125.56 (13)	C11—C13—H13B	108.9
O3—C2—H2	113.7	H13A—C13—H13B	107.7
C3—C2—H2	113.7	C7—C14—H14A	109.5
C1—C2—H2	113.7	C7—C14—H14B	109.5
O3—C3—C2	59.49 (9)	H14A—C14—H14B	109.5
O3—C3—C4	115.98 (14)	C7—C14—H14C	109.5
C2—C3—C4	116.10 (14)	H14A—C14—H14C	109.5
O3—C3—C15	113.34 (14)	H14B—C14—H14C	109.5
C2—C3—C15	122.85 (14)	C3—C15—H15A	109.5
C4—C3—C15	116.18 (14)	C3—C15—H15B	109.5
C3—C4—C5	111.64 (14)	H15A—C15—H15B	109.5
C3—C4—H4A	109.3	C3—C15—H15C	109.5
C5—C4—H4A	109.3	H15A—C15—H15C	109.5
C3—C4—H4B	109.3	H15B—C15—H15C	109.5
C5—C4—H4B	109.3	N—C16—C19	110.83 (14)
H4A—C4—H4B	108.0	N—C16—H16A	109.5
C6—C5—C4	110.84 (14)	C19—C16—H16A	109.5
C6—C5—H5A	109.5	N—C16—H16B	109.5
C4—C5—H5A	109.5	C19—C16—H16B	109.5
C6—C5—H5B	109.5	H16A—C16—H16B	108.1
C4—C5—H5B	109.5	N—C17—C18	111.51 (12)
H5A—C5—H5B	108.1	N—C17—H17A	109.3
C7—C6—C5	127.93 (16)	C18—C17—H17A	109.3
C7—C6—H6	116.0	N—C17—H17B	109.3
C5—C6—H6	116.0	C18—C17—H17B	109.3
C6—C7—C14	125.94 (16)	H17A—C17—H17B	108.0
C6—C7—C8	121.18 (14)	C17—C18—C20	111.23 (15)
C14—C7—C8	112.72 (15)	C17—C18—H18A	109.4
O4—C8—C7	111.41 (13)	C20—C18—H18A	109.4
O4—C8—C9	111.66 (12)	C17—C18—H18B	109.4
C7—C8—C9	110.39 (13)	C20—C18—H18B	109.4
O4—C8—H8	107.7	H18A—C18—H18B	108.0
C7—C8—H8	107.7	C16—C19—C20	110.39 (13)
C9—C8—H8	107.7	C16—C19—H19A	109.6
C10—C9—C8	115.28 (13)	C20—C19—H19A	109.6
C10—C9—H9A	108.5	C16—C19—H19B	109.6
C8—C9—H9A	108.5	C20—C19—H19B	109.6
C10—C9—H9B	108.5	H19A—C19—H19B	108.1
C8—C9—H9B	108.5	C19—C20—C18	109.95 (14)
H9A—C9—H9B	107.5	C19—C20—H20A	109.7
C11—C10—C9	113.65 (11)	C18—C20—H20A	109.7
C11—C10—C1	102.95 (12)	C19—C20—H20B	109.7
C9—C10—C1	115.52 (12)	C18—C20—H20B	109.7
C11—C10—H10	108.1	H20A—C20—H20B	108.2
C9—C10—H10	108.1	C16—N—C13	111.44 (13)
C1—C10—H10	108.1	C16—N—C17	110.02 (12)
C12—C11—C13	109.57 (11)	C13—N—C17	108.34 (11)
C12—C11—C10	104.07 (11)	C12—O2—C1	111.05 (11)
C13—C11—C10	114.55 (13)	C2—O3—C3	60.99 (9)
C12—C11—H11	109.5	C8—O4—H4	109.5
C13—C11—H11	109.5

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N	0.84	2.12	2.9564 (14)	176
C2—H2···O1i	1.00	2.45	3.2622 (15)	138
C4—H4B···O3ii	0.99	2.54	3.3387 (16)	137
C6—H6···O2iii	0.95	2.54	3.2206 (15)	128
C13—H13A···O2i	0.99	2.55	3.5178 (15)	166

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯N	0.84	2.12	2.9564 (14)	176
C2—H2⋯O1i	1.00	2.45	3.2622 (15)	138
C4—H4B⋯O3ii	0.99	2.54	3.3387 (16)	137
C6—H6⋯O2iii	0.95	2.54	3.2206 (15)	128
C13—H13A⋯O2i	0.99	2.55	3.5178 (15)	166

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