Total synthesis of echinopines A and B: Exploiting a bioinspired late-stage intramolecular cyclopropanation

Article abstract of DOI:10.1021/ol202053m

Total synthesis of echinopine A and B have been accomplished, based on a strategy that involved two transition-metal-mediated ene-yne cycloisomerizations. A modified Pd-catalyzed enyne cycloisomerization/ intramolecular Diels-Alder cascade rendered a more

Full text of DOI:10.1021/ol202053m

The Supporting Information was replaced on October 3, 2011: see the Note Added after ASAP for details.
Total Synthesis of Echinopines A and B: Exploiting a
Bio-inspired Late-Stage Intramolecular
Cyclopropanation
Philippe A. Peixoto,a Jean-Alexandre Richard, a Rene Severin, a and David Y.-K. Chen*,b
aChemical Synthesis Laboratory@Biopolis, Institute of Chemical and Engineering Sciences (ICES),
Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way, The Helios Block, #03-08,
Singapore 138667
and
bDepartment of Chemistry, Seoul National University, Gwanak-1 Gwanak-ro, Gwanak-gu, Seoul 151-
742, South Korea
E-mail: davidchen@snu.ac.kr

Supporting Information Available
I)
Experimental Section
Abbreviations
II)
III)
IV)
References
1H and 13C NMR Spectra of Compounds
I)
Experimental Section
Experimental Data for Compounds
General Procedures. All reactions were carried out under a nitrogen or argon atmosphere with dry
solvents under anhydrous conditions, unless otherwise noted. Dry tetrahydrofuran (THF), hexane,
diethyl ether (Et2O), methylene chloride (CH2Cl2), and toluene were obtained by passing commercially
available pre-dried, oxygen-free formulations through activated alumina columns. Methanol (MeOH),
benzene, N,N'-dimethylformamide (DMF), and 1-methyl-2-pyrrolidinone (NMP) were purchased in
anhydrous form and used without further purification. Water, ethyl acetate (EtOAc), diethyl ether
(Et2O), methylene chloride (CH2Cl2), and hexanes were purchased at the highest commercial quality
and used without further purification, unless otherwise stated. Reagents were purchased at the highest
commercial quality and used without further purification, unless otherwise stated. Yields refer to
chromatographically and spectroscopically (1H NMR) homogeneous materials, unless otherwise stated.
Reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25 mm E. Merck silica
gel plates (60F-254) using UV light as visualizing agent and an ethanolic solution of ammonium
molybdate, anisaldehyde, potassium permanganate and heat as developing agents. E. Merck silica gel
(60, particle size 0.0400.063 mm) was used for flash column chromatography. NMR spectra were
recorded on a Bruker AV-600 instrument and calibrated using residual undeuterated solvent as an
internal reference. The following abbreviations were used to explain the multiplicities: s = singlet, d =
doublet, t = triplet, q = quartet, quint = quintet, m = multiplet, pent = pentet, hex = hexet, br = broad. IR
S2

spectra were recorded on a Perkin-Elmer Spectrum One FTIR spectrometer with diamond ATR
accessory. Optical rotation ([α] 2D5 ) were recorded on a Perkin-Elmer Model 341 polarimeter at 25 C
using thermostable optical glass cell (100mm path length). Melting points (m.p.) are uncorrected, and
recorded on a Buchi B-540 melting point apparatus. High-resolution mass spectra (HRMS) were
recorded on an Agilent ESI TOF (time of flight) mass spectrometer at 3500 V emitter voltage.
OHC
OTBS
19
Aldehyde 19: To a stirred solution of 1,4-butanediol (26.0 g, 288.5 mmol) in CH2Cl2
(500 mL) at room temperature was added TBSCl (21.7 g, 144.0 mmol). The resulting mixture was
cooled to 0 C before Et3N (20.0 mL, 144.0 mmol) was slowly added. The resulting mixture was
warmed to room temperature and stirred for 3 h before it was quenched with NH4Cl (250 mL, sat. aq.).
The layers were separated and the organic layer was washed with H2O (200 mL), dried (Na2SO4) and
concentrated in vacuo to afford the corresponding mono-protected alcohol (27.4 g, 93%) as a light
yellow oil, which was used directly without further purification.
To a stirred solution of (COCl)2 (8.07 mL, 95.4 mmol) in CH2Cl2 (400 mL) at 78 °C was added
DMSO (13.6 mL, 190.8 mmol). The resulting mixture was stirred for 15 min before a solution of the
mono-protected alcohol (obtained above, 13.0 g, 63.6 mmol) in CH2Cl2 (100 mL) was added. The
resulting mixture was stirred for 30 min before Et3N (53.2 mL, 381.6 mmol) was added. The resulting
mixture was warmed to room temperature before it was quenched with H2O (250 mL). The layers were
separated and the aqueous layer was extracted with CH2Cl2 (2 × 100 mL). The combined organic layers
were washed with brine (2 × 200 mL), dried (Na2SO4) and concentrated in vacuo to afford aldehyde 19
(12.51 g, 97%) as a light yellow oil, which was used directly without further purification. All physical
characteristics of aldehyde 19 were identical to those reported in literature.[1]
S3

SiMe3
18
+

TMS
Allyl silane 18: To a stirred suspension of freshly prepared Ph3P CH3I (23.4 g, 60
mmol)[2] in THF (120 mL) at 0 °C was added n-BuLi (2.0 M in cyclohexane, 33 mL, 66 mmol). The
resulting mixture was stirred for 30 min before TMSCH2I (10.8 mL, 72 mmol) was added. The resulting
mixture was warmed to room temperature and stirred for 10 h before it was cooled to 0 °C and n-BuLi
(2.0 M in cyclohexane, 27 mL, 54 mmol) was added. The resulting mixture was stirred for 1 h before it
was cooled to 78 °C and a solution of 5-(trimethylsilyl)pent-4-ynal[3] (7.5 g, 49 mmol) in THF (10 mL)
was added. The resulting mixture was warmed to room temperature over a period of 30 min and stirred
for 90 min before it was quenched with pH7 buffer (100 mL, aq.). The resulting mixture was diluted
with EtOAc (200 mL), the layers were separated and the aqueous layer was extracted with EtOAc (2 ×
100 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. Flash column
chromatography (silica gel, hexane) afforded allyl silane 18 (7.18 g, 62%) as a colorless oil. All physical
characteristics of allyl silane 18 were identical to those reported in literature.[4]
OH
10
OH
10
OH
OTBS
TMS
TMS
21
20
Sakurai products 20 and 21: To a
stirred solution of allyl silane 18 (8.4 g, 35.2 mmol) and aldehyde 19 (6.5 g, 32.1 mmol) in CH2Cl2 (400
mL) at 78 °C was added TiCl4 dropwise (3.7 mL, 33.7 mmol). The initial light yellow solution slowly
turned bright orange was stirred for 1 h before it was warmed to room temperature and quenched with
HCl (1.0 N aq., 200 mL). The resulting mixture was diluted with Et2O (800 mL), the layers were
separated and the aqueous layer was extracted with Et2O (2 × 100 mL). The combined organic layers
were washed with H2O (300 mL), dried (Na2SO4) and concentrated in vacuo. Flash column
chromatography (silica gel, hexanes:EtOAc 95:05, 80:20, then 10:90) afforded the Sakurai product 20
(4.67 g, 40%, ca. 3:1 mixture of C10 epimers by 1H NMR) and Sakurai product 21 (2.74 g, 34%, ca. 3:1
mixture of C10 epimers by 1H NMR) as colorless oils.
S4

20: Rf = 0.35 (silica gel, hexanes:EtOAc 90:10); IR (film) νmax 3438, 2955, 2929, 2858, 2174, 1472,
1
1463, 1423, 1388, 1361, 1249, 1096, 1033, 998, 916, 835774, 759 cm1; H NMR (600 MHz, CDCl3,
ca. 3:1 mixture of C10 epimers)  = 5.67–5.54 (m, 1 H), 5.26–5.00 (m, 2 H), 3.65 (t, J = 5.7 Hz, 2 H),
3.57–3.52 (m, 0.3 H), 3.49 (dd, J = 11.3, 4.6 Hz, 0.7 H), 2.60 (s, 0.7 H), 2.39 (s, 0.3 H), 2.28 (ddt, J =
12.8, 7.3, 3.6 Hz, 1 H), 2.20–2.06 (m, 2 H), 1.96–1.85 (m, 1 H), 1.73–1.59 (m, 3 H), 1.54–1.43 (m, 1
H), 1.38 (ddd, J = 9.4, 8.3, 3.7 Hz, 1 H), 0.89 (s, 9 H), 0.13 (s, 9 H), 0.09 (s, 1 H), 0.06 ppm (s, 5 H); 13C
NMR (151 MHz, CDCl3, ca. 3:1 mixture of C10 epimers)  = 138.8, 138.0, 118.5, 117.5, 107.9, 107.7,
85.0, 84.8, 74.1, 73.6, 63.8, 50.2, 49.7, 32.3, 32.0, 30.3, 29.5(3), 29.4(7), 29.4, 26.3 (3C), 26.0, 18.6,
18.2, 0.5(3C), 3.2, 5.0(3C) ppm; HRMS (ESI): calcd for C20H40NaO2Si2 [M + Na+]: 391.2465, found
+
391.2447.
21: Rf = 0.3 (silica gel, hexanes:EtOAc 60:40); IR (film) νmax 3322, 2955, 2896, 2173, 1639, 1422, 1339,
1
1248, 1053, 996, 916, 838, 759 cm1; H NMR (600 MHz, CDCl3, ca. 3:1 mixture of C10 epimers)  =
5.70–5.48 (m, 1 H), 5.33–4.99 (m, 2 H), 3.77–3.60 (m, 2 H), 3.57–3.48 (m, 1 H), 2.84 (s, 1 H), 2.41 (dd,
J = 8.7, 5.7 Hz, 0.3 H), 2.37–2.06 (m, 2.7 H), 1.92–1.78 (m, 1 H), 1.69 (s, 3 H), 1.58–1.44 (m, 1 H),
13
1.44–1.32 (m, 1 H), 0.88 (s, 1 H), 0.13 ppm (s, 9 H); C NMR (151 MHz, CDCl3, ca. 3:1 mixture of
C10 epimers)  = 119.1, 118.3, 107.7, 107.5, 85.2, 85.0, 74.4, 73.7, 63.2, 62.6, 50.2, 49.9, 32.1, 31.8,
31.1, 30.1, 29.7, 29.5, 29.3, 28.0, 26.2, 18.1(4), 18.0(7), 0.5(3C); HRMS (ESI): calcd for
C14H26NaO2Si+ [M + Na+]: 277.1600, found 277.1588.
OTBS
OTBS
10
TMS
22
TBS ether 22: To a stirred solution of alcohol 20 (7.55 g, 20.5 mmol),
diol 21 (3.79 g, 14.9 mmol) and Et3N (22.0 mL, 157.8 mmol) in CH2Cl2 (300 mL) at 0 C was added
TBSOTf (16.3 mL, 70.9 mmol). The resulting mixture was stirred for 1 h before it was quenched with
NaHCO3 (150 mL, sat. aq.). The layers were separated and the aqueous layer was extracted with CH2Cl2
(2 × 100 mL). The combined organic layers were washed with brine (200 mL), dried (Na2SO4) and
S5

concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 98:02  90:10)
afforded the TBS ether 22 (15.18 g, 89%, ca. 3:1 mixture of C10 epimers by 1H NMR) as a colorless oil.
22: Rf = 0.55 (silica gel, hexanes:EtOAc 98:02); IR (film) νmax 2955, 2929, 2895, 2857, 2175, 1472,
1
1463, 1388, 1361, 1250, 1096, 1073, 1053, 1004, 938, 916 834, 773, 760 cm1; H NMR (600 MHz,
CDCl3, ca. 3:1 mixture of C10 epimers)  = 5.62 (ddd, J = 17.2, 10.3, 9.0 Hz, 1 H), 5.16–4.95 (m, 2 H),
3.59 (dt, J = 9.8, 6.1 Hz, 3 H), 2.36–2.21 (m, 2 H), 2.17–2.03 (m, 1 H), 1.73 (tdd, J = 11.4, 8.5, 3.5 Hz,
1 H), 1.62–1.54 (m, 1 H), 1.53–1.32 (m, 4 H), 0.89 (s, 18 H), 0.14 (s, 9 H), 0.06 (s, 3 H), 0.05 (s, 3 H),
0.04 ppm (s, 6 H); 13C NMR (151 MHz, CDCl3, ca. 3:1 mixture of C10 epimers)  = 139.1, 138.3, 117.5,
116.9, 107.9, 84.9, 75.4, 75.3, 63.7, 63.5, 48.5, 48.5, 31.0, 30.5, 29.8, 29.4, 28.8, 28.7, 26.3 (6C),
18.6(8), 18.6(6), 18.5(1), 18.4(7), 18.2, 0.5(3C), 3.9, 4.0, 4.9(2C) ppm; HRMS (ESI): calcd for
+
C26H54NaO2Si3 [M + Na+]: 505.3329, found 505.3337.
OTBS
OH
10
24
Alcohol 24: To a stirred solution of TBS ether 22 (15.18 g, 31.4 mmol) in
CH2Cl2/MeOH (5:1, 300 mL) at 10 °C was added p-TsOH (479 mg, 2.52 mmol). The temperature of
the resulting mixture was maintained between 10 °C and 0 °C and stirred for 3 h before it was
quenched with NaHCO3 (200 mL, sat. aq.). The layers were separated and the aqueous layer was
extracted with CH2Cl2 (2 × 100 mL). The combined organic layers were washed with brine (200 mL),
dried (Na2SO4) and concentrated in vacuo to afford crude alcohol 23 as a yellow oil, which was used
directly without further purification.
To a stirred solution of alcohol 23 (obtained above) in MeOH (300 mL) at room temperature was
added K2CO3 (21.6 g, 156.5 mmol). The resulting mixture was stirred for 3 h before it was quenched
with H2O (200 mL) and diluted with CH2Cl2 (500 mL). The layers were separated and the aqueous layer
was extracted with CH2Cl2 (2 × 150 mL). The combined organic layers were dried (Na2SO4) and
concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 80:20) afforded alkyne
S6

24 (6.38 g, 69% over the two steps, ca. 3:1 mixture of C10 epimers by 1H NMR) as a colorless oil. 24: Rf
= 0.30 (silica gel, hexanes:EtOAc 80:20); IR (film) νmax 3312, 2952, 2929, 2886, 2857, 1639, 1472,
1
1463, 1431, 1361, 1254, 1099, 1057, 1005, 915, 834, 811, 773 cm1; H NMR (600 MHz, CDCl3, ca.
3:1 mixture of C10 epimers)  = 5.60 (tdd, J = 17.3, 10.3, 9.3 Hz, 1 H), 5.16–4.99 (m, 2 H), 3.62 (dd, J =
10.7, 5.4 Hz, 3 H), 2.31 (ddt, J = 10.8, 8.7, 4.3 Hz, 1 H), 2.23 (ddd, J = 16.8, 7.7, 5.0, Hz, 1 H), 2.11–
2.02 (m, 1 H), 1.93 (dd, J = 4.6, 2.0 Hz, 1 H), 1.78 (dtd, J = 13.2, 8.3, 3.6 Hz, 1 H), 1.69–1.64 (m, 2 H),
1.62–1.57 (m, 1 H), 1.55–1.48 (m, 2 H), 1.39 (ddd, J = 13.1, 10.6, 7.9, Hz, 1 H), 0.90 (s, 9 H), 0.07 (s, 3
13
H), 0.06 ppm (s, 3 H); C NMR (151 MHz, CDCl3, ca. 3:1 mixture of C10 epimers)  = 138.8, 138.2,
117.8, 117.2, 84.9, 75.3, 75.1, 68.9, 68.6, 63.5, 63.4, 48.7, 48.5, 30.9, 30.8, 29.5, 29.3, 29.1, 28.4,
26.3(3C), 18.4(9), 18.4(5), 16.8, 16.7, 3.9, 4.1 ppm; HRMS (ESI): calcd for C17H32NaO2 Si+ [M +
Na+]: 319.2069, found 319.2066.
OTBS
10
NO2
26
Nitroolefin 26: To a stirred solution of (COCl)2 (2.06 mL, 24.3 mmol) in CH2Cl2
(120 mL) at 78 °C was added DMSO (3.45 mL, 48.6 mmol). The resulting mixture was stirred for 15
min before a solution of alcohol 24 (4.81 g, 16.2 mmol) in CH2Cl2 (120 mL) was added. The resulting
mixture was stirred for 30 min before Et3N (13.6 mL, 97.6 mmol) was added. The resulting mixture was
warmed to room temperature over 30 min before it was quenched with H2O (100 mL). The layers were
separated and the aqueous layer was extracted with CH2Cl2 (100 mL). The combined organic layers
were washed with brine (200 mL), dried (Na2SO4) and concentrated in vacuo to afford aldehyde 25 as a
light yellow oil, which was used directly without further purification.
To a stirred solution of aldehyde 25 (obtained above) in nitromethane (200 mL) at room
temperature was added TMG (1.0 mL, 7.97 mmol). The resulting mixture was stirred for 5 min before it
was quenched with NH4Cl (100 mL, sat. aq.) and diluted with Et2O (200 mL). The layers were
separated and the aqueous layer was extracted with Et2O (2 × 100 mL). The combined organic layers
S7

were washed with H2O (200 mL), dried (Na2SO4) and concentrated in vacuo to afford the corresponding
nitro alcohol as a light yellow oil, which was used directly without further purification.
To a stirred solution of the nitro alcohol (obtained above) in CH2Cl2 (200 mL) at room
temperature were added pyridine (26 mL, 322 mmol) and acetic anhydride (7.7 mL, 81.6 mmol). The
resulting mixture was stirred for 20 h before it was diluted with CH2Cl2 (200 mL), washed with HCl
(1.0 N aq., 3 × 150 mL), NaHCO3 (100 mL, sat. aq.) and H2O (100 mL). The organic layer was dried
(Na2SO4) and concentrated in vacuo to afford a mixture of nitroolefin 26 and its acetylated precursor.
The crude mixture was dissolved in CH2Cl2 (200 mL) and DMAP (990 mg, 8.11 mmol) was added. The
resulting mixture was stirred for 3.5 h before it was quenched with citric acid (10% wt/wt aq., 100 mL).
The layers were separated and the aqueous layer was extracted with CH2Cl2 (100 mL). The combined
organic layers were dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (silica
gel, hexanes:EtOAc 95:05) afforded nitroolefin 26 (4.1 g, 75% over 3 steps, ca. 3:1 mixture of C10
1
epimers by H NMR) as a colorless oil. 26: Rf = 0.45 (silica gel, hexanes:EtOAc 95:05); IR (film) νmax
3310, 2954, 2929, 2857, 1650, 1525, 1472, 1463, 1432, 1351, 1255, 1094, 1073, 1004, 958, 937, 919,
832, 813, 774 cm1; 1H NMR (600 MHz, CDCl3, ca. 3:1 mixture of C10 epimers)  = 7.29 (dq, J = 16.4,
7.5 Hz, 1 H), 6.99 (ddd, J = 13.4, 3.5, 1.9 Hz, 1 H), 5.61 (m, 1 H), 5.23–5.06 (m, 2 H), 3.71–3.64 (m, 1
H), 2.42–2.24 (m, 3 H), 2.16–2.04 (m, 1 H), 1.96 (s, 1 H), 1.87–1.77 (m, 1 H), 1.75–1.58 (m, 2 H),
1.58–1.48 (m, 1 H), 1.45–1.37 (m, 1 H), 0.93 (s, 9 H), 0.11 (s, 3 H), 0.08 ppm (s, 3 H); 13C NMR (151
MHz, CDCl3, ca. 3:1 mixture of C10 epimers):  = 143.1, 142.7, 140.0, 139.9, 138.0, 137.7, 118.3,
117.8, 84.5, 74.6, 74.2, 68.9(4), 68.8(7), 48.6, 48.5, 32.5, 32.4, 29.2, 29.0, 26.3, 26.1(3C), 25.2, 24.1,
18.5, 18.4, 16.7, 4.0(2C) ppm; HRMS (ESI): calcd for C18H31NNaO3Si+ [M + Na+]: 360.1971, found
360.1965.
S8

OTBS
H
10
H
28
NO2
Tricycle 28: To a stirred solution of Pd(OAc)2 (32 mg, 0.14 mmol) in toluene (10 mL) at
room temperature was added PPh3 (77 mg, 0.28 mmol). The resulting mixture was stirred for 30 min
before an aliquot (2 mL) was added to a solution of ene-yne nitroolefin 26 (95 mg, 0.28 mmol) in
toluene (8 mL). The resulting mixture was heated to 80 °C and stirred for 2.5 h before it was cooled to
room temperature and concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc
98:02  95:05) afforded tricycle 28 (69 mg, 73%, ca. 3:1 mixture of C10 epimers by 1H NMR) as a light
yellow oil. 28: Rf = 0.50 (hexanes:EtOAc 95:05); IR (film) νmax 2952, 2929, 2856, 1546, 1471, 1461,
1
1442, 1376, 1349, 1253, 1082, 1044, 1006, 991, 956, 912, 877, 835, 774 cm1; H NMR (600 MHz,
CDCl3, ca. 3:1 mixture of C10 epimers)  = 4.23–4.13 (m, 0.75 H), 4.12–4.06 (m, 0.25 H), 3.90–3.82 (m,
0.25 H), 3.78 (m, 0.75 H), 3.06 (s, 0.25 H), 2.85 (s, 0.75 H), 2.80 (dd, J = 13.8, 6.6 Hz, 1 H), 2.70 (s, 1
H), 2.66–2.59 (m, 1 H), 2.51 (m, 2 H), 2.35 (m, 1 H), 2.29–2.00 (m, 2 H), 1.85–1.65 (m, 2 H), 1.48 (dd,
J = 12.1, 9.8 Hz, 1 H), 1.38 (d, J = 14.6 Hz, 1 H), 0.91 (s, 7 H), 0.89 (s, 2 H), 0.76 (t, J = 13.5 Hz, 1 H),
13
0.07 (s, 2 H), 0.05 (s, 2 H), 0.03 ppm (s, 2 H); C NMR (151 MHz, CDCl3, ca. 3:1 mixture of C10
epimers):  = 144.4, 142.8, 135.7, 133.6, 88.4, 88.1, 76.3, 74.6, 54.9, 51.4, 41.2, 40.2, 36.1, 35.1, 34.1,
32.1, 31.7, 30.9, 29.7, 29.5, 28.8, 28.5, 28.1, 27.1, 25.8(3C), 21.8, 18.2, 18.1, 4.8, 4.8(6), 4.8(8),
5.0 ppm; HRMS (ESI): calcd for C18H31NNaO3Si+ [M + Na+]: 360.1971, found 360.1963.
OTBS
10
OTBS
10
H
H
H
H
H
H
H
H
15a
15b
O
O
Ketones 15a and 15b: To a stirred solution of tricycle 28 (2.05 g, 6.07
mmol) in CH2Cl2 (250 mL) at room temperature were added freshly prepared o-
nitrobenzenesulfonylhydrazide (13.2 g, 60.8 mmol)[5] and Et3N (25.3 mL, 181.5 mmol). The resulting
S9

suspension was stirred for 7 h before the bright orange solution obtained was diluted with CH2Cl2 (150
mL) and washed with NaHCO3 (3 × 200 mL, sat. aq.). The organic layer was dried (Na2SO4) and
concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 95:05) afforded the
reduced tricycle 28’ (1.75 g, 85%, ca. 3:1 mixture of C10 epimers by 1H NMR) as a colorless oil.
To a stirred solution of the reduced tricycle 28’ (obtained above, 507 mg, 1.50 mmol) in THF
(60 mL) was added t-BuOK (1.0 g, 9 mmol). The resulting red solution was stirred for 5 min before a
solution of Na2HPO4 (1.0 N aq., 45 mL) and Oxone (2.8 g, 4.5 mmol) in H2O (15 mL) was added. The
resulting suspension was stirred for 30 min before H2O (30 mL) was added and the solution was
extracted with EtOAc (3 × 50 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo.
Flash column chromatography (silica gel, hexanes:EtOAc 95:05) afforded ketone 15 (396 mg, 86%, ca.
3:1 mixture of C10 epimers by 1H NMR) as a colorless oil. For analytical purpose the C10 epimers could
be separated and fully characterized.
15a: Rf = 0.60 (silica gel, hexanes:EtOAc 80:20); IR (film) νmax 2950, 2927, 2856, 1707, 1471, 1462,
1
1380, 1360, 1253, 1167, 1077, 1027, 1006, 979, 940, 895, 862, 835, 773 cm1; H NMR (600 MHz,
CDCl3):  = 3.873.84 ppm (m, 1 H), 2.632.57 (m, 2 H), 2.532.45 (m, 2 H), 2.42 (dd, J = 2.2, 14.3
Hz, 1 H), 2.382.31 (m, 1 H), 2.202.14 (m, 1 H), 2.021.93 (m, 2 H), 1.791.60 (m, 5 H), 0.04 (s, 3
H), 1.421.27 (m, 2 H), 0.90 (s, 9 H), 0.05 (s, 3 H); 13C NMR (151 MHz, CDCl3):  = 217.1, 73.7, 48.6,
46.3, 44.7, 40.0, 37.5, 32.9, 29.3, 29.0, 28.9, 25.9(3C), 25.2, 18.0, 4.8, 5.0 ppm; HRMS (ESI): calcd
for C18H33O2Si+ [M + H+]: 309.2250, found 309.2240.
15b: Rf = 0.55 (silica gel, hexanes:EtOAc 80:20); IR (film) νmax 2926, 2855, 1707, 1471, 1462, 1385,
1
1360, 1254, 1175, 1136, 1067, 1005, 940, 901, 866, 835, 773 cm1; H NMR (600 MHz, CDCl3):  =
3.93 ppm (ddd, J = 2.0, 4.8, 11.3 Hz, 1 H), 2.632.47 (m, 2 H), 2.442.38 (m, 1 H), 2.282.22 (m, 1 H),
2.062.00 (m, 2 H), 1.891.85 (m, 1 H), 1.851.77 (m, 1 H), 1.741.60 (m, 4 H), 1.571.54 (m, 2 H),
13
1.441.29 (m, 2 H), 0.87 (s, 9 H), 0.04 (s, 6 H); C NMR (151 MHz, CDCl3):  = 216.2, 73.6, 47.1,
S10

46.3, 44.5, 40.6, 35.1, 33.0, 31.7, 29.7, 29.0, 25.8(3C), 25.0, 18.1, 4.8, 4.9 ppm; HRMS (ESI): calcd
for C18H33O2Si+ [M + H+]: 309.2250, found 309.2240.
OTBS
H
10
H
4
H
13
30
O
Enone 30: To a stirred solution of ketone 15 (612 mg, 1.99 mmol) in THF (70 mL) at 78
°C was added LDA (0.5 M in THF, 12 mL, 6.0 mmol). The resulting mixture was stirred for 30 min
before a solution of PhSeBr (720 mg, 3.06 mmol) in THF (5 mL) was added. The resulting mixture was
stirred for 1 h before it was quenched with NH4Cl (60 mL, sat. aq.) and diluted with EtOAc (120 mL).
The layers were separated and the aqueous layer was extracted with EtOAc (2 × 40 mL). The combined
organic layers were dried (Na2SO4) and concentrated in vacuo.
To a stirred solution of the crude residue (obtained above) in CH2Cl2 (36 mL) at 0 °C was added
pyridine (4.0 mL) followed by H2O2 (40 mL, 18% aq.). The resulting mixture was stirred for 15 min
before it was diluted with H2O (50 mL). The layers were separated and the aqueous layer was extracted
with CH2Cl2 (2 × 70 mL). The combined organic layers were quickly washed with HCl (1.0 N aq., 50
mL), dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel,
hexanes:EtOAc 90:10) afforded enone 30 (362 mg, 59%, ca. 3:1 mixture of C10 epimers by 1H NMR) as
a colorless oil. 30: Rf = 0.45 (hexanes:EtOAc 80:20); IR (film) νmax 2950, 2926, 2855, 1666, 1471,
1461, 1444, 1379, 1359, 1307, 1250, 1183, 1159, 1075, 1000, 894, 835, 774 cm1; 1H NMR (600 MHz,
CDCl3, ca. 3:1 mixture of C10 epimers)  = 6.00 ppm (s, 0.3 H), 5.96 (s, 0.7 H), 3.89 (dd, J = 6.1, 10.3
Hz, 0.3 H), 3.67 (dd, J = 2.1, 7.1 Hz, 0.7 H), 2.742.66 (m, 1 H), 2.642.56 (m, 1 H), 2.552.47 (m, 3
H), 2.472.26 (m, 2 H), 2.031.90 (m, 1 H), 1.811.63 (m, 2 H), 1.601.48 (m, 2 H), 1.361.28 (m, 1
13
H), 0.91 (s, 6.7 H), 0.86 (s, 2.3 H), 0.06 (s, 2.2 H), 0.03 (s, 0.8 H), 0.03 (s, 0.8 H), 0.02 (s, 2.2 H); C
NMR (151 MHz, CDCl3, ca. 3:1 mixture of C10 epimers):  = 203.6, 202.5, 172.1, 170.6, 123.6, 123.2,
77.2, 74.8, 44.4, 44.4, 44.1, 40.8, 40.0, 37.8, 31.2, 31.0, 30.9, 30.8, 29.7, 27.8, 26.3, 25.9(6C), 25.7,
S11

23.1, 22.6, 22.2, 18.1, 4.8, 4.8, 4.9, 4.9 ppm; HRMS (ESI): calcd for C18H31O2Si+ [M + H+]:
307.2093, found 307.2091.
OTBS
H
10
4
H
H
O
13
O
31
Epoxy ketone 31: To a stirred solution of enone 30 (362 mg, 1.18 mmol) in MeOH (70
mL) at °C was added a solution of NaOH (10% wt/wt aq., 9.6 mL, 24 mmol) followed by H2O2 (18%
aq., 11 mL, 58.2 mmol). The resulting mixture was stirred for 20 min before it was quenched with
NH4Cl (100 mL, sat. aq.) and diluted with EtOAc (280 mL). The layers were separated and the organic
layer was thoroughly washed with NH4Cl (100 mL, sat. aq.) and H2O (3 × 100 mL), then dried
(Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 90:10)
afforded the epoxy ketone 31 (351 mg, 92%, ca. 3:1 mixture of C10 epimers by 1H NMR) as a colorless
oil. 31: Rf = 0.55 (silica gel, hexanes:EtOAc 80:20); IR (film) νmax 2926, 2855, 1705, 1462, 1450, 1255,
1077, 1044, 1002, 869, 834, 771 cm1; 1H NMR (600 MHz, CDCl3, ca. 4:1 mixture of C10 epimers):  =
3.93 ppm (dd, J = 5.8, 9.3 Hz, 0.2 H), 3.78 (dd, J = 3.0, 7.3 Hz, 0.8 H), 2.692.46 (m, 2 H), 2.172.04
(m, 2 H), 1.971.88 (m, 1 H), 1.67 (m, 2 H), 1.611.47 (m, 4 H), 1.351.27 (m, 2 H), 0.91 (s, 7.2 H),
13
0.87 (s, 1.8 H), 0.07 (s, 2.4 H), 0.05 (s, 0.6 H), 0.04 (d, J = 1.8 Hz, 0.6 H), 0.04 (s, 2.4 H); C NMR
(151 MHz, CDCl3, ca. 4:1 mixture of C10 epimers):  = 210.5, 209.5, 74.7, 74.7, 70.0, 69.6, 59.8, 59.6,
44.0, 44.0, 43.5, 41.6, 36.4, 34.6, 33.0, 31.3, 28.8, 28.4, 28.4, 27.4, 25.9(3C), 25.8(3C), 24.9, 22.5, 21.8,
21.5, 18.1, 17.9, 4.8, 4.9, 4.9, 5.0 ppm; HRMS (ESI): calcd for C18H31O3Si+ [M + H+] 323.2042,
found 323.2032.
S12

OH
10
OH
10
H
4
H
4
H
H
H
13
H
13
O
O
32a
32b
Keto alkynes 32a and 32b: To a stirred solution of epoxy ketone 31 (70
mg, 0.22 mmol) in CH2Cl2 (14 mL) at room temperature were added TFA (84 L, 1.1 mmol), silica gel
(196 mg) and p-toluenesulfonylhydrazide (207 mg, 1.1 mmol). The resulting mixture was stirred for 20
min before it was filtered, diluted with CH2Cl2 (30 mL) and washed with NaHCO3 (15 mL, sat. aq.).
The organic layer was dried (Na2SO4) and concentrated in vacuo to afford the fragmentation product in
its hydrazone form. The desired keto-alkyne 32 was obtained by dissolving the hydrazone in a mixture
of acetone (2 mL) and THF/HCl (1.0 N aq., 1:1, 10 mL). The solution was stirred at room temperature
for 4 h before it was extracted with EtOAc (3 × 10 mL), dried (Na2SO4) and concentrated in vacuo.
Flash column chromatography (silica gel, hexanes:EtOAc 50:50) afforded the keto-alkyne 32a (33 mg,
78%) and 32b (7 mg, 17%) as colorless oils.
32a: Rf = 0.25 (silica gel, hexanes:EtOAc 40:60); IR (film) νmax 3430, 2927, 1733, 1666, 1453, 1406,
1336, 1164, 1042, 813, 675 cm1; 1H NMR (600 MHz, CDCl3):  = 3.72 (dt, J = 8.8, 5.8 Hz, 1 H), 2.93–
2.78 (m, 1 H), 2.48–2.37 (m, 2 H), 2.37–2.32 (m, 2 H), 2.29–2.23 (m, 1 H), 2.21–2.11 (m, 1 H), 2.09 (d,
J = 2.6 Hz, 1 H), 2.08–2.02 (m, 1 H), 1.97–1.82 (m, 2 H), 1.72–1.58 (m, 2 H), 1.58–1.48 ppm (m, 2 H);
13C NMR (151 MHz, CDCl3):  = 219.1, 87.1, 76.7, 69.9, 50.8, 48.0, 37.4, 34.4(4), 34.4(1), 28.2, 27.5,
+
26.6 ppm; HRMS (ESI): calcd for C12H16NaO2 [M + Na+] 215.1048, found 215.1046.
32b: Rf = 0.45 (silica gel, hexanes:EtOAc 40:60); IR (film) νmax 3445, 3298, 2918, 2850, 1724, 1454,
1
1406, 1359, 1285, 1261, 1156, 1060, 1013, 915, 730, 630 cm1; H NMR (600 MHz, CDCl3):  = 4.08
(s, 1 H), 2.84–2.78 (m, 1 H), 2.53 (tdd, J = 11.4, 5.1, 1.4 Hz, 1 H), 2.47–2.37 (m, 1 H), 2.34–2.26 (m, 1
H), 2.19 (d, J = 2.6 Hz, 1 H), 2.16 (ddd, J = 18.8, 9.7, 5.6 Hz, 1 H), 2.07–1.88 (m, 5 H), 1.70 (ddd, J =
11.2, 6.5, 2.5 Hz, 2 H), 1.54 ppm (ddd, J = 14.2, 11.0, 5.6 Hz, 2 H); 13C NMR (151 MHz, CDCl3):  =
S13

220.7, 87.9, 71.1, 69.4, 48.1, 45.5, 38.0, 34.9, 34.5, 29.1, 28.5, 23.9 ppm; HRMS (ESI): calcd for
+
C12H16NaO2 [M + Na+] 215.1048, found 215.1050.
O
H
4
H
H
13
O
33
Diketone 33: To a stirred solution of keto alkyne 32 (53 mg, 0.28 mmol) in CH2Cl2 (20
mL) at room temperature were added NaHCO3 (235 mg, 2.8 mmol) and DMP (237 mg, 0.56 mmol).
The resulting mixture was stirred for 2 h before it was diluted with CH2Cl2 (20 mL) and quenched with
Na2S2O3 (20 mL, sat. aq.). The layers were separated and the aqueous layer was extracted with CH2Cl2
(2 × 20 mL). The combined organic layers were washed with NaHCO3 (50 mL), dried (Na2SO4) and
concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 70:30  50:50)
afforded diketone 33 (47 mg, 89%) as a colorless oil. 33: Rf = 0.50 (silica gel, hexanes:EtOAc 40:60);
IR (film) νmax 3230, 2925, 2853, 1737, 1700, 1455, 1364, 1166, 674 cm1; 1H NMR (600 MHz, CDCl3):
 = 3.22 (td, J = 4.1, 2.0 Hz, 1 H), 2.97 (ddd, J = 18.9, 13.1, 3.6 Hz, 1 H), 2.90 (ddd, J = 12.4, 10.8, 6.6
Hz, 1 H), 2.59–2.50 (m, 2 H), 2.49–2.43 (m, 1 H), 2.38–2.30 (m, 1 H), 2.27–2.07 (m, 4 H), 2.07–2.00
(m, 1 H), 1.96–1.84 (m, 1 H), 1.50 ppm (ddd, J = 13.9, 12.0, 4.0 Hz, 1 H); 13C NMR (151 MHz,
CDCl3):  = 217.2, 210.7, 83.3, 73.4, 54.7, 47.4, 38.9, 36.9, 35.8, 28.5, 26.4, 21.2 ppm; HRMS (EI):
calcd for C12H14O2, 190.0994, found 190.0989.
O
H
H
4
4
H
H
H
13
H
13
35
34
Diene-yne 35 and ene-yne 34: To a stirred suspension of freshly
prepared Ph3P+CH3I (1.45 g, 3.6 mmol)[2] in THF (80 mL) at 0 °C was added n-BuLi (2.0 M in
cyclohexane, 1.76 mL, 3.53 mmol). The resulting mixture was stirred for 30 min before it was cooled to
20 °C and diketone 33 (136 mg, 0.72 mmol) in THF (5 mL) was added. The resulting mixture was
S14

warmed to 0 °C and stirred for 6 h before it was quenched with NH4Cl (50 mL, sat. aq.). The layers
were separated and the aqueous layer was extracted with Et2O (2 × 50 mL). The combined organic
layers were washed with H2O (50 mL), dried (Na2SO4) and concentrated in vacuo. Flash column
chromatography (silica gel, 100% hexane, then hexanes:EtOAc 95:05  90:10) afforded diene-yne 35
(74 mg, 55%) and ene-yne 34 (41 mg, 30%) as colorless oils.
35: Rf = 0.60 (silica gel, 100% hexanes); IR (film) νmax 3311, 3075, 2925, 2854, 1650, 1631, 1438,
1376, 1309, 1248, 1159, 1096, 1025, 947, 885, 805 cm1; 1H NMR (600 MHz, CDCl3):  = 4.94 (d, J =
2.1 Hz, 1 H), 4.85–4.82 (m, 1 H), 4.81 (d, J = 2.1 Hz, 1 H), 4.76 (d, J = 1.6 Hz, 1 H), 3.04 (dd, J = 4.7,
2.5 Hz, 1 H), 2.93–2.77 (m, 1 H), 2.58–2.45 (m, 1 H), 2.44–2.31 (m, 2 H), 2.28–2.22 (m, 1 H), 2.11 (d,
J = 2.6 Hz, 1 H), 2.03–1.95 (m, 1 H), 1.94–1.85 (m, 1 H), 1.80–1.70 (m, 1 H), 1.68–1.52 (m, 2 H),
0.99–0.84 ppm (m, 2 H); 13C NMR (151 MHz, CDCl3):  = 156.6, 151.8, 108.4, 105.1, 87.1, 69.1, 51.4,
44.9, 40.6, 32.5, 32.4, 30.6, 30.3, 29.7 ppm; HRMS (EI): calcd for C14H18, 186.1409, found 186.1384.
34: Rf = 0.40 (silica gel, hexanes:EtOAc 95:05); IR (film) νmax 3292, 3077, 2933, 2856, 1737, 1634,
1
1450, 1438, 1406, 1361, 1279, 1241, 1208, 1145, 1039, 994, 935, 891, 635 cm1; H NMR (600 MHz,
CDCl3):  = 4.94–4.90 (m, 1 H), 4.85–4.80 (m, 1 H), 3.03 (dd, J = 4.7, 2.6 Hz, 1 H), 2.92–2.78 (m, 1
H), 2.63–2.52 (m, 1 H), 2.51–2.35 (m, 3 H), 2.24 (m, 3 H), 2.08 (d, J = 2.4 Hz, 1 H), 1.93 (m, 1 H),
13
1.85–1.73 (m, 1 H), 1.69–1.62 (m, 1 H), 1.37 ppm (ddd, J = 13.9, 11.2, 4.6 Hz, 1 H); C NMR (151
MHz, CDCl3):  = 219.6, 151.1, 109.9, 86.3, 71.1, 51.1, 48.4, 38.2, 35.9, 32.6, 31.5, 29.4, 27.0 ppm;
HRMS (ESI): calcd for C13H16NaO+ [M + Na+] 211.1099, found 211.1095.
H
4
H
H
13
35
Diene-yne 35: To a stirred solution of ene-yne 34 (16 mg, 0.085 mmol) in THF (8 mL) at
78 °C were added pyridine (137 L, 1.7 mmol) and Tebbe reagent (0.5 M in toluene, 0.68 mL, 0.34
mmol). The resulting mixture was stirred at 78 °C for 15 min, then at 0 °C for 15 min and 5 h at room
S15

temperature before it was cooled to 0 °C and quenched with HCl (1.0 N aq., 10 mL). The resulting
mixture was diluted with Et2O (15 mL), the layers were separated and the aqueous layer was extracted
with Et2O (20 mL). The combined organic layers were washed with H2O (20 mL), dried (Na2SO4) and
concentrated in vacuo. Flash column chromatography (silica gel, 100% hexanes) afforded diene-yne 35
(12 mg, 76%) as a colorless oil and whose analytical data are identical those described above.
H
H
16
OH
Propargyl alcohol 16: To a stirred solution of diene-yne 35 (20 mg, 0.107
mmol) in THF (18 mL) at 78 °C was added n-BuLi (2.0 M in cyclohexane, 0.55 mL, 1.1 mmol). The
resulting mixture was warmed to 20 °C and stirred for 30 min before paraformaldehyde (89 mg, 2.97
mmol) was added. The resulting mixture was stirred for 20 min at room temperature before it was
quenched with H2O (15 mL) and diluted with EtOAc (20 mL). The layers were separated and the
aqueous layer was extracted with EtOAc (3 × 20 mL). The combined organic layers were dried
(Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 90:10
 80:20) afforded propargyl alcohol 16 (20 mg, 86%) as a colorless oil. 16: Rf = 0.40 (silica gel,
hexanes:EtOAc 80:20); IR (film) νmax 3340, 3075, 2930, 2867, 1651, 1631, 1434, 1357, 1225, 1121,
1018, 975, 881 cm1; 1H NMR (600 MHz, CDCl3):  = 4.96–4.89 (m, 1 H), 4.82–4.79 (m, 1 H), 4.77 (d,
J = 2.0 Hz, 1 H), 4.73 (d, J = 1.1 Hz, 1 H), 4.27 (dd, J = 5.7, 1.8 Hz, 2 H), 3.06–3.00 (m, 1 H), 2.92–
2.71 (m, 1 H), 2.47 (dd, J = 16.2, 8.2 Hz, 1 H), 2.42–2.26 (m, 3 H), 2.24–2.16 (m, 1 H), 1.99–1.91 (m, 1
H), 1.91–1.85 (m, 1 H), 1.71 (ddt, J = 14.0, 11.4, 2.4 Hz, 1 H), 1.64–1.57 (m, 1 H), 1.51 (ddd, J = 13.8,
11.2, 4.7 Hz, 1 H), 1.45 (t, J = 6.0 Hz, 1 H), 0.88 ppm (t, J = 7.0 Hz, 1 H); 13C NMR (151 MHz,
CDCl3):  = 156.7, 151.9, 108.3, 105.1, 88.9, 80.2, 51.5, 51.2, 45.1, 40.6, 32.7, 32.4, 30.6, 30.4, 29.8
ppm; HRMS (EI): calcd for C15H20O, 216.1514, found 216.1500.
S16

H
H
17
O
Aldehyde 17: To a stirred solution of propargyl alcohol 16 (9 mg, 0.042 mmol) in
freshly distilled acetone (4 mL) at room temperature was added a stock solution (1.0 mL) containing
CpRu(PPh3)2Cl (36.3 mg, 0.05 mmol in 5 mL of acetone) and CSA (8.7 mg, 0.037 mmol in 5 mL of
acetone). The resulting mixture was heated at 56 °C for 5 min in a sealed tube before In(OTf)3 (1.0 mL
from a stock solution containing 28.1 mg, 0.05 mmol in 5 mL of acetone) was added. The resulting
mixture was stirred at 56 °C for 20 h before it was quenched with NaHCO3 (5 mL, sat. aq.), and diluted
with Et2O (10 mL). The layers were separated and the aqueous layer was extracted with Et2O (2 × 10
mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. Preparative TLC
purification (silica gel, hexanes:CH2Cl2 60:40) afforded aldehyde 17 (2.9 mg, 32%) as a colorless oil.
17: Rf = 0.40 (silica gel, hexanes:EtOAc 90:10); IR (film) 3063, 2924, 2866, 1723, 1635, 1455, 1437,
1197, 1119, 1053, 968, 887, 799, 721, 694 cm1; 1H NMR (600 MHz, CDCl3):  = 9.84 (dd, J = 3.0, 1.8
Hz, 1 H), 4.67 (d, J = 3.0 Hz, 1 H), 4.64 (d, J = 2.4 Hz, 1 H), 2.85 (td, J = 9.6, 2.4 Hz, 1 H), 2.68 (dq, J
= 16.2, 1.8 Hz, 1 H), 2.382.37 (m, 1 H), 2.32 (t, J = 8.1 Hz, 1 H), 2.232.13 (m, 2 H), 2.011.96 (m, 1
H), 1.881.80 (m, 3 H), 1.731.67 (m, 1 H), 1.611.54 (m, 1 H), 1.531.48 (m, 1 H), 1.41 (d, J = 13.8
Hz, 1 H), 1.331.27 (m, 1 H), 0.82 (dd, J = 5.4, 1.8 Hz, 1 H), 0.50 ppm (d, J = 5.4 Hz, 1 H); 13C NMR
(150 MHz, CDCl3):  = 203.1, 154.2, 112.3, 48.7, 48.4, 44.7, 40.6, 40.4, 32.8, 31.1, 30.8, 29.5, 28.5,
25.8, 15.9 ppm.
H
H
HO2C
1
Echinopine A ( )
Echinopine A (1): To a stirred solution of aldehyde 17 (11.3 mg, 0.052 mmol) and 2-
methyl-2-butene (55 µL, 0.52 mmol) in t-BuOH/pH 7 phosphate buffer (1:1, 0.8 mL) at room
temperature was added NaClO2 (0.3 M aq., 349 µL, 0.105 mmol). The resulting mixture was stirred for
S17

1 h before it was filtered through a short pad of anhydrous Na2SO4/SiO2 and concentrated in vacuo.
Flash column chromatography (silica gel, hexanes:EtOAc 4:1) afforded echinopine A (1) (11.4 mg,
94%) as a white solid. 1: Rf = 0.25 (silica gel, hexanes:EtOAc 3:1); m.p. = 104105 °C (EtOAc) [Lit.[6]
m.p. = 99102 °C]; IR (film) 2935, 2866, 1703, 1636, 1453, 1410, 1299, 1231, 948, 886, 666 cm1; 1H
NMR (600 MHz, CDCl3):  = 10.69 (br s, 1 H), 4.64 (d, J = 2.4 Hz, 1 H), 4.61 (d, J = 2.4 Hz, 1 H), 2.81
(td, J = 9.0, 1.8 Hz, 1 H), 2.66 (dd, J = 15.0, 1.2 Hz, 1 H), 2.44 (m, 1 H), 2.27 (t, J = 8.0 Hz, 1 H), 2.16
(m, 1 H), 2.14 (dt, J = 13.8, 4.5 Hz, 1 H), 1.95 (m, 1 H), 1.94 (m, 1 H), 1.82 (td, J = 13.2, 4.2 Hz, 1 H),
1.76 (d, J = 15.0 Hz, 1 H), 1.69 (dddd, J = 13.8, 9.6, 6.6, 2.4 Hz, 1 H), 1.52 (ddd, J = 13.2, 9.6, 3.8 Hz, 1
H), 1.44 (dtd, J = 13.8, 7.2, 1.2 Hz, 1 H), 1.36 (d, J = 13.8 Hz, 1 H), 1.27 (tdd, J = 13.8, 4.2, 3.0 Hz, 1
13
H), 0.73 (dd, J = 5.4, 1.2 Hz, 1 H), 0.50 ppm (d, J = 4.8 Hz, 1 H); C NMR (150 MHz, CDCl3):  =
178.7, 154.3, 112.1, 48.7, 48.5, 41.4, 40.5, 35.2, 32.7, 31.0, 30.5, 29.9, 29.4, 25.7, 16.1 ppm; HRMS
(ESI): calcd for C15H20O2Na+ [M + Na+] 255.1356, found 255.1357.
H
H
MeO2C
2
Echinopine B ( )
Echinopine B (2): To a stirred solution of echinopine A (1) (4.1 mg, 0.018 mmol) in
benzene/MeOH (4:1, 1.5 mL) at room temperature was added TMSCHN2 (2.0 M in Et2O, 13.3 µL,
0.027 mmol). The resulting mixture was stirred for 0.5 h before it was concentrated in vacuo. Flash
column chromatography (silica gel, hexanes:EtOAc 200:1) afforded echinopine B (2) (4.0 mg, 92%) as
a white amorphous solid. 2: Rf = 0.40 (silica gel, hexanes:EtOAc 95:5); IR (film) 3064, 2933, 2866,
1
1740, 1636, 1456, 1434, 1270, 1221, 1165, 1075, 1009, 885 cm1; H NMR (600 MHz, CDCl3):  =
4.63 (d, J = 3.0 Hz, 1 H), 4.60 (d, J = 3.0 Hz, 1 H), 3.68 (s, 3 H), 2.80 (td, J = 9.0, 1.8 Hz, 1 H), 2.64
(dd, J = 15.0, 1.2 Hz, 1 H), 2.39 (m, 1 H), 2.25 (t, J = 8.1 Hz, 1 H), 2.14 (m, 1 H), 2.12 (m, 1 H), 1.93
(m, 2 H), 1.82 (td, J = 13.2, 4.2 Hz, 1 H), 1.72 (d, J = 15.0 Hz, 1 H), 1.65 (m, 1 H), 1.51 (m, 1 H), 1.44
(m, 1 H), 1.35 (d, J = 13.8 Hz, 1 H), 1.26 (m, 1 H), 0.69 (dd, J = 5.1, 1.5 Hz, 1 H), 0.47 ppm (d, J = 5.4
S18

Hz, 1 H); 13C NMR (150 MHz, CDCl3):  = 173.6, 154.3, 111.8, 51.4, 48.5, 48.4, 41.2, 40.5, 35.2, 32.6,
30.9, 30.3, 30.0, 29.3, 25.6, 15.9 ppm; HRMS (ESI): calcd for C16H22O2Na+ [M + Na+] 269.1512, found
269.1514.
Asymmetric Synthesis of ()-22:
OH
TMS
37
TMS alcohol 37: To a stirred solution of 5-hexyne-1-ol (5.7 mL, 50 mmol) in THF
(150 mL) at 78 °C were added n-BuLi (1.55 M in hexane, 71 mL, 110 mmol) and DMAP (1.31 g, 10.6
mmol). The resulting mixture was stirred for 1 h before TMSCl (19.0 mL, 180 mmol) was added. The
resulting mixture was warmed to room temperature and stirred for 2 h before it was quenched with HCl
(1.0 N aq., 50 mL). The resulting mixture was stirred for 30 min before EtOAc (200 mL) was added.
The layers were separated and the aqueous layer was extracted with EtOAc (3 × 50 mL). The combined
organic layers were washed with NaHCO3 (100 mL, sat. aq.), brine (30 mL), dried (Na2SO4) and
concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 80:20) afforded TMS
alcohol 37 (7.60 g, 99%) as a colorless oil. 37: Rf = 0.38 (silica gel, hexanes:EtOAc 80:20). The 1H and
13C NMR spectroscopic data were identical to those reported in literature.[7]
O
HO
TMS
38
Acid 38: To a stirred solution of alcohol 37 (6.34 g, 41 mmol) in DMF (82 mL) at
0 °C was added PDC (54.2 g, 144 mmol). The resulting mixture was stirred for 15 min before it was
warmed to room temperature and stirred for 12 h. Silica gel (100 g) and EtOAc (100 mL) were added
and the resulting mixture was stirred for 10 min before it was filtered through a pad of silica gel and
washed through with EtOAc (3 × 150 mL). The combined filtrate was concentrated in vacuo. Flash
column chromatography (silica gel, hexanes:EtOAc 90:10  70:30) afforded acid 38 (4.34 g, 56%) as a
colorless oil. 38: Rf = 0.28 (silica gel, hexanes:EtOAc 70:30); IR (film) νmax 3006, 2989, 2960, 2902,
S19

1
2175, 1708, 1411, 1275, 1260, 1046, 836, 750, 698, 637 cm1; H NMR (600 MHz, CDCl3):  = 2.50
ppm (t, J = 7.2 Hz, 2 H), 2.32 (t J = 6.6 Hz, 2 H), 1.84 (q, J = 7.1 Hz, 2 H), 0.15 (s, 9 H); 13C NMR (151
MHz, CDCl3):  = 178.7, 105.7, 85.7, 32.5, 23.4, 19.2, 0.1 ppm (3C); HRMS (ESI): calcd for
C9H15O2Si- [M  H+] 183.0841, found 183.0846.
S
O
S
N
TMS
Bn
39
Thiazolidinethione 39: To a stirred solution of DCC (5.67 g, 27.2 mmol) in
CH2Cl2 (100 mL) at 15 °C was added acid 38 (5 g, 27.2 mmol). The resulting mixture was stirred for
30 min before thiazolidinethione[8] (5.69 g, 27.2 mmol) was added followed by DMAP (3.69 g, 29.2
mmol). The resulting mixture was warmed to room temperature over a period of 1 h before it was
filtered through a pad of Celite® and washed through with CH2Cl2 (200 mL). The combined filtrate was
concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 90:10) afforded
thiazolidinethione 39 (5.74 g, 56%) as a yellow oil. 39: Rf = 0.42 (silica gel, hexanes:EtOAc 80:20);
[α] 2D5 = +109.3 (c = 1.00, CHCl3); IR (film) νmax 3029, 2958, 2173, 1695, 1496, 1454, 1363, 1341, 1318,
1
1292, 1265, 1248, 1192, 1155, 1136, 1039, 842, 702, 639 cm1; H NMR (600 MHz, CDCl3):  =
7.367.33 ppm (m, 2 H), 7.307.27 (m, 3 H), 5.405.36 (m, 1 H), 3.51 (ddd, J = 17.7, 8.4, 6.0 Hz, 1 H),
1.15 (s, 9 H), 3.39 (ddd, J = 11.5, 7.2, 0.8 Hz, 1 H), 3.23 (ddd, J = 17.7, 8.4, 6.0 Hz, 1 H), 3.23 (dd, J =
13.2, 3.9 Hz, 1 H), 3.21 (dd, J = 13.1, 10.5 Hz, 1 H), 2.88 (d, J = 11.5 Hz, 1 H), 2.34 (td, J = 7.0, 1.3 Hz,
13
2 H), 1.981.83 (m, 2 H); C NMR (151 MHz, CDCl3):  = 201.0, 173.5, 136.5, 129.4 (2C), 128.9
(2C), 127.2, 106.1, 85.7, 68.5, 37.3, 36.8, 31.9, 23.6, 19.1, 0.1 ppm (3C); HRMS (ESI): calcd for
C19H25NOS2SiNa+ [M + Na+] 398.1045, found 398.1050.
S20

O
OH
O
OH
OH
OTBS
MeO
MeO
40a
40
TMS
TMS
Methyl esters 40 and 40a: To a stirred solution
of thiazolidinethione 39 (4.62 g, 12.3 mmol) in CH2Cl2 (130 mL) at 78 °C was added TiCl4 (1.42 mL,
12.9 mmol). The resulting mixture was stirred for 15 min before i-Pr2NEt (2.25 mL, 12.9 mmol) was
added, and the resulting mixture was stirred for 45 min before NMP (2.49 mL, 25.8 mmol) was added.
The resulting mixture was stirred for 15 min before a solution of aldehyde 19 (3.0 g, 14.8 mmol) in
CH2Cl2 (3 mL) was added. The resulting mixture was warmed to 40 °C before it was warmed to 0
°C over a period of 1.5 h and then quenched with HCl (1.0 N aq., 100 mL). The resulting mixture was
diluted with Et2O (300 mL) and warmed to room temperature. The layers were separated and the
aqueous layer was extracted with Et2O (2 × 100 mL). The combined organic layers were washed with
H2O (80 mL), dried (Na2SO4) and concentrated in vacuo. The aldol product appeared to be unstable on
silica gel and was therefore used directly without further purification.
To a stirred solution of the crude aldol product (obtained above) in MeOH (120 mL) at room
temperature were added imidazole (8.2 g, 120.6 mmol) and DMAP (1.50 g, 12.3 mmol). The resulting
mixture was stirred for 12 h before it was quenched with NH4Cl (200 mL, sat. aq.) and diluted with
EtOAc (200 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3 × 150
mL). The combined organic layers were washed with brine (100 mL), dried (Na2SO4) and concentrated
in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 95:05  30:70) afforded methyl
esters 40 (377 mg, 8%) and 40a (1.96 g, 56%) as a colorless oils and recovered thiazolidinethione (2.25
g, 87%) as a white solid.
40: Rf = 0.50 (silica gel, hexanes:EtOAc 75:25); [α] 25 = 22.4 (c = 1.0, CHCl3); IR (film) νmax 3427,
D
2953, 2929, 2898, 2857, 2175, 1735, 1472, 1463, 1436, 1388, 1361, 1249, 1204, 1162, 1097, 1040,
S21

1005, 938, 835, 775, 760 cm1; 1H NMR (600 MHz, CDCl3):  = 3.84 (ddd, J = 10.1, 7.3, 2.8 Hz, 1 H),
3.70 (s, 3 H), 3.67–3.63 (m, 2 H), 3.20 (d, J = 4.5 Hz, 1 H), 2.60 (ddd, J = 9.6, 5.3, 4.0 Hz, 1 H), 2.35–
2.16 (m, 2 H), 1.98–1.84 (m, 2 H), 1.72–1.63 (m, 2 H), 1.62–1.57 (m, 1 H), 1.50 (ddt, J = 13.9, 9.1, 6.8
Hz, 1 H), 0.89 (s, 9 H), 0.14 (s, 9 H), 0.06 ppm (s, 6 H); 13C NMR (151 MHz, CDCl3):  = 175.0, 106.4,
85.1, 71.8, 63.2, 51.7, 50.2, 31.8, 29.1, 26.4, 25.9(3C), 18.2(8), 18.2(6), 0.1(3C), 5.40(2C) ppm;
+
HRMS (ESI): calcd for C20H40NaO4Si2 [M + Na+] 423.2363, found 423.2359.
40a: Rf = 0.30 (silica gel, hexanes:EtOAc 75:25); [α] 25 = .2 (c = 1.0, CHCl3); IR (film) νmax 3365,
D
1
2954, 2174, 1717, 1436, 1365, 1249, 1205, 1163, 1108, 1042, 912, 838, 759, 732, 698, 639 cm1; H
NMR (600 MHz, CDCl3):  = 3.94–3.83 (m, 1 H), 3.71 (s, 3 H), 3.77–3.59 (m, 2 H), 2.67–2.55 (m, 1
H), 2.37–2.15 (m, 2 H), 1.94 (ddd, J = 13.4, 9.8, 7.4 Hz, 1 H), 1.85 (dtd, J = 13.8, 7.9, 3.8 Hz, 1 H),
13
1.77–1.68 (m, 2 H), 1.64–1.46 (m, 2 H), 0.13 ppm (s, 9 H); C NMR (151 MHz, CDCl3):  = 175.2,
106.2, 85.4, 71.8, 62.7, 51.8, 50.0, 31.6, 29.4, 26.1, 18.2, 0.1(3C) ppm; HRMS (ESI): calcd for
C14H26NaO4Si+ [M + Na+] 309.1498, found 309.1505.
O
OTBS
OTBS
MeO
41
TMS
Bis-TBS ether 41: To a stirred solution of diol 40a (2.32 g, 8.1 mmol) in
CH2Cl2 (80 mL) at 0 °C were added Et3N (6.8 mL, 48.8 mmol) and TBSOTf (5.6 mL, 24.3 mmol). The
resulting mixture was stirred for 30 min before it was quenched with NaHCO3 (100 mL, sat. aq.) and
diluted with CH2Cl2 (100 mL). The layers were separated and the aqueous layer was extracted with
CH2Cl2 (2 × 50 mL). The combined organic layers were washed with NH4Cl (2 × 100 mL, sat. aq.),
brine (50 mL), dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel,
hexanes:EtOAc 95:05  90:10) afforded bis-TBS ether 41 (3.76 g, 90%) as a colorless oil. 41: Rf =
0.80 (silica gel, hexanes:EtOAc 90:10); [α] 25 = +39.5 (c = 1.0, CHCl3); IR (film) νmax 2954, 2929, 2895,
D
S22

2857, 2175, 1737, 1472, 1463, 1435, 1388, 1361, 1275, 1250, 1200, 1164, 1083, 1044, 1005, 939, 833,
1
772 cm1; H NMR (600 MHz, CDCl3):  = 3.98 (q, J = 4.9 Hz, 1 H), 3.67 (s, 3 H), 3.59 (dd, J = 5.5,
3.3 Hz, 2 H), 2.69 (ddd, J = 10.6, 4.8, 3.3 Hz, 1 H), 2.37–2.14 (m, 2 H), 1.90 (ddd, J = 13.5, 10.8, 6.8
Hz, 1 H), 1.77–1.68 (m, 1 H), 1.59–1.47 (m, 4 H), 0.89 (s, 9 H), 0.87 (s, 9 H), 0.13 (s, 9 H), 0.04 ppm
(s, 12 H); 13C NMR (151 MHz, CDCl3):  = 174.3, 106.6, 85.1, 73.1, 63.0, 51.4, 49.3, 31.1, 28.3,
25.9(3C), 25.8(3C), 25.8, 18.3, 18.0(2C), 0.1(3C), 4.3, 4.8, 5.3(2C) ppm; HRMS (ESI): calcd for
+
C26H54NaO4Si3 [M + Na+] 537.3228, found 537.3240.
OH OTBS
OTBS
10
TMS
42
Alcohol 42: To a stirred solution of methyl ester 41 (3.64 g, 7.06
mmol) in CH2Cl2 (70 mL) at 78 °C was added Dibal-H (1.0 M in toluene, 21.0 mL, 21.0 mmol). The
resulting mixture was stirred for 1 h before it was warmed to 0 °C, quenched with HCl (1.0 N aq.,
100mL) and diluted with EtOAc (100 mL). The layers were separated and the aqueous layer was
extracted with EtOAc (2 × 50 mL). The combined organic layers were washed with brine (50 mL), dried
(Na2SO4) and concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc 95:05
 80:20) afforded alcohol 42 (3.38 g, 96%) as a colorless oil. 42: Rf = 0.35 (silica gel, hexanes:EtOAc
90:10); [α] 25 = +35.2 (c = 1.0, CHCl3); IR (film) νmax 3447, 2954, 2929, 2896, 2857, 2174, 1472, 1463,
D
1
1387, 1361, 1249, 1096, 1033, 1005, 939, 832, 773, 760 cm1; H NMR (600 MHz, CDCl3):  = 3.91–
3.83 (m, 1 H), 3.75 (ddd, J = 11.8, 8.7, 3.4 Hz, 1 H), 3.67–3.57 (m, 3 H), 2.92 (dd, J = 6.9, 3.4 Hz, 1 H),
2.36–2.21 (m, 2 H), 2.08–1.97 (m, 1 H), 1.71–1.60 (m, 1 H), 1.58–1.51 (m, 2 H), 1.48–1.35 (m, 3 H),
0.89 (s, 18 H), 0.14 (s, 9 H), 0.13 (s, 3 H), 0.09 (s, 3 H), 0.04 ppm (s, 6 H); 13C NMR (151 MHz,
CDCl3):  = 106.8, 85.1, 75.7, 63.9, 63.0, 43.4, 29.7, 28.4, 26.4, 25.9(4)(3C), 25.8(5)(3C), 18.3, 18.1,
+
17.9, 0.1(3C), 4.2, 4.5, 5.3(2C) ppm; HRMS (ESI): calcd for C25H54NaO3Si3 [M + Na+] 509.3278,
found 509.3297.
S23

O
OTBS
OTBS
10
TMS
43
Aldehyde 43: To a stirred solution of alcohol 42 (3.34 g, 6.86 mmol)
in CH2Cl2 (70 mL) at room temperature was added NaHCO3 (11.51 g, 137.0 mmol) followed by DMP
(5.8 g, 13.7 mmol). The resulting mixture was stirred for 90 min before it was quenched with Na2S2O3
(100 mL, sat. aq.). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2 × 50
mL). The combined organic layers were washed with NaHCO3 (100 mL), dried (Na2SO4) and
concentrated in vacuo. Flash column chromatography (silica gel, hexanes:EtOAc from 95:05  90:10)
afforded aldehyde 43 (2.97 g, 89%) as a colorless oil. 43: Rf = 0.70 (silica gel, hexanes:EtOAc 90:10);
[α] 25 = +46.0 (c = 1.0, CHCl3); IR (film) νmax 2954, 2929, 2896, 2857, 2174, 1725, 1472, 1463, 1434,
D
1407, 1388, 1361, 1250, 1096, 1048, 1005, 968, 938, 833, 773, 760 cm1; 1H NMR (600 MHz, CDCl3):
 = 9.84 (s, 1 H), 4.09 (s, 1 H), 3.60 (s, 2 H), 2.74–2.62 (m, 1 H), 2.40–2.22 (m, 2 H), 1.98 (td, J = 15.0,
6.3 Hz, 1 H), 1.66–1.39 (m, 5 H), 0.89 (s, 9 H), 0.88 (s, 9 H), 0.13 (s, 9 H), 0.08 (s, 6 H), 0.04 ppm (s, 6
H); 13C NMR (151 MHz, CDCl3):  = 204.9, 106.4, 85.5, 72.3, 62.7, 55.5, 30.8, 29.1, 25.9(3C),
25.8(3C), 22.9, 18.3, 18.1, 18.0, 0.1(3C), 4.4, 4.5, 5.1(2C) ppm; HRMS (ESI): calcd for
+
C25H52NaO3Si3 [M + Na+] 507.3122, found 507.3132.
OTBS
OTBS
10
TMS
()-22
Alkene ()-22: To a stirred solution of Ph3P+CH3I (4.92 g, 12.2
mmol) in THF (100 mL) at 0 °C was added n-BuLi (1.6 M in hexane, 7.5 mL, 12.0 mmol). The
resulting homogeneous solution was cooled to 40 °C before a solution of aldehyde 43 (2.95 g, 6.08
mmol) in THF (10 mL) was added. The resulting mixture was warmed to 5 °C over a period of 1.5 h
before it was quenched with NH4Cl (100 mL, sat. aq.) and diluted with EtOAc (100 mL). The layers
were separated and the aqueous layer was extracted with EtOAc (2 × 100 mL). The combined organic
layers were washed with brine (100 mL), dried (Na2SO4) and concentrated in vacuo. Flash column
S24

chromatography (silica gel, hexanes:EtOAc from 98:02  95:05) afforded alkene ()-22 (1.34 g, 46%)
as a colorless oil. ()-22: Rf = 0.55 (silica gel, hexanes:EtOAc 98:02); [α] 25 = 13.7 (c = 1.0, CHCl3); IR
D
(film) νmax 2955, 2929, 2896, 2857, 2176, 1472, 1463, 1406, 1387, 1361, 1249, 1096, 1004, 938, 916,
832, 772, 760 cm1; 1H NMR (600 MHz, CDCl3):  = 5.64 (ddd, J = 17.2, 10.3, 9.0 Hz, 1 H), 5.14–5.02
(m, 2 H), 3.74–3.52 (m, 3 H), 2.39–2.24 (m, 2 H), 2.17–2.05 (m, 1 H), 1.75 (tdd, J = 11.4, 8.5, 3.5 Hz, 1
H), 1.66–1.36 (m, 5 H), 0.92 (m, 9 H), 0.91 (s, 9 H), 0.17 (s, 9 H), 0.08 (s, 3 H), 0.07 ppm (s, 9 H); 13C
NMR (151 MHz, CDCl3):  = 138.7, 116.5, 107.6, 84.5, 74.9, 63.3, 48.2, 30.2, 28.4(3), 28.3(5),
+
26.0(6C), 18.3, 18.1, 17.8, 0.2(3C), 4.3, 4.4, 5.3(2C) ppm; HRMS (ESI): calcd for C26H54NaO2Si3
[M + Na+] 505.3329, found 505.3336.
S25

1
Table 1. H NMR Spectroscopic (600 MHz, CDCl3, 25 °C) Comparison of Synthetic and Natural[9]
Echinopine A (1)
6
7
5
9
H
1
15
13
H
4
8
2
O
10
3
11
12
14
OH
Echinopine A (1)
Synthetic
 H [ppm, mult, J (Hz)]
2.81 (td, J = 9.0, 1.8 Hz)
Natural[9]
 H [ppm, mult, J (Hz)]
2.81 (td, J = 9.1, 2.1 Hz)
No.
1
1
1
2a
2b
3a
3b
4
2.16 (m)
2.16 (m)
1.69 (dddd, J = 13.8, 9.6, 6.6, 2.4 Hz)
1.95 (m)
1.52 (ddd, J = 13.2, 9.6, 3.8 Hz)
--
1.65 (dddd, J = 14.0, 9.7, 6.7, 2.6 Hz)
1.95 (m)
1.52 (ddd, J = 13.5, 9.7, 4.0 Hz)
--
5
2.27 (t, J = 8.0 Hz)
1.44 (dtd, J = 13.8, 7.2, 1.2 Hz)
1.36 (d, J = 13.8 Hz)
2.44 (m)
2.26 (~t, J = ~8.0 Hz)
1.44 (dtd, J = 13.7, 7.4, 0.9 Hz)
1.36 (d, J = 13.7 Hz)
2.43 (m)
6a
6b
7
8a
8b
9a
9b
10
1.94 (m)
1.93 (m)
1.27 (tdd, J = 13.8, 4.2, 3.0 Hz)
2.14 (dt, J = 13.8, 4.5 Hz)
1.82 (td, J = 13.2, 4.2 Hz)
--
1.27 (tdd, J = 13.6, 4.0, 3.0 Hz)
2.12 (dt, J = 13.3, ~4.7 Hz)
1.82 (td, J = 13.3, 4.2 Hz)
--
11a 2.66 (dd, J = 15.0, 1.2 Hz)
11b 1.76 (d, J = 15.0 Hz)
2.66 (dd, J = 15.3, 1.3 Hz)
1.75 (d, J = 15.3 Hz)
--
12
13
--
--
--
14a 4.64 (d, J = 2.4 Hz)
14b 4.61 (d, J = 2.4 Hz)
15a 0.73 (dd, J = 5.4, 1.2 Hz)
15b 0.50 (d, J = 4.8 Hz)
OH 10.69 (br s)
4.63 (d, J = 2.6 Hz)
4.60 (d, J = 2.6 Hz)
0.73 (dd, J = 5.3, 1.3 Hz)
0.50 (d, J = 5.3 Hz)
10.53 (br s)
S26

13
Table 2. C NMR Spectroscopic (150 MHz, CDCl3, 25 °C) Comparison of Synthetic and Natural[9]
Echinopine A (1)
6
7
5
9
H
1
15
13
H
4
8
2
O
10
3
11
12
14
OH
Echinopine A (1)
Synthetic
Natural[9]
No.
 13C (ppm)
 13C (ppm)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
48.7
31.0
25.7
41.4
48.5
30.5
40.5
32.7
29.4
154.3
35.2
178.7
29.9
112.1
16.1
48.7
31.1
25.7
41.5
48.6
30.5
40.6
32.8
29.4
154.3
35.2
178.2
29.9
112.1
16.1
S27

1
Table 3. H NMR Spectroscopic (600 MHz, CDCl3, 25 °C) Comparison of Synthetic and Natural[9]
Echinopine B (2)
Synthetic
 H [ppm, mult, J (Hz)]
2.80 (td, J = 9.0, 1.8 Hz)
Natural[9]
 H [ppm, mult, J (Hz)]
2.80 (br t, J = ~10.0 Hz)
No.
1
1
1
2a
2b
3a
3b
4
2.14 (m)
1.65 (m)
1.93 (m)
1.51 (m)
2.14 (m)
1.65 (m)
1.93 (m)
1.51 (m)
--
--
5
2.25 (t, J = 8.1 Hz)
1.44 (m)
1.35 (d, J = 13.8 Hz)
2.39 (m)
2.25 (~t, J = ~9.0 Hz)
1.44 (m)
1.35 (d, J = 13.8 Hz)
2.39 (m)
6a
6b
7
8a
8b
9a
9a
10
1.93 (m)
1.26 (m)
2.12 (m)
1.82 (td, J = 13.2, 4.2 Hz)
--
1.93 (m)
1.26 (m)
2.11 (m)
1.82 (td, J = 13.2, 4.0 Hz)
--
11a 2.64 (dd, J = 15.1, 1.2 Hz)
11b 1.72 (d, J = 15.0 Hz)
2.65 (dd, J = 15.1, 1.3 Hz)
1.72 (d, J = 15.1 Hz)
--
12
13
--
--
--
14a 4.63 (d, J = 3.0 Hz)
14b 4.60 (d, J = 3.0 Hz)
15a 0.69 (dd, J = 5.1, 1.5 Hz)
15b 0.47 (d, J = 4.0 Hz)
OMe 3.68 (s)
4.63 (d, J = 2.6 Hz)
4.60 (d, J = 2.6 Hz)
0.69 (dd, J = 5.1, 1.3 Hz)
0.47 (d, J = 5.1 Hz)
3.68 (s)
S28

13
Table 4. C NMR Spectroscopic (150 MHz, CDCl3, 25 °C) Comparison of Synthetic and Natural[9]
Echinopine B (2)
Synthetic
Natural[9]
No.
 13C (ppm)
 13C (ppm)
1
2
3
4
5
6
7
8
9
48.5
30.9
25.6
30.0
48.4
30.3
40.5
32.6
29.3
154.3
35.2
173.6
41.2
111.8
15.9
51.4
48.5
30.9
25.4
29.8
48.4
30.3
40.4
32.5
29.3
154.3
35.1
173.7
41.0
111.9
15.7
51.3
10
11
12
13
14
15
OMe
S29

II) Abbreviations
TBS = tert-butyldimethylsilyl
TMS = trimethylsilyl
DMSO = dimethyl sulfoxide
OTf = trifluoromethanesulfonate
p-TsOH = p-toluenesulfonic acid
DMP = Dess-Martin periodinane
Dibal-H = diisobutylaluminium hydride
DMF = N,N'-dimethylformamide
LDA = lithium diisopropylamide
PDC = pyridinium dichromate
DCC = dicyclohexylcarbodiimide
DMAP = 4-dimethylaminopyridine
NMP = N-methylpyrrolidone
TMG = 1,1,3,3-tetramethylguanidine
CSA = camphorsulfonic acid
S30