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

The title compound, C(19)H(29)O(4), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-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 two fused five- and ten-membered rings with the pyrrolidin-1-ylmethyl group as a substituent. The five-membered lactone ring has an envelope conformation, whereas the ten-membered and pyrrolidine rings display approximate chair-chair and twisted conformations, respectively. The dihedral angle between the ten-membered ring and the lactone ring is 18.01 (19)°. An intra-molecular O-H⋯N hydrogen bond occurs. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen-bonding inter-actions.

Related literature

For the isolation and biological activity of 9α-hy­droxy­parthenolide, see: Abdel Sattar et al. (1996 ▶); El Hassany et al. (2004 ▶). For the reactivity of this sesquiterpene, see: Castaneda-Acosta et al. (1993 ▶); Neukirch et al. (2003 ▶); Der-Ren et al. (2006 ▶); Neelakantan et al. (2009 ▶). For conformational analysis, see: Cremer & Pople (1975 ▶)

Experimental

Crystal data

C19H29NO4

M = 335.43

Orthorhombic,

a = 8.1389 (6) Å

b = 10.1788 (7) Å

c = 21.7669 (15) Å

V = 1803.3 (2) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 298 K

0.30 × 0.27 × 0.18 mm

Data collection

Bruker APEXII CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T min = 0.634, T max = 0.746

7656 measured reflections

2110 independent reflections

1220 reflections with I > 2σ(I)

R int = 0.053

Refinement

R[F 2 > 2σ(F 2)] = 0.045

wR(F 2) = 0.121

S = 0.99

2110 reflections

222 parameters

H-atom parameters constrained

Δρmax = 0.15 e Å−3

Δρmin = −0.15 e Å−3

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: APEX2 and SAINT (Bruker, 2005 ▶); data reduction: SAINT; 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/S1600536811030467/zl2390sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811030467/zl2390Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536811030467/zl2390Isup3.cml

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

C19H29NO4	F(000) = 728
Mr = 335.43	Dx = 1.236 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 7656 reflections
a = 8.1389 (6) Å	θ = 3.7–26.4°
b = 10.1788 (7) Å	µ = 0.09 mm−1
c = 21.7669 (15) Å	T = 298 K
V = 1803.3 (2) Å3	PRISM, colourless
Z = 4	0.30 × 0.27 × 0.18 mm

Bruker APEXII CCD area-detector diffractometer	2110 independent reflections
Radiation source: fine-focus sealed tube	1220 reflections with I > 2σ(I)
graphite	Rint = 0.053
Detector resolution: 8.3333 pixels mm-1	θmax = 26.4°, θmin = 4.0°
φ and ω scans	h = −10→9
Absorption correction: multi-scan (SADABS; Bruker, 2008)	k = −10→12
Tmin = 0.634, Tmax = 0.746	l = −16→27
7656 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)] = 0.045	H-atom parameters constrained
wR(F2) = 0.121	w = 1/[σ2(Fo2) + (0.0601P)2] where P = (Fo2 + 2Fc2)/3
S = 0.99	(Δ/σ)max < 0.001
2110 reflections	Δρmax = 0.15 e Å−3
222 parameters	Δρmin = −0.15 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: 0.017 (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	0.2577 (4)	1.0264 (3)	0.09346 (16)	0.0496 (9)
H1	0.2982	1.1080	0.0749	0.059*
C3	0.1673 (5)	1.0469 (4)	0.15028 (16)	0.0548 (10)
C4	0.1500 (5)	1.1871 (4)	0.16990 (18)	0.0673 (11)
H4A	0.2481	1.2346	0.1578	0.081*
H4B	0.1430	1.1901	0.2144	0.081*
C5	−0.0026 (5)	1.2584 (4)	0.14249 (19)	0.0694 (12)
H5A	−0.0984	1.2386	0.1674	0.083*
H5B	0.0151	1.3526	0.1438	0.083*
C6	−0.0347 (5)	1.2170 (3)	0.07708 (16)	0.0508 (10)
H6	0.0391	1.2462	0.0475	0.061*
C7	−0.1572 (4)	1.1435 (3)	0.05791 (15)	0.0427 (8)
C8	−0.1582 (4)	1.0771 (3)	−0.00454 (15)	0.0462 (9)
H8	−0.2722	1.0556	−0.0150	0.055*
C9	−0.0599 (4)	0.9476 (3)	−0.00085 (16)	0.0441 (8)
H9A	−0.0842	0.9051	0.0380	0.053*
H9B	−0.0968	0.8897	−0.0334	0.053*
C10	0.1272 (4)	0.9652 (3)	−0.00631 (15)	0.0428 (8)
H10	0.1484	1.0592	−0.0118	0.051*
C11	0.2305 (4)	0.9192 (3)	0.04834 (16)	0.0469 (9)
H11	0.1811	0.8422	0.0680	0.056*
C12	0.3823 (5)	0.8774 (3)	−0.0393 (2)	0.0580 (10)
C13	0.2083 (4)	0.8935 (3)	−0.05999 (17)	0.0519 (10)
H13	0.1584	0.8063	−0.0639	0.062*
C14	0.1989 (5)	0.9619 (4)	−0.12159 (17)	0.0604 (11)
H14A	0.2482	1.0483	−0.1177	0.072*
H14B	0.2635	0.9126	−0.1511	0.072*
C15	−0.0436 (6)	0.8528 (4)	−0.1647 (2)	0.0802 (14)
H15A	−0.0827	0.8038	−0.1293	0.096*
H15B	0.0333	0.7987	−0.1874	0.096*
C16	−0.1830 (7)	0.8946 (5)	−0.2044 (3)	0.1017 (17)
H16A	−0.2811	0.9096	−0.1801	0.122*
H16B	−0.2067	0.8285	−0.2353	0.122*
C17	−0.1246 (6)	1.0221 (5)	−0.23440 (19)	0.0808 (14)
H17A	−0.1037	1.0089	−0.2778	0.097*
H17B	−0.2065	1.0907	−0.2298	0.097*
C18	0.0303 (6)	1.0581 (4)	−0.20152 (16)	0.0690 (12)
H18A	0.1253	1.0398	−0.2270	0.083*
H18B	0.0303	1.1507	−0.1910	0.083*
C19	0.0421 (5)	0.9509 (4)	0.17490 (18)	0.0735 (13)
H19A	0.0628	0.8653	0.1581	0.110*
H19B	−0.0662	0.9791	0.1634	0.110*
H19C	0.0499	0.9474	0.2189	0.110*
C20	−0.3045 (5)	1.1034 (4)	0.09593 (18)	0.0682 (12)
H20A	−0.2922	1.1361	0.1370	0.102*
H20B	−0.3124	1.0093	0.0969	0.102*
H20C	−0.4025	1.1393	0.0780	0.102*
N	0.0336 (4)	0.9768 (3)	−0.14550 (13)	0.0539 (8)
O1	0.5035 (4)	0.8578 (3)	−0.06984 (15)	0.0824 (9)
O2	0.3922 (3)	0.8876 (2)	0.02235 (13)	0.0600 (7)
O3	0.3332 (3)	0.9963 (3)	0.15201 (12)	0.0662 (8)
O4	−0.0948 (3)	1.1599 (2)	−0.05115 (11)	0.0544 (7)
H4	−0.0741	1.1161	−0.0818	0.060 (13)*

	U11	U22	U33	U12	U13	U23
C1	0.040 (2)	0.055 (2)	0.054 (2)	−0.0002 (18)	−0.0123 (19)	0.0075 (18)
C3	0.046 (2)	0.071 (3)	0.047 (2)	0.004 (2)	−0.0050 (19)	0.011 (2)
C4	0.059 (3)	0.088 (3)	0.055 (2)	0.000 (2)	−0.009 (2)	−0.010 (2)
C5	0.072 (3)	0.070 (3)	0.066 (3)	0.007 (2)	−0.003 (3)	−0.012 (2)
C6	0.050 (2)	0.049 (2)	0.053 (2)	0.0035 (18)	−0.001 (2)	−0.0002 (17)
C7	0.0356 (19)	0.0471 (19)	0.0454 (19)	0.0053 (16)	0.0035 (18)	0.0030 (17)
C8	0.038 (2)	0.054 (2)	0.046 (2)	−0.0014 (15)	−0.0027 (18)	0.0111 (18)
C9	0.043 (2)	0.0413 (18)	0.0484 (19)	−0.0034 (15)	−0.0035 (17)	0.0050 (17)
C10	0.041 (2)	0.0349 (17)	0.052 (2)	0.0005 (15)	−0.0019 (18)	0.0044 (16)
C11	0.038 (2)	0.0424 (19)	0.060 (2)	0.0016 (15)	−0.0031 (19)	0.0104 (17)
C12	0.055 (3)	0.041 (2)	0.078 (3)	0.0097 (19)	0.009 (3)	−0.0028 (19)
C13	0.051 (2)	0.0458 (19)	0.059 (2)	−0.0019 (17)	0.008 (2)	−0.0038 (18)
C14	0.062 (3)	0.064 (2)	0.056 (2)	0.004 (2)	0.012 (2)	−0.007 (2)
C15	0.106 (4)	0.065 (3)	0.069 (3)	−0.026 (3)	−0.011 (3)	−0.011 (2)
C16	0.111 (4)	0.109 (4)	0.085 (3)	−0.026 (4)	−0.022 (3)	−0.012 (3)
C17	0.091 (4)	0.093 (3)	0.059 (2)	0.003 (3)	−0.012 (3)	−0.012 (2)
C18	0.083 (3)	0.079 (3)	0.045 (2)	−0.009 (3)	0.006 (2)	0.004 (2)
C19	0.067 (3)	0.089 (3)	0.065 (2)	−0.011 (3)	0.002 (2)	0.026 (2)
C20	0.046 (2)	0.095 (3)	0.064 (2)	−0.002 (2)	0.008 (2)	0.001 (2)
N	0.062 (2)	0.0553 (18)	0.0444 (16)	−0.0090 (16)	0.0040 (16)	−0.0051 (15)
O1	0.068 (2)	0.0735 (19)	0.106 (2)	0.0188 (16)	0.0221 (19)	−0.0043 (18)
O2	0.0461 (16)	0.0548 (15)	0.0791 (19)	0.0125 (13)	−0.0057 (14)	0.0001 (13)
O3	0.0478 (16)	0.0875 (19)	0.0634 (16)	0.0074 (14)	−0.0176 (14)	0.0097 (14)
O4	0.0635 (17)	0.0531 (14)	0.0466 (14)	0.0046 (14)	0.0035 (14)	0.0102 (13)

C1—O3	1.448 (4)	C12—O1	1.206 (4)
C1—C3	1.454 (5)	C12—O2	1.349 (5)
C1—C11	1.485 (5)	C12—C13	1.495 (5)
C1—H1	0.9800	C13—C14	1.513 (5)
C3—O3	1.446 (4)	C13—H13	0.9800
C3—C4	1.496 (5)	C14—N	1.450 (4)
C3—C19	1.510 (5)	C14—H14A	0.9700
C4—C5	1.558 (5)	C14—H14B	0.9700
C4—H4A	0.9700	C15—N	1.470 (5)
C4—H4B	0.9700	C15—C16	1.489 (6)
C5—C6	1.508 (5)	C15—H15A	0.9700
C5—H5A	0.9700	C15—H15B	0.9700
C5—H5B	0.9700	C16—C17	1.529 (6)
C6—C7	1.315 (4)	C16—H16A	0.9700
C6—H6	0.9300	C16—H16B	0.9700
C7—C20	1.513 (5)	C17—C18	1.495 (6)
C7—C8	1.518 (5)	C17—H17A	0.9700
C8—O4	1.417 (4)	C17—H17B	0.9700
C8—C9	1.544 (5)	C18—N	1.474 (5)
C8—H8	0.9800	C18—H18A	0.9700
C9—C10	1.538 (4)	C18—H18B	0.9700
C9—H9A	0.9700	C19—H19A	0.9600
C9—H9B	0.9700	C19—H19B	0.9600
C10—C13	1.528 (5)	C19—H19C	0.9600
C10—C11	1.530 (4)	C20—H20A	0.9600
C10—H10	0.9800	C20—H20B	0.9600
C11—O2	1.468 (4)	C20—H20C	0.9600
C11—H11	0.9800	O4—H4	0.8200
O3—C1—C3	59.8 (2)	O2—C12—C13	110.3 (3)
O3—C1—C11	119.3 (3)	C12—C13—C14	111.4 (3)
C3—C1—C11	126.3 (3)	C12—C13—C10	103.4 (3)
O3—C1—H1	113.6	C14—C13—C10	115.8 (3)
C3—C1—H1	113.6	C12—C13—H13	108.6
C11—C1—H1	113.6	C14—C13—H13	108.6
O3—C3—C1	59.9 (2)	C10—C13—H13	108.6
O3—C3—C4	114.9 (3)	N—C14—C13	114.4 (3)
C1—C3—C4	115.3 (3)	N—C14—H14A	108.7
O3—C3—C19	113.0 (3)	C13—C14—H14A	108.7
C1—C3—C19	123.4 (4)	N—C14—H14B	108.7
C4—C3—C19	116.9 (4)	C13—C14—H14B	108.7
C3—C4—C5	114.2 (3)	H14A—C14—H14B	107.6
C3—C4—H4A	108.7	N—C15—C16	104.2 (4)
C5—C4—H4A	108.7	N—C15—H15A	110.9
C3—C4—H4B	108.7	C16—C15—H15A	110.9
C5—C4—H4B	108.7	N—C15—H15B	110.9
H4A—C4—H4B	107.6	C16—C15—H15B	110.9
C6—C5—C4	111.7 (3)	H15A—C15—H15B	108.9
C6—C5—H5A	109.3	C15—C16—C17	104.7 (4)
C4—C5—H5A	109.3	C15—C16—H16A	110.8
C6—C5—H5B	109.3	C17—C16—H16A	110.8
C4—C5—H5B	109.3	C15—C16—H16B	110.8
H5A—C5—H5B	107.9	C17—C16—H16B	110.8
C7—C6—C5	126.2 (4)	H16A—C16—H16B	108.9
C7—C6—H6	116.9	C18—C17—C16	105.4 (4)
C5—C6—H6	116.9	C18—C17—H17A	110.7
C6—C7—C20	125.5 (3)	C16—C17—H17A	110.7
C6—C7—C8	122.8 (3)	C18—C17—H17B	110.7
C20—C7—C8	111.4 (3)	C16—C17—H17B	110.7
O4—C8—C7	112.0 (3)	H17A—C17—H17B	108.8
O4—C8—C9	110.9 (3)	N—C18—C17	105.9 (3)
C7—C8—C9	109.3 (3)	N—C18—H18A	110.6
O4—C8—H8	108.2	C17—C18—H18A	110.6
C7—C8—H8	108.2	N—C18—H18B	110.6
C9—C8—H8	108.2	C17—C18—H18B	110.6
C10—C9—C8	114.2 (3)	H18A—C18—H18B	108.7
C10—C9—H9A	108.7	C3—C19—H19A	109.5
C8—C9—H9A	108.7	C3—C19—H19B	109.5
C10—C9—H9B	108.7	H19A—C19—H19B	109.5
C8—C9—H9B	108.7	C3—C19—H19C	109.5
H9A—C9—H9B	107.6	H19A—C19—H19C	109.5
C13—C10—C11	102.2 (3)	H19B—C19—H19C	109.5
C13—C10—C9	115.6 (3)	C7—C20—H20A	109.5
C11—C10—C9	116.6 (3)	C7—C20—H20B	109.5
C13—C10—H10	107.3	H20A—C20—H20B	109.5
C11—C10—H10	107.3	C7—C20—H20C	109.5
C9—C10—H10	107.3	H20A—C20—H20C	109.5
O2—C11—C1	106.4 (3)	H20B—C20—H20C	109.5
O2—C11—C10	105.1 (3)	C14—N—C15	114.1 (3)
C1—C11—C10	111.8 (3)	C14—N—C18	111.9 (3)
O2—C11—H11	111.1	C15—N—C18	103.8 (3)
C1—C11—H11	111.1	C12—O2—C11	110.3 (3)
C10—C11—H11	111.1	C3—O3—C1	60.3 (2)
O1—C12—O2	120.8 (4)	C8—O4—H4	109.5
O1—C12—C13	128.9 (4)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N	0.82	2.17	2.964 (4)	164
C1—H1···O4i	0.98	2.57	3.533 (4)	167
C11—H11···O1ii	0.98	2.50	3.403 (4)	154

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯N	0.82	2.17	2.964 (4)	164
C1—H1⋯O4i	0.98	2.57	3.533 (4)	167
C11—H11⋯O1ii	0.98	2.50	3.403 (4)	154

Symmetry codes: (i) ; (ii) .