O-Benzenedisulfonimide as a reusable acid catalyst for an easy, efficient, and green synthesis of tetrahydroisoquinolines and tetrahydro-β-carbolines through Pictet-Spengler reaction

Article abstract of DOI:10.1016/j.tetlet.2010.09.149

The synthesis of tetrahydroisoquinolines and tetrahydro-β-carbolines, using the Pictet-Spengler reaction, was carried out in the presence of a catalytic amount of o-benzenedisulfonimide, which worked as a Br?nsted acid organocatalyst. The reaction conditi

Full text of DOI:10.1016/j.tetlet.2010.09.149

Tetrahedron Letters 51 (2010) 6356–6359
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Tetrahedron Letters
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o-Benzenedisulfonimide as a reusable acid catalyst for an easy, efficient,
and green synthesis of tetrahydroisoquinolines and tetrahydro-b-carbolines
through Pictet–Spengler reaction
⇑
Margherita Barbero, Stefano Bazzi, Silvano Cadamuro, Stefano Dughera
Dipartimento di Chimica Generale e Chimica Organica, Università di Torino, C.so Massimo d’Azeglio 48, 10125 Torino, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of tetrahydroisoquinolines and tetrahydro-b-carbolines, using the Pictet–Spengler reaction,
was carried out in the presence of a catalytic amount of o-benzenedisulfonimide, which worked as a
Brønsted acid organocatalyst. The reaction conditions were mild and green and good target product
yields were achieved. The catalyst was easily recovered and purified, ready to be used in further reactions
with economic and ecological advantages.
Received 18 August 2010
Revised 24 September 2010
Accepted 29 September 2010
Available online 7 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Homogeneous catalysis
Tetrahydroisoquinoline
Tetrahydro-b-carbolines
Brønsted acid
2-Arylethanamines
The Pictet–Spengler reaction1a–d is a useful and an important
synthetic protocol for the preparation of tetrahydroisoquinoline1e
and tetrahydro-b-carboline ring systems.1f These are present in
numerous natural and synthetic organic compounds and posses
various biological activities. For instance, tetrahydroisoquinolines
show powerful anti-tumor, antimicrobial, anti-HIV activities;1g,h
tetrahydro-b-carbolines are interesting hypnotic, anxiolytic, anti-
microbial, antiviral, anti-tumor, and anti-convulsant compounds.1i
Usually, Brønsted acids (recent examples are: H+ montomorill-
onite,2 trifluoroacetic acid,1g,3 carboxylic acids-thiourea,4 p-tolu-
enesulphonic acid,5 perfluoroctansulphonic acid in water,6 chiral
phosphoric acids7) or Lewis acids (recent examples are: calcium
complexes,8 Yb(OTf)3,9 AuCl3/AgOTf10) are employed as catalysts
to promote this reaction, involving the cyclization of iminium ions
(or imines) resulting from the dehydration reaction of 2-arylethyl-
amine derivatives with aldehydes.
We have recently reported the use of o-benzenedisulfonimide
(1, Fig. 1) in catalytic amounts as a safe, non-volatile, and non-cor-
rosive Brønsted acid in some acid-catalyzed organic reactions, such
as etherification,11,12 esterification,11–13 acetalization,11,12 the Rit-
ter reaction,14 Nazarov electrocyclization,15 disproportionation of
dialkyl diarylmethyl ethers,16 Hosomi–Sakurai reaction17, and
Friedlander annulation.18
In general, all synthetic methods were performed under mild
reaction conditions and showed short reaction times, good selec-
tivity, and the absence or minimal formation of by-products. More-
over, it is worthwhile highlighting another advantage of all the
above reactions: 1 can be easily and almost completely recovered
from the reaction mixtures in high yield, due to its complete solu-
bility in water. This permits its reuse in other reactions, immedi-
ately or after a fast purification step on a cation-exchange resin
without any loss of catalytic activity, with economic and ecological
advantages.
In this Letter we wish to propose a simple, efficient, and green
synthesis of tetrahydroisoquinolines and tetrahydro-b-carbolines
under the Pictet–Spengler protocol in the presence of 1 which acts
as a reusable Brønsted acid catalyst (Schemes 1 and 2).
Firstly, various aromatic and heteroaromatic aldehydes 3a, 3c–g
were reacted with 2-(3,4-dimethoxyphenyl)ethanamine (2a); the
reaction mixture was heated at 80 °C, in the presence of 10 mol %
of 1 and in the absence of a solvent. The reaction times were
between 6 and 12 h. As shown in Table 1 (entries 1 and 5–9), the
target tetrahydroisoquinolines 5a, 5e–i were always obtained in
SO2
NH
SO2
1
⇑
Corresponding author. Tel.: +39 11 6707645; fax: +39 11 6707642.
E-mail address: stefano.dughera@unito.it (S. Dughera).
Figure 1. o-Benzenedisulfonimide 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.09.149

M. Barbero et al. / Tetrahedron Letters 51 (2010) 6356–6359
6357
very simple: it was sufficient to add water to the crude residue,
filter, and wash the resulting solid with additional water on a
Buchner funnel.19
X
O
NH2
1 (cat)
+
R
R'
Y
3
2
Furthermore, 1 was recovered in excellent yields (e.g., Table 2,
entry 1, 89%), by simply evaporating the aqueous washings under
reduced pressure.19 Recovered 1 was reused as a catalyst in other
two consecutive reactions between 2a and 3a. The results are listed
in Table 2. The reaction time increased after each run, but the
yields of 5a and the recovery yield of 1 were always fairly good.
Using acetophenone (3b) as a carbonyl partner, we also ob-
tained good results (Table 1, entry 4). Using the less reactive 2-
(3-methoxyphenyl)ethanamine (2b), the yield of 5b was lower
and the reaction time was longer (24 h, Table 1, entry 2). Reacting
2-phenylethanamine (2c), no traces of 5c were detected; only the
intermediate N-benzyliden-2-phenylethyl amine (4c) formed. This
intermediate cannot cycle due to the lack of electron donating
groups on the aromatic ring (Table 1, entry 3).
To further explore the synthetic usefulness of 1 in Pictet–Spen-
gler reactions we reacted tryptamine 6 with aromatic aldehydes
3a, 3c–g in order to obtain tetrahydro-b-carbolines 8 (Scheme 2).
These reactions needed 20 mol % of 1, reaction times between 8
and 16 h and heating to 80 °C; however, the yields of 8 and the
recovery yield of 1 were always good (Table 3, entries 1–6). It
was always possible to recover 1 in good yields (e.g., Table 3 entry
1, 85%).
2a: X,Y =OMe
3
a
b
c
d
e
f
R
R'
H
3 R
2-thienyl
R'
2b: X = OMe; Y = H
2c: X,Y = H
C6H5
C6H5
g
H
H
H
H
H
Me
H
h nC5H11
2-MeOC6H4
4-MeOC6H4
4-NO2C6H4
4-CNC6H4
i C6H5CH2
j cyclohexyl
H
H
k
t-Bu
H
R
X
X
1 (cat)
N
R'
NH
R'
Y
Y
R
R
4
5
4,5
a
X
Y
R
R'
H
4,5
h
i
X
Y
R'
OMe OMe C6H5
OMe OMe 4-CNC6H4
OMe OMe 2-thienyl
H
H
H
H
H
H
H
b
c
OMe
H
H
H
C6H5
C6H5
H
H
j
OMe OMe
OMe
n
C5H11
nC5H11
d
e
OMe OMe C6H5
Me
H
k
H
OMe OMe 2 -MeOC6H4
OMe OMe 4-MeOC6H4
OMe OMe 4-NO2C6H4
l
OMe OMe C6H5CH2
OMe OMe cyclohexyl
OMe OMe t-Bu
f
H
H
m
n
g
Scheme 1. Synthesis of tetrahydroisoquinolines 5.
It is worth noting that the Pictet–Spengler reactions, performed
with other Brønsted acids as catalysts, usually require the presence
of a solvent, either during the reaction or the work-up3–5,7–10 or
harsher reaction conditions.4,5,8,10
We then examined the extension of this procedure to aliphatic
aldehydes. However, the reaction of 2a with primary aldehyde 3h
gave a small amount of product 16a, which arises from homo-aldol
condensation and imine formation (Table 1, entry 10; Scheme 3) as
well as the target product 5j.7 The amount of 16b significantly in-
creased when 2b was reacted with 3h (Table1, entry 11). Further-
more, the reactions of 6 with 3h furnished only 16c (Table 3, entry
7).
The mechanism of the Pictet–Spengler reaction, described in
Scheme 3, implies the formation of the iminium salt 11, its cycliza-
tion, and subsequent deprotonation to give the final product 12.
However, when tautomerism between imine 13 and amine 14 is
possible (probably favoured by 1; Scheme 3), 14 can react with a
protonated aldehyde initially furnishing the intermediate 15 and
then the product of the homo-aldol condensation 16.7 Since the
cyclization reaction is greatly facilitated by the presence of elec-
tron donating groups on the aromatic ring, we could suppose that
in the presence of two methoxy groups the speed of the cyclization
reaction is greater than the speed with which 13 can tautomerize.
In the presence of only one methoxy group, however, since the
speed of cyclization decreases, the possibility of tautomery be-
tween 13 and 14 increases and accordingly increases the yield of
NH2
O
1 (cat)
+
R
H
N
H
6
3
3 R
3
a
c
d
e
f
R
C6H5
g
h
i
2-thienyl
nC5H11
2-MeOC6H4
4-MeOC6H4
4-NO2C6H4
4-CNC6H4
C6H5CH2
cyclohexyl
t-Bu
j
k
R
N
1 (cat)
H
NH
H
N
H
N
H
R
7
8
7,8
R
7,8 R
a
b
c
d
e
C6H5
f
2-thienyl
n-C5H11
C6H5CH2
cyclohexyl
t-Bu
2-MeOC6H4
4-MeOC6H4
4-NO2C6H4
4-CNC6H4
g
h
i
j
Scheme 2. Synthesis of tetrahydro-b-carbolines 8.
excellent yields, more than 80%. These high yields are independent
of the type and the position of the substituents. The work-up was
Table 1
Synthesis of tetrahydroisoquinolines 5
Entry
Reactantsa
Products and yieldsb (%)
Time (h)
Tetrahydroisoquinolines 5c
Lit. mp (°C)
Mpd (°C)
EI–MS: m/z (%)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2a
2a
2a
2a
2a
2a
3a
3a
3a
3b
3c
3d
3e
3f
5a, 89
5b, 72
4c, 85
5d, 85
5e, 86
5f, 85
5g, 84
5h, 87
5i, 87
6
24
24
8
8
6
10
12
8
111–112
75–76
Viscous oil
96–97
Waxy solid
94–95
142–143
114–115
64–65
110–11120
269 [M+,5]
239 [M+,8]
209 [M+,25]
283 [M+,10]
299 [M+,5]
299 [M+,12]
314 [M+,5]
294 [M+,10]
275 [M+,5]
73–7421
22
—
94–9623
Viscous oil1g
95–9624
140–14124
110–1121g
e
3g
(continued on next page)

6358
M. Barbero et al. / Tetrahedron Letters 51 (2010) 6356–6359
Table 1 (continued)
Entry
Reactantsa
Products and yieldsb (%)
Time (h)
Tetrahydroisoquinolines 5c
Lit. mp (°C)
Mpd (°C)
EI–MS: m/z (%)
10
11
12
13
14
2a
2b
2a
2a
2a
3h
3h
3i
3j
3k
5j, 75f
5k, —g
5l, 82h
5m, 88h
5n, 88
8
12
6
10
8
Viscous oil
—
Viscous oil
Viscous oil
51–52
Oil26
—
263 [M+,15]
—
Oil27
283 [M+,12]
275 [M+,5]
249 [M+,10]
28
50–5130
a
All the reactions were performed with 10 mol % of 1 and at 80 °C.
Yields refer to the pure products.
b
c
d
e
f
Structures and purity of all the products were confirmed by comparison of their physical (mp) and spectral data with those reported in the literature.
Crystallization solvent: MeOH.
In the literature25 only spectral data are reported.
The reaction mixture was dissolved in Et2O (5 ml) and washed with H2O (5 ml). After solvent removal under reduced pressure, the crude residue was chromatographed on
a short flash column, (eluent: CH2Cl2/MeOH 9:1) to provide pure 5j. In the GC and GC/MS analyses of the crude residue 16a, EI–MS, m/z (%) = 345 [M+,45], was also detected.
However, it was impossible to isolate it as pure product.
g
On the GC and GC/MS analyses of the crude residue 4k, EI–MS, m/z (%) = 233 [M+,35], 5k, EI–MS, m/z (%) = 233 [M+,15], and 16b EI–MS, m/z (%) = 315 [M+,20] were
detected (5k and 16b about 1:1 ratio). However, it was impossible to separate them by flash chromatography.
h
Cold water (5 ml) was added to the reaction mixtures, which were cooled to 0–5 °C, under vigorous stirring. The resulting gummy solids were filtered on a Buchner
funnel, placed in a flask and dried under vacuum at room temperature. The resulting viscous oils were pure 5l or 5m.
Table 2
Consecutive reactions with 1
R
NH2
N
RCH2CHO
+
Entry
Time (h)
Yield (%) of 5aa
Recover (%)of 1 (mg)
13
9
10
89b
81
78
84, 92c
80, 74d
80, 59
1
1
2
3
6
9
10
1
1
H2O
Z-
a
Yields refer to the pure products.
The reaction was performed with 5 mmol of 2a and 3a and 10 mol %
NH
14
R
R
b
NH+
Ar
of 1 (110 mg, 0.5 mmol).
11
c
Recovered 1 was used as catalyst in entry 2.
Recovered 1 was used as catalyst in entry 3.
1.RCH2CHO, 1
d
= Ar
2.H2O
1
1
R
Table 3
NH
NH
Synthesis of tetrahydro-b-carbolines 8
Ar
R
Entry Reactantsa Products and
yieldsb (%)
Time
(h)
Tetrahydro-b-carbolines 8c
OH OH
R
Mpd
Lit. mp
EI–MS:
12
15
(°C)
(°C)
m/z (%)
2 H2O
SO2
N
SO2
1
2
3
4
5
6
3a
3c
3d
3e
3f
8a, 82e
8b, 86
8c, 80
8d, 85
8e, 86
8f, 82
12
12
14
12
16
16
161–
162
95–
96
204–
205
170–
171
159–
160
172–
173
—
160–
248
Z =
1613
[M+,5]
278
32
R
R
[M+,8]
278
Ar
N
205–
20634
172–
[M+,10]
293
16
1733
[M+,10]
273
16 Ar
R
35
a
b
c
d
3,4-(MeO)2C6H3
3-MeOC6H4
3-indolyl
n
n
n
C4H9
[M+,12]
254
C4H9
C4H9
C6H5
3g
169–
17037
—
[M+,10]
—
3-indolyl
7
8
9
3h
3i
3j
8g, —f
8h, —g
8i, —h
8j, 78
12
14
16
12
—
—
—
Scheme 3. Mechanism of Pictet–Spengler reaction.
—
—
—
10
3k
93–
94
94.5–
228
95.538
[M+,8]
16. On the other hand, when the indolyl ring is present, tautomer-
ization is faster than cyclization and the only product is 16. To fur-
ther the examination of aliphatic aldehydes, it is worth noting that
the reactions of 2a with 3i–k, under the same conditions as de-
scribed above for aromatic aldehydes, provided excellent yields
of 5l–n (Table 1, entries 12–14).The greater steric hindrance of
aldehydes 3i and 3j probably made their electrophilic attack on
14 more difficult, therefore cyclization was favored. On the other
hand, only 16d was formed and no traces of 8h were detected
when 6 was reacted with 3i (Table 3, entry 8). The reaction be-
tween 6 and 3j also failed (Table 3, entry 9). Obviously, the only po-
sitive result was obtained by reacting 6 with tertiary aldehyde 3k
(Table 3, entry 10).
a
b
c
All the reactions were performed with 6 and 20 mol % of 1 at 80 °C.
Yields refer to the pure products.
Structures and purity of all the products were confirmed by comparison of their
physical (mp) and spectral data with those reported in the literature.
d
Crystallization solvent: MeOH.
The reaction carried out with 10 mol % of 1, after 24 h was not complete, due to
e
the presence of intermediate 7a EI–MS, m/z (%) = 248 [M+,20].
f
On the GC and GC/MS analyses of the crude residue, 16c, EI–MS, m/z (%) = 324
[M+,10] was detected. However, it was impossible to purify by flash chromatogra-
phy. No traces of 8g were detected.
g
On the GC and GC/MS analyses of the crude residue, 16d, EI–MS, m/z (%) = 364
[M+,25] was detected. However, it was impossible to purify by flash chromatogra-
phy. No traces of 8h were detected.
h
On the GC and GC/MS analyses of the crude residue no significant products
were detected. No traces of 8i were detected.

M. Barbero et al. / Tetrahedron Letters 51 (2010) 6356–6359
6359
19. 6,7-Dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline
procedure for the preparation of
Benzenedisulfonimide (1; 10 mol %; 110 mg, 0.5 mmol) was added to
(5a):
representative
In conclusion, we have proposed a mild, easy, efficient, and
green method for the synthesis of tetrahydroisoquinoline and tet-
rahydro-b-carboline through the Pictet–Spengler reaction in the
presence of o-benzenedisulfonimide (1) used as a reusable homo-
geneous catalyst. The advantages of performing the Pictet–Spen-
tetraydroisoquinolines
5:
o-
a
mixture of 2-(3,4-dimethoxyphenyl)ethanamine (2a; 0.91 g, 5 mmol) and
benzaldehyde (3a; 0.53 g, 5 mmol). The mixture was stirred and heated at
80 °C. The reaction was monitored by GC and GC/MS. First, the complete
disappearance of 2a and 3a, then the formation of intermediate 4a and product
5a were observed (30 min), and finally the total interconversion of 4a to 5a
(6 h). Cold water (20 ml) was added to the reaction mixture, which was cooled
to 0–5 °C, under vigorous stirring. The resulting solid was filtered on a Buchner
funnel and washed with additional cold water (5 ml). It was virtually pure (GC,
GC–MS, 1H NMR, 13C NMR) title compound 5a, white solid; yield: 89% (1.61 g).
The aqueous washings were collected and evaporated under reduced pressure.
After removal of the water, virtually pure (1H NMR) o-benzenedisulfonimide
(1) was recovered (92 mg, 84% yield). The same procedure was employed in the
preparation of tetrahydro-b-carbolines 8.
gler reaction in the presence of
1 as a catalyst can be
summarized as follows: (1) the use of a safe, non-volatile, non-cor-
rosive Brønsted acid, (2) good recovery yields of 1 at the end of the
reactions by simply evaporating aqueous washings, (3) the target
products are obtained generally in excellent yields (4) the reactions
are carried out under easy, mild, and green conditions with eco-
nomic and ecological benefits.
20. Coskun, N.; Tuncman, S. Tetrahedron 2006, 62, 1345–1350.
21. Minor, D. L.; Wyrick, S. D.; Charifson, P. S.; Watts, V. J.; Nichols, D. E.; Mailman,
R. B. J. Med. Chem. 1994, 37, 4317–4328.
Acknowledgment
22. Burger, B. V.; Viviers, M. Z.; Bekker, J. P. I.; le Roux, M.; Fish, N.; Fourie, W. B.;
Weibchen, G. J. Chem. Ecol. 2008, 34, 659–671.
23. Horiguchi, Y.; Kodama, H.; Nakamura, M.; Yoshimura, T.; Hanezi, K.; Hamada,
H.; Saitoh, T.; Sano, T. Chem. Pharm. Bull. 2002, 50, 253–257.
24. Aubry, S.; Pellet-Rostang, S.; Faure, R.; Lemaire, M. J. Heterocycl. Chem. 2006, 1,
139–143.
This work was supported by the University of Torino.
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28. 1-Cyclohexyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (5m) is known in
the literature29 but no physical and spectral data are reported. 1H NMR
(200 MHz, CDCl3): d = 6.64 (s, 1H), 6.55 (s, 1H), 3.95 (d, J = 7.0 Hz, 1H) 3.69 (s,
3H), 3.68 (s, 3H), 3.25–3.18 (m,2H), 2.71–2.64 (m, 2H), 2.10–1.86 (m, 2H),
1.60–1.46 (m, 5H), 1.10–0.97 (m, 5H); 13C NMR (50 MHz, CDCl3): d = 148.8,
147.4, 131.1, 127.8, 111.6, 109.5, 56.5, 56.1, 55.9, 43.4, 37.0, 32.1, 29.8, 26.1,
25.6.
29. Gitto, R.; Agnello, S.; Ferro, S.; De Luca, L.; Vullo, D.; Brynda, J.; Mader, P.;
Supuran, C. T.; Chimirri, A. J. Med. Chem. 2010, 53, 2401–2408.
30. 1-(t-Butyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (5n) is known in the
literature31 but no NMR data are reported. 1H NMR (200 MHz, CDCl3): 6.61 (s,
1H), 6.57 (s, 1H), 3. 99 (s, 1H), 3.70 (s, 3H), 3.69 (s, 3H), 3.28–3.20 (m, 2H),
2.69–2.60 (m, 2H), 1.99 (br s, 1H), 0.86 (s, 9H); 13C NMR (50 MHz, CDCl3):
d = 147.5, 146.1, 131.9, 128.9, 112.4, 110.2, 56.4, 56.1, 55.7, 42.3, 25.0.
31. Knabe, J.; Roloff, H. Arch. Pharm. Ber. Dtsch. Pharm. Ges. 1965, 298, 561–565.
32. 1-(2-Methoxyphenyl)-1,2,3,4-tetrahydro-b-carboline (8b) is known in the
literature33 but no physical and spectral data are reported. 1H NMR
(200 MHz, CDCl3): d = 8.00 (br s, 1H), 7.92 (dd, J1 = 7.6 Hz, J2 = 1.7 Hz, 2H),
7.61 (d, J = 7.6 Hz, 1H), 7.32–6.82 (m, 5H), 5.39 (s, 1H), 3.77 (s, 3H), 3.29–3.21
(m, 2H), 2.71–2.62 (m, 2H), 2.12 (br s, 1H); 13C NMR (50 MHz, CDCl3): d = 148.5,
147.3, 136.1, 131.6, 128.4, 127.4, 127.2, 124.6, 121.9, 121.6, 120.6, 118.9, 118.8,
114.0, 56.5, 55.3, 41.3, 22.4.
33. Protiva, M.; Vejdezlek, Z. J.; Rajsner, M. Collect. Czech. Chem. Commun. 1963, 28,
629–636.
13. Barbero, M.; Cadamuro, S.; Dughera, S.; Venturello, P. Synthesis 2008, 3625–
3632.
14. Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S. Eur. J. Org. Chem. 2009, 430–
436.
15. Barbero, M.; Cadamuro, S.; Deagostino, A.; Dughera, S.; Larini, P.; Occhiato, G.;
Prandi, C.; Tabasso, S.; Venturello, P.; Vulcano, R. Synthesis 2009, 2260–2266.
16. Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S.; Ghigo, G. Eur. J. Org. Chem.
2009, 4346–4351.
17. Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S.; Piccinini, C. Synthesis 2010,
315–319.
34. Prajapati, D.; Gohain, M. Synth. Commun. 2008, 38, 4426–4433.
35. 1-(4-Cyanophenyl)-1,2,3,4-tetrahydro-b-carboline (8e) is known in the
literature36 but no physical and spectral data are reported. 1H NMR
(200 MHz, CDCl3): d = 7.93 (br s, 1H), 7.72–7.57 (m, 5H), 7.32–7.28 (m, 1H),
7.20–7.01 (m, 2H), 3.27–3.18 (m, 2H), 2.75–2.64 (m, 2H), 1.99 (br s, 1H); 13C
NMR (50 MHz, CDCl3): d = 148.6, 140.3, 136.5, 132.6, 132.4, 128.6, 127.6, 122.3,
122.2, 119.5, 119.1, 118.6, 113.9, 56.9, 41.7, 22.2.
36. Horvath, D. J. Med. Chem. 1997, 40, 2412–2423.
37. Foye, W. O.; Wang, H.-F. Med. Chem. Res. 1997, 7, 180–191.
38. Kawate, T.; Nakagawa, M.; Yamazaki, H.; Hirayama, M.; Hino, T. Chem. Pharm.
Bull. 1993, 41, 287–291.
18. Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S. Tetrahedron Lett. 2010, 51,
2342–2344.