Polyether antibiotic CP44,161

The crystal structure of antibiotic CP44,161, 6-(7-{2-ethyl-2-[5-(1-hydroxy­methyl)-5-methyl-2,3,4,5-tetra­hydro-2-furyl]-4,10,-­12-tri­methyl-1,6,8-trioxadi­spiro­[4.1.5.3]­pentadec-13-en-9-yl}-4-hydroxy-3,5-di­methyl-6-oxononyl)-2-hydroxy-3-methyl­benzoic acid monohydrate, C₄₃H₆₆O₁₀·H₂O, has been determined by X-ray crystallography. The mol­ecule adopts a cyclic conformation, with a centrally located water mol­ecule contributing to the stability of the conformation through hydrogen-bonding interactions.

S1. Comment

The polyether family of antibiotics has adopted an important role in that its members can act as ionophores transporting ions through biological membranes (Dobler, 1981). A fundamental property of many of the polyether antibiotics is their ability to adopt a cyclic conformation whereby several of the oxygen atoms present in the molecule's backbone are available to complex to a metal ion and transport the ion across a lipophilic membrane.

Salinomycin is a member of the polyether family of antibiotics that was isolated from Streptomyces albus. The structure of salinomycin was elucidated by X-ray analysis of its p-iodophenacyl ester (Kinashi et al., 1975). Salinomycin has a unique tricyclic bis-spiroacetal moiety that has been proposed to act as a hinge to aid metal binding. The cis stereochemistry of the bis-spiroacetal ring system is a key feature of the structure and is implicated in the mechanism of ionophoric action (Mronga et al., 1993).

Closely related to salinomycin is the polyether antibiotic CP44,161 which is produced by three strains of a Dactylosporangium species. CP44,161 exhibits anticoccidial activity and improves feed utilization efficiency in ruminants (Celmer et al., 1978). CP44,161 contains the same cis bis-spiroacetal ring system found in salinomycin. \sch

As part of our synthetic programme directed towards the synthesis of the bis-spiroacetal moiety of antibiotic CP44,161, we needed to establish the stereochemistry of the bis-spiroacetal ring system of our synthetic intermediates by comparison of the NMR data of our compounds with the natural product. In order to do this we needed to establish unequivocally the stereochemistry of bis-spiroacetal ring system of the naturally occurring antibiotic CP44,161 hence a crystallographic analysis of this natural product was carried out.

The crystal structure of CP44,161 (Fig. 1) establishes the cis stereochemistry of the bis-spiroacetal ring system, and demonstrates that the molecule can adopt a cyclic conformation. Presumably contributing to the stabilization of the cyclic conformation, a centrally located water molecule participates in hydrogen-bond interactions with O10 and O8 on one side, and with O4 on the other side of the molecule (Table 1). There is also a weak interaction between the water molecule and O9. The conformation may also be influenced by weak interactions between C8 and O1, and C11 and O5. An oligomeric hydrogen-bond network is formed with O1 hydrogen bonded to O4 on a neighbouring molecule (-x + 1/2, -y, z - 1/2).

The crystal structure of antibiotic CP44,161 suggests that the molecule is likely to be ionophoric, and it should be possible to replace the water molecule with a metal ion.

S2. Experimental

CP44,161 was obtained from the pharmaceutical company Pfizer and was isolated from Dactylosporangium salmoneum Routien sp. nov. The sample of CP44,161 obtained from Pfizer was recrystallized from ethyl acetate.

S3. Refinement

The data did not permit the determination of the absolute structure.

Computing details

Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1997); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: TEXSAN (Molecular Structure Corporation, 1995); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: TEXSAN for Windows (Molecular Structure Corporation, 1997).

Figures

Fig. 1. An ORTEP (Johnson, 1976; Hall et al., 1999) depiction of CP44,161, with displacement ellipsoids shown at the 20% level. Unfilled bonds have been used to emphasize hydrogen bonds.

(CP44161)

Crystal data

C43H66O10·H2O	Dx = 1.156 Mg m^−3
Mr = 760.97	Mo Kα radiation, λ = 0.71069 Å
Orthorhombic, P212121	Cell parameters from 25 reflections
a = 12.373 (2) Å	θ = 8.5–11.9°
b = 31.939 (2) Å	µ = 0.08 mm^−1
c = 11.064 (2) Å	T = 294 K
V = 4372.3 (11) Å^3	Plate, colourless
Z = 4	0.34 × 0.32 × 0.17 mm
F(000) = 1656

Data collection

Rigaku AFC7R diffractometer	2144 reflections with I > 2σ(I)
Radiation source: rotating anode	Rint = 0.049
Graphite monochromator	θmax = 25.0°, θmin = 1.3°
ω:θ scans	h = −1→14
Absorption correction: analytical de Meulenaer & Tompa (1965).	k = −1→37
Tmin = 0.97, Tmax = 0.99	l = −1→13
5472 measured reflections	3 standard reflections every 60 min
4325 independent reflections	intensity decay: 0.0%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.039	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.126	w = 1/[σ^2(Fo^2) + (0.059P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.94	(Δ/σ)max < 0.001
4325 reflections	Δρmax = 0.14 e Å^−3
508 parameters	Δρmin = −0.15 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0043 (5)

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	0.2840 (3)	−0.06781 (10)	0.1497 (3)	0.0754 (9)
H1O	0.2553	−0.0724	0.0842	0.113*
O2	0.3503 (3)	−0.13124 (11)	0.1172 (3)	0.0871 (11)
O3	0.3947 (3)	−0.17610 (11)	0.2989 (4)	0.1016 (12)
H3O	0.3805	−0.1710	0.2280	0.152*
O4	0.3378 (2)	0.07699 (10)	0.4618 (2)	0.0585 (7)
H4O	0.3987	0.0730	0.4885	0.088*
O5	0.5290 (2)	0.11810 (10)	0.3052 (3)	0.0741 (9)
O6	0.4956 (2)	0.18001 (8)	0.5411 (2)	0.0572 (7)
O7	0.5879 (2)	0.18158 (9)	0.7166 (3)	0.0629 (8)
O8	0.6581 (2)	0.11512 (9)	0.6746 (3)	0.0639 (8)
O9	0.7749 (3)	0.04601 (10)	0.5754 (3)	0.0722 (9)
O10	0.6262 (3)	−0.01011 (15)	0.6772 (4)	0.1078 (13)
H10O	0.5997	0.0110	0.6474	0.162*
O11	0.5368 (3)	0.06064 (13)	0.5394 (4)	0.0898 (12)
H11O	0.584 (5)	0.056 (2)	0.483 (6)	0.135*
H12O	0.571 (5)	0.0827 (19)	0.583 (6)	0.135*
C1	0.3379 (3)	−0.10128 (16)	0.1846 (5)	0.0650 (13)
C2	0.3771 (3)	−0.10044 (14)	0.3102 (4)	0.0600 (12)
C3	0.4023 (4)	−0.13976 (19)	0.3616 (5)	0.0783 (15)
C4	0.4334 (5)	−0.1436 (2)	0.4812 (6)	0.0942 (17)
C5	0.4482 (4)	−0.1078 (2)	0.5452 (5)	0.1002 (19)
H5	0.4721	−0.1096	0.6247	0.120*
C6	0.4291 (4)	−0.06892 (19)	0.4960 (5)	0.0811 (14)
H6	0.4421	−0.0452	0.5425	0.097*
C7	0.3907 (3)	−0.06421 (15)	0.3787 (4)	0.0634 (12)
C8	0.3739 (3)	−0.02060 (14)	0.3325 (5)	0.0716 (14)
H8A	0.3858	−0.0206	0.2459	0.086*
H8B	0.4282	−0.0026	0.3684	0.086*
C9	0.2622 (3)	−0.00169 (15)	0.3578 (4)	0.0675 (13)
H9A	0.2072	−0.0205	0.3271	0.081*
H9B	0.2523	0.0007	0.4445	0.081*
C10	0.2466 (3)	0.04121 (13)	0.3007 (4)	0.0598 (11)
H10	0.2485	0.0374	0.2128	0.072*
C11	0.3381 (3)	0.07082 (13)	0.3337 (4)	0.0558 (11)
H11	0.4060	0.0568	0.3128	0.067*
C12	0.3398 (4)	0.11396 (14)	0.2741 (4)	0.0598 (11)
H12	0.2774	0.1303	0.3012	0.072*
C13	0.4445 (4)	0.13675 (14)	0.3075 (4)	0.0587 (11)
C14	0.4373 (4)	0.18231 (14)	0.3379 (4)	0.0623 (12)
H14	0.3799	0.1942	0.2875	0.075*
C15	0.4005 (4)	0.18652 (13)	0.4697 (4)	0.0588 (11)
H15	0.3497	0.1638	0.4870	0.071*
C16	0.3445 (4)	0.22809 (13)	0.4991 (5)	0.0722 (14)
H16	0.3906	0.2511	0.4714	0.087*
C17	0.3304 (4)	0.23179 (15)	0.6342 (5)	0.0790 (14)
H17A	0.2749	0.2122	0.6598	0.095*
H17B	0.3051	0.2598	0.6529	0.095*
C18	0.4322 (4)	0.22334 (14)	0.7062 (4)	0.0717 (13)
H18	0.4847	0.2452	0.6856	0.086*
C19	0.4818 (3)	0.18079 (14)	0.6694 (4)	0.0589 (12)
C20	0.4177 (4)	0.14440 (14)	0.7127 (4)	0.0587 (11)
H20	0.3514	0.1392	0.6760	0.070*
C21	0.4486 (4)	0.11930 (16)	0.7988 (4)	0.0694 (13)
H21	0.4025	0.0982	0.8255	0.083*
C22	0.5569 (4)	0.12416 (16)	0.8544 (4)	0.0693 (13)
H22A	0.5846	0.0969	0.8774	0.083*
H22B	0.5511	0.1411	0.9268	0.083*
C23	0.6345 (4)	0.14472 (16)	0.7667 (4)	0.0642 (13)
C24	0.7433 (4)	0.15703 (17)	0.8192 (4)	0.0796 (15)
H24	0.7650	0.1353	0.8768	0.095*
C25	0.8166 (4)	0.15393 (17)	0.7098 (5)	0.0822 (15)
H25A	0.8896	0.1467	0.7341	0.099*
H25B	0.8186	0.1804	0.6667	0.099*
C26	0.7687 (3)	0.11968 (16)	0.6302 (4)	0.0672 (13)
C27	0.8246 (4)	0.07725 (17)	0.6497 (5)	0.0750 (14)
H27	0.9002	0.0800	0.6246	0.090*
C28	0.8228 (4)	0.05802 (17)	0.7734 (4)	0.0778 (15)
H28A	0.7534	0.0624	0.8122	0.093*
H28B	0.8792	0.0697	0.8241	0.093*
C29	0.8423 (4)	0.01207 (18)	0.7504 (5)	0.0855 (16)
H29A	0.7985	−0.0050	0.8039	0.103*
H29B	0.9178	0.0051	0.7628	0.103*
C30	0.8097 (4)	0.00509 (17)	0.6178 (4)	0.0751 (14)
C31	0.7135 (5)	−0.02399 (16)	0.6043 (5)	0.0828 (15)
H31	0.6903	−0.0236	0.5197	0.099*
C32	0.7369 (5)	−0.06876 (17)	0.6397 (6)	0.114 (2)
H32A	0.7497	−0.0702	0.7252	0.171*
H32B	0.7998	−0.0784	0.5973	0.171*
H32C	0.6762	−0.0861	0.6192	0.171*
C33	0.4489 (7)	−0.1866 (2)	0.5387 (7)	0.154 (3)
H33A	0.4766	−0.1833	0.6192	0.231*
H33B	0.4991	−0.2026	0.4913	0.231*
H33C	0.3808	−0.2009	0.5418	0.231*
C34	0.1345 (3)	0.05906 (17)	0.3331 (5)	0.0783 (15)
H34A	0.1268	0.0601	0.4194	0.117*
H34B	0.0793	0.0414	0.2997	0.117*
H34C	0.1275	0.0868	0.3005	0.117*
C35	0.3397 (4)	0.11093 (18)	0.1345 (4)	0.0884 (16)
H35A	0.3487	0.1384	0.1005	0.133*
H35B	0.2723	0.0993	0.1076	0.133*
H35C	0.3980	0.0932	0.1087	0.133*
C36	0.5412 (4)	0.20660 (15)	0.3090 (4)	0.0786 (14)
H36A	0.5354	0.2347	0.3417	0.094*
H36B	0.6018	0.1929	0.3481	0.094*
C37	0.5625 (6)	0.2092 (2)	0.1753 (5)	0.126 (3)
H37A	0.5828	0.1821	0.1455	0.188*
H37B	0.6199	0.2287	0.1604	0.188*
H37C	0.4982	0.2185	0.1345	0.188*
C38	0.2341 (5)	0.23157 (18)	0.4353 (5)	0.1061 (19)
H38A	0.1904	0.2077	0.4557	0.159*
H38B	0.2448	0.2324	0.3494	0.159*
H38C	0.1982	0.2567	0.4610	0.159*
C39	0.4104 (5)	0.22621 (18)	0.8411 (5)	0.1009 (19)
H39A	0.3858	0.2539	0.8606	0.151*
H39B	0.4756	0.2203	0.8848	0.151*
H39C	0.3558	0.2062	0.8630	0.151*
C40	0.7479 (5)	0.19898 (18)	0.8837 (5)	0.105 (2)
H40A	0.7223	0.2206	0.8306	0.158*
H40B	0.8211	0.2049	0.9069	0.158*
H40C	0.7031	0.1980	0.9546	0.158*
C41	0.7626 (4)	0.13192 (17)	0.4979 (4)	0.0779 (14)
H41A	0.7220	0.1578	0.4911	0.094*
H41B	0.7231	0.1104	0.4545	0.094*
C42	0.8725 (5)	0.1379 (2)	0.4375 (5)	0.112 (2)
H42A	0.9148	0.1574	0.4836	0.167*
H42B	0.8623	0.1486	0.3572	0.167*
H42C	0.9094	0.1115	0.4336	0.167*
C43	0.9039 (5)	−0.00879 (19)	0.5394 (6)	0.111 (2)
H43A	0.8802	−0.0115	0.4572	0.167*
H43B	0.9304	−0.0353	0.5677	0.167*
H43C	0.9606	0.0117	0.5439	0.167*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.077 (2)	0.077 (2)	0.072 (2)	−0.004 (2)	−0.0067 (19)	−0.0098 (18)
O2	0.080 (2)	0.086 (2)	0.095 (3)	0.0075 (19)	−0.004 (2)	−0.034 (2)
O3	0.091 (3)	0.076 (2)	0.138 (4)	0.015 (2)	−0.009 (3)	−0.016 (3)
O4	0.0479 (15)	0.0786 (19)	0.0491 (18)	−0.0058 (16)	−0.0069 (14)	−0.0041 (15)
O5	0.0505 (18)	0.079 (2)	0.093 (2)	−0.0057 (17)	−0.0007 (19)	−0.010 (2)
O6	0.0576 (18)	0.0637 (17)	0.0504 (18)	−0.0051 (15)	0.0038 (15)	−0.0011 (15)
O7	0.0591 (18)	0.0708 (19)	0.0588 (18)	−0.0177 (16)	−0.0035 (16)	−0.0020 (17)
O8	0.0454 (16)	0.083 (2)	0.0636 (19)	−0.0072 (15)	−0.0091 (16)	−0.0104 (17)
O9	0.0618 (19)	0.095 (2)	0.0602 (19)	0.0144 (19)	−0.0111 (17)	−0.0059 (18)
O10	0.066 (2)	0.138 (4)	0.120 (3)	0.010 (2)	−0.003 (2)	0.003 (3)
O11	0.057 (2)	0.102 (3)	0.110 (3)	0.009 (2)	−0.023 (2)	−0.029 (2)
C1	0.040 (2)	0.073 (3)	0.082 (4)	−0.007 (2)	0.012 (3)	−0.020 (3)
C2	0.041 (2)	0.070 (3)	0.069 (3)	−0.004 (2)	−0.002 (2)	−0.012 (3)
C3	0.058 (3)	0.092 (4)	0.085 (4)	0.006 (3)	0.005 (3)	−0.010 (3)
C4	0.079 (4)	0.113 (5)	0.091 (5)	0.034 (4)	0.006 (4)	0.000 (4)
C5	0.074 (4)	0.154 (6)	0.072 (4)	0.029 (4)	−0.003 (3)	0.011 (4)
C6	0.062 (3)	0.110 (4)	0.071 (3)	−0.006 (3)	0.004 (3)	−0.019 (3)
C7	0.040 (2)	0.078 (3)	0.072 (3)	−0.008 (2)	0.008 (2)	−0.010 (3)
C8	0.057 (3)	0.071 (3)	0.087 (4)	−0.021 (2)	0.010 (3)	−0.018 (3)
C9	0.049 (2)	0.077 (3)	0.077 (3)	−0.019 (2)	0.010 (2)	−0.017 (3)
C10	0.049 (2)	0.079 (3)	0.052 (2)	−0.011 (2)	0.003 (2)	−0.009 (2)
C11	0.042 (2)	0.068 (3)	0.057 (3)	−0.003 (2)	0.001 (2)	−0.007 (2)
C12	0.049 (2)	0.072 (3)	0.058 (3)	−0.004 (2)	−0.006 (2)	−0.001 (2)
C13	0.055 (3)	0.068 (3)	0.053 (3)	−0.002 (2)	−0.004 (2)	0.005 (2)
C14	0.069 (3)	0.065 (3)	0.053 (3)	−0.011 (2)	−0.005 (2)	0.010 (2)
C15	0.058 (3)	0.058 (3)	0.060 (3)	−0.003 (2)	−0.007 (2)	0.003 (2)
C16	0.083 (3)	0.055 (3)	0.079 (4)	0.007 (3)	0.005 (3)	0.007 (3)
C17	0.080 (3)	0.061 (3)	0.096 (4)	0.005 (3)	0.010 (3)	−0.011 (3)
C18	0.078 (3)	0.061 (3)	0.077 (3)	−0.005 (3)	0.014 (3)	−0.021 (3)
C19	0.053 (3)	0.065 (3)	0.059 (3)	−0.011 (2)	−0.002 (2)	−0.009 (2)
C20	0.053 (2)	0.062 (3)	0.060 (3)	−0.012 (2)	0.006 (2)	−0.006 (3)
C21	0.064 (3)	0.084 (3)	0.061 (3)	−0.015 (3)	0.004 (3)	0.008 (3)
C22	0.068 (3)	0.084 (3)	0.056 (3)	−0.007 (3)	−0.008 (3)	0.005 (2)
C23	0.062 (3)	0.081 (3)	0.050 (3)	−0.008 (3)	−0.007 (2)	−0.010 (3)
C24	0.062 (3)	0.115 (4)	0.062 (3)	−0.022 (3)	−0.015 (3)	−0.006 (3)
C25	0.053 (3)	0.107 (4)	0.086 (4)	−0.018 (3)	−0.008 (3)	−0.008 (3)
C26	0.043 (2)	0.094 (3)	0.064 (3)	−0.006 (3)	−0.005 (2)	−0.006 (3)
C27	0.049 (3)	0.108 (4)	0.068 (3)	−0.002 (3)	−0.008 (3)	−0.009 (3)
C28	0.058 (3)	0.115 (4)	0.060 (3)	0.003 (3)	−0.024 (2)	0.006 (3)
C29	0.067 (3)	0.110 (4)	0.080 (4)	0.015 (3)	−0.021 (3)	0.001 (3)
C30	0.057 (3)	0.098 (4)	0.070 (3)	0.021 (3)	−0.010 (3)	−0.001 (3)
C31	0.075 (3)	0.098 (4)	0.076 (4)	0.008 (3)	−0.013 (3)	0.000 (3)
C32	0.112 (5)	0.099 (4)	0.130 (5)	0.003 (4)	−0.025 (5)	0.011 (4)
C33	0.167 (7)	0.127 (5)	0.168 (7)	0.075 (6)	0.008 (6)	0.045 (5)
C34	0.044 (2)	0.107 (4)	0.084 (3)	−0.007 (3)	−0.005 (3)	−0.001 (3)
C35	0.079 (3)	0.126 (4)	0.060 (3)	−0.030 (4)	−0.011 (3)	0.013 (3)
C36	0.096 (3)	0.081 (3)	0.059 (3)	−0.032 (3)	0.007 (3)	0.006 (3)
C37	0.156 (6)	0.155 (6)	0.066 (4)	−0.064 (5)	0.017 (4)	0.018 (4)
C38	0.102 (4)	0.106 (4)	0.110 (5)	0.036 (4)	−0.023 (4)	0.005 (4)
C39	0.103 (4)	0.112 (4)	0.088 (4)	−0.002 (4)	0.008 (4)	−0.045 (3)
C40	0.097 (4)	0.134 (5)	0.084 (4)	−0.038 (4)	−0.018 (4)	−0.035 (4)
C41	0.072 (3)	0.095 (3)	0.067 (3)	−0.006 (3)	0.000 (3)	0.006 (3)
C42	0.106 (5)	0.138 (5)	0.091 (4)	−0.005 (4)	0.026 (4)	0.020 (4)
C43	0.089 (4)	0.125 (5)	0.119 (5)	0.037 (4)	0.013 (4)	0.003 (4)

Geometric parameters (Å, º)

O1—C1	1.318 (5)	C21—C22	1.483 (6)
O1—H1O	0.8200	C21—H21	0.9300
O2—C1	1.223 (5)	C22—C23	1.515 (6)
O3—C3	1.355 (6)	C22—H22A	0.9700
O3—H3O	0.8200	C22—H22B	0.9700
O4—C11	1.431 (5)	C23—C24	1.517 (6)
O4—H4O	0.8200	C24—C25	1.516 (7)
O5—C13	1.204 (5)	C24—C40	1.519 (7)
O6—C19	1.430 (5)	C24—H24	0.9800
O6—C15	1.432 (5)	C25—C26	1.524 (6)
O7—C19	1.413 (5)	C25—H25A	0.9700
O7—C23	1.424 (6)	C25—H25B	0.9700
O8—C23	1.420 (5)	C26—C41	1.516 (7)
O8—C26	1.462 (5)	C26—C27	1.537 (7)
O9—C27	1.432 (5)	C27—C28	1.501 (7)
O9—C30	1.454 (6)	C27—H27	0.9800
O10—C31	1.419 (6)	C28—C29	1.509 (7)
O10—H10O	0.8200	C28—H28A	0.9700
O11—H11O	0.87 (6)	C28—H28B	0.9700
O11—H12O	0.96 (6)	C29—C30	1.538 (7)
C1—C2	1.473 (7)	C29—H29A	0.9700
C2—C7	1.394 (6)	C29—H29B	0.9700
C2—C3	1.413 (7)	C30—C31	1.517 (7)
C3—C4	1.384 (8)	C30—C43	1.519 (7)
C4—C5	1.357 (8)	C31—C32	1.511 (7)
C4—C33	1.526 (8)	C31—H31	0.9800
C5—C6	1.376 (7)	C32—H32A	0.9600
C5—H5	0.9300	C32—H32B	0.9600
C6—C7	1.390 (7)	C32—H32C	0.9600
C6—H6	0.9300	C33—H33A	0.9600
C7—C8	1.498 (6)	C33—H33B	0.9600
C8—C9	1.534 (6)	C33—H33C	0.9600
C8—H8A	0.9700	C34—H34A	0.9600
C8—H8B	0.9700	C34—H34B	0.9600
C9—C10	1.521 (6)	C34—H34C	0.9600
C9—H9A	0.9700	C35—H35A	0.9600
C9—H9B	0.9700	C35—H35B	0.9600
C10—C11	1.519 (6)	C35—H35C	0.9600
C10—C34	1.543 (6)	C36—C37	1.506 (7)
C10—H10	0.9800	C36—H36A	0.9700
C11—C12	1.528 (6)	C36—H36B	0.9700
C11—H11	0.9800	C37—H37A	0.9600
C12—C13	1.532 (6)	C37—H37B	0.9600
C12—C35	1.548 (6)	C37—H37C	0.9600
C12—H12	0.9800	C38—H38A	0.9600
C13—C14	1.496 (6)	C38—H38B	0.9600
C14—C15	1.533 (6)	C38—H38C	0.9600
C14—C36	1.535 (6)	C39—H39A	0.9600
C14—H14	0.9800	C39—H39B	0.9600
C15—C16	1.533 (6)	C39—H39C	0.9600
C15—H15	0.9800	C40—H40A	0.9600
C16—C17	1.509 (7)	C40—H40B	0.9600
C16—C38	1.542 (7)	C40—H40C	0.9600
C16—H16	0.9800	C41—C42	1.527 (7)
C17—C18	1.515 (7)	C41—H41A	0.9700
C17—H17A	0.9700	C41—H41B	0.9700
C17—H17B	0.9700	C42—H42A	0.9600
C18—C39	1.520 (7)	C42—H42B	0.9600
C18—C19	1.545 (6)	C42—H42C	0.9600
C18—H18	0.9800	C43—H43A	0.9600
C19—C20	1.486 (6)	C43—H43B	0.9600
C20—C21	1.302 (6)	C43—H43C	0.9600
C20—H20	0.9300
C1—O1—H1O	109.5	C23—C24—C40	116.2 (5)
C3—O3—H3O	109.5	C25—C24—H24	108.0
C11—O4—H4O	109.5	C23—C24—H24	108.0
C19—O6—C15	116.6 (3)	C40—C24—H24	108.0
C19—O7—C23	120.4 (3)	C24—C25—C26	106.0 (4)
C23—O8—C26	111.5 (3)	C24—C25—H25A	110.5
C27—O9—C30	108.3 (4)	C26—C25—H25A	110.5
C31—O10—H10O	109.5	C24—C25—H25B	110.5
H11O—O11—H12O	101 (5)	C26—C25—H25B	110.5
O2—C1—O1	121.3 (5)	H25A—C25—H25B	108.7
O2—C1—C2	123.3 (5)	O8—C26—C41	107.7 (4)
O1—C1—C2	115.4 (4)	O8—C26—C25	104.0 (4)
C7—C2—C3	119.5 (5)	C41—C26—C25	113.1 (4)
C7—C2—C1	124.6 (5)	O8—C26—C27	106.6 (4)
C3—C2—C1	115.8 (4)	C41—C26—C27	112.7 (4)
O3—C3—C4	115.7 (6)	C25—C26—C27	112.1 (4)
O3—C3—C2	122.7 (5)	O9—C27—C28	103.4 (4)
C4—C3—C2	121.6 (5)	O9—C27—C26	109.9 (4)
C5—C4—C3	117.5 (6)	C28—C27—C26	118.8 (4)
C5—C4—C33	121.6 (6)	O9—C27—H27	108.1
C3—C4—C33	120.9 (7)	C28—C27—H27	108.1
C4—C5—C6	122.1 (6)	C26—C27—H27	108.1
C4—C5—H5	119.0	C27—C28—C29	104.0 (4)
C6—C5—H5	119.0	C27—C28—H28A	111.0
C5—C6—C7	121.7 (5)	C29—C28—H28A	111.0
C5—C6—H6	119.2	C27—C28—H28B	111.0
C7—C6—H6	119.2	C29—C28—H28B	111.0
C6—C7—C2	117.3 (5)	H28A—C28—H28B	109.0
C6—C7—C8	117.8 (5)	C28—C29—C30	105.1 (4)
C2—C7—C8	124.7 (4)	C28—C29—H29A	110.7
C7—C8—C9	115.4 (4)	C30—C29—H29A	110.7
C7—C8—H8A	108.4	C28—C29—H29B	110.7
C9—C8—H8A	108.4	C30—C29—H29B	110.7
C7—C8—H8B	108.4	H29A—C29—H29B	108.8
C9—C8—H8B	108.4	O9—C30—C31	106.6 (4)
H8A—C8—H8B	107.5	O9—C30—C43	107.8 (4)
C10—C9—C8	113.2 (4)	C31—C30—C43	111.6 (5)
C10—C9—H9A	108.9	O9—C30—C29	104.8 (4)
C8—C9—H9A	108.9	C31—C30—C29	112.8 (4)
C10—C9—H9B	108.9	C43—C30—C29	112.7 (4)
C8—C9—H9B	108.9	O10—C31—C32	107.1 (5)
H9A—C9—H9B	107.8	O10—C31—C30	110.5 (4)
C11—C10—C9	111.5 (4)	C32—C31—C30	113.8 (5)
C11—C10—C34	112.6 (3)	O10—C31—H31	108.4
C9—C10—C34	110.5 (4)	C32—C31—H31	108.4
C11—C10—H10	107.3	C30—C31—H31	108.4
C9—C10—H10	107.3	C31—C32—H32A	109.5
C34—C10—H10	107.3	C31—C32—H32B	109.5
O4—C11—C10	108.8 (3)	H32A—C32—H32B	109.5
O4—C11—C12	107.7 (3)	C31—C32—H32C	109.5
C10—C11—C12	117.9 (4)	H32A—C32—H32C	109.5
O4—C11—H11	107.4	H32B—C32—H32C	109.5
C10—C11—H11	107.4	C4—C33—H33A	109.5
C12—C11—H11	107.4	C4—C33—H33B	109.5
C11—C12—C13	109.6 (4)	H33A—C33—H33B	109.5
C11—C12—C35	112.0 (4)	C4—C33—H33C	109.5
C13—C12—C35	105.7 (4)	H33A—C33—H33C	109.5
C11—C12—H12	109.8	H33B—C33—H33C	109.5
C13—C12—H12	109.8	C10—C34—H34A	109.5
C35—C12—H12	109.8	C10—C34—H34B	109.5
O5—C13—C14	122.5 (4)	H34A—C34—H34B	109.5
O5—C13—C12	119.7 (4)	C10—C34—H34C	109.5
C14—C13—C12	117.8 (4)	H34A—C34—H34C	109.5
C13—C14—C15	108.5 (4)	H34B—C34—H34C	109.5
C13—C14—C36	113.2 (4)	C12—C35—H35A	109.5
C15—C14—C36	113.7 (4)	C12—C35—H35B	109.5
C13—C14—H14	107.0	H35A—C35—H35B	109.5
C15—C14—H14	107.0	C12—C35—H35C	109.5
C36—C14—H14	107.0	H35A—C35—H35C	109.5
O6—C15—C16	112.3 (4)	H35B—C35—H35C	109.5
O6—C15—C14	105.6 (3)	C37—C36—C14	112.3 (4)
C16—C15—C14	114.3 (4)	C37—C36—H36A	109.1
O6—C15—H15	108.1	C14—C36—H36A	109.1
C16—C15—H15	108.1	C37—C36—H36B	109.1
C14—C15—H15	108.1	C14—C36—H36B	109.1
C17—C16—C15	109.3 (4)	H36A—C36—H36B	107.9
C17—C16—C38	110.2 (4)	C36—C37—H37A	109.5
C15—C16—C38	111.5 (4)	C36—C37—H37B	109.5
C17—C16—H16	108.6	H37A—C37—H37B	109.5
C15—C16—H16	108.6	C36—C37—H37C	109.5
C38—C16—H16	108.6	H37A—C37—H37C	109.5
C16—C17—C18	114.2 (4)	H37B—C37—H37C	109.5
C16—C17—H17A	108.7	C16—C38—H38A	109.5
C18—C17—H17A	108.7	C16—C38—H38B	109.5
C16—C17—H17B	108.7	H38A—C38—H38B	109.5
C18—C17—H17B	108.7	C16—C38—H38C	109.5
H17A—C17—H17B	107.6	H38A—C38—H38C	109.5
C17—C18—C39	110.9 (4)	H38B—C38—H38C	109.5
C17—C18—C19	110.4 (4)	C18—C39—H39A	109.5
C39—C18—C19	112.5 (4)	C18—C39—H39B	109.5
C17—C18—H18	107.6	H39A—C39—H39B	109.5
C39—C18—H18	107.6	C18—C39—H39C	109.5
C19—C18—H18	107.6	H39A—C39—H39C	109.5
O7—C19—O6	104.9 (3)	H39B—C39—H39C	109.5
O7—C19—C20	113.0 (4)	C24—C40—H40A	109.5
O6—C19—C20	111.7 (4)	C24—C40—H40B	109.5
O7—C19—C18	104.8 (3)	H40A—C40—H40B	109.5
O6—C19—C18	108.9 (4)	C24—C40—H40C	109.5
C20—C19—C18	113.0 (4)	H40A—C40—H40C	109.5
C21—C20—C19	124.1 (4)	H40B—C40—H40C	109.5
C21—C20—H20	117.9	C26—C41—C42	114.3 (4)
C19—C20—H20	117.9	C26—C41—H41A	108.7
C20—C21—C22	120.3 (4)	C42—C41—H41A	108.7
C20—C21—H21	119.9	C26—C41—H41B	108.7
C22—C21—H21	119.9	C42—C41—H41B	108.7
C21—C22—C23	110.7 (4)	H41A—C41—H41B	107.6
C21—C22—H22A	109.5	C41—C42—H42A	109.5
C23—C22—H22A	109.5	C41—C42—H42B	109.5
C21—C22—H22B	109.5	H42A—C42—H42B	109.5
C23—C22—H22B	109.5	C41—C42—H42C	109.5
H22A—C22—H22B	108.1	H42A—C42—H42C	109.5
O8—C23—O7	110.8 (4)	H42B—C42—H42C	109.5
O8—C23—C22	107.5 (4)	C30—C43—H43A	109.5
O7—C23—C22	110.5 (4)	C30—C43—H43B	109.5
O8—C23—C24	105.4 (4)	H43A—C43—H43B	109.5
O7—C23—C24	107.1 (4)	C30—C43—H43C	109.5
C22—C23—C24	115.5 (4)	H43A—C43—H43C	109.5
C25—C24—C23	102.0 (4)	H43B—C43—H43C	109.5
C25—C24—C40	114.2 (4)
O2—C1—C2—C7	162.1 (4)	C17—C18—C19—O7	164.9 (4)
O1—C1—C2—C7	−20.4 (6)	C39—C18—C19—O7	−70.6 (5)
O2—C1—C2—C3	−17.6 (6)	C17—C18—C19—O6	53.1 (5)
O1—C1—C2—C3	159.8 (4)	C39—C18—C19—O6	177.6 (4)
C7—C2—C3—O3	−177.6 (4)	C17—C18—C19—C20	−71.7 (5)
C1—C2—C3—O3	2.2 (6)	C39—C18—C19—C20	52.8 (6)
C7—C2—C3—C4	4.4 (7)	O7—C19—C20—C21	10.0 (6)
C1—C2—C3—C4	−175.9 (5)	O6—C19—C20—C21	127.9 (5)
O3—C3—C4—C5	176.1 (5)	C18—C19—C20—C21	−108.8 (5)
C2—C3—C4—C5	−5.7 (8)	C19—C20—C21—C22	−4.4 (7)
O3—C3—C4—C33	−4.6 (8)	C20—C21—C22—C23	−25.9 (6)
C2—C3—C4—C33	173.6 (5)	C26—O8—C23—O7	92.4 (4)
C3—C4—C5—C6	2.7 (9)	C26—O8—C23—C22	−146.8 (4)
C33—C4—C5—C6	−176.6 (6)	C26—O8—C23—C24	−23.1 (5)
C4—C5—C6—C7	1.7 (8)	C19—O7—C23—O8	70.8 (5)
C5—C6—C7—C2	−3.0 (7)	C19—O7—C23—C22	−48.3 (5)
C5—C6—C7—C8	−179.1 (5)	C19—O7—C23—C24	−174.8 (4)
C3—C2—C7—C6	0.0 (6)	C21—C22—C23—O8	−71.2 (5)
C1—C2—C7—C6	−179.7 (4)	C21—C22—C23—O7	49.8 (5)
C3—C2—C7—C8	175.9 (4)	C21—C22—C23—C24	171.6 (4)
C1—C2—C7—C8	−3.9 (6)	O8—C23—C24—C25	32.6 (5)
C6—C7—C8—C9	−88.6 (5)	O7—C23—C24—C25	−85.4 (5)
C2—C7—C8—C9	95.6 (5)	C22—C23—C24—C25	151.1 (5)
C7—C8—C9—C10	−175.6 (4)	O8—C23—C24—C40	157.6 (4)
C8—C9—C10—C11	−52.0 (5)	O7—C23—C24—C40	39.6 (6)
C8—C9—C10—C34	−178.0 (4)	C22—C23—C24—C40	−84.0 (6)
C9—C10—C11—O4	−62.6 (4)	C23—C24—C25—C26	−30.6 (6)
C34—C10—C11—O4	62.2 (5)	C40—C24—C25—C26	−156.8 (4)
C9—C10—C11—C12	174.5 (4)	C23—O8—C26—C41	−116.7 (4)
C34—C10—C11—C12	−60.6 (5)	C23—O8—C26—C25	3.4 (5)
O4—C11—C12—C13	63.2 (4)	C23—O8—C26—C27	122.1 (4)
C10—C11—C12—C13	−173.4 (4)	C24—C25—C26—O8	17.6 (5)
O4—C11—C12—C35	−179.8 (4)	C24—C25—C26—C41	134.1 (5)
C10—C11—C12—C35	−56.3 (5)	C24—C25—C26—C27	−97.2 (5)
C11—C12—C13—O5	43.7 (6)	C30—O9—C27—C28	−37.7 (5)
C35—C12—C13—O5	−77.2 (6)	C30—O9—C27—C26	−165.6 (4)
C11—C12—C13—C14	−138.3 (4)	O8—C26—C27—O9	65.3 (5)
C35—C12—C13—C14	100.8 (5)	C41—C26—C27—O9	−52.6 (5)
O5—C13—C14—C15	−100.9 (5)	C25—C26—C27—O9	178.5 (4)
C12—C13—C14—C15	81.2 (5)	O8—C26—C27—C28	−53.4 (5)
O5—C13—C14—C36	26.4 (6)	C41—C26—C27—C28	−171.4 (4)
C12—C13—C14—C36	−151.5 (4)	C25—C26—C27—C28	59.8 (6)
C19—O6—C15—C16	57.1 (5)	O9—C27—C28—C29	36.2 (5)
C19—O6—C15—C14	−177.7 (3)	C26—C27—C28—C29	158.2 (4)
C13—C14—C15—O6	80.5 (4)	C27—C28—C29—C30	−21.8 (5)
C36—C14—C15—O6	−46.5 (5)	C27—O9—C30—C31	143.4 (4)
C13—C14—C15—C16	−155.5 (4)	C27—O9—C30—C43	−96.7 (5)
C36—C14—C15—C16	77.5 (5)	C27—O9—C30—C29	23.5 (5)
O6—C15—C16—C17	−49.6 (5)	C28—C29—C30—O9	0.0 (5)
C14—C15—C16—C17	−169.9 (4)	C28—C29—C30—C31	−115.7 (5)
O6—C15—C16—C38	−171.7 (4)	C28—C29—C30—C43	116.9 (5)
C14—C15—C16—C38	68.0 (5)	O9—C30—C31—O10	−61.8 (5)
C15—C16—C17—C18	49.9 (6)	C43—C30—C31—O10	−179.3 (4)
C38—C16—C17—C18	172.7 (4)	C29—C30—C31—O10	52.7 (6)
C16—C17—C18—C39	−178.0 (4)	O9—C30—C31—C32	177.6 (5)
C16—C17—C18—C19	−52.7 (5)	C43—C30—C31—C32	60.1 (6)
C23—O7—C19—O6	−103.5 (4)	C29—C30—C31—C32	−67.9 (6)
C23—O7—C19—C20	18.4 (5)	C13—C14—C36—C37	67.3 (6)
C23—O7—C19—C18	141.9 (4)	C15—C14—C36—C37	−168.2 (5)
C15—O6—C19—O7	−169.4 (3)	O8—C26—C41—C42	−179.9 (5)
C15—O6—C19—C20	67.9 (5)	C25—C26—C41—C42	65.8 (6)
C15—O6—C19—C18	−57.6 (4)	C27—C26—C41—C42	−62.6 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O4^i	0.82	1.78	2.584 (4)	165
O3—H3O···O2	0.82	1.80	2.529 (6)	147
O4—H4O···O11	0.82	1.84	2.659 (4)	175
O10—H10O···O11	0.82	2.13	2.942 (6)	170
O11—H11O···O9	0.87 (6)	2.60 (6)	3.009 (4)	110 (5)
O11—H12O···O8	0.96 (6)	1.80 (7)	2.742 (5)	167 (6)
C8—H8A···O1	0.97	2.23	2.757 (5)	113
C11—H11···O5	0.98	2.48	2.822 (5)	100

Symmetry code: (i) −x+1/2, −y, z−1/2.