13-(N,N-Di­methyl­amino)­micheliolide 0.08-hydrate

Bommagani, S.; Penthala, N.R.; Janganati, V.; Parkin, S.; Crooks, P.A.

doi:10.1107/S1600536813030304

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 69| Part 12| December 2013| Pages o1789-o1790

doi:10.1107/S1600536813030304

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13-(N,N-Dimethylamino)micheliolide 0.08-hydrate

Shobanbabu Bommagani,^a Narsimha Reddy Penthala,^a Venumadhav Janganati,^a Sean Parkin ^b and Peter A. Crooks ^a ^*

^aDept. of Pharm. Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA, and ^bDept. of Chemistry, University of Kentucky, Lexington KY 40506, USA
^*Correspondence e-mail: pacrooks@uams.edu

(Received 28 October 2013; accepted 5 November 2013; online 20 November 2013)

The title compound, C₁₇H₂₇NO₃·0.08H₂O {sytematic name: (3R,3aS,9R,9aS,9bS)-3-[(dimethylamino)methyl]-9-hydroxy-6,9-dimethyl-3,3a,4,5,7,8,9,9a-octahydroazuleno[4,5-b]furan-2(9bH)-one 0.08-hydrate}, exhibits intramolecular O—H⋯O hydrogen bonding to form a ring of graph-set motif S(6). As well as this intramolecular hydrogen bond with the lactone-ring O atom, the hydroxy H atom forms an O—H⋯O hydrogen bond to the low-occupancy partial water molecule [occupancy = 0.078 (2)]. The water molecule is correlated with disorder of the N(CH₃)₂ group [major–minor occupancy factors are 0.922 (2):0.078 (2)]. The dihedral angle between the mean planes of the trans-fused seven-membered ring and the lactone ring is 4.42 (9)°.

CCDC reference: 970424

Related literature

For the biological activity of 13-N,N-dimethylamino micheliolide, see: Rodriguez et al. (1976 ); Sethi et al. (1984 ); Acosta & Fixher (1993 ); Zhang et al. (2012 ). For the crystal structure of a similar molecule, see: Acosta et al. (1991 ). The structure was checked with PLATON (Spek, 2009 ) and with an R-tensor (Parkin, 2000 ).

Experimental

Crystal data

C₁₇H₂₇NO₃·0.08H₂O
M_r = 295.01
Orthorhombic, P 2₁ 2₁ 2₁
a = 9.1329 (2) Å
b = 10.5227 (2) Å
c = 16.7194 (3) Å
V = 1606.78 (5) Å³
Z = 4
Cu Kα radiation
μ = 0.66 mm⁻¹
T = 90 K
0.18 × 0.16 × 0.12 mm

Data collection

Bruker X8 Proteum diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2008a ) T_min = 0.854, T_max = 0.942
20070 measured reflections
2925 independent reflections
2908 reflections with I > 2σ(I)
R_int = 0.032

Refinement

R[F² > 2σ(F²)] = 0.025
wR(F²) = 0.067
S = 1.07
2925 reflections
211 parameters
41 restraints
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.13 e Å⁻³
Absolute structure: Flack parameter determined using 1227 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter: −0.01 (3)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O2	0.84	2.35	2.9578 (15)	129
O1W—H1W1⋯O3ⁱ	0.84	2.16	2.845 (12)	139
Symmetry code: (i) $[-x+{\script{1\over 2}}, -y+1, z-{\script{1\over 2}}]$ .

Data collection: APEX2 (Bruker, 2006 ); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b ); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008b); molecular graphics: XP in SHELXTL (Sheldrick, 2008b); software used to prepare material for publication: SHELXL2013.

Supporting information

CCDC reference: 970424

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536813030304/sj5365sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813030304/sj5365Isup2.hkl

checkCIF report

Comment top

Micheliolide (MCL) is a natural product extracted from the plant Michelia champaca. MCL belongs to the class of guaianolide sesquiterpene lactones, which are used for the treatment of cancer (Sethi et al. 1984). The exocyclic double bond in such sesquiterpenes is believed to be responsible for their biological properties because of its exceptional chemical reactivity with nucleophilic groups (Rodriguez et al. 1976). The synthesis of MCL was first reported by Sethi et al. (1984) and its crystal structure was described by Acosta et al. (1991). Recently, the N,N-dimethyl amino analog of micheliolide was reported as a potent anti-leukemic agent (Zhang et al. 2012).

The N,N-dimethyl amino analog of micheliolide was synthesized as described by Zhang et al. (2012). Recrystallization of the compound from hexanes gave colorless needles that were suitable for X-ray analysis. The title molecule, Fig. 1, contains a central seven-membered carbocyclic ring fused to a 5-membered carbocylic ring and a trans lactone ring. The two five membered rings are in half-chair conformations, as reported in the literature (Acosta et al., 1991). The X-ray studies revealed that the title compound exhibits an O—H···O intramolecular hydrogen bond between the hydroxyl group and the lactone ring oxygen atom. The structure contains a low occupancy [7.8 (2)% occupancy] partial water molecule and a small amount of correlated disorder of the N(CH₃)₂ group. The bridge between the seven-membered ring and the lactone ring is trans, giving a dihedral angle between the mean planes of the rings of 4.42 (9)°.

Related literature top

For the biological activity of 13-N,N-dimethylamino micheliolide, see: Rodriguez et al. (1976); Sethi et al. (1984); Acosta & Fixher (1993); Zhang et al. (2012). For the crystal structure of a similar molecule, see: Acosta et al. (1991). The structure was checked with PLATON (Spek, 2009) and with an R-tensor (Parkin, 2000).

Experimental top

The title compound was prepared by the reported literature procedure (Zhang et al., 2012) and recrystallization from hexanes gave colorless needles suitable for X-ray analysis.

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008b); molecular graphics: XP in SHELXTL (Sheldrick, 2008b); software used to prepare material for publication: SHELXL2013 (Sheldrick, 2008b).

Figures top

Fig. 1. A view of the molecule with displacement ellipsoids drawn at the 50% probability level.

(3R,3aS,9R,9aS,9bS)-3-[(Dimethylamino)methyl]-9-hydroxy-6,9-dimethyl-3,3a,4,5,7,8,9,9a-octahydroazuleno[4,5-b]furan-2(9bH)-one 0.08-hydrate top

Crystal data top

C₁₇H₂₇NO₃·0.08H₂O	D_x = 1.220 Mg m⁻³
M_r = 295.01	Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 9518 reflections
a = 9.1329 (2) Å	θ = 5.3–68.3°
b = 10.5227 (2) Å	µ = 0.66 mm⁻¹
c = 16.7194 (3) Å	T = 90 K
V = 1606.78 (5) Å³	Block, colourless
Z = 4	0.18 × 0.16 × 0.12 mm
F(000) = 644

Data collection top

Bruker X8 Proteum diffractometer	2925 independent reflections
Radiation source: fine-focus rotating anode	2908 reflections with I > 2σ(I)
Detector resolution: 5.6 pixels mm^-1	R_int = 0.032
ϕ and ω scans	θ_max = 68.3°, θ_min = 5.3°
Absorption correction: multi-scan (SADABS; Sheldrick, 2008a)	h = −10→8
T_min = 0.854, T_max = 0.942	k = −12→12
20070 measured reflections	l = −16→20

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.025	H-atom parameters constrained
wR(F²) = 0.067	w = 1/[σ²(F_o²) + (0.0378P)² + 0.270P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
2925 reflections	Δρ_max = 0.18 e Å⁻³
211 parameters	Δρ_min = −0.13 e Å⁻³
41 restraints	Absolute structure: Flack parameter determined using 1227 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.01 (3)

Crystal data top

C₁₇H₂₇NO₃·0.08H₂O	V = 1606.78 (5) Å³
M_r = 295.01	Z = 4
Orthorhombic, P2₁2₁2₁	Cu Kα radiation
a = 9.1329 (2) Å	µ = 0.66 mm⁻¹
b = 10.5227 (2) Å	T = 90 K
c = 16.7194 (3) Å	0.18 × 0.16 × 0.12 mm

Data collection top

Bruker X8 Proteum diffractometer	2925 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 2008a)	2908 reflections with I > 2σ(I)
T_min = 0.854, T_max = 0.942	R_int = 0.032
20070 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.025	H-atom parameters constrained
wR(F²) = 0.067	Δρ_max = 0.18 e Å⁻³
S = 1.07	Δρ_min = −0.13 e Å⁻³
2925 reflections	Absolute structure: Flack parameter determined using 1227 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
211 parameters	Absolute structure parameter: −0.01 (3)
41 restraints

Special details top

Experimental. The crystal was mounted with polyisobutene oil on the tip of a fine glass fibre, fastened in a copper mounting pin with electrical solder. It was placed directly into the cold stream of a liquid nitrogen based cryostat, according to published methods (Hope, 1994; Parkin & Hope, 1998).

Diffraction data were collected with the crystal at 90 K, which is standard practice in this laboratory for the majority of flash-cooled crystals.

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 progress was checked using PLATON (Spek, 2009) and by an R-tensor (Parkin, 2000). The final model was further checked with the IUCr utility checkCIF.

The partial occupancy water molecule was modelled on the site of a difference map peak of approximately 0.67 e A-3. It must have the same or smaller occupancy as the minor disorder component of disorder in the main molecule, which is a very small amount (less than 8%). Nevertheless, it gave a noticeably better fit, and a much flatter difference map, and so was retained. Hydrogen atoms for this water were placed so as to make reasonable H-bonds to nearby acceptors. Overall, the fit is good and the absolute configuration is well established.

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.26340 (11)	0.40697 (10)	0.53330 (6)	0.0210 (2)
O2	0.43064 (11)	0.29124 (9)	0.59801 (6)	0.0165 (2)
O3	0.42055 (12)	0.12939 (12)	0.74254 (7)	0.0265 (3)
H3	0.3662	0.1672	0.7098	0.040*
C1	0.80039 (15)	0.21088 (14)	0.69190 (8)	0.0163 (3)
C2	0.81758 (16)	0.08807 (15)	0.73919 (9)	0.0214 (3)
H2A	0.8888	0.0991	0.7833	0.026*
H2B	0.8513	0.0182	0.7041	0.026*
C3	0.66481 (17)	0.06029 (15)	0.77202 (9)	0.0213 (3)
H3A	0.6507	−0.0320	0.7804	0.026*
H3B	0.6485	0.1051	0.8233	0.026*
C4	0.56222 (16)	0.11003 (14)	0.70741 (8)	0.0188 (3)
C5	0.63616 (15)	0.23752 (13)	0.68365 (8)	0.0159 (3)
H5	0.6086	0.3030	0.7243	0.019*
C6	0.59247 (14)	0.28641 (14)	0.60217 (8)	0.0147 (3)
H6	0.6297	0.2268	0.5603	0.018*
C7	0.63770 (16)	0.42119 (13)	0.58082 (8)	0.0160 (3)
H7	0.6194	0.4773	0.6280	0.019*
C8	0.79855 (16)	0.43052 (14)	0.55809 (9)	0.0176 (3)
H8A	0.8169	0.5145	0.5333	0.021*
H8B	0.8211	0.3645	0.5177	0.021*
C9	0.90109 (16)	0.41382 (15)	0.62982 (9)	0.0209 (3)
H9A	1.0007	0.4391	0.6127	0.025*
H9B	0.8700	0.4747	0.6717	0.025*
C10	0.91239 (16)	0.28324 (14)	0.66846 (8)	0.0180 (3)
C11	0.52508 (16)	0.45244 (14)	0.51589 (8)	0.0169 (3)
H11	0.5560	0.4102	0.4650	0.020*
C12	0.39005 (16)	0.38521 (14)	0.54730 (8)	0.0166 (3)
C14	1.06853 (17)	0.24418 (15)	0.68593 (9)	0.0220 (3)
H14A	1.1085	0.2982	0.7284	0.033*
H14B	1.1278	0.2538	0.6375	0.033*
H14C	1.0704	0.1552	0.7033	0.033*
C15	0.55145 (18)	0.01621 (14)	0.63836 (9)	0.0233 (3)
H15A	0.5178	−0.0662	0.6585	0.035*
H15B	0.6479	0.0062	0.6135	0.035*
H15C	0.4817	0.0482	0.5986	0.035*
C13	0.4909 (2)	0.5914 (2)	0.4980 (2)	0.0186 (5)	0.922 (2)
H13A	0.4089	0.5954	0.4593	0.022*	0.922 (2)
H13B	0.4583	0.6334	0.5479	0.022*	0.922 (2)
N1	0.61597 (15)	0.66157 (13)	0.46532 (8)	0.0194 (3)	0.922 (2)
C16	0.6579 (2)	0.6162 (2)	0.38513 (11)	0.0255 (5)	0.922 (2)
H16A	0.6873	0.5268	0.3883	0.038*	0.922 (2)
H16B	0.7399	0.6671	0.3650	0.038*	0.922 (2)
H16C	0.5743	0.6246	0.3488	0.038*	0.922 (2)
C17	0.5765 (2)	0.79590 (17)	0.46031 (11)	0.0294 (4)	0.922 (2)
H17A	0.4966	0.8067	0.4218	0.044*	0.922 (2)
H17B	0.6617	0.8452	0.4428	0.044*	0.922 (2)
H17C	0.5447	0.8259	0.5130	0.044*	0.922 (2)
C13'	0.523 (4)	0.596 (3)	0.494 (3)	0.0186 (5)	0.078 (2)
H13C	0.4480	0.6372	0.5271	0.022*	0.078 (2)
H13D	0.6191	0.6318	0.5094	0.022*	0.078 (2)
N1'	0.4995 (18)	0.6291 (14)	0.4203 (9)	0.0194 (3)	0.078 (2)
C16'	0.656 (3)	0.630 (4)	0.408 (2)	0.0255 (5)	0.078 (2)
H16D	0.6789	0.6777	0.3587	0.038*	0.078 (2)
H16E	0.6917	0.5425	0.4020	0.038*	0.078 (2)
H16F	0.7047	0.6703	0.4533	0.038*	0.078 (2)
C17'	0.439 (3)	0.7572 (17)	0.4127 (14)	0.0294 (4)	0.078 (2)
H17D	0.4467	0.7851	0.3569	0.044*	0.078 (2)
H17E	0.4948	0.8155	0.4470	0.044*	0.078 (2)
H17F	0.3364	0.7569	0.4292	0.044*	0.078 (2)
O1W	0.2432 (13)	0.7614 (11)	0.3700 (7)	0.014 (3)*	0.078 (2)
H1W1	0.1696	0.7606	0.3398	0.022*	0.078 (2)
H2W1	0.2082	0.7455	0.4153	0.022*	0.078 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0166 (5)	0.0232 (5)	0.0233 (5)	0.0005 (4)	−0.0031 (4)	0.0017 (4)
O2	0.0131 (5)	0.0184 (5)	0.0179 (5)	−0.0009 (4)	−0.0010 (4)	0.0031 (4)
O3	0.0163 (5)	0.0348 (6)	0.0284 (6)	0.0003 (5)	0.0050 (5)	0.0113 (5)
C1	0.0156 (7)	0.0191 (7)	0.0143 (6)	0.0009 (6)	−0.0018 (5)	−0.0010 (6)
C2	0.0178 (7)	0.0245 (7)	0.0219 (7)	0.0011 (6)	−0.0012 (6)	0.0042 (6)
C3	0.0212 (8)	0.0231 (8)	0.0197 (7)	−0.0008 (6)	−0.0002 (6)	0.0056 (6)
C4	0.0155 (7)	0.0234 (7)	0.0176 (7)	−0.0016 (6)	0.0013 (6)	0.0051 (6)
C5	0.0151 (7)	0.0174 (7)	0.0152 (6)	−0.0008 (5)	0.0008 (5)	−0.0002 (5)
C6	0.0109 (6)	0.0171 (6)	0.0162 (6)	−0.0005 (5)	0.0003 (5)	−0.0008 (5)
C7	0.0162 (7)	0.0155 (7)	0.0162 (6)	−0.0001 (5)	0.0005 (6)	−0.0011 (5)
C8	0.0170 (7)	0.0151 (7)	0.0207 (7)	−0.0014 (5)	0.0015 (6)	0.0018 (5)
C9	0.0149 (7)	0.0196 (7)	0.0283 (8)	−0.0038 (6)	−0.0010 (6)	0.0000 (6)
C10	0.0161 (7)	0.0196 (7)	0.0181 (6)	0.0001 (6)	−0.0012 (6)	−0.0036 (6)
C11	0.0173 (7)	0.0169 (7)	0.0166 (6)	0.0004 (5)	0.0005 (5)	−0.0001 (5)
C12	0.0189 (7)	0.0166 (7)	0.0143 (6)	0.0006 (5)	−0.0006 (5)	−0.0019 (5)
C14	0.0172 (7)	0.0224 (7)	0.0266 (7)	−0.0007 (6)	−0.0018 (6)	−0.0001 (6)
C15	0.0261 (8)	0.0198 (7)	0.0240 (7)	−0.0063 (6)	−0.0033 (6)	0.0044 (6)
C13	0.0156 (14)	0.0200 (8)	0.0204 (8)	0.0008 (8)	0.0040 (11)	0.0033 (6)
N1	0.0209 (7)	0.0168 (7)	0.0205 (7)	−0.0012 (5)	0.0002 (5)	0.0032 (5)
C16	0.0328 (8)	0.0234 (10)	0.0202 (13)	0.0006 (7)	0.0104 (8)	0.0018 (10)
C17	0.0363 (10)	0.0179 (8)	0.0340 (9)	−0.0005 (8)	0.0027 (8)	0.0020 (7)
C13'	0.0156 (14)	0.0200 (8)	0.0204 (8)	0.0008 (8)	0.0040 (11)	0.0033 (6)
N1'	0.0209 (7)	0.0168 (7)	0.0205 (7)	−0.0012 (5)	0.0002 (5)	0.0032 (5)
C16'	0.0328 (8)	0.0234 (10)	0.0202 (13)	0.0006 (7)	0.0104 (8)	0.0018 (10)
C17'	0.0363 (10)	0.0179 (8)	0.0340 (9)	−0.0005 (8)	0.0027 (8)	0.0020 (7)

Geometric parameters (Å, º) top

O1—C12	1.2021 (18)	C11—H11	1.0000
O2—C12	1.3542 (17)	C14—H14A	0.9800
O2—C6	1.4804 (15)	C14—H14B	0.9800
O3—C4	1.4355 (18)	C14—H14C	0.9800
O3—H3	0.8400	C15—H15A	0.9800
C1—C10	1.334 (2)	C15—H15B	0.9800
C1—C2	1.523 (2)	C15—H15C	0.9800
C1—C5	1.5321 (18)	C13—N1	1.466 (2)
C2—C3	1.528 (2)	C13—H13A	0.9900
C2—H2A	0.9900	C13—H13B	0.9900
C2—H2B	0.9900	N1—C17	1.461 (2)
C3—C4	1.523 (2)	N1—C16	1.474 (2)
C3—H3A	0.9900	C16—H16A	0.9800
C3—H3B	0.9900	C16—H16B	0.9800
C4—C15	1.522 (2)	C16—H16C	0.9800
C4—C5	1.5536 (19)	C17—H17A	0.9800
C5—C6	1.5098 (18)	C17—H17B	0.9800
C5—H5	1.0000	C17—H17C	0.9800
C6—C7	1.5198 (19)	C13'—N1'	1.29 (5)
C6—H6	1.0000	C13'—C16'	1.92 (5)
C7—C8	1.5206 (19)	C13'—H13C	0.9900
C7—C11	1.531 (2)	C13'—H13D	0.9900
C7—H7	1.0000	N1'—C16'	1.45 (2)
C8—C9	1.532 (2)	N1'—C17'	1.460 (19)
C8—H8A	0.9900	C16'—H16D	0.9800
C8—H8B	0.9900	C16'—H16E	0.9800
C9—C10	1.522 (2)	C16'—H16F	0.9800
C9—H9A	0.9900	C17'—O1W	1.93 (3)
C9—H9B	0.9900	C17'—H17D	0.9800
C10—C14	1.513 (2)	C17'—H17E	0.9800
C11—C12	1.516 (2)	C17'—H17F	0.9800
C11—C13	1.525 (3)	O1W—H1W1	0.8400
C11—C13'	1.55 (2)	O1W—H2W1	0.8400

C12—O2—C6	109.14 (11)	C10—C14—H14B	109.5
C4—O3—H3	109.5	H14A—C14—H14B	109.5
C10—C1—C2	123.90 (13)	C10—C14—H14C	109.5
C10—C1—C5	128.30 (14)	H14A—C14—H14C	109.5
C2—C1—C5	107.63 (12)	H14B—C14—H14C	109.5
C1—C2—C3	104.76 (12)	C4—C15—H15A	109.5
C1—C2—H2A	110.8	C4—C15—H15B	109.5
C3—C2—H2A	110.8	H15A—C15—H15B	109.5
C1—C2—H2B	110.8	C4—C15—H15C	109.5
C3—C2—H2B	110.8	H15A—C15—H15C	109.5
H2A—C2—H2B	108.9	H15B—C15—H15C	109.5
C4—C3—C2	103.97 (11)	N1—C13—C11	113.35 (14)
C4—C3—H3A	111.0	N1—C13—H13A	108.9
C2—C3—H3A	111.0	C11—C13—H13A	108.9
C4—C3—H3B	111.0	N1—C13—H13B	108.9
C2—C3—H3B	111.0	C11—C13—H13B	108.9
H3A—C3—H3B	109.0	H13A—C13—H13B	107.7
O3—C4—C15	110.13 (12)	C17—N1—C13	108.44 (15)
O3—C4—C3	108.25 (11)	C17—N1—C16	108.97 (15)
C15—C4—C3	110.78 (13)	C13—N1—C16	112.23 (18)
O3—C4—C5	111.95 (12)	N1—C16—H16A	109.5
C15—C4—C5	113.22 (11)	N1—C16—H16B	109.5
C3—C4—C5	102.16 (12)	H16A—C16—H16B	109.5
C6—C5—C1	113.72 (11)	N1—C16—H16C	109.5
C6—C5—C4	114.20 (12)	H16A—C16—H16C	109.5
C1—C5—C4	104.15 (12)	H16B—C16—H16C	109.5
C6—C5—H5	108.2	N1—C17—H17A	109.5
C1—C5—H5	108.2	N1—C17—H17B	109.5
C4—C5—H5	108.2	H17A—C17—H17B	109.5
O2—C6—C5	108.54 (10)	N1—C17—H17C	109.5
O2—C6—C7	103.19 (11)	H17A—C17—H17C	109.5
C5—C6—C7	117.26 (12)	H17B—C17—H17C	109.5
O2—C6—H6	109.2	N1'—C13'—C11	120 (3)
C5—C6—H6	109.2	N1'—C13'—C16'	49.1 (17)
C7—C6—H6	109.2	C11—C13'—C16'	111 (3)
C6—C7—C8	112.43 (12)	N1'—C13'—H13C	107.4
C6—C7—C11	100.62 (11)	C11—C13'—H13C	107.4
C8—C7—C11	117.25 (12)	C16'—C13'—H13C	141.5
C6—C7—H7	108.7	N1'—C13'—H13D	107.4
C8—C7—H7	108.7	C11—C13'—H13D	107.4
C11—C7—H7	108.7	C16'—C13'—H13D	64.5
C7—C8—C9	112.81 (12)	H13C—C13'—H13D	106.9
C7—C8—H8A	109.0	C13'—N1'—C16'	89 (2)
C9—C8—H8A	109.0	C13'—N1'—C17'	113 (2)
C7—C8—H8B	109.0	C16'—N1'—C17'	111 (2)
C9—C8—H8B	109.0	N1'—C16'—C13'	42.4 (17)
H8A—C8—H8B	107.8	N1'—C16'—H16D	109.5
C10—C9—C8	118.52 (12)	C13'—C16'—H16D	148.7
C10—C9—H9A	107.7	N1'—C16'—H16E	109.5
C8—C9—H9A	107.7	C13'—C16'—H16E	95.9
C10—C9—H9B	107.7	H16D—C16'—H16E	109.5
C8—C9—H9B	107.7	N1'—C16'—H16F	109.5
H9A—C9—H9B	107.1	C13'—C16'—H16F	77.4
C1—C10—C14	120.73 (13)	H16D—C16'—H16F	109.5
C1—C10—C9	126.02 (13)	H16E—C16'—H16F	109.5
C14—C10—C9	113.03 (12)	N1'—C17'—O1W	113.7 (15)
C12—C11—C13	110.41 (12)	N1'—C17'—H17D	109.5
C12—C11—C7	101.57 (11)	O1W—C17'—H17D	72.8
C13—C11—C7	118.86 (16)	N1'—C17'—H17E	109.5
C12—C11—C13'	121.9 (15)	O1W—C17'—H17E	132.9
C7—C11—C13'	112.7 (18)	H17D—C17'—H17E	109.5
C12—C11—H11	108.5	N1'—C17'—H17F	109.5
C13—C11—H11	108.5	O1W—C17'—H17F	38.1
C7—C11—H11	108.5	H17D—C17'—H17F	109.5
O1—C12—O2	121.62 (13)	H17E—C17'—H17F	109.5
O1—C12—C11	128.80 (13)	C17'—O1W—H1W1	164.8
O2—C12—C11	109.58 (12)	C17'—O1W—H2W1	90.8
C10—C14—H14A	109.5	H1W1—O1W—H2W1	103.6

C10—C1—C2—C3	164.39 (14)	C8—C9—C10—C1	−50.3 (2)
C5—C1—C2—C3	−11.20 (15)	C8—C9—C10—C14	135.02 (14)
C1—C2—C3—C4	33.25 (15)	C6—C7—C11—C12	36.38 (13)
C2—C3—C4—O3	−160.27 (12)	C8—C7—C11—C12	158.62 (12)
C2—C3—C4—C15	78.88 (15)	C6—C7—C11—C13	157.67 (14)
C2—C3—C4—C5	−42.00 (14)	C8—C7—C11—C13	−80.10 (18)
C10—C1—C5—C6	45.2 (2)	C6—C7—C11—C13'	168.5 (17)
C2—C1—C5—C6	−139.44 (12)	C8—C7—C11—C13'	−69.3 (17)
C10—C1—C5—C4	170.15 (14)	C6—O2—C12—O1	179.20 (13)
C2—C1—C5—C4	−14.51 (15)	C6—O2—C12—C11	−1.67 (15)
O3—C4—C5—C6	−85.21 (15)	C13—C11—C12—O1	29.4 (2)
C15—C4—C5—C6	40.01 (17)	C7—C11—C12—O1	156.38 (15)
C3—C4—C5—C6	159.18 (11)	C13'—C11—C12—O1	30 (2)
O3—C4—C5—C1	150.16 (11)	C13—C11—C12—O2	−149.67 (17)
C15—C4—C5—C1	−84.62 (14)	C7—C11—C12—O2	−22.67 (14)
C3—C4—C5—C1	34.56 (14)	C13'—C11—C12—O2	−149 (2)
C12—O2—C6—C5	150.78 (11)	C12—C11—C13—N1	−178.49 (19)
C12—O2—C6—C7	25.69 (13)	C7—C11—C13—N1	64.8 (3)
C1—C5—C6—O2	172.18 (11)	C13'—C11—C13—N1	5 (10)
C4—C5—C6—O2	52.82 (15)	C11—C13—N1—C17	−172.80 (19)
C1—C5—C6—C7	−71.48 (16)	C11—C13—N1—C16	66.8 (3)
C4—C5—C6—C7	169.16 (12)	C12—C11—C13'—N1'	−94 (3)
O2—C6—C7—C8	−163.62 (11)	C13—C11—C13'—N1'	−91 (11)
C5—C6—C7—C8	77.15 (15)	C7—C11—C13'—N1'	144 (3)
O2—C6—C7—C11	−38.06 (13)	C12—C11—C13'—C16'	−148.3 (17)
C5—C6—C7—C11	−157.29 (12)	C13—C11—C13'—C16'	−145 (12)
C6—C7—C8—C9	−71.33 (15)	C7—C11—C13'—C16'	91 (3)
C11—C7—C8—C9	172.75 (12)	C11—C13'—N1'—C16'	−93 (3)
C7—C8—C9—C10	69.48 (17)	C11—C13'—N1'—C17'	155 (2)
C2—C1—C10—C14	1.9 (2)	C16'—C13'—N1'—C17'	−112 (2)
C5—C1—C10—C14	176.57 (13)	C17'—N1'—C16'—C13'	114 (2)
C2—C1—C10—C9	−172.40 (13)	C13'—N1'—C17'—O1W	−115 (2)
C5—C1—C10—C9	2.2 (2)	C16'—N1'—C17'—O1W	147.4 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O2	0.84	2.35	2.9578 (15)	129
O1W—H1W1···O3ⁱ	0.84	2.16	2.845 (12)	139

Symmetry code: (i) −x+1/2, −y+1, z−1/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O2	0.84	2.35	2.9578 (15)	129.2
O1W—H1W1···O3ⁱ	0.84	2.16	2.845 (12)	138.7

Symmetry code: (i) −x+1/2, −y+1, z−1/2.

Acknowledgements

This work was supported by the NIH/NCI (grant No. CA158275).

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