(11R)-13-[2-(4-Hydroxy­phen­yl)ethyl­amino]-4,5-ep­oxy-11,13-dihydro­costunolide monohydrate

Nasim, S.; Parkin, S.; Crooks, P.A.

doi:10.1107/S1600536808003863

organic compounds

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ISSN: 2056-9890

Volume 64| Part 3| March 2008| Page o644

doi:10.1107/S1600536808003863

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(11R)-13-[2-(4-Hydroxyphenyl)ethylamino]-4,5-epoxy-11,13-dihydrocostunolide monohydrate

Shama. Nasim,^a Sean Parkin ^b and Peter A. Crooks ^a ^*

^aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA, and ^bDepartment of Chemistry, University of Kentucky, Lexington, KY 40506, USA
^*Correspondence e-mail: pcrooks@email.uky.edu

(Received 25 January 2008; accepted 5 February 2008; online 29 February 2008)

The title compound (systematic name: 12-{[2-(4-hydroxyphenyl)ethyl]aminomethyl}-4,8-dimethyl-3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one monohydrate), C₂₃H₃₁NO₄·H₂O, was obtained by the reaction of tyramine with parthenolide. The configuration of the new chiral center in the title compound is R, establishing the stereospecificity of the amination reaction. The water molecule is disordered over three positions; the site occupancy factors are 0.45, 0.40 and 0.15.

Related literature

For related literature, see: Allen et al. (1987 ); Crooks et al. (2005 ); Desiraju & Steiner (1999 ); Hewlett et al. (1996 ); Nasim et al. (2007a ,b ).

Experimental

Crystal data

C₂₃H₃₁NO₄·H₂O
M_r = 403.50
Monoclinic, P 2₁
a = 10.8307 (7) Å
b = 6.9478 (5) Å
c = 14.4835 (9) Å
β = 94.631 (3)°
V = 1086.32 (12) Å³
Z = 2
Cu Kα radiation
μ = 0.70 mm⁻¹
T = 90.0 (2) K
0.25 × 0.10 × 0.03 mm

Data collection

Bruker X8 Proteum diffractometer
Absorption correction: multi-scan (SADABS in APEX2; Bruker–Nonius, 2004 ) T_min = 0.763, T_max = 0.979
13335 measured reflections
3532 independent reflections
3420 reflections with I > 2σ(I)
R_int = 0.031

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.113
S = 1.07
3532 reflections
276 parameters
7 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.40 e Å⁻³
Δρ_min = −0.20 e Å⁻³
Absolute structure: Flack (1983), 1365 Friedel pairs
Flack parameter: 0.12 (6)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O3	0.94 (3)	2.22 (3)	2.979 (3)	137 (2)
O1′—H1′⋯O1W1ⁱ	0.84	1.75	2.568 (4)	164
O1′—H1′⋯O1W2ⁱ	0.84	2.01	2.832 (6)	166
Symmetry code: (i) $[-x+2, y-{\script{1\over 2}}, -z]$ .

Data collection: APEX2 (Bruker–Nonius, 2004); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 and local procedures.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808003863/hg2375sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808003863/hg2375Isup2.hkl

checkCIF report

Comment top

Parthenolide, is a germacrene sesquiterpene lactone. It has been isolated from several different species of plant in the Asteraceae (Compositae) family, feverfew (Tanacetum parthenium) being one of them. (Hewlett et al., 1996). The title compound was synthesized as part of an ongoing drug discovery effort (Crooks et al., 2005)and is the adduct of the neurotransmiter, tyramine and the cytotoxic sesquiterpene, parthenolide. This compound was found to crystallize as the monohydrate, in contrast to other structurally related parthenolide analogs (Nasim et al., 2007a, 2007b). The side-chain was found to be in a fully extented conformation. The absolute stereochemistry of the newly formed methine carbon at C-11 was found to be R, which is typical of such amine adducts of parthenolide (Nasim et al., 2007a, 2007b). Bond distances and angles within the molecule were quite regular with average normal bond lengths (Allen et al., 1987). A weak hydrogen bond (Desiraju et al., 1999) is observed between N-1H and O3 of the carbonyl oxygen of the 5-membered lactone ring (2.22 (3) A°, 2.97 (3) A°, 137.0 (2) °) (Table 1),

Related literature top

For related literature, see: Allen et al. (1987); Crooks et al. (2005); Desiraju & Steiner (1999); Hewlett et al. (1996); Nasim et al. (2007a,b).

Experimental top

The title compound was prepared utilizing the general procedure reported earlier (Nasim et al., 2007a, 2007b). Anal. (C₂₃H₃₁NO₄. H₂O): C 68.46, H 8.24, N 3.47%. Found C 68.20, H 7.94, N 3.41%.

Computing details top

Data collection: APEX2 (Bruker–Nonius, 2004); cell refinement: APEX2 (Bruker–Nonius, 2004); data reduction: APEX2 (Bruker–Nonius, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX97 (Sheldrick, 2008) and local procedures.

Figures top

	Fig. 1. A view of the asymmetric unit of the title compound, with displacement ellipsoids drawn at the 50% probability level; H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A packing diagram, viewed down the a axis; hydrogen atoms have been omitted for clarity.

12-{[2-(4-hydroxyphenyl)ethyl]aminomethyl}-4,8-dimethyl- 3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one monohydrate top

Crystal data top

C₂₃H₃₁NO₄·H₂O	F(000) = 436
M_r = 403.50	D_x = 1.234 Mg m⁻³
Monoclinic, P2₁	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2yb	Cell parameters from 5637 reflections
a = 10.8307 (7) Å	θ = 3.1–68.0°
b = 6.9478 (5) Å	µ = 0.70 mm⁻¹
c = 14.4835 (9) Å	T = 90 K
β = 94.631 (3)°	Lath, colourless
V = 1086.32 (12) Å³	0.25 × 0.10 × 0.03 mm
Z = 2

Data collection top

Bruker X8 Proteum diffractometer	3532 independent reflections
Radiation source: fine-focus rotating anode	3420 reflections with I > 2σ(I)
Bruker Helios multilayer optics monochromator	R_int = 0.031
Detector resolution: 18 pixels mm^-1	θ_max = 68.1°, θ_min = 3.1°
ω and ϕ scans	h = −12→12
Absorption correction: multi-scan (SADABS in APEX2; Bruker–Nonius, 2004)	k = −8→5
T_min = 0.763, T_max = 0.979	l = −17→17
13335 measured reflections

Refinement top

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 atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.113	w = 1/[σ²(F_o²) + (0.0695P)² + 0.347P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max = 0.009
3532 reflections	Δρ_max = 0.40 e Å⁻³
276 parameters	Δρ_min = −0.21 e Å⁻³
7 restraints	Absolute structure: Flack (1983), 1365 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.12 (6)

Crystal data top

C₂₃H₃₁NO₄·H₂O	V = 1086.32 (12) Å³
M_r = 403.50	Z = 2
Monoclinic, P2₁	Cu Kα radiation
a = 10.8307 (7) Å	µ = 0.70 mm⁻¹
b = 6.9478 (5) Å	T = 90 K
c = 14.4835 (9) Å	0.25 × 0.10 × 0.03 mm
β = 94.631 (3)°

Data collection top

Bruker X8 Proteum diffractometer	3532 independent reflections
Absorption correction: multi-scan (SADABS in APEX2; Bruker–Nonius, 2004)	3420 reflections with I > 2σ(I)
T_min = 0.763, T_max = 0.979	R_int = 0.031
13335 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.113	Δρ_max = 0.40 e Å⁻³
S = 1.07	Δρ_min = −0.21 e Å⁻³
3532 reflections	Absolute structure: Flack (1983), 1365 Friedel pairs
276 parameters	Absolute structure parameter: 0.12 (6)
7 restraints

Special details top

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 > 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.

CIFCHECK squawks about H atoms being detached from their oxygen atom in the third disorder component of the water. They are are in fact 0.85Å from O1W3, but the occupancy factor is only 0.15. They were included so as to get the atom count correct, and no claim is made for their veracity.

This three-component disorder for the water is consistent with the fact that the crystals appeared to be cracking due to solvent loss. The actual crystal chosen was carefully cut so that it did not have any cracks, but still it is quite likely that the three-part disorder is related to this observed tendency for these crystals to dry and crack.

_publ_section_exptl_refinement: H atoms were found in difference Fourier maps and subsequently placed in idealized positions with constrained C—H distances of 0.95 Å (C_sp2—H), 1.00 Å (R₃CH), 0.99 Å (R₂CH₂), 0.98 Å (RCH₃), 0.84 Å (OH) and 0.85 Å (OH₂) except for the NH hydrogen coordinates, which were refined. Hydrogen atom U_iso(H) values were set to 1.2U_eq or 1.5U_eq (RCH₃, OH, OH₂) of the attached atom. Since the water molecule was severely disordered the hydrogen atoms were placed in reasonable but not necessarily correct positions, and were subsequently fixed.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.37395 (12)	0.7648 (2)	0.49755 (9)	0.0254 (3)
O2	0.49033 (12)	0.7364 (2)	0.33035 (10)	0.0271 (3)
O3	0.63676 (15)	0.7794 (3)	0.23432 (11)	0.0412 (4)
C1	0.25041 (19)	0.2241 (3)	0.48640 (15)	0.0280 (4)
H1	0.3290	0.1714	0.5063	0.034*
C2	0.18591 (19)	0.3303 (4)	0.55824 (14)	0.0307 (5)
H2A	0.1861	0.2514	0.6152	0.037*
H2B	0.0987	0.3546	0.5353	0.037*
C3	0.25190 (18)	0.5226 (3)	0.58044 (14)	0.0273 (4)
H3A	0.2013	0.6016	0.6200	0.033*
H3B	0.3328	0.4979	0.6152	0.033*
C4	0.27179 (17)	0.6305 (3)	0.49340 (13)	0.0235 (4)
C5	0.38514 (16)	0.5853 (3)	0.44868 (13)	0.0219 (4)
H5	0.4400	0.4882	0.4824	0.026*
C6	0.39582 (17)	0.5921 (3)	0.34653 (13)	0.0224 (4)
H6	0.3146	0.6296	0.3137	0.027*
C7	0.44268 (17)	0.4046 (3)	0.30577 (14)	0.0237 (4)
H7	0.4961	0.3371	0.3552	0.028*
C8	0.34519 (19)	0.2617 (3)	0.26488 (14)	0.0286 (4)
H8A	0.2733	0.3358	0.2374	0.034*
H8B	0.3807	0.1908	0.2140	0.034*
C9	0.2983 (2)	0.1148 (3)	0.33238 (15)	0.0302 (5)
H9A	0.2557	0.0098	0.2962	0.036*
H9B	0.3705	0.0578	0.3688	0.036*
C10	0.21163 (19)	0.1940 (3)	0.39806 (14)	0.0267 (4)
C11	0.52534 (18)	0.4772 (3)	0.23293 (13)	0.0253 (4)
H11	0.4763	0.4815	0.1714	0.030*
C12	0.55874 (18)	0.6778 (3)	0.26267 (14)	0.0285 (5)
C14	0.08422 (19)	0.2379 (4)	0.35502 (15)	0.0350 (5)
H14A	0.0332	0.2884	0.4024	0.053*
H14B	0.0465	0.1199	0.3285	0.053*
H14C	0.0896	0.3340	0.3060	0.053*
C15	0.15749 (18)	0.7084 (3)	0.44137 (15)	0.0297 (5)
H15A	0.1226	0.8112	0.4776	0.045*
H15B	0.0964	0.6050	0.4308	0.045*
H15C	0.1787	0.7600	0.3817	0.045*
C13	0.63833 (18)	0.3509 (4)	0.22548 (15)	0.0314 (5)
H13A	0.6919	0.3579	0.2841	0.038*
H13B	0.6116	0.2155	0.2161	0.038*
N1	0.70913 (16)	0.4104 (3)	0.14878 (13)	0.0315 (4)
H1N	0.715 (2)	0.545 (5)	0.1522 (19)	0.038*
C2'	0.83004 (18)	0.3144 (4)	0.15110 (14)	0.0316 (5)
H2'1	0.8667	0.3093	0.2159	0.038*
H2'2	0.8861	0.3913	0.1149	0.038*
C3'	0.82123 (19)	0.1106 (4)	0.11202 (15)	0.0340 (5)
H3'1	0.7632	0.0347	0.1470	0.041*
H3'2	0.7871	0.1160	0.0466	0.041*
C4'	0.94557 (18)	0.0102 (4)	0.11730 (14)	0.0289 (5)
C5'	0.9675 (2)	−0.1565 (4)	0.16744 (14)	0.0332 (5)
H5'	0.9027	−0.2106	0.1995	0.040*
C6'	1.0815 (2)	−0.2469 (4)	0.17225 (15)	0.0362 (5)
H6'	1.0937	−0.3632	0.2063	0.043*
C7'	1.17797 (19)	−0.1682 (4)	0.12744 (14)	0.0367 (6)
C8'	1.15766 (19)	−0.0002 (4)	0.07758 (14)	0.0350 (5)
H8'	1.2231	0.0558	0.0469	0.042*
C9'	1.04241 (19)	0.0871 (4)	0.07215 (14)	0.0309 (5)
H9'	1.0294	0.2017	0.0369	0.037*
O1'	1.28929 (16)	−0.2601 (4)	0.13551 (11)	0.0526 (5)
H1'	1.3325	−0.2226	0.0934	0.079*
O1W1	0.5653 (4)	0.2900 (9)	−0.0060 (3)	0.0465 (12)	0.45
H1W1	0.5124	0.2239	0.0206	0.070*	0.45
H2W1	0.5295	0.3987	−0.0044	0.070*	0.45
O1W2	0.5563 (4)	0.4210 (10)	−0.0128 (3)	0.0465 (12)	0.40
H1W2	0.4812	0.3847	−0.0207	0.070*	0.40
H2W2	0.5479	0.5354	0.0065	0.070*	0.40
O1W3	0.5279 (11)	−0.0765 (18)	0.0245 (7)	0.036 (2)*	0.15
H1W3	0.4928	0.0289	0.0367	0.054*	0.15
H2W3	0.6044	−0.0506	0.0349	0.054*	0.15

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0240 (6)	0.0190 (8)	0.0332 (7)	−0.0028 (6)	0.0026 (5)	−0.0055 (6)
O2	0.0275 (7)	0.0209 (8)	0.0336 (7)	−0.0044 (6)	0.0079 (5)	−0.0018 (6)
O3	0.0432 (9)	0.0406 (11)	0.0417 (9)	−0.0141 (8)	0.0154 (7)	−0.0025 (8)
C1	0.0289 (9)	0.0174 (11)	0.0371 (11)	−0.0053 (8)	−0.0010 (8)	0.0026 (9)
C2	0.0308 (10)	0.0297 (12)	0.0313 (10)	−0.0076 (10)	0.0004 (8)	0.0020 (9)
C3	0.0248 (9)	0.0281 (13)	0.0289 (10)	−0.0036 (9)	0.0025 (7)	−0.0031 (9)
C4	0.0219 (9)	0.0194 (11)	0.0288 (9)	−0.0021 (8)	0.0001 (7)	−0.0048 (8)
C5	0.0204 (9)	0.0166 (10)	0.0282 (9)	−0.0009 (7)	−0.0016 (7)	−0.0018 (8)
C6	0.0180 (8)	0.0191 (11)	0.0301 (10)	−0.0009 (7)	0.0020 (7)	−0.0006 (8)
C7	0.0231 (9)	0.0204 (11)	0.0276 (9)	0.0025 (8)	0.0028 (7)	−0.0009 (8)
C8	0.0311 (10)	0.0238 (12)	0.0306 (10)	−0.0030 (9)	0.0012 (8)	−0.0054 (9)
C9	0.0355 (11)	0.0178 (12)	0.0369 (11)	−0.0033 (9)	0.0006 (8)	−0.0033 (9)
C10	0.0295 (10)	0.0176 (11)	0.0323 (10)	−0.0070 (8)	−0.0014 (8)	0.0018 (8)
C11	0.0243 (9)	0.0273 (12)	0.0240 (9)	0.0033 (8)	0.0000 (7)	−0.0008 (8)
C12	0.0253 (9)	0.0319 (13)	0.0283 (10)	−0.0023 (9)	0.0016 (8)	0.0032 (9)
C14	0.0293 (10)	0.0384 (14)	0.0367 (11)	−0.0051 (10)	−0.0019 (8)	−0.0033 (10)
C15	0.0207 (9)	0.0282 (12)	0.0403 (11)	0.0029 (8)	0.0031 (8)	−0.0022 (9)
C13	0.0268 (10)	0.0359 (13)	0.0316 (10)	0.0075 (9)	0.0034 (8)	0.0014 (9)
N1	0.0259 (9)	0.0344 (12)	0.0346 (9)	0.0058 (8)	0.0045 (7)	0.0057 (8)
C2'	0.0208 (9)	0.0407 (15)	0.0331 (10)	0.0041 (9)	0.0016 (8)	0.0003 (10)
C3'	0.0233 (10)	0.0441 (15)	0.0347 (10)	0.0005 (10)	0.0035 (8)	0.0018 (10)
C4'	0.0230 (10)	0.0358 (13)	0.0279 (10)	−0.0010 (9)	0.0030 (7)	−0.0053 (9)
C5'	0.0329 (10)	0.0375 (14)	0.0291 (10)	−0.0032 (10)	0.0014 (8)	−0.0015 (10)
C6'	0.0442 (12)	0.0331 (13)	0.0303 (10)	0.0037 (11)	−0.0025 (9)	−0.0003 (10)
C7'	0.0313 (10)	0.0530 (17)	0.0249 (9)	0.0134 (11)	−0.0037 (8)	−0.0071 (10)
C8'	0.0240 (10)	0.0523 (16)	0.0290 (10)	0.0037 (10)	0.0049 (8)	−0.0002 (10)
C9'	0.0260 (10)	0.0365 (14)	0.0308 (10)	0.0020 (9)	0.0051 (8)	0.0031 (10)
O1'	0.0398 (9)	0.0826 (15)	0.0345 (9)	0.0333 (10)	−0.0025 (7)	−0.0012 (9)
O1W1	0.0196 (11)	0.088 (4)	0.0315 (12)	−0.004 (2)	0.0016 (9)	−0.010 (3)
O1W2	0.0196 (11)	0.088 (4)	0.0315 (12)	−0.004 (2)	0.0016 (9)	−0.010 (3)

Geometric parameters (Å, º) top

O1—C5	1.444 (3)	C14—H14C	0.9800
O1—C4	1.445 (2)	C15—H15A	0.9800
O2—C12	1.339 (3)	C15—H15B	0.9800
O2—C6	1.465 (2)	C15—H15C	0.9800
O3—C12	1.199 (3)	C13—N1	1.460 (3)
C1—C10	1.330 (3)	C13—H13A	0.9900
C1—C2	1.494 (3)	C13—H13B	0.9900
C1—H1	0.9500	N1—C2'	1.468 (3)
C2—C3	1.537 (3)	N1—H1N	0.94 (3)
C2—H2A	0.9900	C2'—C3'	1.525 (4)
C2—H2B	0.9900	C2'—H2'1	0.9900
C3—C4	1.497 (3)	C2'—H2'2	0.9900
C3—H3A	0.9900	C3'—C4'	1.513 (3)
C3—H3B	0.9900	C3'—H3'1	0.9900
C4—C5	1.468 (3)	C3'—H3'2	0.9900
C4—C15	1.498 (3)	C4'—C5'	1.377 (4)
C5—C6	1.494 (3)	C4'—C9'	1.387 (3)
C5—H5	1.0000	C5'—C6'	1.382 (3)
C6—C7	1.533 (3)	C5'—H5'	0.9500
C6—H6	1.0000	C6'—C7'	1.386 (3)
C7—C11	1.524 (3)	C6'—H6'	0.9500
C7—C8	1.533 (3)	C7'—O1'	1.361 (3)
C7—H7	1.0000	C7'—C8'	1.381 (4)
C8—C9	1.528 (3)	C8'—C9'	1.384 (3)
C8—H8A	0.9900	C8'—H8'	0.9500
C8—H8B	0.9900	C9'—H9'	0.9500
C9—C10	1.494 (3)	O1'—H1'	0.8400
C9—H9A	0.9900	O1W1—H1W1	0.8500
C9—H9B	0.9900	O1W1—H2W1	0.8500
C10—C14	1.499 (3)	O1W1—H1W2	1.1302
C11—C12	1.494 (3)	O1W2—H2W1	0.3580
C11—C13	1.517 (3)	O1W2—H1W2	0.8500
C11—H11	1.0000	O1W2—H2W2	0.8500
C14—H14A	0.9800	O1W3—H1W3	0.8500
C14—H14B	0.9800	O1W3—H2W3	0.8500

C5—O1—C4	61.06 (12)	C7—C11—H11	109.1
C12—O2—C6	110.10 (16)	O3—C12—O2	121.2 (2)
C10—C1—C2	128.2 (2)	O3—C12—C11	127.7 (2)
C10—C1—H1	115.9	O2—C12—C11	111.07 (17)
C2—C1—H1	115.9	C10—C14—H14A	109.5
C1—C2—C3	109.84 (17)	C10—C14—H14B	109.5
C1—C2—H2A	109.7	H14A—C14—H14B	109.5
C3—C2—H2A	109.7	C10—C14—H14C	109.5
C1—C2—H2B	109.7	H14A—C14—H14C	109.5
C3—C2—H2B	109.7	H14B—C14—H14C	109.5
H2A—C2—H2B	108.2	C4—C15—H15A	109.5
C4—C3—C2	110.81 (16)	C4—C15—H15B	109.5
C4—C3—H3A	109.5	H15A—C15—H15B	109.5
C2—C3—H3A	109.5	C4—C15—H15C	109.5
C4—C3—H3B	109.5	H15A—C15—H15C	109.5
C2—C3—H3B	109.5	H15B—C15—H15C	109.5
H3A—C3—H3B	108.1	N1—C13—C11	111.50 (19)
O1—C4—C5	59.43 (12)	N1—C13—H13A	109.3
O1—C4—C3	116.76 (16)	C11—C13—H13A	109.3
C5—C4—C3	116.55 (18)	N1—C13—H13B	109.3
O1—C4—C15	112.73 (17)	C11—C13—H13B	109.3
C5—C4—C15	122.83 (17)	H13A—C13—H13B	108.0
C3—C4—C15	115.82 (17)	C13—N1—C2'	112.11 (18)
O1—C5—C4	59.51 (12)	C13—N1—H1N	106.4 (16)
O1—C5—C6	118.33 (17)	C2'—N1—H1N	113.1 (16)
C4—C5—C6	124.39 (16)	N1—C2'—C3'	112.61 (18)
O1—C5—H5	114.5	N1—C2'—H2'1	109.1
C4—C5—H5	114.5	C3'—C2'—H2'1	109.1
C6—C5—H5	114.5	N1—C2'—H2'2	109.1
O2—C6—C5	106.91 (15)	C3'—C2'—H2'2	109.1
O2—C6—C7	105.23 (14)	H2'1—C2'—H2'2	107.8
C5—C6—C7	114.15 (17)	C4'—C3'—C2'	112.36 (18)
O2—C6—H6	110.1	C4'—C3'—H3'1	109.1
C5—C6—H6	110.1	C2'—C3'—H3'1	109.1
C7—C6—H6	110.1	C4'—C3'—H3'2	109.1
C11—C7—C6	102.52 (17)	C2'—C3'—H3'2	109.1
C11—C7—C8	111.82 (16)	H3'1—C3'—H3'2	107.9
C6—C7—C8	117.38 (16)	C5'—C4'—C9'	117.9 (2)
C11—C7—H7	108.2	C5'—C4'—C3'	121.9 (2)
C6—C7—H7	108.2	C9'—C4'—C3'	120.2 (2)
C8—C7—H7	108.2	C4'—C5'—C6'	121.6 (2)
C9—C8—C7	116.07 (17)	C4'—C5'—H5'	119.2
C9—C8—H8A	108.3	C6'—C5'—H5'	119.2
C7—C8—H8A	108.3	C5'—C6'—C7'	120.1 (2)
C9—C8—H8B	108.3	C5'—C6'—H6'	120.0
C7—C8—H8B	108.3	C7'—C6'—H6'	120.0
H8A—C8—H8B	107.4	O1'—C7'—C8'	123.0 (2)
C10—C9—C8	114.82 (19)	O1'—C7'—C6'	118.1 (2)
C10—C9—H9A	108.6	C8'—C7'—C6'	118.9 (2)
C8—C9—H9A	108.6	C7'—C8'—C9'	120.3 (2)
C10—C9—H9B	108.6	C7'—C8'—H8'	119.8
C8—C9—H9B	108.6	C9'—C8'—H8'	119.8
H9A—C9—H9B	107.5	C8'—C9'—C4'	121.1 (2)
C1—C10—C9	120.28 (19)	C8'—C9'—H9'	119.4
C1—C10—C14	125.2 (2)	C4'—C9'—H9'	119.4
C9—C10—C14	114.49 (18)	C7'—O1'—H1'	109.5
C12—C11—C13	112.47 (17)	H1W1—O1W1—H2W1	98.2
C12—C11—C7	104.54 (17)	H1W1—O1W1—H1W2	80.6
C13—C11—C7	112.35 (18)	H2W1—O1W2—H2W2	100.5
C12—C11—H11	109.1	H1W2—O1W2—H2W2	101.3
C13—C11—H11	109.1	H1W3—O1W3—H2W3	103.2

C10—C1—C2—C3	−108.4 (2)	C8—C9—C10—C14	73.6 (2)
C1—C2—C3—C4	49.9 (2)	C6—C7—C11—C12	21.76 (18)
C5—O1—C4—C3	106.5 (2)	C8—C7—C11—C12	148.37 (17)
C5—O1—C4—C15	−115.80 (19)	C6—C7—C11—C13	144.01 (17)
C2—C3—C4—O1	−154.25 (17)	C8—C7—C11—C13	−89.4 (2)
C2—C3—C4—C5	−86.9 (2)	C6—O2—C12—O3	175.4 (2)
C2—C3—C4—C15	69.3 (2)	C6—O2—C12—C11	−5.9 (2)
C4—O1—C5—C6	115.29 (19)	C13—C11—C12—O3	45.5 (3)
C3—C4—C5—O1	−106.82 (19)	C7—C11—C12—O3	167.7 (2)
C15—C4—C5—O1	98.8 (2)	C13—C11—C12—O2	−133.00 (18)
O1—C4—C5—C6	−105.3 (2)	C7—C11—C12—O2	−10.8 (2)
C3—C4—C5—C6	147.85 (19)	C12—C11—C13—N1	−68.5 (2)
C15—C4—C5—C6	−6.5 (3)	C7—C11—C13—N1	173.84 (18)
C12—O2—C6—C5	141.89 (17)	C11—C13—N1—C2'	169.26 (19)
C12—O2—C6—C7	20.2 (2)	C13—N1—C2'—C3'	80.1 (2)
O1—C5—C6—O2	48.0 (2)	N1—C2'—C3'—C4'	−178.24 (18)
C4—C5—C6—O2	118.8 (2)	C2'—C3'—C4'—C5'	119.0 (2)
O1—C5—C6—C7	163.93 (15)	C2'—C3'—C4'—C9'	−59.9 (3)
C4—C5—C6—C7	−125.3 (2)	C9'—C4'—C5'—C6'	−0.8 (3)
O2—C6—C7—C11	−25.34 (18)	C3'—C4'—C5'—C6'	−179.7 (2)
C5—C6—C7—C11	−142.24 (16)	C4'—C5'—C6'—C7'	1.3 (3)
O2—C6—C7—C8	−148.29 (17)	C5'—C6'—C7'—O1'	178.7 (2)
C5—C6—C7—C8	94.8 (2)	C5'—C6'—C7'—C8'	−0.6 (3)
C11—C7—C8—C9	153.28 (18)	O1'—C7'—C8'—C9'	−179.8 (2)
C6—C7—C8—C9	−88.7 (2)	C6'—C7'—C8'—C9'	−0.4 (3)
C7—C8—C9—C10	74.3 (2)	C7'—C8'—C9'—C4'	0.9 (3)
C2—C1—C10—C9	169.1 (2)	C5'—C4'—C9'—C8'	−0.3 (3)
C2—C1—C10—C14	−9.4 (4)	C3'—C4'—C9'—C8'	178.7 (2)
C8—C9—C10—C1	−105.0 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O3	0.94 (3)	2.22 (3)	2.979 (3)	137 (2)
O1′—H1′···O1W1ⁱ	0.84	1.75	2.568 (4)	164
O1′—H1′···O1W2ⁱ	0.84	2.01	2.832 (6)	166

Symmetry code: (i) −x+2, y−1/2, −z.

Experimental details

Crystal data
Chemical formula	C₂₃H₃₁NO₄·H₂O
M_r	403.50
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	90
a, b, c (Å)	10.8307 (7), 6.9478 (5), 14.4835 (9)
β (°)	94.631 (3)
V (Å³)	1086.32 (12)
Z	2
Radiation type	Cu Kα
µ (mm⁻¹)	0.70
Crystal size (mm)	0.25 × 0.10 × 0.03

Data collection
Diffractometer	Bruker X8 Proteum diffractometer
Absorption correction	Multi-scan (SADABS in APEX2; Bruker–Nonius, 2004)
T_min, T_max	0.763, 0.979
No. of measured, independent and observed [I > 2σ(I)] reflections	13335, 3532, 3420
R_int	0.031
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.113, 1.07
No. of reflections	3532
No. of parameters	276
No. of restraints	7
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.40, −0.21
Absolute structure	Flack (1983), 1365 Friedel pairs
Absolute structure parameter	0.12 (6)

Computer programs: APEX2 (Bruker–Nonius, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELX97 (Sheldrick, 2008) and local procedures.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O3	0.94 (3)	2.22 (3)	2.979 (3)	137 (2)
O1'—H1'···O1W1ⁱ	0.84	1.75	2.568 (4)	164.4
O1'—H1'···O1W2ⁱ	0.84	2.01	2.832 (6)	166.3

Symmetry code: (i) −x+2, y−1/2, −z.

Acknowledgements

Financial support from the Kentucky Lung Cancer Research Program is gratefully acknowleged.

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19. CrossRef Web of Science Google Scholar
Bruker–Nonius (2004). APEX2. Bruker–Nonius AXS Inc., Madison, Wisconsin, USA. Google Scholar
Crooks, P. A., Jordan, C. T. & Wei, X. (2005). US Patent Appl. Publ. Cont.-Part. US Ser. No. 888 274. Google Scholar
Desiraju, G. R. & Steiner, T. D. (1999). The Weak Hydrogen Bond in Structural Chemistry and Biology, p. 13. Oxford University Press. Google Scholar
Hewlett, M. J., Begley, M. J., Groenewegen, W. A., Heptinstall, S., Knight, D. W., May, J., Salan, U. & Toplis, D. (1996). J. Chem. Soc. Perkin Trans. 1, pp. 1979–1986.. CrossRef Google Scholar
Nasim, S., Parkin, S. & Crooks, P. A. (2007a). Acta Cryst. E63, o3922. Web of Science CSD CrossRef IUCr Journals Google Scholar
Nasim, S., Parkin, S. & Crooks, P. A. (2007b). Acta Cryst. E63, o4274. Web of Science CSD CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

(11R)-13-[2-(4-Hy­droxy­phen­yl)ethyl­amino]-4,5-ep­­oxy-11,13-di­hydro­costunolide monohydrate

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

(11R)-13-[2-(4-Hydroxyphenyl)ethylamino]-4,5-epoxy-11,13-dihydrocostunolide monohydrate