18-De­oxy-13β,14-dihydrolycoctam: the lycoctamone rearrangement confirmed

The structure of the title compound, C₂₃H₃₅NO₄, contains a unique penta­cyclic ring system wherein one cyclo­hexyl ring adopts a chair conformation, two cyclo­hexyl rings are in boat conformations, and a six-membered heterocyclic ring and a cyclo­pentyl ring are in envelope conformations. The structures of the lycoctamones, α,β-unsaturated aldehydes produced by acid-catalyzed degradation of lactams of lycoctonine-type alkaloids, previously deduced from the results of extensive chemical investigations have been proven to be correct by the determination of the crystal structure of this compound.

S1. Comment

During early work on the structure of the norditerpenoid alkaloid lycoctonine (1) it was discovered that the action of strong acids on the lactam derivative (2) induced the loss of two methanol units and its transformation into a product named lycoctamone (Edwards et al., 1954). Later studies revealed that lycoctamone was actually an αβ-unsaturated aldehyde and, after extensive investigations on this compound and some congeners, resulted in the proposed structure (3) (Benn et al. 1971). As shown here, this structure incorporates a revision of the stereochemistry at C-1 required (Pelletier et al., 1981; Edwards & Przybylska, 1982) as a result of an error in the original assignment in the X-ray crystallography of the derivative of (1), which had established the skeleton of these alkaloids (Przybylska & Marion, 1954; Przybylska, 1961); the same correction needs to be made to all other structures of Benn et al. (1971). The absolute structure of the lycoctonine series of compounds has been established previously (Przybylska & Marion, 1959).

The remarkable reorganization needed to produce (3) from (2) was rationalized as proceeding via a cascade of reactions, viz. a pinacolic rearrangement of (2) to (4), followed by a ring contraction of the protonated ketone via another acid-catalyzed 1,2-alkyl shift of the C-8,9 bond, to generate a carbocation that underwent a retro-Prins reaction with ring cleavage and loss of methanol forming an aldehyde, which finally underwent an acid catalyzed 1,2-elimination of another molecule of methanol. An alternative structure, (5), which would result from a fragmentation of protonated (4) induced by migration of the C-8,17 bond to generate a C-8 carbocation, appeared to be improbable because under the reaction conditions its exocyclic double bond would be expected to migrate to form a conjugated dienal system (Benn et al., 1971).

We now report the result of an X-ray crystallographic study which establishes the carbon skeleton of the lycoctamone system, and confirms the conclusions reached from the chemical investigations.

Sodium borohydride reduction of 18-deoxylycoctamone, (6), prepared from 18-deoxylycoctonam, (7) (Benn et al. 1971), gave the corresponding allylic alcohol (8), which was then subjected to hydrogenation over palladium, a process known to result in hydrogenolysis as well as reduction of the endocyclic double bond, (Edwards et al., 1954; Benn et al. 1971) to afford in good yield 18-deoxy-13β,14-dihydrolycoctam, (9), as a crystalline product. X-ray crystallography of this established the structure reported in this paper. This confirmed its molecular skeleton as that of (3), and not (5), and additionally showed that as expected hydrogenation had occurred from the β-face. Thus the structures assigned to lycoctamone and its analogues have been confirmed.

The structure of (9) contains a unique pentacyclic ring system (Fig. 1) that has not been reported in any stucture contained in the latest version of Cambridge Structural Database (2006 Release, Allen, 2002). The six-membered rings C1—C5/C11 (ring A), C5–C7/C9–C11 (ring B), C7–C11/C17 (ring C) and C4/C5/C11/C17/C19/N1 (ring D) adopt chair, boat, boat and C11-envelope conformations, respectively. The five membered ring, C9/C10/C12–C14 (ring E) exhibits a C13-envelope conformation. The puckering parameters (Cremer & Pople, 1975) for ring A are Q = 0.562 (4) Å, θ = 167.7 (4)° and ϕ = 8(2)°. In ring B, atoms C7 and C11 lie 0.735 (5) and 0.709 (5) Å, respectively, out of the plane formed by the remaining four atoms of the ring, the maximum deviation of any of these fours atoms from the plane being 0.052 (2) Å. Similarly, in ring C, atoms C7 and C11 lie 0.735 (5) and 0.709 (5) Å, respectively, out of the plane formed by the remaining four atoms of the ring, with a maximum deviation of 0.082 (2) Å. In the heterocyclic ring D, atom C11 lies 0.720 (5) Å out of the plane formed by the remaining five atoms, which show large deviations from planarity [between 0.120 (2) and 0.146 (3) Å].

The molecular dimensions in (9) are as expected and the structure is stabilized by strong intermolecular hydrogen bonds of the type O—H···O, linking the molecules into spirals along the b direction; details of hydrogen-bonding geometry have been provided in Table 2.

S2. Experimental

NMR spectra were recorded of samples dissolved in CDCl₃ (¹H at 400 MHz, with residual CHCl₃ as ref. δ_H 7.25 p.p.m.; ¹³C at 100 MHz, with the center line of the solvent resonance δ_C 77.0 p.p.m. as ref.) EIMS were measured using 70 eV sample bombardment. 18-Deoxylycoctamol, (8), m.p. 500–505 K (from Me₂CO–hexanes); EIMS m/z 403.2352, C₂₃H₃₃NO₅ requires 403.2359; ¹H NMR: δ_H 5.38 (1H, br s, H-14), 5.12 (1H, br s, H-15A) and 5.14 (1H, br s, H-15B), 4.19 (1H, d, J = 2 Hz, H-17), 4.13 (2H, br s, H-16), 3.93 (1H, dq, J = 14.1 and 7.1 Hz, H-20A), 3.57 (3H, s, OCH₃), 3.38 (1H, br m), 3.30 (3H, s, OCH₃), 3.21 (1H, d, J = 4.1 Hz, H-6), 3.07 (1H, br m), 2.97 (1H, dq, J = 14.1 and 7.1 Hz, H-20B), 2.39 (3H, m), 1.99 (1H, m), 1.94 (1H, m), 1.58 (1H, dd, J = 4.1 and 2.1 Hz, H-5), 1.31 (2H, m), 1.27 (3H, s, H-18), and 1.12 (3H, t, J = 7.1 Hz, H-21); ¹³C NMR: δ_C 172.6 (s), 149.1 (s), 143.9 (s), 121.5 (d), 113.0 (t), 85.4 (d), 83.3 (d), 61.7 (t), 60.3 (q), 56.9 (d), 56.5 (q), 53.2 (d), 47.7 (d), 39.0 (t), 36.3 (t), 36.0 (t), 25.2 (t), 22.2 (q), and 11.7 (q). 18-Deoxydihydrolycoctamone (9), m.p. 484–486 K (from Me₂CO–hexanes); EIMS m/z 389.2565, C₂₃H₃₅NO₄ requires 389.2566; ¹H NMR: δ_H 5.27 (1H, br s, H-15A), 5.25 (1H, br s, H-15B), 4.08 (1H, d, J = 1.5 Hz, H-17), 3.99 (1H, dq, H-20A), 3.55 (3H, s, OCH₃), 3.28 (3H, s, OCH₃), 3.22 (1H, d, J = 4 Hz, H-6), 3.01 (1H, m), 2.99 (1H, dq, H-20B), 2.76 (1H, m), 2.1–1.8 (4H, m), 1.75–1.55 (4H, m), 1.49 (1H, dd, J = 1.5 and 4 Hz, H-5), 1.26 (3H, s, H-18), 1.13 (3H, t, J = 7.1 Hz, H-21), 0.96 (3H, d, J = (?)Hz, H-15) and 0.94 (1H, m); ¹³C NMR: δ_C 172.7 (s), 144.1 (s), 112.9 (t), 84.5 (d), 83.5 (d), 78.4 (s), 60.2 (q), 56.3 (d), 56.2 (q), 54.1 (d), 50.9 (q), 42.8 (s), 39.2 (t), 39.1 (d), 38.6 (t), 38.5 (s), 36.5 (t), 34.6 (d), 33.3 (t), 25.4 (t), 22.1 (q), 18.8 (q), and 11.7 (q).

S3. Refinement

The H atoms were located in difference Fourier syntheses and were included in the refinements at idealized positions (C—H = 0.96 Å) with isotropic displacement parameters equal to 1.5 (hydroxy atom) and 1.2 (the rest) times the equivalent displacement parameters of the atoms to which they were bonded. The final difference map was free of any chemically significant features. An absolute structure was not established in this analysis; Friedel pairs of reflections were merged.

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: HKL DENZO (Otwinowski & Minor, 1997); data reduction: SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SAPI91 (Fan, 1991); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97).

Figures

Fig. 1. An ORTEPII (Johnson, 1976) drawing of (9), with the crystallographic numbering scheme; displacement ellipsoids have been plotted at the 25% probability level.

18-deoxy-13β,14-dihydrolycoctam

Crystal data

C23H35NO4	F(000) = 424
Mr = 389.52	Dx = 1.244 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 4396 reflections
a = 9.675 (5) Å	θ = 3.8–27.5°
b = 10.401 (6) Å	µ = 0.08 mm^−1
c = 11.063 (7) Å	T = 295 K
β = 110.86 (3)°	Needle, colorless
V = 1040.3 (10) Å^3	0.12 × 0.04 × 0.03 mm
Z = 2

Data collection

Nonius KappaCCD diffractometer	2486 independent reflections
Radiation source: fine-focus sealed tube	1390 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.060
ω and ϕ scans	θmax = 27.5°, θmin = 3.8°
Absorption correction: multi-scan (SORTAV; Blessing, 1997)	h = −12→12
Tmin = 0.990, Tmax = 0.997	k = −12→13
4396 measured reflections	l = −14→14

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.051	w = 1/[σ^2(Fo^2) + (0.057P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.124	(Δ/σ)max < 0.001
S = 1.01	Δρmax = 0.17 e Å^−3
2486 reflections	Δρmin = −0.20 e Å^−3
255 parameters	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.048 (8)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881
Secondary atom site location: difference Fourier map

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

	x	y	z	Uiso*/Ueq
O1	0.7998 (3)	0.2269 (3)	0.3992 (3)	0.0557 (8)
O2	0.5504 (3)	0.0570 (3)	−0.0709 (2)	0.0531 (7)
O3	0.2990 (3)	−0.1443 (3)	0.2343 (3)	0.0531 (7)
O4	0.5389 (3)	−0.3278 (2)	0.3259 (3)	0.0533 (7)
H4	0.5147	−0.3577	0.2527	0.080*
N1	0.6941 (3)	−0.0023 (3)	0.1308 (3)	0.0406 (8)
C1	0.6472 (4)	0.2025 (3)	0.3249 (4)	0.0451 (10)
H1	0.5891	0.2351	0.3726	0.054*
C2	0.6044 (4)	0.2709 (4)	0.1956 (4)	0.0524 (11)
H2A	0.6753	0.2512	0.1558	0.063*
H2B	0.6040	0.3619	0.2101	0.063*
C3	0.4533 (4)	0.2288 (4)	0.1045 (4)	0.0520 (10)
H3A	0.4316	0.2656	0.0201	0.062*
H3B	0.3810	0.2571	0.1397	0.062*
C4	0.4413 (4)	0.0809 (4)	0.0909 (3)	0.0421 (9)
C5	0.4646 (4)	0.0220 (4)	0.2231 (3)	0.0390 (9)
H5	0.3957	0.0640	0.2546	0.047*
C6	0.4379 (4)	−0.1243 (4)	0.2183 (4)	0.0416 (9)
H6	0.4322	−0.1555	0.1350	0.050*
C7	0.5658 (4)	−0.1939 (4)	0.3221 (3)	0.0406 (9)
C8	0.7075 (4)	−0.1644 (4)	0.2980 (3)	0.0410 (9)
C9	0.5828 (4)	−0.1356 (4)	0.4537 (4)	0.0469 (9)
H9	0.4882	−0.1403	0.4633	0.056*
C10	0.6290 (4)	0.0078 (4)	0.4550 (3)	0.0421 (9)
H10	0.5632	0.0583	0.4833	0.051*
C11	0.6205 (4)	0.0550 (4)	0.3196 (3)	0.0389 (8)
C12	0.7788 (4)	0.0156 (4)	0.5672 (4)	0.0537 (11)
H12A	0.7912	0.0996	0.6055	0.064*
H12B	0.8556	0.0001	0.5330	0.064*
C13	0.7708 (5)	−0.0860 (5)	0.6598 (4)	0.0689 (13)
H13	0.7069	−0.0563	0.7034	0.083*
C14	0.6988 (5)	−0.1980 (4)	0.5721 (4)	0.0567 (11)
H14A	0.7671	−0.2448	0.5435	0.068*
H14B	0.6511	−0.2561	0.6122	0.068*
C15	0.8104 (4)	−0.2519 (4)	0.3088 (4)	0.0537 (11)
H15A	0.8991	−0.2304	0.2931	0.064*
H15B	0.7948	−0.3384	0.3316	0.064*
C16	0.9141 (5)	−0.1143 (5)	0.7692 (4)	0.0814 (16)
H16A	0.8982	−0.1814	0.8224	0.098*
H16B	0.9882	−0.1410	0.7353	0.098*
H16C	0.9467	−0.0379	0.8201	0.098*
C17	0.7249 (4)	−0.0230 (3)	0.2719 (3)	0.0380 (9)
H17	0.8251	0.0027	0.3188	0.046*
C18	0.2909 (4)	0.0477 (5)	−0.0095 (4)	0.0561 (11)
H18A	0.2827	−0.0440	−0.0193	0.067*
H18B	0.2132	0.0793	0.0175	0.067*
H18C	0.2825	0.0863	−0.0906	0.067*
C19	0.5656 (4)	0.0415 (4)	0.0441 (3)	0.0410 (9)
C20	0.8143 (4)	−0.0370 (4)	0.0855 (4)	0.0519 (11)
H20A	0.7800	−0.0277	−0.0069	0.062*
H20B	0.8414	−0.1249	0.1082	0.062*
C21	0.9517 (5)	0.0440 (5)	0.1429 (5)	0.0787 (15)
H21A	1.0259	0.0163	0.1096	0.094*
H21B	0.9275	0.1324	0.1202	0.094*
H21C	0.9889	0.0352	0.2354	0.094*
C22	0.8241 (5)	0.3500 (5)	0.4584 (5)	0.0790 (15)
H22A	0.9276	0.3627	0.5058	0.095*
H22B	0.7883	0.4170	0.3952	0.095*
H22C	0.7710	0.3523	0.5169	0.095*
C23	0.2121 (4)	−0.2467 (5)	0.1608 (5)	0.0688 (13)
H23A	0.1220	−0.2545	0.1781	0.083*
H23B	0.1891	−0.2315	0.0702	0.083*
H23C	0.2681	−0.3247	0.1855	0.083*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0521 (16)	0.0482 (18)	0.0597 (17)	−0.0058 (14)	0.0115 (13)	0.0007 (14)
O2	0.0666 (17)	0.0563 (18)	0.0412 (15)	0.0020 (14)	0.0252 (13)	0.0066 (14)
O3	0.0454 (14)	0.0602 (18)	0.0593 (16)	−0.0057 (14)	0.0256 (13)	−0.0040 (15)
O4	0.0697 (17)	0.0387 (16)	0.0509 (16)	−0.0062 (13)	0.0207 (15)	0.0018 (13)
N1	0.0403 (17)	0.0438 (19)	0.0425 (17)	0.0004 (14)	0.0207 (15)	0.0021 (15)
C1	0.045 (2)	0.040 (2)	0.050 (2)	0.0006 (18)	0.0170 (18)	−0.0025 (18)
C2	0.070 (3)	0.035 (2)	0.054 (3)	−0.0012 (19)	0.025 (2)	0.0026 (19)
C3	0.062 (2)	0.046 (2)	0.048 (2)	0.010 (2)	0.019 (2)	0.005 (2)
C4	0.0408 (19)	0.045 (2)	0.040 (2)	0.0005 (17)	0.0139 (16)	0.0016 (18)
C5	0.0395 (19)	0.042 (2)	0.0386 (19)	0.0039 (16)	0.0176 (15)	−0.0012 (17)
C6	0.045 (2)	0.046 (2)	0.0370 (19)	−0.0007 (18)	0.0188 (16)	0.0002 (17)
C7	0.046 (2)	0.041 (2)	0.038 (2)	0.0015 (17)	0.0188 (17)	0.0036 (18)
C8	0.045 (2)	0.042 (2)	0.036 (2)	0.0025 (18)	0.0147 (16)	0.0011 (17)
C9	0.053 (2)	0.048 (2)	0.044 (2)	−0.0056 (19)	0.0230 (18)	0.0019 (19)
C10	0.050 (2)	0.042 (2)	0.037 (2)	0.0063 (18)	0.0188 (17)	−0.0013 (17)
C11	0.0423 (19)	0.039 (2)	0.0374 (19)	0.0016 (17)	0.0163 (15)	0.0001 (17)
C12	0.065 (2)	0.053 (3)	0.041 (2)	−0.003 (2)	0.0157 (19)	−0.0039 (19)
C13	0.081 (3)	0.058 (3)	0.054 (3)	0.002 (2)	0.006 (2)	0.007 (2)
C14	0.069 (3)	0.055 (3)	0.044 (2)	−0.001 (2)	0.018 (2)	0.009 (2)
C15	0.055 (2)	0.051 (2)	0.057 (3)	0.008 (2)	0.023 (2)	0.005 (2)
C16	0.090 (3)	0.074 (4)	0.057 (3)	0.004 (3)	−0.002 (3)	0.012 (3)
C17	0.0383 (19)	0.040 (2)	0.0346 (19)	0.0007 (16)	0.0116 (15)	−0.0009 (16)
C18	0.047 (2)	0.070 (3)	0.049 (2)	0.002 (2)	0.0137 (18)	0.016 (2)
C19	0.047 (2)	0.039 (2)	0.037 (2)	−0.0046 (18)	0.0155 (16)	−0.0016 (18)
C20	0.054 (2)	0.056 (3)	0.058 (3)	0.007 (2)	0.034 (2)	0.003 (2)
C21	0.056 (3)	0.086 (4)	0.104 (4)	−0.014 (3)	0.042 (3)	−0.010 (3)
C22	0.077 (3)	0.060 (3)	0.087 (4)	−0.014 (3)	0.014 (3)	−0.007 (3)
C23	0.058 (2)	0.066 (3)	0.081 (3)	−0.015 (3)	0.022 (2)	−0.004 (3)

Geometric parameters (Å, º)

O1—C22	1.419 (6)	C10—C12	1.538 (5)
O1—C1	1.434 (4)	C10—C11	1.551 (5)
O2—C19	1.238 (4)	C10—H10	0.9599
O3—C23	1.420 (5)	C11—C17	1.529 (5)
O3—C6	1.432 (4)	C12—C13	1.493 (6)
O4—C7	1.420 (4)	C12—H12A	0.9601
O4—H4	0.8200	C12—H12B	0.9600
N1—C19	1.350 (4)	C13—C16	1.509 (6)
N1—C20	1.466 (4)	C13—C14	1.517 (6)
N1—C17	1.497 (5)	C13—H13	0.9600
C1—C2	1.517 (6)	C14—H14A	0.9600
C1—C11	1.553 (5)	C14—H14B	0.9600
C1—H1	0.9600	C15—H15A	0.9600
C2—C3	1.515 (5)	C15—H15B	0.9600
C2—H2A	0.9600	C16—H16A	0.9602
C2—H2B	0.9600	C16—H16B	0.9600
C3—C4	1.547 (5)	C16—H16C	0.9598
C3—H3A	0.9600	C17—H17	0.9600
C3—H3B	0.9600	C18—H18A	0.9600
C4—C18	1.523 (5)	C18—H18B	0.9600
C4—C19	1.525 (5)	C18—H18C	0.9601
C4—C5	1.527 (5)	C20—C21	1.510 (6)
C5—C6	1.541 (5)	C20—H20A	0.9599
C5—C11	1.544 (5)	C20—H20B	0.9599
C5—H5	0.9599	C21—H21A	0.9601
C6—C7	1.537 (5)	C21—H21B	0.9599
C6—H6	0.9599	C21—H21C	0.9600
C7—C8	1.518 (5)	C22—H22A	0.9600
C7—C9	1.532 (5)	C22—H22B	0.9601
C8—C15	1.323 (5)	C22—H22C	0.9599
C8—C17	1.521 (5)	C23—H23A	0.9600
C9—C14	1.533 (5)	C23—H23B	0.9600
C9—C10	1.555 (5)	C23—H23C	0.9600
C9—H9	0.9600
C22—O1—C1	113.1 (3)	C10—C11—C1	109.0 (3)
C23—O3—C6	115.4 (3)	C13—C12—C10	104.6 (3)
C7—O4—H4	109.5	C13—C12—H12A	111.8
C19—N1—C20	118.8 (3)	C10—C12—H12A	109.8
C19—N1—C17	125.5 (3)	C13—C12—H12B	112.9
C20—N1—C17	115.7 (3)	C10—C12—H12B	108.2
O1—C1—C2	109.7 (3)	H12A—C12—H12B	109.5
O1—C1—C11	108.7 (3)	C12—C13—C16	115.5 (4)
C2—C1—C11	116.2 (3)	C12—C13—C14	103.2 (4)
O1—C1—H1	107.9	C16—C13—C14	116.4 (4)
C2—C1—H1	109.6	C12—C13—H13	108.4
C11—C1—H1	104.4	C16—C13—H13	103.4
C3—C2—C1	111.5 (3)	C14—C13—H13	109.8
C3—C2—H2A	108.1	C13—C14—C9	104.5 (3)
C1—C2—H2A	109.5	C13—C14—H14A	112.8
C3—C2—H2B	109.6	C9—C14—H14A	108.3
C1—C2—H2B	108.7	C13—C14—H14B	111.9
H2A—C2—H2B	109.5	C9—C14—H14B	109.6
C2—C3—C4	111.9 (3)	H14A—C14—H14B	109.5
C2—C3—H3A	110.9	C8—C15—H15A	121.0
C4—C3—H3A	108.6	C8—C15—H15B	119.0
C2—C3—H3B	108.1	H15A—C15—H15B	120.0
C4—C3—H3B	107.7	C13—C16—H16A	109.3
H3A—C3—H3B	109.5	C13—C16—H16B	110.1
C18—C4—C19	110.9 (3)	H16A—C16—H16B	109.5
C18—C4—C5	112.6 (3)	C13—C16—H16C	109.0
C19—C4—C5	110.6 (3)	H16A—C16—H16C	109.5
C18—C4—C3	108.4 (3)	H16B—C16—H16C	109.5
C19—C4—C3	105.0 (3)	N1—C17—C8	110.0 (3)
C5—C4—C3	109.0 (3)	N1—C17—C11	111.9 (3)
C4—C5—C6	113.4 (3)	C8—C17—C11	108.4 (3)
C4—C5—C11	110.4 (3)	N1—C17—H17	108.2
C6—C5—C11	110.7 (3)	C8—C17—H17	109.0
C4—C5—H5	106.3	C11—C17—H17	109.3
C6—C5—H5	109.4	C4—C18—H18A	109.1
C11—C5—H5	106.4	C4—C18—H18B	110.3
O3—C6—C7	112.4 (3)	H18A—C18—H18B	109.5
O3—C6—C5	107.0 (3)	C4—C18—H18C	109.1
C7—C6—C5	111.0 (3)	H18A—C18—H18C	109.5
O3—C6—H6	109.5	H18B—C18—H18C	109.5
C7—C6—H6	108.3	O2—C19—N1	121.1 (3)
C5—C6—H6	108.6	O2—C19—C4	119.6 (3)
O4—C7—C8	113.0 (3)	N1—C19—C4	119.2 (3)
O4—C7—C9	108.6 (3)	N1—C20—C21	113.9 (4)
C8—C7—C9	106.8 (3)	N1—C20—H20A	108.9
O4—C7—C6	112.2 (3)	C21—C20—H20A	108.1
C8—C7—C6	108.1 (3)	N1—C20—H20B	108.7
C9—C7—C6	108.0 (3)	C21—C20—H20B	107.7
C15—C8—C7	122.9 (4)	H20A—C20—H20B	109.5
C15—C8—C17	123.5 (3)	C20—C21—H21A	109.7
C7—C8—C17	113.4 (3)	C20—C21—H21B	109.1
C7—C9—C14	116.3 (3)	H21A—C21—H21B	109.5
C7—C9—C10	108.8 (3)	C20—C21—H21C	109.6
C14—C9—C10	106.1 (3)	H21A—C21—H21C	109.5
C7—C9—H9	107.5	H21B—C21—H21C	109.5
C14—C9—H9	108.7	O1—C22—H22A	110.1
C10—C9—H9	109.3	O1—C22—H22B	111.2
C12—C10—C11	118.3 (3)	H22A—C22—H22B	109.5
C12—C10—C9	104.1 (3)	O1—C22—H22C	107.0
C11—C10—C9	112.3 (3)	H22A—C22—H22C	109.5
C12—C10—H10	104.6	H22B—C22—H22C	109.5
C11—C10—H10	109.2	O3—C23—H23A	110.1
C9—C10—H10	107.8	O3—C23—H23B	110.1
C17—C11—C5	104.3 (3)	H23A—C23—H23B	109.5
C17—C11—C10	110.6 (3)	O3—C23—H23C	108.2
C5—C11—C10	107.5 (3)	H23A—C23—H23C	109.5
C17—C11—C1	114.5 (3)	H23B—C23—H23C	109.5
C5—C11—C1	110.7 (3)
C22—O1—C1—C2	78.3 (4)	C6—C5—C11—C1	−179.8 (3)
C22—O1—C1—C11	−153.6 (4)	C12—C10—C11—C17	60.3 (4)
O1—C1—C2—C3	169.7 (3)	C9—C10—C11—C17	−60.9 (4)
C11—C1—C2—C3	45.9 (4)	C12—C10—C11—C5	173.5 (3)
C1—C2—C3—C4	−52.4 (4)	C9—C10—C11—C5	52.3 (4)
C2—C3—C4—C18	−175.8 (3)	C12—C10—C11—C1	−66.4 (4)
C2—C3—C4—C19	−57.3 (4)	C9—C10—C11—C1	172.4 (3)
C2—C3—C4—C5	61.2 (4)	O1—C1—C11—C17	−53.5 (4)
C18—C4—C5—C6	53.3 (4)	C2—C1—C11—C17	70.8 (4)
C19—C4—C5—C6	−71.4 (4)	O1—C1—C11—C5	−171.0 (3)
C3—C4—C5—C6	173.6 (3)	C2—C1—C11—C5	−46.7 (4)
C18—C4—C5—C11	178.1 (3)	O1—C1—C11—C10	71.0 (4)
C19—C4—C5—C11	53.4 (4)	C2—C1—C11—C10	−164.8 (3)
C3—C4—C5—C11	−61.5 (4)	C11—C10—C12—C13	−154.6 (4)
C23—O3—C6—C7	−94.5 (4)	C9—C10—C12—C13	−29.3 (4)
C23—O3—C6—C5	143.4 (3)	C10—C12—C13—C16	170.2 (4)
C4—C5—C6—O3	−105.6 (3)	C10—C12—C13—C14	42.0 (4)
C11—C5—C6—O3	129.8 (3)	C12—C13—C14—C9	−38.0 (4)
C4—C5—C6—C7	131.4 (3)	C16—C13—C14—C9	−165.6 (4)
C11—C5—C6—C7	6.8 (4)	C7—C9—C14—C13	140.6 (4)
O3—C6—C7—O4	55.9 (4)	C10—C9—C14—C13	19.6 (4)
C5—C6—C7—O4	175.7 (3)	C19—N1—C17—C8	99.5 (4)
O3—C6—C7—C8	−178.9 (3)	C20—N1—C17—C8	−78.6 (4)
C5—C6—C7—C8	−59.1 (4)	C19—N1—C17—C11	−21.1 (5)
O3—C6—C7—C9	−63.7 (4)	C20—N1—C17—C11	160.7 (3)
C5—C6—C7—C9	56.1 (4)	C15—C8—C17—N1	80.3 (4)
O4—C7—C8—C15	−14.3 (5)	C7—C8—C17—N1	−104.7 (3)
C9—C7—C8—C15	104.9 (4)	C15—C8—C17—C11	−157.0 (3)
C6—C7—C8—C15	−139.1 (4)	C7—C8—C17—C11	18.0 (4)
O4—C7—C8—C17	170.6 (3)	C5—C11—C17—N1	51.2 (4)
C9—C7—C8—C17	−70.1 (4)	C10—C11—C17—N1	166.4 (3)
C6—C7—C8—C17	45.9 (4)	C1—C11—C17—N1	−70.0 (4)
O4—C7—C9—C14	54.3 (4)	C5—C11—C17—C8	−70.4 (3)
C8—C7—C9—C14	−67.8 (4)	C10—C11—C17—C8	44.8 (4)
C6—C7—C9—C14	176.2 (3)	C1—C11—C17—C8	168.5 (3)
O4—C7—C9—C10	174.0 (3)	C20—N1—C19—O2	−2.7 (5)
C8—C7—C9—C10	51.9 (4)	C17—N1—C19—O2	179.2 (3)
C6—C7—C9—C10	−64.2 (3)	C20—N1—C19—C4	−178.6 (3)
C7—C9—C10—C12	−120.2 (3)	C17—N1—C19—C4	3.4 (5)
C14—C9—C10—C12	5.6 (4)	C18—C4—C19—O2	39.3 (5)
C7—C9—C10—C11	8.9 (4)	C5—C4—C19—O2	165.0 (3)
C14—C9—C10—C11	134.7 (3)	C3—C4—C19—O2	−77.6 (4)
C4—C5—C11—C17	−69.8 (4)	C18—C4—C19—N1	−144.8 (3)
C6—C5—C11—C17	56.6 (4)	C5—C4—C19—N1	−19.1 (5)
C4—C5—C11—C10	172.8 (3)	C3—C4—C19—N1	98.3 (4)
C6—C5—C11—C10	−60.8 (4)	C19—N1—C20—C21	117.1 (4)
C4—C5—C11—C1	53.9 (4)	C17—N1—C20—C21	−64.6 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O2^i	0.82	2.08	2.900 (4)	177

Symmetry code: (i) −x+1, y−1/2, −z.