Total Synthesis of the Daphniphyllum Alkaloid Daphenylline · Total Synthesis of the Daphniphyllum...
Transcript of Total Synthesis of the Daphniphyllum Alkaloid Daphenylline · Total Synthesis of the Daphniphyllum...
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Electronic Supplementary Information
Total Synthesis of the Daphniphyllum Alkaloid
Daphenylline
Zhaoyong Lu,† Yong Li,† Jun Deng, Ang Li*
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Email: [email protected]
I Experimental Procedures and Spectroscopic Data of Compounds S2
II References S19
III HPLC Traces for Measuring Enantiomeric Excess S20
IV 1H and 13C NMR Spectra of Compounds S23
V Comparison of Spectra of Natural and Synthetic Daphenylline S59
VI Crystallographic Data S65
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I Experimental Procedures and Spectroscopic Data of Compounds
General Procedures. All reactions were carried out under an argon atmosphere with dry solvents under
anhydrous conditions, unless otherwise noted. Anhydrous acetonitrile (MeCN) and toluene were
obtained by passing commercially available pre-dried, oxygen-free formulations through activated
alumina columns. Benzene, diethyl ether (Et2O), 1,2-dimethoxyethane (DME), and tetrahydrofuran
(THF) were distilled immediately before use from sodium-benzophenone ketyl. N,N-
Dimethylformamide (DMF), dimethylsulfoxide (DMSO), methylene chloride (CH2Cl2),
triethylamine (Et3N), N,N-diisopropylethylamine (i-Pr2NEt), and 2,6-lutidine were distilled from
calcium hydride and stored under an argon atmosphere. Methanol (MeOH) was distilled form
magnesium and stored under an argon atmosphere. Reagents were purchased at the highest commercial
quality and used without further purification, unless otherwise stated. Solvents for chromatography were
used as supplied by Sinopharm Chemicals. Reactions were monitored by thin layer chromatography
(TLC) carried out on S-2 0.25 mm E. Merck silica gel plates (60F-254) using UV light as visualizing
agent and aqueous ammonium cerium nitrate/ammonium molybdate or basic aqueous potassium
permanganate as developing agent. E. Merck silica gel (60, particle size 0.040–0.063 mm) was used for
flash column chromatography. Preparative thin layer chromatography separations were carried out on
0.25 or 0.50 mm E. Merck silica gel plates (60F-254). NMR spectra were recorded on Bruker AV-400,
DRX-600, or Agilent 500 instrument and calibrated by using residual undeuterated chloroform (δH =
7.26 ppm) and CDCl3 (δC = 77.16 ppm) as internal references. The following abbreviations are used to
designate multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, quint = quintet, br
= broad. IR spectra were recorded on a Thermo Scientific Nicolet 380 FT-IR spectrometer. Melting
points (m.p.) are uncorrected and were recorded on a SGW X-4 apparatus. High-resolution mass spectra
(HRMS) were recorded on a Bruker APEXIII 7.0 Tesla ESI-FT mass spectrometer at a 4000 V emitter
voltage.
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Sulfonylamino cyclohexenone 15: To a stirred solution of 4-hydroxy-3-methylcyclohaxenone 16 (3.42
g, 27.1 mmol),1,2 N-propargyl-2-nitrobenzenesulfonamide 17 (7.16 g, 29.8 mmol), and PPh3 (7.82 g,
29.8 mmol) in THF (40 mL) was added DIAD (6.03 g, 5.91 mL, 29.8 mmol) at 0 °C. The resulting
mixture was stirred at that temperature for 10 min before it was quenched with saturated aq. NaHCO3
solution (100 mL) and extracted with EtOAc (3 × 100 mL). The combined organic phases were washed
with brine (100 mL) and dried over anhydrous Na2SO4. After filtration and evaporation of the solvent,
the residue so obtained was purified by flash column chromatography with EtOAc/petroleum ether (1:5
→ 1:2) to give sulfonylamino cyclohexenone 15 (8.12 g, 23.3 mmol, 86%) as a white solid. 15: Rf =
0.41 (silica, EtOAc:petroleum ether 1:1); [α]28 D = +144.7 (c = 1.0 in CHCl3); IR (film): νmax = 3292, 3259,
3099, 3084, 2950, 2935, 2920, 1674, 1544, 1438, 1361, 1343, 1169, 1147, 1127, 1087, 1031, 921, 880,
852, 788, 742, 727, 655, 599, 557 cm−1; 1H NMR (400 MHz, CDCl3): δ = 8.23 (dd, J = 7.6, 1.6 Hz, 1 H),
7.77–7.69 (m, 2 H), 7.67 (dd, J = 7.3, 1.8 Hz, 1 H), 6.04 (s, 1 H), 4.94 (t, J = 7.3 Hz, 1 H), 4.43 (dd, J =
18.6, 2.4 Hz, 1 H), 3.70 (dd, J = 18.6, 2.4 Hz, 1 H), 2.59 (dt, J = 16.4, 4.5 Hz, 1 H), 2.55–2.45 (m, 1 H),
2.40–2.28 (m, 2 H), 2.13 (t, J = 2.4 Hz, 1 H), 1.91 (s, 3 H) ppm; 13C NMR (101 MHz, CDCl3): δ =
197.3, 159.1, 148.0, 134.3, 133.4, 131.9, 131.8, 131.1, 124.3, 78.3, 74.1, 58.8, 36.6, 34.2, 28.1, 21.3
ppm; HRMS (m/z): [M + Na]+ calcd for C16H16N2O5SNa+ 371.0672; found 371.0666.
Bridged bicyclic compound 20: To a stirred solution of sulfonylamino cyclohexenone 15 (2.05 g, 5.88
mmol) in CH2Cl2 (30 mL) were sequentially added 2,6-lutidine (756 mg, 0.82 mL, 7.06 mmol) and
freshly prepared TBDPSOTf (8.09 mL, 0.8 M in CH2Cl2, 6.47 mmol)3 at −78 °C. The reaction mixture
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was stirred at that temperature for 5 min before it was quenched with saturated aq. NaHCO3 solution (50
mL) and extracted with CH2Cl2 (3 × 100 mL). The combined organic phases were sequentially washed
with aq. citric acid (30 mL, 10 wt%), water (30 mL), and brine (30 mL). The resulting organic layer was
dried over anhydrous Na2SO4 and filtered. After removal of the solvent under vacuum, the residue was
purified by flash column chromatography with EtOAc/petroleum ether (1:10) to give the corresponding
silyl enol ether as a pale yellow oil. The silyl enol ether so obtained was immediately dissolved in
toluene (30 mL). To this solution was added Au(PPh3)Cl (291 mg, 0.588 mmol) followed by a solution
of AgOTf (227 mg, 0.882 mmol) in MeOH (3.0 mL) at 22 °C. After stirring at that temperature for 15
min, the resulting mixture was directly subjected to flash column chromatography for purification using
EtOAc/petroleum ether (1:5 → 1:3) as eluent to give bridged bicyclic compound 20 (1.43 g, 4.10 mmol,
70% over 2 steps) as a pale yellow powder and recovered cyclohexenone 15 (590 mg, 1.69 mmol, 29%).
20: Rf = 0.48 (silica, EtOAc:petroleum ether 1:1); [α]24 D = +35.5 (c = 1.0 in CHCl3); IR (film): νmax =
3096, 2950, 2908, 2858, 1678, 1634, 1542, 1439, 1370,1274, 1249, 1164, 1126, 1078, 943, 920, 778,
729, 740, 655, 609, 570 cm−1; 1H NMR (400 MHz, CDCl3): δ = 8.12–8.08 (m, 1 H), 7.77–7.71 (m, 2 H),
7.71–7.67 (m, 1 H), 6.11 (s, 1 H), 5.00 (s, 1 H), 4.91 (s, 1 H), 4.59 (s, 1 H), 4.13 (d, J = 15.5 Hz, 1 H),
3.89 (d, J = 15.5 Hz, 1 H), 3.19 (s, 1 H), 2.31 (dt, J = 13.1, 3.0 Hz, 1 H), 2.08 (dd, J = 13.1, 3.0 Hz, 1 H),
2.05 (d, J = 1.1 Hz, 3 H) ppm; 13C NMR (101 MHz, CDCl3): δ = 196.6, 155.4, 147.8, 137.1, 134.1,
133.4, 132.1, 130.9, 129.5, 124.7, 114.5, 51.7, 50.2, 46.0, 32.8, 21.9 ppm; HRMS (m/z): [M + Na]+
calcd for C16H16N2O5SNa+ 371.0672; found 371.0667.
Bridged bicyclic amide 21: To a stirred solution of bridged bicyclic compound 20 (2.94 g, 8.44 mmol)
in DMF (5.0 mL) were sequentially added K2CO3 (2.34 g, 16.9 mmol) and p-thiocresol (1.58 g, 12.7
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mmol) at 22 °C. After stirring at that temperature for 1 h, the reaction mixture was directly subjected to
flash column chromatography using EtOAc/petroleum ether (1:10) followed by MeOH/CH2Cl2 (1:100
→ 1:10) as eluent to give the corresponding secondary amine as a pale yellow oil. The secondary amine
so obtained was dissolved in CH2Cl2 (50 mL). To this solution were sequentially added carboxylic acid
14 (2.79 g, 10.1 mmol),4 Et3N (1.71 g, 2.36 mL, 16.9 mmol), HOBt (1.72 g, 12.7 mmol), and EDC•HCl
(2.43 g, 12.7 mmol) at 22 °C. The resulting mixture was stirred at that temperature for 2 h before it was
quenched with saturated aq. NaHCO3 solution (30 mL). After extraction with CH2Cl2 (3 × 50 mL) and
washing with brine (30 mL), the combined organic phases were dried over anhydrous Na2SO4, filtered,
and evaporated under vacuum. The residue so obtained was purified by flash column chromatography
with EtOAc/petroleum ether (1:5 → 1:2) to give bridged bicyclic amide 21 (2.57 g, 6.10 mmol, 72%) as
a white foam. 21: Rf = 0.35 (silica, EtOAc:petroleum ether 1:2); [α]29 D = +62.5 (c = 1.0 in CHCl3); IR
(film): νmax = 2953, 2930, 2881, 2857, 1747, 1681, 1649, 1434, 1272, 1250, 1201, 1182, 1152, 1103,
837, 778 cm−1; 1H NMR (400 MHz, CDCl3) (a mixture of inconsequential diastereomers and amide C–
N bond rotamers): δ = 6.05 (s, 1 H), 5.41–5.39 (m, 0.73 H), 5.02 (s, 0.71 H), 5.00 (s, 0.26 H), 4.98–4.91
(m, 1.24 H), 4.62 (s, 0.19 H), 4.36 (d, J = 7.4 Hz, 0.57 H), 4.28 (d, J = 7.6 Hz, 0.16 H), 4.07 (m, 0.24 H),
3.96–3.93 (m, 0.74 H), 3.88 (s, 0.42 H), 3.84 (s, 0.37 H), 3.71–3.68 (m, 2.87 H), 3.66–3.61 (m, 1.48 H),
3.59–3.53 (m, 0.73 H), 3.47 (s, 0.14 H), 3.43 (s, 0.13 H), 3.24–3.23 (m, 1 H), 2.36–2.23 (m, 1.20 H),
2.21–2.07 (m, 1 H), 2.06–2.00 (m, 1.41 H), 1.99–1.97 (m, 1 H), 1.95–1.93 (m, 2.22 H), 1.90–1.89 (m,
0.56 H), 0.85–0.83 (m, 9 H), 0.03–−0.04 (m, 6 H) ppm; 13C NMR (101 MHz, CDCl3) (a mixture of
inconsequential diastereomers and amide C–N bond rotamers): δ = 197.0, 196.5, 170.4, 170.2, 168.5,
168.4, 168.0, 157.1, 156.6, 154.8, 138.1, 138.0, 137.7, 129.2, 129.0, 128.6, 114.4, 114.1, 113.8, 60.2,
60.1, 52.5, 51.7, 50.7, 50.7, 47.1, 46.8, 46.5, 46.4, 45.3, 45.0, 44.9, 42.8, 33.8, 32.8, 32.7, 32.6, 31.9,
26.0, 25.9, 22.2, 22.1, 21.6, 18.3, 18.3, −5.3, −5.4, −5.4 ppm; HRMS (m/z): [M + H]+ calcd for
C22H36NO5Si+ 422.2357; found 422.2357.
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Bridged tricyclic compound 9: To a stirred solution of amide 21 (2.57 g, 6.10 mmol) in MeCN (25 mL)
was added K2CO3 (1.69 g, 12.2 mmol) at 22 °C. The resulting mixture was heated to 100 °C and stirred
at that temperature for 5 h before it was cooled to 22 °C and quenched with saturated aq. NaHCO3
solution (100 mL). The mixture so obtained was extracted with EtOAc (3 × 100 mL), and the combined
organic phases were washed with brine (50 mL) and dried over anhydrous Na2SO4. After filtration and
evaporation of the solvent, the residue was subjected to flash column chromatography using
EtOAc/petroleum ether (1:3 → 1:1) as eluent to give bridged tricyclic compound 9 (2.21 g, 5.24 mmol,
86%) as a white foam. 9: Rf = 0.40 (silica, EtOAc:petroleum ether 1:1); [α]27 D = −70.0 (c = 1.0 in CHCl3);
IR (film): νmax = 2954, 2930, 2900, 2856, 1736, 1716, 1700, 1471, 1462, 1421, 1389, 1258, 1213, 1172,
1139, 1084, 813, 778, 733, 664 cm−1; 1H NMR (400 MHz, CDCl3): δ = 4.90 (s, 1 H), 4.88 (s, 1 H), 4.46
(d, J = 16.5 Hz, 1 H), 4.13 (td, J = 9.6, 5.4 Hz, 1 H), 3.91 (d, J = 5.5 Hz, 1 H), 3.64 (s, 3 H), 3.61 (dd, J
= 9.7, 5.5 Hz, 1 H), 3.46 (d, J = 16.4 Hz, 1 H), 2.89 (d, J = 3.1 Hz, 1 H), 2.61 (d, J = 15.0 Hz, 1 H), 2.29
(dd, J = 14.7, 4.1 Hz, 1 H), 2.17 (d, J = 15.0 Hz, 1 H), 2.12 (ddd, J = 14.7, 5.7, 1.0 Hz, 1 H), 2.01 (ddd,
J = 14.5, 7.3, 4.2 Hz, 1 H), 1.82–1.72 (m, 1 H), 1.13 (s, 3 H), 0.80 (s, 9 H), −0.03 (s, 6 H) ppm; 13C
NMR (101 MHz, CDCl3): δ = 207.1, 172.3, 170.1, 143.3, 112.2, 60.3, 59.5, 58.0, 52.2, 50.6, 48.3, 45.2,
40.4, 32.9, 25.9, 23.4, 20.6, 18.2, −5.3, −5.4 ppm; HRMS (m/z): [M + Na]+ calcd for C22H35NO5SiNa+
444.2177; found 444.2180. CCDC 917083 contains the supplementary crystallographic data for
desilylated 9 (m.p. 144–147 °C, EtOAc/n-hexane 1:1) and is available free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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trans-Boronate ester 22: To a stirred solution of 2-vinylcyclopentenone (150 mg, 1.39 mmol)5 in
CH2Cl2 (4 mL) were sequentially added pinacol vinylboronate (430 mg, 0.48 mL, 2.78 mmol) and
Hoveyda-Grubbs 2nd generation catalyst (88 mg, 0.14 mmol). The resulting mixture was stirred at 40 oC
for 24 h. The solvent was removed under vacuum and the residue was subjected to flash column
chromatography using EtOAc/petroleum ether (1:8 → 1:3) to give trans-boronate ester 22 (202 mg,
0.863 mmol, 62%) as a colorless oil. 22: Rf = 0.42 (silica, EtOAc:petroleum ether 1:4); IR (film): νmax =
3500, 2978, 2928, 2855, 1708, 1633, 1439, 1379, 1358, 1325, 1257, 1203, 1168, 1144, 1006, 970, 850
cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.62 (t, J = 2.7 Hz, 1 H), 7.06 (d, J = 18.6 Hz, 1 H), 6.46 (d, J =
18.6 Hz, 1 H), 2.63 (d, J = 3.9 Hz, 2 H), 2.48–2.45 (m, 2 H), 1.26 (s, 12 H) ppm; 13C NMR (101 MHz,
CDCl3): δ = 207.6, 160.9, 141.8, 138.7, 138.7, 83.5, 35.8, 26.6, 24.9 ppm.
trans-Triene 23: To a stirred solution of bridged tricyclic ketone 9 (945 mg, 2.24 mmol) in THF (10
mL) was added KHMDS (5.38 mL, 0.5 M in toluene, 2.69 mmol) at −78 °C. The resulting mixture was
stirred at that temperature for 5 min before a solution of PhNTf2 (879 mg, 2.46 mmol) in THF (5 mL)
was added. The mixture so obtained was stirred at that temperature for 5 min before it was quenched
with saturated aq. NaHCO3 solution (50 mL). After extraction with EtOAc (3 × 80 mL) and washing
with brine (30 mL), the combined organic phases were dried over anhydrous Na2SO4, filtered, and
evaporated under vacuum. The residue was purified by flash column chromatography with
EtOAc/petroleum ether (1:6 → 1:3) to give the corresponding enol triflate as a colorless oil. The enol
triflate so obtained was immediately dissolved in DME (15 mL). To this solution were sequentially
added trans-boronate ester 22 (630 mg, 2.69 mmol), K2CO3 (929 mg, 6.72 mmol), and Pd(PPh3)4 (254
mg, 0.22 mmol) at 22 °C. After bubbling with argon for 15 min, the resulting mixture was heated to
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60 °C and stirred at that temperature for 30 min before it was cooled to 22 °C and quenched with
saturated aq. NaHCO3 solution (30 mL). The mixture so obtained was extracted with EtOAc (3 × 50
mL), and the combined organic phases were washed with brine (30 mL) and dried over anhydrous
Na2SO4. After filtration and evaporation of the solvent, the residue was subjected to flash column
chromatography using EtOAc/petroleum ether (1:5 → 1:2) as eluent to give trans-triene 23 (836 mg,
1.63 mmol, 73% over 2 steps) as a white powder. 23: Rf = 0.34 (silica, EtOAc:petroleum ether 1:2); [α]
27 D = −73.2 (c = 1.0 in CHCl3); IR (film): νmax = 2953, 2930, 2897, 2856, 1731, 1702, 1438, 1412, 1279,
1257, 1234, 1215, 1133, 1082, 913, 837, 779, 734 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.50 (t, J =
2.9 Hz, 1 H), 6.94 (d, J = 16.4 Hz, 1 H), 6.43 (d, J = 16.3 Hz, 1 H), 5.58 (s, 1 H), 4.99 (s, 1 H), 4.86 (s, 1
H), 4.54 (d, J = 16.4 Hz, 1 H), 4.22 (td, J = 9.5, 5.7 Hz, 1 H), 3.96 (d, J = 5.0 Hz, 1 H), 3.74 (s, 3 H),
3.70 (dd, J = 9.5, 5.5 Hz, 1 H), 3.63 (d, J = 16.4 Hz, 1 H), 3.40 (s, 1 H), 2.65 (d, J = 4.5 Hz, 2 H), 2.49–
2.47 (m, 2 H), 2.15–2.03 (m, 2 H), 2.01–1.94 (m, 1 H), 1.79 (dd, J = 13.8, 3.4 Hz, 1 H), 1.16 (s, 3 H),
0.90 (s, 9 H), 0.07 (s, 6 H) ppm; 13C NMR (101 MHz, CDCl3): δ = 208.1, 174.0, 170.3, 157.8, 143.2,
141.1, 140.5, 133.8, 131.2, 118.4, 111.0, 60.6, 60.1, 56.3, 52.3, 50.5, 41.2, 35.6, 33.6, 33.3, 26.7, 26.2,
23.7, 18.5, 17.9, −5.1, −5.2 ppm; HRMS (m/z): [M + Na]+ calcd for C29H41NO5SiNa+ 534.2646; found
534.2654.
cis-Triene 12: A solution of trans-triene 22 (107 mg, 0.209 mmol) in benzene (100 mL) in a quartz
vessel was irradiated by an Hg lamp (125 W) at 0 °C for 5 min. After removal of the solvent under
vacuum, the residue was purified by flash column chromatography with EtOAc/petroleum ether (1:3) to
give cis-triene 12 (85.8 mg, 0.168 mmol, 80%) as a pale yellow foam. 12: Rf = 0.39 (silica,
EtOAc:petroleum ether 1:2); [α]25 D = −156.7 (c = 1.0 in CHCl3); IR (film): νmax = 2955, 2928, 2899, 2856,
1733, 1701, 1459, 1438, 1410, 1258, 1233, 1213, 1083, 837, 778 cm−1; 1H NMR (400 MHz, CDCl3): δ
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= 7.52 (t, J = 2.6 Hz, 1 H), 6.03–5.96 (m, 2 H), 5.25 (s, 1 H), 4.90 (s, 1 H), 4.85 (s, 1 H), 4.64 (d, J =
16.4 Hz, 1 H), 4.21 (td, J = 9.9, 5.2 Hz, 1 H), 3.89 (d, J = 4.9 Hz, 1 H), 3.73 (s, 3 H), 3.64 (dt, J = 16.3,
2.2 Hz, 1 H), 3.56 (td, J = 9.9, 5.2 Hz, 1 H), 2.90 (s, 1 H), 2.76–2.68 (m, 1 H), 2.58–2.50 (m, 1 H), 2.45
(ddd, J = 19.1, 6.8, 2.4 Hz, 1 H), 2.33 (ddd, J = 19.1, 6.8, 2.1 Hz, 1 H), 2.11 (ddd, J = 13.8, 5.4, 2.1 Hz,
1 H), 1.80 (ddd, J = 15.6, 9.9, 4.5 Hz, 2 H), 1.68–1.61 (m, 1 H), 1.07 (s, 3 H), 0.87 (s, 9 H), 0.03 (s, 3 H),
0.02 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 209.5, 174.4, 170.0, 160.6, 143.1, 140.9, 139.6, 134.4,
125.7, 121.3, 110.6, 60.1, 59.9, 55.9, 52.2, 50.1, 41.1, 38.3, 34.6, 33.0, 27.1, 26.1, 23.4, 18.5, 17.8, −5.2,
−5.2 ppm; HRMS (m/z): [M + Na]+ calcd for C29H41NO5SiNa+ 534.2646; found 534.2651.
Pentacyclic compound 24: A solution of trans-triene 22 (107 mg, 0.209 mmol) in benzene (100 mL) in
a quartz vessel was irradiated by an Hg lamp (500 W) at 0 °C for 15 min before the solvent was
removed under vacuum. The residue so obtained was subjected to flash column chromatography using
EtOAc/petroleum ether (1:1) as eluent to give pentacyclic compound 24 (76.0 mg, 0.149 mmol, 71%) as
a pale yellow foam. 24: Rf = 0.47 (silica, EtOAc:petroleum ether 1:1); [α]25 D = −470.5 (c = 1.0 in CHCl3);
IR (film): νmax = 2953, 2928, 2893, 2852, 1730, 1707, 1650, 1575, 1424, 1254, 1211, 1138, 1084, 835,
777, 730 cm−1; 1H NMR (400 MHz, CDCl3): δ = 6.52 (dd, J = 6.2, 2.4 Hz, 1 H), 5.95 (d, J = 6.2 Hz, 1
H), 4.93 (s, 1 H), 4.89 (s, 1 H), 4.68 (d, J = 16.8 Hz, 1 H), 4.47 (td, J = 9.1, 6.3 Hz, 1 H), 3.89 (d, J = 5.2
Hz, 1 H), 3.74 (s, 3 H), 3.55–3.45 (m, 2 H), 3.31–3.25 (m, 1 H), 3.13 (s, 1 H), 2.85 (d, J = 6.5 Hz, 1 H),
2.33 (ddd, J = 12.3, 9.0, 3.4 Hz, 1 H), 2.25–2.18 (m, 3 H), 2.14–2.01 (m, 2 H), 1.92 (dd, J = 14.6, 5.3
Hz, 1 H), 1.43–1.56 (m, 1 H), 1.22 (s, 3 H), 0.83 (s, 9 H), −0.00 (s, 3 H), −0.01 (s, 3 H) ppm; 13C NMR
(101 MHz, CDCl3): δ = 204.0, 173.5, 171.1, 146.8, 143.9, 138.1, 124.6, 119.6, 110.1, 62.0, 61.3, 60.6,
54.8, 52.5, 50.3, 41.1, 40.5, 38.9, 36.6, 35.2, 33.3, 26.2, 23.4, 21.5, 18.5, −4.8, −5.0 ppm; HRMS (m/z):
[M + Na]+ calcd for C29H41NO5SiNa+ 534.2646; found 534.2637.
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Pentacyclic indanone 25: A solution of pentacyclic compound 24 (76.0 mg, 0.149 mmol) in DBU (2
mL) was stirred under air at 60 °C for 4 h. The resulting mixture was diluted with CH2Cl2 (30 mL) and
sequentially washed with aq. citric acid (10 mL, 10 wt%) and brine (10 mL). The organic phases were
dried over anhydrous Na2SO4, filtered, and evaporated. The residue so obtained was purified by flash
column chromatography with EtOAc/petroleum ether (1:4 → 1:1) to give pentacyclic indanone 25 (50.9 mg,
0.100 mmol, 67%) as a pale yellow foam. 25: Rf = 0.51 (silica, EtOAc:petroleum ether 1:1); [α]29 D =
−83.4 (c = 1.0 in CHCl3); IR (film): νmax = 2952, 2926, 2895, 2855, 1730, 1708, 1581, 1459, 1441, 1426,
1407, 1290, 1273, 1249, 1210, 1127, 1082, 917, 836, 778, 732 cm−1; 1H NMR (400 MHz, CDCl3): δ =
7.60 (d, J = 7.9 Hz, 1 H), 7.35 (d, J = 7.9 Hz, 1 H), 5.23 (s, 1 H), 4.95 (s, 1 H), 4.68 (d, J = 16.5 Hz, 1
H), 4.11–4.03 (m, 2 H), 3.82 (s, 3 H), 3.68 (br d, J = 16.5 Hz, 1 H), 3.65–3.60 (m, 1 H), 3.58 (br s, 1 H),
3.47 (td, J = 10.1, 4.3 Hz, 1 H), 3.16–3.06 (m, 1 H), 2.74–2.59 (m, 2 H), 2.49–2.41 (m, 1 H), 2.26 (ddd,
J = 13.8, 5.6, 1.5 Hz, 1 H), 1.91 (dd, J = 13.9, 3.8 Hz, 1 H), 1.67 (s, 3 H), 1.36 (ddd, J = 12.5, 10.3, 5.6
Hz, 1 H), 0.80 (s, 9 H), −0.05 (s, 3 H), −0.10 (s, 3 H) ppm; 13C NMR (101 MHz, CDCl3): δ = 206.0,
172.3, 170.5, 156.8, 149.0, 145.1, 137.0, 134.0, 130.7, 122.5, 110.5, 63.3, 60.2, 60.1, 53.7, 52.6, 41.8,
40.4, 36.3, 34.8, 30.9, 26.0, 23.2, 20.6, 18.3, −5.1 ppm; HRMS (m/z): [M + Na]+ calcd for
C29H39NO5SiNa+ 532.2490; found 532.2496.
Hexacyclic lactone 26: A solution of trans-triene 22 (2.2 mg, 0.0041 mmol) in benzene (2 mL) in a
quartz vessel was irradiated by an Hg lamp (500 W) at 0 °C for 15 min under an air atmosphere. After
removal of the solvent under vacuum, the residue was purified by flash column chromatography with
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EtOAc/petroleum ether (1:5 → 1:2) to give hexacyclic lactone 26 (1.6 mg, 0.0029 mmol, 71%) as a pale
yellow foam. 26: Rf = 0.41 (silica, EtOAc:petroleum ether 1:1); IR (film): νmax = 2952, 2930, 2899,
2852, 1766, 1731, 1695, 1445, 1426, 1254, 1241, 1209, 1172, 1126, 1099, 1079, 911, 835, 778, 733
cm−1; 1H NMR (400 MHz, CDCl3): δ = 6.35 (d, J = 5.8 Hz, 1 H), 6.15 (d, J = 5.8 Hz, 1 H), 5.00 (s, 2 H),
4.79 (d, J = 17.2 Hz, 1 H), 4.36 (td, J = 9.9, 5.8 Hz, 1 H), 3.82 (d, J = 5.5 Hz, 1 H), 3.72 (s, 3 H), 3.65
(dt, J = 17.2, 2.4 Hz, 1 H), 3.54 (td, J = 10.2, 4.0 Hz, 1 H), 2.99 (d, J = 4.2 Hz, 1 H), 2.78 (ddd, J = 16.3,
8.1, 4.7 Hz, 1 H), 2.55 (q, J = 6.7 Hz, 1 H), 2.47 (ddd, J = 16.3, 9.0, 4.6 Hz, 1 H), 2.32 (dd, J = 14.9, 4.7
Hz, 1 H), 2.26–2.18 (m, 1 H), 2.03 (d, J = 6.5 Hz, 1 H), 2.00–1.93 (m, 2 H), 1.85 (ddd, J = 12.8, 10.1,
3.9 Hz, 2 H), 1.17 (s, 3 H), 0.88 (s, 9 H), 0.06 (s, 3 H), 0.06 (s, 3 H) ppm; 13C NMR (126 MHz, CDCl3):
δ = 172.4, 170.3, 168.8, 143.9, 138.3, 135.7, 111.7, 110.8, 87.0, 61.3, 60.1, 58.6, 52.5, 48.0, 40.5, 39.5,
34.9, 33.6, 28.4, 26.1, 26.1, 25.5, 23.5, 23.2, 18.5, −4.9, −5.0 ppm; HRMS (m/z): [M + Na]+ calcd for
C29H41NO7SiNa+ 566.2545; found 566..2537.
Hexacyclic hydroxylactone 27: To a stirred solution of hexacyclic lactone 26 (14.5 mg, 0.0267 mmol)
in THF (1.0 mL) in a plastic vial was added HF•py (0.10 mL) at 0 °C. The reaction mixture was stirred
at that temperature for 10 min before it was poured to a saturated aq. NaHCO3 solution (5 mL). After
extraction with CH2Cl2 (4 × 5 mL), the combined organic phases were washed with brine (5 mL), dried
over anhydrous Na2SO4, and filtered. The solvent was evaporated under vacuum, and the residue so
obtained was purified by flash column chromatography with EtOAc/petroleum ether (1:1 → 4:1) to give
the corresponding hexacyclic hydroxylactone 27 (10.5 mg, 0.0245 mmol, 92%) as a white powder. 27:
Rf = 0.31 (silica, EtOAc); m.p. 136–138 °C (EtOAc/n-hexane 1:1); IR (film): νmax = 3328, 2950, 1761,
1729, 1673, 1452, 1431, 1240, 1206, 1172, 1128, 1102, 1069, 913, 731 cm−1; 1H NMR (400 MHz,
CDCl3): δ = 6.45 (d, J = 5.8 Hz, 1 H), 6.14 (d, J = 5.8 Hz, 1 H), 5.03 (s, 2 H), 4.83–4.79 (m, 2 H), 3.88
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(d, J = 5.4 Hz, 1 H), 3.76 (s, 3 H), 3.74–3.68 (m, 2 H), 3.67–3.60 (m, 1 H), 3.03 (d, J = 4.1 Hz, 1 H),
2.78 (ddd, J = 16.5, 8.0, 4.7 Hz, 1 H), 2.51–2.44 (m, 2 H), 2.34 (dd, J = 15.0, 4.6 Hz, 1 H), 2.26–2.17
(m, J = 10.0, 7.9, 3.9 Hz, 1 H), 2.06–1.96 (m, 3 H), 1.91–1.82 (m, 2 H), 1.16 (s, 3 H) ppm; 13C NMR
(126 MHz, CDCl3): δ = 173.8, 170.1, 168.5, 143.3, 138.2, 136.0, 112.2, 110.8, 86.9, 64.5, 61.0, 60.0,
58.8, 52.7, 48.5, 41.0, 39.4, 35.3, 32.9, 28.5, 25.6, 23.6, 23.1 ppm; HRMS (m/z): [M + H]+ calcd for
C23H28NO7+ 430.1860; found 430.1861. CCDC 917085 contains the supplementary crystallographic
data for 27 and is available free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Pentacyclic indenone 29: To a stirred solution of pentacyclic indanone 25 (91.2 mg, 0.179 mmol) in
Et3N (0.50 mL) and CH2Cl2 (2.0 mL) was added TMSOTf (120 mg, 98 μL, 0.537 mmol) at −78 °C. The
reaction mixture was stirred at that temperature for 10 min before it was diluted with CH2Cl2 (20 mL)
and quenched with saturated aq. NaHCO3 solution (20 mL). The resulting mixture was extracted with
CH2Cl2 (3 × 10 mL), and the combined organic phases were washed with brine (10 mL) and dried over
anhydrous MgSO4. After filtration and evaporation of the solvent, the residue (crude trimethylsilyl enol
ether) was dissolved in MeCN (2.0 mL). To this solution was added Pd(OAc)2 (40.2 mg, 0.179 mmol) at
22 °C. The resulting mixture was stirred at that temperature for 1 h before the solvent was removed
under vacuum. The residue so obtained was subjected to flash column chromatography using
EtOAc/petroleum ether (1:5 → 1:2) as eluent to give pentacyclic indenone 30 (73.8 mg, 0.145 mmol,
81% over 2 steps) as a pale yellow foam. 30: Rf = 0.33 (silica, EtOAc:petroleum ether 1:2); [α]27 D =
−48.9 (c = 1.0 in CHCl3); IR (film): νmax = 2951, 2926, 2895, 2855, 1730, 1711, 1444, 1426, 1292, 1276,
1257, 1215, 1128, 1085, 908, 837, 780, 733 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 6.1 Hz,
1 H), 7.30 (d, J = 7.4 Hz, 1 H), 7.19 (d, J = 7.4 Hz, 1 H), 5.90 (d, J = 6.1 Hz, 1 H), 5.17 (s, 1 H), 4.91 (s,
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1 H), 4.66 (d, J = 16.5 Hz, 1 H), 4.24 (td, J = 9.6, 5.5 Hz, 1 H), 3.98 (d, J = 5.6 Hz, 1 H), 3.83 (s, 3 H),
3.68 (dt, J = 16.6, 2.2 Hz, 1 H), 3.58–3.52 (m, 2 H), 2.29–2.21 (m, 2 H), 1.94 (dd, J = 14.0, 3.8 Hz, 1 H),
1.58 (s, 3 H), 1.56–1.51 (m, 1 H), 0.81 (s, 9 H), −0.03 (s, 3 H), −0.06 (s, 3 H) ppm; 13C NMR (101 MHz,
CDCl3): δ = 197.7, 172.6, 170.4, 151.6, 147.6, 146.2, 145.2, 131.7, 131.4, 130.2, 125.5, 121.5, 110.5,
62.7, 60.2, 59.5, 53.2, 52.6, 41.1, 40.3, 35.9, 26.0, 22.7, 22.0, 18.3, −5.1, −5.1 ppm; HRMS (m/z): [M +
Na]+ calcd for C29H37NO5SiNa+ 530.2333; found 530.2334.
Pentacyclic iodoindenone: To a stirred solution of pentacyclic indenone 30 (54.8 mg, 0.108 mmol) in
THF (2.0 mL) in a plastic vial was added HF•py (0.20 mL) at 0 °C. The reaction mixture was stirred at
that temperature for 10 min before it was poured to a saturated aq. NaHCO3 solution (20 mL). After
extraction with CH2Cl2 (4 × 10 mL), the combined organic phases were washed with brine (10 mL),
dried over anhydrous Na2SO4, and filtered. The solvent was evaporated under vacuum, and the residue
so obtained was purified by flash column chromatography with EtOAc/petroleum ether (1:1 → 4:1) to
give the corresponding primary alcohol as a pale yellow oil. The alcohol was dissolved in CH2Cl2 (2.0
mL). To this solution were sequentially added imidazole (36.8 mg, 0.540 mmol), PPh3 (142 mg, 0.540
mmol), and I2 (82.2 mg, 0.324 mmol) at 22 °C. The resulting mixture was stirred at that temperature for
10 min before it was quenched with saturated aq. NaHSO3 solution (5 mL) and extracted with CH2Cl2 (3
× 10 mL). The combined organic phases were washed with brine (5 mL) and dried over anhydrous
Na2SO4. After filtration and evaporation of the solvent under vacuum, the residue was subjected to flash
column chromatography using EtOAc/petroleum ether (1:20) followed by Et2O/CH2Cl2 (1:50 → 1:10)
as eluent to give pentacyclic iodoindenone 11 (50.6 mg, 0.101 mmol, 93% over 2 steps) as a pale yellow
solid. 11: Rf = 0.38 (silica, EtOAc:petroleum ether 1:1); [α]27 D = −21.1 (c = 1.0 in CHCl3); IR (film): νmax
= 2977, 2947, 2896, 1728, 1705, 1442, 1423, 1274, 1243, 1221, 1190, 1167, 1146, 880, 830, 782, 732
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cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 6.2 Hz, 1 H), 7.32 (d, J = 7.4 Hz, 1 H), 7.21 (d, J =
7.4 Hz, 1 H), 5.98 (d, J = 6.2 Hz, 1 H), 5.18 (s, 1 H), 4.93 (s, 1 H), 4.64 (d, J = 16.4 Hz, 1 H), 4.00 (d, J
= 5.6 Hz, 1 H), 3.86 (s, 3 H), 3.78 (ddd, J = 12.0, 9.0, 4.6 Hz, 1 H), 3.69 (dt, J = 16.5, 2.3 Hz, 1 H), 3.60
(s, 1 H), 3.02 (ddd, J = 12.9, 9.0, 4.1 Hz, 1 H), 2.67 (td, J = 12.5, 4.2 Hz, 1 H), 2.25 (ddd, J = 14.0, 5.7,
1.9 Hz, 1 H), 1.94–1.85 (m, 2 H), 1.55 (s, 3 H) ppm; 13C NMR (101 MHz, CDCl3): δ = 197.4, 172.1,
169.7, 151.0, 147.7, 146.0, 144.9, 131.6, 131.0, 130.4, 126.0, 121.8, 110.8, 65.6, 59.5, 53.2, 52.9, 40.9,
40.4, 38.1, 22.7, 22.1, 0.2 ppm; HRMS (m/z): [M + H]+ calcd for C23H23INO4+ 504.0666; found
504.0668.
Hexacyclic ketone 30: To a stirred solution of pentacyclic iodoindenone 11 (44.8 mg, 0.0890 mmol) in
CH2Cl2 (0.50 mL) and toluene (1.50 mL) were sequentially added AIBN (43.8 mg, 0.267 mmol) and
(TMS)3SiH (111 mg, 138 μL 0.445 mmol) at 22 °C. The resulting mixture was bubbled with argon for
15 min and then stirred at 75 °C for 15 min. After cooling to 22 °C, the solvent was removed under
vacuum. The residue so obtained was purified by flash column chromatography with EtOAc/petroleum
ether (1:2 → 2:1) to give hexacyclic ketone 31 (32.9 mg, 0.0872 mmol, 98%) as a white solid. 31: Rf =
0.46 (silica, EtOAc:petroleum ether 2:1); [α]26 D = −96.7 (c = 1.0 in CHCl3); IR (film): νmax = 2948, 1729,
1707, 1586, 1438, 1414, 1287, 1266, 1243, 1211, 1191, 1155, 1044, 1025, 900, 870, 837, 733, 701, 644
cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.55 (d, J = 7.9 Hz, 1 H), 7.27 (d, J = 8.1 Hz, 1 H), 5.12 (s, 1 H),
4.86 (s, 1 H), 4.57 (d, J = 16.5 Hz, 1 H), 4.23 (d, J = 5.4 Hz, 1 H), 3.79–3.76 (m, 5 H), 3.71 (s, 1 H),
3.06 (dd, J = 18.8, 7.8 Hz, 1 H), 2.90 (dt, J = 13.7, 11.2 Hz, 1 H), 2.34 (dd, J = 18.9, 4.5 Hz, 1 H), 2.30–
2.23 (m, 2 H), 2.08 (dd, J = 14.1, 3.6 Hz, 1 H), 1.73 (dd, J = 13.0, 4.4 Hz, 1 H), 1.60 (s, 3 H), 1.33–1.25
(m, 1 H) ppm; 13C NMR (101 MHz, CDCl3): δ = 205.7, 173.7, 171.4, 157.3, 147.1, 144.9, 137.0, 134.1,
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130.4, 122.8, 110.7, 60.0, 58.0, 52.6, 50.6, 48.0, 40.8, 40.6, 36.2, 28.9, 26.0, 22.1, 18.3 ppm; HRMS
(m/z): [M + H]+ calcd for C23H24NO4+ 378.1700; found 378.1695.
Hexacyclic ketolactam 10: To a stirred solution of β-ketoester 31 (24.3 mg, 0.0644 mmol) in CH2Cl2
(2.5 mL) was added Crabtree′s catalyst (10.4 mg, 0.0129 mmol) at 22 °C. The resulting mixture was
stirred under H2 at that temperature for 4 h. After removal of the solvent under vacuum, the residue was
purified by flash column chromatography with EtOAc/petroleum ether (1:2 → 2:1) to give the
hydrogenated compound. The compound so obtained was dissolved in DMSO (2.0 mL). To this solution
was added LiCl•H2O (77.9 mg, 1.29 mmol) at 22 °C. The resulting mixture was allowed to heat to
160 °C and stir at that temperature for 6 h before it was cooled to 22 °C and quenched with saturated aq.
NaHCO3 solution (5 mL). After extraction with CH2Cl2 (3 × 10 mL), the combined organic phases were
washed with brine (10 mL), dried over anhydrous Na2SO4, and filtered. The solvent was evaporated
under vacuum, and the residue so obtained was subjected to flash column chromatography using
EtOAc/petroleum ether (1:1 → 3:1) as eluent to give hexacyclic ketolactam 10 (17.7 mg, 0.0551 mmol,
86%) as a white powder. 10: Rf = 0.23 (silica, EtOAc:petroleum ether 3:1); [α]27 D = −178.4 (c = 0.44 in
CHCl3); m.p. 165–167 °C (EtOAc/n-hexane 1:1); IR (film): νmax = 3491, 2923, 2868, 1705, 1588, 1449,
1419, 1381, 1322, 1305, 1289, 1196, 1106, 1060, 920, 838, 730, 670, 645 cm−1; 1H NMR (400 MHz,
CDCl3): δ = 7.52 (d, J = 7.8 Hz, 1 H), 7.08 (d, J = 7.8 Hz, 1 H), 4.02 (dd, J = 13.8, 8.4 Hz, 1 H), 3.67 (d,
J = 5.3 Hz, 1 H), 3.52 (qd, J = 7.1, 3.0 Hz, 1 H), 2.99 (dd, J = 19.3, 7.8 Hz, 1 H), 2.78 (s, 1 H), 2.65–
2.63 (m, 1 H), 2.43 (dd, J = 13.7, 10.1 Hz, 1 H), 2.28–1.92 (m, 7 H), 1.56–1.46 (m, 4 H), 1.09 (d, J =
6.9 Hz, 3 H) ppm; 13C NMR (101 MHz, CDCl3): δ = 205.8, 174.8, 160.9, 151.0, 135.7, 134.9, 129.6,
122.7, 60.8, 51.4, 50.7, 45.2, 40.7, 40.4, 39.0, 37.5, 31.2, 24.6, 20.4, 20.0, 18.7 ppm; HRMS (m/z): [M +
H]+ calcd for C21H24NO2+ 322.1802; found 322.1800. CCDC 917084 contains the supplementary
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crystallographic data for 10 and is available free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Daphenylline: To a stirred solution of hexacyclic ketolactam 10 (14.0 mg, 0.0436 mmol) in AcOH
(0.20 mL) and MeOH (2.0 mL) was added 10% Pd/C (23.2 mg, 0.0218 mmol) at 22 °C. The resulting
mixture was stirred under H2 at that temperature for 10 h and then purged with bubbling argon for 10
min. The solvent was evaporated under vacuum. The residue so obtained was directly subjected to flash
column chromatography using EtOAc/petroleum ether (1:3 → 1:1) as eluent to give the corresponding
deoxygenated compound. The compound so obtained was dissolved in Et2O (2.0 mL). To this solution
was added LiAH4 (16.5 mg, 0.436 mmol) at 22 °C. The resulting mixture was stirred in a sealed tube at
40 °C for 3 d before it was quenched with Na2SO4•10H2O (200 mg). The resulting mixture was filtrated,
and the filter cake was washed with Et2O (3 × 10 mL). The combined filtrate was concentrated under
vacuum to give daphenylline (8, 8.4 mg, 0.0286 mmol, 66%) as a colorless oil. Daphenylline (8): Rf =
0.28 (silica, MeOH:CH2Cl2 1:20); [α]29 D = −37.4 (c = 0.2 in CHCl3); IR (film): νmax = 2923, 2863, 1465,
1453, 1380, 1168, 1107, 1096, 1062, 1047, 842, 810, 790, 692 cm−1; 1H NMR (400 MHz, CDCl3): δ =
7.03 (d, J = 7.5 Hz, 1 H), 6.87 (d, J = 7.5 Hz, 1 H), 3.50 (qd, J = 8.7, 4.0 Hz, 1 H), 3.18 (dd, J = 10.6,
8.4 Hz, 1 H), 3.05 (d, J = 3.4 Hz, 1 H), 2.82 (ddd, J = 15.2, 8.5, 2.7 Hz, 1 H), 2.77–2.69 (m, 1 H), 2.63
(d, J = 2.3 Hz, 1 H), 2.52 (dd, J = 12.5, 5.2 Hz, 1 H), 2.41 (dd, J = 12.5, 5.4 Hz, 1 H), 2.33 (ddd, J =
12.1, 7.5, 2.9 Hz, 1 H), 2.29–2.22 (m, 2 H), 2.21–2.14 (m, 1 H), 2.09–2.00 (m, 1 H), 1.84–1.77 (m, 3 H),
1.69–1.61 (m, 1 H), 1.60–1.53 (m, 1 H), 1.38 (s, 3 H), 1.35–1.31 (m, 1 H), 1.17 (d, J = 7.1 Hz, 3 H) ppm;
13C NMR (101 MHz, CDCl3): δ = 144.0, 143.2, 140.5, 136.9, 127.0, 122.9, 66.4, 60.7, 51.5, 51.2, 46.2,
43.2, 39.0, 36.3, 34.6, 31.4, 30.0, 29.7, 26.6, 19.9, 18.9 ppm; HRMS (m/z): [M + H]+ calcd for C21H28N+
294.2216; found 294.2208.
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Daphenylline (silica gel): daphenylline (silica gel) was obtained by passing freshly prepared
daphenylline (see the above procedure) through a plug of silica gel column using MeOH/CHCl3 (1:50
→ 1:10) as eluent. Daphenylline (silica gel): IR (film): νmax = 2923, 2868, 1704, 1588, 1449, 1419, 1380,
1322, 1304, 1289, 1196, 1106, 1060, 920, 838, 730, 669, 644 cm−1; 1H NMR (400 MHz, CDCl3): δ =
7.11 (d, J = 7.6 Hz, 1 H), 6.92 (d, J = 7.6 Hz, 1 H), 3.78–3.71 (m, 2 H), 3.52–3.45 (m, 1 H), 2.98 (dd, J
= 13.2, 6.3 Hz, 1 H), 2.87–2.71 (m, 4 H), 2.53–2.34 (m, 4 H), 2.14–2.05 (m, 1 H), 1.98 (dd, J = 14.9, 1.9
Hz, 1 H), 1.94–1.87 (m, 2 H), 1.70–1.58 (m, 2 H), 1.50 (s, 3 H), 1.40–1.36 (m, 1 H), 1.33 (d, J = 7.1 Hz,
3 H) ppm; 13C NMR (101 MHz, CDCl3): δ = 145.1, 144.3, 138.0, 132.9, 127.4, 124.5, 65.6, 58.2, 50.2,
47.4, 45.9, 43.4, 36.9, 36.3, 33.2, 31.4, 28.7, 27.8, 26.2, 18.6, 18.2 ppm. The spectral and physical
properties of daphenylline (silica gel) are identical as those of the authentic sample provided by
Hao (see Part V).
Daphenylline (TFA): To a solution of daphenylline (8.4 mg, 0.0286 μmol) in CDCl3 (0.5 mL) in NMR
tube was added TFA (57.2 μL, 0.50 M in CDCl3, 0.0286 μmol) in portions. The NMR spectra were
directly measured, while other spectral and physical properties were measured by using a sample after
removing the CDCl3 under vacuum. Daphenylline (TFA salt): [α]28 D = −57.7 (c = 0.15 in CHCl3); IR
(film): νmax = 2924, 2853, 1673, 1456, 1415, 1197, 1129, 831, 798, 720 cm−1; 1H NMR (400 MHz,
CDCl3): δ = 7.10 (d, J = 7.6 Hz, 1 H), 6.91 (d, J = 7.6 Hz, 1 H), 3.77 (d, J = 3.7 Hz, 1 H), 3.73–3.69 (m,
1 H), 3.49 (td, J = 10.7, 3.6 Hz, 1 H), 3.02 (dd, J = 13.1, 6.2 Hz, 1 H), 2.86–2.69 (m, 4 H), 2.53–2.33 (m,
4 H), 2.14–2.05 (m, 1 H), 1.97 (dd, J = 14.9, 1.6 Hz, 1 H), 1.93–1.85 (m, 2 H), 1.70–1.58 (m, 2 H), 1.49
(s, 3 H), 1.38–1.30 (m, 1 H), 1.25 (d, J = 7.1 Hz, 3 H) ppm; 13C NMR (101 MHz, CDCl3): δ 144.9,
144.2, 138.2, 133.3, 127.3, 124.3, 65.5, 58.3, 50.2, 47.7, 45.9, 43.4, 37.1, 36.3, 33.3, 31.4, 28.8, 28.0,
26.3, 18.4, 18.3 ppm. The 1H NMR spectrum of daphenylline (TFA) is extremely close to that of the
authentic sample provided by Hao (see Part V), while their 13C NMR spectra are identical. The
gradual changes of the 1H-NMR spectrum during the above titration were also recorded in Part V.
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II References
1. Snyder, S. A., Wespe, D. A. & von Hof, J. M. A concise, stereocontrolled total synthesis of
rippertenol. J. Am. Chem. Soc. 133, 8850–8853 (2011).
2. Piers, E. & Oballa, R. M. Concise total syntheses of the sesquiterpenoids (–)-homalomenol A and
(–)-homalomenol B. J. Org. Chem. 61, 8439–8447 (1996).
3. Uyanik, M., Ishihara, K. & Yamamoto, H. Catalytic diastereoselective polycyclization of
homo(polyprenyl)arene analogues bearing terminal siloxyvinyl groups. Org. Lett. 8, 5649–5652
(2006).
4. Nicolaou, K. C. et al. Total synthesis of the CP-molecules (CP-263,114 and CP-225,917,
phomoidrides B and A). 1. Racemic and asymmetric synthesis of bicyclo[4.3.1] key building
blocks. J. Am. Chem. Soc. 124, 2183–2189 (2002).
5. Ishihara, H., Inomata, K. & Mukaiyama, T. A convenient method for the synthesis of 2-(1-
alkenyl)-2-cyclopentenones. Chem. Lett. 4, 531–534 (1975).
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III HPLC Traces for Measuring Enantiomeric Excess
1. Racemic and optically active 16 were analyzed with HPLC (CHIRALPAK AD-H column, i-
PrOH:hexanes 10:90, 0.7 mL/min) to determine retention time and enantiomeric excesses. For (–)-
16, ee = 98%.
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2. Racemic and optically active 15 were analyzed with HPLC (Phenomenex Lux Cellulose-1 column,
i-PrOH:hexanes 40:60, 0.7 mL/min) to determine retention time and enantiomeric excesses. For
(+)-15, ee = 97%.
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3. Racemic and optically active 25 were analyzed with HPLC (Phenomenex Lux Cellulose-4 column,
i-PrOH:hexanes 40:60, 0.5 mL/min) to determine retention time and enantiomeric excesses. For (–
)-25, ee = 96%. Because of its rigid skeleton containing multiple stereogeneric centers, this
enantiopurity cannot diminish throughout the rest steps toward (–)-daphenylline.
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IV 1H and 13C NMR Spectra of Compounds
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V Comparison of Spectra of Natural and Synthetic Daphenylline
natural daphenylline 1H NMR spectrum (600 MHz, CDCl3)
synthetic daphenylline (passed through silica gel)
1H NMR spectrum (400 MHz, CDCl3)
synthetic daphenylline (protonated by 1 eq of TFA)
1H NMR spectrum (400 MHz, CDCl3)
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natural daphenylline 13C NMR spectrum (151 MHz, CDCl3)
synthetic daphenylline (passed through silica gel)
13C NMR spectrum (101 MHz, CDCl3)
synthetic daphenylline (protonated by 1 eq of TFA)
13C NMR spectrum (101 MHz, CDCl3)
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Figure S1. Gradual changes of the 1H NMR spectrum during titration of daphenylline with TFA.
daphenylline
with 50% of TFA
with 100% of TFA
with 140% of TFA
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Supplementary Table S1. Comparison of 1H NMR (CDCl3) spectroscopic data of natural and synthetic
daphenylline.
Natural δ 1H [ppm, mult, J (Hz)]
600 MHz
Synthetic (silica gel)a δ 1H [ppm, mult, J (Hz)]
400 MHz
Err (Natural–Synthetic)
Δδ (ppm)
7.11 1 H, d, 7.6 7.11 1 H, d, 7.6 0 6.92 1 H, d, 7.6 6.92 1 H, d, 7.6 0
3.81–3.77 2 H, m 3.78–3.71 2 H, m – 3.51–3.47 1 H, m 3.52–3.45 1 H, m −
3.01 1 H, dd, 13.2, 6.2 2.98 1 H, dd, 13.2, 6.3 0.03 2.85–2.73 4 H, m 2.87–2.71 4 H, m − 2.53–2.35 4 H, m 2.53–2.34 4 H, m − 2.12–2.06 1 H, m 2.14–2.05 1 H, m −
1.99 1 H, dd, 14.9, 1.6 1.98 1 H, dd, 14.9, 1.9 0.01 1.93–1.88 2 H, m 1.94–1.87 2 H, m − 1.67–1.60 2 H, m 1.70–1.58 2 H, m −
1.50 3 H, s 1.50 3 H, s 0 1.38–1.34 1 H, m 1.40–1.36 1 H, m −
1.32 3 H, d, 7.2 1.33 3 H, d, 7.1 −0.01 a The synthetic sample was passed through silica gel. See Part I.
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Supplementary Table S2. Comparison of 1H NMR (CDCl3) spectroscopic data of natural and synthetic
daphenylline (continued).
Natural δ 1H [ppm, mult, J (Hz)]
600 MHz
Synthetic (TFA)a δ 1H [ppm, mult, J (Hz)]
400 MHz
Err (Natural–Synthetic)
Δδ (ppm)
7.11 1 H, d, 7.6 7.10 1 H, d, 7.6 0.01 6.92 1 H, d, 7.6 6.91 1 H, d, 7.6 0.01
3.81–3.77 2 H, m 3.77 1 H, d, 3.7 −
3.73–3.69 1 H, m − 3.51–3.47 1 H, m 3.49 1 H, td, 10.7, 3.6 −
3.01 1 H, dd, 13.2, 6.2 3.02 1 H, dd, 13.1, 6.2 −0.01 2.85–2.73 4 H, m 2.86–2.69 4 H, m − 2.53–2.35 4 H, m 2.53–2.33 4 H, m − 2.12–2.06 1 H, m 2.14–2.05 1 H, m −
1.99 1 H, dd, 14.9, 1.6 1.97 1 H, dd, 14.9, 1.6 0.02 1.93–1.88 2 H, m 1.93–1.85 2 H, m − 1.67–1.60 2 H, m 1.70–1.58 2 H, m −
1.50 3 H, s 1.49 3 H, s 0.01 1.38–1.34 1 H, m 1.38–1.30 1 H, m −
1.32 3 H, d, 7.2 1.25 3 H, d, 7.1 0.07 a The synthetic sample was titrated by TFA. See Part I.
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Supplementary Table S3. Comparison of 13C NMR (CDCl3) spectroscopic data of natural and synthetic daphenylline.
Natural δ 13C [ppm] 151 MHz
Synthetic (TFA) δ 13C [ppm] 101 MHz
Err (Natural–Synthetic)
Δδ (ppm)
Synthetic (silica) δ 13C [ppm] 101 MHz
Err (Natural–Synthetic)
Δδ (ppm)
145.1 144.9 0.2 145.1 0
144.2 144.2 0 144.3 −0.1
137.9 138.2 −0.3 138.0 −0.1
133.0 133.3 −0.3 132.9 0.1
127.4 127.3 0.1 127.4 0
124.5 124.3 0.2 124.5 0
65.8 65.5 0.3 65.6 0.2
58.3 58.3 0 58.2 0.1
50.4 50.2 0.2 50.2 0.2
47.5 47.7 −0.2 47.4 0.1
45.9 45.9 0 45.9 0
43.4 43.4 0 43.4 0
37.0 37.1 −0.1 36.9 0.1
36.3 36.3 0 36.3 0
33.2 33.3 −0.1 33.2 0
31.4 31.4 0 31.4 0
28.7 28.8 −0.1 28.7 0
27.9 28.0 −0.1 27.8 0.1
26.3 26.3 0 26.2 0.1
18.5 18.4 0.1 18.6 −0.1
18.2 18.3 −0.1 18.2 0
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VI Crystallographic Data
ORTEP of desilylated 9
Crystal data
C16H23NO6 F(000) = 348
Mr = 325.35 Dx = 1.381 Mg m−3
Monoclinic, P21 Mo Kα radiation, λ = 0.71073 Å
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a = 9.1764 (16) Å Cell parameters from 3670 reflections
b = 6.8574 (12) Å θ = 5.0–56.6°
c = 12.753 (2) Å µ = 0.11 mm−1
β = 102.919 (3)° T = 293 K
V = 782.2 (2) Å3 Prismatic, colorless
Z = 2 0.26 × 0.21 × 0.12 mm
Data collection
CCD area detector
diffractometer 2972 independent reflections
Radiation source: fine-focus sealed tube 2898 reflections with I > 2σ(I)
graphite Rint = 0.021
phi and ω scans θmax = 26.0°, θmin = 1.6°
Absorption correction: empirical (using intensity
measurements)
SADABS
h = −11→7
Tmin = 0.706, Tmax = 1.000 k = −8→8
4709 measured reflections l = −14→15
Refinement
Refinement on F2 Hydrogen site location: inferred from
neighbouring sites
Least-squares matrix: full H atoms treated by a mixture of independent and
constrained refinement
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R[F2 > 2σ(F2)] = 0.040 w = 1/[σ2(Fo
2) + (0.0771P)2 + 0.0861P]
where P = (Fo2 + 2Fc
2)/3
wR(F2) = 0.110 (Δ/σ)max < 0.001
S = 1.03 Δρmax = 0.21 e Å−3
2972 reflections Δρmin = −0.20 e Å−3
220 parameters Extinction correction: SHELXL,
Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraint Extinction coefficient: 0.048 (9)
Primary atom site location: structure-invariant
direct methods
Absolute structure: Flack H D (1983), Acta Cryst.
A39, 876-881
Secondary atom site location: difference Fourier
map Flack parameter: −0.5 (10)
Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using
the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in
distances, angles and torsion angles; correlations between esds in cell parameters are only used when
they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for
estimating esds 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 > 2sigma(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 (Å2)
x y z Uiso*/Ueq
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N1 0.46707 (15) 0.0341 (2) 0.13143 (10) 0.0363 (3)
O1 0.28873 (15) −0.2037 (2) 0.10407 (12) 0.0524 (4)
O2 0.6350 (2) −0.2501 (3) 0.38102 (14) 0.0640 (4)
O3 0.05127 (18) 0.2284 (3) 0.21467 (13) 0.0720 (5)
O4 0.18359 (14) 0.2726 (2) 0.09182 (10) 0.0463 (3)
O5 0.1479 (2) −0.1817 (2) 0.46289 (15) 0.0698 (5)
H5 0.1043 −0.1471 0.5093 0.105*
O6 0.9815 (3) 0.9616 (4) 0.5953 (2) 0.0963 (8)
C1 0.34413 (16) −0.0550 (3) 0.14831 (12) 0.0357 (4)
C2 0.28629 (16) 0.0570 (2) 0.23505 (12) 0.0330 (3)
C3 0.42780 (18) 0.1819 (3) 0.29067 (12) 0.0351 (3)
C4 0.51378 (18) 0.2049 (3) 0.19929 (12) 0.0361 (4)
H4 0.4838 0.3253 0.1587 0.043*
C5 0.52926 (19) 0.0664 (3) 0.38334 (13) 0.0429 (4)
H5A 0.5921 0.1582 0.4309 0.051*
H5B 0.4663 0.0019 0.4245 0.051*
C6 0.62798 (19) −0.0843 (3) 0.34856 (14) 0.0438 (4)
C7 0.72423 (18) −0.0132 (3) 0.27170 (15) 0.0467 (4)
H7 0.8299 −0.0195 0.3087 0.056*
C8 0.68361 (19) 0.1978 (3) 0.24012 (15) 0.0455 (4)
H8A 0.7329 0.2395 0.1842 0.055*
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H8B 0.7145 0.2830 0.3018 0.055*
C9 0.57578 (19) −0.0667 (3) 0.08263 (14) 0.0439 (4)
H9A 0.6163 0.0223 0.0373 0.053*
H9B 0.5283 −0.1744 0.0386 0.053*
C10 0.6991 (2) −0.1414 (3) 0.17282 (17) 0.0471 (4)
C11 0.7705 (3) −0.3057 (4) 0.1653 (2) 0.0699 (7)
H11A 0.7456 −0.3801 0.1029 0.084*
H11B 0.8458 −0.3473 0.2225 0.084*
C12 0.15983 (18) 0.1933 (3) 0.18095 (13) 0.0384 (4)
C13 0.0739 (2) 0.4149 (3) 0.03965 (18) 0.0522 (5)
H13A 0.0798 0.5287 0.0843 0.078*
H13B −0.0244 0.3596 0.0288 0.078*
H13C 0.0939 0.4506 −0.0286 0.078*
C14 0.22717 (19) −0.0934 (3) 0.30546 (14) 0.0403 (4)
H14A 0.1448 −0.1629 0.2598 0.048*
H14B 0.3059 −0.1877 0.3309 0.048*
C15 0.1740 (2) −0.0178 (3) 0.40229 (16) 0.0463 (4)
H15A 0.2494 0.0659 0.4455 0.056*
H15B 0.0828 0.0571 0.3792 0.056*
C16 0.3893 (2) 0.3802 (3) 0.33188 (16) 0.0488 (5)
H16A 0.4797 0.4520 0.3591 0.073*
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H16B 0.3370 0.3616 0.3884 0.073*
H16C 0.3271 0.4516 0.2741 0.073*
H6A 0.975 (4) 0.911 (6) 0.652 (3) 0.096 (11)*
H6B 0.940 (4) 1.078 (8) 0.576 (3) 0.110 (14)*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
N1 0.0346 (6) 0.0415 (8) 0.0328 (6) 0.0009 (6) 0.0077 (5) −0.0035 (6)
O1 0.0458 (7) 0.0531 (8) 0.0579 (8) −0.0090 (6) 0.0108 (6) −0.0248 (7)
O2 0.0728 (10) 0.0575 (10) 0.0610 (8) 0.0025 (8) 0.0136 (7) 0.0216 (7)
O3 0.0542 (9) 0.1026 (14) 0.0669 (9) 0.0328 (9) 0.0298 (7) 0.0275 (9)
O4 0.0404 (6) 0.0535 (8) 0.0456 (6) 0.0120 (6) 0.0111 (5) 0.0092 (6)
O5 0.1002 (13) 0.0538 (10) 0.0696 (10) 0.0017 (9) 0.0493 (9) 0.0086 (8)
O6 0.134 (2) 0.0799 (15) 0.0988 (15) 0.0216 (14) 0.0767 (15) 0.0193 (13)
C1 0.0316 (7) 0.0402 (9) 0.0332 (7) 0.0034 (6) 0.0027 (5) −0.0062 (7)
C2 0.0318 (7) 0.0335 (8) 0.0335 (7) −0.0020 (6) 0.0068 (6) −0.0058 (6)
C3 0.0369 (8) 0.0365 (8) 0.0305 (7) −0.0064 (6) 0.0044 (6) −0.0036 (7)
C4 0.0382 (8) 0.0355 (8) 0.0342 (7) −0.0040 (6) 0.0072 (6) 0.0008 (7)
C5 0.0408 (8) 0.0555 (11) 0.0296 (7) −0.0103 (7) 0.0024 (6) 0.0010 (7)
C6 0.0384 (8) 0.0507 (10) 0.0362 (8) −0.0062 (8) −0.0049 (6) 0.0090 (8)
C7 0.0304 (7) 0.0565 (11) 0.0501 (9) −0.0029 (7) 0.0023 (6) 0.0091 (8)
C8 0.0364 (9) 0.0499 (10) 0.0493 (9) −0.0119 (7) 0.0076 (7) 0.0066 (8)
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C9 0.0432 (8) 0.0508 (11) 0.0410 (8) 0.0057 (8) 0.0167 (7) −0.0001 (8)
C10 0.0364 (8) 0.0519 (11) 0.0569 (10) 0.0025 (7) 0.0190 (8) 0.0103 (8)
C11 0.0695 (15) 0.0671 (15) 0.0767 (15) 0.0225 (12) 0.0235 (12) 0.0149 (13)
C12 0.0358 (8) 0.0417 (9) 0.0370 (7) 0.0009 (7) 0.0068 (6) −0.0045 (7)
C13 0.0450 (9) 0.0492 (11) 0.0591 (11) 0.0119 (9) 0.0047 (8) 0.0110 (10)
C14 0.0411 (8) 0.0367 (9) 0.0450 (9) −0.0052 (7) 0.0137 (7) −0.0025 (7)
C15 0.0495 (9) 0.0441 (10) 0.0504 (9) −0.0036 (8) 0.0221 (7) −0.0010 (8)
C16 0.0593 (11) 0.0433 (11) 0.0442 (9) −0.0085 (8) 0.0127 (8) −0.0146 (8)
Geometric parameters (Å, º)
N1—C1 1.342 (2) C6—C7 1.538 (3)
N1—C9 1.462 (2) C7—C10 1.512 (3)
N1—C4 1.463 (2) C7—C8 1.526 (3)
O1—C1 1.220 (2) C7—H7 0.9800
O2—C6 1.207 (3) C8—H8A 0.9700
O3—C12 1.195 (2) C8—H8B 0.9700
O4—C12 1.321 (2) C9—C10 1.511 (3)
O4—C13 1.452 (2) C9—H9A 0.9700
O5—C15 1.415 (2) C9—H9B 0.9700
O5—H5 0.8200 C10—C11 1.318 (3)
O6—H6A 0.82 (4) C11—H11A 0.9300
O6—H6B 0.89 (5) C11—H11B 0.9300
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C1—C2 1.536 (2) C13—H13A 0.9600
C2—C12 1.529 (2) C13—H13B 0.9600
C2—C14 1.543 (2) C13—H13C 0.9600
C2—C3 1.585 (2) C14—C15 1.517 (2)
C3—C16 1.527 (3) C14—H14A 0.9700
C3—C5 1.549 (2) C14—H14B 0.9700
C3—C4 1.555 (2) C15—H15A 0.9700
C4—C8 1.529 (2) C15—H15B 0.9700
C4—H4 0.9800 C16—H16A 0.9600
C5—C6 1.505 (3) C16—H16B 0.9600
C5—H5A 0.9700 C16—H16C 0.9600
C5—H5B 0.9700
C1—N1—C9 122.08 (15) C4—C8—H8A 110.3
C1—N1—C4 114.55 (13) C7—C8—H8B 110.3
C9—N1—C4 119.53 (14) C4—C8—H8B 110.3
C12—O4—C13 116.10 (14) H8A—C8—H8B 108.6
C15—O5—H5 109.5 N1—C9—C10 107.59 (14)
H6A—O6—H6B 121 (4) N1—C9—H9A 110.2
O1—C1—N1 125.79 (15) C10—C9—H9A 110.2
O1—C1—C2 125.16 (15) N1—C9—H9B 110.2
N1—C1—C2 109.03 (14) C10—C9—H9B 110.2
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C12—C2—C1 109.29 (12) H9A—C9—H9B 108.5
C12—C2—C14 109.93 (13) C11—C10—C9 122.3 (2)
C1—C2—C14 107.92 (14) C11—C10—C7 124.9 (2)
C12—C2—C3 109.57 (14) C9—C10—C7 112.73 (16)
C1—C2—C3 102.25 (12) C10—C11—H11A 120.0
C14—C2—C3 117.40 (13) C10—C11—H11B 120.0
C16—C3—C5 109.78 (14) H11A—C11—H11B 120.0
C16—C3—C4 111.27 (15) O3—C12—O4 122.54 (17)
C5—C3—C4 107.74 (13) O3—C12—C2 124.80 (16)
C16—C3—C2 113.95 (14) O4—C12—C2 112.65 (13)
C5—C3—C2 110.96 (14) O4—C13—H13A 109.5
C4—C3—C2 102.82 (12) O4—C13—H13B 109.5
N1—C4—C8 108.49 (14) H13A—C13—H13B 109.5
N1—C4—C3 103.38 (12) O4—C13—H13C 109.5
C8—C4—C3 113.00 (13) H13A—C13—H13C 109.5
N1—C4—H4 110.6 H13B—C13—H13C 109.5
C8—C4—H4 110.6 C15—C14—C2 117.63 (15)
C3—C4—H4 110.6 C15—C14—H14A 107.9
C6—C5—C3 115.15 (14) C2—C14—H14A 107.9
C6—C5—H5A 108.5 C15—C14—H14B 107.9
C3—C5—H5A 108.5 C2—C14—H14B 107.9
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C6—C5—H5B 108.5 H14A—C14—H14B 107.2
C3—C5—H5B 108.5 O5—C15—C14 107.31 (16)
H5A—C5—H5B 107.5 O5—C15—H15A 110.3
O2—C6—C5 122.35 (18) C14—C15—H15A 110.3
O2—C6—C7 121.5 (2) O5—C15—H15B 110.3
C5—C6—C7 116.08 (17) C14—C15—H15B 110.3
C10—C7—C8 110.40 (15) H15A—C15—H15B 108.5
C10—C7—C6 110.17 (16) C3—C16—H16A 109.5
C8—C7—C6 109.12 (17) C3—C16—H16B 109.5
C10—C7—H7 109.0 H16A—C16—H16B 109.5
C8—C7—H7 109.0 C3—C16—H16C 109.5
C6—C7—H7 109.0 H16A—C16—H16C 109.5
C7—C8—C4 106.89 (14) H16B—C16—H16C 109.5
C7—C8—H8A 110.3
C9—N1—C1—O1 −19.2 (2) C2—C3—C5—C6 78.54 (18)
C4—N1—C1—O1 −177.03 (16) C3—C5—C6—O2 −130.13 (19)
C9—N1—C1—C2 159.15 (14) C3—C5—C6—C7 51.8 (2)
C4—N1—C1—C2 1.35 (19) O2—C6—C7—C10 55.3 (2)
O1—C1—C2—C12 −83.7 (2) C5—C6—C7—C10 −126.69 (16)
N1—C1—C2—C12 97.86 (15) O2—C6—C7—C8 176.62 (17)
O1—C1—C2—C14 35.8 (2) C5—C6—C7—C8 −5.33 (19)
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N1—C1—C2—C14 −142.61 (13) C10—C7—C8—C4 69.06 (19)
O1—C1—C2—C3 160.21 (16) C6—C7—C8—C4 −52.16 (18)
N1—C1—C2—C3 −18.19 (17) N1—C4—C8—C7 −42.06 (18)
C12—C2—C3—C16 31.37 (18) C3—C4—C8—C7 71.95 (19)
C1—C2—C3—C16 147.22 (14) C1—N1—C9—C10 −95.41 (19)
C14—C2—C3—C16 −94.91 (18) C4—N1—C9—C10 61.3 (2)
C12—C2—C3—C5 155.89 (14) N1—C9—C10—C11 146.4 (2)
C1—C2—C3—C5 −88.26 (15) N1—C9—C10—C7 −30.8 (2)
C14—C2—C3—C5 29.60 (19) C8—C7—C10—C11 153.6 (2)
C12—C2—C3—C4 −89.16 (15) C6—C7—C10—C11 −85.8 (2)
C1—C2—C3—C4 26.69 (16) C8—C7—C10—C9 −29.2 (2)
C14—C2—C3—C4 144.55 (15) C6—C7—C10—C9 91.35 (19)
C1—N1—C4—C8 136.72 (15) C13—O4—C12—O3 3.5 (3)
C9—N1—C4—C8 −21.68 (19) C13—O4—C12—C2 −175.69 (15)
C1—N1—C4—C3 16.52 (18) C1—C2—C12—O3 143.4 (2)
C9—N1—C4—C3 −141.88 (15) C14—C2—C12—O3 25.1 (3)
C16—C3—C4—N1 −148.51 (14) C3—C2—C12—O3 −105.3 (2)
C5—C3—C4—N1 91.10 (15) C1—C2—C12—O4 −37.50 (19)
C2—C3—C4—N1 −26.15 (16) C14—C2—C12—O4 −155.78 (15)
C16—C3—C4—C8 94.42 (18) C3—C2—C12—O4 73.79 (17)
C5—C3—C4—C8 −26.0 (2) C12—C2—C14—C15 −65.19 (19)
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C2—C3—C4—C8 −143.22 (15) C1—C2—C14—C15 175.69 (15)
C16—C3—C5—C6 −154.62 (15) C3—C2—C14—C15 60.9 (2)
C4—C3—C5—C6 −33.30 (19) C2—C14—C15—O5 −171.01 (16)
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D· · ·A D—H···A
O5—H5···O6i 0.82 1.89 2.702 (3) 169
O6—H6A· · ·O3ii 0.82 (4) 2.17 (4) 2.974 (3) 169 (4)
O6—H6B· · ·O5iii 0.89 (5) 1.85 (6) 2.747 (3) 179 (4)
Symmetry codes: (i) x−1, y−1, z; (ii) −x+1, y+1/2, −z+1; (iii) −x+1, y+3/2, −z+1.
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ORTEP of (±)-27
Crystal data
C23H27NO7 Z = 4
Mr = 429.46 F(000) = 912
Triclinic, P1 Dx = 1.285 Mg m−3
a = 8.4778 (7) Å Mo Kα radiation, λ = 0.71073 Å
b = 16.8350 (13) Å Cell parameters from 4940 reflections
c = 17.4043 (13) Å θ = 4.4–56.2°
α = 66.474 (1)° µ = 0.10 mm−1
β = 84.743 (2)° T = 293 K
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γ = 77.078 (2)° Prismatic, colorless
V = 2219.8 (3) Å3 0.29 × 0.22 × 0.15 mm
Data collection
CCD area detector
diffractometer 8716 independent reflections
Radiation source: fine-focus sealed tube 6917 reflections with I > 2σ(I)
graphite Rint = 0.0000
phi and ω scans θmax = 26.0°, θmin = 2.2°
Absorption correction: empirical (using intensity
measurements)
SADABS
h = −10→10
Tmin = 0.418, Tmax = 1.000 k = −18→20
8716 measured reflections l = 0→21
Refinement
Refinement on F2 Primary atom site location: structure-invariant
direct methods
Least-squares matrix: full Secondary atom site location: difference Fourier
map
R[F2 > 2σ(F2)] = 0.053 Hydrogen site location: inferred from
neighbouring sites
wR(F2) = 0.153 H-atom parameters constrained
S = 1.08 w = 1/[σ2(Fo
2) + (0.0867P)2 + 0.2578P]
where P = (Fo2 + 2Fc
2)/3
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8716 reflections (Δ/σ)max = 0.010
574 parameters Δρmax = 0.32 e Å−3
0 restraints Δρmin = −0.36 e Å−3
Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using
the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in
distances, angles and torsion angles; correlations between esds in cell parameters are only used when
they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for
estimating esds 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 > 2sigma(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 (Å2)
x y z Uiso*/Ueq Occ. (<1)
O1 0.64147 (19) 0.45382 (11) 0.56678 (9) 0.0625 (4)
O2 0.77073 (18) 0.48832 (9) 0.44786 (8) 0.0514 (3)
O3 1.00048 (15) 0.52588 (8) 0.37286 (7) 0.0420 (3)
O4 0.85391 (17) 0.73217 (9) 0.05117 (8) 0.0486 (3)
O5 0.52849 (19) 0.77661 (11) 0.05814 (11) 0.0641 (4)
H5 0.6194 0.7633 0.0405 0.096*
O6 0.9183 (2) 0.91989 (11) 0.04155 (12) 0.0852 (6)
O7 0.72835 (18) 0.95369 (8) 0.12632 (10) 0.0550 (4)
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O1' 1.3364 (3) −0.12929 (12) 0.26429 (15) 0.1046 (8)
O2' 1.16242 (18) −0.03764 (8) 0.30188 (9) 0.0563 (4)
O3' 1.16442 (16) 0.07440 (8) 0.34645 (8) 0.0460 (3)
O4' 0.58834 (17) 0.30094 (10) 0.29185 (9) 0.0575 (4)
O5' 0.4664 (2) 0.22928 (19) 0.20404 (15) 0.1068 (8)
H5' 0.4878 0.2422 0.2421 0.160*
O6' 0.7222 (2) 0.42691 (10) 0.03897 (9) 0.0680 (5)
O7' 0.70594 (16) 0.47302 (8) 0.14238 (8) 0.0440 (3)
N1 1.07109 (18) 0.72343 (10) 0.12445 (9) 0.0396 (3)
N1' 0.83350 (19) 0.32815 (10) 0.30360 (9) 0.0414 (4)
C1 0.6914 (2) 0.51093 (14) 0.51005 (11) 0.0483 (5)
C2 0.6675 (3) 0.60392 (15) 0.50187 (13) 0.0572 (5)
H2A 0.6699 0.6044 0.5573 0.069*
H2B 0.5612 0.6353 0.4784 0.069*
C3 0.7937 (3) 0.65314 (14) 0.44722 (12) 0.0502 (5)
H3A 0.7678 0.7144 0.4413 0.060*
H3B 0.8998 0.6262 0.4726 0.060*
C4 0.7932 (2) 0.64821 (12) 0.36184 (11) 0.0396 (4)
H4 0.6908 0.6808 0.3325 0.048*
C5 0.8265 (2) 0.54936 (12) 0.37427 (11) 0.0411 (4)
C6 0.7827 (2) 0.54443 (12) 0.29496 (11) 0.0417 (4)
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H6 0.6928 0.5265 0.2855 0.050*
C7 0.8989 (2) 0.57087 (11) 0.24183 (11) 0.0389 (4)
H7 0.9070 0.5761 0.1864 0.047*
C8 1.0178 (2) 0.59135 (11) 0.28839 (10) 0.0376 (4)
C9 0.9407 (2) 0.67606 (11) 0.30516 (10) 0.0363 (4)
H9 1.0164 0.6745 0.3453 0.044*
C10 0.9445 (2) 0.76662 (11) 0.23199 (11) 0.0369 (4)
C11 1.1116 (2) 0.75069 (12) 0.18932 (11) 0.0412 (4)
H11 1.1514 0.8060 0.1635 0.049*
C12 1.2415 (2) 0.67703 (13) 0.24501 (13) 0.0470 (4)
H12A 1.2464 0.6827 0.2980 0.056*
H12B 1.3465 0.6801 0.2179 0.056*
C13 1.1961 (2) 0.58818 (12) 0.25976 (11) 0.0426 (4)
H13 1.2656 0.5403 0.3038 0.051*
C14 1.2281 (2) 0.57398 (12) 0.17908 (12) 0.0437 (4)
C15 1.1864 (2) 0.65830 (13) 0.10116 (12) 0.0485 (5)
H15A 1.2834 0.6808 0.0778 0.058*
H15B 1.1394 0.6463 0.0591 0.058*
C16 0.9154 (2) 0.74887 (11) 0.10304 (10) 0.0375 (4)
C17 0.8265 (2) 0.80022 (10) 0.15515 (10) 0.0356 (4)
C18 0.6500 (2) 0.78975 (12) 0.17505 (11) 0.0402 (4)
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H18A 0.6497 0.7270 0.2014 0.048*
H18B 0.6092 0.8151 0.2160 0.048*
C19 0.5320 (2) 0.83103 (13) 0.10197 (13) 0.0489 (5)
H19A 0.4241 0.8456 0.1230 0.059*
H19B 0.5604 0.8859 0.0629 0.059*
C20 1.2920 (3) 0.49662 (14) 0.17543 (14) 0.0560 (5)
H20A 1.3201 0.4469 0.2245 0.067*
H20B 1.3090 0.4918 0.1238 0.067*
C21 0.9342 (3) 0.83493 (13) 0.27093 (13) 0.0507 (5)
H21A 0.8274 0.8462 0.2931 0.076*
H21B 0.9566 0.8890 0.2288 0.076*
H21C 1.0120 0.8124 0.3152 0.076*
C22 0.8310 (2) 0.89750 (12) 0.10086 (13) 0.0456 (4)
C23 0.7385 (4) 1.04634 (14) 0.0831 (2) 0.0798 (8)
H23A 0.8501 1.0511 0.0747 0.120*
H23B 0.6866 1.0787 0.1162 0.120*
H23C 0.6856 1.0704 0.0298 0.120*
C1' 1.2700 (3) −0.05427 (16) 0.2478 (2) 0.0816 (9)
C2' 1.2696 (4) 0.0186 (2) 0.1583 (2) 0.0621 (8) 0.70
H2'1 1.3725 0.0072 0.1313 0.074* 0.70
H2'2 1.1851 0.0167 0.1255 0.074* 0.70
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C2" 1.3600 (9) 0.0310 (5) 0.2121 (5) 0.0590 (19) 0.30
H2"1 1.3942 0.0416 0.2582 0.071* 0.30
H2"2 1.4544 0.0200 0.1790 0.071* 0.30
C3' 1.2427 (3) 0.10670 (14) 0.16066 (14) 0.0571 (5)
H3'A 1.2373 0.1511 0.1039 0.069* 0.70
H3'B 1.3329 0.1106 0.1886 0.069* 0.70
H3'C 1.2175 0.0955 0.1135 0.069* 0.30
H3'D 1.2885 0.1575 0.1405 0.069* 0.30
C4' 1.0866 (2) 0.12515 (11) 0.20670 (11) 0.0401 (4)
H4' 0.9920 0.1338 0.1737 0.048*
C5' 1.0850 (2) 0.04800 (12) 0.29444 (12) 0.0433 (4)
C6' 0.9159 (2) 0.05465 (12) 0.32775 (12) 0.0474 (5)
H6' 0.8439 0.0189 0.3315 0.057*
C7' 0.8911 (2) 0.12203 (12) 0.35069 (11) 0.0442 (4)
H7' 0.7965 0.1441 0.3735 0.053*
C8' 1.0479 (2) 0.15683 (11) 0.33249 (11) 0.0391 (4)
C9' 1.0727 (2) 0.20254 (11) 0.23565 (10) 0.0352 (4)
H9' 1.1852 0.2095 0.2320 0.042*
C10' 0.9800 (2) 0.29964 (11) 0.19222 (10) 0.0340 (4)
C11' 0.9844 (2) 0.34150 (11) 0.25695 (11) 0.0389 (4)
H11' 0.9830 0.4049 0.2278 0.047*
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C12' 1.1248 (3) 0.29740 (13) 0.31878 (12) 0.0488 (5)
H12C 1.1338 0.3345 0.3482 0.059*
H12D 1.2256 0.2882 0.2894 0.059*
C13' 1.0897 (3) 0.20798 (13) 0.38123 (12) 0.0475 (5)
H13' 1.1863 0.1735 0.4152 0.057*
C14' 0.9536 (3) 0.22806 (13) 0.43760 (12) 0.0529 (5)
C15' 0.8264 (3) 0.30926 (14) 0.39341 (12) 0.0557 (5)
H15C 0.7201 0.2992 0.4153 0.067*
H15D 0.8458 0.3593 0.4029 0.067*
C16' 0.7222 (2) 0.31500 (11) 0.26379 (11) 0.0399 (4)
C17' 0.7910 (2) 0.31756 (11) 0.17823 (10) 0.0355 (4)
C18' 0.7341 (2) 0.25385 (12) 0.14869 (12) 0.0426 (4)
H18C 0.7923 0.2554 0.0976 0.051*
H18D 0.7658 0.1943 0.1907 0.051*
C19' 0.5536 (3) 0.27051 (17) 0.13189 (17) 0.0640 (6)
H19C 0.5102 0.3338 0.1098 0.077*
H19D 0.5392 0.2488 0.0896 0.077*
C20' 0.9455 (4) 0.18098 (18) 0.51869 (14) 0.0794 (8)
H20C 0.8598 0.1976 0.5502 0.095*
H20D 1.0256 0.1312 0.5444 0.095*
C21' 1.0713 (2) 0.34393 (13) 0.11189 (11) 0.0447 (4)
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H21D 1.1835 0.3346 0.1246 0.067*
H21E 1.0262 0.4063 0.0884 0.067*
H21F 1.0616 0.3187 0.0723 0.067*
C22' 0.7364 (2) 0.41118 (12) 0.11147 (11) 0.0396 (4)
C23' 0.6535 (3) 0.56288 (12) 0.08254 (13) 0.0547 (5)
H23D 0.7432 0.5823 0.0477 0.082*
H23E 0.6137 0.6010 0.1120 0.082*
H23F 0.5689 0.5649 0.0483 0.082*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
O1 0.0684 (10) 0.0752 (10) 0.0377 (7) −0.0329 (8) 0.0015 (7) −0.0065 (7)
O2 0.0659 (9) 0.0436 (8) 0.0412 (7) −0.0192 (6) 0.0078 (6) −0.0103 (6)
O3 0.0469 (7) 0.0389 (7) 0.0335 (6) −0.0078 (5) −0.0036 (5) −0.0069 (5)
O4 0.0534 (8) 0.0526 (8) 0.0404 (7) −0.0006 (6) −0.0084 (6) −0.0225 (6)
O5 0.0566 (9) 0.0670 (10) 0.0766 (11) −0.0052 (8) −0.0201 (8) −0.0360 (9)
O6 0.0939 (13) 0.0460 (9) 0.0912 (13) −0.0207 (9) 0.0378 (11) −0.0061 (9)
O7 0.0586 (9) 0.0318 (7) 0.0700 (9) −0.0044 (6) −0.0023 (7) −0.0174 (7)
O1' 0.1106 (16) 0.0481 (10) 0.1285 (17) 0.0096 (10) 0.0435 (14) −0.0300 (11)
O2' 0.0635 (9) 0.0334 (7) 0.0646 (9) −0.0017 (6) 0.0089 (7) −0.0176 (6)
O3' 0.0466 (7) 0.0365 (7) 0.0472 (7) 0.0007 (5) −0.0062 (6) −0.0119 (6)
O4' 0.0432 (8) 0.0635 (9) 0.0554 (8) −0.0083 (7) 0.0131 (6) −0.0167 (7)
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O5' 0.0539 (11) 0.161 (2) 0.1180 (18) −0.0478 (13) 0.0055 (12) −0.0548 (17)
O6' 0.1033 (13) 0.0520 (9) 0.0373 (8) 0.0069 (8) −0.0145 (8) −0.0145 (7)
O7' 0.0548 (8) 0.0310 (6) 0.0403 (7) −0.0022 (5) −0.0062 (6) −0.0101 (5)
N1 0.0386 (8) 0.0403 (8) 0.0343 (7) −0.0028 (6) 0.0008 (6) −0.0118 (6)
N1' 0.0530 (9) 0.0360 (8) 0.0321 (7) −0.0040 (7) 0.0016 (7) −0.0132 (6)
C1 0.0479 (11) 0.0600 (12) 0.0330 (9) −0.0178 (9) −0.0037 (8) −0.0097 (9)
C2 0.0662 (14) 0.0672 (14) 0.0403 (11) −0.0182 (11) 0.0110 (10) −0.0231 (10)
C3 0.0658 (13) 0.0531 (11) 0.0382 (10) −0.0211 (10) 0.0069 (9) −0.0215 (9)
C4 0.0456 (10) 0.0399 (9) 0.0354 (9) −0.0111 (8) 0.0010 (8) −0.0158 (8)
C5 0.0479 (10) 0.0391 (9) 0.0342 (9) −0.0141 (8) 0.0025 (8) −0.0101 (7)
C6 0.0478 (10) 0.0366 (9) 0.0438 (10) −0.0119 (8) −0.0048 (8) −0.0164 (8)
C7 0.0489 (10) 0.0313 (8) 0.0363 (9) −0.0051 (7) −0.0029 (8) −0.0141 (7)
C8 0.0433 (10) 0.0345 (9) 0.0298 (8) −0.0051 (7) −0.0037 (7) −0.0081 (7)
C9 0.0410 (9) 0.0377 (9) 0.0327 (8) −0.0113 (7) −0.0013 (7) −0.0142 (7)
C10 0.0413 (9) 0.0337 (9) 0.0387 (9) −0.0113 (7) 0.0000 (7) −0.0152 (7)
C11 0.0402 (10) 0.0384 (9) 0.0423 (10) −0.0125 (8) −0.0007 (8) −0.0105 (8)
C12 0.0366 (10) 0.0526 (11) 0.0493 (11) −0.0099 (8) −0.0027 (8) −0.0164 (9)
C13 0.0410 (10) 0.0400 (10) 0.0385 (9) −0.0033 (8) −0.0070 (8) −0.0081 (8)
C14 0.0350 (9) 0.0454 (10) 0.0433 (10) −0.0032 (8) 0.0021 (8) −0.0127 (8)
C15 0.0477 (11) 0.0471 (11) 0.0411 (10) 0.0026 (8) 0.0029 (8) −0.0144 (9)
C16 0.0436 (10) 0.0313 (8) 0.0308 (8) −0.0044 (7) −0.0011 (7) −0.0065 (7)
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C17 0.0403 (9) 0.0294 (8) 0.0362 (9) −0.0079 (7) 0.0000 (7) −0.0115 (7)
C18 0.0381 (9) 0.0359 (9) 0.0442 (10) −0.0060 (7) −0.0007 (8) −0.0137 (8)
C19 0.0422 (10) 0.0426 (10) 0.0578 (12) −0.0064 (8) −0.0061 (9) −0.0153 (9)
C20 0.0568 (13) 0.0466 (11) 0.0551 (12) −0.0035 (9) 0.0082 (10) −0.0157 (10)
C21 0.0640 (13) 0.0452 (11) 0.0523 (11) −0.0181 (9) −0.0041 (10) −0.0243 (9)
C22 0.0463 (10) 0.0334 (9) 0.0524 (11) −0.0085 (8) −0.0019 (9) −0.0113 (8)
C23 0.0859 (18) 0.0299 (11) 0.112 (2) −0.0044 (11) −0.0181 (16) −0.0162 (12)
C1' 0.0705 (16) 0.0479 (14) 0.109 (2) −0.0013 (11) 0.0375 (15) −0.0261 (14)
C2' 0.061 (2) 0.0583 (19) 0.069 (2) −0.0055 (15) 0.0127 (16) −0.0335 (17)
C2" 0.041 (4) 0.055 (4) 0.075 (5) −0.003 (3) 0.019 (3) −0.027 (4)
C3' 0.0567 (13) 0.0519 (12) 0.0560 (12) −0.0047 (10) 0.0145 (10) −0.0207 (10)
C4' 0.0391 (9) 0.0374 (9) 0.0438 (10) −0.0045 (7) 0.0001 (8) −0.0176 (8)
C5' 0.0477 (11) 0.0321 (9) 0.0487 (10) −0.0039 (8) 0.0019 (8) −0.0170 (8)
C6' 0.0486 (11) 0.0386 (10) 0.0516 (11) −0.0145 (8) 0.0065 (9) −0.0124 (9)
C7' 0.0464 (10) 0.0375 (10) 0.0409 (10) −0.0063 (8) 0.0074 (8) −0.0102 (8)
C8' 0.0427 (10) 0.0317 (9) 0.0381 (9) −0.0018 (7) −0.0042 (7) −0.0110 (7)
C9' 0.0317 (8) 0.0357 (9) 0.0384 (9) −0.0072 (7) −0.0006 (7) −0.0143 (7)
C10' 0.0361 (9) 0.0320 (8) 0.0338 (8) −0.0086 (7) −0.0004 (7) −0.0116 (7)
C11' 0.0478 (10) 0.0300 (8) 0.0384 (9) −0.0110 (7) −0.0025 (8) −0.0108 (7)
C12' 0.0572 (12) 0.0464 (11) 0.0477 (11) −0.0141 (9) −0.0129 (9) −0.0190 (9)
C13' 0.0577 (12) 0.0420 (10) 0.0412 (10) −0.0051 (9) −0.0150 (9) −0.0142 (8)
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C14' 0.0799 (15) 0.0424 (11) 0.0372 (10) −0.0089 (10) −0.0062 (10) −0.0171 (9)
C15' 0.0830 (16) 0.0469 (11) 0.0334 (10) −0.0025 (10) 0.0021 (10) −0.0178 (9)
C16' 0.0421 (10) 0.0327 (9) 0.0366 (9) 0.0003 (7) 0.0007 (8) −0.0093 (7)
C17' 0.0355 (9) 0.0341 (9) 0.0350 (9) −0.0047 (7) −0.0014 (7) −0.0127 (7)
C18' 0.0416 (10) 0.0392 (10) 0.0468 (10) −0.0061 (8) −0.0073 (8) −0.0161 (8)
C19' 0.0456 (12) 0.0657 (14) 0.0842 (16) −0.0067 (10) −0.0186 (12) −0.0314 (13)
C20' 0.116 (2) 0.0675 (16) 0.0397 (12) −0.0012 (15) −0.0075 (13) −0.0133 (11)
C21' 0.0456 (10) 0.0445 (10) 0.0398 (10) −0.0137 (8) 0.0059 (8) −0.0109 (8)
C22' 0.0423 (10) 0.0387 (9) 0.0339 (9) −0.0037 (7) −0.0027 (7) −0.0121 (7)
C23' 0.0662 (13) 0.0325 (10) 0.0540 (12) −0.0035 (9) −0.0090 (10) −0.0068 (9)
Geometric parameters (Å, º)
O1—C1 1.194 (2) C19—H19A 0.9700
O2—C1 1.360 (2) C19—H19B 0.9700
O2—C5 1.406 (2) C20—H20A 0.9300
O3—C5 1.440 (2) C20—H20B 0.9300
O3—C8 1.462 (2) C21—H21A 0.9600
O4—C16 1.233 (2) C21—H21B 0.9600
O5—C19 1.413 (2) C21—H21C 0.9600
O5—H5 0.8200 C23—H23A 0.9600
O6—C22 1.196 (2) C23—H23B 0.9600
O7—C22 1.321 (2) C23—H23C 0.9600
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O7—C23 1.455 (3) C1'—C2' 1.551 (4)
O1'—C1' 1.190 (3) C1'—C2" 1.650 (8)
O2'—C1' 1.317 (3) C2'—C3' 1.466 (4)
O2'—C5' 1.403 (2) C2'—H2'1 0.9700
O3'—C5' 1.427 (2) C2'—H2'2 0.9700
O3'—C8' 1.457 (2) C2'—H3'C 1.2173
O4'—C16' 1.228 (2) C2"—C3' 1.449 (8)
O5'—C19' 1.403 (3) C2"—H2"1 0.9700
O5'—H5' 0.8200 C2"—H2"2 0.9700
O6'—C22' 1.193 (2) C3'—C4' 1.520 (3)
O7'—C22' 1.320 (2) C3'—H3'A 0.9700
O7'—C23' 1.448 (2) C3'—H3'B 0.9700
N1—C16 1.332 (2) C3'—H3'C 0.9634
N1—C15 1.458 (2) C3'—H3'D 0.9436
N1—C11 1.469 (2) C4'—C9' 1.553 (2)
N1'—C16' 1.325 (2) C4'—C5' 1.562 (3)
N1'—C11' 1.462 (2) C4'—H4' 0.9800
N1'—C15' 1.464 (2) C5'—C6' 1.493 (3)
C1—C2 1.482 (3) C6'—C7' 1.315 (3)
C2—C3 1.522 (3) C6'—H6' 0.9300
C2—H2A 0.9700 C7'—C8' 1.528 (3)
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C2—H2B 0.9700 C7'—H7' 0.9300
C3—C4 1.522 (3) C8'—C13' 1.537 (3)
C3—H3A 0.9700 C8'—C9' 1.565 (2)
C3—H3B 0.9700 C9'—C10' 1.552 (2)
C4—C5 1.552 (3) C9'—H9' 0.9800
C4—C9 1.556 (2) C10'—C21' 1.529 (2)
C4—H4 0.9800 C10'—C11' 1.556 (2)
C5—C6 1.500 (3) C10'—C17' 1.586 (2)
C6—C7 1.313 (3) C11'—C12' 1.526 (3)
C6—H6 0.9300 C11'—H11' 0.9800
C7—C8 1.524 (3) C12'—C13' 1.540 (3)
C7—H7 0.9300 C12'—H12C 0.9700
C8—C13 1.544 (3) C12'—H12D 0.9700
C8—C9 1.558 (2) C13'—C14' 1.513 (3)
C9—C10 1.553 (2) C13'—H13' 0.9800
C9—H9 0.9800 C14'—C20' 1.318 (3)
C10—C21 1.535 (2) C14'—C15' 1.509 (3)
C10—C11 1.558 (3) C15'—H15C 0.9700
C10—C17 1.580 (2) C15'—H15D 0.9700
C11—C12 1.522 (3) C16'—C17' 1.536 (2)
C11—H11 0.9800 C17'—C22' 1.536 (2)
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C12—C13 1.544 (3) C17'—C18' 1.538 (2)
C12—H12A 0.9700 C18'—C19' 1.526 (3)
C12—H12B 0.9700 C18'—H18C 0.9700
C13—C14 1.507 (3) C18'—H18D 0.9700
C13—H13 0.9800 C19'—H19C 0.9700
C14—C20 1.318 (3) C19'—H19D 0.9700
C14—C15 1.518 (3) C20'—H20C 0.9300
C15—H15A 0.9700 C20'—H20D 0.9300
C15—H15B 0.9700 C21'—H21D 0.9600
C16—C17 1.532 (2) C21'—H21E 0.9600
C17—C22 1.537 (2) C21'—H21F 0.9600
C17—C18 1.538 (2) C23'—H23D 0.9600
C18—C19 1.523 (3) C23'—H23E 0.9600
C18—H18A 0.9700 C23'—H23F 0.9600
C18—H18B 0.9700
C1—O2—C5 123.39 (15) C3'—C2'—H2'1 109.4
C5—O3—C8 95.18 (12) C1'—C2'—H2'1 109.4
C19—O5—H5 109.5 C3'—C2'—H2'2 109.4
C22—O7—C23 115.82 (18) C1'—C2'—H2'2 109.4
C1'—O2'—C5' 123.74 (17) H2'1—C2'—H2'2 108.0
C5'—O3'—C8' 95.62 (13) C3'—C2'—H3'C 40.8
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C19'—O5'—H5' 109.5 C1'—C2'—H3'C 145.7
C22'—O7'—C23' 115.85 (14) H2'1—C2'—H3'C 100.8
C16—N1—C15 123.86 (16) H2'2—C2'—H3'C 75.0
C16—N1—C11 114.24 (14) C3'—C2"—C1' 106.8 (5)
C15—N1—C11 120.57 (15) C3'—C2"—H2"1 110.4
C16'—N1'—C11' 114.60 (14) C1'—C2"—H2"1 110.4
C16'—N1'—C15' 123.40 (17) C3'—C2"—H2"2 110.4
C11'—N1'—C15' 120.31 (17) C1'—C2"—H2"2 110.4
O1—C1—O2 116.62 (19) H2"1—C2"—H2"2 108.6
O1—C1—C2 124.61 (19) C2"—C3'—C2' 55.9 (4)
O2—C1—C2 118.73 (16) C2"—C3'—C4' 113.6 (3)
C1—C2—C3 113.92 (18) C2'—C3'—C4' 111.0 (2)
C1—C2—H2A 108.8 C2"—C3'—H3'A 137.0
C3—C2—H2A 108.8 C2'—C3'—H3'A 109.4
C1—C2—H2B 108.8 C4'—C3'—H3'A 109.4
C3—C2—H2B 108.8 C2"—C3'—H3'B 55.7
H2A—C2—H2B 107.7 C2'—C3'—H3'B 109.4
C4—C3—C2 107.99 (16) C4'—C3'—H3'B 109.4
C4—C3—H3A 110.1 H3'A—C3'—H3'B 108.0
C2—C3—H3A 110.1 C2"—C3'—H3'C 108.0
C4—C3—H3B 110.1 C2'—C3'—H3'C 55.6
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C2—C3—H3B 110.1 C4'—C3'—H3'C 108.7
H3A—C3—H3B 108.4 H3'A—C3'—H3'C 57.8
C3—C4—C5 108.60 (15) H3'B—C3'—H3'C 141.8
C3—C4—C9 114.54 (15) C2"—C3'—H3'D 109.4
C5—C4—C9 99.10 (13) C2'—C3'—H3'D 140.4
C3—C4—H4 111.3 C4'—C3'—H3'D 108.5
C5—C4—H4 111.3 H3'A—C3'—H3'D 53.1
C9—C4—H4 111.3 H3'B—C3'—H3'D 58.1
O2—C5—O3 108.36 (14) H3'C—C3'—H3'D 108.6
O2—C5—C6 114.48 (15) C3'—C4'—C9' 114.52 (16)
O3—C5—C6 101.82 (14) C3'—C4'—C5' 109.93 (15)
O2—C5—C4 118.75 (15) C9'—C4'—C5' 98.89 (13)
O3—C5—C4 103.06 (14) C3'—C4'—H4' 111.0
C6—C5—C4 108.39 (14) C9'—C4'—H4' 111.0
C7—C6—C5 105.06 (16) C5'—C4'—H4' 111.0
C7—C6—H6 127.5 O2'—C5'—O3' 109.51 (15)
C5—C6—H6 127.5 O2'—C5'—C6' 114.18 (15)
C6—C7—C8 106.79 (15) O3'—C5'—C6' 102.34 (15)
C6—C7—H7 126.6 O2'—C5'—C4' 117.76 (15)
C8—C7—H7 126.6 O3'—C5'—C4' 102.80 (14)
O3—C8—C7 99.66 (13) C6'—C5'—C4' 108.54 (15)
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O3—C8—C13 112.64 (14) C7'—C6'—C5' 105.01 (17)
C7—C8—C13 120.31 (15) C7'—C6'—H6' 127.5
O3—C8—C9 97.98 (12) C5'—C6'—H6' 127.5
C7—C8—C9 110.20 (14) C6'—C7'—C8' 106.54 (16)
C13—C8—C9 113.01 (14) C6'—C7'—H7' 126.7
C10—C9—C4 126.97 (15) C8'—C7'—H7' 126.7
C10—C9—C8 117.01 (14) O3'—C8'—C7' 99.66 (14)
C4—C9—C8 102.42 (13) O3'—C8'—C13' 112.59 (15)
C10—C9—H9 102.3 C7'—C8'—C13' 120.51 (16)
C4—C9—H9 102.3 O3'—C8'—C9' 97.67 (13)
C8—C9—H9 102.3 C7'—C8'—C9' 110.02 (14)
C21—C10—C9 107.24 (14) C13'—C8'—C9' 113.22 (14)
C21—C10—C11 111.75 (15) C10'—C9'—C4' 127.80 (14)
C9—C10—C11 103.88 (14) C10'—C9'—C8' 116.48 (14)
C21—C10—C17 113.03 (15) C4'—C9'—C8' 102.46 (13)
C9—C10—C17 119.47 (14) C10'—C9'—H9' 102.1
C11—C10—C17 100.92 (13) C4'—C9'—H9' 102.1
N1—C11—C12 107.83 (15) C8'—C9'—H9' 102.1
N1—C11—C10 102.20 (14) C21'—C10'—C9' 107.90 (14)
C12—C11—C10 115.72 (15) C21'—C10'—C11' 111.60 (14)
N1—C11—H11 110.2 C9'—C10'—C11' 104.39 (13)
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C12—C11—H11 110.2 C21'—C10'—C17' 112.88 (14)
C10—C11—H11 110.2 C9'—C10'—C17' 118.55 (13)
C11—C12—C13 107.45 (15) C11'—C10'—C17' 100.99 (13)
C11—C12—H12A 110.2 N1'—C11'—C12' 108.39 (15)
C13—C12—H12A 110.2 N1'—C11'—C10' 102.79 (13)
C11—C12—H12B 110.2 C12'—C11'—C10' 115.19 (15)
C13—C12—H12B 110.2 N1'—C11'—H11' 110.1
H12A—C12—H12B 108.5 C12'—C11'—H11' 110.1
C14—C13—C12 107.32 (15) C10'—C11'—H11' 110.1
C14—C13—C8 112.98 (15) C11'—C12'—C13' 107.39 (16)
C12—C13—C8 109.24 (15) C11'—C12'—H12C 110.2
C14—C13—H13 109.1 C13'—C12'—H12C 110.2
C12—C13—H13 109.1 C11'—C12'—H12D 110.2
C8—C13—H13 109.1 C13'—C12'—H12D 110.2
C20—C14—C13 123.76 (18) H12C—C12'—H12D 108.5
C20—C14—C15 122.50 (18) C14'—C13'—C8' 113.12 (17)
C13—C14—C15 113.69 (16) C14'—C13'—C12' 107.02 (16)
N1—C15—C14 108.44 (15) C8'—C13'—C12' 109.25 (15)
N1—C15—H15A 110.0 C14'—C13'—H13' 109.1
C14—C15—H15A 110.0 C8'—C13'—H13' 109.1
N1—C15—H15B 110.0 C12'—C13'—H13' 109.1
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C14—C15—H15B 110.0 C20'—C14'—C15' 121.7 (2)
H15A—C15—H15B 108.4 C20'—C14'—C13' 124.1 (2)
O4—C16—N1 125.40 (16) C15'—C14'—C13' 114.12 (16)
O4—C16—C17 126.25 (16) N1'—C15'—C14' 108.85 (16)
N1—C16—C17 108.33 (15) N1'—C15'—H15C 109.9
C16—C17—C22 104.69 (14) C14'—C15'—H15C 109.9
C16—C17—C18 113.43 (14) N1'—C15'—H15D 109.9
C22—C17—C18 109.75 (14) C14'—C15'—H15D 109.9
C16—C17—C10 102.08 (13) H15C—C15'—H15D 108.3
C22—C17—C10 108.86 (14) O4'—C16'—N1' 125.42 (17)
C18—C17—C10 117.13 (14) O4'—C16'—C17' 126.08 (17)
C19—C18—C17 117.18 (15) N1'—C16'—C17' 108.47 (15)
C19—C18—H18A 108.0 C22'—C17'—C16' 109.13 (13)
C17—C18—H18A 108.0 C22'—C17'—C18' 106.76 (14)
C19—C18—H18B 108.0 C16'—C17'—C18' 113.98 (15)
C17—C18—H18B 108.0 C22'—C17'—C10' 108.99 (13)
H18A—C18—H18B 107.2 C16'—C17'—C10' 102.16 (13)
O5—C19—C18 114.44 (16) C18'—C17'—C10' 115.64 (14)
O5—C19—H19A 108.6 C19'—C18'—C17' 117.32 (16)
C18—C19—H19A 108.6 C19'—C18'—H18C 108.0
O5—C19—H19B 108.6 C17'—C18'—H18C 108.0
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C18—C19—H19B 108.6 C19'—C18'—H18D 108.0
H19A—C19—H19B 107.6 C17'—C18'—H18D 108.0
C14—C20—H20A 120.0 H18C—C18'—H18D 107.2
C14—C20—H20B 120.0 O5'—C19'—C18' 112.7 (2)
H20A—C20—H20B 120.0 O5'—C19'—H19C 109.1
C10—C21—H21A 109.5 C18'—C19'—H19C 109.1
C10—C21—H21B 109.5 O5'—C19'—H19D 109.1
H21A—C21—H21B 109.5 C18'—C19'—H19D 109.1
C10—C21—H21C 109.5 H19C—C19'—H19D 107.8
H21A—C21—H21C 109.5 C14'—C20'—H20C 120.0
H21B—C21—H21C 109.5 C14'—C20'—H20D 120.0
O6—C22—O7 123.53 (18) H20C—C20'—H20D 120.0
O6—C22—C17 123.35 (18) C10'—C21'—H21D 109.5
O7—C22—C17 113.12 (16) C10'—C21'—H21E 109.5
O7—C23—H23A 109.5 H21D—C21'—H21E 109.5
O7—C23—H23B 109.5 C10'—C21'—H21F 109.5
H23A—C23—H23B 109.5 H21D—C21'—H21F 109.5
O7—C23—H23C 109.5 H21E—C21'—H21F 109.5
H23A—C23—H23C 109.5 O6'—C22'—O7' 123.06 (17)
H23B—C23—H23C 109.5 O6'—C22'—C17' 123.79 (16)
O1'—C1'—O2' 117.4 (2) O7'—C22'—C17' 113.15 (14)
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O1'—C1'—C2' 122.7 (3) O7'—C23'—H23D 109.5
O2'—C1'—C2' 117.8 (2) O7'—C23'—H23E 109.5
O1'—C1'—C2" 125.2 (3) H23D—C23'—H23E 109.5
O2'—C1'—C2" 104.3 (3) O7'—C23'—H23F 109.5
C2'—C1'—C2" 50.4 (3) H23D—C23'—H23F 109.5
C3'—C2'—C1' 111.2 (3) H23E—C23'—H23F 109.5
C5—O2—C1—O1 175.37 (17) C2"—C1'—C2'—C3' −45.2 (3)
C5—O2—C1—C2 −2.4 (3) O1'—C1'—C2"—C3' 150.3 (4)
O1—C1—C2—C3 156.4 (2) O2'—C1'—C2"—C3' −70.1 (5)
O2—C1—C2—C3 −25.9 (3) C2'—C1'—C2"—C3' 44.4 (4)
C1—C2—C3—C4 56.1 (2) C1'—C2"—C3'—C2' −43.5 (4)
C2—C3—C4—C5 −56.9 (2) C1'—C2"—C3'—C4' 56.6 (5)
C2—C3—C4—C9 −166.63 (17) C1'—C2'—C3'—C2" 48.8 (4)
C1—O2—C5—O3 115.61 (18) C1'—C2'—C3'—C4' −56.1 (3)
C1—O2—C5—C6 −131.54 (18) C2"—C3'—C4'—C9' 101.8 (4)
C1—O2—C5—C4 −1.4 (3) C2'—C3'—C4'—C9' 162.6 (2)
C8—O3—C5—O2 173.48 (13) C2"—C3'—C4'—C5' −8.4 (4)
C8—O3—C5—C6 52.45 (15) C2'—C3'—C4'—C5' 52.3 (3)
C8—O3—C5—C4 −59.85 (14) C1'—O2'—C5'—O3' −98.4 (3)
C3—C4—C5—O2 32.2 (2) C1'—O2'—C5'—C6' 147.5 (2)
C9—C4—C5—O2 152.05 (16) C1'—O2'—C5'—C4' 18.5 (3)
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S98
C3—C4—C5—O3 −87.54 (17) C8'—O3'—C5'—O2' −173.70 (14)
C9—C4—C5—O3 32.31 (16) C8'—O3'—C5'—C6' −52.21 (15)
C3—C4—C5—C6 165.07 (16) C8'—O3'—C5'—C4' 60.34 (15)
C9—C4—C5—C6 −75.08 (17) C3'—C4'—C5'—O2' −32.8 (2)
O2—C5—C6—C7 −151.08 (16) C9'—C4'—C5'—O2' −153.05 (16)
O3—C5—C6—C7 −34.41 (17) C3'—C4'—C5'—O3' 87.62 (18)
C4—C5—C6—C7 73.82 (18) C9'—C4'—C5'—O3' −32.62 (16)
C5—C6—C7—C8 0.78 (19) C3'—C4'—C5'—C6' −164.48 (17)
C5—O3—C8—C7 −50.66 (14) C9'—C4'—C5'—C6' 75.29 (17)
C5—O3—C8—C13 −179.39 (14) O2'—C5'—C6'—C7' 152.41 (17)
C5—O3—C8—C9 61.53 (14) O3'—C5'—C6'—C7' 34.19 (19)
C6—C7—C8—O3 32.23 (17) C4'—C5'—C6'—C7' −74.0 (2)
C6—C7—C8—C13 155.72 (16) C5'—C6'—C7'—C8' −0.8 (2)
C6—C7—C8—C9 −70.04 (18) C5'—O3'—C8'—C7' 50.14 (15)
C3—C4—C9—C10 −100.3 (2) C5'—O3'—C8'—C13' 179.09 (15)
C5—C4—C9—C10 144.34 (16) C5'—O3'—C8'—C9' −61.78 (14)
C3—C4—C9—C8 121.29 (16) C6'—C7'—C8'—O3' −31.70 (19)
C5—C4—C9—C8 5.94 (16) C6'—C7'—C8'—C13' −155.24 (17)
O3—C8—C9—C10 175.17 (14) C6'—C7'—C8'—C9' 70.19 (19)
C7—C8—C9—C10 −81.41 (18) C3'—C4'—C9'—C10' 99.0 (2)
C13—C8—C9—C10 56.4 (2) C5'—C4'—C9'—C10' −144.18 (16)
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S99
O3—C8—C9—C4 −41.37 (15) C3'—C4'—C9'—C8' −122.43 (17)
C7—C8—C9—C4 62.06 (17) C5'—C4'—C9'—C8' −5.65 (16)
C13—C8—C9—C4 −160.17 (14) O3'—C8'—C9'—C10' −174.79 (14)
C4—C9—C10—C21 71.0 (2) C7'—C8'—C9'—C10' 81.96 (18)
C8—C9—C10—C21 −155.68 (16) C13'—C8'—C9'—C10' −56.1 (2)
C4—C9—C10—C11 −170.54 (16) O3'—C8'—C9'—C4' 40.99 (15)
C8—C9—C10—C11 −37.24 (19) C7'—C8'—C9'—C4' −62.27 (17)
C4—C9—C10—C17 −59.2 (2) C13'—C8'—C9'—C4' 159.64 (15)
C8—C9—C10—C17 74.1 (2) C4'—C9'—C10'—C21' −70.6 (2)
C16—N1—C11—C12 144.04 (15) C8'—C9'—C10'—C21' 155.61 (15)
C15—N1—C11—C12 −23.3 (2) C4'—C9'—C10'—C11' 170.53 (16)
C16—N1—C11—C10 21.63 (19) C8'—C9'—C10'—C11' 36.78 (18)
C15—N1—C11—C10 −145.71 (16) C4'—C9'—C10'—C17' 59.2 (2)
C21—C10—C11—N1 −152.76 (15) C8'—C9'—C10'—C17' −74.53 (19)
C9—C10—C11—N1 91.95 (15) C16'—N1'—C11'—C12' −143.38 (15)
C17—C10—C11—N1 −32.37 (15) C15'—N1'—C11'—C12' 22.3 (2)
C21—C10—C11—C12 90.37 (19) C16'—N1'—C11'—C10' −21.01 (18)
C9—C10—C11—C12 −24.9 (2) C15'—N1'—C11'—C10' 144.66 (15)
C17—C10—C11—C12 −149.24 (15) C21'—C10'—C11'—N1' 151.07 (14)
N1—C11—C12—C13 −41.20 (19) C9'—C10'—C11'—N1' −92.65 (15)
C10—C11—C12—C13 72.5 (2) C17'—C10'—C11'—N1' 30.89 (15)
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S100
C11—C12—C13—C14 72.73 (18) C21'—C10'—C11'—C12' −91.26 (18)
C11—C12—C13—C8 −50.1 (2) C9'—C10'—C11'—C12' 25.02 (19)
O3—C8—C13—C14 123.58 (16) C17'—C10'—C11'—C12' 148.55 (15)
C7—C8—C13—C14 6.6 (2) N1'—C11'—C12'—C13' 41.61 (19)
C9—C8—C13—C14 −126.52 (16) C10'—C11'—C12'—C13' −72.9 (2)
O3—C8—C13—C12 −117.05 (16) O3'—C8'—C13'—C14' −124.21 (16)
C7—C8—C13—C12 125.92 (17) C7'—C8'—C13'—C14' −7.1 (2)
C9—C8—C13—C12 −7.1 (2) C9'—C8'—C13'—C14' 126.17 (16)
C12—C13—C14—C20 140.0 (2) O3'—C8'—C13'—C12' 116.69 (17)
C8—C13—C14—C20 −99.6 (2) C7'—C8'—C13'—C12' −126.17 (18)
C12—C13—C14—C15 −37.6 (2) C9'—C8'—C13'—C12' 7.1 (2)
C8—C13—C14—C15 82.9 (2) C11'—C12'—C13'—C14' −72.29 (19)
C16—N1—C15—C14 −108.44 (19) C11'—C12'—C13'—C8' 50.5 (2)
C11—N1—C15—C14 57.6 (2) C8'—C13'—C14'—C20' 98.4 (3)
C20—C14—C15—N1 160.81 (19) C12'—C13'—C14'—C20' −141.2 (2)
C13—C14—C15—N1 −21.6 (2) C8'—C13'—C14'—C15' −83.0 (2)
C15—N1—C16—O4 −11.9 (3) C12'—C13'—C14'—C15' 37.4 (2)
C11—N1—C16—O4 −178.73 (16) C16'—N1'—C15'—C14' 107.8 (2)
C15—N1—C16—C17 166.91 (15) C11'—N1'—C15'—C14' −56.6 (2)
C11—N1—C16—C17 0.05 (19) C20'—C14'—C15'—N1' −159.9 (2)
O4—C16—C17—C22 −89.2 (2) C13'—C14'—C15'—N1' 21.4 (3)
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S101
N1—C16—C17—C22 92.08 (16) C11'—N1'—C16'—O4' 178.69 (17)
O4—C16—C17—C18 30.5 (2) C15'—N1'—C16'—O4' 13.5 (3)
N1—C16—C17—C18 −148.30 (15) C11'—N1'—C16'—C17' 0.38 (19)
O4—C16—C17—C10 157.40 (17) C15'—N1'—C16'—C17' −164.80 (15)
N1—C16—C17—C10 −21.36 (17) O4'—C16'—C17'—C22' 86.4 (2)
C21—C10—C17—C16 151.97 (15) N1'—C16'—C17'—C22' −95.32 (17)
C9—C10—C17—C16 −80.44 (17) O4'—C16'—C17'—C18' −32.9 (2)
C11—C10—C17—C16 32.50 (15) N1'—C16'—C17'—C18' 145.44 (15)
C21—C10—C17—C22 41.7 (2) O4'—C16'—C17'—C10' −158.33 (17)
C9—C10—C17—C22 169.24 (15) N1'—C16'—C17'—C10' 19.96 (17)
C11—C10—C17—C22 −77.82 (16) C21'—C10'—C17'—C22' −34.52 (18)
C21—C10—C17—C18 −83.52 (18) C9'—C10'—C17'—C22' −162.06 (14)
C9—C10—C17—C18 44.1 (2) C11'—C10'—C17'—C22' 84.75 (15)
C11—C10—C17—C18 157.01 (14) C21'—C10'—C17'—C16' −149.90 (15)
C16—C17—C18—C19 −67.92 (19) C9'—C10'—C17'—C16' 82.56 (17)
C22—C17—C18—C19 48.8 (2) C11'—C10'—C17'—C16' −30.63 (15)
C10—C17—C18—C19 173.50 (15) C21'—C10'—C17'—C18' 85.71 (18)
C17—C18—C19—O5 85.7 (2) C9'—C10'—C17'—C18' −41.8 (2)
C23—O7—C22—O6 −6.4 (3) C11'—C10'—C17'—C18' −155.01 (14)
C23—O7—C22—C17 173.78 (18) C22'—C17'—C18'—C19' −56.7 (2)
C16—C17—C22—O6 −14.8 (3) C16'—C17'—C18'—C19' 63.8 (2)
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S102
C18—C17—C22—O6 −136.9 (2) C10'—C17'—C18'—C19' −178.17 (16)
C10—C17—C22—O6 93.7 (2) C17'—C18'—C19'—O5' −87.1 (2)
C16—C17—C22—O7 165.00 (16) C23'—O7'—C22'—O6' −0.1 (3)
C18—C17—C22—O7 42.9 (2) C23'—O7'—C22'—C17' −179.88 (16)
C10—C17—C22—O7 −86.45 (19) C16'—C17'—C22'—O6' −153.6 (2)
C5'—O2'—C1'—O1' 174.3 (3) C18'—C17'—C22'—O6' −30.0 (2)
C5'—O2'—C1'—C2' −21.5 (4) C10'—C17'—C22'—O6' 95.6 (2)
C5'—O2'—C1'—C2" 31.0 (4) C16'—C17'—C22'—O7' 26.2 (2)
O1'—C1'—C2'—C3' −156.2 (3) C18'—C17'—C22'—O7' 149.83 (15)
O2'—C1'—C2'—C3' 40.5 (4) C10'—C17'—C22'—O7' −84.60 (17)
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D· · ·A D—H···A
O5—H5···O4 0.82 1.95 2.697 (2) 152
O5′—H5′···O4′ 0.82 1.91 2.679 (3) 156
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S103
ORTEP of 10
Crystal data
C21H25NO3 Dx = 1.299 Mg m−3
Mr = 339.42 Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121 Cell parameters from 2986 reflections
a = 6.6506 (8) Å θ = 4.8–45.4°
b = 8.9644 (11) Å µ = 0.09 mm−1
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S104
c = 29.102 (3) Å T = 293 K
V = 1735.0 (4) Å3 Prismatic, yellow
Z = 4 0.28 × 0.21 × 0.10 mm
F(000) = 728
Data collection
CCD area detector
diffractometer 3402 independent reflections
Radiation source: fine-focus sealed tube 2818 reflections with I > 2σ(I)
graphite Rint = 0.032
phi and ω scans θmax = 26.0°, θmin = 2.4°
Absorption correction: empirical (using intensity
measurements)
SADABS
h = −7→8
Tmin = 0.321, Tmax = 1.000 k = −11→11
10558 measured reflections l = −35→28
Refinement
Refinement on F2 Secondary atom site location: difference Fourier
map
Least-squares matrix: full Hydrogen site location: inferred from
neighbouring sites
R[F2 > 2σ(F2)] = 0.048 H-atom parameters constrained
wR(F2) = 0.130 w = 1/[σ2(Fo2) + (0.0821P)2 + 0.015P]
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S105
where P = (Fo2 + 2Fc
2)/3
S = 1.06 (Δ/σ)max < 0.001
3402 reflections Δρmax = 0.19 e Å−3
228 parameters Δρmin = −0.29 e Å−3
2 restraints Absolute structure: Flack H D (1983), Acta Cryst.
A39, 876-881
Primary atom site location: structure-invariant
direct methods Flack parameter: 0.6 (18)
Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using
the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in
distances, angles and torsion angles; correlations between esds in cell parameters are only used when
they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for
estimating esds 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 > 2sigma(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.
A "B"-level alert is found by CheckCIF for compound 10: "PLAT415 ALERT 2 B Short Inter D-H..H-
X H3B .. H18A .. 2.01 Ang (short non-bonding inter D-H..H-X contact)". This is presumably due to the
strained nature of the 7-membered ring of 10 that may generate severe 1,3-axial interaction.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x y z Uiso*/Ueq
N1 0.5483 (3) 0.7093 (2) 0.94988 (6) 0.0557 (4)
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S106
O1 0.9039 (3) 0.6118 (3) 0.71289 (6) 0.0918 (6)
O2 0.7660 (3) 0.9016 (2) 0.93509 (6) 0.0803 (5)
O3 0.0343 (4) 0.1175 (3) 0.89425 (8) 0.1136 (7)
H3B 0.1098 0.0810 0.8685 0.136*
H3A −0.0451 0.0379 0.8996 0.136*
C1 0.7887 (3) 0.6572 (3) 0.74208 (8) 0.0676 (7)
C2 0.6806 (4) 0.8041 (3) 0.74173 (8) 0.0766 (7)
H2A 0.5884 0.8088 0.7159 0.092*
H2B 0.7760 0.8854 0.7391 0.092*
C3 0.5647 (3) 0.8156 (3) 0.78727 (7) 0.0586 (5)
H3 0.4210 0.8290 0.7811 0.070*
C4 0.5998 (3) 0.6649 (2) 0.81023 (6) 0.0480 (5)
C5 0.7334 (3) 0.5783 (2) 0.78453 (7) 0.0537 (5)
C6 0.8015 (3) 0.4427 (3) 0.80041 (8) 0.0597 (6)
H6 0.8863 0.3839 0.7826 0.072*
C7 0.7409 (3) 0.3968 (2) 0.84320 (8) 0.0559 (5)
H7 0.7882 0.3066 0.8547 0.067*
C8 0.6103 (3) 0.4821 (2) 0.86985 (6) 0.0474 (4)
C9 0.5310 (3) 0.6173 (2) 0.85303 (6) 0.0437 (4)
C10 0.3752 (3) 0.7068 (2) 0.88018 (7) 0.0480 (4)
C11 0.3635 (3) 0.6465 (2) 0.92942 (7) 0.0528 (5)
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H11 0.2452 0.6879 0.9449 0.063*
C12 0.3639 (3) 0.4786 (3) 0.93401 (8) 0.0602 (6)
H12A 0.2586 0.4352 0.9152 0.072*
H12B 0.3413 0.4499 0.9657 0.072*
C13 0.5690 (3) 0.4251 (2) 0.91796 (7) 0.0555 (5)
H13 0.5674 0.3158 0.9171 0.067*
C14 0.7393 (4) 0.4758 (3) 0.95157 (8) 0.0603 (5)
H14 0.8568 0.5023 0.9330 0.072*
C15 0.6749 (4) 0.6152 (3) 0.97788 (7) 0.0634 (6)
H15A 0.6024 0.5860 1.0054 0.076*
H15B 0.7933 0.6706 0.9873 0.076*
C16 0.6103 (4) 0.8319 (2) 0.92742 (7) 0.0560 (5)
C17 0.4496 (4) 0.8669 (2) 0.89233 (7) 0.0578 (5)
H17 0.3396 0.9113 0.9101 0.069*
C18 0.5003 (4) 0.9827 (3) 0.85582 (8) 0.0700 (7)
H18A 0.3749 1.0148 0.8420 0.084*
H18B 0.5570 1.0686 0.8714 0.084*
C19 0.6405 (4) 0.9413 (3) 0.81768 (9) 0.0695 (6)
H19A 0.7685 0.9120 0.8309 0.083*
H19B 0.6638 1.0286 0.7987 0.083*
C20 0.1696 (3) 0.7041 (3) 0.85663 (8) 0.0662 (6)
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H20A 0.0750 0.7600 0.8746 0.099*
H20B 0.1242 0.6028 0.8539 0.099*
H20C 0.1806 0.7476 0.8266 0.099*
C21 0.8028 (5) 0.3542 (4) 0.98450 (11) 0.0918 (9)
H21A 0.6916 0.3284 1.0040 0.138*
H21B 0.9126 0.3891 1.0030 0.138*
H21C 0.8444 0.2679 0.9674 0.138*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
N1 0.0611 (10) 0.0579 (10) 0.0482 (9) −0.0054 (9) −0.0007 (8) −0.0073 (8)
O1 0.0785 (12) 0.1301 (16) 0.0668 (10) −0.0022 (12) 0.0263 (9) −0.0164 (10)
O2 0.0876 (12) 0.0732 (11) 0.0801 (11) −0.0259 (10) −0.0169 (9) −0.0050 (8)
O3 0.1107 (17) 0.1102 (16) 0.1199 (17) 0.0028 (15) 0.0128 (15) −0.0061 (14)
C1 0.0475 (12) 0.1037 (19) 0.0517 (12) −0.0093 (12) 0.0060 (10) −0.0098 (12)
C2 0.0647 (15) 0.102 (2) 0.0635 (14) 0.0067 (15) 0.0104 (11) 0.0168 (13)
C3 0.0465 (11) 0.0726 (14) 0.0567 (12) 0.0034 (10) 0.0001 (9) 0.0121 (10)
C4 0.0373 (9) 0.0599 (12) 0.0469 (10) −0.0026 (8) −0.0049 (8) −0.0064 (8)
C5 0.0418 (10) 0.0692 (13) 0.0500 (11) −0.0049 (10) −0.0010 (8) −0.0131 (9)
C6 0.0457 (11) 0.0660 (14) 0.0674 (14) 0.0036 (10) 0.0020 (10) −0.0245 (11)
C7 0.0512 (11) 0.0485 (11) 0.0678 (13) 0.0021 (10) −0.0033 (10) −0.0117 (9)
C8 0.0420 (10) 0.0466 (10) 0.0536 (11) −0.0043 (8) −0.0041 (8) −0.0088 (8)
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C9 0.0356 (9) 0.0487 (10) 0.0467 (10) −0.0043 (8) −0.0034 (7) −0.0084 (8)
C10 0.0406 (10) 0.0510 (11) 0.0524 (10) 0.0027 (9) 0.0015 (8) −0.0043 (8)
C11 0.0452 (11) 0.0615 (12) 0.0517 (11) 0.0002 (9) 0.0080 (9) −0.0064 (9)
C12 0.0577 (13) 0.0624 (13) 0.0606 (12) −0.0135 (10) 0.0079 (10) 0.0050 (10)
C13 0.0581 (12) 0.0475 (11) 0.0608 (12) −0.0038 (10) 0.0014 (10) 0.0016 (9)
C14 0.0568 (12) 0.0697 (14) 0.0545 (12) −0.0017 (11) −0.0006 (10) 0.0072 (10)
C15 0.0684 (14) 0.0735 (14) 0.0483 (11) −0.0059 (12) −0.0078 (10) 0.0009 (10)
C16 0.0650 (13) 0.0509 (11) 0.0522 (11) −0.0053 (10) −0.0005 (10) −0.0143 (9)
C17 0.0625 (13) 0.0474 (11) 0.0636 (13) 0.0076 (10) 0.0063 (10) −0.0078 (9)
C18 0.0811 (17) 0.0499 (12) 0.0788 (15) 0.0056 (11) −0.0019 (13) 0.0016 (11)
C19 0.0692 (15) 0.0599 (14) 0.0793 (15) −0.0029 (12) 0.0017 (12) 0.0146 (11)
C20 0.0425 (11) 0.0854 (16) 0.0709 (14) 0.0054 (11) −0.0006 (10) −0.0014 (12)
C21 0.094 (2) 0.094 (2) 0.0874 (18) 0.0140 (17) −0.0146 (16) 0.0199 (15)
Geometric parameters (Å, º)
N1—C16 1.343 (3) C10—C17 1.559 (3)
N1—C15 1.444 (3) C11—C12 1.511 (3)
N1—C11 1.477 (3) C11—H11 0.9800
O1—C1 1.214 (3) C12—C13 1.519 (3)
O2—C16 1.230 (3) C12—H12A 0.9700
O3—H3B 0.9606 C12—H12B 0.9700
O3—H3A 0.9015 C13—C14 1.564 (3)
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C1—C5 1.470 (3) C13—H13 0.9800
C1—C2 1.500 (4) C14—C21 1.511 (4)
C2—C3 1.537 (3) C14—C15 1.527 (3)
C2—H2A 0.9700 C14—H14 0.9800
C2—H2B 0.9700 C15—H15A 0.9700
C3—C19 1.519 (3) C15—H15B 0.9700
C3—C4 1.525 (3) C16—C17 1.511 (3)
C3—H3 0.9800 C17—C18 1.523 (3)
C4—C9 1.394 (3) C17—H17 0.9800
C4—C5 1.397 (3) C18—C19 1.496 (4)
C5—C6 1.377 (3) C18—H18A 0.9700
C6—C7 1.372 (3) C18—H18B 0.9700
C6—H6 0.9300 C19—H19A 0.9700
C7—C8 1.393 (3) C19—H19B 0.9700
C7—H7 0.9300 C20—H20A 0.9600
C8—C9 1.409 (3) C20—H20B 0.9600
C8—C13 1.515 (3) C20—H20C 0.9600
C9—C10 1.531 (3) C21—H21A 0.9600
C10—C20 1.530 (3) C21—H21B 0.9600
C10—C11 1.534 (3) C21—H21C 0.9600
C16—N1—C15 125.0 (2) C13—C12—H12B 110.4
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C16—N1—C11 111.78 (17) H12A—C12—H12B 108.6
C15—N1—C11 119.32 (18) C8—C13—C12 109.92 (18)
H3B—O3—H3A 99.9 C8—C13—C14 110.40 (17)
O1—C1—C5 125.8 (3) C12—C13—C14 111.49 (18)
O1—C1—C2 126.3 (2) C8—C13—H13 108.3
C5—C1—C2 107.94 (19) C12—C13—H13 108.3
C1—C2—C3 107.07 (19) C14—C13—H13 108.3
C1—C2—H2A 110.3 C21—C14—C15 110.5 (2)
C3—C2—H2A 110.3 C21—C14—C13 112.9 (2)
C1—C2—H2B 110.3 C15—C14—C13 110.37 (19)
C3—C2—H2B 110.3 C21—C14—H14 107.6
H2A—C2—H2B 108.6 C15—C14—H14 107.6
C19—C3—C4 110.54 (16) C13—C14—H14 107.6
C19—C3—C2 112.7 (2) N1—C15—C14 111.04 (18)
C4—C3—C2 103.99 (19) N1—C15—H15A 109.4
C19—C3—H3 109.8 C14—C15—H15A 109.4
C4—C3—H3 109.8 N1—C15—H15B 109.4
C2—C3—H3 109.8 C14—C15—H15B 109.4
C9—C4—C5 121.10 (19) H15A—C15—H15B 108.0
C9—C4—C3 127.80 (18) O2—C16—N1 125.8 (2)
C5—C4—C3 110.80 (18) O2—C16—C17 127.8 (2)
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C6—C5—C4 121.3 (2) N1—C16—C17 106.38 (19)
C6—C5—C1 128.6 (2) C16—C17—C18 117.2 (2)
C4—C5—C1 110.0 (2) C16—C17—C10 100.74 (16)
C7—C6—C5 118.23 (19) C18—C17—C10 122.65 (18)
C7—C6—H6 120.9 C16—C17—H17 104.9
C5—C6—H6 120.9 C18—C17—H17 104.9
C6—C7—C8 121.6 (2) C10—C17—H17 104.9
C6—C7—H7 119.2 C19—C18—C17 119.1 (2)
C8—C7—H7 119.2 C19—C18—H18A 107.5
C7—C8—C9 120.78 (19) C17—C18—H18A 107.5
C7—C8—C13 116.27 (19) C19—C18—H18B 107.5
C9—C8—C13 122.87 (18) C17—C18—H18B 107.5
C4—C9—C8 116.83 (18) H18A—C18—H18B 107.0
C4—C9—C10 121.52 (18) C18—C19—C3 114.2 (2)
C8—C9—C10 121.66 (17) C18—C19—H19A 108.7
C20—C10—C9 111.44 (16) C3—C19—H19A 108.7
C20—C10—C11 111.58 (17) C18—C19—H19B 108.7
C9—C10—C11 109.38 (16) C3—C19—H19B 108.7
C20—C10—C17 113.59 (19) H19A—C19—H19B 107.6
C9—C10—C17 112.64 (16) C10—C20—H20A 109.5
C11—C10—C17 97.40 (15) C10—C20—H20B 109.5
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N1—C11—C12 110.05 (18) H20A—C20—H20B 109.5
N1—C11—C10 101.55 (16) C10—C20—H20C 109.5
C12—C11—C10 115.70 (18) H20A—C20—H20C 109.5
N1—C11—H11 109.7 H20B—C20—H20C 109.5
C12—C11—H11 109.7 C14—C21—H21A 109.5
C10—C11—H11 109.7 C14—C21—H21B 109.5
C11—C12—C13 106.77 (18) H21A—C21—H21B 109.5
C11—C12—H12A 110.4 C14—C21—H21C 109.5
C13—C12—H12A 110.4 H21A—C21—H21C 109.5
C11—C12—H12B 110.4 H21B—C21—H21C 109.5
O1—C1—C2—C3 −176.1 (2) C9—C10—C11—N1 76.12 (19)
C5—C1—C2—C3 3.0 (3) C17—C10—C11—N1 −41.08 (18)
C1—C2—C3—C19 115.1 (2) C20—C10—C11—C12 80.8 (2)
C1—C2—C3—C4 −4.6 (3) C9—C10—C11—C12 −43.0 (2)
C19—C3—C4—C9 57.3 (3) C17—C10—C11—C12 −160.20 (19)
C2—C3—C4—C9 178.5 (2) N1—C11—C12—C13 −48.0 (2)
C19—C3—C4—C5 −116.4 (2) C10—C11—C12—C13 66.3 (2)
C2—C3—C4—C5 4.8 (2) C7—C8—C13—C12 −153.34 (18)
C9—C4—C5—C6 0.2 (3) C9—C8—C13—C12 29.8 (3)
C3—C4—C5—C6 174.37 (18) C7—C8—C13—C14 83.3 (2)
C9—C4—C5—C1 −177.33 (18) C9—C8—C13—C14 −93.6 (2)
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C3—C4—C5—C1 −3.1 (2) C11—C12—C13—C8 −55.1 (2)
O1—C1—C5—C6 1.8 (4) C11—C12—C13—C14 67.7 (2)
C2—C1—C5—C6 −177.2 (2) C8—C13—C14—C21 −138.1 (2)
O1—C1—C5—C4 179.1 (2) C12—C13—C14—C21 99.4 (2)
C2—C1—C5—C4 0.0 (2) C8—C13—C14—C15 97.7 (2)
C4—C5—C6—C7 −2.5 (3) C12—C13—C14—C15 −24.8 (3)
C1—C5—C6—C7 174.5 (2) C16—N1—C15—C14 −100.0 (2)
C5—C6—C7—C8 1.5 (3) C11—N1—C15—C14 55.9 (3)
C6—C7—C8—C9 1.8 (3) C21—C14—C15—N1 −159.0 (2)
C6—C7—C8—C13 −175.08 (19) C13—C14—C15—N1 −33.4 (3)
C5—C4—C9—C8 3.0 (3) C15—N1—C16—O2 −17.7 (3)
C3—C4—C9—C8 −170.07 (18) C11—N1—C16—O2 −175.2 (2)
C5—C4—C9—C10 −176.32 (17) C15—N1—C16—C17 163.49 (18)
C3—C4—C9—C10 10.6 (3) C11—N1—C16—C17 6.0 (2)
C7—C8—C9—C4 −4.0 (3) O2—C16—C17—C18 12.9 (3)
C13—C8—C9—C4 172.68 (18) N1—C16—C17—C18 −168.36 (18)
C7—C8—C9—C10 175.34 (17) O2—C16—C17—C10 148.5 (2)
C13—C8—C9—C10 −8.0 (3) N1—C16—C17—C10 −32.8 (2)
C4—C9—C10—C20 68.3 (2) C20—C10—C17—C16 162.14 (17)
C8—C9—C10—C20 −111.0 (2) C9—C10—C17—C16 −70.0 (2)
C4—C9—C10—C11 −167.85 (17) C11—C10—C17—C16 44.66 (18)
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C8—C9—C10—C11 12.8 (2) C20—C10—C17—C18 −65.5 (3)
C4—C9—C10—C17 −60.7 (2) C9—C10—C17—C18 62.4 (3)
C8—C9—C10—C17 119.97 (19) C11—C10—C17—C18 177.0 (2)
C16—N1—C11—C12 146.81 (18) C16—C17—C18—C19 74.1 (3)
C15—N1—C11—C12 −12.1 (3) C10—C17—C18—C19 −51.2 (3)
C16—N1—C11—C10 23.7 (2) C17—C18—C19—C3 62.2 (3)
C15—N1—C11—C10 −135.16 (19) C4—C3—C19—C18 −79.6 (2)
C20—C10—C11—N1 −160.11 (18) C2—C3—C19—C18 164.5 (2)
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D· · ·A D—H···A
O3—H3A· · ·O2i 0.90 2.03 2.888 (3) 158
O3—H3B· · ·O1ii 0.96 2.39 3.145 (3) 136
Symmetry codes: (i) x−1, y−1, z; (ii) −x+1, y−1/2, −z+3/2.
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