A pair of epimeric 13-hydroxy-2,3,6,7-tetra­methoxy-8b,11,12,12a,13,13a-hexa­hydro-9H-9a-aza­cyclo­penta­[b]tri­phenyl­ene-10-ones

The structures of two compounds which are intermediates in the synthesis of phenanthroindolizidine alkaloids have been determined. (8bS,13aS,14R,14aR)-8b,9,11,12,13,13a,14,14a-Octa­hydro-14-hydroxy-2,3,6,7-tetra­methoxy­dibenzo­[f,h]pyrrolo[1,2-b]­isoquinolin-11-one acetone solvate, C₂₄H₂₇NO₆·C₃H₆O, (II), crystallizes in a chiral space group with one solvent mol­ecule (acetone) present in the asymmetric unit. On the other hand, (8bS,13aS,14S,14aR)-8b,9,11,12,13,13a,14,14a-octa­hydro-14-hydroxy-2,3,6,7-tetra­methoxy­dibenzo­[f,h]pyrrolo[1,2-b]­isoquinolin-11-one, C₂₄H₂₇NO₆, (III), crystallizes in a centrosymmetric space group with two mol­ecules in the asymmetric unit and with no solvent present. The two mol­ecules in the asymmetric unit of (III) are structurally the same. Compounds (II) and (III) are epimers at the C atom carrying the OH group; otherwise they are very similar in structure.

S1. Comment

In a project involving the synthesis and evaluation of a number of phenanthroindolizidine alkaloids (Li et al., 2001) that are of interest as potential cancer chemotherapeutic agents, we have developed a synthetic route (Zhong et al., 2004; see scheme) to this group of alkaloids via a pair of epimeric intermediates, the title compounds, (II) and (III). Reductive ring closure of optically active (I) using free-radical chemistry (Hays & Fu, 1996, 1999) gives the intermediates (II) and (III) in an approximate 2.3:1 ratio. The key issue in this work was the determination of the relative stereochemistries for (II) and (III), as those epimers did not lend themselves to definitive NMR spectral analyses. Compound (III), with its trans H—C—C—OH arrangement which is necessary for the elimination of water, is readily converted to the 14–14a double-bonded intermediate (IV) (compound not analyzed due to instability). Reduction of the amide function and concomitant rearrangement of the double bond in (IV) produces the natural product tylophorine, which is an antitumor agent (Gao et al., 2004). Optical rotation measurements of bulk samples of (II) and (III) indicate that optical activity is maintained, to give the final product as (S)-(+)-tylophorine (Buckley & Rapoport, 1983; Norlander & Njoroge, 1987), having a single chiral center at the 13a-position. However, the crystal of (II) was obtained as a racemate (see Experimental), indicating that at least a portion of the sample had racemized during ring closure or that the starting material, (I), was partially racemized at the outset. The issue of this apparent partial racemization is presently under study. \sch

The structure of the molecule consists of a semiplanar aromatic system that is torsionally distorted, with an azacyclohexane ring in a chair configuration fused cis to atoms C14 and C17 of a dihydrophenanthrene system. The molecular structures of (II) and (III), apart from their epimeric relationship at C19, are very similar.

One major structural difference between (II) and (III) is the torsion angle between the aromatic rings, defined as the angle between the C5—C6 and C7—C8 bonds. For (II), this angle is 20.0 (3)°, whereas in (III), the corresponding value is found to be 11.0 (3)°. The torsion angles between the C14—C15 and C16—C17 bonds are 53.2 (2) and 48.18 (19)° for (II) and (III), respectively. Taken together, these values are in accord with the statistically observed relationship between these two parameters in these types of systems (Allen, 2002; Bruno et al., 2002). Given the difference in unit-cell contents and the inclusion of acetone in the structure of (II), no straightforward comparison of the torsion angles may be made, although the values are not atypical for the dihydrophenanthrenyl ring system. We note that, in the presence of acetone in the lattice, the number of intermolecular contacts is lower, and we speculate that this leads to the lower torsional value.

While the presence of a solvent of crystallization in (II) disturbs the intermolecular contacts, a direct comparison may be made between the interbond angles and lengths of the two structures. Inspection of the structures of (II) and (III) shows that all bond lengths and angles in the two structures are well within the normal reported ranges and are similar in both structures.

S2. Experimental

To a solution of (I) (2.12 g, 5.00 mmol) in dry benzene (15 ml) in a 100 ml Schlenk tube, was added bis(tributyltin)oxide [(Bu₃Sn)₂O, 0.38 ml, 0.75 mmol], PhSiH₃ (0.31 ml, 2.50 mmol), EtOH (0.585 ml, 2.00 mmol) and 2,2'-azobisisobutyronitrile (AIBN, 90 mg, 0.548 mmol) in benzene (2.0 ml). The vessel was sealed, shaken and placed in an oil bath at 353–358 K. After 12 h, thin-layer chromatography analysis indicated that all of the starting material had been consumed. The mixture was allowed to cool to room temperature, and tetrabutylammonium fluoride (30.0 ml of a 1.0 M solution in tetrahydrofuran, 30.0 mmol) was added with stirring for 2 h, at the end of which time 2 M HCl (15 ml) was added. The reaction mixture was extracted with CH₂Cl₂ (3 × 50 ml), and the combined organic extracts were dried (MgSO₄), filtered, and concentrated. The residue was purified by flash chromatography (eluting with 3:1:0.01 CH₂Cl₂–EtOAc–MeOH) to give 827 mg (69%) of compound (II) in the nonsolvated form. Analysis: [α]_D²² 78.3° (c 0.48, CHCl₃); HREIMS, calculated for C₂₄H₂₇NO₆: 425.1838; found: m/z 425.1842. Compound (III) was obtained as 30% of the final product. Analysis: [α]_D²² −104.2° (c 1.0, CHCl₃)l; HREIMS, calculated for C₂₄H₂₇NO₆: 425.1838; found: m/z 425.1842. Single crystals of (II) as the actone solvate and (III) were obtained from 2:1 acetone–MeOH solutions after partial evaporation. The crystal of (II) was shown to be a racemic mixture, a fact that indicates that either the ring closure of (I) to (II) is accompanied by racemization, or that the starting material, (I), was partially racemized.

S3. Refinement

Most H atoms were introduced at calculated positions and refined by applying a riding model [C—H = 0.93–0.98 Å and U_iso(H) = 1.2U_eq(C), and O—H = 0.82 Å and U_iso(H) = 1.5U_eq(O)]. The hydroxyl H atoms in (III) were located in the difference Fourier maps and refined with contraints on their positions and U_eq. Friedel equivalents were merged before the final refinement.

Computing details

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

Figures

	Fig. 1. A view of the structure of (II), showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms and the acetone solvate molecule have been omitted for clarity.
	Fig. 2. A view of the structure of (III), illustrating one of the two crystallographically independent molecules and showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms have been omitted for clarity.

(II) 8bS,13aS,14R,14aR)-8 b,9,11,12,13,13a,14,14a-octahydro-14-hydroxy-2,3,6,7- tetramethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-11-one acetone solvate

Crystal data

C24H27NO6·C3H6O	F(000) = 1032
Mr = 483.54	Dx = 1.304 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3948 reflections
a = 11.579 (1) Å	θ = 2.2–22.1°
b = 17.4011 (15) Å	µ = 0.09 mm^−1
c = 13.0453 (11) Å	T = 295 K
β = 110.488 (2)°	Block, colorless
V = 2462.2 (4) Å^3	0.50 × 0.20 × 0.15 mm
Z = 4

Data collection

Bruker SMART 1000 CCD area-detector diffractometer	5059 independent reflections
Radiation source: fine-focus sealed tube	2927 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.053
Detector resolution: not measured pixels mm^-1	θmax = 26.4°, θmin = 1.9°
ϕ and ω scans	h = −14→14
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −21→21
Tmin = 0.881, Tmax = 0.986	l = −16→16
24264 measured reflections

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)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.127	H-atom parameters constrained
S = 1.01	w = 1/[σ^2(Fo^2) + (0.0429P)^2 + 0.9647P] where P = (Fo^2 + 2Fc^2)/3
5059 reflections	(Δ/σ)max < 0.001
323 parameters	Δρmax = 0.18 e Å^−3
0 restraints	Δρmin = −0.19 e Å^−3

Special details

Experimental. Data were collected using a Bruker AXS SMART 1000 diffractometer equipped with a CCD area detector and graphite monochromated Mo source. Data were measured using phi–omega scans of 0.3 degrees with an integration time of 20 s. A total of 2424 frames were collected, with the initial 606 frames recollected in the final run.

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
C1	0.1543 (2)	−0.01425 (14)	0.10333 (19)	0.0604 (7)
H1A	0.0819	0.0165	0.0914	0.091*
H1B	0.1309	−0.0630	0.0677	0.091*
H1C	0.2089	0.0116	0.0738	0.091*
C2	0.3529 (2)	−0.06856 (13)	0.53935 (19)	0.0512 (6)
H2A	0.4352	−0.0490	0.5721	0.077*
H2B	0.3532	−0.1231	0.5501	0.077*
H2C	0.3003	−0.0447	0.5729	0.077*
C3	0.25460 (19)	0.03781 (12)	0.28201 (17)	0.0406 (5)
C4	0.30507 (19)	0.02331 (12)	0.39474 (18)	0.0405 (5)
C5	0.34822 (19)	0.08446 (12)	0.46480 (18)	0.0400 (5)
H5A	0.3797	0.0754	0.5398	0.048*
C6	0.34609 (17)	0.15991 (11)	0.42657 (16)	0.0338 (5)
C7	0.40326 (18)	0.22438 (12)	0.50131 (16)	0.0351 (5)
C8	0.49298 (19)	0.21275 (13)	0.60472 (17)	0.0413 (5)
H8	0.5175	0.1629	0.6280	0.050*
C9	0.54587 (19)	0.27339 (13)	0.67293 (17)	0.0427 (5)
C10	0.6539 (2)	0.19243 (15)	0.8237 (2)	0.0653 (7)
H10A	0.5795	0.1747	0.8328	0.098*
H10B	0.7186	0.1952	0.8939	0.098*
H10C	0.6771	0.1574	0.7775	0.098*
C11	0.5103 (2)	0.34864 (13)	0.63814 (18)	0.0438 (6)
C12	0.5331 (3)	0.48237 (14)	0.6793 (2)	0.0772 (9)
H12A	0.5465	0.4939	0.6123	0.116*
H12B	0.5812	0.5166	0.7358	0.116*
H12C	0.4473	0.4886	0.6686	0.116*
C13	0.42294 (19)	0.36036 (12)	0.53622 (17)	0.0412 (5)
H13	0.3992	0.4104	0.5131	0.049*
C14	0.36895 (18)	0.29957 (12)	0.46665 (17)	0.0366 (5)
C15	0.27294 (18)	0.31329 (11)	0.35567 (16)	0.0346 (5)
H15	0.2857	0.3651	0.3320	0.041*
C16	0.28947 (18)	0.25572 (11)	0.27239 (16)	0.0348 (5)
H16	0.3706	0.2657	0.2673	0.042*
C17	0.29183 (18)	0.17365 (11)	0.31445 (16)	0.0337 (5)
C18	0.24728 (19)	0.11188 (12)	0.24380 (18)	0.0391 (5)
H18	0.2118	0.1210	0.1690	0.047*
C19	0.14134 (18)	0.30933 (11)	0.35750 (16)	0.0352 (5)
H19	0.1276	0.2586	0.3838	0.042*
C20	0.04680 (19)	0.32278 (12)	0.24428 (17)	0.0389 (5)
H20	0.0522	0.3762	0.2226	0.047*
C21	0.19377 (18)	0.27097 (12)	0.15938 (17)	0.0388 (5)
H21A	0.2101	0.3203	0.1325	0.047*
H21B	0.1994	0.2315	0.1088	0.047*
C22	−0.08685 (19)	0.30454 (14)	0.23165 (19)	0.0503 (6)
H22A	−0.0900	0.2715	0.2905	0.060*
H22B	−0.1322	0.3513	0.2320	0.060*
C23	−0.1396 (2)	0.26412 (15)	0.1227 (2)	0.0546 (6)
H23A	−0.1898	0.2207	0.1279	0.066*
H23B	−0.1900	0.2990	0.0670	0.066*
C24	−0.0301 (2)	0.23760 (13)	0.09567 (18)	0.0412 (5)
C25	0.1146 (5)	0.5531 (2)	0.2920 (4)	0.160 (2)
H25A	0.1791	0.5893	0.3264	0.240*
H25B	0.1333	0.5050	0.3302	0.240*
H25C	0.0378	0.5724	0.2940	0.240*
C26	0.1050 (3)	0.54174 (18)	0.1774 (4)	0.0904 (11)
C27	0.0418 (5)	0.6002 (2)	0.0957 (4)	0.165 (2)
H27A	0.0305	0.5811	0.0238	0.248*
H27B	0.0907	0.6461	0.1089	0.248*
H27C	−0.0370	0.6114	0.1010	0.248*
N	0.07057 (15)	0.27108 (9)	0.16496 (13)	0.0360 (4)
O1	0.21508 (16)	−0.02587 (8)	0.21755 (12)	0.0577 (5)
O2	0.30827 (16)	−0.05203 (8)	0.42513 (13)	0.0558 (5)
O3	0.63375 (15)	0.26620 (10)	0.77504 (13)	0.0601 (5)
O4	0.56892 (16)	0.40553 (9)	0.71030 (13)	0.0609 (5)
O5	0.12789 (14)	0.36661 (8)	0.43017 (12)	0.0469 (4)
H5	0.0795	0.3515	0.4591	0.070*
O6	−0.03307 (14)	0.19344 (10)	0.02046 (13)	0.0567 (5)
O7	0.1535 (2)	0.48566 (13)	0.1545 (2)	0.1023 (8)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0808 (18)	0.0475 (15)	0.0347 (14)	−0.0087 (13)	−0.0026 (13)	−0.0083 (12)
C2	0.0604 (15)	0.0434 (14)	0.0397 (14)	−0.0048 (11)	0.0052 (11)	0.0065 (11)
C3	0.0467 (12)	0.0346 (12)	0.0330 (13)	−0.0027 (10)	0.0046 (10)	−0.0061 (10)
C4	0.0456 (12)	0.0326 (12)	0.0367 (13)	−0.0003 (9)	0.0060 (10)	−0.0007 (10)
C5	0.0449 (12)	0.0408 (13)	0.0286 (12)	−0.0009 (10)	0.0057 (10)	−0.0001 (10)
C6	0.0346 (11)	0.0351 (12)	0.0292 (11)	−0.0002 (9)	0.0081 (9)	−0.0016 (9)
C7	0.0368 (11)	0.0372 (12)	0.0297 (12)	−0.0037 (9)	0.0095 (9)	−0.0042 (9)
C8	0.0441 (12)	0.0390 (12)	0.0358 (13)	0.0013 (10)	0.0076 (10)	−0.0035 (10)
C9	0.0423 (12)	0.0489 (14)	0.0311 (13)	−0.0043 (10)	0.0055 (10)	−0.0044 (11)
C10	0.0575 (16)	0.0692 (19)	0.0519 (17)	0.0082 (14)	−0.0024 (13)	0.0051 (14)
C11	0.0489 (13)	0.0421 (14)	0.0350 (13)	−0.0129 (10)	0.0079 (11)	−0.0098 (11)
C12	0.107 (2)	0.0448 (16)	0.0533 (18)	−0.0236 (16)	−0.0050 (16)	−0.0075 (14)
C13	0.0513 (13)	0.0341 (12)	0.0335 (13)	−0.0089 (10)	0.0089 (11)	−0.0031 (10)
C14	0.0391 (11)	0.0369 (12)	0.0322 (12)	−0.0068 (9)	0.0106 (9)	−0.0027 (10)
C15	0.0431 (11)	0.0285 (11)	0.0294 (11)	−0.0066 (9)	0.0093 (9)	−0.0002 (9)
C16	0.0373 (11)	0.0370 (12)	0.0304 (12)	−0.0054 (9)	0.0119 (9)	−0.0020 (9)
C17	0.0353 (11)	0.0344 (11)	0.0308 (12)	−0.0002 (9)	0.0110 (9)	−0.0028 (9)
C18	0.0449 (12)	0.0377 (13)	0.0294 (12)	−0.0004 (10)	0.0063 (10)	−0.0016 (10)
C19	0.0469 (12)	0.0276 (11)	0.0303 (11)	−0.0015 (9)	0.0126 (10)	−0.0038 (9)
C20	0.0499 (13)	0.0302 (11)	0.0331 (12)	0.0036 (10)	0.0101 (10)	−0.0008 (9)
C21	0.0481 (12)	0.0372 (12)	0.0330 (12)	−0.0059 (10)	0.0165 (10)	0.0001 (10)
C22	0.0441 (13)	0.0568 (15)	0.0456 (15)	0.0105 (11)	0.0101 (11)	−0.0059 (12)
C23	0.0444 (13)	0.0637 (16)	0.0489 (16)	0.0054 (12)	0.0077 (11)	−0.0059 (13)
C24	0.0449 (12)	0.0409 (13)	0.0323 (12)	−0.0007 (10)	0.0068 (10)	−0.0003 (10)
C25	0.259 (7)	0.102 (3)	0.179 (5)	0.000 (4)	0.153 (5)	−0.019 (3)
C26	0.107 (3)	0.0481 (19)	0.142 (4)	−0.0124 (18)	0.076 (3)	−0.006 (2)
C27	0.202 (5)	0.086 (3)	0.188 (5)	0.040 (3)	0.045 (4)	0.024 (3)
N	0.0396 (9)	0.0365 (10)	0.0287 (10)	−0.0002 (8)	0.0080 (8)	−0.0026 (8)
O1	0.0873 (12)	0.0353 (9)	0.0343 (9)	−0.0065 (8)	0.0007 (9)	−0.0053 (7)
O2	0.0818 (12)	0.0342 (9)	0.0374 (10)	−0.0036 (8)	0.0034 (8)	0.0026 (7)
O3	0.0640 (10)	0.0525 (11)	0.0411 (10)	−0.0007 (8)	−0.0100 (8)	−0.0071 (8)
O4	0.0797 (12)	0.0420 (10)	0.0419 (10)	−0.0156 (8)	−0.0026 (9)	−0.0095 (8)
O5	0.0600 (10)	0.0427 (9)	0.0401 (10)	0.0009 (7)	0.0201 (8)	−0.0106 (7)
O6	0.0571 (10)	0.0644 (11)	0.0458 (10)	−0.0092 (8)	0.0145 (8)	−0.0221 (9)
O7	0.138 (2)	0.0604 (14)	0.139 (2)	0.0010 (14)	0.0865 (18)	0.0021 (14)

Geometric parameters (Å, º)

C1—O1	1.422 (3)	C15—C19	1.534 (3)
C1—H1A	0.9600	C15—C16	1.538 (3)
C1—H1B	0.9600	C15—H15	0.9800
C1—H1C	0.9600	C16—C21	1.526 (3)
C2—O2	1.425 (3)	C16—C17	1.527 (3)
C2—H2A	0.9600	C16—H16	0.9800
C2—H2B	0.9600	C17—C18	1.392 (3)
C2—H2C	0.9600	C18—H18	0.9300
C3—O1	1.369 (2)	C19—O5	1.421 (2)
C3—C18	1.374 (3)	C19—C20	1.517 (3)
C3—C4	1.402 (3)	C19—H19	0.9800
C4—O2	1.366 (2)	C20—N	1.468 (3)
C4—C5	1.377 (3)	C20—C22	1.531 (3)
C5—C6	1.402 (3)	C20—H20	0.9800
C5—H5A	0.9300	C21—N	1.454 (3)
C6—C17	1.396 (3)	C21—H21A	0.9700
C6—C7	1.482 (3)	C21—H21B	0.9700
C7—C14	1.396 (3)	C22—C23	1.510 (3)
C7—C8	1.400 (3)	C22—H22A	0.9700
C8—C9	1.378 (3)	C22—H22B	0.9700
C8—H8	0.9300	C23—C24	1.503 (3)
C9—O3	1.370 (2)	C23—H23A	0.9700
C9—C11	1.400 (3)	C23—H23B	0.9700
C10—O3	1.415 (3)	C24—O6	1.237 (2)
C10—H10A	0.9600	C24—N	1.333 (3)
C10—H10B	0.9600	C25—C26	1.473 (5)
C10—H10C	0.9600	C25—H25A	0.9600
C11—O4	1.371 (2)	C25—H25B	0.9600
C11—C13	1.375 (3)	C25—H25C	0.9600
C12—O4	1.416 (3)	C26—O7	1.214 (3)
C12—H12A	0.9600	C26—C27	1.469 (5)
C12—H12B	0.9600	C27—H27A	0.9600
C12—H12C	0.9600	C27—H27B	0.9600
C13—C14	1.392 (3)	C27—H27C	0.9600
C13—H13	0.9300	O5—H5	0.8200
C14—C15	1.504 (3)
O1—C1—H1A	109.5	C17—C16—H16	107.0
O1—C1—H1B	109.5	C15—C16—H16	107.0
H1A—C1—H1B	109.5	C18—C17—C6	119.22 (19)
O1—C1—H1C	109.5	C18—C17—C16	121.90 (18)
H1A—C1—H1C	109.5	C6—C17—C16	118.80 (17)
H1B—C1—H1C	109.5	C3—C18—C17	121.5 (2)
O2—C2—H2A	109.5	C3—C18—H18	119.2
O2—C2—H2B	109.5	C17—C18—H18	119.2
H2A—C2—H2B	109.5	O5—C19—C20	109.32 (16)
O2—C2—H2C	109.5	O5—C19—C15	108.68 (16)
H2A—C2—H2C	109.5	C20—C19—C15	111.11 (17)
H2B—C2—H2C	109.5	O5—C19—H19	109.2
O1—C3—C18	124.86 (19)	C20—C19—H19	109.2
O1—C3—C4	115.18 (19)	C15—C19—H19	109.2
C18—C3—C4	119.96 (19)	N—C20—C19	110.01 (16)
O2—C4—C5	125.6 (2)	N—C20—C22	103.23 (16)
O2—C4—C3	115.85 (18)	C19—C20—C22	115.49 (18)
C5—C4—C3	118.6 (2)	N—C20—H20	109.3
C4—C5—C6	122.0 (2)	C19—C20—H20	109.3
C4—C5—H5A	119.0	C22—C20—H20	109.3
C6—C5—H5A	119.0	N—C21—C16	110.20 (16)
C17—C6—C5	118.61 (18)	N—C21—H21A	109.6
C17—C6—C7	119.57 (18)	C16—C21—H21A	109.6
C5—C6—C7	121.80 (18)	N—C21—H21B	109.6
C14—C7—C8	118.61 (19)	C16—C21—H21B	109.6
C14—C7—C6	119.05 (18)	H21A—C21—H21B	108.1
C8—C7—C6	122.32 (19)	C23—C22—C20	104.98 (18)
C9—C8—C7	121.6 (2)	C23—C22—H22A	110.8
C9—C8—H8	119.2	C20—C22—H22A	110.8
C7—C8—H8	119.2	C23—C22—H22B	110.8
O3—C9—C8	124.7 (2)	C20—C22—H22B	110.8
O3—C9—C11	115.77 (19)	H22A—C22—H22B	108.8
C8—C9—C11	119.56 (19)	C24—C23—C22	105.53 (18)
O3—C10—H10A	109.5	C24—C23—H23A	110.6
O3—C10—H10B	109.5	C22—C23—H23A	110.6
H10A—C10—H10B	109.5	C24—C23—H23B	110.6
O3—C10—H10C	109.5	C22—C23—H23B	110.6
H10A—C10—H10C	109.5	H23A—C23—H23B	108.8
H10B—C10—H10C	109.5	O6—C24—N	125.7 (2)
O4—C11—C13	125.2 (2)	O6—C24—C23	125.8 (2)
O4—C11—C9	115.74 (19)	N—C24—C23	108.40 (19)
C13—C11—C9	119.04 (19)	C26—C25—H25A	109.5
O4—C12—H12A	109.5	C26—C25—H25B	109.5
O4—C12—H12B	109.5	H25A—C25—H25B	109.5
H12A—C12—H12B	109.5	C26—C25—H25C	109.5
O4—C12—H12C	109.5	H25A—C25—H25C	109.5
H12A—C12—H12C	109.5	H25B—C25—H25C	109.5
H12B—C12—H12C	109.5	O7—C26—C27	122.2 (4)
C11—C13—C14	121.9 (2)	O7—C26—C25	118.7 (4)
C11—C13—H13	119.1	C27—C26—C25	119.0 (4)
C14—C13—H13	119.1	C26—C27—H27A	109.5
C13—C14—C7	119.30 (19)	C26—C27—H27B	109.5
C13—C14—C15	121.27 (19)	H27A—C27—H27B	109.5
C7—C14—C15	119.42 (18)	C26—C27—H27C	109.5
C14—C15—C19	112.42 (17)	H27A—C27—H27C	109.5
C14—C15—C16	110.11 (17)	H27B—C27—H27C	109.5
C19—C15—C16	110.59 (16)	C24—N—C21	127.29 (18)
C14—C15—H15	107.9	C24—N—C20	114.24 (17)
C19—C15—H15	107.9	C21—N—C20	117.74 (16)
C16—C15—H15	107.9	C3—O1—C1	117.70 (17)
C21—C16—C17	115.18 (16)	C4—O2—C2	117.39 (17)
C21—C16—C15	109.96 (17)	C9—O3—C10	117.96 (18)
C17—C16—C15	110.27 (16)	C11—O4—C12	117.41 (18)
C21—C16—H16	107.0	C19—O5—H5	109.5
O1—C3—C4—O2	0.1 (3)	C15—C16—C17—C18	148.42 (19)
C18—C3—C4—O2	179.8 (2)	C21—C16—C17—C6	−160.10 (17)
O1—C3—C4—C5	179.2 (2)	C15—C16—C17—C6	−34.9 (2)
C18—C3—C4—C5	−1.0 (3)	O1—C3—C18—C17	−178.7 (2)
O2—C4—C5—C6	177.3 (2)	C4—C3—C18—C17	1.6 (3)
C3—C4—C5—C6	−1.7 (3)	C6—C17—C18—C3	0.5 (3)
C4—C5—C6—C17	3.8 (3)	C16—C17—C18—C3	177.16 (19)
C4—C5—C6—C7	−174.10 (19)	C14—C15—C19—O5	60.1 (2)
C17—C6—C7—C14	20.5 (3)	C16—C15—C19—O5	−176.37 (16)
C5—C6—C7—C14	−161.60 (19)	C14—C15—C19—C20	−179.56 (16)
C17—C6—C7—C8	−157.90 (19)	C16—C15—C19—C20	−56.0 (2)
C5—C6—C7—C8	20.0 (3)	O5—C19—C20—N	172.00 (16)
C14—C7—C8—C9	1.1 (3)	C15—C19—C20—N	52.1 (2)
C6—C7—C8—C9	179.53 (19)	O5—C19—C20—C22	−71.7 (2)
C7—C8—C9—O3	179.8 (2)	C15—C19—C20—C22	168.38 (17)
C7—C8—C9—C11	−0.6 (3)	C17—C16—C21—N	71.5 (2)
O3—C9—C11—O4	0.6 (3)	C15—C16—C21—N	−53.8 (2)
C8—C9—C11—O4	−179.0 (2)	N—C20—C22—C23	−18.0 (2)
O3—C9—C11—C13	179.7 (2)	C19—C20—C22—C23	−138.13 (19)
C8—C9—C11—C13	0.1 (3)	C20—C22—C23—C24	18.2 (2)
O4—C11—C13—C14	178.9 (2)	C22—C23—C24—O6	169.8 (2)
C9—C11—C13—C14	−0.1 (3)	C22—C23—C24—N	−11.5 (3)
C11—C13—C14—C7	0.6 (3)	O6—C24—N—C21	8.2 (4)
C11—C13—C14—C15	179.64 (19)	C23—C24—N—C21	−170.40 (19)
C8—C7—C14—C13	−1.1 (3)	O6—C24—N—C20	178.2 (2)
C6—C7—C14—C13	−179.58 (19)	C23—C24—N—C20	−0.5 (2)
C8—C7—C14—C15	179.84 (18)	C16—C21—N—C24	−136.0 (2)
C6—C7—C14—C15	1.4 (3)	C16—C21—N—C20	54.4 (2)
C13—C14—C15—C19	−93.5 (2)	C19—C20—N—C24	135.74 (19)
C7—C14—C15—C19	85.5 (2)	C22—C20—N—C24	12.0 (2)
C13—C14—C15—C16	142.73 (19)	C19—C20—N—C21	−53.3 (2)
C7—C14—C15—C16	−38.3 (2)	C22—C20—N—C21	−177.09 (17)
C14—C15—C16—C21	−178.73 (16)	C18—C3—O1—C1	−4.6 (3)
C19—C15—C16—C21	56.4 (2)	C4—C3—O1—C1	175.2 (2)
C14—C15—C16—C17	53.2 (2)	C5—C4—O2—C2	4.2 (3)
C19—C15—C16—C17	−71.7 (2)	C3—C4—O2—C2	−176.73 (19)
C5—C6—C17—C18	−3.2 (3)	C8—C9—O3—C10	−13.8 (3)
C7—C6—C17—C18	174.81 (18)	C11—C9—O3—C10	166.7 (2)
C5—C6—C17—C16	−179.90 (18)	C13—C11—O4—C12	2.7 (4)
C7—C6—C17—C16	−1.9 (3)	C9—C11—O4—C12	−178.3 (2)
C21—C16—C17—C18	23.3 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···O6^i	0.82	1.92	2.737 (2)	Angle

Symmetry code: (i) x, −y+1/2, z+1/2.

(III) (8bS,13aS,14S,14aR)-8 b,9,11,12,13,13a,14,14a-octahydro-14-hydroxy-2,3,6,7- tetramethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-11-one

Crystal data

C24H27NO6	F(000) = 1808
Mr = 425.47	Dx = 1.355 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 8864 reflections
a = 13.0534 (16) Å	θ = 2.3–25.0°
b = 14.9664 (18) Å	µ = 0.10 mm^−1
c = 21.356 (3) Å	T = 293 K
V = 4172.1 (9) Å^3	Fragment, colorless
Z = 8	0.50 × 0.42 × 0.40 mm

Data collection

Bruker SMART 1000 CCD area-detector diffractometer	5663 independent reflections
Radiation source: fine-focus sealed tube	4458 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.035
Detector resolution: not measured pixels mm^-1	θmax = 28.3°, θmin = 1.7°
ϕ and ω scans	h = −17→17
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −19→19
Tmin = 0.953, Tmax = 0.962	l = −27→28
45934 measured reflections

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)] = 0.033	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.086	H-atom parameters constrained
S = 0.98	w = 1/[σ^2(Fo^2) + (0.0549P)^2] where P = (Fo^2 + 2Fc^2)/3
5663 reflections	(Δ/σ)max < 0.001
567 parameters	Δρmax = 0.19 e Å^−3
0 restraints	Δρmin = −0.18 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
C1	−0.38698 (16)	0.6461 (2)	0.10355 (14)	0.0729 (8)
H1A	−0.3781	0.6981	0.1293	0.109*
H1B	−0.4513	0.6183	0.1132	0.109*
H1C	−0.3861	0.6634	0.0603	0.109*
C2	−0.08087 (18)	0.40862 (17)	0.14478 (11)	0.0581 (6)
H2A	−0.0294	0.4047	0.1128	0.087*
H2B	−0.1106	0.3507	0.1514	0.087*
H2C	−0.0503	0.4292	0.1830	0.087*
C3	−0.20793 (13)	0.61648 (16)	0.10554 (9)	0.0450 (5)
C4	−0.12901 (15)	0.55531 (14)	0.11359 (10)	0.0457 (5)
C5	−0.02846 (14)	0.58458 (14)	0.10897 (9)	0.0410 (4)
H5	0.0246	0.5445	0.1162	0.049*
C6	−0.00527 (13)	0.67289 (13)	0.09364 (8)	0.0361 (4)
C7	0.10248 (13)	0.70448 (13)	0.08994 (8)	0.0338 (4)
C8	0.18466 (13)	0.64392 (13)	0.09112 (8)	0.0357 (4)
H8	0.1711	0.5829	0.0917	0.043*
C9	0.28480 (13)	0.67271 (13)	0.09138 (8)	0.0335 (4)
C10	0.35058 (15)	0.52462 (14)	0.10445 (10)	0.0468 (5)
H10A	0.3115	0.5169	0.1421	0.070*
H10B	0.4149	0.4941	0.1084	0.070*
H10C	0.3132	0.5004	0.0696	0.070*
C11	0.30628 (13)	0.76456 (13)	0.08704 (8)	0.0351 (4)
C12	0.43643 (15)	0.87549 (15)	0.07236 (11)	0.0503 (5)
H12A	0.4059	0.8924	0.0332	0.075*
H12B	0.5096	0.8799	0.0691	0.075*
H12C	0.4125	0.9146	0.1049	0.075*
C13	0.22633 (14)	0.82430 (13)	0.08444 (8)	0.0368 (4)
H13	0.2404	0.8851	0.0813	0.044*
C14	0.12380 (13)	0.79549 (13)	0.08639 (8)	0.0346 (4)
C15	0.03773 (13)	0.86356 (13)	0.08722 (8)	0.0364 (4)
H15	0.0598	0.9136	0.0609	0.044*
C16	−0.05984 (13)	0.82460 (14)	0.05676 (8)	0.0379 (4)
H16	−0.0439	0.8168	0.0122	0.046*
C17	−0.08515 (13)	0.73258 (14)	0.08162 (8)	0.0374 (4)
C18	−0.18580 (14)	0.70331 (15)	0.08866 (9)	0.0429 (4)
H18	−0.2393	0.7432	0.0818	0.051*
C19	0.01858 (13)	0.90181 (13)	0.15334 (9)	0.0377 (4)
H19	0.0796	0.9352	0.1663	0.045*
C20	−0.07248 (15)	0.96574 (14)	0.15272 (10)	0.0440 (5)
H20	−0.0539	1.0194	0.1290	0.053*
C21	−0.14634 (15)	0.89314 (15)	0.05988 (9)	0.0439 (5)
H21A	−0.1301	0.9435	0.0330	0.053*
H21B	−0.2093	0.8663	0.0448	0.053*
C22	−0.11493 (17)	0.99393 (18)	0.21682 (11)	0.0600 (6)
H22A	−0.0661	0.9805	0.2498	0.072*
H22B	−0.1296	1.0575	0.2175	0.072*
C23	−0.2124 (2)	0.94022 (18)	0.22547 (11)	0.0631 (6)
H23A	−0.2008	0.8906	0.2538	0.076*
H23B	−0.2665	0.9775	0.2423	0.076*
C24	−0.24051 (16)	0.90671 (15)	0.16120 (10)	0.0503 (5)
C25	0.12520 (18)	0.6868 (2)	0.44443 (15)	0.0762 (8)
H25A	0.1520	0.7465	0.4456	0.114*
H25B	0.0614	0.6847	0.4668	0.114*
H25C	0.1141	0.6693	0.4017	0.114*
C26	0.3180 (2)	0.66777 (19)	0.58921 (12)	0.0718 (7)
H26A	0.3681	0.7144	0.5853	0.108*
H26B	0.3104	0.6521	0.6325	0.108*
H26C	0.2536	0.6883	0.5731	0.108*
C27	0.29411 (15)	0.62605 (14)	0.44984 (10)	0.0460 (5)
C28	0.37175 (15)	0.60827 (14)	0.49247 (10)	0.0438 (5)
C29	0.47152 (15)	0.60509 (14)	0.47247 (9)	0.0424 (4)
H29	0.5228	0.5941	0.5017	0.051*
C30	0.49892 (14)	0.61766 (13)	0.41009 (9)	0.0386 (4)
C31	0.60741 (14)	0.61966 (13)	0.38919 (9)	0.0379 (4)
C32	0.68862 (15)	0.59450 (14)	0.42873 (9)	0.0413 (4)
H32	0.6739	0.5725	0.4684	0.050*
C33	0.78939 (14)	0.60151 (13)	0.41027 (9)	0.0410 (4)
C34	0.8546 (2)	0.5721 (3)	0.51190 (12)	0.0870 (10)
H34A	0.8167	0.6224	0.5275	0.130*
H34B	0.9190	0.5682	0.5334	0.130*
H34C	0.8161	0.5184	0.5189	0.130*
C35	0.81271 (14)	0.63127 (14)	0.34954 (10)	0.0421 (4)
C36	0.93900 (18)	0.6768 (2)	0.27640 (13)	0.0731 (8)
H36A	0.9139	0.6402	0.2428	0.110*
H36B	1.0120	0.6827	0.2729	0.110*
H36C	0.9079	0.7349	0.2741	0.110*
C37	0.73366 (15)	0.65526 (14)	0.31023 (9)	0.0444 (5)
H37	0.7486	0.6746	0.2699	0.053*
C38	0.63171 (14)	0.65119 (14)	0.32969 (8)	0.0412 (4)
C39	0.54856 (14)	0.68634 (15)	0.28707 (9)	0.0455 (5)
H39	0.5706	0.6741	0.2441	0.055*
C40	0.44783 (14)	0.63474 (14)	0.29714 (9)	0.0419 (4)
H40	0.4616	0.5728	0.2849	0.050*
C41	0.41947 (14)	0.63212 (13)	0.36641 (9)	0.0385 (4)
C42	0.31890 (15)	0.63767 (14)	0.38729 (10)	0.0455 (5)
H42	0.2670	0.6495	0.3586	0.055*
C43	0.53451 (16)	0.78797 (15)	0.29227 (10)	0.0498 (5)
H43	0.5988	0.8156	0.2787	0.060*
C44	0.45112 (16)	0.81881 (16)	0.24687 (11)	0.0523 (5)
H44	0.4756	0.8111	0.2038	0.063*
C45	0.36677 (16)	0.66932 (14)	0.25197 (10)	0.0469 (5)
H45A	0.3847	0.6522	0.2096	0.056*
H45B	0.3011	0.6426	0.2620	0.056*
C46	0.4113 (2)	0.91385 (18)	0.25493 (15)	0.0728 (8)
H46A	0.4259	0.9358	0.2968	0.087*
H46B	0.4429	0.9536	0.2247	0.087*
C47	0.29618 (18)	0.90797 (16)	0.24401 (12)	0.0595 (6)
H47A	0.2593	0.9432	0.2748	0.071*
H47B	0.2786	0.9293	0.2025	0.071*
C48	0.27091 (16)	0.81063 (15)	0.25066 (9)	0.0458 (5)
N1	−0.16062 (12)	0.92395 (12)	0.12327 (7)	0.0421 (4)
N2	0.35887 (12)	0.76510 (12)	0.25583 (7)	0.0439 (4)
O1	−0.30562 (11)	0.58452 (12)	0.11522 (8)	0.0637 (5)
O2	−0.15729 (11)	0.46877 (11)	0.12600 (9)	0.0654 (5)
O3	0.36857 (9)	0.61711 (9)	0.09430 (6)	0.0390 (3)
O4	0.40874 (9)	0.78597 (9)	0.08694 (7)	0.0435 (3)
O5	−0.00081 (10)	0.83453 (9)	0.19847 (6)	0.0439 (3)
H5A	0.0536	0.8174	0.2135	0.050*
O6	−0.32067 (13)	0.87013 (14)	0.14628 (10)	0.0756 (5)
O7	0.19539 (11)	0.62821 (13)	0.47251 (8)	0.0686 (5)
O8	0.35066 (11)	0.59153 (10)	0.55475 (7)	0.0510 (4)
O9	0.87204 (10)	0.58299 (12)	0.44724 (7)	0.0546 (4)
O10	0.91417 (10)	0.63643 (11)	0.33464 (7)	0.0543 (4)
O11	0.51549 (13)	0.81767 (11)	0.35438 (7)	0.0601 (4)
H11	0.4692	0.7879	0.3698	0.050*
O12	0.18543 (11)	0.77607 (11)	0.25114 (7)	0.0575 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0214 (10)	0.099 (2)	0.0983 (19)	−0.0018 (12)	0.0010 (11)	−0.0131 (17)
C2	0.0551 (14)	0.0567 (14)	0.0627 (13)	−0.0126 (12)	0.0038 (11)	0.0094 (11)
C3	0.0212 (9)	0.0612 (14)	0.0528 (11)	−0.0070 (9)	0.0000 (8)	−0.0084 (10)
C4	0.0323 (10)	0.0492 (12)	0.0555 (11)	−0.0088 (9)	−0.0001 (9)	0.0017 (9)
C5	0.0250 (9)	0.0452 (11)	0.0528 (10)	−0.0002 (8)	−0.0001 (8)	0.0026 (9)
C6	0.0226 (8)	0.0457 (11)	0.0400 (9)	−0.0020 (8)	−0.0008 (7)	−0.0008 (8)
C7	0.0236 (8)	0.0413 (10)	0.0366 (8)	−0.0006 (7)	0.0007 (7)	0.0014 (8)
C8	0.0251 (8)	0.0384 (10)	0.0434 (9)	−0.0020 (7)	0.0018 (7)	0.0006 (8)
C9	0.0246 (8)	0.0418 (10)	0.0341 (8)	0.0016 (7)	0.0004 (7)	−0.0007 (8)
C10	0.0360 (10)	0.0439 (12)	0.0607 (12)	0.0031 (9)	−0.0007 (9)	0.0026 (9)
C11	0.0223 (8)	0.0459 (11)	0.0372 (8)	−0.0047 (7)	0.0026 (7)	−0.0024 (8)
C12	0.0330 (10)	0.0484 (12)	0.0696 (13)	−0.0100 (9)	0.0052 (9)	0.0019 (10)
C13	0.0303 (9)	0.0362 (10)	0.0438 (9)	−0.0045 (8)	0.0030 (8)	0.0008 (8)
C14	0.0247 (8)	0.0423 (10)	0.0367 (8)	0.0013 (7)	0.0027 (7)	0.0026 (8)
C15	0.0266 (9)	0.0399 (10)	0.0429 (9)	0.0019 (8)	0.0010 (7)	0.0070 (8)
C16	0.0279 (9)	0.0493 (11)	0.0365 (8)	0.0064 (8)	−0.0011 (7)	0.0008 (8)
C17	0.0270 (9)	0.0485 (11)	0.0368 (8)	0.0014 (8)	−0.0022 (7)	−0.0036 (8)
C18	0.0249 (9)	0.0546 (13)	0.0492 (10)	0.0027 (9)	−0.0039 (8)	−0.0065 (10)
C19	0.0258 (9)	0.0397 (10)	0.0476 (10)	0.0006 (8)	−0.0039 (7)	−0.0006 (8)
C20	0.0341 (10)	0.0425 (11)	0.0554 (11)	0.0045 (9)	−0.0056 (9)	−0.0018 (9)
C21	0.0337 (10)	0.0547 (13)	0.0434 (10)	0.0090 (9)	−0.0082 (8)	0.0034 (9)
C22	0.0467 (13)	0.0686 (16)	0.0649 (13)	0.0168 (12)	−0.0095 (11)	−0.0198 (12)
C23	0.0658 (16)	0.0648 (16)	0.0587 (13)	0.0116 (13)	0.0137 (12)	−0.0065 (11)
C24	0.0375 (11)	0.0511 (13)	0.0622 (12)	0.0091 (10)	0.0049 (9)	−0.0051 (10)
C25	0.0385 (13)	0.086 (2)	0.105 (2)	0.0141 (13)	0.0020 (14)	0.0031 (17)
C26	0.0776 (18)	0.0694 (17)	0.0683 (15)	0.0112 (15)	0.0131 (14)	−0.0075 (14)
C27	0.0317 (10)	0.0430 (11)	0.0635 (12)	−0.0003 (9)	0.0077 (9)	0.0036 (10)
C28	0.0401 (11)	0.0385 (11)	0.0527 (11)	−0.0022 (9)	0.0077 (9)	0.0049 (9)
C29	0.0340 (10)	0.0449 (12)	0.0484 (10)	−0.0002 (9)	−0.0003 (8)	0.0043 (8)
C30	0.0311 (9)	0.0379 (10)	0.0468 (10)	0.0006 (8)	0.0004 (8)	0.0019 (8)
C31	0.0301 (9)	0.0401 (11)	0.0435 (9)	0.0015 (8)	0.0014 (7)	0.0000 (8)
C32	0.0335 (10)	0.0455 (11)	0.0449 (10)	0.0006 (9)	0.0004 (8)	0.0075 (8)
C33	0.0327 (10)	0.0390 (10)	0.0515 (10)	0.0033 (8)	−0.0026 (8)	0.0061 (9)
C34	0.0557 (15)	0.148 (3)	0.0571 (14)	0.0225 (18)	−0.0097 (12)	0.0239 (17)
C35	0.0315 (10)	0.0406 (11)	0.0542 (11)	0.0028 (8)	0.0055 (8)	0.0033 (9)
C36	0.0428 (13)	0.099 (2)	0.0777 (16)	0.0114 (14)	0.0183 (11)	0.0373 (15)
C37	0.0348 (10)	0.0557 (13)	0.0426 (9)	0.0060 (9)	0.0043 (8)	0.0061 (9)
C38	0.0303 (10)	0.0512 (12)	0.0420 (9)	0.0037 (9)	0.0004 (8)	0.0000 (8)
C39	0.0317 (10)	0.0649 (14)	0.0399 (9)	0.0044 (10)	0.0003 (8)	0.0019 (9)
C40	0.0354 (10)	0.0429 (11)	0.0476 (10)	0.0039 (9)	−0.0061 (8)	−0.0047 (9)
C41	0.0310 (9)	0.0345 (10)	0.0501 (10)	−0.0014 (8)	−0.0019 (8)	−0.0013 (8)
C42	0.0300 (9)	0.0465 (12)	0.0600 (12)	−0.0012 (9)	−0.0050 (9)	0.0037 (10)
C43	0.0338 (10)	0.0624 (14)	0.0534 (11)	−0.0101 (10)	−0.0049 (9)	0.0135 (10)
C44	0.0378 (11)	0.0618 (14)	0.0573 (12)	−0.0065 (10)	−0.0060 (10)	0.0162 (11)
C45	0.0398 (11)	0.0514 (12)	0.0494 (10)	0.0008 (10)	−0.0098 (9)	−0.0061 (9)
C46	0.0626 (16)	0.0509 (15)	0.105 (2)	−0.0100 (13)	−0.0250 (15)	0.0240 (15)
C47	0.0544 (14)	0.0568 (15)	0.0674 (14)	0.0093 (12)	0.0008 (11)	0.0082 (12)
C48	0.0388 (11)	0.0581 (13)	0.0405 (9)	0.0054 (10)	−0.0007 (8)	0.0027 (9)
N1	0.0289 (8)	0.0509 (10)	0.0467 (8)	0.0078 (7)	−0.0052 (7)	−0.0009 (7)
N2	0.0324 (9)	0.0492 (10)	0.0501 (9)	0.0000 (8)	−0.0060 (7)	0.0039 (8)
O1	0.0230 (7)	0.0739 (11)	0.0942 (12)	−0.0110 (7)	0.0026 (7)	−0.0056 (10)
O2	0.0366 (8)	0.0562 (10)	0.1036 (13)	−0.0128 (7)	−0.0026 (8)	0.0136 (9)
O3	0.0234 (6)	0.0404 (7)	0.0530 (7)	0.0007 (5)	0.0014 (5)	0.0005 (6)
O4	0.0228 (6)	0.0427 (8)	0.0651 (8)	−0.0053 (5)	0.0027 (6)	0.0000 (7)
O5	0.0326 (7)	0.0552 (8)	0.0437 (7)	0.0053 (6)	−0.0018 (5)	0.0065 (6)
O6	0.0383 (9)	0.0897 (14)	0.0987 (13)	−0.0076 (9)	0.0125 (9)	−0.0221 (11)
O7	0.0326 (8)	0.0861 (13)	0.0870 (12)	0.0080 (8)	0.0144 (8)	0.0225 (10)
O8	0.0469 (8)	0.0520 (9)	0.0542 (8)	0.0052 (7)	0.0150 (7)	0.0079 (7)
O9	0.0341 (7)	0.0741 (11)	0.0557 (8)	0.0064 (7)	−0.0049 (6)	0.0161 (8)
O10	0.0307 (7)	0.0695 (10)	0.0626 (9)	0.0063 (7)	0.0083 (6)	0.0177 (8)
O11	0.0635 (10)	0.0515 (9)	0.0654 (9)	−0.0106 (8)	−0.0102 (8)	0.0023 (7)
O12	0.0321 (7)	0.0686 (11)	0.0716 (10)	0.0047 (8)	−0.0008 (7)	0.0020 (8)

Geometric parameters (Å, º)

C1—O1	1.428 (3)	C25—H25A	0.9600
C1—H1A	0.9600	C25—H25B	0.9600
C1—H1B	0.9600	C25—H25C	0.9600
C1—H1C	0.9600	C26—O8	1.423 (3)
C2—O2	1.402 (3)	C26—H26A	0.9600
C2—H2A	0.9600	C26—H26B	0.9600
C2—H2B	0.9600	C26—H26C	0.9600
C2—H2C	0.9600	C27—O7	1.377 (2)
C3—O1	1.378 (2)	C27—C42	1.385 (3)
C3—C18	1.379 (3)	C27—C28	1.388 (3)
C3—C4	1.389 (3)	C28—C29	1.371 (3)
C4—O2	1.373 (3)	C28—O8	1.381 (2)
C4—C5	1.387 (3)	C29—C30	1.392 (3)
C5—C6	1.395 (3)	C29—H29	0.9300
C5—H5	0.9300	C30—C41	1.412 (3)
C6—C17	1.397 (3)	C30—C31	1.485 (3)
C6—C7	1.486 (2)	C31—C38	1.392 (3)
C7—C14	1.392 (3)	C31—C32	1.407 (3)
C7—C8	1.405 (2)	C32—C33	1.377 (3)
C8—C9	1.376 (2)	C32—H32	0.9300
C8—H8	0.9300	C33—O9	1.365 (2)
C9—O3	1.375 (2)	C33—C35	1.405 (3)
C9—C11	1.406 (3)	C34—O9	1.409 (3)
C10—O3	1.421 (2)	C34—H34A	0.9600
C10—H10A	0.9600	C34—H34B	0.9600
C10—H10B	0.9600	C34—H34C	0.9600
C10—H10C	0.9600	C35—O10	1.364 (2)
C11—O4	1.375 (2)	C35—C37	1.378 (3)
C11—C13	1.375 (3)	C36—O10	1.420 (3)
C12—O4	1.422 (3)	C36—H36A	0.9600
C12—H12A	0.9600	C36—H36B	0.9600
C12—H12B	0.9600	C36—H36C	0.9600
C12—H12C	0.9600	C37—C38	1.395 (3)
C13—C14	1.407 (2)	C37—H37	0.9300
C13—H13	0.9300	C38—C39	1.511 (3)
C14—C15	1.517 (2)	C39—C43	1.536 (3)
C15—C19	1.544 (3)	C39—C40	1.540 (3)
C15—C16	1.544 (3)	C39—H39	0.9800
C15—H15	0.9800	C40—C45	1.523 (3)
C16—C17	1.512 (3)	C40—C41	1.525 (3)
C16—C21	1.527 (3)	C40—H40	0.9800
C16—H16	0.9800	C41—C42	1.389 (3)
C17—C18	1.393 (3)	C42—H42	0.9300
C18—H18	0.9300	C43—O11	1.421 (3)
C19—O5	1.417 (2)	C43—C44	1.529 (3)
C19—C20	1.526 (3)	C43—H43	0.9800
C19—H19	0.9800	C44—N2	1.460 (3)
C20—N1	1.453 (2)	C44—C46	1.524 (4)
C20—C22	1.536 (3)	C44—H44	0.9800
C20—H20	0.9800	C45—N2	1.440 (3)
C21—N1	1.442 (2)	C45—H45A	0.9700
C21—H21A	0.9700	C45—H45B	0.9700
C21—H21B	0.9700	C46—C47	1.524 (3)
C22—C23	1.516 (4)	C46—H46A	0.9700
C22—H22A	0.9700	C46—H46B	0.9700
C22—H22B	0.9700	C47—C48	1.500 (3)
C23—C24	1.507 (3)	C47—H47A	0.9700
C23—H23A	0.9700	C47—H47B	0.9700
C23—H23B	0.9700	C48—O12	1.230 (2)
C24—O6	1.223 (3)	C48—N2	1.340 (3)
C24—N1	1.345 (3)	O5—H5A	0.8200
C25—O7	1.403 (3)	O11—H11	0.8200
O1—C1—H1A	109.5	H26A—C26—H26B	109.5
O1—C1—H1B	109.5	O8—C26—H26C	109.5
H1A—C1—H1B	109.5	H26A—C26—H26C	109.5
O1—C1—H1C	109.5	H26B—C26—H26C	109.5
H1A—C1—H1C	109.5	O7—C27—C42	123.68 (19)
H1B—C1—H1C	109.5	O7—C27—C28	117.22 (19)
O2—C2—H2A	109.5	C42—C27—C28	119.07 (18)
O2—C2—H2B	109.5	C29—C28—O8	118.87 (19)
H2A—C2—H2B	109.5	C29—C28—C27	119.72 (19)
O2—C2—H2C	109.5	O8—C28—C27	121.39 (18)
H2A—C2—H2C	109.5	C28—C29—C30	122.50 (18)
H2B—C2—H2C	109.5	C28—C29—H29	118.7
O1—C3—C18	124.08 (19)	C30—C29—H29	118.7
O1—C3—C4	116.05 (19)	C29—C30—C41	117.66 (17)
C18—C3—C4	119.87 (17)	C29—C30—C31	122.36 (17)
O2—C4—C5	124.48 (19)	C41—C30—C31	119.93 (17)
O2—C4—C3	116.52 (17)	C38—C31—C32	117.84 (17)
C5—C4—C3	119.00 (19)	C38—C31—C30	119.89 (17)
C4—C5—C6	121.41 (18)	C32—C31—C30	122.20 (17)
C4—C5—H5	119.3	C33—C32—C31	121.85 (18)
C6—C5—H5	119.3	C33—C32—H32	119.1
C5—C6—C17	119.16 (16)	C31—C32—H32	119.1
C5—C6—C7	121.28 (16)	O9—C33—C32	125.01 (18)
C17—C6—C7	119.56 (17)	O9—C33—C35	115.28 (16)
C14—C7—C8	118.67 (16)	C32—C33—C35	119.70 (17)
C14—C7—C6	120.22 (16)	O9—C34—H34A	109.5
C8—C7—C6	121.10 (16)	O9—C34—H34B	109.5
C9—C8—C7	121.55 (17)	H34A—C34—H34B	109.5
C9—C8—H8	119.2	O9—C34—H34C	109.5
C7—C8—H8	119.2	H34A—C34—H34C	109.5
O3—C9—C8	124.46 (17)	H34B—C34—H34C	109.5
O3—C9—C11	115.84 (15)	O10—C35—C37	124.76 (18)
C8—C9—C11	119.68 (16)	O10—C35—C33	116.34 (17)
O3—C10—H10A	109.5	C37—C35—C33	118.88 (17)
O3—C10—H10B	109.5	O10—C36—H36A	109.5
H10A—C10—H10B	109.5	O10—C36—H36B	109.5
O3—C10—H10C	109.5	H36A—C36—H36B	109.5
H10A—C10—H10C	109.5	O10—C36—H36C	109.5
H10B—C10—H10C	109.5	H36A—C36—H36C	109.5
O4—C11—C13	125.90 (17)	H36B—C36—H36C	109.5
O4—C11—C9	114.95 (16)	C35—C37—C38	121.42 (17)
C13—C11—C9	119.14 (16)	C35—C37—H37	119.3
O4—C12—H12A	109.5	C38—C37—H37	119.3
O4—C12—H12B	109.5	C31—C38—C37	120.26 (17)
H12A—C12—H12B	109.5	C31—C38—C39	120.27 (17)
O4—C12—H12C	109.5	C37—C38—C39	119.38 (17)
H12A—C12—H12C	109.5	C38—C39—C43	112.76 (17)
H12B—C12—H12C	109.5	C38—C39—C40	110.77 (17)
C11—C13—C14	121.43 (17)	C43—C39—C40	112.62 (17)
C11—C13—H13	119.3	C38—C39—H39	106.7
C14—C13—H13	119.3	C43—C39—H39	106.7
C7—C14—C13	119.45 (16)	C40—C39—H39	106.7
C7—C14—C15	120.56 (15)	C45—C40—C41	117.04 (16)
C13—C14—C15	119.95 (16)	C45—C40—C39	109.54 (17)
C14—C15—C19	112.30 (14)	C41—C40—C39	110.83 (15)
C14—C15—C16	110.63 (15)	C45—C40—H40	106.2
C19—C15—C16	113.06 (14)	C41—C40—H40	106.2
C14—C15—H15	106.8	C39—C40—H40	106.2
C19—C15—H15	106.8	C42—C41—C30	119.44 (18)
C16—C15—H15	106.8	C42—C41—C40	122.62 (17)
C17—C16—C21	115.78 (15)	C30—C41—C40	117.80 (16)
C17—C16—C15	112.09 (15)	C27—C42—C41	121.52 (18)
C21—C16—C15	109.74 (16)	C27—C42—H42	119.2
C17—C16—H16	106.2	C41—C42—H42	119.2
C21—C16—H16	106.2	O11—C43—C44	111.91 (19)
C15—C16—H16	106.2	O11—C43—C39	113.46 (16)
C18—C17—C6	118.88 (18)	C44—C43—C39	109.76 (18)
C18—C17—C16	122.02 (17)	O11—C43—H43	107.1
C6—C17—C16	118.93 (15)	C44—C43—H43	107.1
C3—C18—C17	121.47 (19)	C39—C43—H43	107.1
C3—C18—H18	119.3	N2—C44—C46	102.59 (18)
C17—C18—H18	119.3	N2—C44—C43	109.74 (17)
O5—C19—C20	108.21 (15)	C46—C44—C43	116.9 (2)
O5—C19—C15	112.80 (15)	N2—C44—H44	109.1
C20—C19—C15	110.52 (15)	C46—C44—H44	109.1
O5—C19—H19	108.4	C43—C44—H44	109.1
C20—C19—H19	108.4	N2—C45—C40	110.61 (17)
C15—C19—H19	108.4	N2—C45—H45A	109.5
N1—C20—C19	110.53 (16)	C40—C45—H45A	109.5
N1—C20—C22	102.61 (16)	N2—C45—H45B	109.5
C19—C20—C22	116.46 (17)	C40—C45—H45B	109.5
N1—C20—H20	109.0	H45A—C45—H45B	108.1
C19—C20—H20	109.0	C47—C46—C44	105.4 (2)
C22—C20—H20	109.0	C47—C46—H46A	110.7
N1—C21—C16	110.56 (14)	C44—C46—H46A	110.7
N1—C21—H21A	109.5	C47—C46—H46B	110.7
C16—C21—H21A	109.5	C44—C46—H46B	110.7
N1—C21—H21B	109.5	H46A—C46—H46B	108.8
C16—C21—H21B	109.5	C48—C47—C46	105.0 (2)
H21A—C21—H21B	108.1	C48—C47—H47A	110.8
C23—C22—C20	105.41 (18)	C46—C47—H47A	110.8
C23—C22—H22A	110.7	C48—C47—H47B	110.8
C20—C22—H22A	110.7	C46—C47—H47B	110.8
C23—C22—H22B	110.7	H47A—C47—H47B	108.8
C20—C22—H22B	110.7	O12—C48—N2	124.3 (2)
H22A—C22—H22B	108.8	O12—C48—C47	127.5 (2)
C24—C23—C22	105.67 (19)	N2—C48—C47	108.25 (19)
C24—C23—H23A	110.6	C24—N1—C21	127.16 (18)
C22—C23—H23A	110.6	C24—N1—C20	115.83 (17)
C24—C23—H23B	110.6	C21—N1—C20	116.21 (16)
C22—C23—H23B	110.6	C48—N2—C45	124.27 (18)
H23A—C23—H23B	108.7	C48—N2—C44	114.58 (18)
O6—C24—N1	126.3 (2)	C45—N2—C44	118.79 (18)
O6—C24—C23	126.5 (2)	C3—O1—C1	115.97 (19)
N1—C24—C23	107.19 (19)	C4—O2—C2	118.02 (16)
O7—C25—H25A	109.5	C9—O3—C10	117.70 (14)
O7—C25—H25B	109.5	C11—O4—C12	117.84 (16)
H25A—C25—H25B	109.5	C19—O5—H5A	109.5
O7—C25—H25C	109.5	C27—O7—C25	118.41 (19)
H25A—C25—H25C	109.5	C28—O8—C26	114.35 (17)
H25B—C25—H25C	109.5	C33—O9—C34	117.53 (17)
O8—C26—H26A	109.5	C35—O10—C36	116.73 (17)
O8—C26—H26B	109.5	C43—O11—H11	109.5
O1—C3—C4—O2	4.3 (3)	O9—C33—C35—C37	−177.09 (19)
C18—C3—C4—O2	−175.51 (19)	C32—C33—C35—C37	1.8 (3)
O1—C3—C4—C5	−175.43 (18)	O10—C35—C37—C38	−177.6 (2)
C18—C3—C4—C5	4.7 (3)	C33—C35—C37—C38	0.5 (3)
O2—C4—C5—C6	177.29 (19)	C32—C31—C38—C37	1.4 (3)
C3—C4—C5—C6	−3.0 (3)	C30—C31—C38—C37	178.49 (19)
C4—C5—C6—C17	−1.1 (3)	C32—C31—C38—C39	−174.95 (19)
C4—C5—C6—C7	178.79 (18)	C30—C31—C38—C39	2.1 (3)
C5—C6—C7—C14	−167.79 (17)	C35—C37—C38—C31	−2.1 (3)
C17—C6—C7—C14	12.2 (3)	C35—C37—C38—C39	174.29 (19)
C5—C6—C7—C8	11.0 (3)	C31—C38—C39—C43	93.4 (2)
C17—C6—C7—C8	−169.06 (17)	C37—C38—C39—C43	−83.0 (2)
C14—C7—C8—C9	2.6 (3)	C31—C38—C39—C40	−33.8 (3)
C6—C7—C8—C9	−176.18 (16)	C37—C38—C39—C40	149.73 (19)
C7—C8—C9—O3	178.07 (16)	C38—C39—C40—C45	−177.94 (16)
C7—C8—C9—C11	−3.4 (3)	C43—C39—C40—C45	54.7 (2)
O3—C9—C11—O4	−0.6 (2)	C38—C39—C40—C41	51.4 (2)
C8—C9—C11—O4	−179.25 (16)	C43—C39—C40—C41	−75.9 (2)
O3—C9—C11—C13	−179.48 (15)	C29—C30—C41—C42	3.2 (3)
C8—C9—C11—C13	1.9 (3)	C31—C30—C41—C42	−174.55 (18)
O4—C11—C13—C14	−178.37 (17)	C29—C30—C41—C40	−172.81 (18)
C9—C11—C13—C14	0.4 (3)	C31—C30—C41—C40	9.5 (3)
C8—C7—C14—C13	−0.3 (3)	C45—C40—C41—C42	16.6 (3)
C6—C7—C14—C13	178.47 (16)	C39—C40—C41—C42	143.2 (2)
C8—C7—C14—C15	−177.91 (16)	C45—C40—C41—C30	−167.56 (18)
C6—C7—C14—C15	0.9 (3)	C39—C40—C41—C30	−41.0 (2)
C11—C13—C14—C7	−1.1 (3)	O7—C27—C42—C41	−177.9 (2)
C11—C13—C14—C15	176.47 (16)	C28—C27—C42—C41	−0.1 (3)
C7—C14—C15—C19	96.3 (2)	C30—C41—C42—C27	−2.4 (3)
C13—C14—C15—C19	−81.2 (2)	C40—C41—C42—C27	173.34 (19)
C7—C14—C15—C16	−31.0 (2)	C38—C39—C43—O11	−55.3 (2)
C13—C14—C15—C16	151.40 (16)	C40—C39—C43—O11	71.0 (2)
C14—C15—C16—C17	48.18 (19)	C38—C39—C43—C44	178.70 (16)
C19—C15—C16—C17	−78.76 (19)	C40—C39—C43—C44	−55.0 (2)
C14—C15—C16—C21	178.29 (14)	O11—C43—C44—N2	−75.4 (2)
C19—C15—C16—C21	51.3 (2)	C39—C43—C44—N2	51.5 (2)
C5—C6—C17—C18	3.5 (3)	O11—C43—C44—C46	40.8 (3)
C7—C6—C17—C18	−176.48 (16)	C39—C43—C44—C46	167.73 (19)
C5—C6—C17—C16	−171.99 (16)	C41—C40—C45—N2	75.6 (2)
C7—C6—C17—C16	8.1 (2)	C39—C40—C45—N2	−51.6 (2)
C21—C16—C17—C18	19.1 (2)	N2—C44—C46—C47	−20.2 (3)
C15—C16—C17—C18	146.05 (17)	C43—C44—C46—C47	−140.3 (2)
C21—C16—C17—C6	−165.57 (16)	C44—C46—C47—C48	17.4 (3)
C15—C16—C17—C6	−38.6 (2)	C46—C47—C48—O12	172.9 (2)
O1—C3—C18—C17	177.75 (19)	C46—C47—C48—N2	−7.4 (3)
C4—C3—C18—C17	−2.4 (3)	O6—C24—N1—C21	−8.9 (4)
C6—C17—C18—C3	−1.7 (3)	C23—C24—N1—C21	170.71 (19)
C16—C17—C18—C3	173.59 (17)	O6—C24—N1—C20	−178.1 (2)
C14—C15—C19—O5	−55.40 (19)	C23—C24—N1—C20	1.4 (2)
C16—C15—C19—O5	70.65 (19)	C16—C21—N1—C24	−110.3 (2)
C14—C15—C19—C20	−176.68 (15)	C16—C21—N1—C20	59.0 (2)
C16—C15—C19—C20	−50.6 (2)	C19—C20—N1—C24	112.71 (19)
O5—C19—C20—N1	−72.83 (19)	C22—C20—N1—C24	−12.1 (2)
C15—C19—C20—N1	51.1 (2)	C19—C20—N1—C21	−57.8 (2)
O5—C19—C20—C22	43.7 (2)	C22—C20—N1—C21	177.37 (17)
C15—C19—C20—C22	167.68 (18)	O12—C48—N2—C45	11.0 (3)
C17—C16—C21—N1	74.9 (2)	C47—C48—N2—C45	−168.61 (18)
C15—C16—C21—N1	−53.2 (2)	O12—C48—N2—C44	173.31 (19)
N1—C20—C22—C23	17.3 (2)	C47—C48—N2—C44	−6.3 (2)
C19—C20—C22—C23	−103.5 (2)	C40—C45—N2—C48	−143.59 (19)
C20—C22—C23—C24	−17.1 (2)	C40—C45—N2—C44	54.8 (2)
C22—C23—C24—O6	−170.2 (2)	C46—C44—N2—C48	17.1 (2)
C22—C23—C24—N1	10.2 (2)	C43—C44—N2—C48	142.10 (19)
O7—C27—C28—C29	179.8 (2)	C46—C44—N2—C45	−179.54 (19)
C42—C27—C28—C29	1.9 (3)	C43—C44—N2—C45	−54.6 (3)
O7—C27—C28—O8	1.4 (3)	C18—C3—O1—C1	3.2 (3)
C42—C27—C28—O8	−176.58 (19)	C4—C3—O1—C1	−176.6 (2)
O8—C28—C29—C30	177.43 (18)	C5—C4—O2—C2	10.3 (3)
C27—C28—C29—C30	−1.1 (3)	C3—C4—O2—C2	−169.4 (2)
C28—C29—C30—C41	−1.5 (3)	C8—C9—O3—C10	−7.0 (3)
C28—C29—C30—C31	176.20 (19)	C11—C9—O3—C10	174.39 (15)
C29—C30—C31—C38	−166.16 (19)	C13—C11—O4—C12	−11.4 (3)
C41—C30—C31—C38	11.4 (3)	C9—C11—O4—C12	169.84 (16)
C29—C30—C31—C32	10.7 (3)	C42—C27—O7—C25	−34.7 (3)
C41—C30—C31—C32	−171.65 (19)	C28—C27—O7—C25	147.5 (2)
C38—C31—C32—C33	0.9 (3)	C29—C28—O8—C26	110.1 (2)
C30—C31—C32—C33	−176.11 (19)	C27—C28—O8—C26	−71.4 (3)
C31—C32—C33—O9	176.3 (2)	C32—C33—O9—C34	−12.5 (3)
C31—C32—C33—C35	−2.5 (3)	C35—C33—O9—C34	166.3 (2)
O9—C33—C35—O10	1.2 (3)	C37—C35—O10—C36	5.8 (3)
C32—C33—C35—O10	−179.95 (19)	C33—C35—O10—C36	−172.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5A···O12	0.82	2.00	2.818 (2)	179