Synthesis, crystal structure and absolute configuration of (3aS,4R,5S,7aR)-7-(but-3-en-1-yn-1-yl)-2,2-dimethyl-3a,4,5,7a-tetra­hydro-2H-1,3-benzodioxole-4,5-diol

Peixoto de Abreu Lima, A.; Pandolfi, E.; Schapiro, V.; Suescun, L.

doi:10.1107/S2056989024009733

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 80| Part 11| November 2024| Pages 1165-1169

https://doi.org/10.1107/S2056989024009733

Open

access

Synthesis, crystal structure and absolute configuration of (3aS,4R,5S,7aR)-7-(but-3-en-1-yn-1-yl)-2,2-dimethyl-3a,4,5,7a-tetrahydro-2H-1,3-benzodioxole-4,5-diol

Alejandro Peixoto de Abreu Lima,^a ^* Enrique Pandolfi,^a Valeria Schapiro ^a and Leopoldo Suescun ^b

^aLaboratorio de Síntesis Orgánica, Departamento de Química Orgánica, Facultad de Química, Universida de la República, Avenida General Flores 2124, CP 11800, Montevideo, Uruguay, and ^bCryssmat-Lab, Cátedra de Física, DETEMA, Facultad de Química, Universidad de la República, Av. General Flores 2124, CP 11800, Montevideo, Uruguay
^*Correspondence e-mail: apeixoto@fq.edu.uy

Edited by F. F. Ferreira, Universidade Federal do ABC, Brazil (Received 5 July 2024; accepted 4 October 2024; online 11 October 2024)

The absolute configuration of the title compound, C₁₃H₁₆O₄, determined as 1S,2R,3S,4R based on the synthetic pathway, was confirmed by single-crystal X-ray diffraction. The molecule is a relevant intermediary for the synthesis of speciosins, epoxyquinoides or their analogues. The molecule contains fused five- and six-membered rings with two free hydroxyl groups and two protected as an isopropylidenedioxo ring. The packing is directed by hydrogen bonds that define double planes of molecules laying along the ab plane and van der Waals interactions between aliphatic chains that point outwards of the planes.

Keywords: speciosins; epoxide opening; chiral bicycle; crystal structure.

CCDC reference: 2389407

1. Chemical context

Speciosins are a group of epoxyquinoids isolated from fungal origins that exhibit diverse biological activities (Jiang et al., 2009 , 2011 ; Kim et al., 2006 ). So far, only one racemic synthesis has been reported (Hookins et al., 2011 ). We proposed the first synthetic enantioselective approach towards speciosins starting from halodiols obtained from halobenzene (Vila et al., 2013 ). In our reported enantioselective route for the synthesis of speciosin A, we obtained molecule 1 in two steps in 65% yield from the diol A (Fig. 1). Compound 1 had to be epoxidized in order to functionalize the most substituted double bond (Peixoto de Abreu Lima et al., 2019 ). That reaction yielded epoxides 2 and 3, a pair of regioisomers. Despite our efforts, we could not obtain the desired regioselectivity towards 2, and we obtained a mixture of 2 and 3 using a wide variety of solvents, temperature, and concentration (Fig. 2). Another problem we faced was the separation of 2 and 3, which obliged us to continue our synthetic route using the mixture of both epoxides. Treating 2 and 3 under basic conditions we obtained the products of tosylate elimination and epoxide basic opening for each regioisomer (Fig. 3). Diols 4 and 5 could be successfully separated by column chromatography. Compound 4 is a valuable intermediate for the synthesis of speciosin A. On the other hand, 5 may be useful as an intermediate for the synthesis of other epoxyquinoides like harveynone or its analogues (Pandolfi et al., 2013 ; Nagata et al., 1992 ), especially given that it could easily be obtained in higher proportions (Peixoto de Abreu Lima et al., 2019). The epoxide opening in basic aqueous conditions can yield two diastereomers depending on which carbon is attacked by the hydroxyl, though it is expected that the allylic position is more reactive. Thus, it is important to confirm the stereochemistry of the formed diol before continuing with further synthetic steps by means of crystallization and crystal structure determination.

Figure 1
Biotransformation of bromobenzene and alkyne side chain introduction via Sonogashira coupling.

Figure 2
Epoxidation of molecule 1.

Figure 3
Epoxide opening in basic aqueous conditions.

2. Structural commentary

Fig. 4 shows the structure of 5 (the title compound) as determined by single-crystal X-ray diffraction. All bond distances and angles fall within the expected values for this kind of organic molecule. The absolute configuration, determined as 1S,2R,3S,4R based on the synthetic pathway, was confirmed by X-ray diffraction on the basis of anomalous dispersion of light atoms only. The cyclohexene core of the molecule shows puckering angles (Cremer & Pople, 1975 ) of Θ = 61.0 (7)° and Φ = 51.7 (8)°, indicating a conformation between envelope (Θ = 54.7°, Φ = 60°) and screw-boat (Θ = 67.5°, Φ = 30°) with C2 forming the flap. The planar part of the C1–C6–C5–C4–C3 ring (fit of the plane with an r.m.s. deviation of 0.0405 Å) forms a dihedral angle of 52.5 (3)° with the flap (C1–C2–C3). The linear buten-3-en-1-ynyl chain is coplanar with the main part of the ring with a maximum deviation from the plane of 0.21 Å for C10 (see supporting information). The five-membered isopropylidenedioxo ring (O3–C3–C4–O4–C11) is also envelope-shaped with Φ₂ = 289.1 (10)° (idealized Φ₂ = 288°) with O4 forming the flap. The absolute configuration of the four chiral centers and the double bond allows for the five substituents of the cyclohexene ring to be equatorial (O1, O2, C7) or bisectional (O3, O4) with three of the five H atoms being in axial positions.

Figure 4
ORTEP view of the title compound showing the numbering scheme. Ellipsoids are drawn at the 30% probability level.

3. Supramolecular features

In the crystal, molecules are connected through strong O—H⋯O hydrogen bonds (see Table 1 and Fig. 5). Pairs of O2—H2A⋯O3ⁱ hydrogen bonds connect molecules related by a twofold rotation along [010]. O1—H1 groups pointing outwards from the axis form infinite O1—H1⋯O1ⁱⁱ chains along [010] between twofold-screw-rotated equivalent molecules [symmetry codes: (i) $[{1\over 2}]$ − x, y − $[{1\over 2}]$ , 1 − z; (ii) 1 − x, y, 1 − z] as shown in Fig. 6. The combination of both hydrogen bonds provides a strong set of intermolecular interactions that define planes parallel to the ac plane with the but-3-en-1-ynyl chains pointing outwards on both sides. Weak van der Waals interactions connect these planes along [001] as shown in Fig. 7.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O1ⁱ	0.82	2.00	2.803 (3)	167
O2—H2A⋯O3ⁱⁱ	0.82	2.19	2.995 (6)	168
Symmetry codes: (i) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+1]$ ; (ii) .

Figure 5
Unit-cell contents of 5. Note that two hydrogen bonds involving O2 and O3 connect twofold-rotation-related molecules, and a third one connects screw-rotation-related molecules.

Figure 6
View of the unit cell along the [101] direction showing linear chains of molecules connected through O1—H1⋯O1 hydrogen bonds.

Figure 7
View of the unit cell along [010] direction showing the weak interactions between aliphatic chains in parallel hydrogen-bonded molecular planes of 5.

4. Database survey

One dozen entries in the 2024.1 version of the CSD (Groom et al., 2016 ) are related to the title compound sharing a mono-substituted tetrahydroxy-cyclohexene core. The most interesting ones are discussed hereafter. The asymmetric unit of TEDZUA (Buckler et al., 2017 ) contains two independent molecules that only differ from 5 in the substituent at C5 sharing the same absolute structure at all the chiral centers and the isopropylidenedioxo ring containing O3 and O4. The cyclohexene cores show an almost perfect envelope conformation in both molecules, but the shape of the bulky vanillin substituent affects the conformation of the five-membered ring and the positions of O4 substituents of C4 in each molecule making them axial. The packing is directed by π-stacking between vanillin residues and a more complex hydrogen-bond network including one crystallization water molecule. RAQLED (Taher et al., 2017 ) is a tetrahydroxy-cyclohexene with a –Csp–Csp– chain at C5 (ending in a substituted benzene ring) but the hydroxyl groups at C3 and C4 are free (not part of a five-membered ring) and C2 has an inverted absolute configuration making the cyclohexene ring fall between an envelope and a half-chair conformation with two of the OH substituents on C4 and C1 in axial positions. The packing is similar to that of 5 with a complex hydrogen-bond network defining planes of molecules with the non-polar substituents pointing outwards, interacting weakly with parallel planes. RURVEH (Macías et al., 2015 ) and HOYFIN (Tibhe et al., 2018 ) show a tetrahydroxy-cyclohexene core with inverted configurations at C1 and C2 with respect to 5. The ring conformations fall between envelope and half-chair with the flap at the opposite side of the ring plane, keeping both OH substituents close to equatorial positions. RURVEH also shares the isopropylidenedioxo ring including O3 and O4 with 5. The packing in HOYFIN is directed by a complex 3D hydrogen-bond network while two different intermolecular hydrogen bonds define the packing of RURVEH, but in this case linear chains of hydrogen-bonded molecules are observed with weak interactions between parallel chains.

5. Synthesis and crystallization

The synthesis of the title compound was carried out through a mixture of epoxides 2 and 3. The epoxides (400 mg; 1.00 mmol, ratio 2:3 5:1) were dissolved in tetrahydrofuran (40 mL) at room temperature and a solution of potassium hydroxide 10% mV (40 mL) was added (Fig. 3). The mixture was refluxed for 4 h. After completion of the reaction, the mixture was diluted with 50 mL of ethyl acetate. The aqueous fraction was neutralized with 10% HCl and extracted with ethyl acetate (portions of 20 mL) until no further products were seen on the aqueous phase on TLC. The combined ethereal fractions were dried with Na₂SO₄ and filtered. Concentration of the filtrate, followed by column chromatography (hexanes:ethyl acetate 7:3) yielded 4 (177 mg; 81%) and 5 (33 mg; 15%). Small, plate-shaped crystals suitable for X-ray structure analysis were obtained by dissolving 5 in MeOH and slowly evaporating the solvent at room temperature, (m.p.) dec. 435 K. HRMS: C₁₃H₁₆O₄+Na calc:259.0946; exp : 259.0953. [α]^25.5_589nm = −13.10° (0.32 g/100 mL of MeOH). ¹H NMR (400 MHz, CDCl₃) δ (ppm): 6.18 (d, J = 2.1 Hz, 1H), 5.94 (dd, J = 17.6, 11.2 Hz, 1H), 5.71 (dd, J = 17.6, 2.0 Hz, 1H), 5.54 (dd, J = 11.2, 2.1 Hz, 1H), 4.61 (d, J = 6.4 Hz, 1H), 4.18 (d, J = 8.5 Hz, 1H), 4.12 (dd, J = 8.7, 6.3 Hz, 1H), 3.66 (t, J = 8.5 Hz, 1H), 2.90 (br s, 2H), 1.54 (s, 3H), 1.43 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ (ppm): 138.6, 128.0, 119.2, 117.0, 111.1, 89.3, 87.3, 77.4, 74.6, 74.2, 70.4, 28.3, 26.1.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All C and O atoms in the structure were refined anisotropically with restraints applied to the thermal ellipsoids of C9 and C10 and their bond distance that appeared shorter than expected due to significant librational disorder of the final atoms of the chain. Neither C9 nor C10 were split due to the lack of clear alternative positions. All H atoms were located in difference ΔF maps and refined freely in the initial model to confirm the absolute structure of the chiral centers. In the final model they were modeled in geometrically suitable positions and refined as riding with U_iso=1.2/1.5U_eq of the core/terminal parent atom.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₃H₁₆O₄
M_r	236.26
Crystal system, space group	Monoclinic, C2
Temperature (K)	296
a, b, c (Å)	17.4126 (13), 5.0996 (4), 14.9856 (11)
β (°)	109.652 (2)
V (Å³)	1253.17 (16)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.77
Crystal size (mm)	0.38 × 0.26 × 0.12

Data collection
Diffractometer	Bruker D8 Venture/Photon 100 CMOS
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.646, 0.754
No. of measured, independent and observed [I > 2σ(I)] reflections	10420, 2628, 2138
R_int	0.049
(sin θ/λ)_max (Å⁻¹)	0.642

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.080, 0.248, 1.13
No. of reflections	2628
No. of parameters	157
No. of restraints	3
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.41, −0.21
Absolute structure	Flack x determined using 752 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	0.1 (4)
Computer programs: APEX3 and SAINT (Bruker, 2018 ), OLEX2.solve (Bourhis et al., 2015 , Dolomanov et al., 2009 ), SHELXL2019/2 (Sheldrick, 2015 ) and ShelXle (Hübschle et al., 2011 ).

Supporting information

CCDC reference: 2389407

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989024009733/ee2008sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989024009733/ee2008Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989024009733/ee2008Isup3.cml

checkCIF report

Computing details top

(3aS,4R,5S,7aR)-7-(But-3-en-1-yn-1-yl)-2,2-dimethyl-3a,4,5,7a-tetrahydro-2H-1,3-benzodioxole-4,5-diol top

Crystal data top

C₁₃H₁₆O₄	F(000) = 504
M_r = 236.26	D_x = 1.252 Mg m⁻³
Monoclinic, C2	Cu Kα radiation, λ = 1.54178 Å
a = 17.4126 (13) Å	Cell parameters from 7392 reflections
b = 5.0996 (4) Å	θ = 5.2–77.8°
c = 14.9856 (11) Å	µ = 0.77 mm⁻¹
β = 109.652 (2)°	T = 296 K
V = 1253.17 (16) Å³	Plate, colourless
Z = 4	0.38 × 0.26 × 0.12 mm

Data collection top

Bruker D8 Venture/Photon 100 CMOS diffractometer	2628 independent reflections
Radiation source: Cu Incoatec microsource	2138 reflections with I > 2σ(I)
Detector resolution: 10.4167 pixels mm^-1	R_int = 0.049
\j and ω scans	θ_max = 81.6°, θ_min = 5.3°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −22→22
T_min = 0.646, T_max = 0.754	k = −6→6
10420 measured reflections	l = −18→19

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.080	w = 1/[σ²(F_o²) + (0.1316P)² + 0.6357P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.248	(Δ/σ)_max < 0.001
S = 1.13	Δρ_max = 0.41 e Å⁻³
2628 reflections	Δρ_min = −0.21 e Å⁻³
157 parameters	Absolute structure: Flack x determined using 752 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
3 restraints	Absolute structure parameter: 0.1 (4)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

7.1271 (0.0500) x + 3.5828 (0.0094) y + 6.1525 (0.0364) z = 4.8815 (0.0081)

* -0.0395 (0.0049) C1 * 0.0862 (0.0063) C2 * -0.0383 (0.0049) C4 * -0.0247 (0.0051) C5 * 0.0316 (0.0054) C6 * 0.0183 (0.0075) C7 * -0.0331 (0.0100) C8 * -0.1482 (0.0159) C9 * 0.1478 (0.0145) C10 0.7181 (0.0077) C3 1.0769 (0.0080) O1 0.9312 (0.0104) O2 0.6098 (0.0104) O3 0.5627 (0.0104) O4

Rms deviation of fitted atoms = 0.0798

6.7576 (0.0357) x + 3.6373 (0.0092) y + 6.2811 (0.0338) z = 4.8211 (0.0091)

Angle to previous plane (with approximate esd) = 1.364 ( 0.435 )

* -0.0646 (0.0036) C1 * 0.0457 (0.0028) C2 * -0.0264 (0.0029) C4 * 0.0026 (0.0042) C5 * 0.0427 (0.0038) C6 0.6990 (0.0071) C3 0.0448 (0.0094) C7 0.0054 (0.0126) C8 -0.0921 (0.0258) C9 0.2316 (0.0289) C10 1.0394 (0.0069) O1 0.8638 (0.0074) O2 0.5755 (0.0096) O3 0.5959 (0.0094) O4

Rms deviation of fitted atoms = 0.0419

- 1.1053 (0.0796) x - 4.9917 (0.0065) y + 3.0656 (0.0891) z = 0.2849 (0.0528)

Angle to previous plane (with approximate esd) = 52.465 ( 0.318 )

* 0.0000 (0.0000) C2 * 0.0000 (0.0000) C3 * 0.0000 (0.0000) C4

Rms deviation of fitted atoms = 0.0000

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C2	0.3746 (3)	0.1116 (12)	0.4110 (3)	0.0683 (11)
H2	0.398970	0.279483	0.437829	0.082*
C1	0.2844 (3)	0.1188 (12)	0.3889 (4)	0.0709 (12)
H1A	0.261212	−0.053188	0.365494	0.085*
O1	0.2645 (3)	0.1853 (10)	0.4702 (3)	0.0957 (14)
H1	0.252857	0.051859	0.493396	0.144*
O3	0.47692 (19)	0.0935 (9)	0.3375 (3)	0.0779 (11)
O4	0.4120 (2)	0.4298 (8)	0.2405 (3)	0.0750 (10)
C3	0.3927 (3)	0.0527 (10)	0.3215 (3)	0.0635 (11)
H3	0.377713	−0.128755	0.301629	0.076*
C4	0.3504 (3)	0.2420 (11)	0.2399 (3)	0.0661 (11)
H4	0.333731	0.145670	0.179805	0.079*
C5	0.2776 (3)	0.3908 (12)	0.2485 (4)	0.0714 (12)
O2	0.4080 (3)	−0.0979 (11)	0.4766 (3)	0.0939 (13)
H2A	0.433176	−0.036444	0.528898	0.141*
C6	0.2469 (3)	0.3234 (12)	0.3150 (5)	0.0791 (15)
H6	0.199730	0.407119	0.315916	0.095*
C7	0.2395 (3)	0.5872 (13)	0.1767 (4)	0.0790 (14)
C8	0.2085 (4)	0.7380 (16)	0.1167 (5)	0.0968 (19)
C9	0.1732 (7)	0.918 (2)	0.0403 (7)	0.139 (4)
H9	0.190917	0.900463	−0.011464	0.167*
C10	0.1213 (9)	1.096 (3)	0.0339 (11)	0.197 (7)
H10A	0.101128	1.123418	0.083313	0.295*
H10B	0.103243	1.200024	−0.020116	0.295*
C11	0.4859 (3)	0.2806 (12)	0.2714 (4)	0.0750 (14)
C12	0.5552 (4)	0.4617 (17)	0.3208 (8)	0.119 (3)
H12A	0.562490	0.585508	0.276005	0.179*
H12B	0.604292	0.361554	0.347503	0.179*
H12C	0.543123	0.553832	0.370311	0.179*
C13	0.5005 (5)	0.131 (2)	0.1907 (5)	0.113 (3)
H13A	0.459372	−0.001682	0.167864	0.170*
H13B	0.553287	0.049946	0.213143	0.170*
H13C	0.497907	0.250061	0.140183	0.170*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C2	0.064 (2)	0.073 (3)	0.070 (2)	−0.002 (2)	0.024 (2)	0.004 (2)
C1	0.064 (3)	0.072 (3)	0.085 (3)	−0.001 (2)	0.037 (2)	0.002 (3)
O1	0.113 (3)	0.091 (3)	0.109 (3)	−0.006 (3)	0.071 (3)	−0.009 (2)
O3	0.0525 (16)	0.093 (3)	0.090 (2)	0.0072 (17)	0.0260 (15)	0.016 (2)
O4	0.0591 (17)	0.073 (2)	0.100 (2)	0.0048 (16)	0.0359 (16)	0.0134 (19)
C3	0.054 (2)	0.064 (3)	0.074 (3)	0.0032 (19)	0.0240 (19)	0.001 (2)
C4	0.058 (2)	0.069 (3)	0.071 (2)	−0.001 (2)	0.0226 (19)	0.000 (2)
C5	0.057 (2)	0.072 (3)	0.084 (3)	0.005 (2)	0.023 (2)	0.004 (3)
O2	0.102 (3)	0.099 (3)	0.076 (2)	0.009 (3)	0.0231 (19)	0.018 (2)
C6	0.058 (2)	0.077 (3)	0.109 (4)	−0.001 (2)	0.037 (3)	0.003 (3)
C7	0.068 (3)	0.079 (3)	0.087 (3)	−0.005 (3)	0.021 (2)	−0.004 (3)
C8	0.078 (4)	0.098 (4)	0.103 (4)	−0.003 (4)	0.015 (3)	0.010 (4)
C9	0.158 (9)	0.114 (7)	0.116 (6)	−0.019 (6)	0.008 (6)	0.016 (6)
C10	0.196 (13)	0.124 (9)	0.219 (14)	0.009 (9)	0.002 (10)	0.057 (11)
C11	0.063 (3)	0.075 (3)	0.096 (3)	0.002 (2)	0.038 (2)	0.008 (3)
C12	0.069 (3)	0.086 (5)	0.183 (8)	−0.008 (3)	0.016 (4)	0.008 (5)
C13	0.111 (5)	0.138 (6)	0.111 (5)	0.035 (5)	0.064 (4)	0.007 (5)

Geometric parameters (Å, º) top

C2—O2	1.437 (7)	C5—C7	1.457 (8)
C2—C1	1.492 (6)	O2—H2A	0.8200
C2—C3	1.508 (7)	C6—H6	0.9300
C2—H2	0.9800	C7—C8	1.168 (9)
C1—O1	1.414 (7)	C8—C9	1.433 (12)
C1—C6	1.502 (8)	C9—C10	1.264 (16)
C1—H1A	0.9800	C9—H9	0.9300
O1—H1	0.8200	C10—H10A	0.9300
O3—C3	1.420 (5)	C10—H10B	0.9300
O3—C11	1.422 (7)	C11—C12	1.502 (9)
O4—C11	1.431 (6)	C11—C13	1.521 (10)
O4—C4	1.436 (6)	C12—H12A	0.9600
C3—C4	1.538 (7)	C12—H12B	0.9600
C3—H3	0.9800	C12—H12C	0.9600
C4—C5	1.520 (7)	C13—H13A	0.9600
C4—H4	0.9800	C13—H13B	0.9600
C5—C6	1.324 (8)	C13—H13C	0.9600

O2—C2—C1	108.9 (4)	C2—O2—H2A	109.5
O2—C2—C3	107.6 (5)	C5—C6—C1	123.4 (5)
C1—C2—C3	109.1 (4)	C5—C6—H6	118.3
O2—C2—H2	110.4	C1—C6—H6	118.3
C1—C2—H2	110.4	C8—C7—C5	177.7 (7)
C3—C2—H2	110.4	C7—C8—C9	176.9 (10)
O1—C1—C2	111.0 (4)	C10—C9—C8	128.6 (13)
O1—C1—C6	107.3 (5)	C10—C9—H9	115.7
C2—C1—C6	110.1 (4)	C8—C9—H9	115.7
O1—C1—H1A	109.4	C9—C10—H10A	120.0
C2—C1—H1A	109.4	C9—C10—H10B	120.0
C6—C1—H1A	109.4	H10A—C10—H10B	120.0
C1—O1—H1	109.5	O3—C11—O4	106.5 (4)
C3—O3—C11	109.3 (4)	O3—C11—C12	109.1 (5)
C11—O4—C4	103.6 (4)	O4—C11—C12	108.5 (5)
O3—C3—C2	109.5 (4)	O3—C11—C13	107.7 (6)
O3—C3—C4	103.5 (4)	O4—C11—C13	112.4 (5)
C2—C3—C4	113.2 (4)	C12—C11—C13	112.3 (6)
O3—C3—H3	110.1	C11—C12—H12A	109.5
C2—C3—H3	110.1	C11—C12—H12B	109.5
C4—C3—H3	110.1	H12A—C12—H12B	109.5
O4—C4—C5	108.0 (4)	C11—C12—H12C	109.5
O4—C4—C3	104.9 (4)	H12A—C12—H12C	109.5
C5—C4—C3	115.8 (4)	H12B—C12—H12C	109.5
O4—C4—H4	109.3	C11—C13—H13A	109.5
C5—C4—H4	109.3	C11—C13—H13B	109.5
C3—C4—H4	109.3	H13A—C13—H13B	109.5
C6—C5—C7	122.4 (5)	C11—C13—H13C	109.5
C6—C5—C4	119.6 (5)	H13A—C13—H13C	109.5
C7—C5—C4	117.7 (5)	H13B—C13—H13C	109.5

O2—C2—C1—O1	65.4 (6)	C2—C3—C4—C5	−19.9 (6)
C3—C2—C1—O1	−177.4 (5)	O4—C4—C5—C6	−127.6 (5)
O2—C2—C1—C6	−175.9 (5)	C3—C4—C5—C6	−10.4 (7)
C3—C2—C1—C6	−58.7 (6)	O4—C4—C5—C7	58.1 (6)
C11—O3—C3—C2	−122.7 (5)	C3—C4—C5—C7	175.4 (5)
C11—O3—C3—C4	−1.7 (5)	C7—C5—C6—C1	179.1 (5)
O2—C2—C3—O3	−72.8 (5)	C4—C5—C6—C1	5.1 (9)
C1—C2—C3—O3	169.2 (4)	O1—C1—C6—C5	151.3 (6)
O2—C2—C3—C4	172.3 (4)	C2—C1—C6—C5	30.3 (8)
C1—C2—C3—C4	54.2 (6)	C3—O3—C11—O4	22.5 (6)
C11—O4—C4—C5	156.9 (4)	C3—O3—C11—C12	139.5 (5)
C11—O4—C4—C3	32.8 (5)	C3—O3—C11—C13	−98.3 (5)
O3—C3—C4—O4	−19.4 (5)	C4—O4—C11—O3	−34.5 (5)
C2—C3—C4—O4	99.0 (5)	C4—O4—C11—C12	−151.9 (6)
O3—C3—C4—C5	−138.4 (4)	C4—O4—C11—C13	83.2 (6)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O1ⁱ	0.82	2.00	2.803 (3)	167
O2—H2A···O3ⁱⁱ	0.82	2.19	2.995 (6)	168

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

Acknowledgements

The authors wish to thank ANII (EQC_2012_07), CSIC and Facultad de Química-UdelaR for funds to purchase the diffractometer and the financial support of OPCW and PEDECIBA. AP also thanks ANII (POS_NAC_2014_1_102803) and CAP for postgraduate scholarships.

Funding information

Funding for this research was provided by: Agencia Nacional de Investigación e Innovación (grant No. FCE_1_2017_1_135581).

References

Bourhis, L. J., Dolomanov, O. V., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2015). Acta Cryst. A71, 59–75. Web of Science CrossRef IUCr Journals Google Scholar
Bruker (2018). APEX3 and SAINT. Bruker AXS Inc., Madison, Wisonsin, USA. Google Scholar
Buckler, J. N., Taher, E. S., Fraser, N. J., Willis, A. C., Carr, P. D., Jackson, C. J. & Banwell, M. G. (2017). J. Org. Chem. 82, 15, 7869–7886. Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Hookins, D. R., Burns, A. R. & Taylor, R. J. K. (2011). Eur. J. Org. Chem. pp. 451–454. Web of Science CrossRef Google Scholar
Hübschle, C. B., Sheldrick, G. M. & Dittrich, B. (2011). J. Appl. Cryst. 44, 1281–1284. Web of Science CrossRef IUCr Journals Google Scholar
Jiang, M.-Y., Li, Y., Wang, F. & Liu, J.-K. (2011). Phytochemistry, 72, 923–928. Web of Science CrossRef CAS PubMed Google Scholar
Jiang, M.-Y., Zhang, L., Liu, R., Dong, Z.-J. & Liu, J.-K. (2009). J. Nat. Prod. 72, 1405–1409. Web of Science CSD CrossRef PubMed CAS Google Scholar
Kim, H.-J., Vinale, F., Ghisalberti, E. L., Worth, C. M., Sivasithamparam, K., Skelton, B. W. & White, A. H. (2006). Phytochemistry, 67, 2277–2280. Web of Science CSD CrossRef PubMed CAS Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Macías, M. A., Suescun, L., Pandolfi, E., Schapiro, V., Tibhe, G. D. & Mombrú, Á. W. (2015). Acta Cryst. E71, 1013–1016. CSD CrossRef IUCr Journals Google Scholar
Nagata, T., Ando, Y. & Hirota, A. (1992). Biosci. Biotechnol. Biochem. 56, 810–811. CrossRef CAS PubMed Web of Science Google Scholar
Pandolfi, E., Schapiro, V., Heguaburu, V. & Labora, M. (2013). Curr. Org. Synth. 10, 2–42. CrossRef CAS Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Peixoto de Abreu Lima, A., Suescun, L., Pandolfi, E. & Schapiro, V. (2019). New J. Chem. 43, 3653–3655. Web of Science CSD CrossRef Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Taher, E. S., Guest, P., Benton, A., Ma, X., Banwell, M. G., Willis, A. C., Seiser, T., Newton, T. W. & Hutzler, J. (2017). J. Org. Chem. 82, 1, 211–233. Google Scholar
Tibhe, G. D., Macías, M. A., Schapiro, V., Suescun, L. & Pandolfi, E. (2018). Molecules, 23, 1653. Web of Science CSD CrossRef PubMed Google Scholar
Vila, M. A., Brovetto, M., Gamenara, D., Bracco, P., Zinola, G., Seoane, G., Rodríguez, S. & Carrera, I. (2013). J. Mol. Catal. B Enzym. 96, 14–20. Web of Science CrossRef CAS 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.