(11R,13R)-13-(Tetra­lin-1-ylamino)-4,5-ep­oxy-11,13-dihydro­costunolide

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

doi:10.1107/S1600536808003322

organic compounds

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ISSN: 2056-9890

Volume 64| Part 3| March 2008| Page o639

doi:10.1107/S1600536808003322

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(11R,13R)-13-(Tetralin-1-ylamino)-4,5-epoxy-11,13-dihydrocostunolide

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 30 January 2008; online 29 February 2008)

The title compound [systematic name: (12R)-4,8-dimethyl-12-[(1′R)-1′,2′,3′,4′-tetrahydro-1′-naphthyl)aminomethyl]-3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one}, C₂₅H₃₃NO₃, was formed from the reaction of (1R)-1-aminotetralin with parthenolide in methanolic solution. X-ray crystal structure analysis determined that the configuration of the new chiral center in the title compound was R.

Related literature

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

Experimental

Crystal data

C₂₅H₃₃NO₃
M_r = 395.52
Orthorhombic, P 2₁ 2₁ 2₁
a = 8.4952 (13) Å
b = 13.1852 (19) Å
c = 18.771 (3) Å
V = 2102.6 (6) Å³
Z = 4
Cu Kα radiation
μ = 0.64 mm⁻¹
T = 90.0 (2) K
0.30 × 0.28 × 0.18 mm

Data collection

Bruker X8 Proteum diffractometer
Absorption correction: multi-scan (SADABS in APEX2; Bruker Nonius, 2004 ) T_min = 0.782, T_max = 0.894
26461 measured reflections
3849 independent reflections
3813 reflections with I > 2σ(I)
R_int = 0.033

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.110
S = 1.06
3849 reflections
269 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ), 1623 Friedel pairs
Flack parameter: 0.06 (5)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O3	1.01 (3)	2.32 (3)	2.992 (2)	123.5 (18)

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/S1600536808003322/hg2376sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808003322/hg2376Isup2.hkl

checkCIF report

Comment top

Due to the interesting biological activity of parthenolide, we have synthesized a series of amino analogs of parthenolide (Crooks et al., 2005). In order to confirm the configuration of the newly formed methine carbon at C-11 in these molecules, and to obtain more detailed information on the structural conformation of the molecule that may be of value in structure activity relationship studies, the X-ray structure determination of the title compound has been carried out and the results are presented below. The absolute stereochemistry of the newly formed methine at C-11 was found to be R, which is typical in structurally related C-11 aminoparthenolide analogs that result from the reaction of an secondary amino compound with parthenolide (Nasim et al., 2007a, 2007b). Bond distances and angles within the molecule were quite regular with normal bond lengths (Allen et al., 1987). A hydrogen bond is observed between N-1H and O3 of the carbonyl oxygen of the 5-membered lactone ring (Desiraju et al.,1999) (2.32 (3) A°, 2.99 (2) A°, 123.5 (18)°) (Table 1).

Related literature top

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

Experimental top

The title compound was prepared utilizing the general procedure reported earlier (Nasim et al., 2007a, 2007b).

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: SHELXL97 (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.

(12R)-4,8-dimethyl-12-[(1'R)-1',2',3',4'-tetrahydro-1'-naphthyl)aminomethyl]- 3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one top

Crystal data top

C₂₅H₃₃NO₃	F(000) = 856
M_r = 395.52	D_x = 1.249 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9023 reflections
a = 8.4952 (13) Å	θ = 4.1–68.6°
b = 13.1852 (19) Å	µ = 0.64 mm⁻¹
c = 18.771 (3) Å	T = 90 K
V = 2102.6 (6) Å³	Cut block, colourless
Z = 4	0.30 × 0.28 × 0.18 mm

Data collection top

Bruker X8 Proteum diffractometer	3849 independent reflections
Radiation source: fine-focus rotating anode	3813 reflections with I > 2σ(I)
Helios multilayer optics monochromator	R_int = 0.033
Detector resolution: 18 pixels mm^-1	θ_max = 68.6°, θ_min = 4.1°
ω and ϕ scans	h = −10→10
Absorption correction: multi-scan (SADABS in APEX2; Bruker Nonius, 2004)	k = −15→15
T_min = 0.782, T_max = 0.894	l = −22→22
26461 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.043	w = 1/[σ²(F_o²) + (0.0627P)² + 0.7419P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.110	(Δ/σ)_max < 0.001
S = 1.06	Δρ_max = 0.34 e Å⁻³
3849 reflections	Δρ_min = −0.22 e Å⁻³
269 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0147 (7)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983)
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.06 (5)

Crystal data top

C₂₅H₃₃NO₃	V = 2102.6 (6) Å³
M_r = 395.52	Z = 4
Orthorhombic, P2₁2₁2₁	Cu Kα radiation
a = 8.4952 (13) Å	µ = 0.64 mm⁻¹
b = 13.1852 (19) Å	T = 90 K
c = 18.771 (3) Å	0.30 × 0.28 × 0.18 mm

Data collection top

Bruker X8 Proteum diffractometer	3849 independent reflections
Absorption correction: multi-scan (SADABS in APEX2; Bruker Nonius, 2004)	3813 reflections with I > 2σ(I)
T_min = 0.782, T_max = 0.894	R_int = 0.033
26461 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.110	Δρ_max = 0.34 e Å⁻³
S = 1.06	Δρ_min = −0.22 e Å⁻³
3849 reflections	Absolute structure: Flack (1983)
269 parameters	Absolute structure parameter: 0.06 (5)
0 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.

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

	x	y	z	U_iso*/U_eq
N1	0.5361 (2)	0.68044 (12)	0.44880 (10)	0.0365 (4)
H1N	0.597 (3)	0.6648 (19)	0.4042 (13)	0.044*
O1	0.79418 (15)	0.18237 (9)	0.50676 (7)	0.0315 (3)
O2	0.76245 (16)	0.38600 (10)	0.45744 (7)	0.0363 (3)
O3	0.7062 (2)	0.50746 (12)	0.38018 (8)	0.0508 (4)
C1	0.5083 (2)	0.23023 (14)	0.67140 (10)	0.0317 (4)
H1	0.4217	0.2389	0.6400	0.038*
C2	0.5720 (3)	0.12589 (15)	0.67700 (11)	0.0389 (5)
H2A	0.4851	0.0776	0.6862	0.047*
H2B	0.6468	0.1220	0.7173	0.047*
C3	0.6562 (3)	0.09719 (14)	0.60747 (11)	0.0355 (4)
H3A	0.7194	0.0351	0.6152	0.043*
H3B	0.5770	0.0824	0.5702	0.043*
C4	0.7615 (2)	0.18070 (13)	0.58256 (9)	0.0286 (4)
C5	0.6906 (2)	0.25699 (13)	0.53651 (9)	0.0259 (4)
H5	0.5768	0.2449	0.5260	0.031*
C6	0.7381 (2)	0.36493 (13)	0.53249 (10)	0.0275 (4)
H6	0.8375	0.3764	0.5598	0.033*
C7	0.6115 (2)	0.43955 (12)	0.55609 (10)	0.0264 (4)
H7	0.5066	0.4092	0.5449	0.032*
C8	0.6106 (2)	0.47212 (14)	0.63395 (10)	0.0339 (4)
H8A	0.5834	0.5450	0.6361	0.041*
H8B	0.7186	0.4646	0.6531	0.041*
C9	0.4981 (3)	0.41421 (15)	0.68229 (10)	0.0358 (4)
H9A	0.4775	0.4555	0.7254	0.043*
H9B	0.3967	0.4052	0.6571	0.043*
C10	0.5572 (2)	0.31281 (15)	0.70481 (10)	0.0319 (4)
C11	0.6388 (2)	0.52750 (13)	0.50509 (10)	0.0316 (4)
H11	0.7222	0.5723	0.5257	0.038*
C12	0.7038 (3)	0.47736 (15)	0.44038 (11)	0.0368 (4)
C13	0.4960 (2)	0.59112 (14)	0.48985 (11)	0.0341 (4)
H13A	0.4181	0.5502	0.4631	0.041*
H13B	0.4470	0.6121	0.5354	0.041*
C14	0.6724 (3)	0.31561 (18)	0.76475 (11)	0.0470 (5)
H14A	0.7063	0.2464	0.7760	0.070*
H14B	0.6226	0.3460	0.8067	0.070*
H14C	0.7639	0.3563	0.7509	0.070*
C15	0.9019 (2)	0.20263 (16)	0.62710 (11)	0.0378 (5)
H15A	0.9661	0.1412	0.6315	0.057*
H15B	0.8679	0.2247	0.6745	0.057*
H15C	0.9642	0.2564	0.6047	0.057*
C2'	0.4037 (2)	0.74860 (14)	0.43624 (11)	0.0334 (4)
H2'	0.3648	0.7720	0.4838	0.040*
C3'	0.4645 (2)	0.84025 (14)	0.39714 (10)	0.0299 (4)
C4'	0.5552 (2)	0.90996 (15)	0.43477 (11)	0.0352 (4)
H4'	0.5774	0.8975	0.4836	0.042*
C5'	0.6133 (2)	0.99567 (15)	0.40354 (11)	0.0359 (4)
H5'	0.6759	1.0419	0.4301	0.043*
C6'	0.5793 (2)	1.01419 (15)	0.33243 (11)	0.0336 (4)
H6'	0.6179	1.0738	0.3100	0.040*
C7'	0.4899 (2)	0.94620 (15)	0.29450 (10)	0.0329 (4)
H7'	0.4676	0.9593	0.2458	0.040*
C8'	0.4317 (2)	0.85882 (14)	0.32608 (10)	0.0306 (4)
C9'	0.3252 (2)	0.79086 (16)	0.28324 (10)	0.0365 (4)
H9'1	0.3710	0.7807	0.2353	0.044*
H9'2	0.2216	0.8242	0.2773	0.044*
C10'	0.3021 (3)	0.68777 (16)	0.31904 (11)	0.0398 (5)
H10A	0.2149	0.6508	0.2956	0.048*
H10B	0.3991	0.6468	0.3142	0.048*
C11'	0.2645 (2)	0.70309 (14)	0.39664 (10)	0.0346 (4)
H11A	0.2364	0.6371	0.4184	0.042*
H11B	0.1725	0.7488	0.4012	0.042*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0365 (9)	0.0270 (8)	0.0461 (9)	0.0004 (7)	−0.0010 (7)	0.0058 (7)
O1	0.0324 (6)	0.0278 (6)	0.0343 (6)	0.0068 (6)	0.0029 (5)	−0.0040 (5)
O2	0.0362 (7)	0.0304 (7)	0.0421 (7)	0.0045 (6)	0.0123 (6)	0.0074 (6)
O3	0.0659 (11)	0.0398 (8)	0.0465 (9)	0.0060 (8)	0.0143 (8)	0.0147 (7)
C1	0.0326 (9)	0.0326 (9)	0.0299 (8)	−0.0051 (8)	0.0050 (7)	0.0005 (7)
C2	0.0499 (12)	0.0284 (9)	0.0383 (10)	−0.0087 (9)	0.0034 (9)	0.0038 (8)
C3	0.0433 (11)	0.0207 (8)	0.0424 (11)	0.0012 (8)	−0.0013 (9)	0.0006 (8)
C4	0.0293 (9)	0.0231 (8)	0.0333 (9)	0.0058 (7)	0.0009 (7)	−0.0009 (7)
C5	0.0229 (8)	0.0237 (8)	0.0311 (8)	0.0018 (7)	0.0010 (7)	−0.0026 (7)
C6	0.0226 (8)	0.0251 (8)	0.0347 (9)	−0.0021 (7)	−0.0016 (7)	0.0040 (7)
C7	0.0246 (8)	0.0195 (8)	0.0350 (9)	−0.0003 (7)	−0.0022 (7)	0.0006 (7)
C8	0.0423 (11)	0.0220 (8)	0.0376 (10)	−0.0012 (8)	−0.0042 (8)	−0.0033 (8)
C9	0.0395 (11)	0.0324 (10)	0.0355 (10)	0.0075 (9)	0.0057 (8)	−0.0070 (8)
C10	0.0338 (10)	0.0320 (9)	0.0299 (9)	0.0001 (8)	0.0051 (8)	−0.0013 (7)
C11	0.0308 (9)	0.0213 (8)	0.0427 (10)	−0.0030 (7)	−0.0009 (8)	0.0039 (8)
C12	0.0364 (10)	0.0291 (9)	0.0448 (11)	−0.0018 (8)	0.0051 (8)	0.0089 (8)
C13	0.0346 (10)	0.0239 (8)	0.0438 (10)	0.0001 (8)	−0.0017 (8)	0.0043 (8)
C14	0.0593 (14)	0.0448 (12)	0.0369 (10)	−0.0012 (11)	−0.0121 (10)	−0.0034 (9)
C15	0.0315 (10)	0.0373 (10)	0.0444 (11)	0.0078 (8)	−0.0088 (8)	0.0016 (8)
C2'	0.0320 (10)	0.0286 (9)	0.0395 (10)	0.0020 (8)	−0.0002 (8)	0.0009 (8)
C3'	0.0257 (8)	0.0277 (9)	0.0364 (9)	0.0022 (7)	−0.0014 (8)	0.0005 (7)
C4'	0.0334 (10)	0.0326 (10)	0.0395 (10)	−0.0022 (8)	−0.0060 (8)	0.0041 (8)
C5'	0.0299 (9)	0.0312 (9)	0.0466 (11)	−0.0040 (8)	−0.0008 (8)	0.0013 (8)
C6'	0.0263 (9)	0.0292 (9)	0.0454 (10)	0.0008 (8)	0.0033 (8)	0.0070 (8)
C7'	0.0300 (9)	0.0350 (10)	0.0338 (9)	0.0037 (8)	0.0022 (8)	0.0041 (8)
C8'	0.0257 (9)	0.0290 (9)	0.0372 (10)	0.0047 (7)	0.0033 (8)	−0.0031 (8)
C9'	0.0335 (10)	0.0414 (11)	0.0346 (9)	−0.0054 (9)	0.0026 (8)	−0.0099 (8)
C10'	0.0389 (11)	0.0366 (10)	0.0439 (11)	−0.0079 (9)	0.0013 (9)	−0.0101 (9)
C11'	0.0334 (9)	0.0290 (9)	0.0415 (10)	−0.0010 (8)	0.0005 (8)	0.0021 (8)

Geometric parameters (Å, º) top

N1—C13	1.448 (2)	C11—C12	1.489 (3)
N1—C2'	1.459 (2)	C11—C13	1.503 (3)
N1—H1N	1.01 (3)	C11—H11	1.0000
O1—C5	1.433 (2)	C13—H13A	0.9900
O1—C4	1.450 (2)	C13—H13B	0.9900
O2—C12	1.342 (2)	C14—H14A	0.9800
O2—C6	1.451 (2)	C14—H14B	0.9800
O3—C12	1.198 (2)	C14—H14C	0.9800
C1—C10	1.324 (3)	C15—H15A	0.9800
C1—C2	1.482 (3)	C15—H15B	0.9800
C1—H1	0.9500	C15—H15C	0.9800
C2—C3	1.536 (3)	C2'—C3'	1.505 (3)
C2—H2A	0.9900	C2'—C11'	1.521 (3)
C2—H2B	0.9900	C2'—H2'	1.0000
C3—C4	1.494 (3)	C3'—C8'	1.384 (3)
C3—H3A	0.9900	C3'—C4'	1.392 (3)
C3—H3B	0.9900	C4'—C5'	1.365 (3)
C4—C5	1.457 (2)	C4'—H4'	0.9500
C4—C15	1.485 (3)	C5'—C6'	1.387 (3)
C5—C6	1.481 (2)	C5'—H5'	0.9500
C5—H5	1.0000	C6'—C7'	1.374 (3)
C6—C7	1.523 (2)	C6'—H6'	0.9500
C6—H6	1.0000	C7'—C8'	1.387 (3)
C7—C11	1.522 (2)	C7'—H7'	0.9500
C7—C8	1.523 (3)	C8'—C9'	1.506 (3)
C7—H7	1.0000	C9'—C10'	1.529 (3)
C8—C9	1.523 (3)	C9'—H9'1	0.9900
C8—H8A	0.9900	C9'—H9'2	0.9900
C8—H8B	0.9900	C10'—C11'	1.505 (3)
C9—C10	1.489 (3)	C10'—H10A	0.9900
C9—H9A	0.9900	C10'—H10B	0.9900
C9—H9B	0.9900	C11'—H11A	0.9900
C10—C14	1.492 (3)	C11'—H11B	0.9900

C13—N1—C2'	113.94 (16)	C7—C11—H11	108.4
C13—N1—H1N	113.4 (14)	O3—C12—O2	121.07 (19)
C2'—N1—H1N	113.0 (14)	O3—C12—C11	128.96 (19)
C5—O1—C4	60.70 (11)	O2—C12—C11	109.95 (16)
C12—O2—C6	110.53 (15)	N1—C13—C11	111.42 (16)
C10—C1—C2	127.98 (19)	N1—C13—H13A	109.3
C10—C1—H1	116.0	C11—C13—H13A	109.3
C2—C1—H1	116.0	N1—C13—H13B	109.3
C1—C2—C3	109.79 (16)	C11—C13—H13B	109.3
C1—C2—H2A	109.7	H13A—C13—H13B	108.0
C3—C2—H2A	109.7	C10—C14—H14A	109.5
C1—C2—H2B	109.7	C10—C14—H14B	109.5
C3—C2—H2B	109.7	H14A—C14—H14B	109.5
H2A—C2—H2B	108.2	C10—C14—H14C	109.5
C4—C3—C2	111.31 (15)	H14A—C14—H14C	109.5
C4—C3—H3A	109.4	H14B—C14—H14C	109.5
C2—C3—H3A	109.4	C4—C15—H15A	109.5
C4—C3—H3B	109.4	C4—C15—H15B	109.5
C2—C3—H3B	109.4	H15A—C15—H15B	109.5
H3A—C3—H3B	108.0	C4—C15—H15C	109.5
O1—C4—C5	59.08 (11)	H15A—C15—H15C	109.5
O1—C4—C15	113.32 (15)	H15B—C15—H15C	109.5
C5—C4—C15	122.12 (16)	N1—C2'—C3'	108.01 (15)
O1—C4—C3	115.67 (15)	N1—C2'—C11'	115.82 (16)
C5—C4—C3	116.57 (16)	C3'—C2'—C11'	110.19 (16)
C15—C4—C3	116.63 (17)	N1—C2'—H2'	107.5
O1—C5—C4	60.22 (11)	C3'—C2'—H2'	107.5
O1—C5—C6	118.22 (15)	C11'—C2'—H2'	107.5
C4—C5—C6	125.54 (16)	C8'—C3'—C4'	118.90 (17)
O1—C5—H5	114.0	C8'—C3'—C2'	122.89 (17)
C4—C5—H5	114.0	C4'—C3'—C2'	118.20 (17)
C6—C5—H5	114.0	C5'—C4'—C3'	121.92 (19)
O2—C6—C5	105.81 (15)	C5'—C4'—H4'	119.0
O2—C6—C7	105.04 (14)	C3'—C4'—H4'	119.0
C5—C6—C7	114.46 (14)	C4'—C5'—C6'	118.93 (19)
O2—C6—H6	110.4	C4'—C5'—H5'	120.5
C5—C6—H6	110.4	C6'—C5'—H5'	120.5
C7—C6—H6	110.4	C7'—C6'—C5'	119.91 (18)
C11—C7—C6	101.64 (14)	C7'—C6'—H6'	120.0
C11—C7—C8	112.93 (15)	C5'—C6'—H6'	120.0
C6—C7—C8	117.69 (15)	C6'—C7'—C8'	121.19 (18)
C11—C7—H7	108.0	C6'—C7'—H7'	119.4
C6—C7—H7	108.0	C8'—C7'—H7'	119.4
C8—C7—H7	108.0	C3'—C8'—C7'	119.15 (18)
C7—C8—C9	115.68 (16)	C3'—C8'—C9'	122.00 (17)
C7—C8—H8A	108.4	C7'—C8'—C9'	118.71 (17)
C9—C8—H8A	108.4	C8'—C9'—C10'	111.81 (17)
C7—C8—H8B	108.4	C8'—C9'—H9'1	109.3
C9—C8—H8B	108.4	C10'—C9'—H9'1	109.3
H8A—C8—H8B	107.4	C8'—C9'—H9'2	109.3
C10—C9—C8	114.03 (16)	C10'—C9'—H9'2	109.3
C10—C9—H9A	108.7	H9'1—C9'—H9'2	107.9
C8—C9—H9A	108.7	C11'—C10'—C9'	109.47 (16)
C10—C9—H9B	108.7	C11'—C10'—H10A	109.8
C8—C9—H9B	108.7	C9'—C10'—H10A	109.8
H9A—C9—H9B	107.6	C11'—C10'—H10B	109.8
C1—C10—C9	119.88 (18)	C9'—C10'—H10B	109.8
C1—C10—C14	125.72 (19)	H10A—C10'—H10B	108.2
C9—C10—C14	114.40 (17)	C10'—C11'—C2'	111.16 (17)
C12—C11—C13	113.08 (17)	C10'—C11'—H11A	109.4
C12—C11—C7	103.38 (14)	C2'—C11'—H11A	109.4
C13—C11—C7	114.96 (16)	C10'—C11'—H11B	109.4
C12—C11—H11	108.4	C2'—C11'—H11B	109.4
C13—C11—H11	108.4	H11A—C11'—H11B	108.0

C10—C1—C2—C3	−109.7 (2)	C8—C7—C11—C13	−80.1 (2)
C1—C2—C3—C4	45.8 (2)	C6—O2—C12—O3	−176.92 (19)
C5—O1—C4—C15	−114.62 (18)	C6—O2—C12—C11	2.1 (2)
C5—O1—C4—C3	106.90 (17)	C13—C11—C12—O3	33.4 (3)
C2—C3—C4—O1	−155.15 (16)	C7—C11—C12—O3	158.4 (2)
C2—C3—C4—C5	−88.5 (2)	C13—C11—C12—O2	−145.45 (17)
C2—C3—C4—C15	67.8 (2)	C7—C11—C12—O2	−20.5 (2)
C4—O1—C5—C6	116.94 (18)	C2'—N1—C13—C11	−176.27 (16)
C15—C4—C5—O1	99.73 (18)	C12—C11—C13—N1	−69.3 (2)
C3—C4—C5—O1	−105.36 (17)	C7—C11—C13—N1	172.34 (15)
O1—C4—C5—C6	−105.11 (19)	C13—N1—C2'—C3'	176.64 (16)
C15—C4—C5—C6	−5.4 (3)	C13—N1—C2'—C11'	−59.3 (2)
C3—C4—C5—C6	149.53 (17)	N1—C2'—C3'—C8'	108.4 (2)
C12—O2—C6—C5	138.80 (16)	C11'—C2'—C3'—C8'	−19.0 (2)
C12—O2—C6—C7	17.36 (19)	N1—C2'—C3'—C4'	−72.8 (2)
O1—C5—C6—O2	56.9 (2)	C11'—C2'—C3'—C4'	159.81 (17)
C4—C5—C6—O2	128.86 (18)	C8'—C3'—C4'—C5'	−0.3 (3)
O1—C5—C6—C7	172.03 (14)	C2'—C3'—C4'—C5'	−179.21 (18)
C4—C5—C6—C7	−115.99 (19)	C3'—C4'—C5'—C6'	0.7 (3)
O2—C6—C7—C11	−28.52 (17)	C4'—C5'—C6'—C7'	−0.6 (3)
C5—C6—C7—C11	−144.12 (16)	C5'—C6'—C7'—C8'	0.3 (3)
O2—C6—C7—C8	−152.39 (15)	C4'—C3'—C8'—C7'	−0.1 (3)
C5—C6—C7—C8	92.0 (2)	C2'—C3'—C8'—C7'	178.76 (17)
C11—C7—C8—C9	145.45 (17)	C4'—C3'—C8'—C9'	−175.66 (18)
C6—C7—C8—C9	−96.5 (2)	C2'—C3'—C8'—C9'	3.2 (3)
C7—C8—C9—C10	78.9 (2)	C6'—C7'—C8'—C3'	0.1 (3)
C2—C1—C10—C9	168.58 (19)	C6'—C7'—C8'—C9'	175.83 (18)
C2—C1—C10—C14	−10.4 (3)	C3'—C8'—C9'—C10'	−17.3 (3)
C8—C9—C10—C1	−99.0 (2)	C7'—C8'—C9'—C10'	167.10 (17)
C8—C9—C10—C14	80.1 (2)	C8'—C9'—C10'—C11'	47.4 (2)
C6—C7—C11—C12	29.12 (18)	C9'—C10'—C11'—C2'	−66.1 (2)
C8—C7—C11—C12	156.16 (16)	N1—C2'—C11'—C10'	−72.9 (2)
C6—C7—C11—C13	152.84 (16)	C3'—C2'—C11'—C10'	50.1 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O3	1.01 (3)	2.32 (3)	2.992 (2)	123.5 (18)

Experimental details

Crystal data
Chemical formula	C₂₅H₃₃NO₃
M_r	395.52
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	90
a, b, c (Å)	8.4952 (13), 13.1852 (19), 18.771 (3)
V (Å³)	2102.6 (6)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	0.64
Crystal size (mm)	0.30 × 0.28 × 0.18

Data collection
Diffractometer	Bruker X8 Proteum diffractometer
Absorption correction	Multi-scan (SADABS in APEX2; Bruker Nonius, 2004)
T_min, T_max	0.782, 0.894
No. of measured, independent and observed [I > 2σ(I)] reflections	26461, 3849, 3813
R_int	0.033
(sin θ/λ)_max (Å⁻¹)	0.604

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.110, 1.06
No. of reflections	3849
No. of parameters	269
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.34, −0.22
Absolute structure	Flack (1983)
Absolute structure parameter	0.06 (5)

Computer programs: APEX2 (Bruker Nonius, 2004), SHELXS97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELXL97 (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	1.01 (3)	2.32 (3)	2.992 (2)	123.5 (18)

Acknowledgements

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

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.-in-Part of 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
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals 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