General and efficient strategy for erythrinan and homoerythrinan alkaloids: Syntheses of (±)-3-demethoxyerythratidinone and (±)- erysotramidine

Article abstract of DOI:10.1021/ol0607185

A general and efficient strategy to both aromatic-type and nonaromatic-type erythrinan and homoerythrinan alkaloids has been developed. This approach involves a key two-step sequence, an alkylation of a ketone with various N-substituted iodoacetamides fol

Full text of DOI:10.1021/ol0607185

Supporting Information
A General and Efficient Strategy for Erythrinan and Homoerythrinan
Alkaloids: Syntheses of (±)-3-demethoxyerythratidinone and (±)-
Erysotramidine
Shuanhu Gao, Yong Qiang Tu,* Xiangdong Hu, Shaohua Wang, Rongbao Hua,
Yijun Jiang, Yuming Zhao, Xiaohui Fan, Shuyu Zhang
Department of Chemistry & State Key Laboratory of Applied Organic Chemistry, Lanzhou
University, Lanzhou 730000, P. R. China
E-mail: tuyq@lzu.edu.cn
Contents
1. Experimental Procedures and Spectroscopic and Analytical Data of the Products
Synthesis of Compound 13---------------------------------------------------------------S4
Synthesis of Compound 9---------------------------------------------------------------- S4
Synthesis of Compound 14---------------------------------------------------------------S5
Synthesis of Compound 15---------------------------------------------------------------S5
Synthesis of Compound 16---------------------------------------------------------------S6

Synthesis of Compound 17---------------------------------------------------------------S6
Synthesis of Compound 18---------------------------------------------------------------S7
Synthesis of Compound 19---------------------------------------------------------------S7
Synthesis of Compound 20---------------------------------------------------------------S8
Synthesis of Compound 21---------------------------------------------------------------S8
Synthesis of Compound 22---------------------------------------------------------------S9
Synthesis of Compound 23---------------------------------------------------------------S9
Synthesis of Compound 24---------------------------------------------------------------S10
Synthesis of Compound 2-----------------------------------------------------------------S11
Synthesis of Compound 25---------------------------------------------------------------S11
Synthesis of Compound 26---------------------------------------------------------------S11
Synthesis of Compound 10---------------------------------------------------------------S12
Synthesis of Compound 27---------------------------------------------------------------S12
Synthesis of Compound 28---------------------------------------------------------------S13
Synthesis of Compound 29---------------------------------------------------------------S13
Synthesis of Compound 11---------------------------------------------------------------S14
Synthesis of Compound 30---------------------------------------------------------------S14
Synthesis of Compound 31---------------------------------------------------------------S15
Synthesis of Compound 32---------------------------------------------------------------S15
Synthesis of Compound 33---------------------------------------------------------------S16
2. Copies of NMR Spectra of the Products
1H NMR and 13C NMR Spectra of Compound 13----------------------------S17-18
1H NMR and 13C NMR Spectra of Compound 9- ----------------------------S19-20
1H NMR and 13C NMR Spectra of Compound 14----------------------------S21-22
1H NMR and 13C NMR Spectra of Compound 15----------------------------S23-24
1H NMR and 13C NMR Spectra of Compound 16----------------------------S25-26
1H NMR and 13C NMR Spectra of Compound 17----------------------------S27-28
1H NMR and 13C NMR Spectra of Compound 18----------------------------S29-30
1H NMR and 13C NMR Spectra of Compound 19----------------------------S31-32

1H NMR and 13C NMR Spectra of Compound 20----------------------------S33-34
1H NMR and 13C NMR Spectra of Compound 21----------------------------S35-36
1H NMR and 13C NMR Spectra of Compound 22----------------------------S37-38
1H NMR and 13C NMR Spectra of Compound 23----------------------------S39-40
1H NMR and 13C NMR Spectra of Compound 24----------------------------S41-42
1H NMR and 13C NMR Spectra of Compound 2- ----------------------------S43-44
1H NMR and 13C NMR Spectra of Compound 25----------------------------S45-46
1H NMR and 13C NMR Spectra of Compound 26----------------------------S47-48
1H NMR and 13C NMR Spectra of Compound 10----------------------------S49-50
1H NMR and 13C NMR Spectra of Compound 27----------------------------S51-52
1H NMR and 13C NMR Spectra of Compound 28----------------------------S53-54
1H NMR and 13C NMR Spectra of Compound 29----------------------------S55-56
1H NMR and 13C NMR Spectra of Compound 11----------------------------S57-58
1H NMR and 13C NMR Spectra of Compound 30----------------------------S59-60
1H NMR and 13C NMR Spectra of Compound 31----------------------------S61-62
1H NMR and 13C NMR Spectra of Compound 32----------------------------S63-64
1H NMR and 13C NMR Spectra of Compound 33----------------------------S65-66

1. Experimental Procedures and Spectroscopic and Analytical Data of the Products
1
13
Note: H and C NMR spectra were recorded in CDCl
3
solution on Varian Mercury-300 or
4
00 MHz. The MS data were obtained with EI (70 eV), and the relative intensity (%) is given
in brackets. High-resolution mass spectral analysis (HRMS) data were measured on the
Bruker ApexII by means of the SIMS or ESI technique.
1
.1▬▬ Synthesis of amide 13.
H
MeO
MeO
NH2 chloroacetyl chloride
MeO
MeO
N
Cl
N,N-Dimethylaniline
O
o
dry CH Cl , 0 C,
13
1
2
2
2
9
8%
To a solution of 2-(3,4-Dimethoxyphenyl)ethylamine 12 (3.0 g, 16.6 mmol) in dry CH
2
Cl
2
(
100 mL) was added N,N-dimethylaniline (3.36 mL, 26.6 mmol). The mixture was cooled to
o
0
C, and chloroacetyl chloride (1.38 mL, 17.4mmol) was added. After the mixture was
stirred for 1 h, 1 N HCl (50 mL) was added, and the resulting mixture was extracted with
CH Cl (100 mL). The combined extracts were washed with 1 N HCl (25×3 mL) and dried
over Na SO , and concentrated under reduced pressure. Purification of the residue through
2
2
2
4
column chromatography on silica gel (petroleum/EtOAc 4:1 to 1:1) afforded 13 (4.2 g, 98%).
1
H NMR (400 MHz, CDCl
3
): δ = 6.72-6.69 (d, J=11.6, 1H), 6.63-6.67 (m, 2H), 3.88 (s, 2H),
3
.75 (s,3H), 3.73 (s,3H), 3.45-3.38 (dd, J = 17.2, 9.2 Hz, 2H), 2.70-2.65 ppm (t, J=9.2, 2H);
1
3
C NMR (100 MHz, CDCl
3
): δ = 165.5, 148.5, 147.2, 130.5, 120.2, 111.5, 111.0, 55.4, 55.3,
+
4
2.1, 40.7, 34.4 ppm; EI MS (70 eV): m/z (%): 257 (5.2) [M] , 164 (100), 151 (61), 107 (13).
1
.2▬▬ Synthesis of amide 9.
H
H
MeO
MeO
N
MeO
MeO
N
Cl
NaI
I
O
2-Butanone
reflux, 95%
1
3
O
9
To a solution of 13 (3.0 g, 11.6 mmol) in 2-butanone (30 mL) was added NaI (1.92 g, 12.8
mmol). The mixture was heated to reflux for 2 h. The resulting red solution was cooled to
room temperature, then the solvent was removed in vacuo, the obtained residue was diluted with
CH
2
Cl
2
2 2 3
(100 mL). The organic layer was washed with saturated aqueous Na S O (25×3 mL)
and dried over Na
2
SO , and concentrated under reduced pressure. Purification of the residue
4
through column chromatography on silica gel (petroleum/EtOAc 1:1) afforded 9 (3.9 g, 95%).
1
H NMR (400 MHz, CDCl
3
): δ = 6.80-6.78 (d, J=8.0, 1H), 6.73-6.71 (d, J=8.0, 1H), 6.70 (s,
1
H), 3.85 (s, 3H), 3.83 (s, 3H), 3.63 (s, 2H), 3.50-3.45 (dd, J=12.8, 6.42 Hz, 2H), 2.77-2.73
13
ppm (d, J=6.4, 2H); C NMR (100 MHz, CDCl
3
): δ = 116.9, 148.9, 147.7, 130.9, 120.6,
+
111.9, 111.4, 55.8, 41.5, 34.7, -0.5 ppm; EI MS (70 eV): m/z (%): 349 (2) [M] , 198 (0.4),
4

1
64 (100).
1
.3▬▬ Synthesis of N-arylethylhydroindole 14.
MeO
O
OH
O
(
1) NaH, THF,
O
CO Me
2
CO Me
2
reflux,Dimethyl carbonate MeO
HO
O
N
O
(1) NaH, THF,
(
2) then compoud 9
(2) then compoud 9
CO Me
2
O
O
87%
91%
O
O
O
O
8
14
I
Method A:
To a solution of 8 (500 mg, 3.20 mmol) in dry THF (20 mL) was added NaH (231 mg, 12.8
mmol) under argon atmosphere. The mixture was heated to reflux for 30 min and dimethyl
carbonate (1.1 mL, 12.8 mmol) was added. The mixture was stirred at reflux for another 1 h.
A solution of 9 (1.06 g, 3.04 mmol) in THF (8 mL) was added dropwise over a 1 min interval.
The reaction mixture was stirred for an additional 30 min and then allowed to cool to room
temperature. The reaction was quenched by addition of H O (25 mL). The aqueous solution
2
was extracted with CH Cl (3×20 mL). The combined extracts were dried over Na SO and
2
2
2
4
concentrated under reduced pressure. Purification of the residue through column
chromatography on silica gel (petroleum/actone 3:1 to 1:1) afforded 14 (1.15 g, 87%).
Method B:
To a solution of I (500 mg, 2.34 mmol) in dry THF (20 mL) was added NaH (112.1 mg, 2.80
o
mmol) at 0 C under argon atmosphere. The mixture was heated to room temperature for 30
min. A solution of 9 (776 mg, 2.22 mmol) in THF (8 mL) was added dropwise over a 1 min
interval. The reaction mixture was stirred for an additional 30 min at room temperature. The
reaction was quenched by addition of H
CH Cl (3×20 mL). The combined extracts were dried over Na
reduced pressure. Purification of the residue through column chromatography on silica gel
2
O (25 mL). The aqueous solution was extracted with
2
2
2
SO and concentrated under
4
(
petroleum/actone 3:1 to 1:1) afforded 14 (879 mg, 91%).
1
H NMR (400 MHz, CDCl
.75 (s, 3H), 3.64 (s, 3H), 3.55-3.48 (m, 1H), 3.15-3.10 (m, 1H), 2.79-2.74 (m, 2H), 2.71-2.66
d, J=15.9, 1H), 2.34-2.29 (d, J=15.9, 1H), 2.21-2.13 (m, 2H), 2.05-1.91 (m, 1H), 1.65-1.56
3
): δ = 6.67 (m, 3H), 4.80 (s, 1H), 3.86-3.80 (m, 4H), 3.78 (s, 3H),
3
(
(
1
3
m, 2H), 1.41-1.36 ppm (m, 1H); C NMR (100 MHz, CDCl
3
): δ = 174.8, 173.4, 148.7,
1
3
47.3, 131.5, 120.4, 111.9, 111.2, 106.3, 89.8, 64.3, 64.2, 55.6 (2C), 52.2, 49.9, 40.8, 39.9,
+
9.5, 34.7, 30.9, 30.4 ppm; EI MS (70 eV): m/z (%): 435 (0.8) [M] , 255 (2), 227 (0.8), 195
(
2), 164 (100), 151 (16).
1
.4▬▬ Synthesis of 15 and 16.
MeO
MeO
MeO
MeO
MeO
O
O
O
N
actone
N
BF ·Et O
MeO
HO
O
N
O
3
2
dry CH Cl
PTSA, reflux
2 steps 97%
2
2
CO Me
2
CO Me
CO2Me
2
X
O
O
O
1
4
16
15 X=
: 16 (X=O) =4:1
5

To a solution of 14 (1.07 mg, 2.46 mmol) in dry CH
2
Cl
2
(30 mL) was added BF
3
·Et
2
O (0.62
o
mL, 4.9 mmol) at 0 C under argon atmosphere. After the mixture was stirred for 1 h at room
temperature, saturated NaHCO
with CH Cl (30 mL). The combined extracts were washed with saturated NaHCO
and dried over Na SO , and concentrated under reduced pressure. Purification of the residue
3
(15 mL) was added, and the resulting mixture was extracted
2
2
3
(25×3 mL)
2
4
through column chromatography on silica gel (petroleum/actone 4:1 to 1:1) afforded 15 (796
mg) and 16 (178 mg, 97% overall yield).
To a solution of 15 (796 mg, 1.91 mmol) in actone (30 mL) was added cat. PTSA. The
mixture was heated to reflux for 3 h. The resulting solution was cooled to room temperature,
then the solvent was removed in vacuo, the obtained residue was diluted with CH
The organic layer was washed with saturated aqueous NaHCO (25 mL) and dried over
Na SO , and concentrated under reduced pressure. Purification of the residue through column
2 2
Cl (100 mL).
3
2
4
chromatography on silica gel (petroleum/actone 1:1) afforded 16 (712 mg, 99%).
Compound 15
1
H NMR (400 MHz, CDCl ): δ = 6.56 (s, 1H), 6.49 (s, 1H), 4.30-4.25 (m, 1H), 3.99-3.79 (m,
3
4
2
H), 3.77 (s, 3H), 3.76 (s, 3H), 3.19-3.15 (d, J=17.2, 1H), 3.00 (s, 3H), 2.94-2.88 (m, 1H),
.80-2.72 (m, 1H), 2.60-2.49 (m, 3H), 2.15-2.11 (d, J=15.6, 1H), 2.03-1.94 (m, 2H), 1.86-1.80
1
3
(
m, 1H), 1.73-1.66 ppm (m, 1H); C NMR (100 MHz, CDCl
3
): δ = 173.7, 171.4, 147.6,
1
3
46.9, 130.3, 126.7, 111.2, 108.5, 107.9, 65.3, 64.3, 63.4, 55.8, 55.6, 51.4, 50.5, 39.6, 37.8,
+
4.9, 34.5, 30.3, 28.2 ppm; EI MS (70 eV): m/z (%): 417 (0.07) [M] , 303 (6), 258 (3), 244
(
6).
Compound 16
1
H NMR (400 MHz, CDCl ): δ = 6.55 (s, 1H), 6.53 (s, 1H), 4.42-4.34 (m, 1H), 3.80 (s, 6H),
3
3
.30-3.25 (d, J=17.2, 1H), 3.06 (s, 3H), 3.00-2.94 (m, 1H), 2.88-2.75 (m, 3H), 2.61-2.57 (d,
1
3
J=15.6, 1H), 2.45-2.26 ppm (m, 5H); C NMR (100 MHz, CDCl
3
): δ = 208.6, 172.4, 170.5,
1
3
48.0, 147.2, 129.5, 127.0, 111.3, 108.5, 65.8, 56.0, 55.7, 51.9, 50.5, 44.9, 41.7, 35.4, 34.9,
+
4.3, 28.2 ppm; EI MS (70 eV): m/z (%): 373 (6) [M] , 314 (14), 302 (10), 258 (58), 164
(
42).
1
.5▬▬ Synthesis of 17.
MeO
MeO
O
O
o
LDA, THF, -78 C
N
O
HO
O
then, compoud 9,
O
O
87%
8
17
To a solution of lithium diisopropylamide (LDA) (1.88 mmol, from diisopropylamine (0.33
mL, 2.36 mmol) and n-BuLi (0.94 mL, 2.0 M in hexane, 1.88 mmol)) in THF (20 mL) at –78
o
C under argon atmosphere was added dropwise a solution of ketone 8 (246 mg, 1.57 mmol)
o
in THF (5 mL). The mixture was stirred at –78 C for 30 min. A solution of 9 (500 mg, 1.43
mmol) in THF (5 mL) was added dropwise over a 3 min interval. The reaction mixture was
o
stirred for an additional 5 min at –78 C and then allowed to warm to room temperature over
3
2
0 min. The reaction was quenched by addition of H O (25 mL). The aqueous solution was
6

extracted with CH
2
Cl
2
2 4
(3×20 mL). The combined extracts were dried over Na SO and
concentrated under reduced pressure. Purification of the residue through column
chromatography on silica gel (petroleum/actone 4:1 to 1:1) afforded the desired 17 (470 mg,
8
7%).
1
H NMR (400 MHz, CDCl
3
): δ = 6.75-6.64 (m, 3H), 3.98-3.83 (m, 4H), 3.81 (s, 3H), 3.80
(
s, 3H), 3.56-3.50 (m, 2H), 3.25-3.18 (m, 1H), 2.90-2.83 (m, 1H), 2.79-2.71 (m, 1H),
2
1
1
.60-2.54 (m, 1H), 2.32-2.19 (m, 3H), 2.04-1.98 (m, 1H), 1.92-1.83 (m, 2H), 1.70-1.58 (m,
13
H), 1.47-1.42 ppm (m, 1H); C NMR (100 MHz, CDCl
3
): δ = 174.6, 148.8, 147.5, 131.8,
20.6, 112.1, 111.3, 107.7, 89.5, 64.2, 64.0, 55.8 (2C), 40.9, 40.7, 35.9, 35.0, 34.7, 30.7, 30.3
ppm; EI MS (70 eV): m/z (%): 359 (13), 273 (15), 253 (12), 208 (30), 164 (100), 151 (97).
1
.6▬▬ Synthesis of 18 and 19.
MeO
MeO
MeO
MeO
MeO
O
O
O
HO
O
N
O
N
MeO
CF COOH
3
actone
N
dry CH Cl ,
H
PTSA, reflux
steps 96%
2
2
H
9
6%
2
X
O
O
O
1
7
:
19 (X=O) =9:1
18 X=
19
To a solution of 17 (760 mg, 2.01 mmol) in dry CH
2
Cl
2
(20 mL) was added CF
3
COOH (0.31
o
mL, 4.02 mmol) at 0 C under argon atmosphere. After the mixture was stirred for 5 h at room
temperature, saturated NaHCO
with CH Cl (30 mL). The combined extracts were washed with saturated NaHCO
and dried over Na SO , and concentrated under reduced pressure. Purification of the residue
3
(15 mL) was added, and the resulting mixture was extracted
2
2
3
(25×3 mL)
2
4
through column chromatography on silica gel (petroleum/actone 4:1 to 1:1) afforded 18 (623
mg) and 19 (61mg, 96% overall yield).
To a solution of 18 (623 mg, 1.74 mmol) in actone (30 mL) was added cat. PTSA. The
mixture was heated to reflux for 3 h. The resulting solution was cooled to room temperature,
then the solvent was removed in vacuo, the obtained residue was diluted with CH
The organic layer was washed with saturated aqueous NaHCO (25 mL) and dried over
Na SO , and concentrated under reduced pressure. Purification of the residue through column
2 2
Cl (100 mL).
3
2
4
chromatography on silica gel (petroleum/actone 1:1) afforded 19 (548 mg, 99%).
Compound 18
1
H NMR (400 MHz, CDCl ): δ = 6.72 (s, 1H), 6.50 (s, 1H), 4.13-4.08 (m, 1H), 3.95-3.86 (m,
3
4
2
H), 3.82 (s, 3H), 3.80 (s, 3H), 3.16-3.10 (m, 1H), 2.99-2.92 (m, 1H), 2.73-2.70 (m, 1H),
.59-2.54 (m, 1H), 2.43-2.27 (m, 2H), 2.08-1.92 (m, 3H), 1.82-1.77 (m, 1H), 1.68-1.63 ppm
1
3
(
m, 2H); C NMR (100 MHz, CDCl
3
): δ = 174.8, 147.8, 147.3, 123.7, 125.7, 111.7, 107.8,
1
07.6, 64.2, 63.8, 62.0, 56.0, 37.0, 36.9, 36.5, 34.7, 33.2, 30.2, 26.6 ppm; EI MS (70 eV): m/z
+
(
%): 359 (0.5) [M] , 258 (1), 245 (6), 216 (4), 164 (4), 101 (100).
Compound 19
7

1
H NMR (400 MHz, CDCl
3
): δ = 6.67 (s, 1H), 6.56 (s, 1H), 4.38-4.33 (m, 1H), 3.86 (s, 3H),
3
2
1
.84 (s, 3H), 3.08-2.96 (m, 4H), 2.74-2.56 (m, 3H), 2.40-2.39 (m, 1H), 2.33-2.22 (m, 3H),
1
3
.15-2.08 ppm (m, 1H); C NMR (100 MHz, CDCl ): δ = 209.9, 172.0, 148.4, 148.3, 134.3,
3
25.5, 111.8, 107.3, 62.4, 56.3, 55.9, 43.2, 37.7, 37.4, 35.2, 34.7, 33.4, 27.5 ppm; EI MS (70
+
eV): m/z (%): 315 (0.53) [M] , 258 (10), 244 (3), 164 (2), 84 (100).
1
.7▬▬ Synthesis of 20.
MeO
MeO
MeO
MeO
O
O
NaBH , CH OH
N
4
3
N
9
9%
H
H
O
19
20
OH
To a solution of 19 (454 mg, 1.44 mmol) in MeOH (20 mL) was added NaBH
4
(55 mg, 1.44 mmol)
o
at 0 C and the mixture was stirred for 30 min, then the solvent was removed in vacuo, the
2 2 4
obtained residue was diluted with CH Cl (50 mL) and saturated aqueous NH Cl (30 mL), and the
aqueous layer was extracted with CH Cl (20 mL). The combined organic layer was dried over
2
2
anhydrous Na SO4 and concentrated. Purification of the residue through column
2
chromatography on silica gel (petroleum/actone 1:1) afforded 20 (456 mg, 99%).
1
H NMR (400 MHz, CDCl
3
): δ = 6.62 (s, 1H), 6.49 (s, 1H), 4.13-4.08 (m, 1H), 3.92-3.87 (m,
1
2
H), 3.81 (s, 3H), 3.77 (s, 3H), 3.21-3.13 (m, 1H), 3.04-2.96 (m, 1H), 2.66-2.52 (m, 2H),
1
3
3
.27-2.26 (m, 1H), 2.16-2.09 (m, 2H), 1.81-1.37 ppm (m, 4H); C NMR (100 MHz, CDCl ):
δ = 176.6, 147.8, 147.1, 133.2, 126.1, 111.8, 107.4, 67.2, 62.5, 55.9, 55.6, 38.2, 37.1, 36.7,
+
3
4.7, 33.4, 29.6, 26.1 ppm; EI MS (70 eV): m/z (%): 317 (9) [M] , 258 (100), 245 (21), 216
(
11).
1
.8▬▬ Synthesis of 21.
MeO
MeO
MeO
MeO
O
O
N
TBSCl, imidazole
DMF, 86%
N
H
H
OH 20
OTBS 21
To a solution of 20 (458 mg, 1.44 mmol) in dry DMF (5 mL) was added imidazole (235 mg, 3.46
mmol) and TBSCl (262 mg, 1.73 mmol). The reaction mixture was stirred for 1 h at room
temperature, then diluted with EtOAc (100 mL), washed successively with water and brine, dried
over anhydrous Na SO , and evaporated in vacuo. Purification of the residue through column
2
4
chromatography on silica gel (petroleum/actone 5:1) afforded 21 (4534 mg, 86%).
1
H NMR (400 MHz, CDCl ): δ = 6.65 (s, 1H), 6.51 (s, 1H), 4.06-3.98 (m, 2H), 3.80 (s, 3H),
3
3
.76 (s, 3H), 3.19-3.15 (m, 1H), 2.96-2.91 (m, 1H), 2.62-2.52 (m, 3H), 2.28-2.26 (m, 1H),
8

2
.11-2.01 (m, 2H), 1.72-1.62 (m, 3H), 1.50-1.48 (m, 1H), 0.82 (s, 9H), 0.014 (s, 3H), 0.004
13
ppm (s, 3H); C NMR (100 MHz, CDCl ): δ = 174.9, 147.7, 147.1, 133.9, 125.9, 111.8,
3
1
07.5, 67.2, 61.9, 55.9, 55.6, 37.9, 36.9, 36.0, 34.7, 32.1, 29.6, 26.6, 25.6 (3C), 17.8, -4.9, -5.0
+
ppm; EI MS (70 eV): m/z (%): 431 (3) [M] , 416 (1), 374 (15), 258 (100).
1
.9▬▬ Synthesis of 22.
MeO
MeO
MeO
O
O
o
N
(1) LDA, THF, PhSeCl, -78 C
2) NaIO , MeOH, 2 steps 91%
N
MeO
(
4
H
OTBS 21
22
OTBS
To a solution of lithium diisopropylamide (LDA) (1.86 mmol, from diisopropylamine (0.33
mL, 2.32 mmol) and n-BuLi (0.93 mL, 2.0 M in hexane, 1.86 mmol)) in THF (20 mL) at –78
o
C under argon atmosphere was added dropwise a solution of ketone 21 (667 mg, 1.55 mmol)
o
in THF (5 mL). The mixture was stirred at –78 C for 30 min. A solution of PhSeCl (310 mg,
1
.62 mmol) in THF (5 mL) was added dropwise over a 1 min interval. The reaction mixture
o
was stirred for an additional 5 min at –78 C and then allowed to warm to room temperature
over 30 min. The reaction was quenched by addition of H
2
O (25 mL). The aqueous solution
SO and
was extracted with CH Cl (20 mL). The combined extracts were dried over Na
2
2
2
4
concentrated under reduced pressure. The residue was purified by column chromatography and
directly used in the next reaction.
To a solution of the above residue in MeOH:H
The reaction mixture was stirred for 1 h at room temperature, then the solvent was removed in
vacuo, the obtained residue was diluted with CH Cl (50 mL). The organic layer was washed with
brine (25 mL) and dried over anhydrous Na SO and concentrated. Purification of the residue
2 4
O (15:5 mL) was added NaIO (2.0 g, 9.3 mmol).
2
2
2
4
through column chromatography on silica gel (petroleum/actone 3:1) afforded 22 (604 mg,
9
1%).
1
H NMR (400 MHz, CDCl
3
): δ = 6.89 (s, 1H), 6.67 (s, 1H), 5.90 (s, 1H), 4.39 (s, 1H),
4
1
.03-3.96 (m, 1H), 3.80 (s, 6H), 3.45-3.39 (m, 1H), 3.00-2.85 (m, 4H), 2.11-1.99 (m, 2H),
1
3
.83-1.80 (m, 1H), 1.68-1.64 (m, 1H), 0.79 (s, 9H), 0.02 (s, 3H), -0.02 ppm (s, 3H); C NMR
(
100 MHz, CDCl ): δ = 169.8, 160.1, 147.9, 146.5, 129.7, 127.0, 123.9, 112.3, 108.9, 67.5,
3
6
6.0, 56.1, 55.6, 38.2, 36.2, 35.1, 29.3, 28.0, 25.5, 17.8, -5.0, -5.1 ppm; EI MS (70 eV): m/z
+
(
%): 429 (8) [M] , 414 (2), 372 (20), 297 (100), 258 (30).
1
.10▬▬ Synthesis of 23.
MeO
O
MeO
MeO
(
(
1) TBAF, THF
2) MsCl, Et N, CH Cl
2
N
O
3
2
MeO
N
(
3) DBU, THF, reflux
3
steps 85%
2
3
OTBS 22
To a solution of 22 (604 mg, 1.42 mmol) in THF (10 mL) was added TBAF (445 mg, 1.7
9

mmol) at room temperature under argon atmosphere. After the mixture was stirred for 5 h at
room temperature, saturated brine (10 mL) was added, and the resulting mixture was
extracted with CH
25×3 mL) and dried over Na
directly used in the next reaction.
2
Cl
2
(50 mL). The combined extracts were washed with saturated brine
(
2
SO , and concentrated under reduced pressure. The residue was
4
To a solution of the above residue in dry CH
2
Cl
2
(20 mL) was added Et
3
N (0.43 mL, 3.06 mmol).
o
The mixture was cooled to 0 C, and MsCl (0.12 mL, 1.53mmol) was added. After the
mixture was stirred for 1 h, H
with CH Cl (100 mL). The combined extracts were dried over Na
under reduced pressure. The residue was directly used in the next reaction.
To a solution of the above residue in dry THF (20 mL) was added DBU (2.13 mL, 13.3 mmol).
The mixture was heated to reflux for 3 h, then H O (20 mL) was added, and the resulting
4
mixture was extracted with CH Cl (100 mL). The combined extracts were dried over Na SO ,
2
O (20 mL) was added, and the resulting mixture was extracted
2
2
2
SO , and concentrated
4
2
2
2
2
and concentrated under reduced pressure. Purification of the residue through column
chromatography on silica gel (petroleum/actone 3:1) afforded 23 (356 mg, 85% 3 steps).
1
H NMR (400 MHz, CDCl
3
): δ = 6.93 (s, 1H), 6.78-6.74 (m, 1H), 6.64 (s, 1H), 6.25-6.21 (m,
1
H), 5.81 (s, 1H), 3.98-3.92 (m, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 3.52-3.46 (m, 1H), 2.93-2.90
1
3
(
m, 2H), 2.36-2.23 (m, 2H), 2.14-2.09 (m, 1H), 1.80-1.76 ppm (m, 1H); C NMR (100 MHz,
CDCl ): δ = 170.9, 157.7, 147.9, 146.6, 135.8, 128.4, 126.0, 123.7, 118.6, 111.8, 108.3, 64.3,
3
+
5
2
5.7, 55.6, 36.7, 34.7, 26.9, 24.3 ppm; EI MS (70 eV): m/z (%): 297 (100) [M] , 282 (16),
68 (22), 254 (20), 238 (7).
1
.11▬▬ Synthesis of 24.
MeO
MeO
MeO
MeO
O
SeO2,
O
N
H
N
HCO2
1
,4-dioxane
HO
24
23
To a solution containing ( 327mg, 1.1 mmol) of 23 in 5 mL of 1,4-dioxane at room
temperature was added (1.22g 11.0 mmol) of selenium dioxide and (506 mg 11.0 mmol) of
formic acid. The reaction mixture was heated at reflux for 4 days with stirring. After cooling,
0 mL of a 10 % NaOH solution was added and the mixture was extracted with CHCl . The
combined organic layers were dried over anhydrous Na SO4, filtered, and concentrated under
reduced pressure. Purification of the residue by column chromatography (petroleum/actone
1
3
2
1
:1) provided 24 (86 mg, 31%).
1
H NMR (400 MHz, CDCl
s, 1H), 6.33-6.31 (d, 1H, J = 10.0 Hz), 6.01 (s, 1H), 4.32 (brs, 1H), 4.00-3.93 (m, 1H), 3.86
s, 3H), 3.75 (s, 3H), 3.63-3.57 (m, 1H), 3.10-2.96 (m, 2H), 2.83-2.79 (m, 1H), 2.46 (brs, 1H),
3
): δ = 6.88-6.85 (dd, 1H, J = 10.4 and 2.4 Hz), 6.79 (s, 1H), 6.71
(
(
13
1
1
3
.72-1.66 ppm (t, J = 10.8 Hz 1H); C NMR (100 MHz, CDCl ): δ = 170.9, 157.3, 148.5,
47.0, 139.6, 128.6, 126.4, 123.3, 120.0, 112.0, 108.2, 66.6, 66.2, 56.0, 55.9, 44.9, 37.3, 26.9
+
ppm; EI MS (70 eV): m/z (%):313 (6) [M] , 294 (3), 284 (4), 270 (2), 142 (13).
1
0

1
.12▬▬ Synthesis of 2.
MeO
MeO
MeO
MeO
O
O
N
MeI, THF
NaOH
N
HO
MeO
Erysotramidine (2)
24
To a mixture containing (90 mg 0.27 mmol) of 25 in 7 mL of THF and 4 mL of methyl iodide
was added (180 mg 3.2 mmol) of NaOH and (170 mg 0.8 mmol) of tetraethylammonium
bromide. The reaction mixture was stirred for 36 h at room temperature. The solution was
poured into ice-water and the resulting mixture was extracted with CHCl
organic layers were dried over anhydrous Na SO , filtered, and concentrated under reduced
pressure. Purification of the residue through column chromatography on silica gel
3
. The combined
2
4
(
petroleum/actone 2:1) afforded (80 mg 91%) of (±)-erysotramidine 2.
1
H NMR (400 MHz, CDCl
3
): δ = 6.91-6.88 (dd, 1H, J = 10.0 and 2.0 Hz), 6.78 (s, 1H), 6.71
(
s, 1H), 6.33-6.31 (d, 1H, J = 10.0 Hz), 6.01 (s, 1H), 3.99-3.94 (m, 1H), 3.85 (m, 1H), 3.85 (s,
3
1
1
H), 3.75 (s, 3H), 3.63-3.57 (m, 1H), 3.33 (s, 3H), 3.10-2.96 (m, 2H), 2.82-2.78 (m, 1H),
1
3
.72-1.66 ppm (m, 1H); C NMR (100 MHz, CDCl ): δ = 170.8, 157.0, 148.6, 147.0, 136.3,
3
28.7, 126.5, 124.0, 120.2, 112.3, 108.3, 74.9, 66.3, 56.3, 56.1, 55.9, 41.4, 37.2, 27.0 ppm; EI
+
MS (70 eV): m/z (%): 327 (85) [M] , 312 (57), 297 (18), 296 (68), 295 (36), 294 (100), 284
(
15), 266 (48), 252 (24), 238 (14), 224 (15).
.13▬▬ Synthesis of 25.
1
CH NO2
3
O
CHO
AcONH4,AcOH
O
NO2
o
25
8
0 C, 90%
To a solution of Furfural (3.0 g, 31.3 mmol) in AcOH (100 mL) was added CH
3
NO
2
(3.4 mL,
o
6
2.6 mmol) and AcONH
4
(7.2 g, 94.9 mmol). The mixture was heated to 80 C for 5 h. Then,
the resulting red solution was poured into ice water (100 mL). The mixture was filtered and
washed with CH CH OH (100 mL). The obtained yellow solid was further dried and afforded 25
3
2
(
3.9 g, 90%).
1
H NMR (400 MHz, CDCl ): δ = 7.78-7.72 (bs, 1H), 7.56 (bs, 1H), 7.51-7.45 (m, 1H), 6.89
3
1
3
(
bs, 1H), ppm 6.56-6.54 (bs, 1H); C NMR (100 MHz, CDCl
3
): δ = 146.8, 146.4, 134.6,
+
1
25.3, 120.1, 113.2 ppm; EI MS (70 eV): m/z (%): 139 (42) [M] , 122(6), 96 (77), 92 (62), 83
(
73).
.14▬▬ Synthesis of 26.
1
(
1) LiAlH , THF, reflux
4
O
Cl
(
2) chloroacetyl chloride,
O
NO2
O
N
N,N-Dimethylaniline,
H
2
5
o
dry CH Cl , 0 C,
2
2
2
6
8
8% 2 steps
11

o
To a solution of LiAlH
4.0 g, 28.8 mmol) under argon atmosphere over a 30 min interval. The solution was stirred at
reflux for an additional 4 h. Then, the reaction mixture was cooled to room temperature and H O
4
(3.3 g, 86.3 mmol) in dry THF (200 mL) was slowly added at 0 C 25
(
2
(
20 mL) was slowly added. The obtained residue was filtered, and washed with CH
The combined organic solution was dried over Na SO , and concentrated under reduced
pressure. The residue was directly used in the next reaction.
2 2
Cl (100 mL).
2
4
To a solution of the above residue in dry CH
2
Cl
2
(100 mL) was added N,N-dimethylaniline
o
(
5.5 mL, 43.2 mmol). The mixture was cooled to 0 C and chloroacetyl chloride (2.4 mL, 30.2
mmol) was added. After the mixture was stirred for 1 h, 1 N HCl (50 mL) was added, and the
resulting mixture was extracted with CH Cl (100 mL). The combined extracts were washed
with 1 N HCl (25×3 mL) and dried over Na SO , and concentrated under reduced pressure.
Purification of the residue through column chromatography on silica gel (petroleum/EtOAc
2
2
2
4
4
:1 to 1:1) afforded 26 (4.8 g, 88% 2 steps).
1
H NMR (400 MHz, CDCl
3
): δ = 7.25 (bs, 1H), 7.00 (bs, 1H), 6.22-6.21 (bs, 1H), 6.01-6.00
1
3
(
bs, 1H), 3.93 (s, 2H), 3.50-3.46 (m, 2H), 2.81-2.78 ppm (t, 2H); C NMR (100 MHz,
CDCl ): δ = 165.9, 152.2, 141.4, 110.1, 106.2, 42.3, 38.9, 27.5 ppm; EI MS (70 eV): m/z (%):
3
+
1
87 (9) [M] , 186 (64), 108 (30), 106 (15), 97 (26).
1
.15▬▬ Synthesis of 10.
O
O
NaI
Cl
I
O
N
H
6
2-Butanone
reflux, 90%
O
N
H
10
2
To a solution of 26 (3.8 g, 20.3 mmol) in 2-butanone (50 mL) was added NaI (3.6 g, 24.3
mmol). The mixture was heated to reflux for 2 h. The resulting red solution was cooled to
room temperature, then the solvent was removed in vacuo, the obtained residue was diluted with
CH
and dried over Na
through column chromatography on silica gel (petroleum/EtOAc 1:1) afforded 10 (5.1 g,
2
Cl
2
2 2 3
(200 mL). The organic layer was washed with saturated aqueous Na S O (25×3 mL)
2
SO , and concentrated under reduced pressure. Purification of the residue
4
9
0%).
1
H NMR (400 MHz, CDCl
3
): δ = 7.27-7.25 (m, 1H), 7.17 (bs, 1H), 6.24-6.23 (bs, 1H),
1
3
6
.04-6.03 (bs, 1H), 3.64 (s, 2H), 3.49-3.44 (t, 2H), 2.83-2.80 ppm (t, 2H); C NMR (100
MHz, CDCl ): δ = 167.8, 152.4, 141.3, 110.1, 106.2, 38.7, 27.4, -0.43 ppm; EI MS (70 eV):
3
+
m/z (%): 279 (3) [M] , 169 (7), 141 (9), 127(1), 94 (100).
1
.16▬▬ Synthesis of 27.
n-BuLi, THF
Cl
O
I
Cl
O
93%
27
o
A solution of n-BuLi (36.6 mL, 73.2 mmol, 2.0 M in hexane) was added at –78 C over 15
min to a solution of 2-methyl furan (5 g, 61 mmol) in dry THF (100 mL), and then the
12

o
mixture was stirred for 0.5 h at –78 C. A solution of 1-chloro-3-iodopropane (6.23 mL, 58
mmol) in THF (15 mL) was added dropwise over a 10 min interval. The reaction mixture was
o
stirred for an additional 30 min at –78 C and then allowed to warm to room temperature over
3
0 min. The reaction was quenched by addition of H
extracted with Et O (50×3 mL). The combined extracts were washed with saturated brine
25×3 mL) and dried over Na SO and concentrated under reduced pressure. Purification of
the residue through column chromatography on silica gel (petroleum/EtOAc 40:1) afforded
2
O (100 mL). The aqueous solution was
2
(
2
4
2
7 (9.0 g, 93%).
1
H NMR (400 MHz, CDCl ): δ = 5.88 (bs, 1H), 5.83 (bs, 1H), 3.55-3.52 (m, 2H), 2.74-2.71 (t,
3
1
3
J=7.6, 2H), 2.23 (s, 3H), 2.08-2.04 ppm (m, 2H); C NMR (100 MHz, CDCl
3
): δ = 152.3,
+
1
50.5, 106.1, 105.8, 44.0, 30.9, 25.1, 13.4 ppm; EI MS (70 eV): m/z (%): 158 (1) [M] , 108
(
5), 95 (100).
1
.17▬▬ Synthesis of 28.
NaN3
Cl
N3
o
O
DMF, 80 C
97%
O
27
28
To a solution of 27 (8.24 g, 52 mmol) in DMF (20 mL) was added NaN
3
(10 g, 156 mmol).
o
The mixture was heated to 75 C for 2 h. The resulting solution was cooled to room
temperature and diluted with Et
saturated brine and dried over Na SO , and concentrated under reduced pressure. Purification
O (200 mL). The organic layer was washed successively with
2
2
4
of the residue through column chromatography on silica gel (petroleum/EtOAc 20:1) afforded
2
8 (8.3 g, 97%).
1
H NMR (400 MHz, CDCl ): δ = 5.89 (bs, 1H), 5.83 (bs, 1H), 3.30-3.26 (m, 2H), 2.67-2.63 (t,
3
1
3
J=6.8, 2H), 2.23 (s, 3H), 1.90-1.86 ppm (m, 2H); C NMR (100 MHz, CDCl
): δ = 152.4,
3
1
1
50.4, 105.9, 105.7, 50.4, 27.3, 24.9, 13.2 ppm; EI MS (70 eV): m/z (%): 137 (22), 122 (43),
09 (100), 95 (66).
1
.18▬▬ Synthesis of 29.
(
1) LiAlH , THF
4
H
N
N3
O
(2) chloroacetyl chloride,
O
Cl
N,N-Dimethylaniline,
O
2
8
o
dry CH Cl , 0 C,
2
2
2
9
9
5%
o
To a solution of LiAlH (4.6 g, 121.5 mmol) in dry THF (200 mL) was slowly added at 0 C 28
4
(
8.0 g, 48.5 mmol) under argon atmosphere over a 30 min interval. The solution was stirred at
o
room temperature for an additional 1 h. Then, the reaction mixture was cooled to 0 C again and
H
2
O (20 mL) was slowly added. The obtained residue was filtered, and washed with CH
mL). The combined organic solution was dried over Na SO , and concentrated under reduced
pressure. The residue was directly used in the next reaction.
2 2
Cl (100
2
4
1
3

To a solution of the above residue in dry CH
2
Cl
2
(100 mL) was added N,N-dimethylaniline
o
(
9.22 mL, 72.8 mmol). The mixture was cooled to 0 C, and chloroacetyl chloride (4.0 mL,
5
0.9 mmol) was added. After the mixture was stirred for 1 h, 1 N HCl (50 mL) was added,
Cl (100 mL). The combined extracts were
washed with 1 N HCl (25×3 mL) and dried over Na SO , and concentrated under reduced
pressure. Purification of the residue through column chromatography on silica gel
and the resulting mixture was extracted with CH
2
2
2
4
(
petroleum/EtOAc 4:1 to 1:1) afforded 29 (9.9 g, 95% 2 steps).
1
H NMR (400 MHz, CDCl
3
): δ = 6.96 (bs, 1H), 5.80 (bs, 1H), 5.76 (bs, 1H), 3.94 (s, 2H),
1
3
3
.28-3.24 (m, 2H), 2.56-2.53 (t, J=7.2 Hz, 2H), 2.16 (s, 3H), 1.83-1.77 ppm (m, 2H);
C
NMR (100 MHz, CDCl ): δ = 165.8, 152.5, 150.1, 105.6, 42.3, 39.0, 27.3, 25.0, 13.1 ppm; EI
3
+
MS (70 eV): m/z (%): 215 (23) [M] , 138 (11), 122 (75), 107 (48), 95 (100).
1
.19▬▬ Synthesis of 11.
H
H
NaI
N
N
O
Cl
2
-Butanone
reflux, 95%
O
I
O
29
11
O
To a solution of 29 (10 g, 46.4 mmol) in 2-butanone (50 mL) was added NaI (8.4 g, 55.7
mmol). The mixture was heated to reflux for 2 h. The resulting red solution was cooled to
room temperature, then the solvent was removed in vacuo, the obtained residue was diluted with
CH Cl (200 mL). The organic layer was washed with saturated aqueous Na S O (25×3 mL)
2
2
2
2
3
and dried over Na SO , and concentrated under reduced pressure. Purification of the residue
2 4
through column chromatography on silica gel (petroleum/EtOAc 1:1) afforded 11 (13.9 g,
9
8%).
1
H NMR (400 MHz, CDCl ): δ = 7.36 (bs, 1H), 5.83 (bs, 1H), 5.79 (bs, 1H), 3.69 (s, 2H),
3
1
3
3
.28-3.23 (m, 2H), 2.61-2.57 (t, J=7.6 Hz, 2H), 2.19 (s, 3H), 1.84-1.80 ppm (m, 2H);
C
NMR (100 MHz, CDCl ): δ = 168.0, 152.8, 150.1, 105.7, 39.6, 27.4, 25.1, 13.4, -0.3 ppm; EI
3
+
MS (70 eV): m/z (%): 307 (3) [M] , 180 (42), 169 (10), 141 (19), 95 (47), 72 (100).
1
.20▬▬ Synthesis of 30.
O
O
O
o
HO
N
O
LDA, THF, -78 C
then, compoud
O
O
10, 84%
O
3
0
8
To a solution of lithium diisopropylamide (LDA) (1.3 mmol, from diisopropylamine (0.21
o
mL, 1.5 mmol) and n-BuLi (0.65 mL, 2.0 M in hexane, 1.3 mmol)) in THF (50 mL) at –78 C
under argon atmosphere was added dropwise a solution of ketone 8 (156 mg, 1.0 mmol) in
o
THF (8 mL). The mixture was stirred at –78 C for 30 min. A solution of 10 (251 mg, 0.9
mmol) in THF (10 mL) was added dropwise over a 3 min interval. The reaction mixture was
1
4

o
stirred for an additional 5 min at –78 C and then allowed to warm to room temperature over
0 min. The reaction was quenched by addition of H O (25 mL). The aqueous solution was
extracted with CH Cl (3×20 mL). The combined extracts were dried over Na SO and
3
2
2
2
2
4
concentrated under reduced pressure. Purification of the residue through column
chromatography on silica gel (petroleum/actone 4:1 to 1:1) afforded the desired 30 (232 mg,
8
4%).
1
3
H NMR (400 MHz, CDCl ): δ = 7.26 (bs, 1H), 6.23-6.22 (bs, 1H), 6.02-6.01 (bs, 1H), 3.87
(
s, 4H), 3.63-3.54 (m, 1H), 3.35-3.25 (m, 1H), 2.97-2.80 (m, 2H), 2.80-2.53 (m, 1H),
2
1
1
.35-2.28 (m, 1H), 2.22-2.15 (m, 1H), 2.04-1.98 (m, 1H), 1.88-1.82 (m, 2H), 1.69-1.66 (m,
1
3
H), 1.46-1.39 ppm (m, 2H); C NMR (100 MHz, CDCl ): δ = 174.9, 153.0, 141.2, 110.1,
3
07.7, 106.1, 89.6, 64.2, 64.0, 40.7, 37.6, 35.9, 35.6, 30.6, 30.3, 27.5 ppm; EI MS (70 eV):
+
m/z (%): 307 (2) [M] , 289 (11), 226 (4), 208 (11), 203 (8), 197 (15), 122 (33), 94 (100).
1
.21▬▬ Synthesis of 31.
O
O
O
HO
O
o
N
O
LDA, THF, -78 C
then, compoud
O
O
11, 86%
3
1
8
To a solution of lithium diisopropylamide (LDA) (5.0 mmol, from diisopropylamine (0.9 mL,
o
6
.2 mmol) and n-BuLi (2.5 mL, 2.0 M in hexane, 5.0 mmol)) in THF (50 mL) at –78 C under
argon atmosphere was added dropwise a solution of ketone 8 (610 mg, 3.9 mmol) in THF (8
o
mL). The mixture was stirred at –78 C for 30 min. A solution of 11 (1.1 g, 3.5 mmol) in THF
(
10 mL) was added dropwise over a 3 min interval. The reaction mixture was stirred for an
o
additional 5 min at –78 C and then allowed to warm to room temperature over 30 min. The
2
reaction was quenched by addition of H O (25 mL). The aqueous solution was extracted with
CH Cl (3×20 mL). The combined extracts were dried over Na SO and concentrated under
2
2
2
4
reduced pressure. Purification of the residue through column chromatography on silica gel
(
petroleum/actone 4:1 to 1:1) afforded the desired 31 (1.0 g, 86%).
1
H NMR (400 MHz, CD
3
COCD
3
): δ = 5.92 (bs, 1H), 5.86 (bs, 1H), 5.14 (s, 1H), 3.89 (s, 4H),
3
2
.39-3.32 (m, 1H), 3.20-3.14 (m, 1H), 2.61-2.55 (m, 3H), 2.39-2.36 (m, 1H), 2.19 (s, 3H),
1
3
.11-1.81 (m, 6H), 1.72-1.65 (m, 1H), 1.54-1.48 (m, 1H), 1.41-1.35 ppm (m, 1H); C NMR
(
100 MHz, CD COCD ): δ = 174.7, 153.9, 150.1, 107.9, 106.2, 105.7, 89.6, 64.3, 64.2, 40.6,
8.3, 36.7, 36.1, 31.0, 30.9, 28.1, 25.8, 13.0 ppm; EI MS (70 eV): m/z (%): 335 (0.1) [M] ,
3
3
+
3
3
17 (16), 231 (14), 209 (11), 123 (85), 95 (100).
1
.22▬▬ Synthesis of 32.
1
5

O
O
O
O
HO
N
O
N
CF COOH
3
H
dry CH Cl ,
2
2
7
5%
O
O
3
0
32
To a solution of 30 (100 mg, 0.32 mmol) in dry CH
2
Cl
2
(5 mL) was added CF
3
COOH (0.05
o
mL, 0.65 mmol) at 0 C under argon atmosphere. After the mixture was stirred for 24 h at
room temperature, saturated NaHCO
extracted with CH Cl (30 mL). The combined extracts were washed with saturated NaHCO
5×8 mL) and dried over Na SO , and concentrated under reduced pressure. Purification of
3
(5 mL) was added, and the resulting mixture was
2
2
3
(
2
4
the residue through column chromatography on silica gel (petroleum/actone 4:1 to 1:1)
afforded 32 (59 mg 75%).
1
H NMR (400 MHz, CDCl
3
): δ = 7.32 (bs, 1H), 6.28 (bs, 1H), 4.51-4.46 (m, 1H), 3.08-3.01
(
m, 1H), 2.88-2.79 (m, 3H), 2.72-2.61 (m, 2H), 2.55-2.40 (m, 2H), 2.35-2.27 (m, 1H),
1
3
2
1
.21-2.14 ppm (m, 3H); C NMR (100 MHz, CDCl ): δ = 208.9, 172.3, 147.3, 142.3, 123.4,
3
06.0, 60.7, 41.8, 37.6, 36.8, 35.3, 34.2, 31.9, 23.1 ppm; EI MS (70 eV): m/z (%): 245 (7)
+
[
M] , 195 (3), 188 (100), 174 (31), 160 (18), 146 (10).
1
.23▬▬ Synthesis of 33.
O
O
O
HO
O
O
N
O
CF COOH
N
3
dry CH Cl ,
H
2
2
8
3%
3
1
O
33
To a solution of 31 (500 mg, 1.5 mmol) in dry CH
2
Cl
2
(15 mL) was added CF
3
COOH (0.23
o
mL, 3.0 mmol) at 0 C under argon atmosphere. After the mixture was stirred for 24 h at room
temperature, saturated NaHCO
with CH Cl (30 mL). The combined extracts were washed with saturated NaHCO
and dried over Na SO , and concentrated under reduced pressure. Purification of the residue
3
(15 mL) was added, and the resulting mixture was extracted
2
2
3
(10×3 mL)
2
4
through column chromatography on silica gel (petroleum/actone 4:1 to 1:1) afforded 33 (338
mg, 83%).
1
H NMR (400 MHz, CDCl
3
): δ = 5.77 (s, 1H), 4.28-4.22 (m, 1H), 2.92-2.57 (m, 6H),
1
3
2
.36-2.17 (m, 5H), 2.14 (s, 3H), 2.00-1.94 (m, 1H), 1.86-1.81 ppm (m, 2H); C NMR (100
MHz, CDCl ): δ = 209.9, 172.9, 149.8, 148.6, 126.2, 104.5, 62.2, 42.8, 39.5, 36.8, 36.7, 34.9,
3
+
3
1.7, 26.4, 25.0, 13.2 ppm; EI MS (70 eV): m/z (%): 273 (13) [M] , 216 (100), 202 (53), 188
(
16).
3. Copies of NMR Spectra of the Products
1
6