total synthesis of the daphniphyllum alkaloid daphenylline · total synthesis of the daphniphyllum...

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SUPPLEMENTARY INFORMATIONDOI: 10.1038/NCHEM.1694

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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

© 2013 Macmillan Publishers Limited. All rights reserved.



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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




S11

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




S12

(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,




S13

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




S14

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,




S15

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




S16

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.




S17

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.




S18

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).




S19

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%.




S20

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%.




S21

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.




S22

IV 1H and 13C NMR Spectra of Compounds




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S24




S25




S26




S27




S28




S29




S30




S31




S32




S33




S34




S35




S36




S37




S38




S39




S40




S41




S42




S43




S44




S45




S46




S48




S49




S50




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S53




S54




S56




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S58

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)




S59

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)




S60

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




S61

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.




S62

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


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.




S63

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


Δδ (ppm)

Synthetic (silica) δ 13C [ppm] 101 MHz


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




S64

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




S65

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




S66

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




S67

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*




S68

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*




S69

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)




S70

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




S71

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




S72

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




S73

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)




S74

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)




S75

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.




S76

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




S77

γ = 77.078 (2)° Prismatic, colorless

V = 2219.8 (3) Å3 0.29 × 0.22 × 0.15 mm

Data collection

CCD area detector






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]


2)/3




S78

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












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)




S79

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)




S80

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)




S81

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




S82

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*




S83

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)




S84

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*


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)




S85

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)




S86

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)




S87

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)


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




S88

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)




S89

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)




S90

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




S91

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




S92

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)




S93

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)




S94

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




S95

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




S96

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)




S97

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)




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)




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)




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)




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)




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)


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




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




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






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]




S105


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











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.


x y z Uiso*/Ueq

N1 0.5483 (3) 0.7093 (2) 0.94988 (6) 0.0557 (4)




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)




S107

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)




S108

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*


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)




S109

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)


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)




S110

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




S111

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)




S112

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




S113

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)




S114

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)




S115

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)


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.


total synthesis of the daphniphyllum alkaloid daphenylline · total synthesis of the daphniphyllum...

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