3-(5,7-Di­methoxy-2,2-di­methyl-2H-benzo­[b]­pyran-6-yl)­propionic acid: a potential inhibitor against Leishmania

The title acid, C₁₆H₂₀O₅, was extracted from Adiscanthus fusciflorus (Rutaceae) and is shown to inhibit adenine phospho­ribosyl­transferase (APRT) enzyme activity. This compound crystallizes in the centrosymmetric space group C2/c with one mol­ecule in the asymmetric unit. There is one strong hydrogen bond, with O_D...O_A = 2.6238 (12) Å and O_D—H...O_A = 171.1 (17)° involving the COOH group, forming a cyclic dimer about a center of symmetry. The packing of the mol­ecules is additionally stabilized by one C—H...O [C_D...O_A = 2.9820 (16) Å and C_D—H...O_A = 101.8 (10)°] and two C—H...π intermolecular hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 120 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.033
• wR factor = 0.090
• Data-to-parameter ratio = 9.8

checkCIF/PLATON results

No syntax errors found



Alert level C
REFNR01_ALERT_3_C  Ratio of reflections to parameters is < 10 for a
            centrosymmetric structure
            sine(theta)/lambda               -0.1862
            Proportion of unique data used    1.0000
            Ratio reflections to parameters   9.8376
PLAT088_ALERT_3_C Poor Data / Parameter Ratio ....................       9.84
PLAT152_ALERT_1_C Supplied and Calc Volume s.u. Inconsistent .....          ?
PLAT355_ALERT_3_C Long    O-H Bond (0.82A)   O21    -   H21      =       1.04 Ang.
PLAT432_ALERT_2_C Short Inter X...Y Contact  O21    ..  C16      =       2.98 Ang.

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion

---

Computing details

Data collection: COLLECT (Nonius, 1997-2002); cell refinement: HKL SCALEPACK (Otwinowski & Minor, 1997); data reduction: HKL SCALEPACK and DENZO (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

(I)

Crystal data

C16H20O5	F(000) = 1248
Mr = 292.32	Dx = 1.278 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 3662 reflections
a = 23.3022 (3) Å	θ = 1.0–27.5°
b = 10.2248 (2) Å	µ = 0.10 mm^−1
c = 15.0785 (3) Å	T = 120 K
β = 122.273 (1)°	Prism, colorless
V = 3037.60 (9) Å^3	0.16 × 0.14 × 0.10 mm
Z = 8

Data collection

Nonius KappaCCD diffractometer	Rint = 0.016
CCD rotation images, thick slices scans	θmax = 25°, θmin = 3.2°
5170 measured reflections	h = −27→27
2666 independent reflections	k = −12→12
2207 reflections with I > 2σ(I)	l = −17→17

Refinement

Refinement on F^2	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ^2(Fo^2) + (0.0472P)^2 + 0.8048P] where P = (Fo^2 + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.033	(Δ/σ)max < 0.001
wR(F^2) = 0.090	Δρmax = 0.19 e Å^−3
S = 1.05	Δρmin = −0.16 e Å^−3
2666 reflections	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
271 parameters	Extinction coefficient: 0.0043 (7)
0 restraints

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C13	−0.17318 (8)	0.34247 (15)	−0.33222 (12)	0.0334 (3)
C15	−0.05400 (8)	0.52785 (13)	0.08274 (13)	0.0337 (3)
O20	0.19639 (4)	0.32730 (9)	0.38925 (7)	0.0278 (2)
C16	0.11583 (7)	0.05665 (14)	0.00327 (12)	0.0311 (3)
O19	0.10000 (4)	0.14355 (9)	0.06192 (7)	0.0295 (2)
C10	0.08016 (7)	0.30486 (13)	0.18803 (10)	0.0255 (3)
C7	0.03408 (6)	0.18379 (12)	0.01653 (10)	0.0238 (3)
C8	0.02258 (6)	0.26705 (12)	0.08000 (9)	0.0228 (3)
C6	−0.01759 (6)	0.14873 (12)	−0.08405 (10)	0.0251 (3)
C1	−0.19220 (6)	0.23845 (13)	−0.28030 (10)	0.0266 (3)
C9	−0.04311 (6)	0.31305 (12)	0.03743 (9)	0.0225 (3)
O18	−0.05724 (4)	0.39039 (9)	0.09929 (7)	0.0264 (2)
C12	0.16551 (6)	0.22373 (12)	0.37012 (10)	0.0237 (3)
C5	−0.08228 (6)	0.19751 (12)	−0.12295 (9)	0.0241 (3)
C4	−0.09670 (6)	0.28131 (12)	−0.06393 (9)	0.0232 (3)
C2	−0.21218 (7)	0.30046 (13)	−0.20982 (10)	0.0279 (3)
O17	−0.13316 (4)	0.15304 (8)	−0.21922 (7)	0.0281 (2)
C3	−0.16684 (6)	0.32264 (13)	−0.10918 (10)	0.0264 (3)
C11	0.10199 (6)	0.19405 (13)	0.26714 (10)	0.0255 (3)
C14	−0.24721 (8)	0.14828 (15)	−0.36001 (12)	0.0365 (4)
O21	0.18620 (5)	0.12654 (9)	0.43794 (7)	0.0310 (3)
H15A	−0.0075 (8)	0.5516 (15)	0.0955 (12)	0.043 (4)*
H13B	−0.1350 (9)	0.3943 (16)	−0.2781 (13)	0.046 (4)*
H13C	−0.2115 (9)	0.4033 (16)	−0.3742 (13)	0.048 (4)*
H13A	−0.1610 (8)	0.3016 (16)	−0.3807 (13)	0.044 (4)*
H15C	−0.0874 (9)	0.5523 (16)	0.0104 (14)	0.048 (5)*
H16C	0.1074 (7)	0.0998 (15)	−0.0635 (13)	0.039 (4)*
H10B	0.1197 (8)	0.3351 (14)	0.1849 (11)	0.033 (4)*
H15B	−0.0607 (8)	0.5762 (17)	0.1354 (13)	0.051 (5)*
H16B	0.1651 (9)	0.0324 (16)	0.0529 (12)	0.045 (4)*
H10A	0.0662 (7)	0.3796 (14)	0.2119 (11)	0.029 (4)*
H6	−0.0088 (7)	0.0894 (14)	−0.1260 (11)	0.027 (3)*
H16A	0.0867 (7)	−0.0216 (15)	−0.0184 (11)	0.032 (4)*
H14B	−0.2889 (9)	0.1962 (16)	−0.4113 (14)	0.049 (4)*
H2	−0.2618 (8)	0.3299 (14)	−0.2456 (12)	0.036 (4)*
H14A	−0.2314 (8)	0.1021 (16)	−0.4013 (13)	0.046 (4)*
H3	−0.1779 (7)	0.3663 (14)	−0.0630 (12)	0.034 (4)*
H21	0.2319 (10)	0.1540 (19)	0.5044 (16)	0.071 (6)*
H11B	0.1105 (7)	0.1106 (15)	0.2426 (11)	0.037 (4)*
H11A	0.0669 (8)	0.1733 (14)	0.2818 (11)	0.037 (4)*
H14C	−0.2578 (9)	0.0818 (18)	−0.3218 (13)	0.055 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C13	0.0360 (8)	0.0343 (8)	0.0309 (8)	−0.0002 (7)	0.0185 (7)	0.0030 (7)
C15	0.0415 (9)	0.0255 (7)	0.0368 (8)	0.0071 (6)	0.0227 (7)	−0.0003 (6)
O20	0.0253 (5)	0.0259 (5)	0.0261 (5)	−0.0027 (4)	0.0096 (4)	0.0019 (4)
C16	0.0290 (8)	0.0293 (8)	0.0369 (8)	0.0038 (6)	0.0189 (7)	−0.0045 (6)
O19	0.0224 (5)	0.0316 (5)	0.0309 (5)	0.0049 (4)	0.0118 (4)	−0.0041 (4)
C10	0.0250 (7)	0.0239 (7)	0.0250 (7)	0.0004 (5)	0.0116 (6)	−0.0006 (5)
C7	0.0220 (6)	0.0213 (6)	0.0264 (7)	0.0020 (5)	0.0119 (6)	0.0018 (5)
C8	0.0237 (7)	0.0210 (6)	0.0222 (7)	0.0000 (5)	0.0112 (6)	0.0011 (5)
C6	0.0268 (7)	0.0217 (7)	0.0263 (7)	0.0012 (5)	0.0139 (6)	−0.0018 (5)
C1	0.0218 (6)	0.0264 (7)	0.0244 (7)	0.0013 (5)	0.0075 (6)	0.0019 (5)
C9	0.0272 (7)	0.0205 (6)	0.0233 (7)	0.0013 (5)	0.0158 (6)	0.0016 (5)
O18	0.0305 (5)	0.0274 (5)	0.0254 (5)	0.0030 (4)	0.0177 (4)	0.0002 (4)
C12	0.0236 (6)	0.0259 (7)	0.0247 (7)	0.0020 (5)	0.0149 (6)	0.0013 (5)
C5	0.0246 (7)	0.0219 (6)	0.0218 (6)	−0.0012 (5)	0.0097 (6)	0.0004 (5)
C4	0.0226 (7)	0.0221 (7)	0.0249 (7)	0.0000 (5)	0.0127 (6)	0.0032 (5)
C2	0.0224 (7)	0.0301 (7)	0.0293 (7)	0.0011 (6)	0.0126 (6)	0.0038 (6)
O17	0.0242 (5)	0.0265 (5)	0.0240 (5)	0.0021 (4)	0.0064 (4)	−0.0027 (4)
C3	0.0248 (7)	0.0283 (7)	0.0278 (7)	0.0025 (5)	0.0151 (6)	0.0028 (6)
C11	0.0236 (7)	0.0260 (7)	0.0249 (7)	−0.0021 (5)	0.0115 (6)	−0.0005 (5)
C14	0.0274 (8)	0.0342 (8)	0.0320 (8)	−0.0024 (6)	0.0053 (7)	−0.0027 (7)
O21	0.0317 (5)	0.0276 (5)	0.0242 (5)	−0.0041 (4)	0.0086 (4)	0.0043 (4)

Geometric parameters (Å, º)

C13—C1	1.5202 (18)	C6—C5	1.3859 (18)
C13—H13B	0.982 (17)	C6—H6	0.974 (14)
C13—H13C	0.991 (17)	C1—O17	1.4664 (15)
C13—H13A	1.005 (17)	C1—C2	1.5089 (18)
C15—O18	1.4365 (16)	C1—C14	1.5140 (19)
C15—H15A	1.024 (16)	C9—O18	1.3899 (14)
C15—H15C	0.976 (18)	C9—C4	1.4009 (17)
C15—H15B	1.016 (18)	C12—O21	1.3188 (15)
O20—C12	1.2252 (15)	C12—C11	1.4965 (17)
C16—O19	1.4338 (15)	C5—O17	1.3717 (15)
C16—H16C	1.018 (16)	C5—C4	1.3995 (17)
C16—H16B	1.011 (17)	C4—C3	1.4575 (17)
C16—H16A	0.985 (15)	C2—C3	1.3261 (19)
O19—C7	1.3692 (15)	C2—H2	1.025 (16)
C10—C8	1.5063 (17)	C3—H3	0.971 (15)
C10—C11	1.5223 (18)	C11—H11B	0.991 (15)
C10—H10B	0.996 (15)	C11—H11A	0.978 (16)
C10—H10A	0.972 (14)	C14—H14B	0.990 (18)
C7—C6	1.3886 (18)	C14—H14A	0.994 (17)
C7—C8	1.4095 (17)	C14—H14C	1.004 (18)
C8—C9	1.3882 (17)	O21—H21	1.04 (2)
C1—C13—H13B	109.5 (9)	O17—C1—C13	107.84 (10)
C1—C13—H13C	110.9 (9)	C2—C1—C13	110.68 (11)
H13B—C13—H13C	107.5 (14)	C14—C1—C13	111.91 (12)
C1—C13—H13A	110.9 (9)	C8—C9—O18	118.70 (10)
H13B—C13—H13A	110.3 (13)	C8—C9—C4	123.13 (11)
H13C—C13—H13A	107.7 (13)	O18—C9—C4	118.12 (10)
O18—C15—H15A	110.4 (9)	C9—O18—C15	112.76 (9)
O18—C15—H15C	111.2 (10)	O20—C12—O21	122.90 (11)
H15A—C15—H15C	106.3 (13)	O20—C12—C11	123.42 (11)
O18—C15—H15B	107.2 (9)	O21—C12—C11	113.66 (11)
H15A—C15—H15B	109.1 (12)	O17—C5—C6	117.31 (11)
H15C—C15—H15B	112.7 (13)	O17—C5—C4	120.69 (11)
O19—C16—H16C	111.4 (8)	C6—C5—C4	121.83 (12)
O19—C16—H16B	105.1 (9)	C5—C4—C9	117.31 (11)
H16C—C16—H16B	112.4 (12)	C5—C4—C3	118.03 (11)
O19—C16—H16A	110.5 (8)	C9—C4—C3	124.54 (11)
H16C—C16—H16A	106.8 (12)	C3—C2—C1	121.39 (12)
H16B—C16—H16A	110.8 (13)	C3—C2—H2	122.5 (8)
C7—O19—C16	117.86 (10)	C1—C2—H2	116.0 (8)
C8—C10—C11	112.85 (11)	C5—O17—C1	117.27 (9)
C8—C10—H10B	109.9 (8)	C2—C3—C4	119.69 (12)
C11—C10—H10B	109.7 (8)	C2—C3—H3	123.0 (9)
C8—C10—H10A	108.7 (8)	C4—C3—H3	117.3 (9)
C11—C10—H10A	109.4 (8)	C12—C11—C10	113.18 (11)
H10B—C10—H10A	106.0 (11)	C12—C11—H11B	106.2 (8)
O19—C7—C6	123.74 (11)	C10—C11—H11B	113.4 (8)
O19—C7—C8	114.30 (11)	C12—C11—H11A	107.1 (9)
C6—C7—C8	121.95 (11)	C10—C11—H11A	111.6 (9)
C9—C8—C7	116.95 (11)	H11B—C11—H11A	104.8 (12)
C9—C8—C10	122.60 (11)	C1—C14—H14B	112.4 (10)
C7—C8—C10	120.45 (11)	C1—C14—H14A	110.3 (9)
C5—C6—C7	118.83 (12)	H14B—C14—H14A	106.4 (13)
C5—C6—H6	120.5 (8)	C1—C14—H14C	108.7 (10)
C7—C6—H6	120.6 (8)	H14B—C14—H14C	110.1 (14)
O17—C1—C2	110.29 (10)	H14A—C14—H14C	108.9 (13)
O17—C1—C14	104.40 (11)	C12—O21—H21	107.8 (11)
C2—C1—C14	111.48 (11)
C16—O19—C7—C6	−2.23 (18)	O18—C9—C4—C5	−176.57 (10)
C16—O19—C7—C8	178.91 (11)	C8—C9—C4—C3	176.88 (11)
O19—C7—C8—C9	178.85 (10)	O18—C9—C4—C3	−0.69 (18)
C6—C7—C8—C9	−0.03 (18)	O17—C1—C2—C3	28.36 (16)
O19—C7—C8—C10	−0.03 (16)	C14—C1—C2—C3	143.85 (14)
C6—C7—C8—C10	−178.91 (11)	C13—C1—C2—C3	−90.90 (15)
C11—C10—C8—C9	107.22 (14)	C6—C5—O17—C1	−154.61 (11)
C11—C10—C8—C7	−73.97 (15)	C4—C5—O17—C1	29.92 (16)
O19—C7—C6—C5	−178.64 (11)	C2—C1—O17—C5	−41.33 (14)
C8—C7—C6—C5	0.14 (19)	C14—C1—O17—C5	−161.20 (11)
C7—C8—C9—O18	177.00 (10)	C13—C1—O17—C5	79.63 (13)
C10—C8—C9—O18	−4.15 (17)	C1—C2—C3—C4	−2.76 (19)
C7—C8—C9—C4	−0.56 (18)	C5—C4—C3—C2	−12.07 (18)
C10—C8—C9—C4	178.29 (11)	C9—C4—C3—C2	172.08 (12)
C8—C9—O18—C15	95.58 (13)	O20—C12—C11—C10	0.79 (17)
C4—C9—O18—C15	−86.74 (14)	O21—C12—C11—C10	−177.71 (10)
C7—C6—C5—O17	−175.07 (10)	C8—C10—C11—C12	171.40 (10)
C7—C6—C5—C4	0.33 (19)	O17—C2—C3—C4	12.76 (13)
O17—C5—C4—C9	174.38 (10)	C2—C3—C4—C5	−12.07 (18)
C6—C5—C4—C9	−0.87 (18)	C3—C4—C5—C6	−177.03 (11)
O17—C5—C4—C3	−1.78 (17)	C4—C5—C6—C7	0.33 (19)
C6—C5—C4—C3	−177.03 (11)	C5—C6—C7—C8	0.14 (19)
C8—C9—C4—C5	1.00 (18)	C6—C7—C8—C9	−0.03 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O21—H21···O20^i	1.04 (2)	1.59 (2)	2.6238 (12)	171.1 (17)
C16—H16B···O21^ii	1.011 (17)	2.607 (15)	2.9820 (16)	101.8 (10)
C15—H15A···CgBz^iii	1.024 (16)	2.814 (16)	3.5534 (15)	129.4 (11)
C16—H16A···CgBz^iv	0.985 (15)	2.756 (15)	3.6568 (15)	152.2 (11)

Symmetry codes: (i) −x+1/2, −y+1/2, −z+1; (ii) x, −y, z−1/2; (iii) −x, −y+1, −z; (iv) −x, −y, −z.