Synthesis, crystal structure and bioactivities of α-asaronol

α-Asaronol [or (E)-3′-hy­droxy­asarone; systematic name: (E)-3-(2,4,5-trimethoxy­phenyl)prop-2-en-1-ol; C₁₂H₁₆O₄] was synthesized towards the development of a potential anti­epileptic drug. Following purification by recrystallization, single crystals of α-asaronol were obtained by a liquid inter­face diffusion method at room tem­per­ature. The product was characterized by ¹H and ¹³C NMR, and FT–IR spectroscopic analysis. X-ray crystallography revealed the title crystal to belong to the ortho­rhom­bic space group P2₁2₁2₁. Preliminary bioassays with mouse neuroblastoma N2a cells demonstrated the neuroprotective activities of the synthesized α-asaronol.

Computing details

Data collection: APEX2 (Bruker, 2015); cell refinement: SAINT (Bruker, 2015); data reduction: SAINT (Bruker, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2019 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

(E)-3-(2,4,5-Trimethoxyphenyl)prop-2-en-1-ol

Crystal data

C12H16O4	Dx = 1.244 Mg m^−3
Mr = 224.25	Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P212121	Cell parameters from 9210 reflections
a = 4.9935 (1) Å	θ = 2.7–72.3°
b = 7.1864 (2) Å	µ = 0.77 mm^−1
c = 33.3673 (7) Å	T = 300 K
V = 1197.40 (5) Å^3	Block, clear light colourless
Z = 4	0.23 × 0.15 × 0.13 mm
F(000) = 480

Data collection

Bruker APEXII CCD diffractometer	2332 reflections with I > 2σ(I)
Radiation source: sealed X-ray tube	Rint = 0.044
Graphite monochromator	θmax = 72.4°, θmin = 2.7°
phi and ω scans	h = −5→6
45491 measured reflections	k = −8→8
2362 independent reflections	l = −41→41

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) + (0.0653P)^2 + 0.1245P] where P = (Fo^2 + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.036	(Δ/σ)max < 0.001
wR(F^2) = 0.106	Δρmax = 0.23 e Å^−3
S = 1.04	Δρmin = −0.14 e Å^−3
2362 reflections	Extinction correction: SHELXL2019 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
153 parameters	Extinction coefficient: 0.0077 (14)
0 restraints	Absolute structure: Flack x determined using 909 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: dual	Absolute structure parameter: 0.04 (3)
Hydrogen site location: mixed

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
O1	0.4322 (4)	0.2913 (2)	0.30530 (5)	0.0792 (5)
O2	0.1014 (3)	0.5605 (2)	0.29059 (4)	0.0618 (4)
O3	0.3861 (4)	0.8801 (2)	0.41131 (5)	0.0859 (6)
O4	1.1084 (3)	0.3294 (2)	0.49694 (5)	0.0693 (4)
C1	0.4295 (4)	0.4337 (2)	0.33262 (5)	0.0517 (4)
C2	0.2508 (4)	0.5786 (2)	0.32452 (5)	0.0484 (4)
C3	0.2347 (4)	0.7286 (2)	0.35050 (6)	0.0527 (4)
H3	0.116158	0.825254	0.345167	0.063*
C4	0.3949 (4)	0.7350 (3)	0.38448 (6)	0.0538 (4)
C5	0.5741 (4)	0.5931 (3)	0.39316 (5)	0.0499 (4)
C6	0.5866 (4)	0.4433 (3)	0.36651 (6)	0.0529 (4)
H6	0.705237	0.346609	0.371846	0.063*
C7	0.6377 (6)	0.1590 (3)	0.30841 (8)	0.0757 (7)
H7A	0.622147	0.070754	0.286938	0.114*
H7B	0.623493	0.095419	0.333619	0.114*
H7C	0.808187	0.220340	0.306795	0.114*
C8	−0.0771 (5)	0.7079 (3)	0.28094 (7)	0.0713 (6)
H8A	−0.165774	0.680737	0.256091	0.107*
H8B	0.021689	0.821845	0.278378	0.107*
H8C	−0.207963	0.720614	0.301848	0.107*
C9	0.1827 (7)	1.0141 (4)	0.40817 (8)	0.0843 (8)
H9A	0.203584	1.081945	0.383585	0.126*
H9B	0.193954	1.098494	0.430410	0.126*
H9C	0.011359	0.953503	0.408376	0.126*
C10	0.7326 (4)	0.6011 (3)	0.43021 (6)	0.0553 (4)
H10	0.683718	0.691693	0.448720	0.066*
C11	0.9339 (5)	0.4955 (3)	0.44000 (6)	0.0615 (5)
H11	0.991306	0.407710	0.421409	0.074*
C12	1.0796 (5)	0.5059 (3)	0.47927 (6)	0.0630 (5)
H12A	1.255373	0.559841	0.474984	0.076*
H12B	0.981865	0.586666	0.497386	0.076*
H4	0.956 (6)	0.284 (4)	0.4987 (9)	0.077 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0884 (11)	0.0659 (9)	0.0833 (10)	0.0314 (9)	−0.0279 (9)	−0.0287 (8)
O2	0.0681 (8)	0.0609 (8)	0.0564 (7)	0.0175 (8)	−0.0137 (7)	−0.0041 (6)
O3	0.1055 (13)	0.0671 (9)	0.0851 (11)	0.0267 (10)	−0.0252 (10)	−0.0308 (8)
O4	0.0505 (8)	0.0767 (10)	0.0806 (10)	0.0018 (8)	−0.0067 (7)	0.0186 (8)
C1	0.0554 (10)	0.0457 (9)	0.0539 (9)	0.0084 (8)	−0.0033 (8)	−0.0058 (7)
C2	0.0497 (9)	0.0478 (9)	0.0478 (8)	0.0048 (8)	−0.0009 (7)	0.0024 (7)
C3	0.0568 (10)	0.0415 (8)	0.0596 (9)	0.0094 (8)	0.0003 (8)	0.0014 (7)
C4	0.0587 (10)	0.0466 (9)	0.0562 (9)	0.0046 (9)	0.0020 (8)	−0.0057 (7)
C5	0.0485 (9)	0.0520 (9)	0.0491 (8)	−0.0009 (9)	0.0019 (7)	−0.0003 (7)
C6	0.0500 (9)	0.0480 (9)	0.0606 (9)	0.0108 (8)	−0.0046 (8)	0.0013 (7)
C7	0.0832 (16)	0.0594 (12)	0.0845 (15)	0.0235 (12)	−0.0010 (13)	−0.0157 (11)
C8	0.0712 (13)	0.0746 (13)	0.0681 (11)	0.0192 (12)	−0.0138 (11)	0.0102 (10)
C9	0.109 (2)	0.0563 (12)	0.0878 (15)	0.0261 (14)	0.0031 (15)	−0.0160 (12)
C10	0.0551 (10)	0.0551 (10)	0.0558 (9)	0.0030 (9)	−0.0007 (8)	−0.0042 (8)
C11	0.0660 (11)	0.0582 (10)	0.0602 (10)	0.0083 (11)	−0.0019 (9)	−0.0019 (9)
C12	0.0553 (10)	0.0653 (11)	0.0682 (11)	−0.0023 (10)	−0.0104 (10)	0.0048 (10)

Geometric parameters (Å, º)

O1—C1	1.371 (2)	C6—H6	0.9300
O1—C7	1.403 (3)	C7—H7A	0.9600
O2—C2	1.362 (2)	C7—H7B	0.9600
O2—C8	1.421 (3)	C7—H7C	0.9600
O3—C4	1.375 (2)	C8—H8A	0.9600
O3—C9	1.404 (3)	C8—H8B	0.9600
O4—C12	1.406 (3)	C8—H8C	0.9600
O4—H4	0.83 (3)	C9—H9A	0.9600
C1—C2	1.398 (2)	C9—H9B	0.9600
C1—C6	1.378 (3)	C9—H9C	0.9600
C2—C3	1.386 (3)	C10—H10	0.9300
C3—H3	0.9300	C10—C11	1.301 (3)
C3—C4	1.388 (3)	C11—H11	0.9300
C4—C5	1.387 (3)	C11—C12	1.501 (3)
C5—C6	1.398 (3)	C12—H12A	0.9700
C5—C10	1.469 (3)	C12—H12B	0.9700
C1—O1—C7	117.65 (17)	H7A—C7—H7C	109.5
C2—O2—C8	117.44 (16)	H7B—C7—H7C	109.5
C4—O3—C9	119.67 (19)	O2—C8—H8A	109.5
C12—O4—H4	107 (2)	O2—C8—H8B	109.5
O1—C1—C2	115.71 (16)	O2—C8—H8C	109.5
O1—C1—C6	125.27 (17)	H8A—C8—H8B	109.5
C6—C1—C2	119.02 (16)	H8A—C8—H8C	109.5
O2—C2—C1	116.08 (15)	H8B—C8—H8C	109.5
O2—C2—C3	124.22 (16)	O3—C9—H9A	109.5
C3—C2—C1	119.71 (16)	O3—C9—H9B	109.5
C2—C3—H3	119.9	O3—C9—H9C	109.5
C2—C3—C4	120.21 (17)	H9A—C9—H9B	109.5
C4—C3—H3	119.9	H9A—C9—H9C	109.5
O3—C4—C3	122.56 (17)	H9B—C9—H9C	109.5
O3—C4—C5	116.25 (17)	C5—C10—H10	116.4
C5—C4—C3	121.19 (16)	C11—C10—C5	127.21 (19)
C4—C5—C6	117.54 (16)	C11—C10—H10	116.4
C4—C5—C10	119.65 (16)	C10—C11—H11	117.8
C6—C5—C10	122.76 (17)	C10—C11—C12	124.4 (2)
C1—C6—C5	122.33 (16)	C12—C11—H11	117.8
C1—C6—H6	118.8	O4—C12—C11	111.78 (18)
C5—C6—H6	118.8	O4—C12—H12A	109.3
O1—C7—H7A	109.5	O4—C12—H12B	109.3
O1—C7—H7B	109.5	C11—C12—H12A	109.3
O1—C7—H7C	109.5	C11—C12—H12B	109.3
H7A—C7—H7B	109.5	H12A—C12—H12B	107.9
O1—C1—C2—O2	0.1 (3)	C4—C5—C10—C11	−169.4 (2)
O1—C1—C2—C3	−179.93 (19)	C5—C10—C11—C12	−177.2 (2)
O1—C1—C6—C5	179.9 (2)	C6—C1—C2—O2	−179.95 (17)
O2—C2—C3—C4	179.89 (18)	C6—C1—C2—C3	0.0 (3)
O3—C4—C5—C6	179.74 (19)	C6—C5—C10—C11	13.4 (3)
O3—C4—C5—C10	2.4 (3)	C7—O1—C1—C2	169.6 (2)
C1—C2—C3—C4	−0.1 (3)	C7—O1—C1—C6	−10.4 (3)
C2—C1—C6—C5	−0.1 (3)	C8—O2—C2—C1	−178.38 (19)
C2—C3—C4—O3	−179.8 (2)	C8—O2—C2—C3	1.6 (3)
C2—C3—C4—C5	0.2 (3)	C9—O3—C4—C3	9.8 (3)
C3—C4—C5—C6	−0.2 (3)	C9—O3—C4—C5	−170.1 (2)
C3—C4—C5—C10	−177.59 (18)	C10—C5—C6—C1	177.44 (19)
C4—C5—C6—C1	0.1 (3)	C10—C11—C12—O4	130.8 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O4^i	0.83 (3)	1.93	2.7527 (14)	178.2

Symmetry code: (i) x−1/2, −y+1/2, −z+1.