(23R,231S,25S)-231,26-Ep­oxy-23-ethyl­furost-20(22)-en-3β-ol

Guerrero-Luna, G.; Hernández-Linares, M.-G.; Cárdenas García, M.; Bernès, S.

doi:10.1107/S2414314623003449

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 8| Part 4| April 2023| x230344

https://doi.org/10.1107/S2414314623003449

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(23R,23¹S,25S)-23¹,26-Epoxy-23-ethylfurost-20(22)-en-3β-ol

Gabriel Guerrero-Luna,^a María-Guadalupe Hernández-Linares,^a,^b Maura Cárdenas García ^c and Sylvain Bernès ^d ^*

^aInstituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Av. San Claudio y 18 Sur, 72570 Puebla, Pue., Mexico, ^bLaboratorio de Investigación del Jardín Botánico, Benemérita Universidad Autónoma de Puebla, Av. San Claudio y 18 Sur, 72570 Puebla, Pue., Mexico, ^cFacultad de Medicina, Benemérita Universidad Autónoma de Puebla, 13 Sur 2702, 72420 Puebla, Pue., Mexico, and ^dInstituto de Física, Benemérita Universidad Autónoma de Puebla, Av. San Claudio y 18 Sur, 72570 Puebla, Pue., Mexico
^*Correspondence e-mail: sylvain_bernes@hotmail.com

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 12 April 2023; accepted 16 April 2023; online 21 April 2023)

The title compound, C₂₉H₄₆O₃, is a steroid synthesized through a rearrangement of a sarsasapogenin derivative in acidic medium. The newly formed ring F is a tetrahydro-2H-pyran heterocycle substituted by two methyl groups placed in equatorial positions. This ring displays a chair conformation, while dihydrofuran ring E, to which it is bonded, has an envelope conformation. The molecules are associated by weak O—H⋯O hydrogen bonds to form chains running in the [101] direction in the crystal.

Keywords: crystal structure; tetrahydropyran; sarsasapogenin; rearrangement reaction; hydrogen bond.

CCDC reference: 2256805

Structure description

The title steroid (2) was synthesized, starting from a derivative of sarsasapogenin (1), through a cleavage of ring F in acidic medium, followed by a Michael-type nucleophilic attack that affords a tetrahydro-2H-pyran ring bonded to the steroidal E ring (Fig. 1). The crystal structure of 1·0.5H₂O has been reported previously (Viñas-Bravo et al., 2003 ). On the other hand, the mechanism for the rearrangement 1→2 was described previously using a diosgenin derivative as substrate, instead of sarsasapogenin (del Río et al., 2006 ). As expected from this mechanism, both methyl groups substituting the pyran ring in 2 are placed in equatorial positions, defining the stereochemistry for atoms C25 and C27 as S,S (Fig. 2). The pyran ring adopts a chair conformation, characterized by a puckering amplitude q = 0.578 (4) Å. Surprisingly, the Cambridge Structural Database (Version 5.43, with all updates; Groom et al., 2016 ) does not contain any structure including the same heterocycle. However, many polysubstituted monocyclic tetrahydro-2H-pyran structures have been characterized by X-ray diffraction, showing that the chair conformation is almost always stabilized (e.g. Burton et al., 2007 ). Only a few exceptions to this rule are known, for some large molecules with steric hindrance issues (e.g. Aydillo et al., 2013 ).

Figure 1
The synthesis of the title compound, 2, starting from 1. The atom-numbering scheme follows the recommendations of IUPAC (Moss, 1989

). Key R/S configurations are displayed in red. pTsOH is p-toluenesulfonic acid.

Figure 2
The molecular structure of the title compound, 2, with displacement ellipsoids for non-H atoms drawn at the 50% probability level.

The 2,3-dihydrofuran ring E in 2 is close to being planar due to the presence of the C20=C22 double bond [1.324 (5) Å], also evidenced by a vibration at 1627 cm⁻¹ in the IR spectrum. The conformation can be described as an envelope with atom C16 as the flap, which belongs to the C—C bond fusing the D and E rings. The E ring has a small puckering amplitude, q = 0.184 (4) Å. A very similar conformation was observed in other steroids having the same E ring (Shen et al., 2013 ; Jeong & Fuchs, 1994 ). The remainder of the molecular structure, i.e. the A/B/C/D steroidal nucleus, is identical to that of sarsasapogenin, with cis-fused A/B rings.

The crystal structure is very simple, since it is based on a single weak O—H⋯O hydrogen bond, involving the hydroxy group at C3 and the O-atom acceptor of the tetrahydro-2H-pyran ring, O26 (Table 1 and Fig. 3). The molecules form infinite chains, running in the [101] direction. Neighbouring chains in the crystal are related by the twofold screw axis parallel to [010] in the space group P2₁.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3A⋯O26ⁱ	0.87 (4)	2.11 (4)	2.943 (4)	159 (5)
Symmetry code: (i) x+1, y, z+1.

Figure 3
Part of the crystal structure of the title compound, 2, showing chains formed via O—H⋯O hydrogen bonds (dashed bonds). For symmetry code (i), see Table 1

The molecular structure of 2 is embedded in a broader project aimed at targeting steroidal compounds which could interact with signalling pathways that control skeletal muscle atrophy and hypertrophy (Cohen et al., 2015 ). Indeed, the web tool SwissTargetPrediction (Daina et al., 2019 ) predicts that compound 2 presents a binding affinity for androgen and estrogen receptors, as well as for PI3K enzyme.

Synthesis and crystallization

In a round-bottomed flask was dissolved 275 mg (0.62 mmol) of 1 and 150 mg of pTsOH (ca 0.9 mmol) in 5 ml of benzene, and this mixture was refluxed for 30 min. The crude was then evaporated and the resulting solid dissolved in CH₂Cl₂, washed with distilled H₂O, dried over Na₂SO₄ and evaporated in vacuo to dryness. The residue was purified by chromatography over silica gel with hexane/EtOAc (4:1 v:v) as eluent, to give 268 mg of 2 (97% yield). IR (ν, cm⁻¹): 2998 (C—H), 1627 (C=C). ¹H NMR (500 MHz, CDCl₃): δ (ppm) 4.70 (1H, m, H-16), 4.08 (1H, m, H-3), 3.79 (1H, ddd, J_26eq,26ax = 11.0, J_26eq,25 = 3.4 Hz, J_26eq,24eq = 1.4, H-26eq), 3.36 (1H, dq, J_23 (1),23 = 9.54, J_{23 (1),23 (2)} = 6.2 Hz, H-23¹), 2.98 (1H, dd, J_26ax,26eq = J_26ax,25 = 11.0 Hz, H-26ax), 2.46 (1H, d, J_17,16 = 10.0 Hz, H-17), 2.40 (1H, ddd, J_23,23 (1) = 9.54, J_23,24eq = 3.4, J_23,24ax = 11.0 Hz, H-23), 1.57 (3H, s, CH₃-21), 1.11 (3H, d, J_{23 (2),23 (1)} = 6.5 Hz, C-23²), 0.95 (3H, s, CH₃-19), 0.76 (3H, d, J_27,25 = 7.0 Hz, CH₃-27), 0.67 (3H, s, CH₃-18). ¹³C NMR (125 MHz, CDCl₃): δ (ppm) 152.5 (C-22), 105.0 (C-20), 85.0 (C-16), 73.4 (C-23¹), 73.3 (C-26), 67.1 (C-3), 64.3 (C-17), 55.1 (C-14), 44.0 (C-9), 41.5 (C-10), 41.3 (C-23), 40.1 (C-5), 39.8 (C-4), 36.5 (C-6), 36.3 (C-15), 35.3 (C-1), 35.0 (C-12), 30.9 (C-2), 30.0 (C-13), 27.9 (C-7), 26.7 (C-8), 26.5 (C-25), 23.9 (C-24), 21.7 (C-11), 20.1 (CH₃-23²), 17.0 (CH₃-19), 14.8 (CH₃-27), 14.3 (CH₃-18), 11.9 (CH₃-21).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were placed in calculated positions, with C—H = 1.00 (methine CH), 0.99 (methylene CH₂) or 0.98 Å (methyl CH₃). Atom H3A (of the hydroxy group) was refined with free coordinates. Isotropic displacement parameters for the H atoms were calculated as U_iso(H) = xU_eq(carrier atom), with x = 1.5 for methyl groups and the hydroxy H atom, and x = 1.2 for the other H atoms. The methyl groups were allowed to rotate but not to tip. Due to the absence of anomalous scatterers, the absolute configuration could not be determined and was set according to the starting material.

Table 2
Experimental details

Crystal data
Chemical formula	C₂₉H₄₆O₃
M_r	442.66
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	153
a, b, c (Å)	6.3829 (7), 12.6897 (8), 15.9539 (17)
β (°)	101.308 (8)
V (Å³)	1267.1 (2)
Z	2
Radiation type	Ag Kα, λ = 0.56083 Å
μ (mm⁻¹)	0.05
Crystal size (mm)	0.24 × 0.16 × 0.07

Data collection
Diffractometer	Stoe Stadivari
Absorption correction	Multi-scan (X-AREA; Stoe & Cie, 2018 )
T_min, T_max	0.519, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	15499, 4669, 2283
R_int	0.102
(sin θ/λ)_max (Å⁻¹)	0.624

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.077, 0.70
No. of reflections	4669
No. of parameters	298
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.16, −0.18
Computer programs: X-AREA (Stoe & Cie, 2018), SHELXT2018 (Sheldrick, 2015a ), SHELXL2018 (Sheldrick, 2015b ), XP in SHELXTL-Plus (Sheldrick, 2008 ), Mercury (Macrae et al., 2020 ) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 2256805

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2414314623003449/bt4138sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314623003449/bt4138Isup2.hkl

checkCIF report

Computing details top

Data collection: X-AREA (Stoe & Cie, 2018); cell refinement: X-AREA (Stoe & Cie, 2018); data reduction: X-AREA (Stoe & Cie, 2018); program(s) used to solve structure: SHELXT2018 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: XP in SHELXTL-Plus (Sheldrick, 2008) and Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

(23R,23¹S,25S)-23¹,26-Epoxy-23-ethylfurost-20(22)-en-3β-ol top

Crystal data top

C₂₉H₄₆O₃	F(000) = 488
M_r = 442.66	D_x = 1.160 Mg m⁻³
Monoclinic, P2₁	Ag Kα radiation, λ = 0.56083 Å
a = 6.3829 (7) Å	Cell parameters from 7481 reflections
b = 12.6897 (8) Å	θ = 2.4–27.7°
c = 15.9539 (17) Å	µ = 0.05 mm⁻¹
β = 101.308 (8)°	T = 153 K
V = 1267.1 (2) Å³	Irregular, colourless
Z = 2	0.24 × 0.16 × 0.07 mm

Data collection top

Stoe Stadivari diffractometer	4669 independent reflections
Radiation source: Sealed X-ray tube, Axo Astix-f Microfocus source	2283 reflections with I > 2σ(I)
Graded multilayer mirror monochromator	R_int = 0.102
Detector resolution: 5.81 pixels mm^-1	θ_max = 20.5°, θ_min = 2.4°
ω scans	h = −7→7
Absorption correction: multi-scan (X-AREA; Stoe & Cie, 2018)	k = −15→15
T_min = 0.519, T_max = 1.000	l = −19→19
15499 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.043	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.077	w = 1/[σ²(F_o²) + (0.0188P)²] where P = (F_o² + 2F_c²)/3
S = 0.70	(Δ/σ)_max < 0.001
4669 reflections	Δρ_max = 0.16 e Å⁻³
298 parameters	Δρ_min = −0.17 e Å⁻³
1 restraint	Extinction correction: (SHELXL2018; Sheldrick 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 constraints	Extinction coefficient: 0.0100 (10)
Primary atom site location: dual

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

	x	y	z	U_iso*/U_eq
C1	0.7075 (7)	0.3112 (3)	0.7615 (3)	0.0303 (10)
H1A	0.621334	0.309403	0.806762	0.036*
H1B	0.674723	0.246376	0.726844	0.036*
C2	0.9432 (7)	0.3097 (3)	0.8037 (3)	0.0335 (11)
H2A	0.972593	0.247124	0.841295	0.040*
H2B	1.030808	0.303861	0.759143	0.040*
C3	1.0065 (6)	0.4089 (3)	0.8563 (2)	0.0353 (10)
H3	1.165276	0.410355	0.875704	0.042*
O3	0.9070 (5)	0.4036 (2)	0.93021 (18)	0.0447 (8)
H3A	0.972 (8)	0.449 (3)	0.967 (3)	0.067*
C4	0.9355 (6)	0.5075 (3)	0.8039 (2)	0.0313 (10)
H4A	1.024977	0.515500	0.760204	0.038*
H4B	0.961535	0.569582	0.842168	0.038*
C5	0.7003 (7)	0.5073 (3)	0.7592 (2)	0.0304 (10)
H5	0.612950	0.506869	0.804783	0.036*
C6	0.6443 (7)	0.6089 (3)	0.7069 (3)	0.0369 (12)
H6A	0.487038	0.614593	0.689524	0.044*
H6B	0.695409	0.670465	0.743349	0.044*
C7	0.7433 (7)	0.6119 (3)	0.6272 (2)	0.0332 (11)
H7A	0.900717	0.615808	0.644573	0.040*
H7B	0.693851	0.675862	0.593581	0.040*
C8	0.6827 (6)	0.5142 (3)	0.5712 (2)	0.0257 (9)
H8	0.524350	0.514261	0.550355	0.031*
C9	0.7450 (6)	0.4127 (3)	0.6240 (2)	0.0234 (9)
H9	0.902181	0.417847	0.646833	0.028*
C10	0.6379 (6)	0.4079 (3)	0.7034 (2)	0.0255 (9)
C11	0.7125 (7)	0.3130 (3)	0.5679 (3)	0.0287 (10)
H11A	0.775839	0.252065	0.602689	0.034*
H11B	0.557409	0.299583	0.549940	0.034*
C12	0.8121 (7)	0.3202 (3)	0.4879 (2)	0.0283 (10)
H12A	0.969689	0.322403	0.505309	0.034*
H12B	0.773442	0.256685	0.452232	0.034*
C13	0.7352 (6)	0.4182 (3)	0.4354 (2)	0.0229 (9)
C14	0.7897 (6)	0.5144 (3)	0.4943 (2)	0.0235 (9)
H14	0.947049	0.511511	0.517207	0.028*
C15	0.7515 (7)	0.6089 (3)	0.4321 (2)	0.0314 (11)
H15A	0.597790	0.626844	0.416707	0.038*
H15B	0.832343	0.671696	0.457074	0.038*
C16	0.8341 (7)	0.5686 (3)	0.3548 (2)	0.0288 (10)
H16	0.975553	0.601243	0.352721	0.035*
O16	0.6841 (4)	0.58617 (17)	0.27418 (16)	0.0291 (7)
C17	0.8563 (6)	0.4468 (3)	0.3631 (3)	0.0251 (10)
H17	1.010420	0.427022	0.380546	0.030*
C18	0.4938 (5)	0.4103 (3)	0.3978 (2)	0.0277 (9)
H18A	0.466708	0.349055	0.359841	0.042*
H18B	0.446279	0.474441	0.365412	0.042*
H18C	0.415055	0.402417	0.444388	0.042*
C19	0.3914 (5)	0.4007 (4)	0.6764 (3)	0.0373 (10)
H19A	0.339983	0.455995	0.634456	0.056*
H19B	0.326656	0.410169	0.726717	0.056*
H19C	0.351771	0.331534	0.650887	0.056*
C20	0.7720 (5)	0.4121 (3)	0.2728 (2)	0.0246 (9)
C21	0.7993 (7)	0.3020 (3)	0.2430 (3)	0.0340 (11)
H21A	0.720725	0.253044	0.273020	0.051*
H21B	0.951313	0.283437	0.255138	0.051*
H21C	0.743733	0.297329	0.181338	0.051*
C22	0.6775 (6)	0.4928 (3)	0.2281 (2)	0.0261 (10)
C23	0.5667 (6)	0.5036 (3)	0.1365 (2)	0.0268 (9)
H23	0.585841	0.436189	0.106392	0.032*
C24	0.6676 (6)	0.5930 (3)	0.0927 (2)	0.0300 (10)
H24A	0.662424	0.659391	0.124732	0.036*
H24B	0.819359	0.576203	0.093234	0.036*
C25	0.5498 (7)	0.6076 (3)	0.0008 (3)	0.0338 (10)
H25	0.565143	0.541937	−0.032062	0.041*
C26	0.3142 (7)	0.6251 (3)	0.0011 (3)	0.0381 (12)
H26A	0.297184	0.690286	0.033231	0.046*
H26B	0.235255	0.634484	−0.058357	0.046*
O26	0.2251 (4)	0.53738 (19)	0.03962 (17)	0.0344 (8)
C27	0.3263 (6)	0.5230 (3)	0.1284 (2)	0.0276 (10)
H27	0.304525	0.587849	0.161257	0.033*
C28	0.6418 (7)	0.6999 (3)	−0.0415 (3)	0.0475 (13)
H28A	0.612316	0.765851	−0.014044	0.071*
H28B	0.575716	0.702249	−0.102335	0.071*
H28C	0.796571	0.690815	−0.035290	0.071*
C29	0.2096 (6)	0.4323 (3)	0.1596 (3)	0.0335 (11)
H29A	0.059098	0.451242	0.155687	0.050*
H29B	0.274301	0.416708	0.219255	0.050*
H29C	0.219447	0.370062	0.124274	0.050*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.036 (3)	0.033 (2)	0.022 (2)	−0.002 (2)	0.008 (2)	0.004 (2)
C2	0.037 (3)	0.032 (2)	0.033 (3)	0.002 (2)	0.010 (2)	0.007 (2)
C3	0.031 (2)	0.048 (2)	0.027 (2)	−0.004 (2)	0.005 (2)	0.007 (2)
O3	0.050 (2)	0.0554 (19)	0.0292 (19)	−0.0094 (18)	0.0075 (16)	−0.0026 (17)
C4	0.033 (3)	0.035 (2)	0.024 (2)	−0.004 (2)	0.001 (2)	−0.002 (2)
C5	0.031 (3)	0.032 (2)	0.028 (2)	0.002 (2)	0.007 (2)	0.000 (2)
C6	0.042 (3)	0.032 (2)	0.035 (3)	0.008 (2)	0.004 (2)	−0.006 (2)
C7	0.045 (3)	0.0236 (19)	0.029 (3)	0.005 (2)	0.002 (2)	0.0007 (19)
C8	0.025 (2)	0.0226 (19)	0.026 (2)	0.000 (2)	−0.0029 (19)	−0.003 (2)
C9	0.022 (2)	0.0236 (17)	0.025 (2)	0.004 (2)	0.0046 (18)	0.001 (2)
C10	0.020 (2)	0.031 (2)	0.024 (2)	0.002 (2)	0.0025 (19)	0.001 (2)
C11	0.033 (3)	0.022 (2)	0.030 (2)	0.0007 (19)	0.004 (2)	0.002 (2)
C12	0.030 (3)	0.026 (2)	0.029 (3)	0.0032 (18)	0.007 (2)	0.0023 (19)
C13	0.023 (2)	0.0224 (18)	0.024 (2)	0.002 (2)	0.0064 (18)	0.0032 (19)
C14	0.022 (2)	0.0216 (18)	0.025 (2)	−0.0012 (19)	0.0010 (19)	0.004 (2)
C15	0.040 (3)	0.0238 (19)	0.029 (3)	−0.004 (2)	0.001 (2)	0.0005 (19)
C16	0.030 (3)	0.026 (2)	0.027 (2)	−0.0041 (18)	−0.003 (2)	0.0039 (19)
O16	0.0371 (18)	0.0245 (14)	0.0235 (16)	0.0008 (13)	0.0006 (14)	0.0011 (12)
C17	0.015 (2)	0.028 (2)	0.032 (3)	0.0028 (16)	0.004 (2)	0.0017 (18)
C18	0.028 (2)	0.0282 (18)	0.026 (2)	0.000 (2)	0.0025 (18)	−0.001 (2)
C19	0.025 (2)	0.049 (2)	0.039 (3)	0.001 (2)	0.009 (2)	−0.004 (2)
C20	0.022 (2)	0.0290 (19)	0.025 (2)	−0.001 (2)	0.0094 (18)	0.001 (2)
C21	0.042 (3)	0.031 (2)	0.031 (3)	0.004 (2)	0.010 (2)	0.003 (2)
C22	0.024 (2)	0.029 (2)	0.027 (2)	−0.0041 (19)	0.008 (2)	−0.0045 (19)
C23	0.028 (2)	0.0256 (19)	0.026 (2)	0.000 (2)	0.0030 (19)	0.000 (2)
C24	0.030 (3)	0.033 (2)	0.027 (2)	−0.0035 (19)	0.006 (2)	0.0073 (19)
C25	0.037 (3)	0.035 (2)	0.028 (2)	−0.005 (2)	0.003 (2)	0.006 (2)
C26	0.037 (3)	0.043 (2)	0.030 (3)	0.001 (2)	−0.005 (2)	0.009 (2)
O26	0.0336 (18)	0.0410 (17)	0.0252 (17)	−0.0081 (14)	−0.0027 (14)	0.0052 (13)
C27	0.025 (2)	0.034 (2)	0.022 (2)	0.0020 (19)	0.0002 (19)	−0.0017 (19)
C28	0.050 (4)	0.056 (3)	0.036 (3)	−0.006 (3)	0.008 (3)	0.014 (2)
C29	0.030 (3)	0.043 (3)	0.029 (2)	−0.002 (2)	0.010 (2)	0.003 (2)

Geometric parameters (Å, º) top

C1—C2	1.523 (5)	C15—H15A	0.9900
C1—C10	1.551 (5)	C15—H15B	0.9900
C1—H1A	0.9900	C16—O16	1.462 (4)
C1—H1B	0.9900	C16—C17	1.556 (4)
C2—C3	1.523 (5)	C16—H16	1.0000
C2—H2A	0.9900	O16—C22	1.391 (4)
C2—H2B	0.9900	C17—C20	1.501 (5)
C3—O3	1.446 (4)	C17—H17	1.0000
C3—C4	1.524 (5)	C18—H18A	0.9800
C3—H3	1.0000	C18—H18B	0.9800
O3—H3A	0.87 (4)	C18—H18C	0.9800
C4—C5	1.531 (5)	C19—H19A	0.9800
C4—H4A	0.9900	C19—H19B	0.9800
C4—H4B	0.9900	C19—H19C	0.9800
C5—C6	1.539 (5)	C20—C22	1.324 (5)
C5—C10	1.550 (5)	C20—C21	1.498 (5)
C5—H5	1.0000	C21—H21A	0.9800
C6—C7	1.527 (5)	C21—H21B	0.9800
C6—H6A	0.9900	C21—H21C	0.9800
C6—H6B	0.9900	C22—C23	1.500 (5)
C7—C8	1.532 (5)	C23—C27	1.535 (5)
C7—H7A	0.9900	C23—C24	1.538 (5)
C7—H7B	0.9900	C23—H23	1.0000
C8—C14	1.517 (5)	C24—C25	1.522 (5)
C8—C9	1.548 (5)	C24—H24A	0.9900
C8—H8	1.0000	C24—H24B	0.9900
C9—C11	1.540 (5)	C25—C26	1.521 (5)
C9—C10	1.554 (5)	C25—C28	1.525 (5)
C9—H9	1.0000	C25—H25	1.0000
C10—C19	1.550 (5)	C26—O26	1.441 (4)
C11—C12	1.537 (5)	C26—H26A	0.9900
C11—H11A	0.9900	C26—H26B	0.9900
C11—H11B	0.9900	O26—C27	1.449 (4)
C12—C13	1.525 (5)	C27—C29	1.507 (5)
C12—H12A	0.9900	C27—H27	1.0000
C12—H12B	0.9900	C28—H28A	0.9800
C13—C14	1.538 (5)	C28—H28B	0.9800
C13—C18	1.543 (5)	C28—H28C	0.9800
C13—C17	1.552 (5)	C29—H29A	0.9800
C14—C15	1.545 (5)	C29—H29B	0.9800
C14—H14	1.0000	C29—H29C	0.9800
C15—C16	1.521 (5)

C2—C1—C10	114.6 (3)	C16—C15—H15A	111.2
C2—C1—H1A	108.6	C14—C15—H15A	111.2
C10—C1—H1A	108.6	C16—C15—H15B	111.2
C2—C1—H1B	108.6	C14—C15—H15B	111.2
C10—C1—H1B	108.6	H15A—C15—H15B	109.1
H1A—C1—H1B	107.6	O16—C16—C15	113.0 (3)
C3—C2—C1	111.4 (3)	O16—C16—C17	105.0 (3)
C3—C2—H2A	109.3	C15—C16—C17	107.8 (3)
C1—C2—H2A	109.3	O16—C16—H16	110.3
C3—C2—H2B	109.3	C15—C16—H16	110.3
C1—C2—H2B	109.3	C17—C16—H16	110.3
H2A—C2—H2B	108.0	C22—O16—C16	106.4 (3)
O3—C3—C2	107.4 (3)	C20—C17—C13	120.5 (3)
O3—C3—C4	110.7 (3)	C20—C17—C16	101.5 (3)
C2—C3—C4	111.0 (3)	C13—C17—C16	104.2 (3)
O3—C3—H3	109.2	C20—C17—H17	109.9
C2—C3—H3	109.2	C13—C17—H17	109.9
C4—C3—H3	109.2	C16—C17—H17	109.9
C3—O3—H3A	107 (3)	C13—C18—H18A	109.5
C3—C4—C5	114.5 (3)	C13—C18—H18B	109.5
C3—C4—H4A	108.6	H18A—C18—H18B	109.5
C5—C4—H4A	108.6	C13—C18—H18C	109.5
C3—C4—H4B	108.6	H18A—C18—H18C	109.5
C5—C4—H4B	108.6	H18B—C18—H18C	109.5
H4A—C4—H4B	107.6	C10—C19—H19A	109.5
C4—C5—C6	110.7 (3)	C10—C19—H19B	109.5
C4—C5—C10	112.8 (3)	H19A—C19—H19B	109.5
C6—C5—C10	111.4 (3)	C10—C19—H19C	109.5
C4—C5—H5	107.2	H19A—C19—H19C	109.5
C6—C5—H5	107.2	H19B—C19—H19C	109.5
C10—C5—H5	107.2	C22—C20—C21	128.3 (4)
C7—C6—C5	112.4 (3)	C22—C20—C17	109.3 (3)
C7—C6—H6A	109.1	C21—C20—C17	122.4 (3)
C5—C6—H6A	109.1	C20—C21—H21A	109.5
C7—C6—H6B	109.1	C20—C21—H21B	109.5
C5—C6—H6B	109.1	H21A—C21—H21B	109.5
H6A—C6—H6B	107.9	C20—C21—H21C	109.5
C6—C7—C8	111.5 (3)	H21A—C21—H21C	109.5
C6—C7—H7A	109.3	H21B—C21—H21C	109.5
C8—C7—H7A	109.3	C20—C22—O16	114.2 (3)
C6—C7—H7B	109.3	C20—C22—C23	132.4 (4)
C8—C7—H7B	109.3	O16—C22—C23	113.4 (3)
H7A—C7—H7B	108.0	C22—C23—C27	111.7 (3)
C14—C8—C7	111.6 (3)	C22—C23—C24	110.6 (3)
C14—C8—C9	109.5 (3)	C27—C23—C24	110.2 (3)
C7—C8—C9	110.3 (3)	C22—C23—H23	108.1
C14—C8—H8	108.5	C27—C23—H23	108.1
C7—C8—H8	108.5	C24—C23—H23	108.1
C9—C8—H8	108.5	C25—C24—C23	110.9 (3)
C11—C9—C8	112.1 (3)	C25—C24—H24A	109.5
C11—C9—C10	114.2 (3)	C23—C24—H24A	109.5
C8—C9—C10	111.6 (3)	C25—C24—H24B	109.5
C11—C9—H9	106.0	C23—C24—H24B	109.5
C8—C9—H9	106.0	H24A—C24—H24B	108.1
C10—C9—H9	106.0	C26—C25—C24	108.5 (3)
C19—C10—C5	109.9 (3)	C26—C25—C28	110.9 (3)
C19—C10—C1	106.0 (3)	C24—C25—C28	111.1 (3)
C5—C10—C1	106.8 (3)	C26—C25—H25	108.8
C19—C10—C9	111.2 (3)	C24—C25—H25	108.8
C5—C10—C9	109.4 (3)	C28—C25—H25	108.8
C1—C10—C9	113.5 (3)	O26—C26—C25	111.2 (3)
C12—C11—C9	113.7 (3)	O26—C26—H26A	109.4
C12—C11—H11A	108.8	C25—C26—H26A	109.4
C9—C11—H11A	108.8	O26—C26—H26B	109.4
C12—C11—H11B	108.8	C25—C26—H26B	109.4
C9—C11—H11B	108.8	H26A—C26—H26B	108.0
H11A—C11—H11B	107.7	C26—O26—C27	112.1 (3)
C13—C12—C11	111.3 (3)	O26—C27—C29	105.4 (3)
C13—C12—H12A	109.4	O26—C27—C23	110.4 (3)
C11—C12—H12A	109.4	C29—C27—C23	113.6 (3)
C13—C12—H12B	109.4	O26—C27—H27	109.1
C11—C12—H12B	109.4	C29—C27—H27	109.1
H12A—C12—H12B	108.0	C23—C27—H27	109.1
C12—C13—C14	107.6 (3)	C25—C28—H28A	109.5
C12—C13—C18	110.5 (3)	C25—C28—H28B	109.5
C14—C13—C18	112.2 (3)	H28A—C28—H28B	109.5
C12—C13—C17	116.4 (3)	C25—C28—H28C	109.5
C14—C13—C17	100.5 (3)	H28A—C28—H28C	109.5
C18—C13—C17	109.3 (3)	H28B—C28—H28C	109.5
C8—C14—C13	114.1 (3)	C27—C29—H29A	109.5
C8—C14—C15	118.8 (3)	C27—C29—H29B	109.5
C13—C14—C15	103.6 (3)	H29A—C29—H29B	109.5
C8—C14—H14	106.5	C27—C29—H29C	109.5
C13—C14—H14	106.5	H29A—C29—H29C	109.5
C15—C14—H14	106.5	H29B—C29—H29C	109.5
C16—C15—C14	102.9 (3)

C10—C1—C2—C3	56.8 (4)	C18—C13—C14—C15	−70.0 (4)
C1—C2—C3—O3	70.1 (4)	C17—C13—C14—C15	46.1 (4)
C1—C2—C3—C4	−51.1 (4)	C8—C14—C15—C16	−166.3 (3)
O3—C3—C4—C5	−68.4 (4)	C13—C14—C15—C16	−38.5 (4)
C2—C3—C4—C5	50.8 (4)	C14—C15—C16—O16	131.1 (3)
C3—C4—C5—C6	−179.1 (3)	C14—C15—C16—C17	15.5 (4)
C3—C4—C5—C10	−53.6 (5)	C15—C16—O16—C22	−135.1 (3)
C4—C5—C6—C7	71.5 (4)	C17—C16—O16—C22	−17.8 (4)
C10—C5—C6—C7	−54.9 (5)	C12—C13—C17—C20	95.8 (4)
C5—C6—C7—C8	54.7 (4)	C14—C13—C17—C20	−148.4 (3)
C6—C7—C8—C14	−177.2 (3)	C18—C13—C17—C20	−30.2 (5)
C6—C7—C8—C9	−55.3 (4)	C12—C13—C17—C16	−151.3 (3)
C14—C8—C9—C11	−49.8 (4)	C14—C13—C17—C16	−35.5 (4)
C7—C8—C9—C11	−173.0 (4)	C18—C13—C17—C16	82.6 (4)
C14—C8—C9—C10	−179.5 (3)	O16—C16—C17—C20	17.8 (4)
C7—C8—C9—C10	57.4 (4)	C15—C16—C17—C20	138.5 (3)
C4—C5—C10—C19	167.6 (3)	O16—C16—C17—C13	−108.1 (4)
C6—C5—C10—C19	−67.1 (4)	C15—C16—C17—C13	12.7 (4)
C4—C5—C10—C1	53.1 (4)	C13—C17—C20—C22	102.3 (4)
C6—C5—C10—C1	178.3 (4)	C16—C17—C20—C22	−12.0 (4)
C4—C5—C10—C9	−70.1 (4)	C13—C17—C20—C21	−78.2 (5)
C6—C5—C10—C9	55.1 (4)	C16—C17—C20—C21	167.5 (3)
C2—C1—C10—C19	−173.3 (3)	C21—C20—C22—O16	−178.3 (3)
C2—C1—C10—C5	−56.1 (4)	C17—C20—C22—O16	1.2 (5)
C2—C1—C10—C9	64.5 (4)	C21—C20—C22—C23	0.7 (7)
C11—C9—C10—C19	−64.1 (4)	C17—C20—C22—C23	−179.9 (4)
C8—C9—C10—C19	64.5 (4)	C16—O16—C22—C20	11.1 (4)
C11—C9—C10—C5	174.4 (3)	C16—O16—C22—C23	−168.1 (3)
C8—C9—C10—C5	−57.0 (4)	C20—C22—C23—C27	112.5 (5)
C11—C9—C10—C1	55.3 (4)	O16—C22—C23—C27	−68.5 (4)
C8—C9—C10—C1	−176.2 (3)	C20—C22—C23—C24	−124.5 (5)
C8—C9—C11—C12	49.6 (4)	O16—C22—C23—C24	54.5 (4)
C10—C9—C11—C12	177.9 (3)	C22—C23—C24—C25	−177.5 (3)
C9—C11—C12—C13	−53.6 (4)	C27—C23—C24—C25	−53.6 (4)
C11—C12—C13—C14	56.6 (4)	C23—C24—C25—C26	54.9 (4)
C11—C12—C13—C18	−66.2 (4)	C23—C24—C25—C28	177.0 (3)
C11—C12—C13—C17	168.4 (3)	C24—C25—C26—O26	−58.8 (4)
C7—C8—C14—C13	180.0 (3)	C28—C25—C26—O26	179.0 (3)
C9—C8—C14—C13	57.6 (4)	C25—C26—O26—C27	62.2 (4)
C7—C8—C14—C15	−57.3 (4)	C26—O26—C27—C29	177.6 (3)
C9—C8—C14—C15	−179.7 (3)	C26—O26—C27—C23	−59.3 (4)
C12—C13—C14—C8	−61.0 (4)	C22—C23—C27—O26	177.7 (3)
C18—C13—C14—C8	60.7 (4)	C24—C23—C27—O26	54.4 (4)
C17—C13—C14—C8	176.8 (3)	C22—C23—C27—C29	−64.2 (4)
C12—C13—C14—C15	168.3 (3)	C24—C23—C27—C29	172.6 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3A···O26ⁱ	0.87 (4)	2.11 (4)	2.943 (4)	159 (5)

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

Funding information

Funding for this research was provided by: Consejo Nacional de Ciencia y Tecnología (grant Nos. 168178 and 171508).

References

Aydillo, C., Navo, C. D., Busto, J. H., Corzana, F., Zurbano, M. M., Avenoza, A. & Peregrina, J. M. (2013). J. Org. Chem. 78, 10968–10977. CSD CrossRef CAS PubMed Google Scholar
Burton, S., Fronczek, F. R. & Maverick, A. W. (2007). Acta Cryst. E63, o2661–o2662. Web of Science CSD CrossRef IUCr Journals Google Scholar
Cohen, S., Nathan, J. A. & Goldberg, A. L. (2015). Nat. Rev. Drug Discov. 14, 58–74. CrossRef CAS PubMed Google Scholar
Daina, A., Michielin, O. & Zoete, V. (2019). Nucleic Acids Res. 47, W357–W364. Web of Science CrossRef CAS PubMed 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
Jeong, J. U. & Fuchs, P. L. (1994). J. Am. Chem. Soc. 116, 773–774. CSD CrossRef CAS Google Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235. Web of Science CrossRef CAS IUCr Journals Google Scholar
Moss, G. P. (1989). Pure Appl. Chem. 61, 1783–1822. CrossRef CAS Google Scholar
Río, R. E. del, Santillán, R., Sandoval-Ramírez, J., Meza-Reyes, S., Montiel-Smith, S., Viñas-Bravo, O. & Farfán, N. (2006). J. Mex. Chem. Soc. 50, 119–125. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Shen, L. Q., Tang, Y. & Huang, S. Y. (2013). Res. Chem. Intermed. 39, 2043–2047. CSD CrossRef CAS Google Scholar
Stoe & Cie (2018). X-AREA and X-RED32. Stoe & Cie, Darmstadt, Germany. Google Scholar
Viñas-Bravo, O., Hernández-Linares, G., Mata-Esma, M. Y., Martínez-Pascual, R., Montiel-Smith, S., Meza-Reyes, S., Bernès, S., Sandoval-Ramírez, J. & Iglesias-Arteaga, M. A. (2003). Arkivoc, part xi, pp. 163–171. Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar

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