research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

Crystal structure of (E)-13-(pyrimidin-5-yl)parthenolide

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

Edited by G. Smith, Queensland University of Technology, Australia (Received 2 October 2015; accepted 12 November 2015; online 28 November 2015)

The title compound, C19H22N2O3, {systematic name (1aR,4E,7aS,8E,10aS,10bR)-1a,5-dimethyl-8-[(pyrimidin-5-yl)­methylid­ene]-2,3,6,7,7a,8,10a,10b-octa­hydro­oxireno[2′,3′:9,10]cyclo­deca­[1,2-b]furan-9(1aH)-one} was obtained from the reaction of parthenolide [systematic name (1aR,7aS,10aS,10bR,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] with 5-bromo­pyrimidine under Heck reaction conditions, and was identified as an E isomer. The mol­ecule possesses ten-, five- (lactone) and three-membered (epoxide) rings with a pyrimidine group as a substituent. The ten-membered ring displays an approximate chair–chair conformation, while the lactone ring shows a flattened envelope-type conformation. The dihedral angle between the pyrimidine moiety and the lactone ring system is 29.43 (7)°.

1. Chemical context

Parthenolide (PTL) is a sesquiterpene lactone known to significantly target cancer stem cells, which are the putative roots of all types of cancer (Gopal et al., 2007[Gopal, Y. N. V., Arora, T. S. & Van Dyke, M. W. (2007). Chem. Biol. 14, 813-823.]). PTL has been isolated from several different plant species, feverfew leaf (Tanacetum parthenium) being one of the major sources (Awang, 1989[Awang, D. V. C. (1989). Can. Pharm. J. 122, 266-270.]). PTL exhibits a wide range of biological activities, such as anti-inflammatory, anti-bacterial, anti-fungal, and cytotoxic properties (Picman, 1986[Picman, A. K. (1986). Biochem. Syst. Ecol. 14, 255-281.]). Consequently, PTL was discovered to be capable of inducing robust apoptosis in primary acute myelogenous leukemia (AML) cells (Guzman et al., 2007[Guzman, M. L., Rossi, R. M., Neelakantan, S., Li, X., Corbett, C. A., Hassane, D. C., Becker, M. W., Bennett, J. M., Sullivan, E., Lachowicz, J. L., Vaughan, A., Sweeney, C. J., Matthews, W., Carroll, M., Liesveld, J. L., Crooks, P. A. & Jordan, C. T. (2007). Blood, 110, 4427-4435.]), proving to be equally effective among all subpopulations within primary AML specimens, including leukemia stem cells (LSCs). Gopal et al. (2007[Gopal, Y. N. V., Arora, T. S. & Van Dyke, M. W. (2007). Chem. Biol. 14, 813-823.]) reported that PTL specifically depletes HDAC1 protein without affecting other class I/II HDACs (histone de­acetyl­ases). Nasim et al. (2008[Nasim, S. & Crooks, P. A. (2008). Bioorg. Med. Chem. Lett. 18, 3870-3873.]) reported the anti-leukemic activity of amino­parthenolide analogues. Han et al. (2009[Han, C., Barrios, F. J., Riofski, M. V. & Colby, D. A. (2009). J. Org. Chem. 74, 7176-7179.]) reported on bioactive derivatives of Heck products of PTL. Recently, Penthala et al. (2014a[Penthala, N. R., Bommagani, S., Janganati, V., MacNicol, K. B., Cragle, C. E., Madadi, N. R., Hardy, L. L., MacNicol, A. M. & Crooks, P. A. (2014a). Eur. J. Med. Chem. 85, 517-525.]) reported the anti-cancer activity of PTL–Heck products. Recently we (Penthala et al., 2014b[Penthala, N. R., Bommagani, S., Janganati, V., Parkin, S. & Crooks, P. A. (2014b). Acta Cryst. E70, o1092-o1093.]) reported the crystal structure of 13-{4-[Z–2-cyano-2-(3,4,5-tri­meth­oxy­phen­yl)ethen­yl]phen­yl} parthenolide, an analog of PTL, which was found to have the E configuration at C-13. The inter­esting biological properties of PTL directed our attention to design and synthesize additional bioactive derivatives. In order to obtain detailed information on the structural conformation of the current mol­ecule, including assignment of the absolute configuration of the four stereocentres, and to establish the geometry of the exocyclic double bond, a single crystal X-ray structure determination has been carried out.

[Scheme 1]

2. Structural commentary

The title compound is shown in Fig. 1[link]. The PTL substructure of the mol­ecule contains a ten-membered carbocyclic ring (chair–chair conformation) fused to a lactone ring (flattened envelope-type conformation), and an epoxide ring, as previously reported (Castañeda-Acosta & Fisher, 1993[Castañeda-Acosta, J., Fischer, N. H. & Vargas, D. (1993). J. Nat. Prod. 56, 90-98.]). The title compound contains an E-exocyclic olefinic bond C11=C13. The pyrimidine ring is twisted out of the plane of the furan ring, making a dihedral angle of 29.43 (7)°. The C11=C13—C16 bond angle of 127.89 (16)° deviates from the ideal value of 120°, but other bond lengths and angles are largely unremarkable. The four chiral carbon atoms in PTL were determined using 1354 quotients (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]) as follows: C4(R),C5(R),C6(S),C7(S) for the arbitrary atom-numbering scheme used, and is consistent with previous studies (Penthala et al., 2013[Penthala, N. R., Janganati, V., Parkin, S., Varughese, K. I. & Crooks, P. A. (2013). Acta Cryst. E69, o1709-o1710.]).

[Figure 1]
Figure 1
The mol­ecular structure of the title compound with probability ellipsoids drawn at the 50% probability level.

3. Supra­molecular features

There are no classical hydrogen bonds and no ππ inter­actions. There are a few C—H⋯N and C—H⋯O short contacts, but none that have the right geometry to be considered as non-classical hydrogen bonds. Inter­molecular contacts thus appear to be limited to van der Waals inter­actions.

4. Database survey

A search of the November 2014 release of the Cambridge Structure Database (Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662-671.]) for the PTL substructure gave 24 hits. Two of these (PARTEN: Quick & Rogers, 1976[Quick, A. & Rogers, D. (1976). J. Chem. Soc. Perkin Trans. 2, pp. 465-469.]; PARTEN01: Bartsch et al., 1983[Bartsch, H.-H., Jarchow, O. & Schmalle, H. W. (1983). Z. Kristallogr. 162, 15-17.]) give the structure of PTL itself, with the remaining 22 being substituted variants of PTL. Of these substituted parthenolides, only four CSD entries: HORZOF (Penthala et al., 2014b[Penthala, N. R., Bommagani, S., Janganati, V., Parkin, S. & Crooks, P. A. (2014b). Acta Cryst. E70, o1092-o1093.]), HUKLAB, HUKLEF (Han et al., 2009[Han, C., Barrios, F. J., Riofski, M. V. & Colby, D. A. (2009). J. Org. Chem. 74, 7176-7179.]) and QILGEZ (Penthala et al., 2013[Penthala, N. R., Janganati, V., Parkin, S., Varughese, K. I. & Crooks, P. A. (2013). Acta Cryst. E69, o1709-o1710.]), are substituted at the exocyclic double bond.

5. Synthesis and crystallization

Synthetic procedures: The title compound, containing the PTL substructure, was synthesized by the previously reported literature procedure (Han et al., 2009[Han, C., Barrios, F. J., Riofski, M. V. & Colby, D. A. (2009). J. Org. Chem. 74, 7176-7179.]). In brief, parthenolide (1 mmol), 5-bromo­pyrimidine (1.1 mmol), tri­ethyl­amine (3.0 mmol) and 5 mol% of palladium acetate were charged into di­methyl­formamide (2 ml) at room temperature. The reactants were stirred at 333–343 K for 24 h. After completion of the reaction, the reaction mass was extracted into diethyl ether (2 × 30 ml). The combined organic layers were dried over anhydrous sodium sulfate, concentrated and purified by column chromatography. The title compound was recrystallized from a mixture of hexane and acetone (9:1), which gave colourless needles upon slow evaporation of the solution at room temperature over 24 h.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1[link]. H atoms were found in difference Fourier maps, but subsequently included in the refinement using riding models, with constrained distances set to 0.95 Å (Csp2H), 0.98 Å (RCH3), 0.99 Å (R2CH2) and 1.00 Å (R3CH). Uiso(H) parameters were set to values of either 1.2Ueq or 1.5Ueq (RCH3 only) of the attached atom. The absolute structure parameter [−0.04 (3)] was determined directly from the diffraction data using 1354 Parsons quotients (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]), with the four chiral carbon atoms assigned to be R,R,S,S for the arbitrarily numbered atoms C4, C5, C6, C7, respectively.

Table 1
Experimental details

Crystal data
Chemical formula C19H22N2O3
Mr 326.38
Crystal system, space group Monoclinic, P21
Temperature (K) 90
a, b, c (Å) 10.3526 (2), 7.2612 (1), 11.9198 (2)
β (°) 108.1210 (6)
V3) 851.60 (2)
Z 2
Radiation type Cu Kα
μ (mm−1) 0.70
Crystal size (mm) 0.25 × 0.13 × 0.10
 
Data collection
Diffractometer Bruker X8 Proteum
Absorption correction Multi-scan (SADABS; Bruker, 2006[Bruker (2006). APEX2, SAINT and SADABS. Bruker-AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.850, 0.942
No. of measured, independent and observed [I > 2σ(I)] reflections 11370, 3020, 3013
Rint 0.032
(sin θ/λ)max−1) 0.602
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.027, 0.068, 1.05
No. of reflections 3020
No. of parameters 220
No. of restraints 1
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.15, −0.14
Absolute structure Flack x determined using 1354 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 −0.04 (3)
Computer programs: APEX2 and SAINT (Bruker, 2006[Bruker (2006). APEX2, SAINT and SADABS. Bruker-AXS Inc., Madison, Wisconsin, USA.]), SHELXS97, SHELXTL and XP in SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and CIFFIX (Parkin, 2013[Parkin, S. (2013). CIFFIX. http://xray.uky.edu/people/parkin/programs/ciffix]).

Refinement progress was checked using PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]) and by an R-tensor (Parkin, 2000[Parkin, S. (2000). Acta Cryst. A56, 157-162.]).

Supporting information


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, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and CIFFIX (Parkin, 2013).

(1aR,4E,7aS,8E,10aS,10bR)-1a,5-Dimethyl-8-[(pyrimidin-5-yl)methylidene]-2,3,6,7,7a,8,10a,10b-octahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-9(1aH)-one top
Crystal data top
C19H22N2O3F(000) = 348
Mr = 326.38Dx = 1.273 Mg m3
Monoclinic, P21Cu Kα radiation, λ = 1.54178 Å
a = 10.3526 (2) ÅCell parameters from 9908 reflections
b = 7.2612 (1) Åθ = 4.5–68.2°
c = 11.9198 (2) ŵ = 0.70 mm1
β = 108.1210 (6)°T = 90 K
V = 851.60 (2) Å3Solvent-rounded block, colourless
Z = 20.25 × 0.13 × 0.10 mm
Data collection top
Bruker X8 Proteum
diffractometer
3020 independent reflections
Radiation source: fine-focus rotating anode3013 reflections with I > 2σ(I)
Detector resolution: 5.6 pixels mm-1Rint = 0.032
φ and ω scansθmax = 68.2°, θmin = 4.5°
Absorption correction: multi-scan
(SADABS; Bruker, 2006)
h = 1210
Tmin = 0.850, Tmax = 0.942k = 88
11370 measured reflectionsl = 1413
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.027 w = 1/[σ2(Fo2) + (0.0326P)2 + 0.1773P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.068(Δ/σ)max < 0.001
S = 1.05Δρmax = 0.15 e Å3
3020 reflectionsΔρmin = 0.14 e Å3
220 parametersExtinction correction: SHELXL-2014, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.010 (2)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack x determined using 1354 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013).
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 0.04 (3)
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.

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

The crystals were large, and could not be cut to size without inducing damage by crushing, leading to shattered, frayed ends. These damaged parts could easily be dissolved away, however, to give solvent-rounded undamaged pieces of optimal size for data collection.

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*/Ueq
O10.59428 (12)0.24072 (19)0.48957 (10)0.0228 (3)
O20.30633 (12)0.25486 (17)0.43887 (10)0.0195 (3)
O30.12397 (13)0.29255 (19)0.49855 (11)0.0266 (3)
C10.57679 (17)0.5285 (2)0.19945 (14)0.0185 (4)
H1A0.58330.64390.23840.022*
C20.70386 (17)0.4134 (3)0.23289 (16)0.0208 (4)
H2A0.78090.48810.22570.025*
H2B0.69150.30760.17810.025*
C30.73676 (17)0.3417 (3)0.36116 (15)0.0202 (4)
H3A0.81460.25540.37920.024*
H3B0.76150.44600.41730.024*
C40.61322 (17)0.2447 (2)0.37345 (14)0.0178 (4)
C50.51035 (16)0.3615 (2)0.40010 (13)0.0165 (3)
H5A0.53530.49480.41180.020*
C60.35977 (16)0.3252 (2)0.34753 (14)0.0159 (3)
H6A0.34450.23210.28290.019*
C70.27894 (16)0.5036 (2)0.29783 (13)0.0149 (3)
H7A0.33960.61130.32920.018*
C80.22800 (16)0.5184 (3)0.16174 (14)0.0176 (4)
H8A0.14340.59230.13760.021*
H8B0.20580.39360.12780.021*
C90.33322 (17)0.6078 (3)0.11062 (14)0.0185 (4)
H9A0.28840.63580.02610.022*
H9B0.36380.72580.15190.022*
C100.45591 (17)0.4887 (2)0.12176 (14)0.0179 (4)
C110.16862 (16)0.5027 (2)0.35605 (14)0.0159 (3)
C120.19100 (17)0.3425 (3)0.43718 (14)0.0184 (4)
C130.06867 (17)0.6212 (3)0.35248 (14)0.0179 (4)
H13A0.00960.58720.39610.021*
C140.42876 (19)0.3267 (3)0.03864 (16)0.0269 (4)
H14A0.51400.26090.04730.040*
H14B0.39080.37050.04280.040*
H14C0.36390.24340.05730.040*
C150.57578 (18)0.0643 (2)0.30934 (18)0.0239 (4)
H15A0.50120.00720.33110.036*
H15B0.65480.01790.33120.036*
H15C0.54700.08610.22400.036*
C160.03901 (16)0.7977 (2)0.28928 (14)0.0180 (4)
C170.13568 (18)0.9097 (3)0.26601 (18)0.0244 (4)
H17A0.22810.87190.29330.029*
N180.10538 (16)1.0688 (2)0.20684 (16)0.0293 (4)
C190.02533 (19)1.1156 (3)0.17269 (17)0.0252 (4)
H19A0.04851.22650.12870.030*
N200.12697 (15)1.0248 (2)0.19312 (14)0.0256 (4)
C210.09291 (18)0.8673 (3)0.25279 (15)0.0219 (4)
H21A0.16210.79940.27130.026*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0188 (6)0.0306 (7)0.0176 (6)0.0061 (5)0.0035 (5)0.0092 (5)
O20.0187 (6)0.0200 (6)0.0221 (6)0.0038 (5)0.0098 (5)0.0064 (5)
O30.0242 (6)0.0305 (8)0.0303 (7)0.0031 (6)0.0162 (5)0.0097 (6)
C10.0218 (8)0.0163 (8)0.0197 (8)0.0006 (7)0.0100 (7)0.0024 (7)
C20.0184 (8)0.0208 (9)0.0254 (9)0.0018 (7)0.0101 (7)0.0001 (7)
C30.0157 (8)0.0216 (9)0.0228 (8)0.0016 (7)0.0053 (6)0.0004 (7)
C40.0163 (8)0.0184 (8)0.0174 (8)0.0036 (7)0.0031 (6)0.0040 (7)
C50.0175 (8)0.0173 (8)0.0141 (7)0.0020 (7)0.0043 (6)0.0031 (6)
C60.0173 (8)0.0162 (8)0.0154 (7)0.0002 (6)0.0068 (6)0.0012 (6)
C70.0155 (7)0.0147 (8)0.0142 (7)0.0011 (6)0.0041 (6)0.0008 (6)
C80.0172 (8)0.0201 (8)0.0143 (8)0.0005 (7)0.0034 (6)0.0003 (7)
C90.0209 (8)0.0195 (8)0.0147 (7)0.0018 (7)0.0051 (6)0.0044 (7)
C100.0221 (8)0.0190 (9)0.0150 (7)0.0003 (7)0.0092 (7)0.0026 (7)
C110.0153 (7)0.0170 (8)0.0143 (7)0.0021 (7)0.0031 (6)0.0010 (7)
C120.0166 (8)0.0206 (9)0.0187 (8)0.0004 (7)0.0065 (6)0.0014 (7)
C130.0144 (8)0.0213 (9)0.0175 (8)0.0011 (7)0.0044 (6)0.0018 (7)
C140.0258 (9)0.0321 (11)0.0219 (8)0.0041 (8)0.0061 (7)0.0061 (8)
C150.0206 (8)0.0177 (9)0.0346 (10)0.0023 (7)0.0105 (8)0.0005 (7)
C160.0175 (8)0.0190 (9)0.0161 (7)0.0009 (7)0.0032 (6)0.0044 (7)
C170.0156 (8)0.0189 (9)0.0350 (10)0.0005 (7)0.0024 (8)0.0019 (8)
N180.0209 (8)0.0216 (9)0.0409 (10)0.0014 (6)0.0030 (7)0.0062 (7)
C190.0240 (9)0.0183 (9)0.0288 (9)0.0021 (8)0.0016 (7)0.0019 (8)
N200.0206 (8)0.0232 (8)0.0304 (8)0.0042 (6)0.0043 (6)0.0003 (7)
C210.0194 (8)0.0219 (9)0.0253 (9)0.0026 (7)0.0084 (7)0.0024 (7)
Geometric parameters (Å, º) top
O1—C51.444 (2)C8—H8B0.9900
O1—C41.457 (2)C9—C101.508 (2)
O2—C121.348 (2)C9—H9A0.9900
O2—C61.4585 (19)C9—H9B0.9900
O3—C121.210 (2)C10—C141.507 (3)
C1—C101.337 (2)C11—C131.336 (2)
C1—C21.504 (2)C11—C121.484 (2)
C1—H1A0.9500C13—C161.470 (2)
C2—C31.549 (2)C13—H13A0.9500
C2—H2A0.9900C14—H14A0.9800
C2—H2B0.9900C14—H14B0.9800
C3—C41.507 (2)C14—H14C0.9800
C3—H3A0.9900C15—H15A0.9800
C3—H3B0.9900C15—H15B0.9800
C4—C51.471 (2)C15—H15C0.9800
C4—C151.505 (3)C16—C171.383 (3)
C5—C61.511 (2)C16—C211.393 (2)
C5—H5A1.0000C17—N181.339 (2)
C6—C71.556 (2)C17—H17A0.9500
C6—H6A1.0000N18—C191.330 (2)
C7—C111.510 (2)C19—N201.327 (3)
C7—C81.546 (2)C19—H19A0.9500
C7—H7A1.0000N20—C211.335 (3)
C8—C91.547 (2)C21—H21A0.9500
C8—H8A0.9900
C5—O1—C460.94 (10)H8A—C8—H8B107.8
C12—O2—C6111.31 (12)C10—C9—C8113.70 (14)
C10—C1—C2128.05 (17)C10—C9—H9A108.8
C10—C1—H1A116.0C8—C9—H9A108.8
C2—C1—H1A116.0C10—C9—H9B108.8
C1—C2—C3110.73 (14)C8—C9—H9B108.8
C1—C2—H2A109.5H9A—C9—H9B107.7
C3—C2—H2A109.5C1—C10—C14124.58 (16)
C1—C2—H2B109.5C1—C10—C9121.22 (16)
C3—C2—H2B109.5C14—C10—C9114.20 (15)
H2A—C2—H2B108.1C13—C11—C12119.20 (15)
C4—C3—C2108.68 (14)C13—C11—C7132.19 (16)
C4—C3—H3A110.0C12—C11—C7108.42 (13)
C2—C3—H3A110.0O3—C12—O2121.43 (16)
C4—C3—H3B110.0O3—C12—C11128.78 (16)
C2—C3—H3B110.0O2—C12—C11109.75 (13)
H3A—C3—H3B108.3C11—C13—C16127.89 (16)
O1—C4—C559.08 (10)C11—C13—H13A116.1
O1—C4—C15112.05 (15)C16—C13—H13A116.1
C5—C4—C15121.46 (15)C10—C14—H14A109.5
O1—C4—C3118.08 (14)C10—C14—H14B109.5
C5—C4—C3116.40 (15)H14A—C14—H14B109.5
C15—C4—C3116.73 (15)C10—C14—H14C109.5
O1—C5—C459.97 (10)H14A—C14—H14C109.5
O1—C5—C6120.41 (14)H14B—C14—H14C109.5
C4—C5—C6122.16 (14)C4—C15—H15A109.5
O1—C5—H5A114.5C4—C15—H15B109.5
C4—C5—H5A114.5H15A—C15—H15B109.5
C6—C5—H5A114.5C4—C15—H15C109.5
O2—C6—C5109.48 (12)H15A—C15—H15C109.5
O2—C6—C7106.97 (12)H15B—C15—H15C109.5
C5—C6—C7112.07 (13)C17—C16—C21115.11 (16)
O2—C6—H6A109.4C17—C16—C13124.52 (15)
C5—C6—H6A109.4C21—C16—C13120.31 (15)
C7—C6—H6A109.4N18—C17—C16123.19 (16)
C11—C7—C8115.01 (13)N18—C17—H17A118.4
C11—C7—C6102.45 (13)C16—C17—H17A118.4
C8—C7—C6115.15 (13)C19—N18—C17115.52 (17)
C11—C7—H7A107.9N20—C19—N18127.34 (18)
C8—C7—H7A107.9N20—C19—H19A116.3
C6—C7—H7A107.9N18—C19—H19A116.3
C7—C8—C9112.99 (13)C19—N20—C21115.48 (15)
C7—C8—H8A109.0N20—C21—C16123.23 (17)
C9—C8—H8A109.0N20—C21—H21A118.4
C7—C8—H8B109.0C16—C21—H21A118.4
C9—C8—H8B109.0
C10—C1—C2—C3110.99 (19)C2—C1—C10—C148.9 (3)
C1—C2—C3—C453.54 (19)C2—C1—C10—C9171.47 (16)
C5—O1—C4—C15114.44 (16)C8—C9—C10—C1107.23 (18)
C5—O1—C4—C3105.54 (17)C8—C9—C10—C1473.07 (19)
C2—C3—C4—O1152.28 (15)C8—C7—C11—C1356.5 (2)
C2—C3—C4—C584.95 (18)C6—C7—C11—C13177.78 (17)
C2—C3—C4—C1569.54 (18)C8—C7—C11—C12128.73 (15)
C4—O1—C5—C6111.94 (17)C6—C7—C11—C123.06 (16)
C15—C4—C5—O198.43 (17)C6—O2—C12—O3172.90 (16)
C3—C4—C5—O1108.37 (16)C6—O2—C12—C119.33 (18)
O1—C4—C5—C6109.10 (17)C13—C11—C12—O35.6 (3)
C15—C4—C5—C610.7 (2)C7—C11—C12—O3178.86 (18)
C3—C4—C5—C6142.53 (15)C13—C11—C12—O2171.94 (15)
C12—O2—C6—C5132.85 (14)C7—C11—C12—O23.59 (18)
C12—O2—C6—C711.21 (17)C12—C11—C13—C16172.57 (15)
O1—C5—C6—O236.7 (2)C7—C11—C13—C161.7 (3)
C4—C5—C6—O2108.24 (17)C11—C13—C16—C1729.8 (3)
O1—C5—C6—C7155.20 (14)C11—C13—C16—C21153.17 (17)
C4—C5—C6—C7133.25 (15)C21—C16—C17—N183.7 (3)
O2—C6—C7—C118.19 (16)C13—C16—C17—N18179.10 (17)
C5—C6—C7—C11128.18 (14)C16—C17—N18—C191.1 (3)
O2—C6—C7—C8133.78 (14)C17—N18—C19—N201.7 (3)
C5—C6—C7—C8106.23 (15)N18—C19—N20—C211.4 (3)
C11—C7—C8—C9153.12 (15)C19—N20—C21—C161.7 (3)
C6—C7—C8—C988.08 (18)C17—C16—C21—N204.0 (2)
C7—C8—C9—C1069.71 (19)C13—C16—C21—N20178.66 (16)
 

Acknowledgements

This work was supported by NIH/NCI grant CA158275.

References

First citationAwang, D. V. C. (1989). Can. Pharm. J. 122, 266–270.  Google Scholar
First citationBartsch, H.-H., Jarchow, O. & Schmalle, H. W. (1983). Z. Kristallogr. 162, 15–17.  Google Scholar
First citationBruker (2006). APEX2, SAINT and SADABS. Bruker-AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationCastañeda-Acosta, J., Fischer, N. H. & Vargas, D. (1993). J. Nat. Prod. 56, 90–98.  PubMed Web of Science Google Scholar
First citationGopal, Y. N. V., Arora, T. S. & Van Dyke, M. W. (2007). Chem. Biol. 14, 813–823.  Web of Science CrossRef PubMed CAS Google Scholar
First citationGroom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662–671.  Web of Science CSD CrossRef CAS Google Scholar
First citationGuzman, M. L., Rossi, R. M., Neelakantan, S., Li, X., Corbett, C. A., Hassane, D. C., Becker, M. W., Bennett, J. M., Sullivan, E., Lachowicz, J. L., Vaughan, A., Sweeney, C. J., Matthews, W., Carroll, M., Liesveld, J. L., Crooks, P. A. & Jordan, C. T. (2007). Blood, 110, 4427–4435.  Web of Science CrossRef PubMed CAS 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 citationNasim, S. & Crooks, P. A. (2008). Bioorg. Med. Chem. Lett. 18, 3870–3873.  Web of Science CSD 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/ciffix  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., Bommagani, S., Janganati, V., MacNicol, K. B., Cragle, C. E., Madadi, N. R., Hardy, L. L., MacNicol, A. M. & Crooks, P. A. (2014a). Eur. J. Med. Chem. 85, 517–525.  Web of Science CrossRef CAS PubMed Google Scholar
First citationPenthala, N. R., Bommagani, S., Janganati, V., Parkin, S. & Crooks, P. A. (2014b). Acta Cryst. E70, o1092–o1093.  CSD CrossRef IUCr Journals Google Scholar
First citationPenthala, N. R., Janganati, V., Parkin, S., Varughese, K. I. & Crooks, P. A. (2013). Acta Cryst. E69, o1709–o1710.  CSD CrossRef CAS IUCr Journals Google Scholar
First citationPicman, A. K. (1986). Biochem. Syst. Ecol. 14, 255–281.  CrossRef CAS Web of Science Google Scholar
First citationQuick, A. & Rogers, D. (1976). J. Chem. Soc. Perkin Trans. 2, pp. 465–469.  CSD CrossRef Web of Science Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds