Glabridin.

In the title compound, C20H20O4 {systematic name: 4-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[2,3-f]chromen-3-yl]benz-ene-1,3-diol}, the hydro-pyran ring linked to the pendant benzene ring adopts an envelope conformation, with the methyne C atom forming the flap. In the crystal, the -OH group at the 3-position of the benzene ring forms an O-H⋯O hydrogen bond to a chromene O-atom acceptor, whereas the -OH group at the 1-position forms an O-H⋯π inter-action with a neighboring benzene ring. The O-H⋯O hydrogen bonds form [001] chains and the O-H⋯π bonds cross-link the chains into (101) sheets. The absolute structure was assumed to be the same as that deduced from previous studies for the natural product.

Related literature

For background to the pharmacological activity of the title compound, see: Fukai et al. (2000 ▶); Messier & Grenier; (2011 ▶); Thiyagarajan et al. (2011 ▶); Ahn et al. (2012 ▶); Choi (2005 ▶). For the assignment of the absolute structure, see: Kim et al. (2009 ▶).

Experimental

Crystal data

C20H20O4

M = 324.36

Orthorhombic,

a = 6.4301 (4) Å

b = 12.0307 (7) Å

c = 21.0690 (13) Å

V = 1629.87 (17) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 293 K

0.22 × 0.14 × 0.07 mm

Data collection

Bruker APEX CCD diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2003 ▶) T min = 0.984, T max = 0.994

15459 measured reflections

2866 independent reflections

2551 reflections with I > 2σ(I)

R int = 0.045

Refinement

R[F 2 > 2σ(F 2)] = 0.046

wR(F 2) = 0.095

S = 1.16

2866 reflections

225 parameters

2 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.15 e Å−3

Δρmin = −0.17 e Å−3

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 2003 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶) and publCIF (Westrip, 2010 ▶).

Click here for additional data file.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812048647/hb6989sup1.cif

Click here for additional data file.

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812048647/hb6989Isup2.hkl

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S1600536812048647/hb6989Isup3.cml

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

C20H20O4	F(000) = 688
Mr = 324.36	Dx = 1.322 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2104 reflections
a = 6.4301 (4) Å	θ = 3.3–21.0°
b = 12.0307 (7) Å	µ = 0.09 mm−1
c = 21.0690 (13) Å	T = 293 K
V = 1629.87 (17) Å3	Block, colourless
Z = 4	0.22 × 0.14 × 0.07 mm

Bruker APEX CCD diffractometer	2866 independent reflections
Radiation source: fine-focus sealed tube	2551 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.045
Frames, each covering 0.3 ° in ω scans	θmax = 25.0°, θmin = 1.9°
Absorption correction: multi-scan (SADABS; Bruker, 2003)	h = −7→7
Tmin = 0.984, Tmax = 0.994	k = −14→14
15459 measured reflections	l = −25→25

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)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.095	H atoms treated by a mixture of independent and constrained refinement
S = 1.16	w = 1/[σ2(Fo2) + (0.0365P)2 + 0.2296P] where P = (Fo2 + 2Fc2)/3
2866 reflections	(Δ/σ)max < 0.001
225 parameters	Δρmax = 0.15 e Å−3
2 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 > 2σ(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
O1	0.7767 (3)	0.66156 (13)	0.23880 (7)	0.0443 (4)
O2	1.0695 (3)	0.80853 (13)	0.05050 (7)	0.0477 (5)
C1	0.9085 (4)	0.56254 (19)	0.23598 (11)	0.0417 (6)
C2	1.1009 (4)	0.5878 (2)	0.19907 (11)	0.0458 (6)
H2	1.2221	0.5486	0.2080	0.055*
C3	1.1042 (4)	0.6644 (2)	0.15409 (11)	0.0424 (6)
H3	1.2243	0.6754	0.1303	0.051*
C4	0.9211 (4)	0.73112 (18)	0.14167 (10)	0.0326 (5)
C5	0.7586 (4)	0.72632 (18)	0.18500 (10)	0.0370 (6)
C6	0.5850 (4)	0.7914 (2)	0.17877 (12)	0.0479 (6)
H6	0.4783	0.7876	0.2085	0.057*
C7	0.5712 (4)	0.8631 (2)	0.12745 (12)	0.0466 (6)
H7	0.4530	0.9070	0.1230	0.056*
C8	0.7277 (4)	0.87146 (18)	0.08254 (11)	0.0366 (5)
C9	0.9013 (4)	0.80460 (18)	0.09051 (10)	0.0340 (5)
C10	1.0643 (4)	0.88701 (19)	−0.00121 (10)	0.0431 (6)
H10A	1.0019	0.8517	−0.0380	0.052*
H10B	1.2055	0.9076	−0.0123	0.052*
C11	0.9426 (4)	0.99118 (18)	0.01485 (10)	0.0357 (5)
H11	1.0017	1.0217	0.0540	0.043*
C12	0.7201 (4)	0.95505 (19)	0.02970 (12)	0.0435 (6)
H12A	0.6376	1.0188	0.0424	0.052*
H12B	0.6567	0.9223	−0.0076	0.052*
C13	0.9633 (4)	1.07917 (18)	−0.03561 (10)	0.0353 (5)
C14	1.1391 (4)	1.14759 (18)	−0.03656 (10)	0.0364 (6)
C15	1.1636 (4)	1.23098 (19)	−0.08114 (11)	0.0378 (5)
H15	1.2811	1.2760	−0.0802	0.045*
C16	1.0135 (4)	1.24727 (18)	−0.12703 (10)	0.0372 (6)
C17	0.8386 (4)	1.1812 (2)	−0.12775 (11)	0.0449 (6)
H17	0.7366	1.1918	−0.1585	0.054*
C18	0.8159 (4)	1.09882 (19)	−0.08240 (11)	0.0425 (6)
H18	0.6970	1.0549	−0.0833	0.051*
C19	0.9574 (5)	0.5352 (3)	0.30460 (12)	0.0639 (8)
H19A	1.0368	0.5946	0.3230	0.096*
H19B	1.0363	0.4675	0.3065	0.096*
H19C	0.8300	0.5261	0.3278	0.096*
C20	0.7812 (6)	0.4713 (2)	0.20419 (15)	0.0721 (9)
H20A	0.6555	0.4593	0.2278	0.108*
H20B	0.8608	0.4038	0.2031	0.108*
H20C	0.7472	0.4934	0.1617	0.108*
O3	1.2858 (3)	1.12753 (14)	0.00917 (9)	0.0536 (5)
H3A	1.362 (4)	1.1797 (18)	0.0133 (14)	0.064*
O4	1.0477 (3)	1.33015 (16)	−0.16975 (8)	0.0551 (5)
H4A	0.957 (4)	1.334 (2)	−0.1969 (11)	0.066*

	U11	U22	U33	U12	U13	U23
O1	0.0529 (11)	0.0443 (9)	0.0356 (9)	0.0025 (8)	0.0083 (8)	0.0037 (8)
O2	0.0485 (11)	0.0493 (10)	0.0452 (9)	0.0166 (9)	0.0169 (9)	0.0160 (8)
C1	0.0460 (15)	0.0360 (13)	0.0431 (13)	−0.0006 (11)	0.0002 (13)	0.0026 (11)
C2	0.0429 (16)	0.0503 (15)	0.0443 (14)	0.0106 (13)	0.0013 (12)	0.0064 (12)
C3	0.0391 (14)	0.0493 (14)	0.0389 (13)	0.0042 (12)	0.0071 (12)	0.0038 (12)
C4	0.0349 (12)	0.0318 (11)	0.0312 (11)	−0.0027 (10)	0.0009 (11)	−0.0031 (10)
C5	0.0418 (14)	0.0341 (12)	0.0351 (12)	−0.0048 (11)	0.0001 (11)	−0.0035 (10)
C6	0.0435 (15)	0.0524 (15)	0.0479 (14)	0.0039 (13)	0.0142 (13)	0.0032 (12)
C7	0.0337 (14)	0.0463 (14)	0.0598 (15)	0.0073 (12)	0.0054 (13)	0.0070 (13)
C8	0.0328 (13)	0.0336 (12)	0.0433 (13)	−0.0014 (11)	−0.0025 (12)	−0.0027 (11)
C9	0.0347 (13)	0.0339 (11)	0.0335 (12)	−0.0036 (10)	0.0048 (11)	−0.0061 (10)
C10	0.0521 (15)	0.0446 (13)	0.0326 (12)	0.0064 (12)	0.0058 (12)	0.0053 (11)
C11	0.0381 (13)	0.0372 (12)	0.0319 (12)	0.0005 (11)	−0.0050 (11)	−0.0018 (10)
C12	0.0403 (15)	0.0419 (13)	0.0482 (14)	0.0067 (12)	−0.0014 (12)	0.0038 (12)
C13	0.0405 (14)	0.0350 (12)	0.0304 (12)	0.0018 (11)	−0.0035 (11)	−0.0038 (10)
C14	0.0383 (14)	0.0353 (12)	0.0355 (12)	0.0014 (11)	−0.0093 (11)	−0.0044 (11)
C15	0.0370 (14)	0.0352 (12)	0.0413 (12)	−0.0063 (11)	−0.0006 (11)	−0.0031 (11)
C16	0.0463 (15)	0.0352 (12)	0.0302 (12)	0.0006 (12)	−0.0021 (11)	−0.0016 (10)
C17	0.0506 (16)	0.0469 (14)	0.0372 (13)	−0.0027 (13)	−0.0152 (12)	0.0017 (12)
C18	0.0447 (15)	0.0426 (13)	0.0402 (13)	−0.0106 (12)	−0.0083 (13)	0.0005 (12)
C19	0.067 (2)	0.076 (2)	0.0484 (16)	0.0029 (18)	0.0022 (16)	0.0185 (15)
C20	0.086 (2)	0.0478 (16)	0.082 (2)	−0.0106 (18)	−0.008 (2)	−0.0059 (16)
O3	0.0471 (11)	0.0522 (11)	0.0616 (11)	−0.0086 (9)	−0.0261 (10)	0.0097 (10)
O4	0.0654 (13)	0.0539 (11)	0.0462 (10)	−0.0134 (11)	−0.0119 (9)	0.0168 (9)

O1—C5	1.380 (3)	C11—C12	1.528 (3)
O1—C1	1.463 (3)	C11—H11	0.9800
O2—C9	1.372 (3)	C12—H12A	0.9700
O2—C10	1.442 (2)	C12—H12B	0.9700
C1—C2	1.493 (4)	C13—C18	1.388 (3)
C1—C19	1.516 (3)	C13—C14	1.398 (3)
C1—C20	1.524 (4)	C14—O3	1.369 (3)
C2—C3	1.321 (3)	C14—C15	1.383 (3)
C2—H2	0.9300	C15—C16	1.380 (3)
C3—C4	1.449 (3)	C15—H15	0.9300
C3—H3	0.9300	C16—O4	1.361 (3)
C4—C5	1.389 (3)	C16—C17	1.377 (3)
C4—C9	1.400 (3)	C17—C18	1.384 (3)
C5—C6	1.370 (3)	C17—H17	0.9300
C6—C7	1.386 (3)	C18—H18	0.9300
C6—H6	0.9300	C19—H19A	0.9600
C7—C8	1.385 (3)	C19—H19B	0.9600
C7—H7	0.9300	C19—H19C	0.9600
C8—C9	1.386 (3)	C20—H20A	0.9600
C8—C12	1.501 (3)	C20—H20B	0.9600
C10—C11	1.516 (3)	C20—H20C	0.9600
C10—H10A	0.9700	O3—H3A	0.802 (17)
C10—H10B	0.9700	O4—H4A	0.820 (17)
C11—C13	1.506 (3)
C5—O1—C1	118.37 (17)	C13—C11—H11	107.3
C9—O2—C10	117.92 (18)	C10—C11—H11	107.3
O1—C1—C2	109.58 (18)	C12—C11—H11	107.3
O1—C1—C19	105.0 (2)	C8—C12—C11	108.17 (19)
C2—C1—C19	111.7 (2)	C8—C12—H12A	110.1
O1—C1—C20	107.1 (2)	C11—C12—H12A	110.1
C2—C1—C20	111.3 (2)	C8—C12—H12B	110.1
C19—C1—C20	112.0 (2)	C11—C12—H12B	110.1
C3—C2—C1	121.9 (2)	H12A—C12—H12B	108.4
C3—C2—H2	119.0	C18—C13—C14	116.2 (2)
C1—C2—H2	119.0	C18—C13—C11	124.1 (2)
C2—C3—C4	120.2 (2)	C14—C13—C11	119.7 (2)
C2—C3—H3	119.9	O3—C14—C15	121.8 (2)
C4—C3—H3	119.9	O3—C14—C13	116.3 (2)
C5—C4—C9	117.7 (2)	C15—C14—C13	121.9 (2)
C5—C4—C3	118.02 (19)	C16—C15—C14	119.9 (2)
C9—C4—C3	124.2 (2)	C16—C15—H15	120.0
C6—C5—O1	118.1 (2)	C14—C15—H15	120.0
C6—C5—C4	121.8 (2)	O4—C16—C17	123.2 (2)
O1—C5—C4	120.0 (2)	O4—C16—C15	117.0 (2)
C5—C6—C7	118.9 (2)	C17—C16—C15	119.8 (2)
C5—C6—H6	120.6	C16—C17—C18	119.5 (2)
C7—C6—H6	120.6	C16—C17—H17	120.3
C8—C7—C6	122.1 (2)	C18—C17—H17	120.3
C8—C7—H7	118.9	C17—C18—C13	122.7 (2)
C6—C7—H7	118.9	C17—C18—H18	118.7
C7—C8—C9	117.4 (2)	C13—C18—H18	118.7
C7—C8—C12	122.1 (2)	C1—C19—H19A	109.5
C9—C8—C12	120.3 (2)	C1—C19—H19B	109.5
O2—C9—C8	122.7 (2)	H19A—C19—H19B	109.5
O2—C9—C4	115.1 (2)	C1—C19—H19C	109.5
C8—C9—C4	122.2 (2)	H19A—C19—H19C	109.5
O2—C10—C11	112.64 (17)	H19B—C19—H19C	109.5
O2—C10—H10A	109.1	C1—C20—H20A	109.5
C11—C10—H10A	109.1	C1—C20—H20B	109.5
O2—C10—H10B	109.1	H20A—C20—H20B	109.5
C11—C10—H10B	109.1	C1—C20—H20C	109.5
H10A—C10—H10B	107.8	H20A—C20—H20C	109.5
C13—C11—C10	112.19 (18)	H20B—C20—H20C	109.5
C13—C11—C12	115.3 (2)	C14—O3—H3A	111 (2)
C10—C11—C12	107.10 (19)	C16—O4—H4A	113 (2)
C5—O1—C1—C2	40.3 (3)	C3—C4—C9—O2	1.3 (3)
C5—O1—C1—C19	160.4 (2)	C5—C4—C9—C8	0.3 (3)
C5—O1—C1—C20	−80.5 (3)	C3—C4—C9—C8	−176.3 (2)
O1—C1—C2—C3	−28.0 (3)	C9—O2—C10—C11	31.4 (3)
C19—C1—C2—C3	−143.8 (3)	O2—C10—C11—C13	171.8 (2)
C20—C1—C2—C3	90.2 (3)	O2—C10—C11—C12	−60.7 (3)
C1—C2—C3—C4	3.5 (4)	C7—C8—C12—C11	147.1 (2)
C2—C3—C4—C5	11.3 (3)	C9—C8—C12—C11	−28.3 (3)
C2—C3—C4—C9	−172.2 (2)	C13—C11—C12—C8	−177.54 (18)
C1—O1—C5—C6	156.1 (2)	C10—C11—C12—C8	56.8 (2)
C1—O1—C5—C4	−29.1 (3)	C10—C11—C13—C18	99.2 (3)
C9—C4—C5—C6	−0.6 (3)	C12—C11—C13—C18	−23.7 (3)
C3—C4—C5—C6	176.2 (2)	C10—C11—C13—C14	−81.4 (3)
C9—C4—C5—O1	−175.14 (19)	C12—C11—C13—C14	155.7 (2)
C3—C4—C5—O1	1.7 (3)	C18—C13—C14—O3	−179.3 (2)
O1—C5—C6—C7	175.3 (2)	C11—C13—C14—O3	1.2 (3)
C4—C5—C6—C7	0.6 (4)	C18—C13—C14—C15	0.7 (3)
C5—C6—C7—C8	−0.4 (4)	C11—C13—C14—C15	−178.7 (2)
C6—C7—C8—C9	0.2 (4)	O3—C14—C15—C16	179.0 (2)
C6—C7—C8—C12	−175.3 (2)	C13—C14—C15—C16	−1.1 (3)
C10—O2—C9—C8	0.9 (3)	C14—C15—C16—O4	−179.5 (2)
C10—O2—C9—C4	−176.63 (19)	C14—C15—C16—C17	0.8 (3)
C7—C8—C9—O2	−177.5 (2)	O4—C16—C17—C18	−179.9 (2)
C12—C8—C9—O2	−1.9 (3)	C15—C16—C17—C18	−0.2 (3)
C7—C8—C9—C4	−0.2 (3)	C16—C17—C18—C13	−0.2 (4)
C12—C8—C9—C4	175.5 (2)	C14—C13—C18—C17	−0.1 (3)
C5—C4—C9—O2	177.88 (19)	C11—C13—C18—C17	179.3 (2)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4A···O1i	0.82 (2)	2.02 (2)	2.841 (3)	177 (3)
O3—H3A···Cg4ii	0.80 (2)	2.51 (2)	3.213 (2)	148 (3)

Table 1

Hydrogen-bond geometry (Å, °)

Cg4 is the centroid of the C13–C18 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4A⋯O1i	0.82 (2)	2.02 (2)	2.841 (3)	177 (3)
O3—H3A⋯Cg4ii	0.80 (2)	2.51 (2)	3.213 (2)	148 (3)

Symmetry codes: (i) ; (ii) .