Supporting Information

Gram-Scale, Seven-Step Total Synthesis of (−)-Colchicine

Xiao Liang, † Lei Li, †,‡ Kun Wei, † and Yu-Rong Yang*,†

†
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany,
Chinese Academy of Sciences, Kunming 650201, China ‡University of Chinese Academy of Sciences, Beijing
100049, China

Email: yangyurong@mail.kib.ac.cn

Table of Contents

General Information..........................................................................................................................S2
Experimental Procedures..................................................................................................................S3
Optimization Tables......................................................................................................................S3
Synthetic Procedures and Characterization Data..........................................................................S9
Comparison of NMR data for Commercial vs. Synthetic (–)-Colchicine.............................S18
References...................................................................................................................................S20
NMR Spectral Copies....................................................................................................................S21
Crystal Data of Allocolchicinoid 17................................................................................................S29
High Resolution Mass Spectra........................................................................ ...................... ........S42

S1
General Information
Unless otherwise stated, all oxygen or moisture sensitive reactions were conducted in flame-dried
glassware under an atmosphere of nitrogen. All solvents were purified and dried according to standard
methods prior to use. (S)-L and (rac)-L were prepared according to the reported procedure.1 Reagents
were purchased from commercial sources and were used without further purification.
Chromatographic purification of products was accomplished using forced-flow chromatography
on 200-300 mesh silica gel supplied by Tsingtao Haiyang Chemicals (China). The TLC glass plates
were performed on 0.20 mm silica gel GF254 plates supplied by Yantai Chemicals (China), and
visualized with UV light (254 nm), exposure to iodine vapor, or basic aqueous potassium permanganate
(KMnO4).
1
H and 13C NMR spectra were acquired on Bruker Avance III 400 and 600 NMR spectrometer.
Chemical shifts were given in parts per million (ppm) with reference to residual solvent signals [1H
NMR: CDCl3 (7.26), 13C NMR: CDCl3 (77.16); 1H NMR:CD3OD (3.31), 13C NMR: CD3OD: (49.00)].
Peak multiplicities were recorded as follows: s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet, br = broad singlet. Infrared (IR) spectra were recorded on a BRUKER Tensor-27 Fourier-
Transform Infrared spectrometer. High resolution mass spectral (HRMS) data were obtained at the
mass spectrometry service operated at Agilent 6540 Q-TOF spectrometer for electrospray ionization
(ESI) and were reported as (m/z). X-ray diffraction was conducted using Bruker APEX DUO
diffractometer with graphite-monochromated CuKα radiation. Optical rotations were measured on a
Jasco P-1020 polarimeter. Melting points were measured on a WRX-5A melting point apparatus.
HPLC analysis was performed on an Agilent 1260 series system using Daicel Chiralpak AD-H and IC
columns with n-hexane and i-PrOH as solvents.

S2
Experimental Procedures

Optimization Tables
Ir-Catalyzed Allylic Amination Reaction with AcNH2a

General Procedure
[Ir(cod)Cl]2 (2.0 mg, 3 mol%) and (S)-L (6.0 mg, 12 mol%) were dissolved in solvent under an
atmosphere of nitrogen. The mixture was vigorously stirred for 15 min at room temperature. To the
resulting solution were added sequentially allylic alcohol (0.1 mmol, 1.0 equiv), AcNH2 (12.0 mg, 0.2
mmol, 2.0 equiv), and promoter (20 mol%). The reaction was stirred at room temperature and
monitored by TLC. The crude reaction mixture was quenched with sat. aq. NaHCO3 (5 mL) and diluted
with EtOAc (10 mL). The layers were separated and then the aqueous phase was extracted with EtOAc
(2 x 10 mL), combined organic layers dried over Na2SO4, filtered, and concentrated under reduced
pressure. The crude residue was purified by silica gel flash chromatography to afford the desired
product.

entry R promoter solvent T isolated yield (%) ee (%)b

1c TBS maleic acid DCE (0.25 M) rt trace −

2d TBS m-ClC6H4COOH DCE (0.25 M) 50 C <5 −

3 TBS Zn(OTf)2 1,4-dioxane (0.5 M) rt 30 96

4 TBS Sc(OTf)3 1,4-dioxane/DMF (5:1, 0.5 M) rt 36 98

5 TBS Sc(OTf)3 1,4-dioxane/DMF (10:1, 0.25 M) rt 36 >99

6 TBS Sc(OTf)3 1,4-dioxane/DMF (10:1, 0.25 M) 50 C 39 >99

7 TBS Sc(OTf)3 1,4-dioxane/DMF (10:1, 0.25 M) 80 C 40 92

8e TBS Sc(OTf)3 1,4-dioxane/DMF (10:1, 0.25 M) 50 C 33 95

S3
 9 TBS BF3Et2O 1,4-dioxane (0.25 M) rt 78 95

10 H BF3Et2O 1,4-dioxane (0.5 M) rt 90 >99

11f H BF3Et2O 1,4-dioxane (0.5 M) rt 93 >99

a
Unless indicated otherwise, the reactions were performed on a 0.1 mmol scale. bEnantiomeric excess was determined
by HPLC analysis (R = TBS, Chiralpak IC; R = H, Chiralpak AD-H). c0.75 equiv of promoter was used. d0.5 equiv
of promoter was used. eRun on 0.5 mmol scale. fRun on 10.0 mmol scale.

Ir-Catalyzed Allylic Amination Reaction with NH3SO3a 2

General Procedure
[Ir(coe)2Cl]2 (4.5 mg, 2.5 mol%), (S)-L (10.0 mg, 10 mol%), NH3SO3 (23 mg, 0.24 mmol, 1.2
equiv) were placed in a round bottom flask with a magnetic stir bar. The reaction vessel was purged
with nitrogen, DMF (80 μL, 1.0 mmol, 5.0 equiv) was added followed by solvent (0.33 M). After
vigorous stirring for 10 min, allylic alcohol 13 (36 mg, 0.2 mmol, 1.0 equiv) was added to the reaction
mixture. The reaction was stirred at room temperature for 24 h. Et3N (0.11 mL, 0.8 mmol, 4.0 equiv.)
was then added followed by AcCl (28 μL, 0.4 mmol, 2.0 equiv) and the resulting mixture was stirred
at room temperature for 4 h. The reaction was then purified by flash chromatography (petroleum
ether/EtOAc 1:1 to 1:2) to give the resulting products 14 and 14.

entry solvent yield of 14 (%)b yield of 14 (%)b ee of 14 (%)c

1 DCE <5 42 86

2 1,4-dioxane 36 30 87

3 2-MeTHF 27 30 88
a
Unless indicated otherwise, the reactions were performed on a 0.2 mmol scale. bIsolated yields. c Enantiomeric
excess was determined by HPLC analysis (Chiralpak AD-H).

S4
Suzuki Cross-Coupling Reaction a

entry conditions isolated yield (%)

BH3·THF (1.2 eq.), 0 °C to rt, then H2O (15.0 eq.), 15 (1.2 eq.), Pd(PPh3)4
1 −
(10 mol%), K3PO4 (2.0 eq.), toluene, 85 C.

9-BBN (2.0 eq.), 50 °C, then H2O (15.0 eq.), 15 (1.2 eq.), Pd(PPh3)4 (10
2 23
mol%), K3PO4 (2.0 eq.), 1, 4-dioxane, 85 C.

9-BBN (4.0 eq.) 50 °C, then H2O (15.0 eq.), 15 (1.2 eq.), Pd(dppf)Cl2 (3
3 21
mol%), AsPh3 (3 mol%), Cs2CO3 (2.0 eq.), DMF, 50 C.

9-BBN (2.0 eq.) rt to 50 °C, then 15 (2.0 eq.), Pd(dppf)Cl2 (3 mol%), CsF
4 34
(3.0 eq.), 60 C.

9-BBN (3.0 eq.) 0 °C to rt, then 15 (2.0 eq.), Pd(dppf)Cl2 (3 mol%), CsF
5 51
(3.0 eq.), 60 C.

9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (2.0 eq.), Pd(dppf)Cl2 (3
6 30
mol%), CH3ONa (3.0 eq.), 75 C.

9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (3.0 eq.), Pd(PPh3)4 (10 mol%),
7 28
Ba(OH)2·8H2O (3.0 eq.), reflux.

9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (3.0 eq.), Pd(PPh3)4 (10 mol%),
8 25
NaOH (3.0 eq.), reflux.

9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (2.0 eq.), Pd(OAc)2 (10 mol%),
9 42
Xphos (15 mol%), KF (3.0 eq.), 60 C.

9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (2.0 eq.), Pd(OAc)2 (10 mol%),
10 10
PPh3 (30 mol%), DIPEA (10.0 eq), 70 C.

9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (2.0 eq.), Pd(OAc)2 (10 mol%),
11 30
PCy3 (30 mol%), DIPEA (10.0 eq.), 70 °C.

S5
 9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (2.0 eq.), Pd(OAc)2 (10 mol%),
12 10
Xphos (15 mol%), DIPEA (10.0 eq.), 70 °C.

9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (3.0 eq.), Pd(PPh3)4 (5 mol%),
13 50
Et3N (10.0 eq.), reflux.

9-BBN (3.0 eq.), rt, then H2O (15.0 eq.), 15 (3.0 equiv), Pd(PPh3)4 (10
14 25
mol%), DIPEA (10.0 equiv), reflux.

9-BBN (3.0 eq.), 0 °C to rt, then H2O (15.0 eq.), 15 (1.2 eq.), Pd(PPh3)4 (10
15 62
mol%), K3PO4 (2.0 eq.), DMF, reflux.

9-BBN (3.0 eq.), 0 °C to rt, then H2O (15.0 eq.), 15 (3.0 eq.), Pd(PPh3)4 (5
16b 65
mol%) K3PO4 (3.0 eq.), DMF, reflux.

9-BBN (3.0 eq.), 0 °C to rt, then H2O (15.0 eq.), 15 (3.0 eq.), Pd(PPh3)4 (5
17c 56
mol%), K3PO4 (3.0 eq.), DMF, reflux.
a
Unless indicated otherwise, the reactions were performed on a 0.1 – 0.2 mmol scale. bRun on 2.0 mmol scale. cRun
on 9.28 mmol scale.

Intermolecular Heck-Hydrogenation Reaction 3

Note: the reaction was performed on 0.2 mmol scale, and the isolated yield of 16 was improved
while the enantiomeric excess significantly decreased.

S6
Intramolecular Oxidative Coupling Reaction of Compound 16a

entry conditions yield (%) b

1 PhI(OAc)2 (1.0 eq.), AcOH (2.0 eq.), HFIP, rt trace

2 PIFA (1.0 eq.), MeOH, rt, then evaporation, BF3 Et2O (2.0 eq.), DCM, –40 °C. 53

3 PIFA (1.0 eq.), BF3Et2O (2.0 eq.). TFA/TFAA/DCM (4:1:5), –40 °C. 54

4 PIFA (1.0 eq.), MeOH, rt, then evaporation, Sc(OTf)3 (0.2 eq.), DCM, 0 °C. 55

5 PIFA (1.0 eq.), MsOH (2.0 eq.), THF, rt, then Na2S2O3 (0.1 eq.), 80 °C. trace

6 PIFA (1.0 eq.), BF3·Et2O (2.0 eq.), THF/MeOH (5:1), rt 35

7 PIFA (1.0 eq.), BF3·Et2O (2.0 eq.), DCM/MeOH (5:1), rt.. 59

8 (t-Bu-O)2 (3.0 eq.), FeCl3 (0.15 eq.), HFIP, rt. −

9 H5IO6 (0.5 eq.), DMF (2.5 eq.), HFIP, rt. −

10 PIFA (1.0 eq.), BF3·Et2O (2.0 eq.), HFIP, 0 °C to rt. trace

11 K2S2O8 (2.0 eq.), TBAHS (0.1 eq.), TFA, rt. <5

12 PIFA (1.0 eq.), TFA/DCM (2:1), rt. 50

13 PIFA (1.0 eq.), AcOH/DCM (2:1), rt. 45

14 PIFA (1.0 eq.), MeOH/TFA (5:1), rt. 42

15 PIFA (1.0 eq.), MeOH, rt; no evaporation, then BF3 Et2O (3.0 eq.), DCM, rt 78

15 PhI(OAc)2 (1.0 eq.), MeOH, rt; no evaporation, then BF3 Et2O (3.0 eq.), DCM, rt 82

16c PhI(OAc)2 (1.0 eq.), MeOH, rt; no evaporation, then BF3 Et2O (3.0 eq.), DCM, rt 80
a
Unless indicated otherwise, the reactions were performed on a 0.05 mmol scale. bIsolated yields. cRun on 1.3 mmol
scale.

S7
Cyclopropane Ring-Cleavage Reaction of Compound 19a

entry acid eq. of acid additive T (C) t (h) yield (%)b 1/1c

1 TFA 10.0 − rt 1 80 1:1

2 BF3·Et2O 1.1 − rt 0.25 84 1:3.3

3 p-TSA·H2O 1.1 − rt 1 82 1:6.3

4 BF3·Et2O 2.2 4 Å molecular sieves rt 18 65 1:2.7

5 TFA 10.0 4 Å molecular sieves rt 12 78 3.6:1

6 TFA 10.0 4 Å molecular sieves 40 2 88 8:1

a
Unless indicated otherwise, the reactions were performed on a 0.025 mmol scale. bYields of 1 plus 1. cDetermined
by 1H NMR of crude reaction mixture.

S8
Synthetic Procedures and Characterization Data

To a solution of isovanillin 12 (1.52 g, 10.0 mmol, 1.0 equiv) in THF (150 mL) was added a
solution of vinylmagnesium bromide (40 mL, 1.0 M in THF, 40.0 mmol, 4.0 equiv) at 0 °C in an ice
bath. The reaction mixture was stirred for 10 min at 0 °C and then quenched with sat. aq. NH4Cl (30
mL), The layers were separated and then the aqueous phase was extracted with EtOAc (2 × 100 mL),
combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under
reduced pressure. The crude residue 13 was used in the subsequent step without further purification.
A flame-dried100 mL round-bottom flask equipped with a stir bar was charged with [Ir(cod)Cl]2
(201 mg, 0.3 mmol, 3 mol%), (S)-L (611 mg, 1.2 mmol, 12 mol%) and 1,4-dioxane (15 mL) under an
atmosphere of nitrogen. After vigorous stirring for 10 min at room temperature, a solution of the crude
product 13 in 5 mL 1,4-dioxane obtained in the prior transformation, AcNH2 (1.18 g, 20.0 mmol, 2.0
equiv), and promoter BF3·Et2O (252 μL, 2.0 mmol, 20 mol%) were added sequentially to the resulting
solution. The reaction mixture was stirred for 30 min at room temperature and then quenched with sat.
aq. NaHCO3 (5 mL). The layers were separated and then the aqueous phase was extracted with EtOAc
(2 × 50 mL), combined organic layers were washed with brine, dried over Na2SO4, filtered, and
concentrated under reduced pressure. The crude residue was purified by silica gel flash
chromatography (petroleum ether/EtOAc 1:1 to 1:2) to afford the desired product 14 (2.05 g, 93%
yield, 2 steps) as a yellow oil.

Data for compound 13

Compound 13 was isolated for characterization purposes by purifying a small amount of crude by
column chromatography (petroleum ether/EtOAc 2:1).
Rf: 0.31 (petroleum ether/EtOAc 2:1).
Physical state: white solid
m.p.: 93 − 95 C.

S9
1H NMR (400 MHz, CDCl3) δ 6.95 (s, 1H), 6.85 (q, J = 8.3 Hz, 2H), 6.03 (ddd, J = 16.8, 10.3, 5.9 Hz,
1H), 5.65 (s, 1H), 5.34 (d, J = 17.1 Hz, 1H), 5.18 (d, J = 10.3 Hz, 1H), 5.12 (d, J = 5.3 Hz, 1H), 3.89
(s, 3H), 1.92 (s, 1H).
13C NMR (100 MHz, CDCl3) δ 146.3, 145.8, 140.3, 136.2, 118.1, 115.0, 112.9, 110.7, 75.1, 56.1.
IR (KBr): 3447, 3192, 2897, 1615, 1599, 1537, 1437, 1386, 1279, 1255, 1181, 1159, 1026, 976, 869,
809, 763, 488 cm-1.
HRMS (ESI): calc. for C10H11O3 [M−H]−: 179.0714, found: 179.0714.

Data for compound 14

Rf: 0.63 (EtOAc).
Physical state: yellow oil
1H NMR (400 MHz, CDCl3) δ 6.86 (s, 1H), 6.83 − 6.76 (m, 2H), 5.97 (ddd, J = 15.9, 10.4, 5.1 Hz,
1H), 5.80 – 5.67 (m, 1H), 5.74 (s, 1H), 5.60 – 5.48 (m, 1H), 5.29 – 5.15 (m, 2H), 3.88 (s, 3H), 2.02
(s, 3H).
13C NMR (100 MHz, CDCl3) δ 169.3, 146.3, 146.0, 137.4, 133.9, 119.1, 115.6, 113.6, 110.9, 56.1,
54.8, 23.5.
IR (KBr): 3281, 3084, 2841, 1651, 1636, 1511, 1441, 1276, 1133, 1028, 812, 762, 610 cm-1.
HRMS (ESI): calc. for C12H14NO3 [M−H]−: 220.0979, found: 220.0979.
Optical rotation: [α]D23.0 = −108.17 (c 0.82, CHCl3).
HPLC analysis indicated that the enantiomeric excess of the product was >99% [Diacel Chiralpak
AD-H; hexanes/i-PrOH = 80/20; flow rate =1.0 mL/min; 25 C; detection wavelength = 210 nm; t1 =
10.128 min; t2 = 11.126 min (major)].
Racemicte compound 14 was acquired by using the above procedure with racemic ligand (rac)-L
instead of (S)-L.

S10
rac-14

S11
 To a solution of compound 14 (2.05 g, 9.28 mmol, 1.0 equiv) in THF (5 mL) was added a solution
of 9-BBN (56 mL, 0.5 M in THF, 27.8 mmol, 3.0 equiv) at 0 °C in an ice bath. The reaction mixture
was warmed up slowly to room temperature and stirred for 4 h. And then the reaction was cooled down
to 0 C in an ice bath, quenched with H2O (2.5 mL,139 mmol, 15.0 equiv) and vigorously stirred for
another 15 min. To the resulting mixture were added successively 15 (6.8 g, 27.8 mmol, 3.0 equiv),
Pd(PPh3)4 (535 mg, 0.5 mmol, 5 mol%), powdered K3PO4 (5.9 g, 27.8 mmol, 3.0 equiv) and DMF (9
mL,1.0 M). The resulting solution was degassed under a stream of nitrogen for 0.5 h, and then heated
to reflux in an oil bath and stirred for 2 h. After the mixture was cooled down to room temperature,
quenched with H2O (30 mL) and diluted with EtOAc (100 mL). The layers were separated and the
aqueous phase was extracted with EtOAc (2 × 100 mL), combined organic layers were washed with
brine (3 × 10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude
residue was purified by silica gel flash chromatography (petroleum ether/EtOAc 1:1 to 1:2) to afford
the desired product 16 (2.02g, 56% yield) as a yellow oil.

Data for compound 16

Rf: 0.58 (EtOAc).
Physical state: yellow oil.
1H NMR (400 MHz, CDCl3) δ 6.87 (s, 1H), 6.83 − 6.75 (m, 2H), 6.35 (s, 2H), 5.92 (s, 1H), 5.79 (d, J
= 8.2 Hz, 1H), 4.91 (q, J = 7.6 Hz, 1H), 3.86 (s, 3H), 3.82 (s, 6H), 3.80 (s, 3H), 2.60 − 2.41 (m, 2H),
2.22 – 2.08 (m, 1H), 2.07 − 1.94 (m, 1H), 1.95 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 169.4, 153.2, 146.2, 146.1, 137.3, 136.2, 135.1, 118.8, 112.7, 110.9,
105.3, 60.9, 56.2, 56.1, 53.1, 37.6, 33.1, 23.6.
IR (KBr): 3355, 2939, 2839, 1652, 1591, 1509, 1459, 1275, 1240, 1127, 1008, 811, 763, 598 cm-1.
HRMS (ESI): calc. for C21H27NO6Na [M+Na]+: 412.1731, found: 412.1730.
Optical rotation: [α]D20.8 = −52.52 (c 0.46, CHCl3).

S12
 To a solution of compound 16 (2.02 g, 5.2 mmol, 1.0 equiv) in MeOH (10 mL, 0.5 M) was added
solid PhI(OAc)2 (1.67 g, 5.2 mmol, 1.0 equiv) at room temperature. After stirring for 5 min, this
mixture was transferred slowly to a solution of BF3·Et2O (2.0 mL, 15.6 mmol, 3.0 equiv) in DCM (520
mL, 0.01 M) via the syringe over 30 min. The reaction mixture was stirred for 10 min and quenched
with sat. aq. NaHCO3 (30 mL). The layers were separated and the aqueous phase was extracted with
CHCl3 (3 × 50 mL), combined organic layers were washed with brine, dried over Na2SO4, filtered, and
concentrated under reduced pressure. The crude residue 17 was used in the subsequent step without
further purification.
The above crude reside 17 was dissolved in MeOH (26 mL, 0.2 M), and powered NaHCO3 (872
mg, 10.4 mmol, 2.0 equiv), PhI(OAc)2 (1.67 g, 5.2 mmol, 1.0 equiv) were added at room temperature.
After stirring for 5 min, the reaction mixture was quenched with sat. aq. Na2S2O3 (20 mL) and diluted
with Et2O/EtOAc (1:1, 80 mL), the layers were separated and the aqueous phase was extracted with
Et2O/EtOAc (1:1, 4 × 80 mL), combined organic layers were washed with brine, dried over Na2SO4,
filtered, and concentrated under reduced pressure. The crude residue 18 was used in the subsequent
step without further purification.

S13
 To a solution of trimethyl sulfoxonium iodide (2.2 g, 10 mmol) in DMSO (20 mL) was added
slowly NaH (440 mg, 60% dispersion in mineral oil, 11 mmol) at room temperature, and the resulting
mixture was stirred at room temperature until gas evolution had ceased. An aliquot (10.5 mL, 1.0 equiv)
of this solution was added dropwise via the syringe to a stirred solution of the above crude residue 18
in DMSO (13 mL, 0.4 M). The reaction mixture was stirred at room temperature for 10 min, and then
poured into water and extracted with Et2O/EtOAc (1:1, 4 × 80 mL), The combined organic phase was
washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude
residue 19 was used in the subsequent step without further purification.
A solution of the above crude residue 19 in DCM (100 mL, 0.05 M) was treated with 4 Å molecular
sieves (6.0 g) at room temperature. After stirring for 15 min, TFA (3.8 mL, 52 mmol, 10.0 equiv) was
added dropwise to the resulting suspension. The reaction was heated to 40 C in an oil bath and stirred
for 2 h. And then the mixture was cooled to room temperature, quenched with sat. aq. NaHCO3 (50
mL), the layers were separated and the aqueous phase was extracted with CHCl3(4 ×50 mL), combined
organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced
pressure. The crude residue was purified by silica gel flash chromatography (petroleum ether/acetone
1:1 to 1:4) to afford colchicine 1 (1.1 g, 53% yield, 4 steps) as a dark yellow solid.

Data for compound 17 4

Compound 17 was isolated for characterization purposes by purifying a small amount of crude by
column chromatography (petroleum ether/EtOAc 1:1 to 1:4). A sample of compound 17 for X-ray
analysis was recrystallized from n-hexane/ acetone (2:1) via slow evaporation to afford colorless
needles.
Rf: 0.43 (EtOAc).
Physical state: light yellow solid.
m.p.: 130 − 133 C.
1H NMR (600 MHz, CD3OD): δ 7.00 (s, 1H), 6.80 (s, 1H), 6.72 (s, 1H), 4.58 (dd, J = 12.4, 6.0 Hz,
1H), 3.88 (s, 3H), 3.87 (s, 3H), 3.85 (s, 3H), 3.53 (s, 3H), 2.56 – 2.44 (m, 1H), 2.31 – 2.21 (m, 2H),
2.00 (s, 3H), 1.94 – 1.86 (m, 1H).
13C NMR (150 MHz, CD3OD): δ 172.4, 153.8, 152.0, 147.3, 147.0, 142.4, 136.9, 134.0, 126.7, 126.6,
114.8, 111.2, 109.1, 61.6, 61.3, 56.7, 56.6, 50.0, 40.3, 31.6, 22.6.

S14
IR (ATR): 3296, 2936, 2837, 1655, 1589, 1510, 1490, 1406, 1294, 1240, 1127, 1106, 1050, 780 cm-1.
HRMS (ESI): calc. for C21H25NO6Na [M+Na]+: 410.1574, found: 410.1573.
Optical rotation: [α]D20.8 = −45.32 (c 0.75, CHCl3).

Data for compound 18

Compound 18 was isolated for characterization purposes by purifying a small amount of crude by
column chromatography (petroleum ether/EtOAc 1:1 to 1:2).
Rf: 0.52 (EtOAc).
Physical state: yellow viscous oil.
1H NMR (400 MHz, CDCl3) δ 6.49 (s, 1H), 6.43 (s, 1H), 6.11 (d, J = 7.8 Hz, 1H), 6.01 (s, 1H), 4.57
– 4.44 (m, 1H), 3.89 (s, 3H), 3.87 (s, 3H), 3.76 (s, 3H), 3.43 (s, 3H), 3.41 (s, 3H), 2.72 (td, J = 13.5,
6.9 Hz, 1H), 2.59 (dd, J = 13.8, 6.2 Hz, 1H), 2.18 (tt, J = 13.2, 6.9 Hz, 1H), 1.98 (s, 3H), 1.73 – 1.62
(m, 1H).
13C NMR (100 MHz, CDCl3) δ 195.5, 169.4, 156.9, 153.6, 152.1, 141.7, 135.7, 133.8, 132.8, 121.9,
118.6, 107.8, 91.9, 61.7, 61.4, 56.2, 50.7, 50.3, 49.7, 34.0, 30.3, 23.2.
IR (KBr): 3371, 2941, 2836, 1672, 1596, 1538, 1490, 1460, 1324, 1105, 869, 753, 598 cm-1.
HRMS (ESI): calc. for C22H27NO7Na [M+Na]+: 440.1680, found: 440.1683.
Optical rotation: [α]D21.2 = 36.74 (c 0.55, CHCl3).

Data for compound 19

Compound 19 was isolated for characterization purposes by purifying a small amount of crude by
column chromatography (petroleum ether/EtOAc 1:1 to 1:5).
Rf: 0.32 (EtOAc).
Physical state: light yellow oil.
1H NMR (600 MHz, CD3OD) δ 6.76 (s, 1H), 5.68 (d, J = 1.1 Hz, 1H), 4.25 (dd, J = 11.6, 6.7 Hz, 1H),
3.86 (s, 3H), 3.82 (s, 3H), 3.73 (s, 3H), 3.49 (s, 3H), 3.26 – 3.20 (m, 4H), 2.79 (dd, J = 13.9, 8.2 Hz,
1H), 2.10 – 2.00 (m, 1H), 1.94 (s, 3H), 1.86 (td, J = 12.2, 8.6 Hz, 1H), 1.36 (dd, J = 9.0, 4.0 Hz, 1H),
1.14 (dd, J = 7.3, 4.0 Hz, 1H).
13C NMR (150 MHz, CD3OD) δ 190.9, 172.2, 171.4, 154.6, 154.2, 142.6, 138.6, 124.2, 115.9, 110.0,
97.2, 63.1, 61.6, 56.6, 52.4, 51.0, 49.3, 34.8, 33.2, 30.2, 29.8, 27.1, 22.4.

S15
IR (KBr): 3344, 2940, 2836, 1671, 1537, 1488, 1463, 1324, 1240, 1111, 1043, 761, 595 cm-1.
HRMS (ESI): calc. for C23H29NO7Na [M+Na]+: 454.1836, found: 454.1834.
Optical rotation: [α]D22.9 = −63.03 (c 0.54, CHCl3).

Data for colchicine 1

Rf: 0.38 (acetone).
Physical state: dark yellow solid.
m.p.: 144 − 146 C.
1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 5.9 Hz, 1H), 7.64 (s, 1H), 7.33 (d, J = 10.7 Hz, 1H), 6.88
(d, J = 10.9 Hz, 1H), 6.51 (s, 1H), 4.63 dt, J = 11.7, 5.6 Hz, 1H), 3.99 (s, 3H), 3.91 (s, 3H), 3.88 (s,
3H), 3.63 (s, 3H), 2.57 − 2.42 (m, 1H), 2.41 – 2.26 (m, 2H), 2.02 − 1.90 (m, 1H), 1.92 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 179.6, 170.3, 164.1, 153.6, 153.0, 151.2, 141.7, 137.2, 135.8, 134.4,
130.4, 125.6, 113.1, 107.4, 61.6, 61.4, 56.5, 56.2, 52.9, 36.3, 29.9, 22.7.
IR (KBr): 3431, 3281, 2938, 2839, 1664, 1616, 1589, 1564, 1488, 1252, 1140, 1094, 1019, 843, 485
cm-1.
HRMS (ESI): calc. for C22H25NO6Na [M+Na]+: 422.1574, found: 422.1576.
Optical rotation: [α]D24.8 = −129.75 (c 0.54, CHCl3).

HPLC analysis indicated that the enantiomeric excess of the product was >99% [Diacel Chiralpak
AD-H; hexanes/i-PrOH = 80/20; flow rate =1.0 mL/min; 25 C; detection wavelength = 210 nm; t1 =
8.226 min; t2 = 13.395 min (major)].

S16
rac-1

Comparison of 1H NMR Data for Commercial vs. Synthetic (–)-Colchicine5

S17
 Commercially Available (–)-Colchicine (1)
Synthetic (–)-Colchicine (1)
Position (Purchased from Aladdin Industrial Corporation)
1H
NMR, 400 MHz, CD3Cl
1H
NMR, 400 MHz, CD3Cl

4 6.52 (s, 1H) 6.51 (s, 1H)

5 2.50 (m, 1H); 2.35 (m, 1H) 2.49 (m, 1H); 2.34 (m, 1H)

6 2.35 (m, 1H); 1.96 (m, 1H) 2.34 (m, 1H); 1.95 (m, 1H)

7 4.64 (dt, J = 11.8, 5.7 Hz, 1H 4.63 (dt, J = 11.7, 5.6 Hz, 1H)

8 7.63 (s, 1H) 7.64 (s, 1H)

11 6.89 (d, J = 10.9 Hz, 1H) 6.88 (d, J = 10.9 Hz, 1H)

12 7.34 (d, J = 10.7 Hz, 1H) 7.33 (d, J = 10.7 Hz, 1H)

14 1.94 (s, 3H) 1.92 (s, 3H)

1-OCH3 3.64 (s, 3H) 3.63 (s, 3H)

2-OCH3 3.93 (s, 3H) 3.91 (s, 3H)

3-OCH3 3.89 (s, 3H) 3.88 (s, 3H)

10-OCH3 4.00 (s, 3H) 3.99 (s, 3H)

NH 8.38 (d, J = 6.0 Hz, 1H) 8.53 (d, J = 5.9 Hz, 1H)

S18
Comparison of 13C NMR Data for Commercial vs. Synthetic (–)-Colchicine5

Commercially Available (–)-Colchicine (1)

Synthetic (–)-Colchicine (1)
Position (Purchased from Aladdin Industrial Corporation)
1H NMR, 400 MHz, CD3Cl
1
H NMR, 400 MHz, CD3Cl

1 151.3 151.2

2 141.7 141.7

3 153.6 153.6

4 107.4 107.3

4a 134.4 134.4

5 30.0 29.9

6 36.4 36.3

7 52.9 52.9

7a 152.9 153.0

8 130.5 130.4

9 179.6 179.6

10 164.1 164.1

11 113.1 113.1

12 135.8 135.8

12a 137.2 137.2

12b 125.7 125.6

13 170.3 170.3

14 22.8 22.7

1-OCH3 61.7 61.6

2-OCH3 61.5 61.4

3-OCH3 56.2 56.2

10-OCH3 56.6 56.5

S19
References
[1] Difieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew. Chem. Int. Ed., 2007, 46, 3139.
[2] Lafrance, M.; Roggen, M.; Carreira, E. M. Angew. Chem. Int. Ed., 2012, 51, 3470.
[3] Geoghegan, K.; Kelleher, S.; Evans, P. J. Org. Chem., 2011, 76, 2187.
[4] Takubo, K.; Furutsu, K.; Ide, T.; Nemoto, H., Ueda, Y.; Tsujikawa, K.; Ikawa, T.; Yoshimitsu, T.;
Akai, S. Eur. J. Org. Chem., 2016, 8, 1562.
[5] Meksuriyen, D.; Lin, L. J.; Cordell, G. A.; Mukhopadhyay, S.; Banerjee, S. K. J. Nat. Prod., 1988,
51, 88.

S20
NMR Spectra

S21
S22
S23
S24
S25
S26
S27
 Commercial
400 MHz, CDCl3

Synthetic
400 MHz, CDCl3

Commercial
100 MHz, CDCl3

Synthetic
100 MHz, CDCl3

S28
Crystal data for compound 17: C21H25NO6·C3H6O, M = 445.50, a = 10.0751(2) Å, b = 11.1470(2)
Å, c = 10.2012(2) Å, α = 90°, β = 93.3300(10)°, γ = 90°, V = 1143.73(4) Å3, T = 100(2) K, space group
P21, Z = 2, μ(CuKα) = 0.783 mm-1, 11302 reflections measured, 3768 independent reflections (Rint =
0.0353). The final R1 values were 0.0346 (I > 2σ(I)). The final wR(F2) values were 0.0906 (I > 2σ(I)).
The final R1 values were 0.0346 (all data). The final wR(F2) values were 0.0906 (all data). The
goodness of fit on F2 was 1.054. Flack parameter = 0.11(4).

Displacement ellipsoids are drawn at the 30% probability level.

Table 1 Crystal data and structure refinement for compound 17.

Identification code cu_af16070_0m

Empirical formula C24H31NO7
Formula weight 445.50
Temperature/K 100
Wavelength 1.54178 Å
Crystal system Monoclinic
Space group P21
Unit cell dimensions a = 10.0751(2) Å α = 90.
b = 11.1470(2) Å β = 93.3300(10).
c = 10.2012(2) Å γ = 90.
Volume 1143.73(4) Å3
Z 2

S29
Density (calculated) 1.294 g/cm3
Absorption coefficient 0.783 mm−1
F(000) 476
Crystal size 0.850 × 0.640 × 0.340 mm3
Theta range for data collection 4.341 to 69.270°.
Index ranges −12<=h<=11, −13<=k<=12, −10<=l<=11
Reflections collected 11302
Independent reflections 3768 [Rint = 0.0353]
Completeness to theta = 67.679° 96.0 %
Absorption correction Semi-empirical from equivalents
Refinement method Full-matrix least-squares on F2
Data/restraints/parameters 3768/1/298
Goodness-of-fit on F2 1.054
Final R indices [I>2sigma(I)] R1 = 0.0346, wR2 = 0.0906
R indices (all data) R1 = 0.0346, wR2 = 0.0906
Absolute structure parameter 0.11 (4)
Extinction coefficient 0.0206 (15)
Largest diff. peak and hole 0.254 and −0.224 e Å−3

S30
Table 2 Atomic Coordinates (× 104) and Equivalent Isotropic Displacement Parameters (Å2 ×
103) for cu_af16070_0m. Ueq is defined as one third of the trace of the orthogonalized UIJ
tensor.

x y z U(eq)

N(1) 1767(2) −294(2) 3173(2) 22(1)

O(2) 2412(2) 1630(2) 3163(2) 33(1)

O(3) −2211(2) 2130(2) 8235(2) 26(1)

O(4) 2447(1) 2030(2) 8206(2) 22(1)

O(5) 5913(2) −1824(2) 5590(2) 32(1)

O(6) 5721(2) −1398(2) 8166(2) 28(1)

O(7) 5811(4) 873(4) 1692(4) 119(2)

O(1) 138(2) 3176(2) 8692(2) 24(1)

C(1) 194(3) 3283(3) 10087(3) 36(1)

C(2) 100(2) 2024(2) 8214(2) 20(1)

C(3) 1267(2) 1450(2) 7888(2) 18(1)

C(4) 1224(2) 343(2) 7240(2) 19(1)

C(5) 2461(2) −253(2) 6830(2) 20(1)

C(6) 2584(2) −526(2) 5500(2) 19(1)

C(7) 1414(2) −272(2) 4535(2) 20(1)

C(8) 2249(2) 672(2) 2581(2) 21(1)

C(9) −3492(2) 1617(3) 7908(3) 35(1)

C(10) −1130(2) 1474(2) 7904(2) 22(1)

C(11) 3038(2) 2540(2) 7080(2) 25(1)

C(12) −14(2) −180(2) 6913(2) 20(1)

C(13) −66(2) −1343(2) 6145(2) 23(1)

C(14) 266(2) −1156(2) 4707(2) 24(1)

C(15) 2570(3) 505(2) 1175(3) 31(1)

C(16) 3757(2) −1042(2) 5114(2) 23(1)

S31
 C(17) 4788(2) −1321(2) 6021(2) 22(1)

C(18) 4653(2) −1078(2) 7350(2) 22(1)

C(19) 5509(3) −1472(3) 9524(3) 34(1)

C(20) 3503(2) −530(2) 7747(2) 20(1)

C(21) −1186(2) 378(2) 7257(2) 21(1)

C(22) 8115(4) 778(4) 1831(4) 61(1)

C(23) 6799(4) 854(3) 2398(4) 53(1)

C(24) 6753(4) 876(3) 3866(4) 57(1)

Table 3 Bond Lengths [Å] and Angles [°] for Compound 17

N(1)-C(8) 1.339(3) N(1)-C(7) 1.455(3)

N(1)-H(1) 0.8800 O(2)-C(8) 1.228(3)

O(3)-C(10) 1.370(3) O(3)-C(9) 1.433(3)

O(4)-C(3) 1.376(3) O(4)-C(11) 1.441(3)

O(5)-C(17) 1.360(3) O(5)-H(5) 0.8400

O(6)-C(18) 1.369(3) O(6)-C(19) 1.416(3)

O(7)-C(23) 1.193(4) O(1)-C(2) 1.373(3)

O(1)-C(1) 1.426(3) C(1)-H(1A) 0.9800

C(1)-H(1B) 0.9800 C(1)-H(1C) 0.9800

C(2)-C(3) 1.396(3) C(2)-C(10) 1.402(3)

C(3)-C(4) 1.399(3) C(4)-C(12) 1.399(3)

C(4)-C(5) 1.493(3) C(5)-C(20) 1.400(3)

C(5)-C(6) 1.402(3) C(6)-C(16) 1.391(3)

C(6)-C(7) 1.519(3) C(7)-C(14) 1.537(3)

C(7)-H(7) 1.0000 C(8)-C(15) 1.501(3)

C(9)-H(9A) 0.9800 C(9)-H(9B) 0.9800

C(9)-H(9C) 0.9800 C(10)-C(21) 1.388(3)

C(11)-H(11A) 0.9800 C(11)-H(11B) 0.9800

S32
C(11)-H(11C) 0.9800 C(12)-C(21) 1.397(3)

C(12)-C(13) 1.514(3) C(13)-C(14) 1.538(3)

C(13)-H(13A) 0.9900 C(13)-H(13B) 0.9900

C(14)-H(14A) 0.9900 C(14)-H(14B) 0.9900

C(15)-H(15A) 0.9800 C(15)-H(15B) 0.9800

C(15)-H(15C) 0.9800 C(16)-C(17) 1.385(3)

C(16)-H(16) 0.9500 C(17)-C(18) 1.398(3)

C(18)-C(20) 1.391(3) C(19)-H(19A) 0.9800

C(19)-H(19B) 0.9800 C(19)-H(19C) 0.9800

C(20)-H(20) 0.9500 C(21)-H(21) 0.9500

C(22)-C(23) 1.479(6) C(22)-H(22A) 0.9800

C(22)-H(22B) 0.9800 C(22)-H(22C) 0.9800

C(23)-C(24) 1.501(5) C(24)-H(24A) 0.9800

C(24)-H(24B) 0.9800 C(24)-H(24C) 0.9800

C(8)-N(1)-C(7) 122.12(19) C(8)-N(1)-H(1) 118.9

C(7)-N(1)-H(1) 118.9 C(10)-O(3)-C(9) 116.6(2)

C(3)-O(4)-C(11) 112.87(17) C(17)-O(5)-H(5) 109.5

C(18)-O(6)-C(19) 116.85(18) C(2)-O(1)-C(1) 115.55(18)

O(1)-C(1)-H(1A) 109.5 O(1)-C(1)-H(1B) 109.5

H(1A)-C(1)-H(1B) 109.5 O(1)-C(1)-H(1C) 109.5

H(1A)-C(1)-H(1C) 109.5 H(1B)-C(1)-H(1C) 109.5

O(1)-C(2)-C(3) 120.46(19) O(1)-C(2)-C(10) 119.65(19)

C(3)-C(2)-C(10) 119.4(2) O(4)-C(3)-C(2) 117.19(19)

O(4)-C(3)-C(4) 121.91(18) C(2)-C(3)-C(4) 120.9(2)

C(12)-C(4)-C(3) 118.8(2) C(12)-C(4)-C(5) 119.7(2)

C(3)-C(4)-C(5) 121.39(19) C(20)-C(5)-C(6) 119.5(2)

C(20)-C(5)-C(4) 121.13(19) C(6)-C(5)-C(4) 119.3(2)

C(16)-C(6)-C(5) 119.2(2) C(16)-C(6)-C(7) 122.26(19)

C(5)-C(6)-C(7) 118.51(19) N(1)-C(7)-C(6) 113.12(18)

S33
N(1)-C(7)-C(14) 109.00(18) C(6)-C(7)-C(14) 111.55(18)

N(1)-C(7)-H(7) 107.6 C(6)-C(7)-H(7) 107.6

C(14)-C(7)-H(7) 107.6 O(2)-C(8)-N(1) 121.6(2)

O(2)-C(8)-C(15) 122.7(2) N(1)-C(8)-C(15) 115.8(2)

O(3)-C(9)-H(9A) 109.5 O(3)-C(9)-H(9B) 109.5

H(9A)-C(9)-H(9B) 109.5 O(3)-C(9)-H(9C) 109.5

H(9A)-C(9)-H(9C) 109.5 H(9B)-C(9)-H(9C) 109.5

O(3)-C(10)-C(21) 125.1(2) O(3)-C(10)-C(2) 114.6(2)

C(21)-C(10)-C(2) 120.20(19) O(4)-C(11)-H(11A) 109.5

O(4)-C(11)-H(11B) 109.5 H(11A)-C(11)-H(11B) 109.5

O(4)-C(11)-H(11C) 109.5 H(11A)-C(11)-H(11C) 109.5

H(11B)-C(11)-H(11C) 109.5 C(21)-C(12)-C(4) 120.6(2)

C(21)-C(12)-C(13) 120.4(2) C(4)-C(12)-C(13) 118.9(2)

C(12)-C(13)-C(14) 112.00(18) C(12)-C(13)-H(13A) 109.2

C(14)-C(13)-H(13A) 109.2 C(12)-C(13)-H(13B) 109.2

C(14)-C(13)-H(13B) 109.2 H(13A)-C(13)-H(13B) 107.9

C(7)-C(14)-C(13) 113.75(18) C(7)-C(14)-H(14A) 108.8

C(13)-C(14)-H(14A) 108.8 C(7)-C(14)-H(14B) 108.8

C(13)-C(14)-H(14B) 108.8 H(14A)-C(14)-H(14B) 107.7

C(8)-C(15)-H(15A) 109.5 C(8)-C(15)-H(15B) 109.5

H(15A)-C(15)-H(15B) 109.5 C(8)-C(15)-H(15C) 109.5

H(15A)-C(15)-H(15C) 109.5 H(15B)-C(15)-H(15C) 109.5

C(17)-C(16)-C(6) 121.3(2) C(17)-C(16)-H(16) 119.3

C(6)-C(16)-H(16) 119.3 O(5)-C(17)-C(16) 119.0(2)

O(5)-C(17)-C(18) 121.5(2) C(16)-C(17)-C(18) 119.5(2)

O(6)-C(18)-C(20) 125.2(2) O(6)-C(18)-C(17) 115.0(2)

C(20)-C(18)-C(17) 119.8(2) O(6)-C(19)-H(19A) 109.5

O(6)-C(19)-H(19B) 109.5 H(19A)-C(19)-H(19B) 109.5

O(6)-C(19)-H(19C) 109.5 H(19A)-C(19)-H(19C) 109.5

S34
 H(19B)-C(19)-H(19C) 109.5 C(18)-C(20)-C(5) 120.5(2)

C(18)-C(20)-H(20) 119.7 C(5)-C(20)-H(20) 119.7

C(10)-C(21)-C(12) 120.0(2) C(10)-C(21)-H(21) 120.0

C(12)-C(21)-H(21) 120.0 C(23)-C(22)-H(22A) 109.5

C(23)-C(22)-H(22B) 109.5 H(22A)-C(22)-H(22B) 109.5

C(23)-C(22)-H(22C) 109.5 H(22A)-C(22)-H(22C) 109.5

H(22B)-C(22)-H(22C) 109.5 O(7)-C(23)-C(22) 120.0(4)

O(7)-C(23)-C(24) 121.9(4) C(22)-C(23)-C(24) 118.1(3)

C(23)-C(24)-H(24A) 109.5 C(23)-C(24)-H(24B) 109.5

H(24A)-C(24)-H(24B) 109.5 C(23)-C(24)-H(24C) 109.5

H(24A)-C(24)-H(24C) 109.5 H(24B)-C(24)-H(24C) 109.5

Table 4. Anisotropic Displacement Parameters (Å2x 103) for Compound 17. The anisotropic
displacement factor exponent takes the form: -2π2 [h2a*2U11 + ... + 2 h k a* b* U12].

U11 U22 U33 U23 U13 U12

N(1) 31(1) 19(1) 15(1) -4(1) 1(1) -3(1)

O(2) 37(1) 22(1) 41(1) -6(1) 19(1) -6(1)

O(3) 21(1) 30(1) 29(1) -2(1) 3(1) 5(1)

O(4) 21(1) 26(1) 18(1) -2(1) 2(1) -3(1)

O(5) 31(1) 43(1) 23(1) -1(1) 7(1) 15(1)

O(6) 25(1) 39(1) 21(1) -3(1) 0(1) 10(1)

O(7) 91(2) 124(3) 133(3) -76(3) -67(2) 56(2)

O(1) 32(1) 23(1) 17(1) -1(1) 2(1) 5(1)

C(1) 55(2) 34(2) 20(1) -5(1) -1(1) 2(1)

C(2) 27(1) 19(1) 14(1) 3(1) 2(1) 1(1)

C(3) 22(1) 22(1) 10(1) 4(1) 1(1) 0(1)

C(4) 22(1) 21(1) 14(1) 2(1) 3(1) 1(1)

C(5) 23(1) 18(1) 18(1) 0(1) 3(1) -2(1)

S35
 C(6) 24(1) 15(1) 18(1) 0(1) 3(1) -2(1)

C(7) 28(1) 19(1) 14(1) -1(1) 2(1) -2(1)

C(8) 18(1) 23(1) 22(1) 1(1) 2(1) 2(1)

C(9) 20(1) 44(2) 42(2) -6(1) 4(1) 6(1)

C(10) 24(1) 26(1) 16(1) 6(1) 3(1) 4(1)

C(11) 21(1) 26(1) 29(1) 5(1) 3(1) -3(1)

C(12) 26(1) 22(1) 13(1) 5(1) 2(1) -2(1)

C(13) 24(1) 22(1) 22(1) 1(1) 4(1) -5(1)

C(14) 26(1) 23(1) 21(1) -3(1) 2(1) -5(1)

C(15) 39(1) 32(1) 25(1) 5(1) 9(1) 4(1)

C(16) 32(1) 21(1) 16(1) -2(1) 6(1) 1(1)

C(17) 26(1) 21(1) 21(1) -2(1) 7(1) 2(1)

C(18) 23(1) 24(1) 20(1) 1(1) 2(1) 2(1)

C(19) 38(1) 44(2) 21(1) 0(1) -3(1) 14(1)

C(20) 25(1) 20(1) 16(1) -1(1) 4(1) 2(1)

C(21) 20(1) 25(1) 18(1) 6(1) 1(1) -2(1)

C(22) 90(3) 49(2) 44(2) 2(2) 9(2) -16(2)

C(23) 68(2) 28(2) 62(2) -14(1) -21(2) 14(2)

C(24) 71(2) 35(2) 65(2) -10(2) 11(2) 11(2)

Table 5. Hydrogen Coordinates (× 104) and Isotropic Displacement Parameters (Å2x 103) for
Compound 17.

x y z U eq

H(1) 1660 -964 2722 26

H(5) 6344 -2151 6223 48

H(1A) -580 2884 10431 54

H(1B) 191 4133 10330 54

H(1C) 1010 2905 10458 54

S36
 H(7) 1080 552 4724 24

H(9A) -3597 1487 6958 53

H(9B) -4186 2164 8179 53

H(9C) -3569 848 8364 53

H(11A) 3422 1898 6565 38

H(11B) 3740 3104 7374 38

H(11C) 2356 2964 6536 38

H(13A) -967 -1694 6171 27

H(13B) 574 -1919 6566 27

H(14A) 502 -1941 4329 28

H(14B) -537 -857 4205 28

H(15A) 1905 921 602 47

H(15B) 2563 -352 962 47

H(15C) 3453 838 1042 47

H(16) 3852 -1206 4211 27

H(19A) 5348 -667 9866 51

H(19B) 6297 -1818 9990 51

H(19C) 4736 -1982 9655 51

H(20) 3424 -343 8647 25

H(21) -2021 8 7048 25

H(22A) 8471 -35 1955 91

H(22B) 8723 1355 2272 91

H(22C) 8021 961 891 91

H(24A) 5826 917 4104 85

H(24B) 7237 1579 4216 85

H(24C) 7166 145 4235 85

Table 6. Torsion Angles [°] for Compound 17.

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C(1)-O(1)-C(2)-C(3) -95.3(2) C(1)-O(1)-C(2)-C(10) 92.3(3)

C(11)-O(4)-C(3)-C(2) -105.9(2) C(11)-O(4)-C(3)-C(4) 72.8(3)

O(1)-C(2)-C(3)-O(4) 7.3(3) C(10)-C(2)-C(3)-O(4) 179.64(18)

O(1)-C(2)-C(3)-C(4) -171.42(19) C(10)-C(2)-C(3)-C(4) 0.9(3)

O(4)-C(3)-C(4)-C(12) -178.22(19) C(2)-C(3)-C(4)-C(12) 0.4(3)

O(4)-C(3)-C(4)-C(5) -1.6(3) C(2)-C(3)-C(4)-C(5) 177.09(19)

C(12)-C(4)-C(5)-C(20) -125.8(2) C(3)-C(4)-C(5)-C(20) 57.6(3)

C(12)-C(4)-C(5)-C(6) 54.9(3) C(3)-C(4)-C(5)-C(6) -121.7(2)

C(20)-C(5)-C(6)-C(16) -1.6(3) C(4)-C(5)-C(6)-C(16) 177.7(2)

C(20)-C(5)-C(6)-C(7) 177.0(2) C(4)-C(5)-C(6)-C(7) -3.6(3)

C(8)-N(1)-C(7)-C(6) -85.9(3) C(8)-N(1)-C(7)-C(14) 149.3(2)

C(16)-C(6)-C(7)-N(1) -16.5(3) C(5)-C(6)-C(7)-N(1) 164.95(19)

C(16)-C(6)-C(7)-C(14) 106.9(2) C(5)-C(6)-C(7)-C(14) -71.7(2)

C(7)-N(1)-C(8)-O(2) -0.3(3) C(7)-N(1)-C(8)-C(15) 179.8(2)

C(9)-O(3)-C(10)-C(21) 1.5(3) C(9)-O(3)-C(10)-C(2) 178.5(2)

O(1)-C(2)-C(10)-O(3) -5.9(3) C(3)-C(2)-C(10)-O(3) -178.31(19)

O(1)-C(2)-C(10)-C(21) 171.27(19) C(3)-C(2)-C(10)-C(21) -1.1(3)

C(3)-C(4)-C(12)-C(21) -1.6(3) C(5)-C(4)-C(12)-C(21) -178.31(19)

C(3)-C(4)-C(12)-C(13) 176.63(19) C(5)-C(4)-C(12)-C(13) -0.1(3)

C(21)-C(12)-C(13)-C(14) 106.2(2) C(4)-C(12)-C(13)-C(14) -72.0(3)

N(1)-C(7)-C(14)-C(13) 171.93(19) C(6)-C(7)-C(14)-C(13) 46.3(3)

C(12)-C(13)-C(14)-C(7) 40.6(3) C(5)-C(6)-C(16)-C(17) 1.9(3)

C(7)-C(6)-C(16)-C(17) -176.7(2) C(6)-C(16)-C(17)-O(5) -180.0(2)

C(6)-C(16)-C(17)-C(18) -0.2(3) C(19)-O(6)-C(18)-C(20) 17.5(3)

C(19)-O(6)-C(18)-C(17) -163.7(2) O(5)-C(17)-C(18)-O(6) -0.8(3)

C(16)-C(17)-C(18)-O(6) 179.4(2) O(5)-C(17)-C(18)-C(20) 178.0(2)

C(16)-C(17)-C(18)-C(20) -1.7(3) O(6)-C(18)-C(20)-C(5) -179.3(2)

C(17)-C(18)-C(20)-C(5) 2.0(3) C(6)-C(5)-C(20)-C(18) -0.3(3)

C(4)-C(5)-C(20)-C(18) -179.6(2) O(3)-C(10)-C(21)-C(12) 176.9(2)

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 C(2)-C(10)-C(21)-C(12) 0.0(3) C(4)-C(12)-C(21)-C(10) 1.4(3)

C(13)-C(12)-C(21)-C(10) -176.8(2)

Table 7. Hydrogen Bonds for Compound 17 (Å and °).

D-H...A d(D-H) d(H...A) d(D...A) <(DHA)

C(22)-H(22A)...O(1)#1 0.98 2.55 3.450(5) 153.3

C(19)-H(19B)...O(4)#2 0.98 2.52 3.440(3) 155.7

C(19)-H(19A)...O(7)#3 0.98 2.56 3.426(4) 148.0

C(15)-H(15C)...O(7) 0.98 2.43 3.303(4) 148.1

C(9)-H(9C)...O(6)#4 0.98 2.61 3.466(4) 146.2

O(5)-H(5)...O(6) 0.84 2.27 2.688(2) 110.7

O(5)-H(5)...O(2)#1 0.84 1.93 2.681(2) 148.4

N(1)-H(1)...O(1)#5 0.88 2.44 3.128(3) 134.8

N(1)-H(1)...O(3)#5 0.88 2.42 3.253(3) 158.9

C(22)-H(22A)...O(1)#1 0.98 2.55 3.450(5) 153.3

C(19)-H(19B)...O(4)#2 0.98 2.52 3.440(3) 155.7

C(19)-H(19A)...O(7)#3 0.98 2.56 3.426(4) 148.0

C(15)-H(15C)...O(7) 0.98 2.43 3.303(4) 148.1

C(9)-H(9C)...O(6)#4 0.98 2.61 3.466(4) 146.2

O(5)-H(5)...O(6) 0.84 2.27 2.688(2) 110.7

O(5)-H(5)...O(2)#1 0.84 1.93 2.681(2) 148.4

N(1)-H(1)...O(1)#5 0.88 2.44 3.128(3) 134.8

N(1)-H(1)...O(3)#5 0.88 2.42 3.253(3) 158.9

C(22)-H(22A)...O(1)#1 0.98 2.55 3.450(5) 153.3

C(19)-H(19B)...O(4)#2 0.98 2.52 3.440(3) 155.7

C(19)-H(19A)...O(7)#3 0.98 2.56 3.426(4) 148.0

C(15)-H(15C)...O(7) 0.98 2.43 3.303(4) 148.1

C(9)-H(9C)...O(6)#4 0.98 2.61 3.466(4) 146.2

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O(5)-H(5)...O(6) 0.84 2.27 2.688(2) 110.7

O(5)-H(5)...O(2)#1 0.84 1.93 2.681(2) 148.4

N(1)-H(1)...O(1)#5 0.88 2.44 3.128(3) 134.8

N(1)-H(1)...O(3)#5 0.88 2.42 3.253(3) 158.9

N(1)-H(1)...O(3)#5 0.88 2.42 3.253(3) 158.9

N(1)-H(1)...O(1)#5 0.88 2.44 3.128(3) 134.8

O(5)-H(5)...O(2)#1 0.84 1.93 2.681(2) 148.4

O(5)-H(5)...O(6) 0.84 2.27 2.688(2) 110.7

C(9)-H(9C)...O(6)#4 0.98 2.61 3.466(4) 146.2

C(15)-H(15C)...O(7) 0.98 2.43 3.303(4) 148.1

C(19)-H(19A)...O(7)#3 0.98 2.56 3.426(4) 148.0

C(19)-H(19B)...O(4)#2 0.98 2.52 3.440(3) 155.7

C(22)-H(22A)...O(1)#1 0.98 2.55 3.450(5) 153.3

N(1)-H(1)...O(3)#5 0.88 2.42 3.253(3) 158.9

N(1)-H(1)...O(1)#5 0.88 2.44 3.128(3) 134.8

O(5)-H(5)...O(2)#1 0.84 1.93 2.681(2) 148.4

O(5)-H(5)...O(6) 0.84 2.27 2.688(2) 110.7

C(9)-H(9C)...O(6)#4 0.98 2.61 3.466(4) 146.2

C(15)-H(15C)...O(7) 0.98 2.43 3.303(4) 148.1

C(19)-H(19A)...O(7)#3 0.98 2.56 3.426(4) 148.0

C(19)-H(19B)...O(4)#2 0.98 2.52 3.440(3) 155.7

C(22)-H(22A)...O(1)#1 0.98 2.55 3.450(5) 153.3

N(1)-H(1)...O(3)#5 0.88 2.42 3.253(3) 158.9

N(1)-H(1)...O(1)#5 0.88 2.44 3.128(3) 134.8

O(5)-H(5)...O(2)#1 0.84 1.93 2.681(2) 148.4

O(5)-H(5)...O(6) 0.84 2.27 2.688(2) 110.7

C(9)-H(9C)...O(6)#4 0.98 2.61 3.466(4) 146.2

C(15)-H(15C)...O(7) 0.98 2.43 3.303(4) 148.1

C(19)-H(19A)...O(7)#3 0.98 2.56 3.426(4) 148.0

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C(19)-H(19B)...O(4)#2 0.98 2.52 3.440(3) 155.7

C(22)-H(22A)...O(1)#1 0.98 2.55 3.450(5) 153.3

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High Resolution Mass Spectra

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