PROCEDURE FOR CRYSTALLIZATION OF (22£)-(24R)-2-METHYLENE-22- DEHYDRO- la,24,25-TRIHYDROXY- 19-NOR- VITAMIN D ₃

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

[0001] The present application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/573,387, filed on October 17, 2017, the content of which is incorporated herein by reference in its entirety.

BACKGROUND

[0002] The field of the invention relates to vitamin D compounds, and more particularly to (22E)-2-methylene-22-dehydro-la,24,25-trihydroxy-19-nor-vita min D ₃ analogs and their pharmaceutical uses. In particular, the field of the invention relates to procedures for crystallizing vitamin D compounds such as (22£)-(24R)-2-methylene-22-dehydro-la,24,25- trihydroxy-19-nor- vitamin D ₃ .

[0003] Purification of organic compounds, especially those designated for pharmaceutical use, is of considerable importance for chemists synthesizing such compounds. Preparation of the compound usually requires many synthetic steps and, therefore, the final product can be contaminated not only with side-products derived from the last synthetic step of the procedure but also with compounds that were formed in previous steps. Even chromatographic purification, which is a very efficient but relatively time-consuming process, does not usually provide compounds which are sufficiently pure to be used as drugs.

[0004] Depending on the method used to synthesize la-hydroxy itamin D compounds, different minor undesirable compounds can accompany the final product. Thus, for example, if direct C-1 hydroxylation of the 5,6-trans geometric isomer of vitamin D is performed, followed by SeOi NMO oxidation and photochemical irradiation, (see Andrews et al., J. Org. Chem. 51, 1635 (1986); Calverley et al., Tetrahedron 43, 4609 (1987); Choudry et al, J. Org. Chem. 58, 1496 (1993)), the final la-hydroxy vitamin D product can be contaminated with 1β- hydroxy- as well as 5,6-trans isomers. If the method consists of C-l allylic oxidation of the 4- phenyl-l,2,4-triazoline-3,5-dione adduct of the pre-vitamin D compound, followed by cycloreversion of the modified adduct under basic conditions, (see Nevinckx et al, Tetrahedron 4 9419 (1991); Vanmaele et al, Tetrahedron 41, 141 (1985) and 40, 1179 (1994); Vanmaele et al, Tetrahedron Lett. 23. 995 (1982)), one can expect that the desired la-hydroxy vitamin can be contaminated with the pre-vitamin 5(10), 6,8-triene and 1β- hydroxy isomer. One of the most useful C-l hydroxylation methods, of very broad scope and numerous applications, is the experimentally simple procedure elaborated by Paaren et al, J. Org. Chem. 45, 3253 (1980); and Proc. Natl. Acad. Sci U.S.A. 75, 2080 (1978). This method consists of allylic oxidation of 3,5-cyclovitamin D derivatives, readily obtained from the buffered solvolysis of vitamin D tosylates, with Se0 ₂ /t-BuOOH and subsequent acid- catalyzed cycloreversion to the desired la-hydroxy compounds. Taking into account this synthetic path it is reasonable to assume that the final product can be contaminated with the la-hydroxy epimer, the 5,6-trans isomer and the pre-vitamin D form, la-hydroxy vitamin D ₄ is another undesirable contaminant found in la-hydroxy vitamin D compounds synthesized from vitamin D ₂ or from ergosterol. la-hydroxyvitamin D ₄ results from C-l oxidation of vitamin D ₄ , which in turn is derived from contamination of the commercial ergosterol material. Typically, the final product may contain up to about 1.5% by weight la- hydroxyvitamin D ₄ . Thus, a purification technique that would eliminate or substantially reduce the amount of la-hydroxyvitamin D ₄ in the final product to less than about 0.1-0.2% would be highly desirable.

[0005] The vitamin D conjugated triene system is not only heat- and light-sensitive but it is also prone to oxidation, leading to the complex mixture of very polar compounds. Oxidation usually happens when a vitamin D compound has been stored for a prolonged time. Other types of processes that can lead to a partial decomposition of vitamin D compounds consist of some water-elimination reactions. The driving force for these reactions is the allylic (la-) and homoallylic (3β-) position of the hydroxy groups. The presence of such above-mentioned oxidation and elimination products can be easily detected by thin-layer chromatography.

[0006] Usually, all la-hydroxylatation procedures require at least one chromatographic purification. However, even chromatographically purified la-hydroxy vitamin D compounds, although showing consistent spectroscopic data that suggests homogeneity, do not meet the purity criteria required for therapeutic agents that can be orally, parenterally or transdermally administered.

[0007] Therefore, improved purification procedures for vitamin D compounds are desirable such as crystallization procedures. Here, the present inventors disclose procedures for crystallizing (22E)-(24^)-2-methylene-22-dehydro-la,24,25-trihydroxy-19-no r-vitamin D3.

SUMMARY

[0008] Disclosed herein are procedures for purifying (22E)-(24R)-2-methylene-22-dehydro- la,24,25-trihydroxy-19-nor-vitamin D3, otherwise referred to as "WT-51" by means of crystallization to obtain WT-51 in crystalline form.

[0009] The disclosed crystallization procedures utilize a solvent to dissolve WT-51. The solvent plays an important role in the crystallization procedure, and is typically an individual liquid substance or a suitable mixture of different liquids. For crystallizing WT-51, the most appropriate solvent and/or solvent system is characterized by the following factors: (1) low toxicity; (2) low boiling point (e.g. less than about 100, 90, or 80 °C); (3) significant dependence of solubility properties with regard to temperature (condition necessary for providing satisfactory crystallization yield); and (4) relatively low cost.

[0010] Interestingly, a mixture of ethyl acetate and hexane was found to be a suitable solvent for the crystallization of WT-51. In particular, it was determined that a mixture of about 20% to about 30% ethyl acetate (v/v) with about 80% to about 70% hexane (v/v) was a suitable solvent for the crystallization of WT-51. In the disclosed method, WT-51 first was dissolved in ethyl acetate and hexane was added dropwise to reach a saturation point. After sitting at room temperature, crystals of WT-51 began to grow after about 1 hour. The ethyl acetate/hexane solvent mixture also was easy to remove by evaporation or other well-known methods. The precipitated crystals were sufficiently large to assure their recovery by filtration or other means, and thus were suitable for X-ray diffraction analysis.

[0011] Accordingly, the present invention provides a compound having the formula:

in crystalline form. More specifically, the compound may be referred to as (22E)-(24R)-2- methylene-22-dehydro-la,24,25-trihydroxy-19-nor-vitamin D ₃ , or "WT-51" in crystalline form.

[0012] The crystalline forms of WT-51 may be formulated as a pharmaceutical composition comprising a crystalline form of WT-51 and a suitable carrier. The pharmaceutical compositions may be administered to a subject in need thereof for treating a variety of conditions that are treated and/or prevented by vitamin D compounds. [0013] In some embodiments, the crystalline forms of WT-51 disclosed herein may be utilized in methods for treating and/or preventing skin diseases, disorders, and conditions in a subject in need thereof. These may include, but are not limited to psoriasis, acne, lack of adequate skin firmness, lack of adequate dermal hydration, and insufficient sebum secretion.

[0014] In further embodiments, the crystalline forms of WT-51 disclosed herein may be utilized in methods for treating and/or preventing cell proliferative diseases or disorders such as cancer in a subject in need thereof. These may include, but are not limited to leukemia, colon cancer, breast cancer, skin cancer, and prostate cancer.

[0015] In even further embodiments, the crystalline forms of WT-51 disclosed herein may be utilized in methods for treating and/or preventing autoimmune diseases and disorders in a subject in need thereof. These may include, but are not limited to multiple sclerosis, diabetes mellitus, lupus, host versus graft reaction, and rejection of transplants.

[0016] In even further embodiments, the crystalline forms of WT-51 disclosed herein may be utilized in methods for treating and/or preventing inflammatory diseases. These may include, but are not limited to rheumatoid arthritis, asthmas, and inflammatory bowel diseases. The crystalline forms of WT-51 may be utilized specifically in methods of treating or preventing inflammatory bowel diseases that include Crohn's disease and ulcerative colitis.

[0017] In even further embodiments, the crystalline forms of WT-51 disclosed herein may be utilized in methods for treating and/or preventing obesity, inhibiting adipocyte differentiation, inhibiting SCD-1 gene transcription, and/or reducing body fat.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is an illustration of one embodiment of a three dimensional molecular structure for WT-51 as defined by the atomic positional parameters discovered and set forth herein. [0019] Figure 2 is an illustration of one embodiment of a three dimensional molecular structure for WT-51 as defined by the atomic positional parameters discovered and set forth herein.

[0020] Figure 3 is an illustration of one embodiment of a three dimensional molecular structure for WT-51 as defined by the atomic positional parameters discovered and set forth herein.

[0021] Figure 4 is an illustration of three dimensional molecular structures for WT-51 as defined by the atomic positional parameters discovered and set forth herein.

DETAILED DESCRIPTION

[0022] The disclosed subject matter further may be described utilizing terms as defined below.

[0023] Unless otherwise specified or indicated by context, the terms "a", "an", and "the" mean "one or more." For example, the phrases "a compound" and "an analog" should be interpreted to mean "one or more compounds" and "one or more analogs," respectively.

[0024] As used herein, "about", "approximately," "substantially," and "significantly" will be understood by persons of ordinary skill in the art and will vary to some extent on the context in which they are used. If there are uses of the term which are not clear to persons of ordinary skill in the art given the context in which it is used, "about" and "approximately" will mean plus or minus <10% of the particular term and "substantially" and "significantly" will mean plus or minus >10% of the particular term.

[0025] As used herein, the terms "include" and "including" have the same meaning as the terms "comprise" and "comprising." The transitional term "comprising" should be interpreted as being "open-ended" such that a claim utilizing the term "comprising" should be interpreted as requiring the recited components but being permitted to include other additional components. The transitional term "consisting essentially of should be interpreted as being "partially closed" such that a claim utilizing the term "consisting essentially of should be interpreted as requiring the recited components and permitting only other additional components that do not materially affect the basic and novel characteristics of the claimed subject matter. The transitional term "consisting" should be interpreted as being "closed" such that a claim utilizing the term "consisting" should be interpreted as requiring the recited components and permitting no other additional components.

[0026] As used herein, the terms "native hormone" and "la,25(OH)2D3" may be used interchangeably.

[0027] As used herein, the compound "WT-51" refers to (22E)-(24R)-2-methylene-22- dehydro-la,24,25-trihydroxy-19-nor-vitamin D ₃ . Methods for synthesizing WT-51 are disclosed, for example, in U.S. Patent No. 9,416,102, the content of which is incorporated herein by reference in its entirety.

[0028] As disclosed herein, the crystalline forms of WT-51 may be utilized to treat and/or prevent diseases or disorders in a subject in need thereof. The terms "subject," "patient," and "individual" may be used interchangeably herein.

[0029] A subject in need thereof may include any animal. The animal may be a human, a domestic animal such as a dog or a cat, or an agricultural animal, especially those that provide meat for human consumption, such as fowl like chickens, turkeys, pheasant or quail, as well as bovine, ovine, caprine, or porcine animals.

[0030] A subject in need thereof may refer to subject having or at risk for acquiring a disease or disorders associated with vitamin D activity. For example, a subject in need thereof may include a subject having or at risk for acquiring bone diseases and disorders, which may include, metabolic bone diseases and disorders where an increase in bone mass is desirable such as osteoporosis (e.g. , senile osteoporosis, postmenopausal osteoporosis, steroid-induced osteoporosis, and low bone-turnover osteoporosis), osteopenia, and osteomalacia. A subject in need thereof may also include a subject in need of an increase in bone strength.

[0031] A subject in need thereof may include a subject having or at risk for developing skin diseases, disorders, and conditions. These may include, but are not limited to psoriasis, acne, lack of adequate skin firmness, lack of adequate dermal hydration, and insufficient sebum secretion.

[0032] A subject in need thereof may include a subject having or at risk for developing cell proliferative diseases or disorders such as cancer. These may include, but are not limited to leukemia, colon cancer, breast cancer, skin cancer, and prostate cancer.

[0033] A subject in need thereof may include a subject having or at risk for developing autoimmune diseases and disorders. These may include, but are not limited to multiple sclerosis, diabetes mellitus, lupus, host versus graft reaction, and rejection of transplants.

[0034] A subject in need thereof may include a subject having or at risk for developing an inflammatory disease or disorder. These may include, but are not limited to rheumatoid arthritis, asthmas, and inflammatory bowel diseases. A subject in need thereof may include having or at risk for developing Crohn's disease and ulcerative colitis.

[0035] A subject in need thereof may include a subject having or at risk for developing obesity. A subject in need thereof may include a subject in need of or desirous of inhibiting adipocyte differentiation, inhibiting SCD-1 gene transcription, and/or reducing body fat.

[0036] A subject in need thereof may include a subject having or at risk for developing secondary hyperparathyroidism. In particular, a subject in need thereof may include a subject having or at risk for developing secondary hyperparathyroidism of renal osteodystrophy.

[0037] For prevention and/or treatment purposes, the crystalline forms of WT-51 may be formulated for pharmaceutical applications as a solution in innocuous solvents, or as an emulsion, suspension or dispersion in suitable solvents or carriers, or as pills, tablets or capsules, together with solid carriers, according to conventional methods known in the art. Any such formulations may also contain other pharmaceutically-acceptable and non-toxic excipients such as stabilizers, anti-oxidants, binders, coloring agents or emulsifying or taste- modifying agents.

[0038] The crystalline forms of WT-51 may be administered orally, topically, parenterally, rectally, nasally, sublingually or transdermally. The compound is advantageously administered by injection or by intravenous infusion or suitable sterile solutions, or in the form of liquid or solid doses via the alimentary canal, or in the form of creams, ointments, patches, or similar vehicles suitable for transdermal applications.

[0039] A dose of from O.O^g to 1000 μg per day of the crystalline forms of WT-51, preferably from about O.^g to about 500 μg per day, is appropriate for prevention and/or treatment purposes, such dose being adjusted according to the disease to be treated, its severity and the response of the subject as is well understood in the art. Because the compound exhibits specificity of action, each may be suitably administered alone, or together with graded doses of another active vitamin D compound (e.g., lCX-hydroxy vitamin D ₂ or D3, or la,25-dihydroxyvitamin D ₃ ) in situations where different degrees of bone mineral mobilization and calcium transport stimulation is found to be advantageous.

[0040] Compositions for use in the above-mentioned treatments comprise an effective amount of crystalline forms of WT-51 as the active ingredient, and a suitable carrier. An effective amount of such compound for use in accordance with this invention is from about 0.01 μg to about 1000 μg per gm of composition, preferably from about 0.1 g to about 500 g per gram of composition, and may be administered topically, transdermally, orally, rectally, nasally, sublingually, or parenterally in dosages of from about 0.0^g/day to about 1000 μg/day, and preferably from about 0.1 μg/day to about 500 μg/day. [0041] The formulations of the present invention comprise an active ingredient in association with a pharmaceutically acceptable carrier therefore and optionally other therapeutic ingredients. The carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulations and not deleterious to the recipient thereof.

[0042] Formulations of the present invention suitable for oral administration may be in the form of discrete units as capsules, sachets, tablets or lozenges, each containing a predetermined amount of the active ingredient, for example, in the form of a crystalline powder or crystalline granules.

[0043] The formulations may conveniently be presented in dosage unit form and may be prepared by any of the methods well known in the art of pharmacy. By the term "dosage unit" is meant a unitary, i.e. a single dose which is capable of being administered to a subject as a physically and chemically stable unit dose comprising either the active ingredient as such or a mixture of it with solid or liquid pharmaceutical diluents or carriers.

EXAMPLES

[0044] The following Examples are illustrative and are not intended to limit the scope of the claimed subject matter.

[0045] Example 1 - Preparation of (22£)-(24R -2-methylene-22-dehydro-la,24,25- trihydroxy-19-nor- vitamin D ₃ (WT-51)

[0046] (22E)-(24^)-2-methylene-22-dehydro-la,24,25-trihydroxy-19-no r- vitamin D ₃ (WT- 51) was synthesized as previously described. (See U.S. Patent No. 9,416,102, the content of which is incorporated herein by reference in its entirety).

[0047] (22£)-Des-A, _J B-8 -benzoyloxy-24-oxo-25-[(triethylsilyl)oxy]-22-dehydrocholest an

(3). To a stirred solution of 2 (Scheme 1; 250 mg; 0.64 mmol) in tetrahydrofuran (1.5 ml) 1 M solution of lithium hexamethyldisilazide in tetrahydrofuran (700 μΐ; 0.70 mmol) was added dropwise. After 1 h a solution of l ¹ (200 mg; 0.64 mmol) in tetrahydrofuran (1.5 ml) was added via cannula. The reaction mixture was stirred for 3 days. Then saturated aqueous solution of NH ₄ C1 (2 ml), brine (2 ml) and water (5 ml) was added at 0°C and the resulting mixture was extracted with methylene dichloride (3 x 50 ml). Organic phase was dried over anhydrous Na ₂ S0 ₄ , concentrated under reduced pressure and the residue was purified by column chromatography (2 - 5% ethyl acetate/hexane) to give 200 mg (0.39 mmol; 61% yield) of 3. [a] _D = +94.3 (c 1.1, CHC1 ₃ ); 1H NMR (400 MHz, CDC1 ₃ ) δ 0.60 (6H, q, / = 7.9 Hz), 0.95 (9H, t, i = 7.9 Hz), 1.10 (3H, s), 1.12 (3H, d, / = 6.6 Hz), 1.34 (6H, s), 2.04 (2H, m) 2.32 (1H, m), 5.42 (1H, br d, / = 1.9 Hz), 6.71 (1H, d, / = 15.4 Hz), 6.84 (1H, dd, / = 15.4 Hz, J = 8.6 Hz), 7.45 (2H, t, = 7.4 Hz), 7.56 (1H, t, J = 7.4 Hz), 8.05 (2H, d, = 7.4 Hz); ¹³ C NMR (101 MHz, CDCI3) δ 6.5, 7.0, 13.8, 18.0, 19.2, 22.6, 27.0, 27.1, 27.2, 30.5, 39.8, 42.2, 51.4, 55.4, 72.0, 78.8, 121.7, 128.4, 129.5, 132.7, 153.2, 166.4, 203.2; Exact mass (ESI) calculated for C ₃₁ H ₄₉ 0 ₄ Si ([M + H] ⁺ ) 513.3395, found 513.3405.

[0048] (22£)-Des-A,B-8 -benzoyloxy-24-hydroxy-25-[(triethylsilyl)oxy]-22- dehydrocholestan (4, mixture of 24-isomers). To a stirred solution of 3 (200 mg; 0.39 mmol) in tetrahydrofuran (1.5 ml) and ethanol (4.5 ml) CeCl ₃ x 7H ₂ 0 (298 mg; 0.80 mmol) and NaB¾ (46 mg; 1.20 mmol) was added at 0°C. After 30 min. saturated aqueous solution of NH4CI (2 ml) and water (5 ml) were added and the mixture was extracted with methylene dichloride (3 x 40 ml). Organic phase was dried over anhydrous Na ₂ S0 ₄ , concentrated under reduced pressure and the residue was purified by column chromatography (5 - 15% ethyl acetate/hexane) to give 180 mg (0.35 mmol; 90% yield) of 4 as a mixture of 24- diastereoisomers. Exact mass (ESI) calculated for C ₃₁ H ₅ o0 ₄ SiNa ([M + Na] ⁺ ) 537.3371, found 537.3380.

[0049] (22£;)-Des-A,β-8β-benzo loxy-24,25-di-[(triethylsilyl)ox ]-22-dehydrocholestan (5, mixture of 24-isomers). To a stirred solution of 4 (150 mg; 0.29 mmol) and 2,6-lutidine (67 μΐ; 62 mg; 0.58 mmol) in methylene dichloride (1 ml) triethylsilyl trifluoromethanesulfonate (79 μΐ; 92 mg; 0.35 mmol) was added dropwise at -50°C. After 20 min. wet methylene dichloride (1 ml) and water (5 ml) was added and the mixture was extracted with methylene dichloride (3 x 25 ml). Organic phase was dried over anhydrous Na ₂ S0 ₄ and concentrated under reduced pressure. The residue was purified by column chromatography (hexane - 3% ethyl acetate/hexane) to give 165 mg (0.26 mmol; 90% yield) of 5. Exact mass (ESI) calculated for (ΓΜ + Na] ⁺ ) 651.4236, found 651.4234.

[0050] (22£)-Des-A,fi-24,25-di-[(triethylsilyl)oxy]-22-dehydrochol estan-8 -ol (6, mixture of 24-isomers). A solution of 5 (160 mg; 0.25 mmol) in tetrahydrofuran (3 ml) was treated with a 3 M solution of methylmagnesium bromide in diethyl ether (750 μΐ; 2.25 mmol) for 5 h at 0°C. Saturated aqueous solution of NH ₄ C1 (2 ml), brine (2 ml) and water (5 ml) was carefully added and the mixture was extracted with methylene dichloride (3 x 25 ml). Organic phase was dried over anhydrous Na ₂ S0 ₄ and concentrated under reduced pressure. The residue was purified on a silica gel Sep-Pack cartridge (5 - 15% ethyl acetate/hexane) to give 106 mg (0.20 mmol; 81% yield) of 6. Exact mass (ESI) calculated for C3oH ₆ o0 ₃ Si ₂ Na ([M + Na] ⁺ ) 547.3974, found 547.3957.

[0051] (22£)-Des-A,B-24,25-di-[(triethylsilyl)oxy]-22-dehydrochole stan-8-one (7, mixture of 24-isomers). A solution of 6 (65 mg; 120 μιηοΐ) and pyridinium p- toluenesulfonate (2 crystals) in methylene dichloride (6 ml) was treated with pyridinium dichromate (150 mg; 400 μηιοΐ) for 3 h. The mixture was purified on a silica gel Sep-Pack cartridge (3 - 7% ethyl acetate/hexane) to give 54 mg (103 μιηοΐ; 86%) of 7. Exact mass (ESI) calculated for C ₃ oH ₅₈ 0 ₃ Si ₂ Na ([M + Na] ⁺ ) 545.3817, found 545.3817.

[0052] (22£)-(24R)-2-Methylene-22-dehydro-la,24,25-trihydroxy-19-n orvitamin D ₃ (10, WT-51) and (22E)-(24S)-2-Methylene-22-dehydro-la,24,25-trihydroxy-19- norvitamin D ₃ (11, WT-52). To a stirred solution of 8 (87 mg; 150 μιηοΐ) in tetrahydrofuran (1.5 ml) two drops of 1.8 M phenyl lithium solution in di-rc-butyl ether was added at -25°C and the solution turned deep orange. Then stoichiometric amount of phenyl lithium solution (78 μΐ; 140 μιηοΐ) was added dropwise. After 20 min. the mixture was cooled to -78°C and a solution of 7 (53 mg; 101 μηιοΐ) in tetrahydrofuran (0.75 ml) was transferred via cannula. The mixture was stirred for 2 h, warmed to 0°C and stirred for next 2 h. Saturated aqueous solution of NH4CI (1 ml), brine (1 ml) and water (5 ml) was carefully added and the mixture was extracted with hexane (3 x 25 ml). Organic phase was dried over Na ₂ S0 ₄ and concentrated under reduced pressure. The residue was purified on a silica gel Sep-Pack cartridge (hexane - 2% ethyl acetate/hexane) to give 90 mg of crude 9. Crude 9 was dissolved in acetonitrile (2 ml) and treated with (+)-camphor- 10- sulfonic acid (40 mg; 172 μιηοΐ) for 2 days. The mixture was purified on a previously treated with 10 drops of triethylamine silica gel Sep-Pack cartridge (10 - 30% 2-propanol/hexane) to give 28 mg (65 μιηοΐ; 64% yield from 7) of 10 and 11 as a mixture of diastereoisomers. The mixture was separated on HPLC (15% water/methanol; Zorbax-Eclipse XDB C18 5 μιη; 3.5 ml/min.; R _t = 5.30 min. for 10 and R _t = 5.80 min. for 11) to give 9.5 mg (22 μιηοΐ; 22% yield from 7) of 10 and 13.5 mg (31μιηο1; 31% yield from 7) of 11. X-ray analysis of 11 (Figure 7) has shown 245 configuration. 10: UV (EtOH) X _max = 245, 252, 262 nm; 1H NMR (500 MHz, CD ₃ OD) δ 0.60 (3H, s), 1.07 (3H, d, J = 6.6 Hz), 2 x 1.13 (3H each, s), 2.25-2.31 (2H, m), 2.48 (1H, dd, J = 13.4 Hz, J = 3.8 Hz), 2.66 (1H, dd, J = 13.2 Hz, J = 4.3 Hz), 2.85 (1H, dd, J = 12.2 Hz, J = 3.8 Hz), 3.73 (1H, d, J = 7.4 Hz), 4.37 (1H, m), 4.41 (1H, m), 5.04 (1H, s), 5.05 (1H, s), 5.43 (1H, dd, / = 15.4 Hz, / = 7.5 Hz), 5.52 (1H, dd, J = 15.4 Hz, J = 8.6 Hz), 5.90 (1H, d, J = 11.1 Hz), 6.26 (1H, d, = 11.1 Hz); 11: UV (EtOH) λ _ΜΧ = 244, 252, 261 nm; 1H NMR (500 MHz, CD ₃ OD) δ 0.60 (3H, s), 1.06 (3H, d, J = 6.6 Hz), 1.12 (3H, s), 1.13 (3H, s), 1.65-1.70 (2H, m), 1.79-1.83 (1H, m), 1.93-2.07 (2H, m), 2.13 (1H, m), 2.25-2.31 (2H, m), 2.48 (1H, dd, / = 13.3 Hz, / = 3.9 Hz), 2.67 (1H, dd, = 13.2 Hz, / = 4.3 Hz), 2.85 (1H, dd, / = 12.2 Hz, J = 3.7 Hz), 3.75 (1H, d, J = 6.7 Hz), 4.37 (1H, m), 4.41 (1H, m), 5.04 (1H, s), 5.06 (1H, s), 5.45 (1H, dd, J = 15.4 Hz, J = 6.9 Hz), 5.57 (1H, dd, J = 15.4 Hz, J = 8.4 Hz), 5.90 (1H, d, = 11.1 Hz), 6.26 (1H, d, = 11.1 Hz); MS (EI) m/z 430 (M ⁺ , 10), 396 (7), 253 (22), 9100); exact mass (ESI) calculated for C ₂ 7H ₄ 20 ₄ Na ([M + Na] ⁺ ) 453.2976, found 453.2977.



(i) LiHMDS, THF, 61%; (ii) NaBH ₄ , CeCI ₃ x7H ₂ 0, EtOH, THF, 90%; (iii) TESOTf, 2,6-lutidine, CH ₂ CI ₂ , 90%; (iv) MeMgBr, Et ₂ 0, THF, 81%; (v) PDC, PPTS, CH ₂ CI ₂ , 86%; (vi) PhLi, (n-Bu) ₂ 0, THF; (vii) CSA, MeCN, 22% of 10 from 7 and 31% of 11 from 7. [0053] Example 2 - Preparation of l-(Dimetoxyphosphoryl)-3-methyl-3- r(triethylsilyl)oxyl -2-butanone

[0054] 3-Methyl-3-[(triethylsilyl)oxy]-2-butanone (13). To a stirred solution of 3- hydroxy-3-methyl-2-butanone (Scheme 2; 1.20 ml; 1.16 g; 11.4 mmol) and 2,6-lutidine (1.86 ml; 1.71 g; 16.0 mmol) in methylene dichloride (30 ml) triethylsilyl trifluoromethanesulfonate (3.11 ml; 3.61 g; 13.7 mmol) was added dropwise at -50°C. After 20 min. wet methylene dichloride (5 ml) and water (50 ml) was added and the mixture was extracted with methylene dichloride (3 x 100 ml). Organic phase was dried over anhydrous Na ₂ S0 ₄ and concentrated under reduced pressure. The residue was purified by column chromatography (hexane - 3% ethyl acetate/hexane) to give 2.40 g (10.4 mmol; 91% yield) of 13. 1H NMR (500 MHz, CDC1 ₃ ) δ 0.63 (6H, q, / = 7.9 Hz), 0.97 (9H, t, J = 7.9 Hz), 1.33 (6H, s), 2.23 (3H, s); ¹³ C NMR (126 MHz, CDC1 ₃ ) δ 6.5, 7.0, 27.0, 27.7, 79.7, 214.0; MS (EI) m/z 216 ([M - Et] ⁺ , 100), 173 (81), 172 (30) 115 (68), 87 (67); exact mass calculated for C ₉ H ₁₉ 0 ₂ Si ([M - Et] ⁺ ) 187.1149, found 187.1144.

[0055] l-Bromo-3-methyl-3-[(triethylsilyl)oxy]-2-butanone (14). To a stirred solution of 13 (2.40 g; 10.4 mmol) and triethylamine (2.92 ml; 2.12 g; 21.0 mmol) in methylene dichloride (50 ml) triethylsilyl trifluoromethanesulfonate (2.37 ml; 2.75 g; 10.4 mmol) was added dropwise at 0°C. After 15 min. N-bromosuccinimide (2.05 g; 11.5 mmol) was added and a cooling bath was removed. After 30 min. saturated aqueous solution of NH4CI (10 ml) and water (50 ml) was added and the mixture was extracted with methylene dichloride (3 x 100 ml). Organic phase was dried over anhydrous Na ₂ S0 ₄ and concentrated under reduced pressure. The residue was purified by column chromatography (hexane - 5% ethyl acetate/hexane) to give 1.55 g (5.25 mmol; 50% yield) of 14. 1H NMR (400 MHz, CDCI3) 6 0.64 (6H, q, J = 7.9 Hz), 0.97 (9H, t, J = 7.9 Hz), 1.41 (6H, s), 4.44 (2H, s); ¹³ C NMR (101 MHz, CDC1 ₃ ) δ 6.5, 7.0, 27.8, 33.6, 80.4, 206.2; MS (EI) m/z 294 and 296 ([M - Et] ⁺ , 24 and 23), 187 (45), 173 (100); exact mass calculated for C ₉ H ₁₈ 0 ₂ BrSi ([M - Et] ⁺ ) 265.0254, found 265.0247.

[0056] l-(Dimetoxyphosphoryl)-3-methyl-3-[(triethylsilyl)oxy]-2-but anone (2). A solution of 14 (1.55 g; 5.25 mmol) and trimethyl phosphite (514 μΐ; 782 mg; 6.31 mmol) in toluene (20 ml) was refluxed for 3 days. The mixture was purified by column chromatography (5 - 15% 2-propanol/hexane) to give 1.54 g (4.75 mmol; 90% yield) of 2. 1H NMR (400 MHz, CDCls) δ 0.65 (6H, q, J = 7.9 Hz), 0.98 (9H, t, J = 7.9 Hz), 1.36 (6H, s), 3.40 (2H, d, JH-P = 20.7 Hz) 3.80 (6H, d, J„. _P = 11.2 Hz); ¹³ C NMR (101 MHz, CDC1 ₃ ) δ 6.4, 6.9, 26.8, 33.7 (d, JCP = 137.8 Hz), 52.8 (d, J _C . _P = 6.7 Hz) 80.0, 207.1 (d, J _C . _P = 6.0 Hz); MS (EI) m/z 324 ([M - Et] ⁺ , 98), 238 (65), 211 (61), 173 (100); exact mass calculated for CnH^OsPSi ([M - Et] ⁺ ) 295.1126, found 295.1126.

Scheme II.

14

(i) TESOTf, 2,6-lutidine, CH ₂ CI ₂ , 91 %; (ii) TESOTf, Et ₃ N, CH ₂ CI ₂ ; NBS, 50%; (iii) P(OMe) ₃ , PhMe, 90%.

[0057] Example 3 - Crystallization of (22£)-(24R)-2-methylene-22-dehydro-la,24.25- trihydroxy-19-nor- vitamin (WT-51) and X-ray Diffraction Analysis

[0058] Crystallization of (22E)-(24i? -2-methylene-22-dehvdro-la,24,25-trihvdroxy-19-nor- vitamin (WT-51) from ethyl acetate/hexane. WT-51 (15 mg) was placed in a 4 mL vial and dissolved in ethyl acetate (0.3 mL). Next, hexane (1 mL) was added dropwise to reach a saturation point. The vial then was sealed and left at room temperature. After about 1 hour, crystals began to grow and the mixture was left for the next 2 days at room temperature to obtain crystals. The obtained crystals were filtered off, and washed with a small volume of ethyl acetate/hexane, and dried to give crystalline WT-51.

[0059] Experimental. The crystals thus obtained were suitable for X-ray diffraction analysis and were analyzed accordingly. (See, e.g., U.S. Patent Nos. 9,212,137; 9,040,729; 8,940,916; 8,884,039; 8,519,169; 8,420,839; and 8,404,874; the contents of which are incorporated herein by reference in their entireties). Crystal data and structure refinement are provided in Table 1.

Atomic coordinates (A x 104) and equivalent isotropic displacement parameters (A2 x 103) are provided in Table 2. Bond lengths [A] and angles [o] are provided in Table 3. Anisotropic displacement parameters (A2 x 103) are provided in Table 4. Hydrogen coordinates (A x 104) and isotropic displacement parameters (A2 x 103) are provided in Table 5. Torsion angles [°] are provided in Table 6. The three dimensional structure of WT-51 as defined by the physical data and atomic positional parameters disclosed in Table 1-6 is illustrated in Figures 1-4.

[0060] In the foregoing description, it will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention. Thus, it should be understood that although the present invention has been illustrated by specific embodiments and optional features, modification and/or variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention.

[0061] Citations to a number of references are made herein. The cited references are incorporated by reference herein in their entireties. In the event that there is an inconsistency between a definition of a term in the specification as compared to a definition of the term in a cited reference, the term should be interpreted based on the definition in the specification.

Table 1. Crystal data and structure refinement.

Empirical formula C27 H42 04 1.33 H20

Formula weight 454, 430.62 without H20

Temperature 100(2) K

Wavelength 1.54178 A

Crystal system Monoclinic

Space group P2i

Unit cell dimensions a = 16.3058(9) A oc= 90°

b = 10.0461(6) A β= 109.001(3)° c = 26.0527(15) A γ = 90°

Volume 4035.1(4) A ³

Z 6

Density (calculated) 1.076 Mg/m ³

Absorption coefficient 0.561 mm- ¹

F(000) 1430

Crystal size 0.05 x 0.04 x 0.3 mm

Theta range for data collection 2.843 to 62.415°

Index ranges -17<=h<=18, -1 K=k<=l 1, -29<=1<=29 Reflections collected 32723

Independent reflections 12241 [R(int) = 0.0582]

Completeness to theta = 62.415∞ 98.4 %

Absorption correction None

Refinement method Full-matrix least-squares on F ²

Data / restraints / parameters 12241 / 1 / 874

Goodness-of-fit on F ² 0.975

Final R indices [I>2sigma(I)] Rl = 0.0790, wR2 = 0.2184

R indices (all data) Rl = 0.1014, wR2 = 0.2408

Absolute structure parameter -0.17(18)

Extinction coefficient n/a

Largest diffi peak and hole 0.567 and -0.300 e/A ³ Table 2. Atomic coordinates (A x 10^) and equivalent isotropic displacement parameters (A ² x 10 ³ ). U(eq) is defined as one third of the trace of the orthogonalized U¾ tensor. x y z U(eq)

0(301) 6552(3) 2722(4) 428(2) 49(1)

0(303) 4579(3) 5562(4) -120(2) 46(1)

0(325) 11671(3) 5441(5) -2184(2) 53(1)

0(203) 11026(3) 12936(5) -2518(2) 57(1)

C(313) 8967(4) 9428(6) -546(2) 38(1)

0(124) 11921(4) 7064(5) -2990(3) 72(2)

C(304) 5725(4) 6688(7) 611(3) 44(2)

0(201) 11630(4) 9648(5) -3406(2) 66(1)

C(307) 7340(4) 7516(6) -145(3) 39(1)

0(324) 12479(3) 7376(6) -1520(2) 75(2)

C(308) 7586(4) 8560(6) -379(3) 40(1)

C(301) 6137(4) 4013(6) 306(3) 41(1)

C(314) 8188(4) 8424(6) -713(3) 44(1)

C(305) 6433(4) 6501(7) 367(3) 43(1)

C(208) 14684(4) 13712(7) -2040(3) 47(2)

C(322) 10647(4) 8846(6) -1325(3) 43(2)

0(225) 18480(5) 13560(8) -4317(3) 94(2)

C(318) 9576(4) 9160(7) 29(3) 43(1)

C(206) 13318(4) 12615(7) -2010(3) 50(2)

C(323) 11278(4) 7972(6) -1240(3) 43(2)

C(302) 5481(4) 4256(6) 596(3) 41(1)

C(201) 11723(5) 10653(7) -3010(3) 55(2)

C(324) 11554(4) 7334(7) -1682(3) 46(2)

C(306) 6697(4) 7526(6) 129(3) 42(1)

C(207) 14030(4) 12840(7) -2223(3) 48(2)

C(309) 7254(4) 9950(7) -395(3) 49(2)

C(311) 7985(4) 11008(7) -264(3) 47(2)

C(214) 15368(4) 13883(7) -2298(3) 45(2)

C(303) 5043(4) 5572(6) 453(3) 42(1)

C(312) 8602(4) 10837(6) -598(3) 45(2)

C(320) 10347(4) 9470(6) -892(3) 43(1) C(116) 15160(5) 6779(8) -3503(3) 59(2)

C(213) 16311(4) 13705(6) -1905(3) 47(2)

C(217) 16828(4) 13959(7) -2303(3) 47(2)

C(122) 14092(5) 7380(8) -2811(3) 60(2)

C(310) 6822(4) 5116(6) 441(3) 45(2)

C(218) 16451(4) 12268(7) -1694(3) 52(2)

C(215) 15340(4) 13101(7) -2801(3) 51(2)

C(316) 9336(4) 7469(7) -984(3) 53(2)

C(224) 18653(5) 13644(9) -3389(3) 65(2)

C(204) 12028(5) 11528(8) -1886(3) 58(2)

C(317) 9419(4) 9013(6) -966(3) 40(1)

C(205) 12722(5) 11644(7) -2149(3) 54(2)

0(224) 19531(4) 13319(8) -3334(3) 92(2)

C(321) 10433(5) 10985(7) -917(3) 53(2)

C(202) 11033(5) 10607(7) -2746(3) 51(2)

C(221) 18384(5) 14028(9) -1629(3) 65(2)

C(222) 18099(4) 13898(8) -2615(3) 56(2)

C(211) 15769(5) 14574(8) -1157(3) 55(2)

C(216) 16251(4) 13334(8) -2844(3) 52(2)

C(203) 11129(5) 11614(7) -2305(3) 55(2)

C(315) 8600(5) 7119(7) -756(4) 56(2)

0(125) 11863(4) 6217(7) -4057(3) 87(2)

C(123) 13277(5) 7328(7) -3136(3) 57(2)

C(209) 14825(4) 14636(7) -1557(3) 50(2)

C(21 ) 10387(5) 9739(8) -2883(3) 62(2)

C(223) 18421(4) 13128(8) -2917(3) 57(2)

C(220) 17787(4) 13490(7) -2159(3) 52(2)

C(113) 16305(5) 8318(8) -3020(3) 59(2)

C(31 ) 5296(4) 3395(8) 927(3) 54(2)

C(212) 16454(5) 14718(7) -1443(3) 52(2)

C(124) 12621(5) 6367(7) -3085(3) 58(2)

C(109) 18167(6) 8135(12) -2900(4) 84(3)

C(118) 15998(6) 9540(8) -3386(4) 67(2)

C(210) 12638(5) 10600(8) -2584(3) 58(2)

C(120) 14783(5) 8325(8) -2834(3) 60(2)

C(325) 11230(5) 5933(7) -1819(4) 62(2) C(117) 15515(5) 7568(7) -2960(3) 56(2)

C(114) 16688(5) 7251(8) -3298(3) 61(2)

C(125) 12262(6) 5423(9) -3583(3) 67(2)

C(115) 15894(5) 6740(9) -3762(4) 70(2)

C(112) 17014(6) 8704(9) -2482(4) 74(2)

C(108) 17490(5) 7676(9) -3420(4) 71(2)

C(327) 10241(6) 6013(11) -2169(5) 92(3)

C(225) 18085(6) 13090(11) -3935(4) 80(3)

C(121) 15094(6) 9096(9) -2289(4) 76(2)

C(326) 11405(15) 5040(10) -1354(6) 167(9)

C(110) 18041(6) 7167(12) -4961(5) 96(3)

C(106) 18316(7) 8145(14) -4050(6) 111(4)

C(105) 18494(7) 8022(12) -4501(4) 88(3)

C(126) 12992(7) 4649(11) -3681(4) 89(3)

C(107) 17582(6) 7649(10) -3906(4) 77(2)

C(227) 18119(9) 11566(12) -3930(5) 109(4)

C(127) 11601(8) 4481(10) -3500(5) 98(3)

C(226) 17180(7) 13662(16) -4092(5) 111(4)

C(102) 19431(7) 6890(12) -5163(6) 101(4)

C(l l l) 17838(7) 9140(12) -2587(4) 99(4)

C(119) 19688(8) 6800(13) -5578(6) 108(4)

C(103) 19834(7) 7840(30) -4706(6) 172(10)

0(101) 18130(18) 5540(30) -5610(11) 430(20)

C(104) 19200(9) 8823(19) -4595(6) 139(6)

C(101) 18663(11) 6117(17) -5085(9) 150(7)

0(103) 20288(7) 7240(30) -4191(5) 353(19)

0(2) 16200(20) 15120(70) -5679(17) 630(50)

0(1) 17476(7) 12886(13) -5340(4) 145(4)

0(3) 14250(30) 3980(130) -4710(20) 890(110)

0(4) 15000(40) 830(100) -4827(11) 960(100) Table 3. Bond lengths [A] and angles [°].

O(301)-C(301) 1.449(8)

O(301)-H(30A) 0.8400

O(303)-C(303) 1.439(8)

O(303)-H(30B) 0.8400

0(325)-C(325) 1.451(8)

0(325)-H(32A) 0.8400

O(203)-C(203) 1.428(9)

O(203)-H(20A) 0.8400

C(313)-C(312) 1.524(9)

C(313)-C(318) 1.526(9)

C(313)-C(317) 1.562(8)

C(313)-C(314) 1.569(8)

0(124)-C(124) 1.427(9)

0(124)-H(12A) 0.8400

C(304)-C(305) 1.500(9)

C(304)-C(303) 1.538(9)

C(304)-H(30C) 0.9900

C(304)-H(30D) 0.9900

O(201)-C(201) 1.417(9)

O(201)-H(20B) 0.8400

C(307)-C(308) 1.338(9)

C(307)-C(306) 1.448(8)

C(307)-H(30E) 0.9500

0(324)-C(324) 1.428(8)

0(324)-H(32B) 0.8400

C(308)-C(309) 1.493(9)

C(308)-C(314) 1.515(8)

C(301)-C(302) 1.518(8)

C(301)-C(310) 1.530(9)

C(301)-H(30F) 1.0000

C(314)-C(315) 1.494(9)

C(314)-H(31A) 1.0000

C(305)-C(306) 1.342(9)

C(305)-C(310) 1.515(10) C(208) -C(207) 1.342(10)

C(208) -C(214) 1.488(9)

C(208) -C(209) 1.521(10)

C(322) -C(323) 1.316(9)

C(322) -C(320) 1.503(9)

C(322) -H(32C) 0.9500

0(225; -C(225) 1.430(11)

0(225; -H(22A) 0.8400

C(318) -H(31B) 0.9800

C(318) -H(31C) 0.9800

C(318) -H(31D) 0.9800

C(206) -C(205) 1.340(10)

C(206) -C(207) 1.459(9)

C(206) -H(20C) 0.9500

C(323) -C(324) 1.510(9)

C(323) -H(32D) 0.9500

C(302) -C(319) 1.324(9)

C(302) -C(303) 1.491(9)

C(201) -C(202) 1.498(10)

C(201) -C(210) 1.543(10)

C(201) -H(20D) 1.0000

C(324) -C(325) 1.506(10)

C(324) -H(32E) 1.0000

C(306) -H(30G) 0.9500

C(207) -H(20E) 0.9500

C(309) -C(311) 1.550(9)

C(309) -H(30H) 0.9900

C(309) -H(30I) 0.9900

C(311) -C(312) 1.539(9)

C(311) -H(31E) 0.9900

C(311) -H(31F) 0.9900

C(214) -C(215) 1.514(10)

C(214) -C(213) 1.555(9)

C(214) -H(21A) 1.0000

C(303) -H(30J) 1.0000

C(312) -H(31G) 0.9900 C(312) -H(31H) 0.9900

C(320) -C(321) 1.531(10)

C(320) -C(317) 1.533(8)

C(320) -H(32F) 1.0000

C(116) -C(115) 1.553(11)

C(116) -C(117) 1.560(11)

C(116) -H(l lA) 0.9900

C(116) -H(l lB) 0.9900

C(213) -C(212) 1.535(10)

C(213) -C(218) 1.535(10)

C(213) -C(217) 1.555(9)

C(217) -C(216) 1.551(10)

C(217) -C(220) 1.557(9)

C(217) -H(21B) 1.0000

C(122) -C(123) 1.323(11)

C(122) -C(120) 1.489(11)

C(122) -H(12B) 0.9500

C(310) -H(31I) 0.9900

C(310) -H(31J) 0.9900

C(218) -H(21C) 0.9800

C(218) -H(21D) 0.9800

C(218) -H(21E) 0.9800

C(21 ) -C(216) 1.544(9)

C(215) -H(21F) 0.9900

C(215) -H(21G) 0.9900

C(316) -C(315) 1.542(9)

C(316) -C(317) 1.556(10)

C(316) -H(31K) 0.9900

C(316) -H(31L) 0.9900

C(224) -0(224) 1.429(10)

C(224) -C(223) 1.492(11)

C(224) -C(225) 1.528(13)

C(224) -H(22B) 1.0000

C(204) -C(205) 1.506(10)

C(204) -C(203) 1.519(11)

C(204) -H(20F) 0.9900 C(204) -H(20G) 0.9900

C(317) -H(31M) 1.0000

C(205) -C(210) 1.517(11)

0(224; -H(22C) 0.8400

C(321) -H(32G) 0.9800

C(321) -H(32H) 0.9800

C(321) -H(32I) 0.9800

C(202) -C(219) 1.324(10)

C(202) -C(203) 1.501(10)

C(221) -C(220) 1.507(11)

C(221) -H(22D) 0.9800

C(221) -H(22E) 0.9800

C(221) -H(22F) 0.9800

C(222) -C(223) 1.327(10)

C(222) -C(220) 1.495(10)

C(222) -H(22G) 0.9500

C(211) -C(212) 1.539(10)

C(211) -C(209) 1.554(10)

C(211) -H(21H) 0.9900

C(211) -H(21I) 0.9900

C(216) -H(21J) 0.9900

C(216) -H(21K) 0.9900

C(203) -H(20H) 1.0000

C(315) -H(31N) 0.9900

C(315) -H(310) 0.9900

0(125; -C(125) 1.437(11)

0(125; -H(12C) 0.8400

C(123) -C(124) 1.477(11)

C(123) -H(12D) 0.9500

C(209) -H(20I) 0.9900

C(209) -H(20J) 0.9900

C(219) -H(21L) 0.9500

C(219) -H(21M) 0.9500

C(223) -H(22H) 0.9500

C(220) -H(22I) 1.0000

C(113) -C(114) 1.536(12) C(113)-C(118) 1.535(11)

C(113) -C(112) 1.549(12)

C(113) -C(117) 1.544(11)

C(319) -H(31P) 0.9500

C(31 ) -H(31Q) 0.9500

C(212) -H(210) 0.9900

C(212) -H(21P) 0.9900

C(124) -C(125) 1.558(12)

C(124) -H(12E) 1.0000

C(109) -C(lll) 1.503(17)

C(109) -C(108) 1.515(13)

C(109) -H(IOA) 0.9900

C(109) -H(IOB) 0.9900

C(118) -H(llC) 0.9800

C(118) -H(llD) 0.9800

C(118) -H(llE) 0.9800

C(210) -H(21Q) 0.9900

C(210) -H(21R) 0.9900

C(120) - I17) 1.539(11)

C(120) -C(121) 1.550(12)

C(120) -H(12F) 1.0000

C(325) -C(326) 1.460(15)

C(325) -C(327) 1.574(13)

C(117) -H(llF) 1.0000

C(114) -C(108) 1.505(11)

C(114) -C(115) 1.544(11)

C(114) -H(llG) 1.0000

C(125) -C(127) 1.502(13)

C(125) -C(126) 1.513(13)

C(115) -H(llH) 0.9900

C(115) -H(lll) 0.9900

C(112) -C(lll) 1.520(14)

C(112) -H(llJ) 0.9900

C(112) -H(llK) 0.9900

C(108) -C(107) 1.323(13)

C(327) -H(32J) 0.9800 C(327) -H(32K) 0.9800

C(327) -H(32L) 0.9800

C(225) -C(226) 1.511(14)

C(225) -C(227) 1.531(16)

C(121) -H(12G) 0.9800

C(121) -H(12H) 0.9800

C(121) -H(12I) 0.9800

C(326) -H(32M) 0.9800

C(326) -H(32N) 0.9800

C(326) -H(320) 0.9800

C(110) -C(105) 1.463(16)

C(110) -C(lOl) 1.569(18)

C(110) -H(l lL) 0.9900

C(110) -H(l lM) 0.9900

C(106) -C(105) 1.306(16)

C(106) -C(107) 1.453(14)

C(106) -H(IOC) 0.9500

C(105) -C(104) 1.489(15)

C(126) -H(12J) 0.9800

C(126) -H(12K) 0.9800

C(126) -H(12L) 0.9800

C(107) -H(IOD) 0.9500

C(227) -H(22J) 0.9800

C(227) -H(22K) 0.9800

C(227) -H(22L) 0.9800

C(127) -H(12M) 0.9800

C(127) -H(12N) 0.9800

C(127) -H(120) 0.9800

C(226) -H(22M) 0.9800

C(226) -H(22N) 0.9800

C(226) -H(220) 0.9800

C(102) -C(119) 1.283(17)

C(102) -C(103) 1.50(2)

C(102) -C(lOl) 1.542(18)

C(l l l) -H(l lN) 0.9900

C(l l l) -H(l lO) 0.9900 C(119) -H(l lP) 0.9500

C(119) -H(11Q 0.9500

C(103) -0(103) 1.436(18)

C(103) -C(104) 1.52(3)

C(103) -H(IOE) 1.0000

0(101) -C(lOl) 1.48(3)

0(101) -H(IOJ) 0.8400

C(104) -H(IOF) 0.9900

C(104) -H(10G 0.9900

C(101) -H(10H 1.0000

0(103) -H(IOI) 0.8400

C(301) -0(301) -H(30A) 109.5

C(303) -0(303) -H(30B) 109.5

C(325) -0(325) -H(32A) 109.5

C(203) -0(203) -H(20A) 109.5

C(312) -C(313) -C(318) 111.2(5)

C(312) -C(313) -C(317) 116.4(5)

C(318) -C(313) -C(317) 109.6(5)

C(312) -C(313) -C(314) 108.3(5)

C(318) -C(313) -C(314) 111.6(5)

C(317) -C(313) -C(314) 99.1(5)

C(124) -0(124) -H(12A) 109.5

C(305) -C(304) -C(303) 112.7(5)

C(305) -C(304) -H(30C) 109.0

C(303) -C(304) -H(30C) 109.0

C(305) -C(304) -H(30D) 109.1

C(303) -C(304) -H(30D) 109.1

H(30C )-C(304 -H(30D) 107.8

C(201) -0(201) -H(20B) 109.5

C(308) -C(307) -C(306) 126.3(6)

C(308) -C(307) -H(30E) 116.8

C(306) -C(307) -H(30E) 116.9

C(324) -0(324) -H(32B) 109.5

C(307) -C(308) -C(309) 125.9(5)

C(307) -C(308) -C(314) 122.5(5) C(309) -C(308) -C(314) 111.3(5)

0(301) -C(301) -C(302) 112.9(5)

0(301) -C(301) -C(310) 110.1(5)

C(302) -C(301) -C(310) 110.5(5)

0(301) -C(301) -H(30F) 107.7

C(302) -C(301) -H(30F) 107.7

C(310) -C(301) -H(30F) 107.7

C(315) -C(314) -C(308) 120.9(6)

C(31 ) -C(314) -C(313) 104.0(5)

C(308) -C(314) -C(313) 113.6(5)

C(315) -C(314) -H(31A) 105.7

C(308) -C(314) -H(31A) 105.7

C(313) -C(314) -H(31A) 105.7

C(306) -C(305) -C(304) 120.4(6)

C(306) -C(305) -C(310) 125.4(6)

C(304) -C(305) -C(310) 114.1(6)

C(207) -C(208) -C(214) 122.7(6)

C(207) -C(208) -C(209) 125.5(6)

C(214) -C(208) -C(209) 111.7(6)

C(323) -C(322) -C(320) 125.4(6)

C(323) -C(322) -H(32C) 117.3

C(320) -C(322) -H(32C) 117.3

C(225) -0(225) -H(22A) 109.4

C(313) -C(318) -H(31B) 109.5

C(313) -C(318) -H(31C) 109.4

H(31B )-C(318 )-H(31C) 109.5

C(313) -C(318) -H(31D) 109.5

H(31B )-C(318 )-H(31D) 109.5

H(31C )-C(318 )-H(31D) 109.5

C(205) -C(206) -C(207) 127.4(7)

C(205) -C(206) -H(20C) 116.3

C(207) -C(206) -H(20C) 116.3

C(322) -C(323) -C(324) 124.5(6)

C(322) -C(323) -H(32D) 117.8

C(324) -C(323) -H(32D) 117.8

C(31 ) -C(302) -C(303) 123.3(6) C(319)-C(302)-C(301) 124.5(6)

C(303)-C(302)-C(301) 112.2(5)

O(201)-C(201)-C(202) 113.2(6)

O(201)-C(201)-C(210) 110.4(6)

C(202)-C(201)-C(210) 111.3(6)

O(201)-C(201)-H(20D) 107.2

C(202)-C(201)-H(20D) 107.2

C(210)-C(201)-H(20D) 107.2

0(324)-C(324)-C(325) 110.7(6)

0(324)-C(324)-C(323) 108.0(5)

C(325)-C(324)-C(323) 114.1(6)

0(324)-C(324)-H(32E) 108.0

C(325)-C(324)-H(32E) 108.0

C(323)-C(324)-H(32E) 107.9

C(305)-C(306)-C(307) 127.9(6)

C(305)-C(306)-H(30G) 116.0

C(307)-C(306)-H(30G) 116.1

C(208)-C(207)-C(206) 127.2(6)

C(208)-C(207)-H(20E) 116.4

C(206)-C(207)-H(20E) 116.4

C(308)-C(309)-C(311) 112.9(5)

C(308)-C(309)-H(30H) 109.0

C(311)-C(309)-H(30H) 109.0

C(308)-C(309)-H(30I) 109.0

C(311)-C(309)-H(30I) 109.0

H(30H)-C(309)-H(30I) 107.8

C(312)-C(311)-C(309) 113.3(6)

C(312)-C(311)-H(31E) 108.9

C(309)-C(311)-H(31E) 108.9

C(312)-C(311)-H(31F) 108.9

C(309)-C(311)-H(31F) 108.9

H(31E)-C(311)-H(31F) 107.7

C(208)-C(214)-C(215) 121.0(6)

C(208)-C(214)-C(213) 114.5(5)

C(215)-C(214)-C(213) 104.8(5)

C(208)-C(214)-H(21A) 105.0 C(215) -C(214) -H(21A) 105.1

C(213) -C(214) -H(21A) 105.1

0(303; -C(303; -C(302) 107.4(5)

0(303; -C(303; -C(304) 111.9(5)

C(302) -C(303) -C(304) 109.5(5)

0(303; -C(303; -H(30J) 109.4

C(302) -C(303) -H(30J) 109.4

C(304) -C(303) -H(30J) 109.4

C(313) -C(312) -C(311) 111.2(5)

C(313) -C(312) -H(31G) 109.4

C(311) -C(312) -H(31G) 109.4

C(313) -C(312) -H(31H) 109.4

C(311) -C(312) -H(31H) 109.4

H(31G)-C(312)-H(31H) 108.0

C(322) -C(320) -C(321) 109.1(5)

C(322) -C(320) -C(317) 109.3(5)

C(321) -C(320) -C(317) 113.1(5)

C(322) -C(320) -H(32F) 108.4

C(321) -C(320) -H(32F) 108.4

C(317) -C(320) -H(32F) 108.4

C(115) -C(116) -C(117) 107.2(6)

C(115) -C(116) -H(l lA) 110.3

C(117) -C(116) -H(l lA) 110.2

C(115) -C(116) -H(l lB) 110.3

C(117) -C(116) -H(l lB) 110.3

H(11A)-C(116)-H(11B) 108.5

C(212) -C(213) -C(218) 112.0(6)

C(212) -C(213) -C(217) 115.9(5)

C(218) -C(213) -C(217) 110.1(6)

C(212) -C(213) -C(214) 107.8(5)

C(218) -C(213) -C(214) 110.1(5)

C(217) -C(213) -C(214) 100.2(5)

C(213) -C(217) -C(216) 103.8(5)

C(213) -C(217) -C(220) 120.6(6)

C(216) -C(217) -C(220) 111.2(5)

C(213) -C(217) -H(21B) 106.8 C(216)-C(217)-H(21B) 106.8

C(220)-C(217)-H(21B) 106.8

C(123)-C(122)-C(120) 128.0(7)

C(123)-C(122)-H(12B) 116.0

C(120)-C(122)-H(12B) 115.9

C(305)-C(310)-C(301) 113.1(5)

C(305)-C(310)-H(31I) 109.0

C(301)-C(310)-H(31I) 109.0

C(305)-C(310)-H(31J) 109.0

C(301)-C(310)-H(31J) 109.0

H(31I)-C(310)-H(31J) 107.8

C(213)-C(218)-H(21C) 109.5

C(213)-C(218)-H(21D) 109.5

H(21C)-C(218)-H(21D) 109.5

C(213)-C(218)-H(21E) 109.4

H(21C)-C(218)-H(21E) 109.5

H(21D)-C(218)-H(21E) 109.5

C(214)-C(215)-C(216) 103.1(5)

C(214)-C(215)-H(21F) 111.1

C(216)-C(215)-H(21F) 111.1

C(214)-C(215)-H(21G) 111.2

C(216)-C(215)-H(21G) 111.2

H(21F)-C(215)-H(21G) 109.1

C(315)-C(316)-C(317) 106.7(5)

C(315)-C(316)-H(31K) 110.4

C(317)-C(316)-H(31K) 110.4

C(315)-C(316)-H(31L) 110.4

C(317)-C(316)-H(31L) 110.4

H(31K)-C(316)-H(31L) 108.6

0(224)-C(224)-C(223) 110.6(7)

0(224)-C(224)-C(225) 107.0(7)

C(223)-C(224)-C(225) 113.7(7)

0(224)-C(224)-H(22B) 108.4

C(223)-C(224)-H(22B) 108.5

C(225)-C(224)-H(22B) 108.5

C(205)-C(204)-C(203) 111.2(6) C(205)-C(204)-H(20F) 109.4

C(203)-C(204)-H(20F) 109.3

C(205)-C(204)-H(20G) 109.4

C(203)-C(204)-H(20G) 109.4

H(20F)-C(204)-H(20G) 108.0

C(320)-C(317)-C(316) 112.0(5)

C(320)-C(317)-C(313) 120.2(5)

C(316)-C(317)-C(313) 103.3(5)

C(320)-C(317)-H(31M) 106.8

C(316)-C(317)-H(31M) 106.8

C(313)-C(317)-H(31M) 106.8

C(206)-C(205)-C(204) 121.3(7)

C(206)-C(205)-C(210) 125.9(7)

C(204)-C(205)-C(210) 112.7(6)

C(224)-0(224)-H(22C) 109.5

C(320)-C(321)-H(32G) 109.5

C(320)-C(321)-H(32H) 109.5

H(32G)-C(321)-H(32H) 109.5

C(320)-C(321)-H(32I) 109.5

H(32G)-C(321)-H(32I) 109.5

H(32H)-C(321)-H(32I) 109.5

C(219)-C(202)-C(201) 123.2(7)

C(219)-C(202)-C(203) 121.7(7)

C(201)-C(202)-C(203) 115.1(6)

C(220)-C(221)-H(22D) 109.5

C(220)-C(221)-H(22E) 109.4

H(22D)-C(221)-H(22E) 109.5

C(220)-C(221)-H(22F) 109.5

H(22D)-C(221)-H(22F) 109.5

H(22E)-C(221)-H(22F) 109.5

C(223)-C(222)-C(220) 127.9(7)

C(223)-C(222)-H(22G) 116.1

C(220)-C(222)-H(22G) 116.0

C(212)-C(211)-C(209) 112.8(6)

C(212)-C(211)-H(21H) 109.0

C(209)-C(211)-H(21H) 109.0 C(212)-C(211)-H(21I) 109.0

C(209)-C(211)-H(21I) 109.0

H(21H)-C(211)-H(21I) 107.8

C(215)-C(216)-C(217) 107.9(5)

C(215)-C(216)-H(21J) 110.2

C(217)-C(216)-H(21J) 110.1

C(215)-C(216)-H(21K) 110.1

C(217)-C(216)-H(21K) 110.1

H(21J)-C(216)-H(21K) 108.4

O(203)-C(203)-C(202) 111.1(6)

O(203)-C(203)-C(204) 107.2(6)

C(202)-C(203)-C(204) 110.3(6)

O(203)-C(203)-H(20H) 109.4

C(202)-C(203)-H(20H) 109.4

C(204)-C(203)-H(20H) 109.4

C(314)-C(315)-C(316) 104.7(5)

C(314)-C(315)-H(31N) 110.8

C(316)-C(315)-H(31N) 110.8

C(314)-C(315)-H(310) 110.8

C(316)-C(315)-H(310) 110.8

H(31N)-C(315)-H(310) 108.9

C(125)-0(125)-H(12C) 109.5

C(122)-C(123)-C(124) 125.1(7)

C(122)-C(123)-H(12D) 117.5

C(124)-C(123)-H(12D) 117.4

C(208)-C(209)-C(211) 112.4(6)

C(208)-C(209)-H(20I) 109.1

C(211)-C(209)-H(20I) 109.1

C(208)-C(209)-H(20J) 109.1

C(211)-C(209)-H(20J) 109.1

H(20I)-C(209)-H(20J) 107.9

C(202)-C(219)-H(21L) 120.0

C(202)-C(219)-H(21M) 120.0

H(21L)-C(219)-H(21M) 120.0

C(222)-C(223)-C(224) 122.8(7)

C(222)-C(223)-H(22H) 118.6 C(224)-C(223)-H(22H) 118.6

C(222)-C(220)-C(221) 110.2(6)

C(222)-C(220)-C(217) 107.5(6)

C(221)-C(220)-C(217) 114.2(6)

C(222)-C(220)-H(22I) 108.2

C(221)-C(220)-H(22I) 108.3

C(217)-C(220)-H(22I) 108.2

C(114)-C(113)-C(118) 111.5(6)

C(114)-C(113)-C(112) 107.6(7)

C(118)-C(113)-C(112) 111.0(7)

C(114)-C(113)-C(117) 100.8(6)

C(118)-C(113)-C(117) 109.8(6)

C(112)-C(113)-C(117) 115.6(6)

C(302)-C(319)-H(31P) 120.0

C(302)-C(319)-H(31Q) 120.0

H(31P)-C(319)-H(31Q) 120.0

C(213)-C(212)-C(211) 111.7(6)

C(213)-C(212)-H(210) 109.3

C(211)-C(212)-H(210) 109.3

C(213)-C(212)-H(21P) 109.3

C(211)-C(212)-H(21P) 109.3

H(210)-C(212)-H(21P) 107.9

0(124)-C(124)-C(123) 109.7(6)

0(124)-C(124)-C(125) 109.7(6)

C(123)-C(124)-C(125) 114.3(7)

0(124)-C(124)-H(12E) 107.6

C(123)-C(124)-H(12E) 107.6

C(125)-C(124)-H(12E) 107.6

C(l l l)-C(109)-C(108) 113.9(8)

C(111)-C(109)-H(10A) 108.8

C(108)-C(109)-H(10A) 108.8

C(111)-C(109)-H(10B) 108.8

C(108)-C(109)-H(10B) 108.8

H(10A)-C(109)-H(10B) 107.7

C(113)-C(118)-H(11C) 109.4

C(113)-C(118)-H(11D) 109.5 H(11C)-C(118)-H(11D) 109.5

C(113)-C(118)-H(11E) 109.5

H(11C)-C(118)-H(11E) 109.5

H(11D)-C(118)-H(11E) 109.5

C(205)-C(210)-C(201) 110.2(6)

C(205)-C(210)-H(21Q) 109.6

C(201)-C(210)-H(21Q) 109.6

C(205)-C(210)-H(21R) 109.7

C(201)-C(210)-H(21R) 109.5

H(21Q)-C(210)-H(21R) 108.1

C(122)-C(120)-C(117) 110.0(6)

C(122)-C(120)-C(121) 108.1(6)

C(117)-C(120)-C(121) 113.4(7)

C(122)-C(120)-H(12F) 108.4

C(117)-C(120)-H(12F) 108.4

C(121)-C(120)-H(12F) 108.4

0(325)-C(325)-C(326) 109.2(8)

0(325)-C(325)-C(324) 105.3(5)

C(326)-C(325)-C(324) 114.7(8)

0(325)-C(325)-C(327) 105.7(7)

C(326)-C(325)-C(327) 113.5(11)

C(324)-C(325)-C(327) 107.7(7)

C(120)-C(117)-C(113) 120.7(6)

C(120)-C(117)-C(116) 111.2(6)

C(113)-C(117)-C(116) 103.4(6)

C(120)-C(117)-H(11F) 106.9

C(113)-C(117)-H(11F) 106.9

C(116)-C(117)-H(11F) 107.0

C(108)-C(114)-C(113) 114.7(7)

C(108)-C(114)-C(115) 119.5(7)

C(113)-C(114)-C(115) 103.6(6)

C(108)-C(114)-H(11G) 106.0

C(113)-C(114)-H(11G) 106.0

C(115)-C(114)-H(11G) 106.0

0(125)-C(125)-C(127) 109.2(8)

0(125)-C(125)-C(126) 107.4(7) C(127) -C(125)-C(126) 110.0(8)

0(125) -C(125)-C(124) 108.7(7)

C(127) -C(125)-C(124) 111.0(7)

C(126) -C(125)-C(124) 110.5(7)

C(114) -C(115)-C(116) 102.7(7)

C(114) -C(115)-H(11H) 111.2

C(116) -C(115)-H(11H) 111.3

C(114) -C(115)-H(11I) 111.2

C(116) -C(115)-H(11I) 111.2

H(11H)-C(115)-H(11I) 109.2

C(l l l) -C(112)-C(113) 110.6(8)

C(l l l) -C(112)-H(11J) 109.5

C(113) -C(112)-H(11J) 109.5

C(l l l) -C(112)-H(11K) 109.5

C(113) -C(112)-H(11K) 109.5

H(11J) -C(112)-H(11K) 108.1

C(107) -C(108)-C(114) 125.1(8)

C(107) -C(108)-C(109) 125.9(8)

C(114) -C(108)-C(109) 109.1(8)

C(325) -C(327)-H(32J) 109.5

C(325) -C(327)-H(32K) 109.4

H(32J) -C(327)-H(32K) 109.5

C(325) -C(327)-H(32L) 109.5

H(32J) -C(327)-H(32L) 109.5

H(32K )-C(327)-H(32L) 109.5

0(225) -C(225)-C(224) 104.8(8)

0(225) -C(225)-C(226) 107.9(8)

C(224) -C(225)-C(226) 110.8(8)

0(225) -C(225)-C(227) 108.2(8)

C(224) -C(225)-C(227) 110.4(8)

C(226) -C(225)-C(227) 114.3(11)

C(120) -C(121)-H(12G) 109.5

C(120) -C(121)-H(12H) 109.5

H(12G)-C(121)-H(12H) 109.5

C(120)-C(121)-H(12I) 109.5

H(12G)-C(121)-H(12I) 109.5 H(12H)-C(121)-H(12I) 109.5

C(325)-C(326)-H(32M) 109.5

C(325)-C(326)-H(32N) 109.4

H(32M)-C(326)-H(32N) 109.5

C(325)-C(326)-H(320) 109.5

H(32M)-C(326)-H(320) 109.5

H(32N)-C(326)-H(320) 109.5

C(105)-C(110)-C(101) 112.0(11)

C(105)-C(110)-H(11L) 109.2

C(101)-C(110)-H(11L) 109.3

C(105)-C(110)-H(11M) 109.1

C(101)-C(110)-H(11M) 109.2

H(11L)-C(110)-H(11M) 107.9

C(105)-C(106)-C(107) 129.9(11)

C(105)-C(106)-H(10C) 115.0

C(107)-C(106)-H(10C) 115.0

C(106)-C(105)-C(110) 126.2(10)

C(106)-C(105)-C(104) 120.5(12)

C(110)-C(105)-C(104) 113.3(10)

C(125)-C(126)-H(12J) 109.4

C(125)-C(126)-H(12K) 109.5

H(12J)-C(126)-H(12K) 109.5

C(125)-C(126)-H(12L) 109.6

H(12J)-C(126)-H(12L) 109.5

H(12K)-C(126)-H(12L) 109.5

C(108)-C(107)-C(106) 126.7(10)

C(108)-C(107)-H(10D) 116.6

C(106)-C(107)-H(10D) 116.6

C(225)-C(227)-H(22J) 109.5

C(225)-C(227)-H(22K) 109.4

H(22J)-C(227)-H(22K) 109.5

C(225)-C(227)-H(22L) 109.6

H(22J)-C(227)-H(22L) 109.5

H(22K)-C(227)-H(22L) 109.5

C(125)-C(127)-H(12M) 109.4

C(125)-C(127)-H(12N) 109.5 H(12M)-C(127)-H(12N) 109.5

C(125)-C(127)-H(120) 109.5

H(12M)-C(127)-H(120) 109.5

H(12N)-C(127)-H(120) 109.5

C(225)-C(226)-H(22M) 109.5

C(225)-C(226)-H(22N) 109.6

H(22M)-C(226)-H(22N) 109.5

C(225)-C(226)-H(220) 109.3

H(22M)-C(226)-H(220) 109.5

H(22N)-C(226)-H(220) 109.5

C(119)-C(102)-C(103) 122.4(12)

C(119)-C(102)-C(101) 125.2(15)

C(103)-C(102)-C(101) 112.3(13)

C(109)-C(l l l)-C(112) 113.4(9)

C(109)-C(111)-H(11N) 108.9

C(112)-C(111)-H(11N) 108.9

C(109)-C(l l l)-H(l lO) 108.9

C(112)-C(l l l)-H(110) 108.9

H(11N)-C(111)-H(110) 107.7

C(102)-C(119)-H(11P) 120.1

C(102)-C(119)-H(11Q) 119.9

H(11P)-C(119)-H(11Q) 120.0

O(103)-C(103)-C(104) 105.7(14)

O(103)-C(103)-C(102) 116(2)

C(104)-C(103)-C(102) 114.5(10)

O(103)-C(103)-H(10E) 106.8

C(104)-C(103)-H(10E) 106.7

C(102)-C(103)-H(10E) 106.8

C(101)-O(101)-H(10J) 109.6

C(105)-C(104)-C(103) 106.8(14)

C(105)-C(104)-H(10F) 110.2

C(103)-C(104)-H(10F) 110.2

C(105)-C(104)-H(10G) 110.6

C(103)-C(104)-H(10G) 110.6

H(10F)-C(104)-H(10G) 108.6

O(101)-C(101)-C(102) 109.5(13) O(101)-C(101)-C(110) 103.3(18)

C(102)-C(101)-C(110) 107.2(12)

O(101)-C(101)-H(10H) 112.0

C(102)-C(101)-H(10H) 112.2

C(110)-C(101)-H(10H) 112.2

C(103)-O(103)-H(10I) 109.4

Table 4. Anisotropic displacement parameters (A ² x 10 ³ ). The anisotropic

displacement factor exponent takes the form: -2π ² [h ² a* ² Un + . . . + 2hka*£>*U ₁₂ ]

Ul l U22 U33 U23 U13 U12

0(301) 42(2) 32(2) 82(3) 4(2) 32(2) 0(2)

0(303) 39(2) 44(2) 60(3) 0(2) 22(2) 3(2)

0(325) 58(3) 48(3) 69(3) -14(2) 41(2) -5(2)

0(203) 55(3) 47(3) 77(3) -5(2) 34(2) -2(2)

C(313) 29(3) 41(3) 51(3) -3(3) 23(3) -4(3)

0(124) 83(4) 44(3) 115(5) -2(3) 70(3) 2(3)

C(304) 37(3) 41(3) 61(4) -1(3) 27(3) -2(3)

0(201) 75(3) 50(3) 77(3) -11(3) 30(3) -1(3)

C(307) 31(3) 32(3) 62(4) -3(3) 24(3) -1(2)

0(324) 41(2) 102(4) 92(4) -49(3) 37(3) -17(3)

C(308) 29(3) 41(3) 58(4) -3(3) 24(3) -2(2)

C(301) 35(3) 41(3) 55(4) 4(3) 26(3) -1(3)

C(314) 40(3) 41(3) 59(4) -6(3) 29(3) -5(3)

C(305) 36(3) 46(4) 53(4) -5(3) 22(3) -2(3)

C(208) 45(3) 52(4) 48(4) 7(3) 22(3) 7(3)

C(322) 38(3) 40(3) 63(4) -2(3) 32(3) -6(3)

0(225) 99(5) 119(6) 82(4) 19(4) 54(4) 25(4)

C(318) 37(3) 44(3) 56(4) 2(3) 26(3) 1(3)

C(206) 51(4) 49(4) 51(4) 2(3) 21(3) 2(3)

C(323) 39(3) 38(3) 62(4) -8(3) 30(3) -8(3)

C(302) 33(3) 46(4) 50(4) 0(3) 22(3) -6(3)

C(201) 58(4) 40(4) 74(5) -3(3) 33(4) 1(3)

C(324) 38(3) 51(4) 56(4) -6(3) 27(3) 5(3)

C(306) 32(3) 38(3) 61(4) 0(3) 22(3) -1(3)

C(207) 48(3) 47(4) 52(4) 0(3) 21(3) 5(3)

C(309) 39(3) 50(4) 67(4) 10(3) 30(3) 6(3)

C(311) 41(3) 38(3) 71(4) 2(3) 31(3) 3(3)

C(214) 45(3) 42(3) 53(4) 2(3) 20(3) 3(3)

C(303) 40(3) 45(4) 49(4) -3(3) 26(3) -1(3)

C(312) 42(3) 41(3) 63(4) 5(3) 32(3) 1(3)

C(320) 38(3) 46(4) 54(4) -4(3) 28(3) -1(3) C(116) 51(4) 58(4) 76(5) -8(4) 32(4) -2(3)

C(213) 45(3) 43(4) 59(4) 0(3) 25(3) -2(3)

C(217) 47(3) 44(3) 58(4) 1(3) 27(3) -1(3)

C(122) 75(5) 49(4) 63(5) 6(3) 34(4) 9(4)

C(310) 35(3) 45(4) 62(4) 5(3) 25(3) -2(3)

C(218) 48(4) 46(4) 63(4) 6(3) 17(3) -1(3)

C(215) 45(3) 55(4) 59(4) -4(3) 24(3) -1(3)

C(316) 48(4) 48(4) 80(5) -13(4) 45(3) -8(3)

C(224) 57(4) 69(5) 74(5) 5(4) 30(4) 14(4)

C(204) 59(4) 59(4) 61(5) -3(4) 26(4) -16(4)

C(317) 36(3) 40(3) 53(4) -8(3) 26(3) -3(3)

C(205) 55(4) 48(4) 60(4) 0(3) 23(3) 4(3)

0(224) 71(4) 126(6) 92(4) 6(4) 45(3) 16(4)

C(321) 50(4) 42(4) 80(5) -10(3) 40(4) -6(3)

C(202) 52(4) 44(4) 59(4) 5(3) 21(3) -3(3)

C(221) 48(4) 72(5) 81(5) -7(4) 29(4) -5(4)

C(222) 48(4) 49(4) 76(5) -6(4) 27(3) -1(3)

C(211) 60(4) 54(4) 56(4) -3(3) 25(3) -10(3)

C(216) 48(3) 59(4) 59(4) 4(3) 29(3) 4(3)

C(203) 53(4) 51(4) 69(5) -5(4) 29(4) -8(3)

C(315) 57(4) 38(4) 92(5) -12(3) 52(4) -8(3)

0(125) 71(4) 110(5) 85(4) 14(4) 33(3) -13(4)

C(123) 63(4) 50(4) 70(5) 9(4) 37(4) 9(4)

C(209) 50(4) 47(4) 61(4) 2(3) 28(3) 2(3)

C(21 ) 55(4) 58(4) 72(5) -7(4) 21(4) -10(4)

C(223) 56(4) 52(4) 72(5) -4(4) 34(4) -2(3)

C(220) 48(4) 46(4) 71(5) -4(3) 30(3) -3(3)

C(113) 70(4) 49(4) 61(4) 3(4) 23(4) -7(4)

C(31 ) 50(4) 57(4) 65(4) 11(4) 34(3) 4(3)

C(212) 49(4) 50(4) 60(4) -4(3) 23(3) -1(3)

C(124) 61(4) 46(4) 79(5) 7(3) 40(4) 8(3)

C(109) 63(5) 99(7) 89(6) 6(6) 25(5) -19(5)

C(118) 77(5) 47(4) 80(5) 1(4) 31(4) -9(4)

C(210) 50(4) 48(4) 79(5) -3(4) 26(4) 0(3)

C(120) 71(5) 50(4) 66(5) 8(4) 31(4) 2(4)

C(325) 76(5) 48(4) 86(5) -13(4) 60(4) -11(4) C(117) 59(4) 45(4) 66(4) 11(3) 25(3) -2(3)

C(114) 55(4) 57(4) 76(5) 11(4) 26(4) -1(4)

C(125) 83(5) 64(5) 68(5) 2(4) 41(4) 0(4)

C(115) 62(5) 64(5) 90(6) -12(4) 31(4) -11(4)

C(112) 76(5) 65(5) 78(6) 17(4) 18(4) -13(4)

C(108) 55(4) 71(5) 87(6) 12(5) 21(4) -8(4)

C(327) 64(5) 96(7) 123(8) -50(6) 40(5) -24(5)

C(225) 90(6) 89(7) 76(6) 14(5) 46(5) 19(5)

C(121) 86(6) 66(5) 83(6) 0(5) 38(5) -6(5)

C(326) 390(30) 47(5) 125(10) -17(6) 176(15) -8(9)

C(110) 67(5) 115(8) 117(8) 8(7) 46(6) -17(6)

C(106) 82(7) 130(10) 122(10) -23(8) 33(7) -43(7)

C(105) 81(6) 109(8) 86(7) 6(6) 44(5) -11(6)

C(126) 100(7) 82(6) 99(7) -29(6) 51(6) 0(6)

C(107) 64(5) 78(6) 98(7) 3(5) 40(5) -13(4)

C(227) 156(11) 98(8) 75(7) -22(6) 41(7) -17(8)

C(127) 137(9) 68(6) 113(8) -14(5) 75(7) -33(6)

C(226) 81(6) 172(13) 87(7) 3(7) 38(6) 35(8)

C(102) 79(6) 101(8) 132(10) 52(7) 46(7) 17(6)

C(l l l) 90(7) 103(8) 80(6) 12(6) -7(5) -41(6)

C(119) 94(8) 95(8) 151(12) 31(8) 59(8) 7(6)

C(103) 56(6) 370(30) 98(9) 59(15) 37(6) -12(12)

0(101) 530(40) 430(30) 520(30) -380(30) 460(30) -380(30)

C(104) 123(10) 195(16) 122(10) -25(10) 71(9) -76(11)

C(101) 150(13) 134(12) 229(19) -24(13) 149(14) -14(10)

0(103) 107(7) 840(60) 131(9) 200(19) 70(7) 168(17)

0(2) 300(30) 990(120) 400(50) -240(70) -180(40) -70(50)

0(1) 153(8) 198(11) 101(6) -15(6) 63(6) 33(8)

0(3) 350(50) 2000(300) 460(60) -400(120) 300(50) -400(110)

0(4) 500(60) 2000(300) 210(20) 480(80) -140(30) -160(110) Table 5. Hydrogen coordinates (A x 10 ⁴ ) and isotropic displacement parameters

(A ² x l0 ³ ). x y z U(eq)

H(30A) 6176 2121 325 73

H(30B) 4245 6222 -201 69

H(32A) 11486 4676 -2293 80

H(20A) 10549 12997 -2770 85

H(12A) 11774 6665 -2750 107

H(30C) 5436 7553 489 53

H(30D) 5985 6717 1011 53

H(20B) 11722 8900 -3254 99

H(30E) 7615 6690 -159 47

H(32B) 12682 7487 -1182 112

H(30F) 5822 4048 -93 49

H(31A) 7833 8669 -1092 53

H(32C) 10358 9105 -1690 52

H(22A) 18172 13343 -4632 141

H(31B) 9800 8250 51 65

H(31C) 10060 9792 117 65

H(31D) 9257 9266 287 65

H(20C) 13271 13226 -1743 59

H(32D) 11581 7724 -875 52

H(20D) 11669 11530 -3200 66

H(32E) 11321 7887 -2018 55

H(30G) 6429 8359 142 50

H(20E) 14031 12311 -2525 57

H(30H) 6938 10034 -130 59

H(30I) 6837 10129 -761 59

H(31E) 7719 11904 -335 56

H(31F) 8326 10956 127 56

H(21A) 15329 14837 -2412 55

H(30J) 4622 5693 656 50

H(31G) 8285 11030 -984 54 H(31H) 9085 11481 -470 54

H(32F) 10733 9154 -530 51

H(11A) 14998 5863 -3433 71

H(11B) 14640 7225 -3751 71

H(21B) 16826 14943 -2362 57

H(12B) 14256 6735 -2530 71

H(31I) 7203 5010 822 54

H(31J) 7187 5016 205 54

H(21C) 16353 11655 -2001 78

H(21D) 17046 12167 -1447 78

H(21E) 16042 12066 -1500 78

H(21F) 14882 13442 -3125 62

H(21G) 15237 12143 -2756 62

H(31K) 9194 7144 -1361 64

H(31L) 9887 7054 -760 64

H(22B) 18593 14635 -3398 78

H(20F) 12101 12250 -1617 70

H(20G) 12091 10667 -1692 70

H(31M) 9046 9350 -1328 48

H(22C) 19861 13609 -3036 138

H(32G) 10238 11397 -635 79

H(32H) 11040 11220 -855 79

H(32I) 10074 11307 -1274 79

H(22D) 18173 13754 -1333 98

H(22E) 18970 13676 -1563 98

H(22F) 18397 15002 -1646 98

H(22G) 18062 14821 -2699 67

H(21H) 15853 15294 -885 66

H(21I) 15857 13714 -961 66

H(21J) 16213 13940 -3151 63

H(21K) 16503 12479 -2909 63

H(20H) 10683 11442 -2125 66

H(31N) 8176 6510 -1004 67

H(310) 8835 6690 -395 67

H(12C) 12249 6619 -4146 130

H(12D) 13100 7957 -3423 69 H(20I) 14418 14390 -1361 60

H(20J) 14692 15561 -1689 60

H(21L) 10346 9104 -3160 93

H(21M) 9965 9750 -2703 93

H(22H) 18508 12210 -2828 68

H(22I) 17797 12496 -2138 63

H(31P) 4865 3604 1087 80

H(31Q) 5594 2569 1005 80

H(210) 16427 15630 -1592 62

H(21P) 17039 14587 -1176 62

H(12E) 12901 5800 -2760 70

H(10A) 18388 7351 -2666 100

H(10B) 18660 8528 -2990 100

H(11C) 15758 10201 -3197 100

H(11D) 16491 9929 -3470 100

H(11E) 15551 9271 -3723 100

H(21Q) 12741 9706 -2416 69

H(21R) 13079 10761 -2763 69

H(12F) 14524 8977 -3133 72

H(11F) 15745 6896 -2665 67

H(11G) 16871 6501 -3032 74

H(11H) 15990 5824 -3870 84

H(11I) 15759 7329 -4083 84

H(11J) 16801 9437 -2305 89

H(11K) 17143 7931 -2232 89

H(32J) 9908 6342 -1943 138

H(32K) 10168 6622 -2475 138

H(32L) 10033 5125 -2307 138

H(12G) 15550 9726 -2294 114

H(12H) 14605 9584 -2239 114

H(12I) 15324 8466 -1989 114

H(32M) 11108 5369 -1107 250

H(32N) 11194 4146 -1479 250

H(320) 12031 5007 -1163 250

H(11L) 17781 7726 -5286 115

H(11M) 17564 6696 -4879 115 H(10C) 18730 8635 -3772 134

H(12J) 13278 4095 -3364 134

H(12K) 12757 4080 -4001 134

H(12L) 13413 5271 -3743 134

H(10D) 17120 7265 -4191 92

H(22J) 17851 11224 -3670 163

H(22K) 17803 11227 -4294 163

H(22L) 18724 11272 -3824 163

H(12M) 11870 3937 -3176 146

H(12N) 11118 4989 -3451 146

H(120) 11383 3901 -3818 146

H(22M) 16896 13354 -3835 166

H(22N) 17213 14637 -4082 166

H(220) 16845 13368 -4459 166

H(11N) 17725 9989 -2791 119

H(110) 18295 9307 -2234 119

H(11P) 20148 7348 -5603 162

H(11Q) 19417 6187 -5860 162

H(10E) 20268 8376 -4813 206

H(10J) 18421 4963 -5709 638

H(10F) 19496 9369 -4271 167

H(10G) 18961 9424 -4910 167

H(10H) 18859 5427 -4794 180

H(10I) 20735 6854 -4210 530

Table 6. Torsion angles [°].

C(306)-C(307)-C(308)-C(309) 1.2(11)

C(306)-C(307)-C(308)-C(314) -172.7(6)

C(307)-C(308)-C(314)-C(315) -5.4(10)

C(309)-C(308)-C(314)-C(315) 179.9(6)

C(307)-C(308)-C(314)-C(313) -130.1(6)

C(309)-C(308)-C(314)-C(313) 55.3(7)

C(312)-C(313)-C(314)-C(315) 169.1(6)

C(318)-C(313)-C(314)-C(315) -68.2(6)

C(317)-C(313)-C(314)-C(315) 47.2(6)

C(312)-C(313)-C(314)-C(308) -57.6(7)

C(318)-C(313)-C(314)-C(308) 65.1(7)

C(317)-C(313)-C(314)-C(308) -179.5(5)

C(303)-C(304)-C(305)-C(306) 134.1(6)

C(303)-C(304)-C(305)-C(310) -48.6(8)

C(320)-C(322)-C(323)-C(324) 178.5(6)

O(301 )-C(301 )-C(302)-C(319) 0.1(9)

C(310)-C(301 )-C(302)-C(319) -123.7(7)

0(301 )-C(301 )-C(302)-C(303) -178.4(5)

C(310)-C(301 )-C(302)-C(303) 57.8(7)

C(322)-C(323)-C(324)-0(324) 134.3(6)

C(322)-C(323)-C(324)-C(325) -102.2(8)

C(304)-C(305)-C(306)-C(307) -177.2(6)

C(310)-C(305)-C(306)-C(307) 5.8(11)

C(308)-C(307)-C(306)-C(305) 179.8(7)

C(214)-C(208)-C(207)-C(206) -178.5(6)

C(209)-C(208)-C(207)-C(206) 1.4(11)

C(205)-C(206)-C(207)-C(208) -171.5(7)

C(307)-C(308)-C(309)-C(311) 135.4(7)

C(314)-C(308)-C(309)-C(311) -50.2(8)

C(308)-C(309)-C(311 )-C(312) 50.3(8)

C(207)-C(208)-C(214)-C(215) 2.2(10)

C(209)-C(208)-C(214)-C(215) -177.7(6)

C(207)-C(208)-C(214)-C(213) -124.7(7)

C(209)-C(208)-C(214)-C(213) 55.4(7) C(31 )-C(302)-C(303)-O(303) -116.4(7)

C(301)-C(302)-C(303)-O(303) 62.1(6)

C(31 )-C(302)-C(303)-C(304) 122.0(7)

C(301)-C(302)-C(303)-C(304) -59.5(7)

C(305)-C(304)-C(303)-O(303) -64.5(7)

C(305)-C(304)-C(303)-C(302) 54.4(7)

C(318)-C(313)-C(312)-C(311) -67.7(7)

C(317)-C(313)-C(312)-C(311 ) 165.7(5)

C(314)-C(313)-C(312)-C(311) 55.2(7)

C(309)-C(311)-C(312)-C(313) -53.4(8)

C(323)-C(322)-C(320)-C(321) 121.7(7)

C(323)-C(322)-C(320)-C(317) -114.2(7)

C(208)-C(214)-C(213)-C(212) -58.0(7)

C(215)-C(214)-C(213)-C(212) 167.2(6)

C(208)-C(214)-C(213)-C(218) 64.5(8)

C(215)-C(214)-C(213)-C(218) -70.3(7)

C(208)-C(214)-C(213)-C(217) -179.5(6)

C(215)-C(214)-C(213)-C(217) 45.7(6)

C(212)-C(213)-C(217)-C(216) -151.8(6)

C(218)-C(213)-C(217)-C(216) 79.8(6)

C(214)-C(213)-C(217)-C(216) -36.1(6)

C(212)-C(213)-C(217)-C(220) 82.9(8)

C(218)-C(213)-C(217)-C(220) -45.5(8)

C(214)-C(213)-C(217)-C(220) -161.4(6)

C(306)-C(305)-C(310)-C(301) -136.2(7)

C(304)-C(305)-C(310)-C(301) 46.6(8)

O(301 )-C(301 )-C(310)-C(305) -175.3(5)

C(302)-C(301 )-C(310)-C(305) -49.9(7)

C(208)-C(214)-C(215)-C(216) -167.4(6)

C(213)-C(214)-C(215)-C(216) -36.2(7)

C(322)-C(320)-C(317)-C(316) 53.9(7)

C(321)-C(320)-C(317)-C(316) 175.7(6)

C(322)-C(320)-C(317)-C(313) 175.5(5)

C(321)-C(320)-C(317)-C(313) -62.7(8)

C(315)-C(316)-C(317)-C(320) 150.4(6)

C(315)-C(316)-C(317)-C(313) 19.6(7) C(312)-C(313)-C(317)-C(320) 78.8(7)

C(318)-C(313)-C(317)-C(320) -48.5(7)

C(314)-C(313)-C(317)-C(320) -165.4(6)

C(312)-C(313)-C(317)-C(316) -155.4(6)

C(318)-C(313)-C(317)-C(316) 77.3(6)

C(314)-C(313)-C(317)-C(316) -39.6(6)

C(207)-C(206)-C(205)-C(204) 179.1(7)

C(207)-C(206)-C(205)-C(210) -3.3(12)

C(203)-C(204)-C(205)-C(206) 120.9(7)

C(203)-C(204)-C(205)-C(210) -57.0(8)

O(201 )-C(201 )-C(202)-C(219) -1.9(10)

C(210)-C(201 )-C(202)-C(219) -127.0(8)

O(201 )-C(201 )-C(202)-C(203) 177.3(6)

C(210)-C(201 )-C(202)-C(203) 52.2(8)

C(214)-C(215)-C(216)-C(217) 12.7(7)

C(213)-C(217)-C(216)-C(215) 15.3(7)

C(220)-C(217)-C(216)-C(215) 146.5(6)

C(219)-C(202)-C(203)-O(203) -115.1(8)

C(201)-C(202)-C(203)-O(203) 65.7(8)

C(219)-C(202)-C(203)-C(204) 126.1(8)

C(201)-C(202)-C(203)-C(204) -53.1(8)

C(205)-C(204)-C(203)-O(203) -67.2(8)

C(205)-C(204)-C(203)-C(202) 53.9(8)

C(308)-C(314)-C(315)-C(316) -164.8(6)

C(313)-C(314)-C(315)-C(316) -35.7(7)

C(317)-C(316)-C(315)-C(314) 9.9(8)

C( 120)-C( 122)-C( 123)-C( 124) -179.3(7)

C(207)-C(208)-C(209)-C(211) 130.6(7)

C(214)-C(208)-C(209)-C(211) -49.5(8)

C(212)-C(211 )-C(209)-C(208) 49.5(8)

C(220)-C(222)-C(223)-C(224) 175.5(7)

0(224)-C(224)-C(223)-C(222) 125.8(8)

C(225)-C(224)-C(223)-C(222) -113.7(9)

C(223)-C(222)-C(220)-C(221) 112.0(8)

C(223)-C(222)-C(220)-C(217) -122.9(8)

C(213)-C(217)-C(220)-C(222) -179.2(6) C(216)-C(217)-C(220)-C(222) 59.0(7)

C(213)-C(217)-C(220)-C(221 ) -56.6(9)

C(216)-C(217)-C(220)-C(221 ) -178.4(6)

C(218)-C(213)-C(212)-C(211) -65.7(8)

C(217)-C(213)-C(212)-C(211) 166.8(6)

C(214)-C(213)-C(212)-C(211) 55.6(7)

C(209)-C(211)-C(212)-C(213) -53.7(8)

C( 122)-C( 123)-C( 124)-0( 124) 118.6(8)

C(122)-C(123)-C(124)-C(125) -117.7(9)

C(206)-C(205)-C(210)-C(201) -122.8(8)

C(204)-C(205)-C(210)-C(201) 54.9(8)

O(201 )-C(201 )-C(210)-C(205) -177.8(6)

C(202)-C(201 )-C(210)-C(205) -51.2(8)

C(123)-C(122)-C(120)-C(117) -115.6(9)

C( 123)-C(l 22)-C( 120)-C( 121) 120.0(9)

0(324)-C(324)-C(325)-0(325) -49.3(8)

C(323)-C(324)-C(325)-0(325) -171.4(6)

0(324)-C(324)-C(325)-C(326) 70.8(11)

C(323)-C(324)-C(325)-C(326) -51.3(12)

0(324)-C(324)-C(325)-C(327) -161.7(7)

C(323)-C(324)-C(325)-C(327) 76.2(8)

C(122)-C(120)-C(117)-C(113) 178.5(7)

C(121)-C(120)-C(117)-C(113) -60.3(9)

C(122)-C(120)-C(l 17)-C(116) 57.2(8)

C(121)-C(120)-C(117)-C(116) 178.4(6)

C( 114)-C( 113)-C( 117)-C( 120) -164.4(7)

C( 118)-C(l 13)-C( 117)-C( 120) -46.7(9)

C( 112)-C(l 13)-C( 117)-C( 120) 79.9(9)

C(114)-C(113)-C(117)-C(116) -39.4(7)

C( 118)-C( 113)-C( 117)-C( 116) 78.3(7)

C( 112)-C( 113)-C( 117)-C( 116) -155.1(7)

C( 115)-C( 116)-C( 117)-C( 120) 148.5(7)

C( 115)-C( 116)-C( 117)-C( 113) 17.5(8)

C(118)-C(113)-C(114)-C(108) 63.2(9)

C(112)-C(113)-C(114)-C(108) -58.8(8)

C(117)-C(113)-C(114)-C(108) 179.7(7) C(118)-C(113)-C(114)-C(115) -68.8(8)

C(112)-C(113)-C(114)-C(115) 169.2(6)

C( 117)-C(l 13)-C( 114)-C( 115) 47.7(7)

0( 124)-C( 124)-C( 125)-0( 125) 63.8(8)

C(123)-C(124)-C(125)-0(125) -59.9(9)

0( 124)-C( 124)-C( 125)-C( 127) -56.3(9)

C(123)-C(124)-C(125)-C(127) 180.0(8)

0( 124)-C( 124)-C( 125)-C( 126) -178.6(7)

C(123)-C(124)-C(125)-C(126) 57.7(9)

C(108)-C(114)-C(115)-C(116) -165.5(7)

C(113)-C(114)-C(115)-C(116) -36.4(8)

C(117)-C(116)-C(115)-C(114) 11.3(8)

C(114)-C(113)-C(112)-C(l l l) 55.2(10)

C(118)-C(113)-C(112)-C(l l l) -67.0(10)

C(117)-C(113)-C(112)-C(l l l) 167.0(8)

C(113)-C(114)-C(108)-C(107) -124.0(10)

C(115)-C(114)-C(108)-C(107) -0.1(13)

C(l 13)-C(114)-C(108)-C(109) 56.0(10)

C(115)-C(114)-C(108)-C(109) 179.8(8)

C(l l l)-C(109)-C(108)-C(107) 129.2(11)

C(l l l)-C(109)-C(108)-C(114) -50.8(11)

0(224)-C(224)-C(225)-0(225) -50.2(9)

C(223)-C(224)-C(225)-0(225) -172.6(7)

0(224)-C(224)-C(225)-C(226) -166.3(9)

C(223)-C(224)-C(225)-C(226) 71.3(11)

0(224)-C(224)-C(225)-C(227) 66.1(10)

C(223)-C(224)-C(225)-C(227) -56.3(10)

C(107)-C(106)-C(105)-C(110) -9(2)

C( 107)-C( 106)-C( 105)-C( 104) 168.6(14)

C(101)-C(110)-C(105)-C(106) -120.2(15)

C(101)-C(110)-C(105)-C(104) 61.6(15)

C(l 14)-C(108)-C(107)-C(106) 174.8(10)

C( 109)-C( 108)-C( 107)-C( 106) -5.2(18)

C(105)-C(106)-C(107)-C(108) 171.5(14)

C(108)-C(109)-C(l l l)-C(112) 51.9(12)

C(113)-C(112)-C(l l l)-C(109) -53.9(11) C(l 19)-C(102)-C(103)-O(103) -114.4(13)

C(101)-C(102)-C(103)-O(103) 68.6(15)

C(119)-C(102)-C(103)-C(104) 122.2(13)

C(101)-C(102)-C(103)-C(104) -54.8(18)

C( 106)-C( 105)-C( 104)-C( 103) 123.0(14)

C(110)-C(105)-C(104)-C(103) -58.7(15)

0( 103)-C( 103)-C( 104)-C( 105) -73.2(19)

C( 102)-C( 103)-C( 104)-C( 105) 55.4(16)

C(119)-C(102)-C(101)-O(101) -15(2)

C(103)-C(102)-C(101)-O(101) 162.2(19)

C( 11 )-C( 102)-C( 101 )-C( 110) -126.2(14)

C(103)-C(102)-C(101)-C(110) 50.7(19)

C(105)-C(l 10)-C(101)-O(101) -170.0(13)

C(105)-C(110)-C(101)-C(102) -54.4(17)

Symmetry transformations used to generate equivalent atoms: