SUPPORTING INFORMATION
Total Synthesis of Clerobungin A via a Cascade Cyclization Reaction
James Mease and Keith P. Reber* Department of Chemistry Towson University 8000 York Road Towson, MD 21252 e-mail:
[email protected]
SI-1
Table of Contents 1
H NMR, 13C NMR, and selected 2D NMR Spectra
SI-3 – SI-33
ether 13
SI-3–SI-4
phenol 14
SI-5–SI-6
benzoquinol 15
SI-7–SI-8
aldehyde 9
SI-9–SI-10
tricyclic enone (±)-11
SI-11–SI-17
DEPT-135 spectrum of (±)-11
SI-13
COSY spectrum of (±)-11
SI-14
HETCOR spectrum of (±)-11
SI-15
HMBC spectrum of (±)-11
SI-16
Full 1H and 13C assignments for (±)-11
SI-17
(±)-clerobungin A (1)
SI-18–SI23
COSY spectrum of (±)-clerobungin A (1)
SI-20
HETCOR spectrum of (±)-clerobungin A (1)
SI-21
HMBC spectrum of (±)-clerobungin A (1)
SI-22
NOESY spectrum of (±)-clerobungin A (1)
SI-23
Full 1H and 13C assignments for synthetic and natural clerobungin A (1)
SI-24
1H
SI-25
NMR comparison of synthetic and natural clerobungin A (1)
13C
NMR comparison of synthetic and natural clerobungin A (1)
tricyclic alcohol (±)-16
SI-26 SI-27–SI33
DEPT-135 spectrum of (±)-16
SI-29
COSY spectrum of (±)-16
SI-30
HETCOR spectrum of (±)-16
SI-31
HMBC spectrum of (±)-16
SI-32
Full 1H and 13C assignments for (±)-16
SI-33
HPLC chromatograms for the preparative resolution of enone (±)-11
SI-34
UV-Visible spectrum of (±)-1
SI-35
Circular dichroism spectrum of (+)-1
SI-36
Circular dichroism spectrum of (–)-1
SI-37
Overlay of circular dichroism spectra of (+)-1 and (–)-1
SI-38
SI-2
13 NMR (400 MHz, CDCl3) 1H
SI-3
13 NMR (100 MHz, CDCl3) 13C
SI-4
14 NMR (400 MHz, CDCl3) 1H
SI-5
14 NMR (100 MHz, CDCl3) 13C
SI-6
15 NMR (400 MHz, CDCl3) 1H
SI-7
15 NMR (100 MHz, CDCl3) 13C
SI-8
9 NMR (400 MHz, CDCl3) 1H
SI-9
9 NMR (100 MHz, CDCl3) 13C
SI-10
(±)-11 NMR (400 MHz, CDCl3) 1H
SI-11
(±)-11 NMR (100 MHz, CDCl3) 13C
SI-12
(±)-11 DEPT-135 (100 MHz, CDCl3)
SI-13
(±)-11 COSY (CDCl3)
SI-14
(±)-11 HETCOR (CDCl3)
SI-15
(±)-11 HMBC (CDCl3)
SI-16
Full 1H and 13C NMR Assignments for Tricyclic Enone 11
13C
1H
shift (ppm) (100 MHz, CDCl3)
shift (ppm) (400 MHz, CDCl3)
C1
78.1
4.63 (1H, dd, J = 8.1 Hz, 6.8 Hz)
C2
41.8
C3
197.0
N/A
C4
130.4
6.10 (1H, d, J = 10.2 Hz)
C5
145.3
6.74 (1H, d, J = 10.2 Hz)
C6
77.3
N/A
C7
42.1
C8
66.6
C9
73.8
C10
105.2
2.79 (1H, dd, J = 15.9 Hz, 6.7 Hz) 2.65 (1H, ddd, J = 15.9 Hz, 8.2 Hz, 0.8 Hz)
2.13 (1H, ddd, J = 14.4 Hz, 7.2 Hz, 4.3 Hz) 1.99 (1H, ddd, J = 14.4 Hz, 7.2 Hz, 4.3 Hz) 4.03 (1H, ddd, J = 12.6 Hz, 6.7 Hz, 4.0 Hz) 3.87 (1H, ddd, J = 12.6 Hz, 7.2 Hz, 4.3 Hz) 3.79 (1H, d, J = 12.8 Hz) 3.65 (1H, ddd, J = 12.8 Hz, 1.8 Hz, 0.8 Hz) 5.60 (1H, d, J = 1.6 Hz)
SI-17
(±)-clerobungin A (1) 1H NMR (400 MHz, CDCl3)
SI-18
(±)-clerobungin A (1) 13C NMR (100 MHz, CDCl3)
SI-19
(±)-clerobungin A (1) COSY (CDCl3)
SI-20
(±)-clerobungin A (1) HETCOR (CDCl3)
SI-21
(±)-clerobungin A (1) HMBC (CDCl3)
SI-22
(±)-clerobungin A (1) NOESY (CDCl3)
SI-23
NMR Comparison of Synthetic and Natural Clerobungin A
Reported 13C shift in ppm (100 MHz, CDCl3)
Observed 13C shift in ppm (100 MHZ, CDCl3)
Reported 1H shift in ppm (400 MHz, CDCl3)
Observed 1H shift in ppm (400 MHz, CDCl3)
C1
81.2
81.2
4.77 (dd, J = 4.2, 2.4 Hz)
4.77 (dd, J = 4.1, 2.4 Hz)
C2
42.8
42.8
2.67 (dd, J = 16.5, 2.3 Hz)
2.66 (dd, J = 16.4, 2.3 Hz)
2.47 (dd, J = 16.5, 4.2 Hz)
2.47 (dd, J = 16.4, 4.3 Hz)
C3
209.3
209.6
N/A
N/A
C4
33.9
33.9
2.54 (ddd, J = 18.9, 13.6, 5.0 Hz)
2.54 (ddd, J = 18.9, 13.4, 5.0 Hz)
2.27 (ddd, J = 18.9, 4.4, 2.5 Hz)
2.27 (ddd, J = 18.9, 4.2, 2.2 Hz)
C5
31.4
31.4
2.13 (ddd, J = 14.7, 5.1, 2.5 Hz)
2.12 (ddd, J = 14.7, 5.0, 2.4 Hz)
1.95 (m)
1.99-1.91 (m)
C6
79.6
79.7
N/A
N/A
C7
41.4
41.4
2.19 (ddd, J = 11.5, 7.0, 3.9 Hz)
2.19 (ddd, J = 11.5, 7.0, 3.8 Hz)
1.94 (m)
1.99-1.91 (m)
C8
69.0
69.1
4.13 (ddd, J = 12.4, 6.7, 1.1 Hz)
4.12 (ddd, J = 12.1, 6.4, 0.7 Hz)
3.77 (ddd, J = 12.4, 11.5, 4.9 Hz)
3.76 (ddd, J = 11.9, 11.9, 4.9 Hz)
C9
76.6
76.7
3.88 (d, J = 12.8 Hz)
3.88 (d, J = 12.8 Hz)
3.46 (dd, J = 12.8, 1.0 Hz)
3.46 (dd, J = 12.8, 0.6 Hz)
C10
103.1
103.1
5.33 (s)
5.32 (s)
_________________________________________________________________________________________ Zhu, H.; Huan, L.; Chen, C.; Yang, J.; He, J.; Cheng, Y.; Yao, G.; Luo, Z.; Xue, Y.; Zhang, Y. Tetrahedron Lett. 2014, 55, 2277.
SI-24
1
H NMR Comparison of Synthetic (top) and Natural (bottom) Clerobungin A
Synthetic (±)-clerobungin A (400 MHz, CDCl3)
Natural (±)-clerobungin A (400 MHz, CDCl3)
_____________________________________________________________________________________________ Zhu, H.; Huan, L.; Chen, C.; Yang, J.; He, J.; Cheng, Y.; Yao, G.; Luo, Z.; Xue, Y.; Zhang, Y. Tetrahedron Lett. 2014, 55, 2277.
SI-25
13
C NMR Comparison of Synthetic (top) and Natural (bottom) Clerobungin A
Synthetic (±)-clerobungin A (100 MHz, CDCl3)
Natural (±)-clerobungin A (100 MHz, CDCl3)
____________________________________________________________________________________________ Zhu, H.; Huan, L.; Chen, C.; Yang, J.; He, J.; Cheng, Y.; Yao, G.; Luo, Z.; Xue, Y.; and Zhang, Y. Tetrahedron Lett. 2014, 55, 2277.
SI-26
(±)-16 NMR (400 MHz, C6D6) 1H
SI-27
(±)-16 NMR (100 MHz, C6D6) 13C
SI-28
(±)-16 DEPT-135 (100 MHz, C6D6)
SI-29
(±)-16 COSY (C6D6)
SI-30
(±)-16 HETCOR (C6D6)
SI-31
(±)-16 HMBC (C6D6)
SI-32
Full 1H and 13C NMR Assignments for Tricyclic Alcohol 16
13C
1H
shift (ppm) (100 MHz, C6D6)
shift (ppm) (400 MHz, C6D6)
C1
78.5
3.63 (1H, dd, J = 9.1 Hz, 6.4 Hz)
C2
38.2
C3
66.9
3.16 (1H, dddd, J = 10.2 Hz, 10.2 Hz, 4.4 Hz, 4.4 Hz)
C4
30.4
1.60 (1H, m) 1.48 (1H, m)
C5
31.4
1.84 (1H, ddd, J = 15.0 Hz, 3.4 Hz, 3.4 Hz) 0.96 (1H, ddd, J = 14.5 Hz, 13.3 Hz, 4.8 Hz)
C6
79.4
N/A
C7
43.6
C8
66.0
C9
72.5
C10
102.9
5.15 (1H, d, J = 1.9 Hz)
OH
N/A
1.63-1.42 (1H, m)
1.90 (1H, dddd, J = 12.6 Hz, 4.1 Hz, 4.1 Hz, 1.9 Hz) 1.48 (1H, m)
1.53 (1H, m) 1.20 (1H, ddd, J = 14.5 Hz, 6.2 Hz, 3.0 Hz) 3.79 (1H, ddd, J = 12.2 Hz, 8.4 Hz, 3.0 Hz) 3.62-3.56 (1H, m) 3.59 (1H, d, J = 12.4 Hz) 3.45 (1H, dd, J = 12.5 Hz, 1.9 Hz)
SI-33
HPLC Chromatograms for the Preparative Resolution of Enone (±)-11
Index
Time (min)
Area (%)
Peak-1
1.70
100.00
Index
Time (min)
Area (%)
Peak-2
1.92
100.00
Preparative Method: CHIRALPAK® AS-H (2 x 25 cm) 20% isopropanol / CO2, 100 bar 70 mL/min, 220 nm Inj. Vol.: 1 mL, 5 mg/mL ethanol: DCM Lotus Separations, LLC. Princeton University, Frick Laboratory, room B20, Princeton, NJ 08544-0000, www.lotusseparations.com
SI-34
UV-Visible Spectrum of (±)-1
UV (1.5 mM in CH3CN) λmax, nm: 193, 264.
Instrument Parameters: Start (nm) Stop (nm) X Mode Y Mode UV-Vis Scan Rate (nm/min) UV-Vis Data Interval (nm) UV-vis Ave. Time (sec) Beam Mode Baseline Correction
400.0 190.0 Nanometers Abs 600.0 1.00 0.1000 Dual Beam On
SI-35
2 0 200
1 Abs
500
2
3
-500
200 0 CD [mdeg] -200
500
Circular Dichroism Spectrum of (+)-1
200 0 CD [mdeg] -200 -500 3 2 Abs
1 0 200
Instrument Parameters: Temperature Cell Length Photometric Mode Measure Range Data pitch Sensitivity D.I.T. Bandwidth Scanning Speed Solvent Sample Concentration
250
300 350 Wavelength [nm]
25.01 °C 10 mm CD, Abs 400 – 200 nm 1 nm Low 2 sec 1.00 nm 100 nm/min CH3CN 3 mM
SI-36
400
2 0 200
1 Abs
500
2
3
-500
200 0 CD [mdeg] -200
500
Circular Dichroism Spectrum of (–)-1
200 0 CD [mdeg] -200 -500 3 2 Abs
1 0 200
Instrument Parameters: Temperature Cell Length Photometric Mode Measure Range Data pitch Sensitivity D.I.T. Bandwidth Scanning Speed Solvent Sample Concentration
250
300 350 Wavelength [nm]
25.01 °C 10 mm CD, Abs 400 – 200 nm 1 nm Low 2 sec 1.00 nm 100 nm/min CH3CN 3 mM
SI-37
400
2 0 200
1 Abs
500
2
3
-500
200 0 CD [mdeg] -200
500
Overlay of Circular Dichroism Spectra of (+)-1 and (–)-1
200 0 CD [mdeg] -200 -500 3 2 Abs
1 0 200
Instrument Parameters: Temperature Cell Length Photometric Mode Measure Range Data pitch Sensitivity D.I.T. Bandwidth Scanning Speed Solvent Sample Concentration
250
300 350 Wavelength [nm]
25.01 °C 10 mm CD, Abs 400 – 200 nm 1 nm Low 2 sec 1.00 nm 100 nm/min CH3CN 3 mM
SI-38
400
