Crystal structure of (1R,3aR,7aR)-1-{(S)-1-[(2R,5S)-5-(3-hy­droxy­pentan-3-yl)tetra­hydro­furan-2-yl]eth­yl}-7a-methyl-2,3,3a,4,5,6,7,7a-octa­hydro-1H-inden-4-one

Martínez, A.; Santalla, H.; Garrido, F.; Barry, A.H.; Gaye, M.; Fall Diop, Y.

doi:10.1107/S2056989016020648

research communications

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ISSN: 2056-9890

Volume 73| Part 2| February 2017| Pages 115-117

https://doi.org/10.1107/S2056989016020648

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Crystal structure of (1R,3aR,7aR)-1-{(S)-1-[(2R,5S)-5-(3-hydroxypentan-3-yl)tetrahydrofuran-2-yl]ethyl}-7a-methyl-2,3,3a,4,5,6,7,7a-octahydro-1H-inden-4-one

Andrea Martínez,^a Hugo Santalla,^a Fátima Garrido,^a Aliou Hamady Barry,^b Mohamed Gaye ^c ^* and Yagamare Fall Diop ^a

^aDipartamento Química Orgínica, Facultade de Química, Universidade de Vigo, E-36310, Vigo, Spain, ^bDépartement de Chimie, Faculté des Sciences, Université de Nouakchott, Nouakchott, Mauritania, and ^cDépartement de Chimie, Faculté des Sciences et Techniques, Université Cheikh Anta Diop, Dakar, Senegal
^*Correspondence e-mail: mlgayeastou@yahoo.fr

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 16 December 2016; accepted 29 December 2016; online 6 January 2017)

The title compound, C₂₁H₃₆O₃, contains an oxolane ring, and six defined stereocentres and may serve as a useful synthon for the synthesis of calcitriol analogues. The configurations of the chiral C atoms of the side chain were unambiguously established in the refinement. In the crystal, C—H⋯O and extremely weak O—H⋯O hydrogen bonds arising from the sterically hindered alcohol group link the molecules into a three-dimensional network.

Keywords: crystal structure; calcitriol; vitamin D; hydrogen bonding.

CCDC reference: 1522774

1. Chemical context

The discovery of vitamin D3 (calcitriol) and its biological activity had a very important impact in the search for analogues of Vitamin D. In the structure of vitamin D, it is recognized that the side chain is the main site of metabolic degradation. Synthetic chemists have devoted considerable efforts to varying this chain in order to prepare analogues of vitamin D (Dai & Posner, 1994 ; Zhu et al., 1995 ; Posner & Kahraman, 2003 ) and study the degradation metabolisms of these new molecules. Our ongoing interest in the chemistry of heterocyclic compounds, and particularly in the synthesis of vitamin D analogues, has led us to develop several methods for the synthesis of these compounds (Fernández et al., 2016 ; Gándara et al., 2009 ). We have also looked at their biological activities which are reported in the literature (Maehr et al., 2004 ). Recently, we reported the synthesis of a new vitamin D2 analogue and the evaluation of its biological activity on colon cancer (Gándara et al., 2012 ). In a continuation of our work on the analogues of vitamin D, we synthesized two new molecules of cacitriol from an oxolane ring and its side chains (Martínez et al., 2013 ). In this study we present the structure of a new analog of calcitriol with six stereo centres.

2. Structural commentary

The molecular structure of the title compound is shown in Fig. 1: the compound crystallizes in the non-centrosymmetric space group P2₁ and the absolute structure was unambiguously established. The molecule contains a cyclopentane ring trans-fused to a cyclohexanone ring. The lateral chain contains an oxolane ring. The cyclohexanone ring adopts a chair conformation, the cyclopentane ring is an envelope (flap atom = C5) and the heterocyclic ring is twisted about C13—O2. The configurations of the stereogenic centres are C5(R), C6(R), C9(R), C11(S), C13(R) and C16(S). All bond distances and angles are within their expected ranges. The Csp³—Csp² bonds involving C1 [1.499 (3) and 1.500 (3) Å) are naturally slightly shorter than the Csp³—Csp³ bonds [1.514 (3)–1.549 (5) Å]. The C1=O1 bond length [1.208 (3) Å] is typical of a C=O double bond, confirming oxidation of the starting alcohol.

Figure 1
An ORTEP view of the title compound with displacement ellipsoids plotted at the 50% probability level.

3. Supramolecular features

In the crystal, C2—H2B⋯O1=C hydrogen bonds (Table 1, Fig. 2) link the molecules into C(4) chains, which propagate parallel to [101]. The chains are linked through very weak C(2) O3—H3O⋯O3 hydrogen bonds, giving rise to a three-dimensional supramolecular architecture. The O—H⋯O hydrogen bond is very long, presumably due to steric hindrance of the –OH group.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3O⋯O3ⁱ	0.82	2.67	3.4495 (9)	161
C2—H2B⋯O1ⁱⁱ	0.97	2.57	3.273 (3)	130
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+2]$ ; (ii) $[-x+2, y-{\script{1\over 2}}, -z+1]$ .

Figure 2
The packing of the title compound showing hydrogen bonds as dashed lines. [Symmetry codes: (i)-x + 2, y − $[{1\over 2}]$ , −z + 1, (ii)-x + 1, y + $[{1\over 2}]$ , −z + 2.]

4. Database survey

A survey of the Cambridge Structural Database (Version 5.38, last update Nov 2016; Groom et al., 2016 ) for the bicyclic moiety fragment (1S,3aR,7aR)-1-ethyl-7a-methyl-octahydroinden-4-one) of the title compound revealed just three matches, viz. EFEHEE (Pietraszek et al., 2013 ), LESNEE (Rivadulla et al., 2013 ) and ZEBZIP (Schwarz et al., 1995 ). In each case, the shared C—C bond of the [4.3.0]-bicyclic moiety presents a trans configuration, as does the structure reported here.

5. Synthesis and crystallization

To a solution of diol 2 (0.18 mmol) in CH₂Cl₂ (5 ml), pyridinium dichromate (PDC) (0.37 mmol) was added, and the mixture stirred at room temperature for 12 h, then the solvent was evaporated and the residue was chromatographed on sílica gel using (10% EtOAc/hexane) to afford ketone 1. The title compound was recrystallized as colourless blocks using a solvent mixture of hexane/ethyl ether (1:1).

Compound 1: white solid; m.p. 382–384 K. yield: 83%; R_f: 0.54 (30% EtOAc/hexane). [α]₂₀^D = +31.39° (c 1.0, CDCl₃). ¹H NMR (CDCl₃, δ): 3.87 (1H, m, H-5′), 3.72 (1H, m, H-2′), 2.44 (1H, dd, J = 11.2, 7.4 Hz), 2.49–1.8 (6H, m), 1.79–1.65 (4H, m), 1.65–1.28 (8H, m), 1.27 (3H, d, J = 9.7 Hz), 0.95 (3H, d, J = 6.7 Hz, CH₃-21), 0.88 (6H,q, J = 7.6 Hz, CH₃-Et), 0.67 (3H, S, CH₃-18). ¹³C NMR (CDCl₃, δ): 211.91 (C=O), 82.17 (CH-2′), 80.67 (CH-5′), 74.96 (C-3′′), 61.49 (CH-14), 54.50, 50.25 (CH-17, CH-13), 41.01 (CH₂), 38.97 (CH₂), 38.12 (CH-20), 28.65 (CH₂), 26.93 (CH₂), 26.23 (CH₂), 24.98 (CH₂), 24.52 (CH₂), 24.04 (CH₂), 19.21 (CH₂), 12.70 (CH₃-21), 12.55 (CH₃-18), 8.02 (CH₃-Et), 7.52 (CH₃-Et). IR (NaCl, cm⁻¹): 3532, 2964, 2939, 2881, 2347, 1714, 1460, 1381, 1246, 1136,1077, 958, 837. MS (ESI⁺) [m/z, (%)]: 359.25 [(M + Na)⁺, (54)]; 319.26 [(M − OH)⁺,(100)]; 301.25 (15). HRMS (ESI⁺): calculated for C₂₁H₃₆NaO₃, 359.25567 g mol⁻¹; found: 359.2556 g mol⁻¹.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The hydroxy H atom was located from a difference Fourier map and relocated to an idealized (O—H = 0.82Å) location. The other H atoms (CH, CH₂ and CH₃ groups) were placed geometrically and refined as riding atoms with U_iso(H) = 1.2U_eq(C) (1.5 for CH₃ groups).

Table 2
Experimental details

Crystal data
Chemical formula	C₂₁H₃₆O₃
M_r	336.50
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	296
a, b, c (Å)	9.4601 (3), 6.3779 (2), 16.7425 (4)
β (°)	104.196 (1)
V (Å³)	979.32 (5)
Z	2
Radiation type	Cu Kα
μ (mm⁻¹)	0.58
Crystal size (mm)	0.25 × 0.12 × 0.10

Data collection
Diffractometer	Bruker SMART APEX CCD
Absorption correction	Multi-scan SADABS (Bruker, 2016 )
T_min, T_max	0.662, 0.753
No. of measured, independent and observed [I > 2σ(I)] reflections	13069, 3679, 3594
R_int	0.036
(sin θ/λ)_max (Å⁻¹)	0.613

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.097, 1.05
No. of reflections	3679
No. of parameters	222
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)	0.14, −0.14
Absolute structure	Flack x determined using 1566 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	−0.07 (7)
Computer programs: APEX3 and SAINT (Bruker, 2016), SHELXT (Sheldrick, 2015a ), SHELXL-2014/7 (Sheldrick, 2015b ) and ORTEP-3 for Windows (Farrugia, 2012 ).

Supporting information

CCDC reference: 1522774

Crystal structure: contains datablocks I, shelx. DOI: https://doi.org/10.1107/S2056989016020648/hb7644sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989016020648/hb7644Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989016020648/hb7644Isup3.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL-2014/7 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL-2014/7 (Sheldrick, 2015b).

(1R,3aR,7aR)-1-{(S)-1-[(2R,5S)-5-(3-Hydroxypentan-3-yl)tetrahydrofuran-2-yl]ethyl}-7a-methyl-2,3,3a,4,5,6,7,7a-octahydro-1H-inden-4-one top

Crystal data top

C₂₁H₃₆O₃	F(000) = 372
M_r = 336.50	D_x = 1.141 Mg m⁻³
Monoclinic, P2₁	Cu Kα radiation, λ = 1.54178 Å
a = 9.4601 (3) Å	Cell parameters from 9988 reflections
b = 6.3779 (2) Å	θ = 2.4–28.6°
c = 16.7425 (4) Å	µ = 0.58 mm⁻¹
β = 104.196 (1)°	T = 296 K
V = 979.32 (5) Å³	Block, colourless
Z = 2	0.25 × 0.12 × 0.10 mm

Data collection top

Bruker SMART APEX CCD diffractometer	3679 independent reflections
Radiation source: fine-focus sealed tube	3594 reflections with I > 2σ(I)
Detector resolution: 8.3333 pixels mm^-1	R_int = 0.036
φ and ω scans	θ_max = 71.0°, θ_min = 2.7°
Absorption correction: multi-scan SADABS (Bruker, 2016)	h = −11→11
T_min = 0.662, T_max = 0.753	k = −7→7
13069 measured reflections	l = −20→20

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.033	w = 1/[σ²(F_o²) + (0.0549P)² + 0.0933P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.097	(Δ/σ)_max < 0.001
S = 1.05	Δρ_max = 0.14 e Å⁻³
3679 reflections	Δρ_min = −0.14 e Å⁻³
222 parameters	Extinction correction: SHELXL-2014/7 (Sheldrick 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.0034 (10)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack x determined using 1566 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
Secondary atom site location: difference Fourier map	Absolute structure parameter: −0.07 (7)

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.

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

	x	y	z	U_iso*/U_eq
O1	0.9190 (2)	0.6570 (3)	0.46585 (10)	0.0761 (5)
O2	0.41676 (15)	0.5028 (2)	0.80627 (9)	0.0555 (4)
O3	0.44001 (17)	0.3383 (4)	0.97018 (11)	0.0768 (5)
H3O	0.480163	0.453143	0.975052	0.115*
C1	0.9416 (2)	0.6116 (3)	0.53792 (13)	0.0552 (5)
C2	1.0862 (2)	0.6426 (4)	0.59799 (15)	0.0651 (6)
H2A	1.147857	0.727399	0.572289	0.078*
H2B	1.133002	0.507331	0.611064	0.078*
C3	1.0739 (2)	0.7482 (4)	0.67748 (15)	0.0630 (6)
H3A	1.054571	0.896302	0.667028	0.076*
H3B	1.166385	0.735483	0.717955	0.076*
C4	0.9536 (2)	0.6548 (4)	0.71321 (12)	0.0523 (4)
H4A	0.981399	0.514090	0.732883	0.063*
H4B	0.943984	0.738532	0.759957	0.063*
C5	0.80678 (19)	0.6465 (3)	0.65022 (10)	0.0412 (4)
C6	0.82896 (19)	0.5162 (3)	0.57614 (11)	0.0456 (4)
H6	0.868329	0.380487	0.598623	0.055*
C7	0.6765 (2)	0.4733 (4)	0.52444 (13)	0.0626 (6)
H7A	0.673148	0.343325	0.493967	0.075*
H7B	0.642601	0.586840	0.485945	0.075*
C8	0.5838 (2)	0.4576 (4)	0.58867 (12)	0.0562 (5)
H8A	0.502692	0.554932	0.575205	0.067*
H8B	0.545476	0.316752	0.589496	0.067*
C9	0.68560 (18)	0.5124 (3)	0.67337 (10)	0.0422 (4)
H9	0.731850	0.380868	0.696278	0.051*
C10	0.7521 (3)	0.8691 (3)	0.62341 (14)	0.0589 (5)
H10A	0.653632	0.862000	0.590462	0.088*
H10B	0.813277	0.930699	0.591728	0.088*
H10C	0.755209	0.953355	0.671323	0.088*
C11	0.6037 (2)	0.5963 (3)	0.73561 (12)	0.0474 (4)
H11	0.553105	0.724547	0.712223	0.057*
C12	0.7015 (3)	0.6528 (5)	0.81908 (14)	0.0695 (6)
H12A	0.766322	0.538155	0.839097	0.104*
H12B	0.642665	0.680515	0.857150	0.104*
H12C	0.757405	0.775343	0.813787	0.104*
C13	0.4871 (2)	0.4371 (3)	0.74389 (13)	0.0500 (4)
H13	0.413816	0.429521	0.691234	0.060*
C14	0.5382 (3)	0.2155 (4)	0.77004 (18)	0.0672 (6)
H14A	0.633369	0.217278	0.808473	0.081*
H14B	0.543273	0.130859	0.722683	0.081*
C15	0.4227 (3)	0.1314 (4)	0.81102 (19)	0.0726 (7)
H15A	0.467379	0.066789	0.863599	0.087*
H15B	0.361078	0.028941	0.776109	0.087*
C16	0.3342 (2)	0.3267 (3)	0.82279 (13)	0.0532 (5)
H16	0.240605	0.323844	0.781623	0.064*
C17	0.0673 (3)	0.1360 (5)	0.86855 (17)	0.0792 (8)
H17A	0.077247	0.115555	0.813379	0.119*
H17B	0.009832	0.259036	0.870492	0.119*
H17C	0.020167	0.016174	0.885197	0.119*
C18	0.2170 (3)	0.1631 (4)	0.92637 (15)	0.0613 (5)
H18A	0.272883	0.036389	0.924591	0.074*
H18B	0.205358	0.177567	0.982067	0.074*
C19	0.3051 (2)	0.3499 (3)	0.90802 (13)	0.0506 (4)
C20	0.2324 (2)	0.5598 (3)	0.91465 (13)	0.0543 (5)
H20A	0.298507	0.670669	0.907616	0.065*
H20B	0.145850	0.570583	0.869632	0.065*
C21	0.1888 (3)	0.5971 (5)	0.99509 (15)	0.0750 (7)
H21A	0.153005	0.737676	0.995988	0.113*
H21B	0.272144	0.577529	1.040541	0.113*
H21C	0.113814	0.499588	0.999528	0.113*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.1052 (13)	0.0728 (11)	0.0592 (9)	−0.0108 (10)	0.0371 (9)	0.0039 (8)
O2	0.0597 (8)	0.0400 (7)	0.0789 (9)	0.0002 (6)	0.0399 (7)	−0.0013 (6)
O3	0.0565 (8)	0.0872 (12)	0.0808 (11)	0.0013 (9)	0.0058 (8)	0.0121 (10)
C1	0.0704 (12)	0.0458 (10)	0.0583 (11)	0.0007 (9)	0.0326 (10)	−0.0009 (9)
C2	0.0582 (11)	0.0691 (14)	0.0773 (14)	−0.0098 (11)	0.0346 (11)	0.0008 (12)
C3	0.0544 (11)	0.0678 (14)	0.0690 (13)	−0.0168 (10)	0.0191 (10)	−0.0012 (10)
C4	0.0473 (9)	0.0599 (11)	0.0501 (9)	−0.0094 (9)	0.0129 (8)	−0.0010 (9)
C5	0.0460 (8)	0.0364 (9)	0.0433 (8)	0.0003 (7)	0.0150 (7)	0.0002 (7)
C6	0.0499 (9)	0.0429 (9)	0.0469 (9)	0.0016 (8)	0.0177 (7)	−0.0020 (8)
C7	0.0580 (11)	0.0794 (16)	0.0504 (10)	−0.0021 (11)	0.0133 (9)	−0.0143 (10)
C8	0.0446 (9)	0.0656 (13)	0.0573 (11)	−0.0028 (9)	0.0106 (8)	−0.0132 (10)
C9	0.0417 (8)	0.0392 (9)	0.0475 (9)	−0.0008 (7)	0.0142 (7)	−0.0020 (7)
C10	0.0729 (13)	0.0402 (10)	0.0700 (13)	0.0075 (9)	0.0299 (11)	0.0051 (9)
C11	0.0493 (9)	0.0417 (9)	0.0565 (10)	−0.0005 (7)	0.0228 (8)	−0.0038 (8)
C12	0.0716 (13)	0.0848 (17)	0.0594 (12)	−0.0226 (13)	0.0300 (10)	−0.0189 (12)
C13	0.0483 (9)	0.0452 (10)	0.0623 (11)	−0.0007 (8)	0.0244 (8)	−0.0052 (8)
C14	0.0746 (14)	0.0435 (11)	0.0989 (18)	0.0047 (10)	0.0503 (14)	0.0000 (11)
C15	0.0794 (15)	0.0432 (11)	0.1116 (19)	−0.0006 (11)	0.0550 (15)	−0.0024 (12)
C16	0.0538 (10)	0.0430 (10)	0.0695 (12)	−0.0031 (9)	0.0277 (9)	−0.0007 (9)
C17	0.0825 (16)	0.0829 (18)	0.0812 (15)	−0.0360 (14)	0.0372 (13)	−0.0116 (14)
C18	0.0705 (13)	0.0470 (11)	0.0751 (13)	−0.0012 (10)	0.0345 (11)	0.0064 (10)
C19	0.0470 (9)	0.0462 (10)	0.0603 (11)	0.0007 (8)	0.0165 (8)	0.0039 (8)
C20	0.0638 (11)	0.0476 (10)	0.0560 (11)	0.0007 (9)	0.0233 (9)	0.0001 (8)
C21	0.1001 (18)	0.0679 (15)	0.0673 (14)	0.0002 (13)	0.0401 (14)	−0.0036 (12)

Geometric parameters (Å, º) top

O1—C1	1.208 (3)	C10—H10C	0.9600
O2—C13	1.432 (2)	C11—C12	1.518 (3)
O2—C16	1.433 (2)	C11—C13	1.531 (3)
O3—C19	1.437 (2)	C11—H11	0.9800
O3—H3O	0.8200	C12—H12A	0.9600
C1—C2	1.499 (3)	C12—H12B	0.9600
C1—C6	1.500 (3)	C12—H12C	0.9600
C2—C3	1.521 (3)	C13—C14	1.523 (3)
C2—H2A	0.9700	C13—H13	0.9800
C2—H2B	0.9700	C14—C15	1.523 (3)
C3—C4	1.530 (3)	C14—H14A	0.9700
C3—H3A	0.9700	C14—H14B	0.9700
C3—H3B	0.9700	C15—C16	1.540 (3)
C4—C5	1.525 (2)	C15—H15A	0.9700
C4—H4A	0.9700	C15—H15B	0.9700
C4—H4B	0.9700	C16—C19	1.525 (3)
C5—C10	1.540 (3)	C16—H16	0.9800
C5—C6	1.549 (2)	C17—C18	1.517 (4)
C5—C9	1.553 (2)	C17—H17A	0.9600
C6—C7	1.514 (3)	C17—H17B	0.9600
C6—H6	0.9800	C17—H17C	0.9600
C7—C8	1.548 (3)	C18—C19	1.527 (3)
C7—H7A	0.9700	C18—H18A	0.9700
C7—H7B	0.9700	C18—H18B	0.9700
C8—C9	1.546 (3)	C19—C20	1.521 (3)
C8—H8A	0.9700	C20—C21	1.521 (3)
C8—H8B	0.9700	C20—H20A	0.9700
C9—C11	1.539 (2)	C20—H20B	0.9700
C9—H9	0.9800	C21—H21A	0.9600
C10—H10A	0.9600	C21—H21B	0.9600
C10—H10B	0.9600	C21—H21C	0.9600

C13—O2—C16	106.49 (15)	C13—C11—H11	107.3
C19—O3—H3O	109.5	C9—C11—H11	107.3
O1—C1—C2	123.2 (2)	C11—C12—H12A	109.5
O1—C1—C6	123.6 (2)	C11—C12—H12B	109.5
C2—C1—C6	113.21 (17)	H12A—C12—H12B	109.5
C1—C2—C3	113.09 (18)	C11—C12—H12C	109.5
C1—C2—H2A	109.0	H12A—C12—H12C	109.5
C3—C2—H2A	109.0	H12B—C12—H12C	109.5
C1—C2—H2B	109.0	O2—C13—C14	103.51 (17)
C3—C2—H2B	109.0	O2—C13—C11	110.25 (15)
H2A—C2—H2B	107.8	C14—C13—C11	117.17 (17)
C2—C3—C4	113.19 (18)	O2—C13—H13	108.5
C2—C3—H3A	108.9	C14—C13—H13	108.5
C4—C3—H3A	108.9	C11—C13—H13	108.5
C2—C3—H3B	108.9	C13—C14—C15	104.13 (17)
C4—C3—H3B	108.9	C13—C14—H14A	110.9
H3A—C3—H3B	107.8	C15—C14—H14A	110.9
C5—C4—C3	112.45 (16)	C13—C14—H14B	110.9
C5—C4—H4A	109.1	C15—C14—H14B	110.9
C3—C4—H4A	109.1	H14A—C14—H14B	108.9
C5—C4—H4B	109.1	C14—C15—C16	104.18 (18)
C3—C4—H4B	109.1	C14—C15—H15A	110.9
H4A—C4—H4B	107.8	C16—C15—H15A	110.9
C4—C5—C10	110.68 (17)	C14—C15—H15B	110.9
C4—C5—C6	107.05 (14)	C16—C15—H15B	110.9
C10—C5—C6	111.29 (15)	H15A—C15—H15B	108.9
C4—C5—C9	116.71 (14)	O2—C16—C19	109.67 (16)
C10—C5—C9	111.36 (15)	O2—C16—C15	105.70 (15)
C6—C5—C9	99.07 (14)	C19—C16—C15	115.24 (19)
C1—C6—C7	120.41 (17)	O2—C16—H16	108.7
C1—C6—C5	111.94 (16)	C19—C16—H16	108.7
C7—C6—C5	104.92 (15)	C15—C16—H16	108.7
C1—C6—H6	106.2	C18—C17—H17A	109.5
C7—C6—H6	106.2	C18—C17—H17B	109.5
C5—C6—H6	106.2	H17A—C17—H17B	109.5
C6—C7—C8	103.70 (16)	C18—C17—H17C	109.5
C6—C7—H7A	111.0	H17A—C17—H17C	109.5
C8—C7—H7A	111.0	H17B—C17—H17C	109.5
C6—C7—H7B	111.0	C17—C18—C19	115.5 (2)
C8—C7—H7B	111.0	C17—C18—H18A	108.4
H7A—C7—H7B	109.0	C19—C18—H18A	108.4
C9—C8—C7	106.92 (16)	C17—C18—H18B	108.4
C9—C8—H8A	110.3	C19—C18—H18B	108.4
C7—C8—H8A	110.3	H18A—C18—H18B	107.5
C9—C8—H8B	110.3	O3—C19—C20	109.23 (18)
C7—C8—H8B	110.3	O3—C19—C16	109.91 (16)
H8A—C8—H8B	108.6	C20—C19—C16	110.00 (16)
C11—C9—C8	113.34 (14)	O3—C19—C18	104.20 (17)
C11—C9—C5	120.18 (15)	C20—C19—C18	113.14 (16)
C8—C9—C5	103.14 (14)	C16—C19—C18	110.19 (17)
C11—C9—H9	106.4	C21—C20—C19	115.33 (19)
C8—C9—H9	106.4	C21—C20—H20A	108.4
C5—C9—H9	106.4	C19—C20—H20A	108.4
C5—C10—H10A	109.5	C21—C20—H20B	108.4
C5—C10—H10B	109.5	C19—C20—H20B	108.4
H10A—C10—H10B	109.5	H20A—C20—H20B	107.5
C5—C10—H10C	109.5	C20—C21—H21A	109.5
H10A—C10—H10C	109.5	C20—C21—H21B	109.5
H10B—C10—H10C	109.5	H21A—C21—H21B	109.5
C12—C11—C13	111.35 (17)	C20—C21—H21C	109.5
C12—C11—C9	114.32 (16)	H21A—C21—H21C	109.5
C13—C11—C9	108.95 (15)	H21B—C21—H21C	109.5
C12—C11—H11	107.3

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3O···O3ⁱ	0.82	2.67	3.4495 (9)	161
C2—H2B···O1ⁱⁱ	0.97	2.57	3.273 (3)	130

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

Acknowledgements

The work of the MS and X-ray divisions of the research support service of the University of Vigo (CACTI) is also gratefully acknowledged. Andrea Martínez thanks the University of Vigo for a PhD fellowship.

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