Crystal structure of (1S,2R,4R,9S,11S,12R)-9α-hy-droxy-4,8-dimethyl-12-[(thio-morpholin-4-yl)meth-yl]-3,14-dioxatri-cyclo-[9.3.0.0(2,4)]tetra-dec-7-en-13-one.

The title compound, C19H29NO4S, was synthesised from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatri-cyclo-[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 the plant Anvillea radiata. The mol-ecule is built up from two fused five- and ten-membered rings, with an additional ep-oxy ring system and a thio-morpholine group as a substituent. The ten-membered ring adopts an approximate chair-chair conformation, while the thio-morpholine ring displays a chair conformation and the five-membered ring has an envelope conformation, with the C atom closest to the hy-droxy group forming the flap. An intra-molecular O-H⋯N hydrogen bond closes an S(8) ring. The crystal structure features weak C-H⋯O hydrogen-bonding inter-actions, which link the mol-ecules into [010] chains.

Related literature

For background to the medicinal uses of the plant Anvillea radiata, see: El Hassany et al. (2004 ▸); Abdel Sattar et al. (1996 ▸). For the reactivity of this sesquiterpene, see: Hwang et al. (2006 ▸); Neelakantan et al. (2009 ▸); Loubidi et al. (2014 ▸).

Experimental

Crystal data

C19H29NO4S

M = 367.49

Monoclinic,

a = 11.920 (2) Å

b = 6.7919 (13) Å

c = 12.144 (3) Å

β = 101.659 (6)°

V = 962.9 (3) Å3

Z = 2

Mo Kα radiation

μ = 0.19 mm−1

T = 296 K

0.33 × 0.17 × 0.04 mm

Data collection

Bruker APEXII CCD diffractometer

12288 measured reflections

3940 independent reflections

3749 reflections with I > 2σ(I)

R int = 0.033

Refinement

R[F 2 > 2σ(F 2)] = 0.031

wR(F 2) = 0.083

S = 1.03

3940 reflections

229 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.23 e Å−3

Δρmin = −0.18 e Å−3

Absolute structure: Flack & Bernardinelli (2000 ▸), 1799 Friedel pairs

Absolute structure parameter: 0.04 (7)

Data collection: APEX2 (Bruker, 2009 ▸); cell refinement: SAINT-Plus (Bruker, 2009 ▸); data reduction: SAINT-Plus; 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, 2012 ▸) and PLATON (Spek, 2009 ▸); software used to prepare material for publication: WinGX (Farrugia, 2012 ▸).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S205698901500170X/hb7355sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S205698901500170X/hb7355Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901500170X/hb7355Isup3.cml

Click here for additional data file.

. DOI: 10.1107/S205698901500170X/hb7355fig1.tif

Mol­ecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.

Click here for additional data file.

b x y z . DOI: 10.1107/S205698901500170X/hb7355fig2.tif

Partial packing view showing the C—H⋯O inter­actions (dashed lines) and the formation of a chain parallel to the b axis. H atoms not involved in hydrogen bonding have been omitted for clarity. [Symmetry code: (i) x, −1 + y, z.]

CCDC reference: 1045641

Additional supporting information: crystallographic information; 3D view; checkCIF report

C19H29NO4S	F(000) = 396
Mr = 367.49	Dx = 1.268 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 3940 reflections
a = 11.920 (2) Å	θ = 2.7–26.4°
b = 6.7919 (13) Å	µ = 0.19 mm−1
c = 12.144 (3) Å	T = 296 K
β = 101.659 (6)°	Platelet, colourless
V = 962.9 (3) Å3	0.33 × 0.17 × 0.04 mm
Z = 2

Bruker APEXII CCD diffractometer	3749 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.033
Graphite monochromator	θmax = 26.4°, θmin = 2.7°
ω and φ scans	h = −14→14
12288 measured reflections	k = −8→8
3940 independent reflections	l = −15→15

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)] = 0.031	H-atom parameters constrained
wR(F2) = 0.083	w = 1/[σ2(Fo2) + (0.0458P)2 + 0.1195P] where P = (Fo2 + 2Fc2)/3
S = 1.03	(Δ/σ)max < 0.001
3940 reflections	Δρmax = 0.23 e Å−3
229 parameters	Δρmin = −0.18 e Å−3
1 restraint	Absolute structure: Flack & Bernardinelli (2000), 1799 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.04 (7)

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'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
S	0.75906 (4)	0.44169 (9)	0.12214 (4)	0.05970 (15)
C11	0.47717 (11)	0.9710 (2)	0.29664 (11)	0.0287 (3)
H11	0.4771	1.0444	0.2271	0.034*
O2	0.35347 (8)	1.10088 (15)	0.40682 (8)	0.0328 (2)
O4	0.40208 (10)	0.43397 (19)	0.20264 (11)	0.0488 (3)
H4	0.4583	0.5054	0.2205	0.073*
C10	0.37095 (11)	0.8366 (2)	0.28037 (11)	0.0256 (3)
H10	0.3907	0.7195	0.3274	0.031*
O1	0.53049 (10)	1.22191 (19)	0.44127 (10)	0.0458 (3)
C12	0.46117 (12)	1.1124 (2)	0.38823 (12)	0.0317 (3)
O3	0.13476 (9)	0.9267 (2)	0.45208 (10)	0.0465 (3)
C2	0.22047 (12)	0.8371 (2)	0.39912 (12)	0.0325 (3)
H2	0.2684	0.7399	0.4466	0.039*
N2	0.60890 (10)	0.70195 (19)	0.25656 (10)	0.0310 (3)
C15	0.59162 (12)	0.8638 (2)	0.33252 (12)	0.0328 (3)
H15A	0.6533	0.9583	0.3362	0.039*
H15B	0.5962	0.8108	0.4075	0.039*
C9	0.32885 (13)	0.7685 (2)	0.15807 (12)	0.0315 (3)
H9A	0.3845	0.8096	0.1145	0.038*
H9B	0.2576	0.8361	0.1277	0.038*
C3	0.09931 (13)	0.7784 (2)	0.36578 (15)	0.0394 (4)
C1	0.28464 (11)	0.9606 (2)	0.33070 (11)	0.0286 (3)
H1	0.2315	1.0297	0.2711	0.034*
C19	0.64040 (14)	0.7794 (3)	0.15414 (13)	0.0387 (3)
H19A	0.7141	0.8447	0.1737	0.046*
H19B	0.5841	0.8762	0.1201	0.046*
C6	0.18706 (13)	0.4410 (2)	0.27405 (15)	0.0422 (4)
H6	0.2559	0.4241	0.3251	0.051*
C7	0.19578 (13)	0.4844 (2)	0.16970 (15)	0.0415 (4)
C17	0.69958 (13)	0.5726 (3)	0.31802 (13)	0.0399 (4)
H17A	0.6805	0.5356	0.3892	0.048*
H17B	0.7711	0.6451	0.3343	0.048*
C8	0.30887 (14)	0.5453 (2)	0.14119 (14)	0.0377 (3)
H8	0.3042	0.5174	0.0612	0.045*
C4	0.06950 (15)	0.5785 (3)	0.40637 (17)	0.0495 (4)
H4A	−0.0082	0.5813	0.4192	0.059*
H4B	0.1205	0.5488	0.4773	0.059*
C16	0.71589 (16)	0.3889 (3)	0.25369 (16)	0.0496 (4)
H16A	0.6447	0.3153	0.2384	0.059*
H16B	0.7737	0.3070	0.2997	0.059*
C18	0.64687 (16)	0.6178 (3)	0.07026 (14)	0.0498 (4)
H18A	0.6606	0.6759	0.0012	0.060*
H18B	0.5739	0.5497	0.0529	0.060*
C13	0.02051 (14)	0.8583 (3)	0.26257 (18)	0.0547 (5)
H13A	−0.0544	0.8785	0.2784	0.082*
H13B	0.0157	0.7660	0.2019	0.082*
H13C	0.0500	0.9812	0.2416	0.082*
C5	0.07965 (16)	0.4157 (3)	0.32077 (19)	0.0537 (5)
H5A	0.0811	0.2881	0.3570	0.064*
H5B	0.0132	0.4197	0.2597	0.064*
C14	0.09689 (18)	0.4951 (4)	0.06943 (19)	0.0679 (6)
H14A	0.0262	0.4726	0.0938	0.102*
H14B	0.1066	0.3965	0.0155	0.102*
H14C	0.0952	0.6230	0.0355	0.102*

	U11	U22	U33	U12	U13	U23
S	0.0614 (3)	0.0736 (3)	0.0469 (2)	0.0211 (3)	0.0173 (2)	−0.0094 (3)
C11	0.0308 (7)	0.0301 (7)	0.0252 (6)	−0.0049 (5)	0.0051 (5)	0.0005 (5)
O2	0.0317 (5)	0.0312 (5)	0.0355 (5)	−0.0028 (4)	0.0070 (4)	−0.0086 (4)
O4	0.0411 (6)	0.0332 (6)	0.0703 (8)	0.0046 (5)	0.0068 (5)	−0.0056 (6)
C10	0.0270 (6)	0.0242 (6)	0.0249 (6)	−0.0015 (5)	0.0034 (5)	−0.0009 (5)
O1	0.0422 (6)	0.0481 (7)	0.0460 (6)	−0.0143 (5)	0.0061 (5)	−0.0175 (6)
C12	0.0325 (7)	0.0309 (7)	0.0310 (7)	−0.0039 (6)	0.0044 (5)	−0.0015 (6)
O3	0.0366 (5)	0.0539 (7)	0.0539 (7)	−0.0044 (6)	0.0205 (5)	−0.0164 (6)
C2	0.0283 (7)	0.0357 (7)	0.0339 (8)	0.0011 (6)	0.0072 (6)	−0.0026 (6)
N2	0.0291 (5)	0.0378 (6)	0.0271 (6)	0.0022 (5)	0.0077 (4)	0.0028 (5)
C15	0.0280 (7)	0.0415 (8)	0.0282 (7)	−0.0020 (6)	0.0039 (5)	−0.0038 (6)
C9	0.0353 (7)	0.0320 (7)	0.0259 (7)	−0.0036 (6)	0.0029 (5)	−0.0033 (6)
C3	0.0290 (7)	0.0384 (8)	0.0525 (10)	−0.0007 (6)	0.0123 (6)	−0.0048 (7)
C1	0.0277 (6)	0.0267 (7)	0.0294 (6)	0.0008 (6)	0.0008 (5)	−0.0027 (6)
C19	0.0427 (8)	0.0431 (9)	0.0325 (8)	−0.0002 (7)	0.0130 (6)	0.0051 (7)
C6	0.0388 (8)	0.0243 (7)	0.0621 (10)	−0.0001 (7)	0.0069 (7)	0.0012 (8)
C7	0.0381 (8)	0.0299 (8)	0.0531 (10)	−0.0042 (6)	0.0012 (7)	−0.0095 (7)
C17	0.0355 (8)	0.0521 (10)	0.0322 (8)	0.0092 (7)	0.0067 (6)	0.0046 (7)
C8	0.0419 (8)	0.0321 (8)	0.0373 (8)	−0.0015 (6)	0.0034 (6)	−0.0106 (6)
C4	0.0364 (9)	0.0519 (11)	0.0640 (11)	−0.0091 (8)	0.0191 (8)	0.0040 (9)
C16	0.0498 (9)	0.0484 (11)	0.0504 (10)	0.0141 (8)	0.0097 (8)	0.0056 (8)
C18	0.0586 (11)	0.0602 (11)	0.0312 (8)	0.0090 (9)	0.0107 (7)	−0.0017 (8)
C13	0.0335 (8)	0.0461 (10)	0.0776 (14)	0.0004 (8)	−0.0054 (8)	−0.0018 (9)
C5	0.0491 (9)	0.0350 (9)	0.0782 (13)	−0.0101 (8)	0.0157 (9)	0.0050 (9)
C14	0.0487 (10)	0.0836 (17)	0.0633 (13)	−0.0162 (11)	−0.0080 (9)	−0.0134 (11)

S—C18	1.810 (2)	C1—H1	0.9800
S—C16	1.810 (2)	C19—C18	1.510 (3)
C11—C12	1.510 (2)	C19—H19A	0.9700
C11—C15	1.530 (2)	C19—H19B	0.9700
C11—C10	1.5410 (18)	C6—C7	1.325 (3)
C11—H11	0.9800	C6—C5	1.512 (2)
O2—C12	1.3500 (17)	C6—H6	0.9300
O2—C1	1.4592 (16)	C7—C14	1.516 (2)
O4—C8	1.424 (2)	C7—C8	1.516 (2)
O4—H4	0.8200	C17—C16	1.505 (3)
C10—C9	1.5396 (19)	C17—H17A	0.9700
C10—C1	1.5476 (19)	C17—H17B	0.9700
C10—H10	0.9800	C8—H8	0.9800
O1—C12	1.1983 (18)	C4—C5	1.539 (3)
O3—C2	1.4471 (18)	C4—H4A	0.9700
O3—C3	1.454 (2)	C4—H4B	0.9700
C2—C3	1.474 (2)	C16—H16A	0.9700
C2—C1	1.495 (2)	C16—H16B	0.9700
C2—H2	0.9800	C18—H18A	0.9700
N2—C19	1.4674 (19)	C18—H18B	0.9700
N2—C17	1.4735 (19)	C13—H13A	0.9600
N2—C15	1.4758 (19)	C13—H13B	0.9600
C15—H15A	0.9700	C13—H13C	0.9600
C15—H15B	0.9700	C5—H5A	0.9700
C9—C8	1.542 (2)	C5—H5B	0.9700
C9—H9A	0.9700	C14—H14A	0.9600
C9—H9B	0.9700	C14—H14B	0.9600
C3—C13	1.507 (3)	C14—H14C	0.9600
C3—C4	1.511 (3)
C18—S—C16	96.67 (8)	C18—C19—H19B	109.3
C12—C11—C15	109.33 (11)	H19A—C19—H19B	108.0
C12—C11—C10	104.37 (11)	C7—C6—C5	128.33 (16)
C15—C11—C10	114.62 (12)	C7—C6—H6	115.8
C12—C11—H11	109.4	C5—C6—H6	115.8
C15—C11—H11	109.4	C6—C7—C14	125.47 (17)
C10—C11—H11	109.4	C6—C7—C8	121.62 (15)
C12—O2—C1	111.34 (10)	C14—C7—C8	112.74 (17)
C8—O4—H4	109.5	N2—C17—C16	112.94 (13)
C9—C10—C11	113.63 (12)	N2—C17—H17A	109.0
C9—C10—C1	115.55 (11)	C16—C17—H17A	109.0
C11—C10—C1	102.81 (11)	N2—C17—H17B	109.0
C9—C10—H10	108.2	C16—C17—H17B	109.0
C11—C10—H10	108.2	H17A—C17—H17B	107.8
C1—C10—H10	108.2	O4—C8—C7	111.77 (14)
O1—C12—O2	121.46 (14)	O4—C8—C9	111.68 (13)
O1—C12—C11	127.91 (14)	C7—C8—C9	111.03 (13)
O2—C12—C11	110.62 (11)	O4—C8—H8	107.4
C2—O3—C3	61.08 (10)	C7—C8—H8	107.4
O3—C2—C3	59.68 (10)	C9—C8—H8	107.4
O3—C2—C1	119.82 (13)	C3—C4—C5	111.69 (15)
C3—C2—C1	125.59 (13)	C3—C4—H4A	109.3
O3—C2—H2	113.7	C5—C4—H4A	109.3
C3—C2—H2	113.7	C3—C4—H4B	109.3
C1—C2—H2	113.7	C5—C4—H4B	109.3
C19—N2—C17	110.84 (12)	H4A—C4—H4B	107.9
C19—N2—C15	110.78 (12)	C17—C16—S	112.55 (13)
C17—N2—C15	107.95 (11)	C17—C16—H16A	109.1
N2—C15—C11	113.93 (11)	S—C16—H16A	109.1
N2—C15—H15A	108.8	C17—C16—H16B	109.1
C11—C15—H15A	108.8	S—C16—H16B	109.1
N2—C15—H15B	108.8	H16A—C16—H16B	107.8
C11—C15—H15B	108.8	C19—C18—S	112.36 (12)
H15A—C15—H15B	107.7	C19—C18—H18A	109.1
C10—C9—C8	115.79 (13)	S—C18—H18A	109.1
C10—C9—H9A	108.3	C19—C18—H18B	109.1
C8—C9—H9A	108.3	S—C18—H18B	109.1
C10—C9—H9B	108.3	H18A—C18—H18B	107.9
C8—C9—H9B	108.3	C3—C13—H13A	109.5
H9A—C9—H9B	107.4	C3—C13—H13B	109.5
O3—C3—C2	59.24 (9)	H13A—C13—H13B	109.5
O3—C3—C13	113.05 (14)	C3—C13—H13C	109.5
C2—C3—C13	122.86 (15)	H13A—C13—H13C	109.5
O3—C3—C4	116.16 (15)	H13B—C13—H13C	109.5
C2—C3—C4	115.81 (15)	C6—C5—C4	111.07 (15)
C13—C3—C4	116.52 (15)	C6—C5—H5A	109.4
O2—C1—C2	107.44 (11)	C4—C5—H5A	109.4
O2—C1—C10	105.77 (10)	C6—C5—H5B	109.4
C2—C1—C10	111.70 (12)	C4—C5—H5B	109.4
O2—C1—H1	110.6	H5A—C5—H5B	108.0
C2—C1—H1	110.6	C7—C14—H14A	109.5
C10—C1—H1	110.6	C7—C14—H14B	109.5
N2—C19—C18	111.59 (15)	H14A—C14—H14B	109.5
N2—C19—H19A	109.3	C7—C14—H14C	109.5
C18—C19—H19A	109.3	H14A—C14—H14C	109.5
N2—C19—H19B	109.3	H14B—C14—H14C	109.5

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N2	0.82	2.21	3.0278 (18)	176
C2—H2···O1i	0.98	2.51	3.2948 (19)	137
C6—H6···O2ii	0.93	2.59	3.2526 (19)	129

Table 1

Hydrogen-bond geometry (, )

DHA	DH	HA	D A	DHA
O4H4N2	0.82	2.21	3.0278(18)	176
C2H2O1i	0.98	2.51	3.2948(19)	137
C6H6O2ii	0.93	2.59	3.2526(19)	129

Symmetry codes: (i) ; (ii) .