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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 10| October 2014| Pages o1092-o1093

Crystal structure of (E)-13-{4-[(Z)-2-cyano-2-(3,4,5-tri­meth­­oxy­phen­yl)ethen­yl]phen­yl}parthenolide methanol hemisolvate

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

Edited by J. Simpson, University of Otago, New Zealand (Received 22 May 2014; accepted 26 August 2014; online 6 September 2014)

The title compound, C33H35NO6 [systematic name: (Z)-3-(4-{(E)-[(E)-1a,5-dimethyl-9-oxo-2,3,7,7a-tetra­hydro­oxireno[2′,3′:9,10]cyclo­deca­[1,2-b]furan-8(1aH,6H,9H,10aH,10bH)-yl­idene]meth­yl}phen­yl)-2-(3,4,5-tri­meth­oxy­phen­yl)acrylo­ni­trile methanol hemisolvate], C33H35NO6·0.5CH3OH, was prepared by the reaction of (Z)-3-(4-iodo­phen­yl)-2-(3,4,5-tri­meth­oxy­phen­yl)acrylo­nitrile with parthenolide [systematic name: (E)-1a,5-dimethyl-8-methyl­ene-2,3,6,7,7a,8,10a,10b-octa­hy­dro­oxireno[2′,3′:9,10]cyclo­deca­[1,2-b]furan-9(1aH)-one] under Heck reaction conditions. The mol­ecule is built up from fused ten-, five- (lactone) and three-membered (epoxide) rings with a {4-[(Z)-2-cyano-2-(3,4,5-tri­meth­oxy­phen­yl)ethen­yl]phen­yl}methyl­idene group as a substituent. The 4-[(Z)-2-cyano-2-(3,4,5-tri­meth­oxy­phen­yl)ethen­yl]phenyl group on the parthenolide exocyclic double bond is oriented in a trans position to the lactone ring to form the E isomer. The dihedral angle between the benzene ring of the phenyl moiety and the lactone ring mean plane is 21.93 (4)°.

1. Related literature

For the biological activity of parthenolide, see: Hall et al. (1979[Hall, I. H., Lee, K. H., Starnes, C. O., Sumida, Y., Wu, R. Y., Waddell, T. G., Cochran, J. W. & Gerhart, K. G. (1979). J. Pharm. Sci. 68, 537-542.]). For the biological activity of parthenolide derivatives similar to the title compound, see: Hanson et al. (1970[Hanson, R. L., Lardy, H. A. & Kupchan, S. M. (1970). Science, 168, 378-380.]); Hehner et al. (1998[Hehner, S. P., Heinrich, M., Bork, P. M., Vogt, M., Ratter, F., Lehmann, V., Osthoff, K. S., Dröge, W. & Schmitz, M. L. (1998). J. Biol. Chem. 273, 1288-1297.]); Kupchan et al. (1971[Kupchan, S. M., Eakin, M. A. & Thomas, A. M. (1971). J. Med. Chem. 14, 1147-1152.]); Neelakantan et al. (2009[Neelakantan, S., Nasim, S., Guzman, M. L., Jordan, C. T. & Crooks, P. A. (2009). Bioorg. Med. Chem. Lett. 19, 4346-4349.]); Oka et al., 2007[Oka, D., Nishimura, K., Shiba, M., Nakai, Y., Arai, Y., Nakayama, M., Takayama, H., Inoue, H., Okuyama, A. & Nonomura, N. (2007). Int. J. Cancer, 120, 2576-2581.]); Ralstin et al. (2006[Ralstin, M. C., Gage, E. A., Yip-Schneider, M. T., Klein, P. J., Wiebke, E. A. & Schmidt, C. M. (2006). Mol. Cancer Res. 4, 387-399.]); Sun et al. (2006[Sun, H.-X., Zheng, Q.-F. & Tu, J. (2006). Bioorg. Med. Chem. 14, 1189-1198.]); Penthala et al. (2013b[Penthala, N. R., Sonar, V. N., Horn, J., Leggas, M., Yadlapalli, J. S. & Crooks, P. A. (2013b). Medchemcomm, 4, 1073-1078.]). For the synthesis and crystal structures of similar mol­ecules, see: Han et al. (2009[Han, C., Barrios, F. J., Riofski, M. V. & Colby, D. A. (2009). J. Org. Chem. 74, 7176-7179.]); Penthala et al. (2013a[Penthala, N. R., Janganati, V., Parkin, S., Varughese, K. I. & Crooks, P. A. (2013a). Acta Cryst. E69, o1709-o1710.]). For details of the experimental procedure, see: Hope (1994[Hope, H. (1994). Prog. Inorg. Chem. 41, 1-19.]); Parkin & Hope (1998[Parkin, S. & Hope, H. (1998). J. Appl. Cryst. 31, 945-953.]);

[Scheme 1]

2. Experimental

2.1. Crystal data

  • C33H35NO6·0.5CH4O

  • Mr = 557.64

  • Orthorhombic, P 21 21 21

  • a = 9.3347 (2) Å

  • b = 16.2442 (3) Å

  • c = 19.2580 (4) Å

  • V = 2920.18 (10) Å3

  • Z = 4

  • Cu Kα radiation

  • μ = 0.71 mm−1

  • T = 90 K

  • 0.18 × 0.15 × 0.10 mm

2.1.2. Data collection

  • Bruker X8 Proteum diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 2008b[Sheldrick, G. M. (2008b). SADABS. University of Göttingen, Germany.]) Tmin = 0.836, Tmax = 0.963

  • 40379 measured reflections

  • 5349 independent reflections

  • 5303 reflections with I > 2σ(I)

  • Rint = 0.036

2.1.3. Refinement

  • R[F2 > 2σ(F2)] = 0.024

  • wR(F2) = 0.065

  • S = 1.03

  • 5349 reflections

  • 387 parameters

  • H-atom parameters constrained

  • Δρmax = 0.14 e Å−3

  • Δρmin = −0.13 e Å−3

  • Absolute structure: Flack x determined using 2283 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])

  • Absolute structure parameter: 0.02 (2)

Data collection: APEX2 (Bruker, 2006[Bruker (2006). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008a[Sheldrick, G. M. (2008a). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2008a[Sheldrick, G. M. (2008a). Acta Cryst. A64, 112-122.]); molecular graphics: XP in SHELXTL (Sheldrick, 2008a[Sheldrick, G. M. (2008a). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008a[Sheldrick, G. M. (2008a). Acta Cryst. A64, 112-122.]), CIFFIX (Parkin, 2013[Parkin, S. (2013). CIFFIX, http://xray.uky.edu/people/parkin/programs/ciffix .]), PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]) and local program (Parkin, 2000[Parkin, S. (2000). Acta Cryst. A56, 157-162.]).

Supporting information


Comment top

Parthenolide (PTL) and its analogs belong to the class of sesquiterpene lactones. These compounds are currently being used in the development of anti-cancer agents for the treatment of hematological tumours (Sun et al., 2006; Hehner et al., 1998; Ralstin et al. 2006; Oka et al., 2007; Kupchan et al., 1971 and Hanson et al., 1970). Recently, we have reported the crystal structure of (E)-13-(4-aminophenyl)parthenolide, a Heck reaction derivative of parthenolide (Penthala et al. 2013a), and we have also reported on Z-2-(3,4,5-trimethoxyphenyl)acrylonitrile analogs (Penthala et al. 2013b) as anti-cancer agents. As part of a program for the development of parthenolide analogs as anti-leukemic agents (Neelakantan et al. 2009), and small molecule analogs as anti-cancer agents, our research group is focusing on the synthesis of E-olefinic analogues of PTL which can be obtained from the reaction of parthenolide with iodoaromatic reagents utilizing Heck chemistry (Han et al. 2009). The title compound was obtained from the reaction of parthenolide with (Z)-3-(4-iodophenyl) -2-(3,4,5- trimethoxyphenylacrylonitrile under Heck reaction conditions. To obtain detailed information on the structure of the title compound and to establish the geometry of the exocyclic C13—C14 double bond, a single-crystal X-ray structure determination has been carried out.

Recrystallization of the title compound from methanol afforded light yellow coloured crystals that were suitable for X-ray analysis. The X-ray studies revealed that the title compound was identified as the E-isomer (conformation about the exocyclic methylidene CC bond; the conformation about the CC bond in the ten-membered ring is also E). The molecule is built up from fused ten-, five- (lactone) and three-membered (epoxide) rings with a (Z)-3-(4-phenyl)-2-(3,4,5- trimethoxyphenyl)acrylonitrile group as a substituent. The dihedral angle between the benzene ring of the phenyl moiety and the lactone ring mean plane is 21.93 (4) Å.

Related literature top

For the biological activity of parthenolide, see: Hall et al. (1979). For the biological activity of parthenolide derivatives similar to the title compound, see: Hanson et al. (1970); Hehner et al. (1998); Kupchan et al. (1971); Neelakantan et al. (2009); Oka et al., 2007); Ralstin et al. (2006); Sun et al. (2006); Penthala et al. (2013b). For the synthesis and crystal structures of similar molecules, see: Han et al. (2009); Penthala et al. (2013a). For details of the experimental procedure, see: Hope (1994); Parkin & Hope (1998);

Experimental top

A mixture of parthenolide (1.0 mmol), diisopropylethylamine (3.0 mmol), and (Z)-3-(4-iodophenyl)-2-(3,4,5-trimethoxyphenyl acrylonitrile (1.1 mmol) in toluene (1 ml) was treated with palladium (II) ferrocene (0.01 mmol) and then stirred at 353 K for 24 h. The reaction mixture was cooled to room temperature, water (8 ml) was added, and the mixture was extracted with ethyl acetate (10 mlx3). The separated organics were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The obtained crude residue was purified using silica flash chromatography (7:3, hexanes/EtOAc) to afford the title compound, which was recrystallized from methanol as light yellow coloured crystals suitable for X-ray analysis (87% yield; M·P.: 478–480 K); 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 3.6 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.46 (s, 1H), 6.88 (s, 2H), 5.29 (d, J = 11.2 Hz, 1H), 3.94 (s, 6H, 2xOCH3), 3.90 (s, 3H, OCH3), 3.3 (m, 1H), 2.85 (d, J = 8.4 Hz, 1H), 2.41–2.46 (m, 1H), 2.10–2.27 (m, 5H), 1.69 (s, 3H, CH3), 1.46–1.55 (m, 2H), 1.32 (s, 3H, CH3), 1.27–1.30 (m, 1H) p.p.m.. 13C NMR (100 MHz, CDCl3): δ 17.60,17.70, 24.54, 30.58, 36.33, 42.13, 47.16, 55.60, 61.27, 61.94, 66.71, 83.30, 103.75, 113.21, 118.04, 125.48, 129.53, 129.95, 130.56, 130.97, 134.88, 134.96, 135.69, 137.06, 139.77, 140.34, 153.89, 170.85 p.p.m..

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms were found in difference Fourier maps, but subsequently included in the refinement using riding models, with constrained distances set to 0.95%A (Csp2H), 0.98Å (RCH3), 0.99Å (R2CH2), 1.00Å (R3CH) and 0.84Å (OH). Uiso(H) parameters were set to values of either 1.2Ueq or 1.5Ueq (RCH3 and OH only) of the attached atom.

The partial occupancy methanol molecule refined to an occupancy of about one half. For the final rounds of refinement its occupancy was fixed at exactly 0.5 for the sake of simplicity. This is reasonable because other crystals from the same batch would almost certainly have had varying amounts of solvent incorporated, due to unpredictable rates of solvent loss dependent on such things as crystal handling. The position of this half-occupancy methanol is consistent with an O—H···π weak hydrogen bonding interaction in which the distance between atom O1M and the centroid of the trimethoxyphenyl ring (C24-C29) is 3.212 (3)Å.

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2 (Bruker, 2006); data reduction: APEX2 (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2008a); molecular graphics: XP in SHELXTL (Sheldrick, 2008a); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008a), CIFFIX (Parkin, 2013), PLATON (Spek, 2009) and local program (Parkin, 2000).

Figures top
[Figure 1] Fig. 1. A view of the molecule with displacement ellipsoids drawn at the 50% probability level.
(Z)-3-(4-{(E)-[(E)-1a,5-Dimethyl-9-oxo-2,3,7,7a-tetrahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-8(1aH,6H,9H,10aH,10bH)-ylidene]methyl}phenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile methanol hemisolvate top
Crystal data top
C33H35NO6·0.5CH4ODx = 1.268 Mg m3
Mr = 557.64Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P212121Cell parameters from 9693 reflections
a = 9.3347 (2) Åθ = 3.6–68.4°
b = 16.2442 (3) ŵ = 0.71 mm1
c = 19.2580 (4) ÅT = 90 K
V = 2920.18 (10) Å3Irregular cut wedge, pale yellow
Z = 40.18 × 0.15 × 0.10 mm
F(000) = 1188
Data collection top
Bruker X8 Proteum
diffractometer
5349 independent reflections
Radiation source: fine-focus rotating anode5303 reflections with I > 2σ(I)
Detector resolution: 5.6 pixels mm-1Rint = 0.036
ϕ and ω scansθmax = 68.4°, θmin = 3.6°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008b)
h = 1111
Tmin = 0.836, Tmax = 0.963k = 1319
40379 measured reflectionsl = 2023
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.024 w = 1/[σ2(Fo2) + (0.0363P)2 + 0.5907P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.065(Δ/σ)max < 0.001
S = 1.03Δρmax = 0.14 e Å3
5349 reflectionsΔρmin = 0.13 e Å3
387 parametersExtinction correction: SHELXL2014 (Sheldrick, 2008a), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.00092 (14)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack x determined using 2283 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 0.02 (2)
Crystal data top
C33H35NO6·0.5CH4OV = 2920.18 (10) Å3
Mr = 557.64Z = 4
Orthorhombic, P212121Cu Kα radiation
a = 9.3347 (2) ŵ = 0.71 mm1
b = 16.2442 (3) ÅT = 90 K
c = 19.2580 (4) Å0.18 × 0.15 × 0.10 mm
Data collection top
Bruker X8 Proteum
diffractometer
5349 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008b)
5303 reflections with I > 2σ(I)
Tmin = 0.836, Tmax = 0.963Rint = 0.036
40379 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.024H-atom parameters constrained
wR(F2) = 0.065Δρmax = 0.14 e Å3
S = 1.03Δρmin = 0.13 e Å3
5349 reflectionsAbsolute structure: Flack x determined using 2283 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
387 parametersAbsolute structure parameter: 0.02 (2)
0 restraints
Special details top

Experimental. The crystal was mounted with polyisobutene oil on the tip of a fine glass fibre, which was fastened in a copper mounting pin with electrical solder. It was placed directly into the cold gas 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
O10.48351 (13)0.18048 (7)0.54248 (6)0.0242 (3)
O20.35142 (13)0.32648 (7)0.48438 (5)0.0210 (2)
O30.34451 (13)0.45934 (7)0.45520 (6)0.0237 (3)
O40.02191 (12)0.41510 (7)0.22367 (6)0.0225 (3)
O50.14060 (12)0.30869 (7)0.31036 (5)0.0219 (2)
O60.30389 (14)0.18270 (7)0.26366 (6)0.0261 (3)
N10.35753 (19)0.14312 (9)0.01607 (8)0.0311 (4)
C10.35744 (17)0.04178 (10)0.37932 (8)0.0203 (3)
H10.43180.05900.34890.024*
C20.40090 (19)0.01340 (10)0.43865 (9)0.0231 (3)
H2A0.46170.05860.42080.028*
H2B0.31430.03810.45980.028*
C30.48435 (19)0.03537 (10)0.49458 (9)0.0249 (4)
H3A0.50000.00010.53580.030*
H3B0.57920.05160.47610.030*
C40.40199 (18)0.11124 (10)0.51545 (8)0.0213 (3)
C50.42653 (17)0.18504 (10)0.47296 (8)0.0187 (3)
H50.50050.17720.43600.022*
C60.31309 (17)0.24713 (9)0.45417 (8)0.0180 (3)
H60.21820.22880.47270.022*
C70.30239 (17)0.26039 (9)0.37424 (8)0.0170 (3)
H70.39090.23760.35220.020*
C80.17085 (17)0.21982 (10)0.33974 (8)0.0197 (3)
H8A0.09320.21520.37450.024*
H8B0.13620.25590.30190.024*
C90.20236 (18)0.13380 (10)0.30982 (8)0.0211 (3)
H9A0.12110.11680.28010.025*
H9B0.28870.13700.28010.025*
C100.22602 (17)0.06913 (9)0.36481 (8)0.0189 (3)
C110.30617 (16)0.35309 (9)0.36819 (8)0.0175 (3)
C120.33264 (17)0.38809 (9)0.43821 (8)0.0191 (3)
C130.29827 (17)0.40414 (9)0.31380 (8)0.0188 (3)
H130.29590.46100.32540.023*
C140.09048 (18)0.04115 (11)0.39995 (9)0.0253 (4)
H14A0.11210.00480.43130.038*
H14B0.02130.02310.36480.038*
H14C0.04980.08690.42670.038*
C150.2653 (2)0.09726 (11)0.55515 (9)0.0265 (4)
H15A0.28740.07150.59990.040*
H15B0.20210.06100.52830.040*
H15C0.21750.15010.56310.040*
C160.29273 (16)0.38648 (9)0.23919 (8)0.0175 (3)
C170.33360 (19)0.31137 (10)0.20977 (8)0.0217 (3)
H170.36990.26900.23890.026*
C180.32232 (19)0.29741 (10)0.13921 (8)0.0226 (3)
H180.35140.24590.12070.027*
C190.26861 (17)0.35823 (10)0.09458 (8)0.0182 (3)
C200.23537 (17)0.43490 (10)0.12358 (8)0.0189 (3)
H200.20370.47820.09420.023*
C210.24764 (17)0.44897 (9)0.19415 (8)0.0191 (3)
H210.22520.50180.21230.023*
C220.24427 (18)0.34952 (10)0.01995 (8)0.0202 (3)
H220.21310.39860.00220.024*
C230.25803 (18)0.28451 (10)0.02315 (8)0.0201 (3)
C240.22173 (17)0.28790 (10)0.09850 (8)0.0201 (3)
C250.13268 (17)0.35015 (10)0.12349 (8)0.0194 (3)
H250.09030.38820.09220.023*
C260.10621 (17)0.35628 (10)0.19439 (8)0.0188 (3)
C270.16914 (17)0.30063 (10)0.24085 (8)0.0189 (3)
C280.25283 (18)0.23611 (10)0.21509 (8)0.0213 (3)
C290.27962 (18)0.22993 (10)0.14397 (8)0.0229 (3)
H290.33720.18630.12660.027*
C300.07334 (18)0.45919 (11)0.17877 (8)0.0228 (3)
H30A0.13500.42010.15410.034*
H30B0.13270.49660.20640.034*
H30C0.01750.49100.14510.034*
C310.26452 (18)0.32355 (10)0.35293 (8)0.0219 (3)
H31A0.33520.35520.32650.033*
H31B0.23620.35470.39430.033*
H31C0.30650.27090.36710.033*
C320.3951 (2)0.11810 (11)0.24020 (9)0.0294 (4)
H32A0.47580.14160.21430.044*
H32B0.43140.08730.28020.044*
H32C0.34090.08100.20990.044*
C330.31313 (19)0.20649 (10)0.00030 (8)0.0219 (3)
O1M0.4544 (3)0.42249 (17)0.16592 (16)0.0371 (6)0.5
H1M0.37050.40540.15960.056*0.5
C1M0.5516 (4)0.3704 (3)0.1313 (2)0.0338 (8)0.5
H1M10.64140.40010.12300.051*0.5
H1M20.57050.32180.16000.051*0.5
H1M30.51040.35320.08680.051*0.5
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0286 (6)0.0255 (6)0.0187 (5)0.0042 (5)0.0075 (5)0.0020 (5)
O20.0323 (6)0.0182 (5)0.0125 (5)0.0012 (5)0.0003 (5)0.0012 (4)
O30.0345 (7)0.0187 (5)0.0181 (5)0.0004 (5)0.0002 (5)0.0042 (4)
O40.0247 (6)0.0275 (6)0.0153 (5)0.0082 (5)0.0013 (5)0.0017 (5)
O50.0190 (6)0.0349 (6)0.0118 (5)0.0016 (5)0.0008 (4)0.0001 (5)
O60.0331 (7)0.0291 (6)0.0161 (5)0.0110 (5)0.0011 (5)0.0044 (5)
N10.0477 (10)0.0227 (7)0.0228 (7)0.0045 (7)0.0131 (7)0.0036 (6)
C10.0219 (8)0.0184 (7)0.0205 (8)0.0015 (6)0.0034 (6)0.0030 (6)
C20.0208 (8)0.0193 (7)0.0293 (9)0.0014 (6)0.0023 (7)0.0014 (7)
C30.0251 (8)0.0239 (8)0.0258 (8)0.0009 (7)0.0036 (7)0.0060 (7)
C40.0245 (8)0.0228 (8)0.0165 (7)0.0033 (7)0.0049 (7)0.0017 (6)
C50.0200 (8)0.0223 (8)0.0137 (7)0.0030 (6)0.0017 (6)0.0007 (6)
C60.0217 (8)0.0178 (7)0.0145 (7)0.0029 (6)0.0008 (6)0.0011 (6)
C70.0189 (7)0.0183 (7)0.0137 (7)0.0018 (6)0.0008 (6)0.0001 (6)
C80.0226 (8)0.0192 (7)0.0172 (7)0.0022 (6)0.0032 (6)0.0011 (6)
C90.0252 (8)0.0208 (8)0.0174 (7)0.0003 (6)0.0019 (6)0.0049 (6)
C100.0232 (8)0.0165 (7)0.0169 (7)0.0015 (6)0.0018 (6)0.0057 (6)
C110.0179 (7)0.0192 (7)0.0154 (7)0.0020 (6)0.0005 (6)0.0017 (6)
C120.0209 (8)0.0205 (8)0.0158 (7)0.0009 (6)0.0022 (6)0.0000 (6)
C130.0206 (7)0.0175 (7)0.0183 (7)0.0008 (6)0.0012 (6)0.0012 (6)
C140.0209 (8)0.0256 (8)0.0295 (9)0.0005 (7)0.0010 (7)0.0009 (7)
C150.0329 (9)0.0265 (8)0.0201 (8)0.0039 (7)0.0032 (7)0.0039 (7)
C160.0160 (7)0.0200 (7)0.0165 (7)0.0013 (6)0.0008 (6)0.0002 (6)
C170.0293 (9)0.0201 (7)0.0158 (7)0.0052 (7)0.0011 (6)0.0029 (6)
C180.0316 (9)0.0192 (8)0.0172 (7)0.0065 (7)0.0005 (7)0.0003 (6)
C190.0194 (7)0.0205 (7)0.0147 (7)0.0005 (6)0.0011 (6)0.0015 (6)
C200.0196 (7)0.0192 (7)0.0178 (7)0.0018 (6)0.0006 (6)0.0040 (6)
C210.0226 (8)0.0164 (7)0.0183 (7)0.0002 (6)0.0002 (6)0.0005 (6)
C220.0245 (8)0.0202 (7)0.0159 (7)0.0027 (7)0.0007 (6)0.0042 (6)
C230.0226 (8)0.0219 (8)0.0158 (7)0.0015 (7)0.0013 (6)0.0023 (6)
C240.0237 (8)0.0215 (7)0.0151 (7)0.0016 (6)0.0008 (6)0.0014 (6)
C250.0215 (8)0.0227 (7)0.0140 (7)0.0003 (6)0.0002 (6)0.0006 (6)
C260.0177 (7)0.0217 (7)0.0170 (7)0.0006 (6)0.0011 (6)0.0024 (6)
C270.0174 (7)0.0263 (8)0.0130 (7)0.0016 (6)0.0006 (6)0.0010 (6)
C280.0225 (8)0.0245 (8)0.0168 (7)0.0003 (7)0.0003 (6)0.0029 (6)
C290.0277 (8)0.0229 (8)0.0181 (8)0.0047 (7)0.0028 (6)0.0007 (6)
C300.0222 (8)0.0269 (8)0.0192 (8)0.0048 (7)0.0010 (6)0.0031 (7)
C310.0230 (8)0.0264 (8)0.0165 (7)0.0005 (7)0.0029 (6)0.0007 (6)
C320.0359 (10)0.0292 (9)0.0231 (8)0.0125 (8)0.0005 (8)0.0024 (7)
C330.0301 (8)0.0225 (8)0.0130 (7)0.0001 (7)0.0046 (6)0.0031 (6)
O1M0.0289 (13)0.0360 (14)0.0465 (16)0.0027 (12)0.0055 (12)0.0064 (13)
C1M0.0213 (17)0.044 (2)0.0359 (19)0.0039 (15)0.0058 (16)0.0010 (18)
Geometric parameters (Å, º) top
O1—C51.4426 (18)C14—H14B0.9800
O1—C41.454 (2)C14—H14C0.9800
O2—C121.3500 (19)C15—H15A0.9800
O2—C61.4587 (18)C15—H15B0.9800
O3—C121.208 (2)C15—H15C0.9800
O4—C261.3602 (19)C16—C171.398 (2)
O4—C301.4321 (19)C16—C211.400 (2)
O5—C271.3713 (18)C17—C181.382 (2)
O5—C311.4381 (19)C17—H170.9500
O6—C281.3619 (19)C18—C191.402 (2)
O6—C321.425 (2)C18—H180.9500
N1—C331.151 (2)C19—C201.400 (2)
C1—C101.334 (2)C19—C221.462 (2)
C1—C21.508 (2)C20—C211.383 (2)
C1—H10.9500C20—H200.9500
C2—C31.547 (2)C21—H210.9500
C2—H2A0.9900C22—C231.349 (2)
C2—H2B0.9900C22—H220.9500
C3—C41.507 (2)C23—C331.440 (2)
C3—H3A0.9900C23—C241.491 (2)
C3—H3B0.9900C24—C291.395 (2)
C4—C51.470 (2)C24—C251.395 (2)
C4—C151.505 (2)C25—C261.391 (2)
C5—C61.506 (2)C25—H250.9500
C5—H51.0000C26—C271.401 (2)
C6—C71.558 (2)C27—C281.398 (2)
C6—H61.0000C28—C291.396 (2)
C7—C111.511 (2)C29—H290.9500
C7—C81.544 (2)C30—H30A0.9800
C7—H71.0000C30—H30B0.9800
C8—C91.540 (2)C30—H30C0.9800
C8—H8A0.9900C31—H31A0.9800
C8—H8B0.9900C31—H31B0.9800
C9—C101.508 (2)C31—H31C0.9800
C9—H9A0.9900C32—H32A0.9800
C9—H9B0.9900C32—H32B0.9800
C10—C141.505 (2)C32—H32C0.9800
C11—C131.338 (2)O1M—C1M1.408 (5)
C11—C121.484 (2)O1M—H1M0.8400
C13—C161.466 (2)C1M—H1M10.9800
C13—H130.9500C1M—H1M20.9800
C14—H14A0.9800C1M—H1M30.9800
C5—O1—C460.96 (10)C4—C15—H15A109.5
C12—O2—C6111.14 (11)C4—C15—H15B109.5
C26—O4—C30117.40 (12)H15A—C15—H15B109.5
C27—O5—C31114.60 (12)C4—C15—H15C109.5
C28—O6—C32117.42 (12)H15A—C15—H15C109.5
C10—C1—C2127.16 (15)H15B—C15—H15C109.5
C10—C1—H1116.4C17—C16—C21117.62 (14)
C2—C1—H1116.4C17—C16—C13123.93 (14)
C1—C2—C3111.01 (13)C21—C16—C13118.42 (14)
C1—C2—H2A109.4C18—C17—C16121.39 (15)
C3—C2—H2A109.4C18—C17—H17119.3
C1—C2—H2B109.4C16—C17—H17119.3
C3—C2—H2B109.4C17—C18—C19120.96 (14)
H2A—C2—H2B108.0C17—C18—H18119.5
C4—C3—C2110.34 (14)C19—C18—H18119.5
C4—C3—H3A109.6C20—C19—C18117.49 (14)
C2—C3—H3A109.6C20—C19—C22116.35 (14)
C4—C3—H3B109.6C18—C19—C22126.16 (15)
C2—C3—H3B109.6C21—C20—C19121.39 (14)
H3A—C3—H3B108.1C21—C20—H20119.3
O1—C4—C559.12 (10)C19—C20—H20119.3
O1—C4—C15112.24 (13)C20—C21—C16120.93 (14)
C5—C4—C15122.56 (15)C20—C21—H21119.5
O1—C4—C3117.45 (14)C16—C21—H21119.5
C5—C4—C3116.05 (14)C23—C22—C19131.73 (15)
C15—C4—C3116.40 (14)C23—C22—H22114.1
O1—C5—C459.92 (10)C19—C22—H22114.1
O1—C5—C6121.09 (13)C22—C23—C33122.00 (14)
C4—C5—C6124.78 (14)C22—C23—C24123.24 (15)
O1—C5—H5113.6C33—C23—C24114.74 (14)
C4—C5—H5113.6C29—C24—C25120.25 (14)
C6—C5—H5113.6C29—C24—C23119.87 (14)
O2—C6—C5108.87 (12)C25—C24—C23119.86 (14)
O2—C6—C7106.71 (12)C26—C25—C24119.76 (15)
C5—C6—C7112.02 (12)C26—C25—H25120.1
O2—C6—H6109.7C24—C25—H25120.1
C5—C6—H6109.7O4—C26—C25124.05 (14)
C7—C6—H6109.7O4—C26—C27115.54 (13)
C11—C7—C8114.26 (13)C25—C26—C27120.41 (15)
C11—C7—C6102.28 (12)O5—C27—C28121.77 (14)
C8—C7—C6114.66 (13)O5—C27—C26118.71 (14)
C11—C7—H7108.4C28—C27—C26119.43 (14)
C8—C7—H7108.4O6—C28—C29124.43 (15)
C6—C7—H7108.4O6—C28—C27115.43 (13)
C9—C8—C7113.36 (13)C29—C28—C27120.14 (14)
C9—C8—H8A108.9C24—C29—C28119.87 (15)
C7—C8—H8A108.9C24—C29—H29120.1
C9—C8—H8B108.9C28—C29—H29120.1
C7—C8—H8B108.9O4—C30—H30A109.5
H8A—C8—H8B107.7O4—C30—H30B109.5
C10—C9—C8113.42 (12)H30A—C30—H30B109.5
C10—C9—H9A108.9O4—C30—H30C109.5
C8—C9—H9A108.9H30A—C30—H30C109.5
C10—C9—H9B108.9H30B—C30—H30C109.5
C8—C9—H9B108.9O5—C31—H31A109.5
H9A—C9—H9B107.7O5—C31—H31B109.5
C1—C10—C14125.32 (15)H31A—C31—H31B109.5
C1—C10—C9120.92 (15)O5—C31—H31C109.5
C14—C10—C9113.76 (14)H31A—C31—H31C109.5
C13—C11—C12118.88 (14)H31B—C31—H31C109.5
C13—C11—C7132.60 (14)O6—C32—H32A109.5
C12—C11—C7108.40 (13)O6—C32—H32B109.5
O3—C12—O2121.34 (14)H32A—C32—H32B109.5
O3—C12—C11128.93 (15)O6—C32—H32C109.5
O2—C12—C11109.63 (13)H32A—C32—H32C109.5
C11—C13—C16130.38 (15)H32B—C32—H32C109.5
C11—C13—H13114.8N1—C33—C23177.04 (16)
C16—C13—H13114.8C1M—O1M—H1M109.5
C10—C14—H14A109.5O1M—C1M—H1M1109.5
C10—C14—H14B109.5O1M—C1M—H1M2109.5
H14A—C14—H14B109.5H1M1—C1M—H1M2109.5
C10—C14—H14C109.5O1M—C1M—H1M3109.5
H14A—C14—H14C109.5H1M1—C1M—H1M3109.5
H14B—C14—H14C109.5H1M2—C1M—H1M3109.5
C10—C1—C2—C3107.33 (19)C11—C13—C16—C1718.2 (3)
C1—C2—C3—C451.42 (18)C11—C13—C16—C21163.60 (17)
C5—O1—C4—C15115.66 (16)C21—C16—C17—C183.6 (2)
C5—O1—C4—C3105.42 (16)C13—C16—C17—C18178.17 (16)
C2—C3—C4—O1154.06 (13)C16—C17—C18—C190.3 (3)
C2—C3—C4—C587.00 (17)C17—C18—C19—C203.8 (2)
C2—C3—C4—C1568.71 (18)C17—C18—C19—C22176.49 (17)
C4—O1—C5—C6114.86 (17)C18—C19—C20—C213.4 (2)
C15—C4—C5—O198.13 (16)C22—C19—C20—C21176.89 (15)
C3—C4—C5—O1107.79 (15)C19—C20—C21—C160.6 (2)
O1—C4—C5—C6108.93 (16)C17—C16—C21—C204.1 (2)
C15—C4—C5—C610.8 (2)C13—C16—C21—C20177.64 (15)
C3—C4—C5—C6143.28 (15)C20—C19—C22—C23176.47 (17)
C12—O2—C6—C5135.46 (13)C18—C19—C22—C233.8 (3)
C12—O2—C6—C714.37 (17)C19—C22—C23—C334.2 (3)
O1—C5—C6—O244.08 (18)C19—C22—C23—C24177.52 (16)
C4—C5—C6—O2116.99 (15)C22—C23—C24—C29159.30 (17)
O1—C5—C6—C7161.85 (13)C33—C23—C24—C2919.1 (2)
C4—C5—C6—C7125.24 (16)C22—C23—C24—C2519.2 (3)
O2—C6—C7—C1111.56 (16)C33—C23—C24—C25162.36 (15)
C5—C6—C7—C11130.62 (13)C29—C24—C25—C262.5 (2)
O2—C6—C7—C8135.79 (13)C23—C24—C25—C26175.96 (15)
C5—C6—C7—C8105.15 (15)C30—O4—C26—C2516.8 (2)
C11—C7—C8—C9147.81 (13)C30—O4—C26—C27164.02 (14)
C6—C7—C8—C994.58 (15)C24—C25—C26—O4179.51 (15)
C7—C8—C9—C1070.67 (17)C24—C25—C26—C270.4 (2)
C2—C1—C10—C148.4 (3)C31—O5—C27—C2863.9 (2)
C2—C1—C10—C9171.04 (14)C31—O5—C27—C26119.53 (16)
C8—C9—C10—C1104.35 (17)O4—C26—C27—O50.7 (2)
C8—C9—C10—C1475.17 (18)C25—C26—C27—O5179.93 (14)
C8—C7—C11—C1354.0 (2)O4—C26—C27—C28177.44 (14)
C6—C7—C11—C13178.52 (17)C25—C26—C27—C283.4 (2)
C8—C7—C11—C12130.10 (14)C32—O6—C28—C292.5 (2)
C6—C7—C11—C125.60 (16)C32—O6—C28—C27177.21 (15)
C6—O2—C12—O3172.42 (15)O5—C27—C28—O60.3 (2)
C6—O2—C12—C1110.86 (17)C26—C27—C28—O6176.89 (14)
C13—C11—C12—O32.6 (3)O5—C27—C28—C29179.97 (15)
C7—C11—C12—O3179.18 (17)C26—C27—C28—C293.4 (2)
C13—C11—C12—O2173.76 (14)C25—C24—C29—C282.5 (2)
C7—C11—C12—O22.78 (18)C23—C24—C29—C28176.03 (15)
C12—C11—C13—C16170.76 (16)O6—C28—C29—C24179.82 (16)
C7—C11—C13—C164.8 (3)C27—C28—C29—C240.5 (2)

Experimental details

Crystal data
Chemical formulaC33H35NO6·0.5CH4O
Mr557.64
Crystal system, space groupOrthorhombic, P212121
Temperature (K)90
a, b, c (Å)9.3347 (2), 16.2442 (3), 19.2580 (4)
V3)2920.18 (10)
Z4
Radiation typeCu Kα
µ (mm1)0.71
Crystal size (mm)0.18 × 0.15 × 0.10
Data collection
DiffractometerBruker X8 Proteum
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 2008b)
Tmin, Tmax0.836, 0.963
No. of measured, independent and
observed [I > 2σ(I)] reflections
40379, 5349, 5303
Rint0.036
(sin θ/λ)max1)0.603
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.024, 0.065, 1.03
No. of reflections5349
No. of parameters387
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.14, 0.13
Absolute structureFlack x determined using 2283 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Absolute structure parameter0.02 (2)

Computer programs: APEX2 (Bruker, 2006), SHELXS97 (Sheldrick, 2008a), SHELXL2014 (Sheldrick, 2008a), XP in SHELXTL (Sheldrick, 2008a), SHELXL97 (Sheldrick, 2008a), CIFFIX (Parkin, 2013), PLATON (Spek, 2009) and local program (Parkin, 2000).

 

Acknowledgements

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

References

First citationBruker (2006). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationHall, I. H., Lee, K. H., Starnes, C. O., Sumida, Y., Wu, R. Y., Waddell, T. G., Cochran, J. W. & Gerhart, K. G. (1979). J. Pharm. Sci. 68, 537–542.  CrossRef CAS PubMed Web of Science Google Scholar
First citationHan, C., Barrios, F. J., Riofski, M. V. & Colby, D. A. (2009). J. Org. Chem. 74, 7176–7179.  Web of Science CSD CrossRef PubMed CAS Google Scholar
First citationHanson, R. L., Lardy, H. A. & Kupchan, S. M. (1970). Science, 168, 378–380.  CrossRef CAS PubMed Web of Science Google Scholar
First citationHehner, S. P., Heinrich, M., Bork, P. M., Vogt, M., Ratter, F., Lehmann, V., Osthoff, K. S., Dröge, W. & Schmitz, M. L. (1998). J. Biol. Chem. 273, 1288–1297.  Web of Science CrossRef CAS PubMed Google Scholar
First citationHope, H. (1994). Prog. Inorg. Chem. 41, 1–19.  CrossRef CAS Web of Science Google Scholar
First citationKupchan, S. M., Eakin, M. A. & Thomas, A. M. (1971). J. Med. Chem. 14, 1147–1152.  CrossRef CAS PubMed Web of Science Google Scholar
First citationNeelakantan, S., Nasim, S., Guzman, M. L., Jordan, C. T. & Crooks, P. A. (2009). Bioorg. Med. Chem. Lett. 19, 4346–4349.  Web of Science CrossRef PubMed CAS Google Scholar
First citationOka, D., Nishimura, K., Shiba, M., Nakai, Y., Arai, Y., Nakayama, M., Takayama, H., Inoue, H., Okuyama, A. & Nonomura, N. (2007). Int. J. Cancer, 120, 2576–2581.  Web of Science CrossRef PubMed CAS Google Scholar
First citationParkin, S. (2000). Acta Cryst. A56, 157–162.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationParkin, S. (2013). CIFFIX, http://xray.uky.edu/people/parkin/programs/ciffixGoogle Scholar
First citationParkin, S. & Hope, H. (1998). J. Appl. Cryst. 31, 945–953.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationParsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationPenthala, N. R., Janganati, V., Parkin, S., Varughese, K. I. & Crooks, P. A. (2013a). Acta Cryst. E69, o1709–o1710.  CSD CrossRef CAS IUCr Journals Google Scholar
First citationPenthala, N. R., Sonar, V. N., Horn, J., Leggas, M., Yadlapalli, J. S. & Crooks, P. A. (2013b). Medchemcomm, 4, 1073–1078.  Web of Science CrossRef CAS PubMed Google Scholar
First citationRalstin, M. C., Gage, E. A., Yip-Schneider, M. T., Klein, P. J., Wiebke, E. A. & Schmidt, C. M. (2006). Mol. Cancer Res. 4, 387–399.  Web of Science CrossRef PubMed CAS Google Scholar
First citationSheldrick, G. M. (2008a). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2008b). SADABS. University of Göttingen, Germany.  Google Scholar
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSun, H.-X., Zheng, Q.-F. & Tu, J. (2006). Bioorg. Med. Chem. 14, 1189–1198.  Web of Science CrossRef PubMed CAS Google Scholar

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Volume 70| Part 10| October 2014| Pages o1092-o1093
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