Vadimezan: 2-(5,6-dimethyl-9-oxo-9H-xanthen-4-yl)acetic acid.

In the title mol-ecule, C(17)H(14)O(4), the C atom of the carboxyl group deviates by 1.221 (3) Å from the plane [maximum deviation = 0.0122(2) Å] of the tricycic ring system. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers, and π-π inter-actions [centroid-centroid distances = 3.491 (3), 3.591 (3), 3.639 (3) and 3.735 (3) Å] link these dimers into layers parallel to the ac plane. Weak inter-molecular C-H⋯O inter-actions further consolidate the crystal packing.

Related literature

For general background to and recent reviews of vascular-disrupting agents and the development of Vadimezan (DMXAA, ASA404), a promising small-mol­ecule tumor-vascular disrupting agent in phase III clinical trials, see: McKeage & Baguley (2010 ▶); Head & Jameson (2010 ▶); Ching (2008 ▶); Patterson & Rustin (2007 ▶); Hinnen & Eskens (2007 ▶); Lippert (2007 ▶). For a recent clinical study of Vadimezan, see: Pili et al. (2010 ▶); McKeage et al. (2008 ▶, 2009 ▶). For studies of the mol­ecular mechanisms and signal pathways of Vadimezan, see: Zhan et al. (2010 ▶); Cheng et al. (2010 ▶); Roberts et al. (2008 ▶). For the biological and pharmacological activity of Vadimezan analogues with structure–activity relationships, see: Gobbi et al. (2006 ▶); Woon et al. (2005 ▶). For the synthesis and spectroscopic data for Vadimezan, see: Yang & Denny (2009 ▶); Atwell et al. (2002 ▶). For related xanthone structures, see: Yu et al. (2008 ▶); Zhang et al. (2007 ▶).

Experimental

Crystal data

C17H14O4

M = 282.28

Triclinic,

a = 6.7854 (19) Å

b = 9.826 (3) Å

c = 10.532 (3) Å

α = 71.435 (7)°

β = 82.741 (9)°

γ = 83.142 (9)°

V = 658.0 (3) Å3

Z = 2

Mo Kα radiation

μ = 0.10 mm−1

T = 163 K

0.50 × 0.50 × 0.37 mm

Data collection

Rigaku AFC10/Saturn724+ diffractometer

6284 measured reflections

2955 independent reflections

2304 reflections with I > 2σ(I)

R int = 0.018

Refinement

R[F 2 > 2σ(F 2)] = 0.040

wR(F 2) = 0.094

S = 1.00

2955 reflections

195 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.26 e Å−3

Δρmin = −0.17 e Å−3

Data collection: CrystalClear (Rigaku/MSC, 2008 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXL97 (Sheldrick, 2008 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶) and PLATON (Spek, 2009 ▶).

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810028394/cv2747sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810028394/cv2747Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C17H14O4	Z = 2
Mr = 282.28	F(000) = 296
Triclinic, P1	Dx = 1.425 Mg m−3
a = 6.7854 (19) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.826 (3) Å	Cell parameters from 1944 reflections
c = 10.532 (3) Å	θ = 3.0–27.5°
α = 71.435 (7)°	µ = 0.10 mm−1
β = 82.741 (9)°	T = 163 K
γ = 83.142 (9)°	Block, colorless
V = 658.0 (3) Å3	0.50 × 0.50 × 0.37 mm

Rigaku AFC10/Saturn724+ diffractometer	2304 reflections with I > 2σ(I)
Radiation source: Rotating Anode	Rint = 0.018
graphite	θmax = 27.5°, θmin = 3.4°
Detector resolution: 28.5714 pixels mm-1	h = −8→8
phi and ω scans	k = −11→12
6284 measured reflections	l = −13→13
2955 independent reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.094	H atoms treated by a mixture of independent and constrained refinement
S = 1.00	w = 1/[σ2(Fo2) + (0.0346P)2 + 0.226P] where P = (Fo2 + 2Fc2)/3
2955 reflections	(Δ/σ)max < 0.001
195 parameters	Δρmax = 0.26 e Å−3
0 restraints	Δρmin = −0.17 e Å−3

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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.21097 (13)	0.40487 (9)	0.72385 (9)	0.0215 (2)
O2	0.36821 (16)	0.20951 (10)	0.43040 (10)	0.0335 (3)
O3	0.49314 (15)	0.35197 (11)	0.95899 (10)	0.0312 (2)
O4	0.23835 (16)	0.47712 (12)	1.03729 (11)	0.0361 (3)
C1	0.3402 (2)	0.03641 (14)	0.70661 (15)	0.0278 (3)
H1	0.3796	−0.0144	0.6431	0.033*
C2	0.3195 (2)	−0.03755 (15)	0.84129 (16)	0.0330 (3)
H2	0.3434	−0.1395	0.8710	0.040*
C3	0.2632 (2)	0.03676 (15)	0.93484 (15)	0.0306 (3)
H3	0.2494	−0.0159	1.0279	0.037*
C4	0.2271 (2)	0.18497 (14)	0.89551 (14)	0.0252 (3)
C5	0.18653 (18)	0.63568 (13)	0.56645 (13)	0.0208 (3)
C6	0.20182 (18)	0.72389 (13)	0.43318 (13)	0.0221 (3)
C7	0.25597 (19)	0.66243 (14)	0.32918 (13)	0.0248 (3)
H7	0.2664	0.7233	0.2386	0.030*
C8	0.29413 (19)	0.51639 (14)	0.35551 (13)	0.0238 (3)
H8	0.3301	0.4772	0.2833	0.029*
C9	0.32191 (19)	0.26831 (14)	0.51829 (13)	0.0232 (3)
C10	0.30347 (19)	0.18691 (14)	0.66213 (13)	0.0223 (3)
C11	0.24803 (18)	0.25830 (13)	0.75729 (13)	0.0212 (3)
C12	0.22678 (17)	0.48664 (13)	0.59068 (12)	0.0188 (3)
C13	0.28044 (18)	0.42500 (13)	0.48780 (13)	0.0202 (3)
C14	0.1303 (2)	0.69521 (15)	0.68242 (14)	0.0298 (3)
H14A	0.1279	0.6159	0.7671	0.036*	0.50
H14B	−0.0020	0.7477	0.6734	0.036*	0.50
H14C	0.2284	0.7608	0.6823	0.036*	0.50
H14D	0.1084	0.8004	0.6481	0.036*	0.50
H14E	0.2382	0.6686	0.7418	0.036*	0.50
H14F	0.0078	0.6554	0.7330	0.036*	0.50
C15	0.1628 (2)	0.88493 (14)	0.39994 (15)	0.0291 (3)
H15A	0.0275	0.9087	0.4362	0.035*
H15B	0.1761	0.9292	0.3021	0.035*
H15C	0.2594	0.9217	0.4399	0.035*
C16	0.1661 (2)	0.26804 (15)	0.99384 (14)	0.0293 (3)
H16A	0.1462	0.1991	1.0854	0.035*
H16B	0.0369	0.3240	0.9720	0.035*
C17	0.3156 (2)	0.36947 (15)	0.99384 (13)	0.0260 (3)
H4O	0.345 (3)	0.541 (2)	1.032 (2)	0.076 (7)*

	U11	U22	U33	U12	U13	U23
O1	0.0261 (5)	0.0176 (4)	0.0205 (5)	−0.0008 (3)	−0.0016 (4)	−0.0061 (4)
O2	0.0449 (6)	0.0277 (5)	0.0326 (6)	0.0000 (4)	−0.0035 (5)	−0.0171 (4)
O3	0.0298 (5)	0.0314 (5)	0.0339 (6)	0.0002 (4)	−0.0023 (4)	−0.0133 (4)
O4	0.0322 (6)	0.0397 (6)	0.0430 (6)	0.0003 (5)	−0.0014 (5)	−0.0241 (5)
C1	0.0279 (7)	0.0212 (7)	0.0377 (8)	−0.0008 (5)	−0.0081 (6)	−0.0125 (6)
C2	0.0367 (8)	0.0185 (7)	0.0426 (9)	−0.0008 (6)	−0.0115 (7)	−0.0053 (6)
C3	0.0334 (8)	0.0252 (7)	0.0295 (7)	−0.0046 (6)	−0.0071 (6)	−0.0010 (6)
C4	0.0227 (7)	0.0253 (7)	0.0272 (7)	−0.0041 (5)	−0.0031 (5)	−0.0063 (6)
C5	0.0184 (6)	0.0207 (6)	0.0249 (7)	−0.0018 (5)	−0.0017 (5)	−0.0094 (5)
C6	0.0185 (6)	0.0198 (6)	0.0279 (7)	−0.0021 (5)	−0.0036 (5)	−0.0063 (5)
C7	0.0239 (7)	0.0266 (7)	0.0215 (7)	−0.0030 (5)	−0.0030 (5)	−0.0034 (5)
C8	0.0233 (7)	0.0278 (7)	0.0226 (7)	−0.0029 (5)	−0.0016 (5)	−0.0108 (5)
C9	0.0211 (6)	0.0232 (7)	0.0290 (7)	−0.0019 (5)	−0.0038 (5)	−0.0127 (6)
C10	0.0197 (6)	0.0206 (6)	0.0287 (7)	−0.0021 (5)	−0.0052 (5)	−0.0089 (5)
C11	0.0185 (6)	0.0179 (6)	0.0273 (7)	−0.0024 (5)	−0.0042 (5)	−0.0060 (5)
C12	0.0159 (6)	0.0199 (6)	0.0206 (6)	−0.0030 (5)	−0.0019 (5)	−0.0058 (5)
C13	0.0175 (6)	0.0209 (6)	0.0241 (7)	−0.0025 (5)	−0.0030 (5)	−0.0089 (5)
C14	0.0385 (8)	0.0228 (7)	0.0289 (7)	−0.0018 (6)	0.0008 (6)	−0.0108 (6)
C15	0.0318 (8)	0.0218 (7)	0.0317 (8)	−0.0016 (5)	−0.0032 (6)	−0.0053 (6)
C16	0.0307 (7)	0.0295 (7)	0.0246 (7)	−0.0036 (6)	0.0015 (6)	−0.0053 (6)
C17	0.0320 (7)	0.0270 (7)	0.0165 (6)	0.0022 (6)	−0.0036 (5)	−0.0045 (5)

O1—C11	1.3690 (15)	C7—C8	1.3708 (19)
O1—C12	1.3746 (15)	C7—H7	0.9500
O2—C9	1.2301 (15)	C8—C13	1.3953 (18)
O3—C17	1.2225 (17)	C8—H8	0.9500
O4—C17	1.3108 (16)	C9—C10	1.4680 (19)
O4—H4O	1.00 (2)	C9—C13	1.4688 (18)
C1—C2	1.370 (2)	C10—C11	1.3883 (18)
C1—C10	1.4032 (18)	C12—C13	1.3925 (17)
C1—H1	0.9500	C14—H14A	0.9800
C2—C3	1.395 (2)	C14—H14B	0.9800
C2—H2	0.9500	C14—H14C	0.9800
C3—C4	1.3816 (19)	C14—H14D	0.9800
C3—H3	0.9500	C14—H14E	0.9800
C4—C11	1.4011 (19)	C14—H14F	0.9800
C4—C16	1.5030 (19)	C15—H15A	0.9800
C5—C6	1.3937 (18)	C15—H15B	0.9800
C5—C12	1.4031 (17)	C15—H15C	0.9800
C5—C14	1.5045 (18)	C16—C17	1.505 (2)
C6—C7	1.4021 (19)	C16—H16A	0.9900
C6—C15	1.5057 (18)	C16—H16B	0.9900
Cg1···Cg2i	3.491 (3)	Cg2···Cg2i	3.735 (3)
Cg1···Cg2ii	3.591 (3)	Cg2···Cg2ii	3.639 (3)
C11—O1—C12	119.45 (10)	C12—C13—C9	120.73 (12)
C17—O4—H4O	109.3 (12)	C8—C13—C9	121.21 (11)
C2—C1—C10	120.21 (13)	C5—C14—H14A	109.5
C2—C1—H1	119.9	C5—C14—H14B	109.5
C10—C1—H1	119.9	H14A—C14—H14B	109.5
C1—C2—C3	120.06 (13)	C5—C14—H14C	109.5
C1—C2—H2	120.0	H14A—C14—H14C	109.5
C3—C2—H2	120.0	H14B—C14—H14C	109.5
C4—C3—C2	121.64 (13)	C5—C14—H14D	109.5
C4—C3—H3	119.2	H14A—C14—H14D	141.1
C2—C3—H3	119.2	H14B—C14—H14D	56.3
C3—C4—C11	117.33 (12)	H14C—C14—H14D	56.3
C3—C4—C16	122.88 (13)	C5—C14—H14E	109.5
C11—C4—C16	119.79 (12)	H14A—C14—H14E	56.3
C6—C5—C12	117.71 (11)	H14B—C14—H14E	141.1
C6—C5—C14	122.29 (11)	H14C—C14—H14E	56.3
C12—C5—C14	120.00 (12)	H14D—C14—H14E	109.5
C5—C6—C7	119.79 (12)	C5—C14—H14F	109.5
C5—C6—C15	120.53 (11)	H14A—C14—H14F	56.3
C7—C6—C15	119.67 (12)	H14B—C14—H14F	56.3
C8—C7—C6	121.37 (12)	H14C—C14—H14F	141.1
C8—C7—H7	119.3	H14D—C14—H14F	109.5
C6—C7—H7	119.3	H14E—C14—H14F	109.5
C7—C8—C13	120.32 (12)	C6—C15—H15A	109.5
C7—C8—H8	119.8	C6—C15—H15B	109.5
C13—C8—H8	119.8	H15A—C15—H15B	109.5
O2—C9—C10	122.46 (12)	C6—C15—H15C	109.5
O2—C9—C13	122.77 (12)	H15A—C15—H15C	109.5
C10—C9—C13	114.77 (11)	H15B—C15—H15C	109.5
C11—C10—C1	118.59 (12)	C4—C16—C17	113.59 (11)
C11—C10—C9	120.20 (11)	C4—C16—H16A	108.8
C1—C10—C9	121.21 (12)	C17—C16—H16A	108.8
O1—C11—C10	122.88 (12)	C4—C16—H16B	108.8
O1—C11—C4	114.95 (11)	C17—C16—H16B	108.8
C10—C11—C4	122.17 (12)	H16A—C16—H16B	107.7
O1—C12—C13	121.97 (11)	O3—C17—O4	123.02 (14)
O1—C12—C5	115.28 (11)	O3—C17—C16	123.28 (12)
C13—C12—C5	122.75 (12)	O4—C17—C16	113.68 (12)
C12—C13—C8	118.06 (11)
C10—C1—C2—C3	−0.5 (2)	C16—C4—C11—O1	0.55 (18)
C1—C2—C3—C4	0.0 (2)	C3—C4—C11—C10	−0.25 (19)
C2—C3—C4—C11	0.4 (2)	C16—C4—C11—C10	−179.84 (12)
C2—C3—C4—C16	179.95 (13)	C11—O1—C12—C13	−0.27 (17)
C12—C5—C6—C7	−0.03 (18)	C11—O1—C12—C5	−179.83 (11)
C14—C5—C6—C7	179.62 (12)	C6—C5—C12—O1	179.53 (11)
C12—C5—C6—C15	−179.37 (12)	C14—C5—C12—O1	−0.13 (17)
C14—C5—C6—C15	0.28 (19)	C6—C5—C12—C13	−0.03 (19)
C5—C6—C7—C8	0.2 (2)	C14—C5—C12—C13	−179.69 (12)
C15—C6—C7—C8	179.51 (12)	O1—C12—C13—C8	−179.58 (11)
C6—C7—C8—C13	−0.2 (2)	C5—C12—C13—C8	−0.05 (19)
C2—C1—C10—C11	0.6 (2)	O1—C12—C13—C9	0.23 (18)
C2—C1—C10—C9	−179.11 (13)	C5—C12—C13—C9	179.75 (11)
O2—C9—C10—C11	−179.09 (12)	C7—C8—C13—C12	0.19 (19)
C13—C9—C10—C11	0.80 (17)	C7—C8—C13—C9	−179.61 (12)
O2—C9—C10—C1	0.6 (2)	O2—C9—C13—C12	179.41 (12)
C13—C9—C10—C1	−179.46 (12)	C10—C9—C13—C12	−0.47 (17)
C12—O1—C11—C10	0.62 (17)	O2—C9—C13—C8	−0.8 (2)
C12—O1—C11—C4	−179.77 (11)	C10—C9—C13—C8	179.32 (11)
C1—C10—C11—O1	179.34 (12)	C3—C4—C16—C17	116.51 (15)
C9—C10—C11—O1	−0.91 (19)	C11—C4—C16—C17	−63.93 (17)
C1—C10—C11—C4	−0.24 (19)	C4—C16—C17—O3	−25.38 (19)
C9—C10—C11—C4	179.51 (12)	C4—C16—C17—O4	155.89 (12)
C3—C4—C11—O1	−179.87 (11)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4O···O3iii	1.00 (2)	1.63 (2)	2.633 (1)	173.25 (2)
C16—H16B···O4iv	0.99	2.52	3.460 (1)	158 (1)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4O⋯O3iii	1.00 (2)	1.63 (2)	2.633 (1)	173.25 (2)
C16—H16B⋯O4iv	0.99	2.52	3.460 (1)	158 (1)

Symmetry codes: (iii) ; (iv) .