(−)-Fern-7-en-3α-ol from Sebastiania brasiliensis

The structure of a fernane isolated from S. brasiliensis was established as fern-7en-3α-ol, C₃₀H₅₀O. Rings A and D assume a chair conformation, while rings B and C adopt a twist-boat conformation. Rings A/B, C/D, and D/E are trans fused. The relative orientation of the hydroxy group and that of the iso­propyl group is α.

Key indicators

• Single-crystal X-ray study
• T = 170 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.044
• wR factor = 0.103
• Data-to-parameter ratio = 7.7

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT029_ALERT_3_A _diffrn_measured_fraction_theta_full Low .....       0.98

Alert level B
PLAT420_ALERT_2_B D-H Without Acceptor       O1     -   H1C               ?

Author Response: The hydroxy group is the only functional group present in the molecule and the packing in the crystal precludes its hydrogen bonding to the hydroxyl in another molecule.

Alert level C
REFNR01_ALERT_3_C  Ratio of reflections to parameters is < 8 for a
            non-centrosymmetric structure, where ZMAX < 18
            sine(theta)/lambda               -0.0502
            Proportion of unique data used    1.0000
            Ratio reflections to parameters   7.6768
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical          ?
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) ...       7.68
PLAT222_ALERT_3_C Large Non-Solvent    H     Ueq(max)/Ueq(min) .       3.04 Ratio
PLAT391_ALERT_3_C Deviating Methyl C30     H-C-H Bond Angle ....     101.00 Deg.
PLAT415_ALERT_2_C Short Inter D-H..H-X      H1C     .. H24C    =       2.15 Ang.

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           28.31
           From the CIF: _reflns_number_total               3278
           Count of symmetry unique reflns         3350
           Completeness (_total/calc)             97.85%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present           no

   1 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   6 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   5 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion

---

S1. Comment

The growing number of deaths due to tuberculosis (TB) and the existence of strains of TB resistant to existing drugs has created an urgent need for the identification of leads for new antimycobacterial drugs. There are 8 million new cases of tuberculosis each year (Dye et al., 1999) and it is estimated that this number will increase to 10 million cases per year. There are an estimated 3 million deaths due to TB every year. Strains of TB resistant to existing drugs are found in nearly every country (Cohn et al., 1997), and a percentage of these are resistant to multiple drugs making effective treatment extremely expensive and in many cases impossible. Most patients in developing countries, where TB is an even bigger problem than elsewhere in the world, can not afford expensive drug treatments. There have been no new drugs developed for TB in over 30 years. Current activity in new drug development has centered around the rifamycins, rifabutin, rifapentine and KRM-1648, some of which exhibit cross-resistance with rifampin. It is in this regard that the bioassay guided fractionation of the antitubercular methanol extract of S. brasiliensis Spreng. (Euphorbiaceae), found active against the H₃₇Rv strain (ATCC 27294) of Mycobacterium tuberculosis, was initiated, leading to the isolation of the title compound, (I).

X-ray crystallographic analysis of (I) was undertaken to unequivocally establish the structure and to assign the relative stereochemistry at C3. Although (I) has previously been reported in the literature (Nakane et al., 1999), this is the first report of its isolation from S. brasiliensis and of its crystal structure. The X-ray structure of (I) can now serve as a standard for comparison of related fernanes. With reference to the Scheme, the absolute configuration at all chiral centers is 3R, 5S, 9R, 10S, 13S, 14S, 17R, 18R, 21R.

As shown in Fig. 1, rings A and D assume a chair conformation, while rings B and C adopt a twist-boat conformation. The A/B, C/D, and D/E ring junctions are trans fused about the C5—C10, C13—C14 and C17—C18 bonds, respectively. The relative orientation of the hydroxyl group at C3, and that of the isopropyl group at C21 is α. No hydrogen bonds were detected between the hydroxyl groups of screw-related molecules; however, the molecules pack such that the hydroxyls of adjacent molecules are as close to each other as possible [5.075 (2) Å]. The distance between hydroxyls related by unit translation along the b axis is 7.5526 (11) Å. Hydrogen bonding was observed between the C24 methyl H and the hydroxyl oxygen of screw-related molecule with a bond length 2.72 (3) Å and a bond angle of 162 (2)°.

S2. Experimental

The antitubercular CH₂Cl₂–MeOH extract of S. brasiliensis was chromatographed on a silica gel column with increasing concentrations of EtOAc in n-hexane. The fraction eluting with 10% EtOAc in n-hexane was found to inhibit the growth of Mycobacterium tuberculosis H₃₇Rv (ATCC 27294) by 90% at 50 µg ml⁻¹ concentration. This fraction, when treated with ether, gave a crystalline substance which on thin-layer chronatography (TLC) showed essentially one major spot. Preparative silica gel TLC of this fraction followed by crystallization led to the isolation of fern-7-en-3α-ol, (I). Crystals were obtained by slow evaporation of n-hexane/acetone. Colorless shining transparent rectangular rods were formed after 3 d.

S3. Refinement

H-atom positions were easily visible in difference Fourier maps and all H atoms were allowed to refine freely, except for the hydroxyl H atom, which was constrained to an O—H distance of 0.84 Å and a C—O—H angle of 109.47°. Due to the absence of any heavy atoms, anomalous dispersion could not be used to define absolute configuration. In the final cycles of refinement, all Friedel pairs were merged. The enantiomer was selected based on the observed negative optical rotation of the compound in solution and the fact that this is the most common enantiomer observed in nature (Ahmad & Atta-ur-Rahman, 1994).

Computing details

Data collection: SMART (Bruker, 1997); cell refinement: SMART; data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Bruker, 1997); program(s) used to refine structure: SHELXL97 (Bruker, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL.

Figures

Fig. 1. A displacement ellipsoid plot (50% probability) of (I).

(I)

Crystal data

C30H50O	F(000) = 476
Mr = 426.70	Dx = 1.130 Mg m^−3
Monoclinic, P21	Melting point = 240–241 K
Hall symbol: P 2yb	Mo Kα radiation, λ = 0.71073 Å
a = 12.4234 (18) Å	Cell parameters from 4025 reflections
b = 7.5526 (11) Å	θ = 2.5–23.5°
c = 13.628 (2) Å	µ = 0.07 mm^−1
β = 101.320 (3)°	T = 170 K
V = 1253.8 (3) Å^3	Parallelepiped, colorless
Z = 2	0.35 × 0.27 × 0.19 mm

Data collection

Bruker SMART CCD area-detector diffractometer	3278 independent reflections
Radiation source: fine-focus sealed tube	2947 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.036
ϕ and ω scans	θmax = 28.3°, θmin = 1.5°
Absorption correction: multi-scan (SADABS; Sheldrick, 2000)	h = −16→16
Tmin = 0.978, Tmax = 0.988	k = −10→10
15904 measured reflections	l = −18→17

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.103	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0564P)^2 + 0.2128P] where P = (Fo^2 + 2Fc^2)/3
3278 reflections	(Δ/σ)max = 0.001
427 parameters	Δρmax = 0.29 e Å^−3
1 restraint	Δρmin = −0.21 e Å^−3

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.

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 > σ(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	1.40579 (14)	0.6237 (3)	0.89158 (15)	0.0510 (5)
H1C	1.4412	0.5297	0.9071	0.076*
C1	1.19096 (19)	0.4868 (3)	0.90714 (18)	0.0311 (5)
H1A	1.221 (2)	0.450 (4)	0.847 (2)	0.037*
H1B	1.146 (2)	0.382 (4)	0.922 (2)	0.037*
C2	1.2852 (2)	0.5247 (4)	0.99506 (19)	0.0369 (6)
H2A	1.254 (2)	0.557 (5)	1.058 (2)	0.044*
H2B	1.327 (2)	0.425 (5)	1.004 (2)	0.044*
C3	1.35494 (19)	0.6777 (4)	0.97270 (18)	0.0336 (5)
H3	1.413 (2)	0.704 (4)	1.029 (2)	0.040*
C4	1.28847 (16)	0.8509 (3)	0.94791 (16)	0.0258 (4)
C5	1.18708 (16)	0.8123 (3)	0.86352 (15)	0.0217 (4)
H5	1.221 (2)	0.790 (4)	0.8061 (18)	0.026*
C6	1.11519 (17)	0.9759 (3)	0.83414 (16)	0.0255 (4)
H6A	1.157 (2)	1.067 (4)	0.8076 (18)	0.031*
H6B	1.096 (2)	1.034 (4)	0.8975 (19)	0.031*
C7	1.01005 (16)	0.9370 (3)	0.76111 (15)	0.0233 (4)
H7	0.967 (2)	1.039 (4)	0.7398 (18)	0.028*
C8	0.97350 (17)	0.7761 (3)	0.73325 (14)	0.0197 (4)
C9	1.04349 (16)	0.6136 (3)	0.77089 (16)	0.0220 (4)
H9	1.0982 (19)	0.602 (4)	0.7289 (18)	0.026*
C10	1.11547 (16)	0.6477 (3)	0.87714 (15)	0.0216 (4)
C11	0.9784 (2)	0.4394 (3)	0.76279 (18)	0.0302 (5)
H11A	0.941 (2)	0.428 (4)	0.818 (2)	0.036*
H11B	1.028 (2)	0.340 (4)	0.773 (2)	0.036*
C12	0.89420 (19)	0.4119 (3)	0.66383 (17)	0.0277 (5)
H12A	0.917 (2)	0.319 (4)	0.625 (2)	0.033*
H12B	0.824 (2)	0.367 (4)	0.6792 (19)	0.033*
C13	0.86880 (16)	0.5793 (3)	0.59792 (14)	0.0207 (4)
C14	0.86016 (15)	0.7426 (3)	0.66738 (15)	0.0195 (4)
C15	0.81611 (16)	0.9046 (3)	0.60218 (15)	0.0211 (4)
H15A	0.8088 (19)	1.003 (4)	0.6475 (18)	0.025*
H15B	0.871 (2)	0.937 (4)	0.5645 (17)	0.025*
C16	0.70575 (17)	0.8726 (3)	0.52982 (16)	0.0235 (4)
H16A	0.689 (2)	0.975 (4)	0.492 (2)	0.028*
H16B	0.649 (2)	0.852 (4)	0.5701 (18)	0.028*
C17	0.71043 (16)	0.7145 (3)	0.45998 (15)	0.0203 (4)
C18	0.75713 (17)	0.5554 (3)	0.52701 (15)	0.0219 (4)
H18	0.7031 (19)	0.543 (4)	0.5713 (18)	0.026*
C19	0.7379 (2)	0.3959 (3)	0.45675 (18)	0.0321 (5)
H19A	0.793 (2)	0.387 (4)	0.418 (2)	0.038*
H19B	0.738 (2)	0.285 (5)	0.487 (2)	0.038*
C20	0.6246 (2)	0.4369 (3)	0.39086 (17)	0.0317 (5)
H20A	0.625 (2)	0.419 (4)	0.322 (2)	0.038*
H20B	0.565 (2)	0.360 (4)	0.405 (2)	0.038*
C21	0.59718 (16)	0.6344 (3)	0.40981 (15)	0.0234 (4)
H21	0.5518 (19)	0.639 (4)	0.4634 (18)	0.028*
C22	0.52988 (18)	0.7246 (3)	0.31581 (16)	0.0275 (5)
H22	0.570 (2)	0.715 (4)	0.263 (2)	0.033*
C23	1.2616 (2)	0.9247 (4)	1.04572 (17)	0.0308 (5)
H23A	1.221 (2)	1.033 (4)	1.034 (2)	0.037*
H23B	1.327 (2)	0.962 (4)	1.091 (2)	0.037*
H23C	1.220 (2)	0.841 (4)	1.079 (2)	0.037*
C24	1.36140 (19)	0.9912 (4)	0.9116 (2)	0.0381 (6)
H24A	1.375 (2)	0.967 (4)	0.845 (2)	0.046*
H24B	1.324 (2)	1.115 (5)	0.907 (2)	0.046*
H24C	1.431 (2)	1.000 (4)	0.963 (2)	0.046*
C25	1.04205 (18)	0.6771 (3)	0.95397 (17)	0.0279 (5)
H25A	0.990 (2)	0.584 (4)	0.9500 (19)	0.034*
H25B	1.084 (2)	0.677 (4)	1.020 (2)	0.034*
H25C	1.002 (2)	0.785 (4)	0.9427 (19)	0.034*
C26	0.96283 (17)	0.6049 (3)	0.54017 (17)	0.0252 (4)
H26A	1.030 (2)	0.558 (4)	0.5769 (18)	0.030*
H26B	0.9486 (19)	0.538 (4)	0.4752 (19)	0.030*
H26C	0.972 (2)	0.721 (4)	0.5256 (19)	0.030*
C27	0.78122 (18)	0.7102 (3)	0.74065 (17)	0.0280 (5)
H27A	0.708 (2)	0.688 (4)	0.7058 (19)	0.034*
H27B	0.779 (2)	0.817 (4)	0.782 (2)	0.034*
H27C	0.805 (2)	0.611 (4)	0.785 (2)	0.034*
C28	0.77462 (19)	0.7631 (3)	0.37817 (17)	0.0273 (5)
H28A	0.787 (2)	0.663 (4)	0.337 (2)	0.033*
H28B	0.732 (2)	0.853 (4)	0.3342 (19)	0.033*
H28C	0.846 (2)	0.810 (4)	0.4057 (19)	0.033*
C29	0.4211 (2)	0.6248 (5)	0.2819 (2)	0.0460 (7)
H29A	0.436 (3)	0.493 (5)	0.272 (3)	0.055*
H29B	0.377 (3)	0.632 (5)	0.334 (2)	0.055*
H29C	0.379 (3)	0.678 (5)	0.223 (2)	0.055*
C30	0.5061 (2)	0.9195 (4)	0.33158 (19)	0.0366 (6)
H30A	0.457 (2)	0.967 (4)	0.273 (2)	0.044*
H30B	0.473 (2)	0.941 (4)	0.390 (2)	0.044*
H30C	0.573 (2)	0.997 (4)	0.348 (2)	0.044*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0347 (9)	0.0695 (14)	0.0480 (11)	0.0208 (10)	0.0064 (8)	−0.0156 (10)
C1	0.0330 (12)	0.0234 (11)	0.0322 (12)	0.0074 (10)	−0.0049 (10)	0.0001 (9)
C2	0.0370 (13)	0.0315 (13)	0.0350 (13)	0.0102 (10)	−0.0106 (11)	0.0002 (10)
C3	0.0247 (10)	0.0443 (14)	0.0280 (11)	0.0076 (10)	−0.0039 (9)	−0.0055 (10)
C4	0.0210 (9)	0.0329 (12)	0.0223 (10)	−0.0011 (9)	0.0009 (8)	−0.0001 (9)
C5	0.0201 (9)	0.0263 (10)	0.0184 (9)	−0.0022 (8)	0.0031 (8)	−0.0010 (8)
C6	0.0272 (10)	0.0193 (10)	0.0272 (10)	−0.0063 (8)	−0.0010 (9)	0.0007 (8)
C7	0.0220 (9)	0.0194 (10)	0.0258 (10)	0.0011 (8)	−0.0017 (8)	0.0029 (8)
C8	0.0205 (9)	0.0184 (9)	0.0198 (9)	0.0017 (7)	0.0031 (7)	0.0015 (8)
C9	0.0215 (9)	0.0178 (9)	0.0249 (10)	0.0013 (8)	0.0004 (8)	−0.0005 (8)
C10	0.0212 (9)	0.0192 (10)	0.0224 (9)	0.0019 (8)	−0.0004 (7)	0.0010 (8)
C11	0.0340 (12)	0.0190 (11)	0.0324 (11)	−0.0015 (9)	−0.0064 (9)	0.0065 (9)
C12	0.0327 (11)	0.0163 (10)	0.0307 (11)	−0.0023 (9)	−0.0021 (9)	0.0016 (9)
C13	0.0226 (9)	0.0163 (9)	0.0219 (9)	−0.0004 (7)	0.0011 (8)	−0.0004 (7)
C14	0.0182 (9)	0.0169 (9)	0.0225 (9)	−0.0016 (7)	0.0020 (7)	−0.0010 (7)
C15	0.0213 (9)	0.0149 (10)	0.0256 (10)	−0.0003 (7)	0.0012 (8)	−0.0011 (8)
C16	0.0227 (10)	0.0204 (10)	0.0254 (11)	0.0026 (8)	0.0001 (8)	−0.0029 (8)
C17	0.0188 (9)	0.0207 (10)	0.0215 (9)	−0.0024 (7)	0.0046 (7)	−0.0007 (8)
C18	0.0241 (10)	0.0184 (9)	0.0228 (10)	−0.0034 (8)	0.0039 (8)	−0.0014 (8)
C19	0.0378 (12)	0.0197 (11)	0.0337 (12)	−0.0025 (9)	−0.0053 (10)	−0.0045 (9)
C20	0.0366 (12)	0.0281 (12)	0.0265 (11)	−0.0093 (10)	−0.0039 (9)	−0.0026 (10)
C21	0.0220 (9)	0.0268 (11)	0.0206 (9)	−0.0047 (8)	0.0021 (8)	0.0000 (8)
C22	0.0256 (10)	0.0339 (12)	0.0216 (10)	−0.0037 (9)	0.0014 (8)	0.0013 (9)
C23	0.0314 (11)	0.0362 (13)	0.0222 (10)	0.0003 (10)	−0.0013 (9)	−0.0032 (10)
C24	0.0256 (11)	0.0539 (17)	0.0330 (12)	−0.0134 (12)	0.0011 (10)	−0.0003 (12)
C25	0.0290 (11)	0.0289 (12)	0.0264 (10)	−0.0033 (9)	0.0067 (9)	0.0037 (9)
C26	0.0219 (10)	0.0255 (11)	0.0278 (10)	0.0044 (8)	0.0041 (8)	−0.0031 (9)
C27	0.0239 (10)	0.0347 (12)	0.0257 (10)	−0.0025 (9)	0.0055 (9)	−0.0012 (10)
C28	0.0269 (10)	0.0301 (12)	0.0260 (10)	−0.0028 (9)	0.0082 (9)	0.0020 (9)
C29	0.0352 (13)	0.0601 (19)	0.0351 (13)	−0.0152 (13)	−0.0118 (11)	0.0150 (14)
C30	0.0336 (12)	0.0429 (14)	0.0299 (12)	0.0111 (11)	−0.0022 (10)	0.0005 (11)

Geometric parameters (Å, º)

O1—C3	1.436 (3)	C16—H16A	0.93 (3)
O1—H1C	0.8400	C16—H16B	0.99 (3)
C1—C2	1.529 (3)	C17—C28	1.537 (3)
C1—C10	1.541 (3)	C17—C18	1.551 (3)
C1—H1A	1.00 (3)	C17—C21	1.560 (3)
C1—H1B	1.01 (3)	C18—C19	1.528 (3)
C2—C3	1.510 (4)	C18—H18	0.99 (2)
C2—H2A	1.03 (3)	C19—C20	1.545 (3)
C2—H2B	0.91 (3)	C19—H19A	0.95 (3)
C3—C4	1.549 (3)	C19—H19B	0.93 (3)
C3—H3	0.97 (3)	C20—C21	1.563 (3)
C4—C24	1.538 (3)	C20—H20A	0.94 (3)
C4—C23	1.541 (3)	C20—H20B	0.98 (3)
C4—C5	1.557 (3)	C21—C22	1.544 (3)
C5—C6	1.531 (3)	C21—H21	1.01 (2)
C5—C10	1.561 (3)	C22—C30	1.526 (4)
C5—H5	0.98 (2)	C22—C29	1.537 (3)
C6—C7	1.508 (3)	C22—H22	0.96 (3)
C6—H6A	0.97 (3)	C23—H23A	0.96 (3)
C6—H6B	1.04 (3)	C23—H23B	0.96 (3)
C7—C8	1.326 (3)	C23—H23C	0.98 (3)
C7—H7	0.95 (3)	C24—H24A	0.98 (3)
C8—C9	1.533 (3)	C24—H24B	1.04 (4)
C8—C14	1.535 (3)	C24—H24C	0.99 (3)
C9—C11	1.537 (3)	C25—H25A	0.95 (3)
C9—C10	1.567 (3)	C25—H25B	0.95 (3)
C9—H9	0.98 (2)	C25—H25C	0.95 (3)
C10—C25	1.534 (3)	C26—H26A	0.96 (3)
C11—C12	1.550 (3)	C26—H26B	1.00 (3)
C11—H11A	0.96 (3)	C26—H26C	0.91 (3)
C11—H11B	0.97 (3)	C27—H27A	0.96 (3)
C12—C13	1.547 (3)	C27—H27B	0.99 (3)
C12—H12A	0.95 (3)	C27—H27C	0.97 (3)
C12—H12B	1.00 (3)	C28—H28A	0.97 (3)
C13—C18	1.538 (3)	C28—H28B	0.99 (3)
C13—C26	1.543 (3)	C28—H28C	0.96 (3)
C13—C14	1.571 (3)	C29—H29A	1.03 (4)
C14—C15	1.548 (3)	C29—H29B	0.98 (3)
C14—C27	1.550 (3)	C29—H29C	0.96 (3)
C15—C16	1.543 (3)	C30—H30A	0.97 (3)
C15—H15A	0.98 (3)	C30—H30B	0.98 (3)
C15—H15B	0.96 (2)	C30—H30C	1.00 (3)
C16—C17	1.535 (3)
C3—O1—H1C	109.5	C17—C16—H16B	109.8 (16)
C2—C1—C10	113.1 (2)	C15—C16—H16B	108.3 (14)
C2—C1—H1A	110.1 (15)	H16A—C16—H16B	109 (2)
C10—C1—H1A	107.7 (17)	C16—C17—C28	110.60 (18)
C2—C1—H1B	111.3 (15)	C16—C17—C18	107.02 (16)
C10—C1—H1B	109.5 (16)	C28—C17—C18	115.14 (18)
H1A—C1—H1B	105 (2)	C16—C17—C21	115.63 (17)
C3—C2—C1	111.5 (2)	C28—C17—C21	109.04 (17)
C3—C2—H2A	108.2 (19)	C18—C17—C21	99.13 (16)
C1—C2—H2A	109.7 (16)	C19—C18—C13	119.81 (18)
C3—C2—H2B	109 (2)	C19—C18—C17	104.31 (16)
C1—C2—H2B	106.2 (19)	C13—C18—C17	117.79 (16)
H2A—C2—H2B	112 (3)	C19—C18—H18	105.3 (15)
O1—C3—C2	107.1 (2)	C13—C18—H18	105.3 (13)
O1—C3—C4	111.6 (2)	C17—C18—H18	102.3 (15)
C2—C3—C4	112.82 (18)	C18—C19—C20	102.65 (19)
O1—C3—H3	107.4 (17)	C18—C19—H19A	111.4 (18)
C2—C3—H3	111.2 (18)	C20—C19—H19A	111.7 (17)
C4—C3—H3	106.5 (19)	C18—C19—H19B	116.1 (18)
C24—C4—C23	105.7 (2)	C20—C19—H19B	110.8 (18)
C24—C4—C3	109.24 (19)	H19A—C19—H19B	104 (2)
C23—C4—C3	108.29 (18)	C19—C20—C21	107.34 (18)
C24—C4—C5	109.46 (18)	C19—C20—H20A	111.5 (17)
C23—C4—C5	115.19 (17)	C21—C20—H20A	110.2 (19)
C3—C4—C5	108.81 (18)	C19—C20—H20B	113.6 (16)
C6—C5—C4	112.83 (18)	C21—C20—H20B	109.7 (18)
C6—C5—C10	110.92 (16)	H20A—C20—H20B	104 (2)
C4—C5—C10	117.29 (17)	C22—C21—C17	119.18 (18)
C6—C5—H5	104.7 (15)	C22—C21—C20	112.57 (18)
C4—C5—H5	101.9 (14)	C17—C21—C20	103.63 (17)
C10—C5—H5	107.9 (16)	C22—C21—H21	107.3 (14)
C7—C6—C5	113.62 (18)	C17—C21—H21	104.6 (14)
C7—C6—H6A	110.4 (15)	C20—C21—H21	109.0 (16)
C5—C6—H6A	109.9 (16)	C30—C22—C29	109.4 (2)
C7—C6—H6B	108.5 (14)	C30—C22—C21	113.40 (19)
C5—C6—H6B	110.1 (15)	C29—C22—C21	109.5 (2)
H6A—C6—H6B	104 (2)	C30—C22—H22	108.9 (18)
C8—C7—C6	124.83 (19)	C29—C22—H22	107.3 (16)
C8—C7—H7	121.1 (16)	C21—C22—H22	108.1 (16)
C6—C7—H7	113.9 (16)	C4—C23—H23A	111.5 (16)
C7—C8—C9	119.87 (18)	C4—C23—H23B	111.2 (16)
C7—C8—C14	122.80 (18)	H23A—C23—H23B	102 (2)
C9—C8—C14	117.28 (17)	C4—C23—H23C	112.9 (17)
C8—C9—C11	113.94 (16)	H23A—C23—H23C	108 (2)
C8—C9—C10	111.15 (17)	H23B—C23—H23C	110 (2)
C11—C9—C10	113.84 (17)	C4—C24—H24A	113.2 (19)
C8—C9—H9	106.8 (16)	C4—C24—H24B	110.6 (17)
C11—C9—H9	107.4 (16)	H24A—C24—H24B	106 (2)
C10—C9—H9	102.7 (14)	C4—C24—H24C	107.6 (18)
C25—C10—C1	110.20 (18)	H24A—C24—H24C	112 (2)
C25—C10—C5	113.29 (18)	H24B—C24—H24C	107 (3)
C1—C10—C5	109.18 (17)	C10—C25—H25A	110.1 (16)
C25—C10—C9	110.28 (17)	C10—C25—H25B	111.2 (16)
C1—C10—C9	108.83 (17)	H25A—C25—H25B	107 (2)
C5—C10—C9	104.86 (16)	C10—C25—H25C	112.2 (16)
C9—C11—C12	115.65 (18)	H25A—C25—H25C	107 (2)
C9—C11—H11A	110.2 (18)	H25B—C25—H25C	109 (2)
C12—C11—H11A	108.8 (16)	C13—C26—H26A	111.2 (15)
C9—C11—H11B	110.3 (17)	C13—C26—H26B	111.6 (14)
C12—C11—H11B	108.8 (17)	H26A—C26—H26B	105 (2)
H11A—C11—H11B	102 (2)	C13—C26—H26C	111.8 (16)
C13—C12—C11	114.94 (18)	H26A—C26—H26C	110 (2)
C13—C12—H12A	109.4 (17)	H26B—C26—H26C	107 (2)
C11—C12—H12A	110.7 (16)	C14—C27—H27A	111.7 (15)
C13—C12—H12B	108.3 (16)	C14—C27—H27B	109.6 (16)
C11—C12—H12B	109.4 (15)	H27A—C27—H27B	107 (2)
H12A—C12—H12B	103 (2)	C14—C27—H27C	111.4 (15)
C18—C13—C26	111.96 (16)	H27A—C27—H27C	109 (2)
C18—C13—C12	108.97 (16)	H27B—C27—H27C	108 (2)
C26—C13—C12	108.06 (17)	C17—C28—H28A	113.3 (16)
C18—C13—C14	108.10 (16)	C17—C28—H28B	107.9 (15)
C26—C13—C14	110.91 (16)	H28A—C28—H28B	108 (2)
C12—C13—C14	108.78 (16)	C17—C28—H28C	112.0 (15)
C8—C14—C15	112.69 (16)	H28A—C28—H28C	106 (2)
C8—C14—C27	105.85 (16)	H28B—C28—H28C	109 (2)
C15—C14—C27	107.30 (17)	C22—C29—H29A	110.2 (18)
C8—C14—C13	108.57 (15)	C22—C29—H29B	109.8 (19)
C15—C14—C13	109.45 (16)	H29A—C29—H29B	107 (3)
C27—C14—C13	113.01 (17)	C22—C29—H29C	111 (2)
C16—C15—C14	114.39 (17)	H29A—C29—H29C	112 (3)
C16—C15—H15A	109.9 (14)	H29B—C29—H29C	107 (3)
C14—C15—H15A	107.6 (15)	C22—C30—H30A	110.2 (19)
C16—C15—H15B	109.4 (14)	C22—C30—H30B	113.7 (19)
C14—C15—H15B	107.3 (15)	H30A—C30—H30B	108 (2)
H15A—C15—H15B	108 (2)	C22—C30—H30C	114.8 (18)
C17—C16—C15	112.40 (17)	H30A—C30—H30C	109 (3)
C17—C16—H16A	109.7 (17)	H30B—C30—H30C	100 (2)
C15—C16—H16A	107.3 (16)
C10—C1—C2—C3	−57.7 (3)	C7—C8—C14—C27	−92.6 (2)
C1—C2—C3—O1	−64.7 (2)	C9—C8—C14—C27	84.8 (2)
C1—C2—C3—C4	58.5 (3)	C7—C8—C14—C13	145.8 (2)
O1—C3—C4—C24	−51.2 (2)	C9—C8—C14—C13	−36.8 (2)
C2—C3—C4—C24	−171.90 (19)	C18—C13—C14—C8	−175.90 (16)
O1—C3—C4—C23	−165.9 (2)	C26—C13—C14—C8	−52.8 (2)
C2—C3—C4—C23	73.4 (2)	C12—C13—C14—C8	65.9 (2)
O1—C3—C4—C5	68.2 (2)	C18—C13—C14—C15	−52.5 (2)
C2—C3—C4—C5	−52.4 (2)	C26—C13—C14—C15	70.6 (2)
C24—C4—C5—C6	−61.2 (2)	C12—C13—C14—C15	−170.71 (16)
C23—C4—C5—C6	57.7 (3)	C18—C13—C14—C27	67.0 (2)
C3—C4—C5—C6	179.52 (18)	C26—C13—C14—C27	−169.91 (17)
C24—C4—C5—C10	168.07 (19)	C12—C13—C14—C27	−51.2 (2)
C23—C4—C5—C10	−73.0 (3)	C8—C14—C15—C16	176.26 (17)
C3—C4—C5—C10	48.8 (2)	C27—C14—C15—C16	−67.6 (2)
C4—C5—C6—C7	−173.43 (17)	C13—C14—C15—C16	55.3 (2)
C10—C5—C6—C7	−39.5 (2)	C14—C15—C16—C17	−56.2 (2)
C5—C6—C7—C8	8.4 (3)	C15—C16—C17—C28	−74.6 (2)
C6—C7—C8—C9	−4.0 (3)	C15—C16—C17—C18	51.6 (2)
C6—C7—C8—C14	173.30 (19)	C15—C16—C17—C21	160.91 (18)
C7—C8—C9—C11	160.8 (2)	C26—C13—C18—C19	63.0 (2)
C14—C8—C9—C11	−16.6 (3)	C12—C13—C18—C19	−56.5 (3)
C7—C8—C9—C10	30.6 (3)	C14—C13—C18—C19	−174.56 (19)
C14—C8—C9—C10	−146.84 (17)	C26—C13—C18—C17	−65.6 (2)
C2—C1—C10—C25	−74.5 (3)	C12—C13—C18—C17	174.90 (18)
C2—C1—C10—C5	50.6 (3)	C14—C13—C18—C17	56.8 (2)
C2—C1—C10—C9	164.5 (2)	C16—C17—C18—C19	168.81 (17)
C6—C5—C10—C25	−56.5 (2)	C28—C17—C18—C19	−67.8 (2)
C4—C5—C10—C25	75.2 (2)	C21—C17—C18—C19	48.3 (2)
C6—C5—C10—C1	−179.70 (17)	C16—C17—C18—C13	−55.6 (2)
C4—C5—C10—C1	−48.1 (2)	C28—C17—C18—C13	67.8 (2)
C6—C5—C10—C9	63.8 (2)	C21—C17—C18—C13	−176.08 (17)
C4—C5—C10—C9	−164.54 (17)	C13—C18—C19—C20	−172.57 (19)
C8—C9—C10—C25	63.8 (2)	C17—C18—C19—C20	−38.1 (2)
C11—C9—C10—C25	−66.5 (2)	C18—C19—C20—C21	12.6 (2)
C8—C9—C10—C1	−175.22 (17)	C16—C17—C21—C22	81.3 (2)
C11—C9—C10—C1	54.5 (2)	C28—C17—C21—C22	−44.1 (3)
C8—C9—C10—C5	−58.5 (2)	C18—C17—C21—C22	−164.80 (19)
C11—C9—C10—C5	171.22 (18)	C16—C17—C21—C20	−152.75 (18)
C8—C9—C11—C12	43.2 (3)	C28—C17—C21—C20	81.9 (2)
C10—C9—C11—C12	172.0 (2)	C18—C17—C21—C20	−38.80 (19)
C9—C11—C12—C13	−13.2 (3)	C19—C20—C21—C22	147.0 (2)
C11—C12—C13—C18	−158.3 (2)	C19—C20—C21—C17	16.9 (2)
C11—C12—C13—C26	79.8 (2)	C17—C21—C22—C30	−56.2 (3)
C11—C12—C13—C14	−40.7 (3)	C20—C21—C22—C30	−177.8 (2)
C7—C8—C14—C15	24.4 (3)	C17—C21—C22—C29	−178.7 (2)
C9—C8—C14—C15	−158.26 (17)	C20—C21—C22—C29	59.7 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C24—H24C···O1^i	0.99 (3)	2.72 (3)	3.677 (3)	162 (3)

Symmetry code: (i) −x+3, y+1/2, −z+2.