Synthetic study on the T3P-promoted one-pot preparation of 1-substituted-3,4-dihydro-β-carbolines by the reaction of tryptamine with carboxylic acids

Article abstract of DOI:10.1016/j.tetlet.2016.03.067

A novel and efficient one-pot method has been developed for the synthesis of 1-substituted-3,4-dihydro-β-carbolines from tryptamine and a wide variety of carboxylic acids. The reaction was successfully applied to the synthesis of an important alkaloid har

Full text of DOI:10.1016/j.tetlet.2016.03.067

Tetrahedron Letters 57 (2016) 1953–1957
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ò
Synthetic study on the T3P -promoted one-pot preparation
of 1-substituted-3,4-dihydro-b-carbolines by the reaction
of tryptamine with carboxylic acids
a,b,
⇑
, Tamás Földesi b,c, Alajos Grün , Balázs Volk , György Keglevich ,
b
c
b
Péter Ábrányi-Balogh
Mátyás Milen
a
b,c
Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Organic Chemistry, 1519 Budapest, POB 286, Hungary
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, POB 91, Hungary
Egis Pharmaceuticals Plc., Directorate of Drug Substance Development, 1475 Budapest, POB 100, Hungary
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel and efficient one-pot method has been developed for the synthesis of 1-substituted-3,4-dihydro-
b-carbolines from tryptamine and a wide variety of carboxylic acids. The reaction was successfully
applied to the synthesis of an important alkaloid harmalan as well as dihydro-eudistomin-U. This repre-
Received 21 January 2016
Revised 11 March 2016
Accepted 21 March 2016
Available online 22 March 2016
Ò
sents the first case in which 1-propanephosphonic acid cyclic anhydride (T3P ) has been used in the
Bischler–Napieralski reaction. Unexpectedly it was observed that less than two equivalents of the T3PÒ
reagent were sufficient for the two consecutive reactions.
Keywords:
b-Carbolines
Ó 2016 Elsevier Ltd. All rights reserved.
Bischler–Napieralski reaction
Ring closure
One-pot synthesis
Ò
T3P
Introduction
reagents, for example treatment of the amide formed from trypta-
1
4
15
mine with POCl
3
2
or P O
5
in solvents with high boiling points,
b-Carbolines, incorporating a tricyclic pyrido[3,4-b]indole scaf-
fold, form a prominent group of alkaloids. b-Carbolines and their
reduced analogs, such as dihydro- and tetrahydro-b-carbolines
such as toluene or xylenes. In the last decades, milder reaction con-
ditions have also been described such as the use of polyphosphoric
1
1
6
acid (PPA) or ester (PPE) in dichloromethane, Ph
3
P in tetra-
1
7
18
19
can be found in various plants, mammalian and marine inverte-
chloromethane, Tf
in dichloromethane.
Recently, we reported the application of 1-propanephosphonic
2
O/DMAP, (COCl)
2
/FeCl
3
,
and (PhO)
3
PꢀCl
2
2
20
brates. Both simple and complex b-carboline derivatives possess
a broad spectrum of biological and pharmacological activities
3
4
5
Ò
including antimicrobial, antimalarial, antithrombotic, parasitici-
acid cyclic anhydride (T3P ) in the synthesis of a-aminophospho-
6
7
8
9
21
22
23
Ò
dal, anti-HIV, anti-Alzheimer, and antifungal effects. An impor-
tant member of the tetrahydro-b-carboline family is tadalafil, a
commercially available drug for the treatment of erectile dysfunc-
nates, phosphinic esters and amides. The T3P reagent is a
versatile promoter of a wide range of transformations, including
condensation, oxidation, rearrangement, and various other func-
tional group transformations, therefore its application in synthesis
1
0
tion. Furthermore, simple b-carbolines have been used as starting
2
4
materials in the preparation of many indole alkaloids and other
is swiftly increasing. Herein, we report a one-pot procedure for
11
physiologically active compounds.
the synthesis of 1-substituted-3,4-dihydro-b-carbolines from tryp-
Ò
Various methodologies have been reported in the literature for
the construction of the b-carboline skeleton.12 Among these, the
Bischler–Napieralski reaction, described in 1893 by August
Bischler and Bernard Napieralski, is one of the most important
procedures for the synthesis of 3,4-dihydro-b-carbolines from
tamine and the corresponding carboxylic acids using T3P as the
condensation reagent. To the best of our knowledge, this reagent
has not yet been applied in the Bischler–Napieralski reaction.
Results and discussion
1
3
tryptamine. In general, this cyclization reaction requires harsh
First, the reaction of tryptamine (1) and benzoic acid (2a) was
investigated. Heating the two components in a microwave (MW)
reactor at 150 °C for 30 min without solvent or in toluene resulted
⇑
Corresponding author. Tel.: +36 1 3826961; fax: +36 1 4633648.
E-mail address: abpeter@gmail.com (P. Ábrányi-Balogh).
http://dx.doi.org/10.1016/j.tetlet.2016.03.067
040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
0

1
954
P. Ábrányi-Balogh et al. / Tetrahedron Letters 57 (2016) 1953–1957
in the formation of the tryptamine benzoate salt (3a). However,
when the T3P reagent (solution in ethyl acetate) was also added
under MW conditions, acylation took place giving rise to the
Table 1
a
Ò
Optimization of the Bischler–Napieralski reaction
Entry
T3PÒ equivb
T (°C)
t (h)
Heating
Yield (%)
formation of N
quent Bischler–Napieralski cyclization in
b
-benzoyltryptamine (4a), which underwent subse-
consecutive and
1
2
3
4
5
6
1.25
1.5
1.5
1.5
1.5
2
100
100
120
120
120
120
2
2
1.5
2
1.5
1.5
MW
MW
MW
MW
D
74
80
81
76
61
58
a
one-pot manner, leading to the expected 1-phenyl-3,4-dihydro-b-
carboline (5a, Scheme 1). The reaction conditions were optimized
and the results are shown in Table 1. When utilizing 1.25 equiv
D
Ò
of the T3P reagent at 100 °C for 2 h, the yield of 5a was 74%
a
Table 1, entry 1). Upon increasing the amount of the T3PÒ reagent
Reaction conditions: tryptamine (2.5 mmol), benzoic acid (1 equiv), 30–50 W.
5
(
b
0 w/w% in EtOAc solution.
to 1.5 equiv, the yield increased to 80% (entry 2). At 120 °C, 1.5 h
was sufficient for reaction completion to afford product 5a in
8
1% yield (entry 3). A longer reaction time (2 h) at 120 °C resulted
O
P
O
P
Pr
in the formation of product 5a in a lower yield (76%) due to the
appearance of by-products, which were detected by TLC and
HPLC–MS (entry 4).
Pr
Pr
O
O
OH
O
HO
O
HO
P
H2O
2
H O
O
O
O P
+
P
P
HO
P
O
O
P
Comparative thermal experiments were also carried out at
Pr Pr
Pr
O
O
HO
20 °C using 1.5 or 2 equiv of the T3PÒ reagent in a sealed tube
HO
1
Pr
P
Pr
O
O
Pr
leading to yields of 61% and 58%, respectively, after 1.5 h (entries
, 6). From the above results it can be concluded that MW irradia-
T3P®
®
T3P . H O
2
5
tion was beneficial in the one-pot synthesis of 1-phenyl-3,4-
Scheme 2. Two-step reaction of T3PÒ with two equivalents of water.
dihydro-b-carboline (5a) by the reaction of tryptamine (1) and
Ò
benzoic acid (2a) in the presence of T3P .
It is noteworthy that both the amidation and the ring closure
reactions, altogether involving the elimination of two molecules
on HPLC–MS, in reaction A the conversion of tryptamine was 56%
with N -benzoyltryptamine (4a) and 1-phenyl-3,4-dihydro-b-car-
b
Ò
of water, take place in the presence of only 1.5 equiv of T3P . This
boline (5a) detected in 27% and 29%, respectively. In reaction B,
the cyclization to 5a took place with 85% conversion. Therefore,
it can be concluded, that the water adduct of T3PÒ is able to cat-
alyze both the acylation of tryptamine and the subsequent
Bischler–Napieralski cyclization of the amide.
can be explained by assuming that the T3PÒ molecule can react not
only in its cyclic form, but also in the open-chain compound
Ò
(
(
T3P ꢀH
2 2
O) formed from the formal uptake of a H O molecule
Scheme 2).
Ò
To examine this hypothesis, two experiments were performed
After optimization of the reaction conditions (1.5 equiv T3P ,
using 0.5 equiv of T3PÒ (MW, 120 °C, 1.5 h). When benzoyl-
tryptamine (4a) was used as the starting compound, the cycliza-
tion to 5a took place with 70% conversion. In the reaction of
MW, 120 °C, 1.5 h) for 1-phenyl-3,4-dihydro-b-carboline (5a), the
reaction scope was extended to substituted benzoic acids (2b–k),
as well as aliphatic (2l–o) and heterocyclic carboxylic acids
(2p–s) in order to synthesize the corresponding 1-substituted-3,
4-dihydro-b-carbolines. The results summarized in Scheme 3 and
Table 2 demonstrate that aryl substituents in the meta or para posi-
tion did not have a significant effect on conversion or yields. Only
the highly electron donating methoxy group facilitated (Table 2,
entry 5) and the highly electron withdrawing nitro group (entry
11) hindered the reaction significantly, which could be explained
by the activation or the deactivation of the nitrilium cation respec-
tively. In the cases of ortho substituents (entries 6, 7, 10) the lower
yields and longer reaction times can be explained by steric effects.
With aliphatic carboxylic acids (entries 12–15) a reaction time of
2 h was necessary for full conversion, and a slight correlation could
be found between the increasing size of the aliphatic group and the
decreasing yields. The best yield (95%) was achieved in the synthe-
Ò
tryptamine (1), benzoic acid (2a) and 0.5 equiv of T3P , the reac-
b
tion mixture contained, based on HPLC–MS, N -benzoyltryptamine
(4a, 79%) and 1-phenyl-3,4-dihydro-b-carboline (5a, 15%). The
findings of these two experiments show that one molecule of
Ò
T3P can promote the elimination of more than two molecules of
2
H O. Therefore it is plausible to assume that the open-chain deriva-
Ò
tive of T3P , which is formed in the ring opening step and contains
two anhydride moieties, is still reactive and may serve as a reagent
for the further reaction steps. Additionally, further evidence comes
Ò
from an earlier study which found that the T3P -promoted esteri-
fication of phosphinic acids could also be performed using less
Ò 23
than an equimolar amount of T3P . To further support this the-
Ò
ory, the T3P reagent was mixed with one equivalent of H
2
O in
order to hydrolyze the cyclic anhydride. After the exothermic reac-
tion, tryptamine and one equivalent of benzoic acid (reaction A) or
1
c,25
sis of harmalan (5l), an important harmala-alkaloid.
Ivanov and
N
b
-benzoyltryptamine (reaction B) were added and the mixture
co-workers previously applied polyphosphoric acid (PPA) and
heated under the standard conditions (MW, 120 °C, 1.5 h). Based
isolated 5l from the reaction of tryptamine and acetic acid in 77%
O
3
4
2
NH3+
O
NH2
O
MW
T3P
N
H
5
4a
4
b
N
®
P
Ph
6
7
P
1
+
Ph
OH
9a
N
H
N
H
-H
2
O
Ph
EtOAc
N
H
4a
-H
2
O
8a
N
H
5a
9
-O
8
Ph
1
2a
3a
P = T3P® or T3P® H O
.
2
O
N
N
H
N
Ph
N
Ph
N
H
N
H
Ph
N
H
H
N
H
Ph
Scheme 1. Reaction of tryptamine and benzoic acid in the presence of T3PÒ with a schematic mechanism proceeding through the nitrilium ion.

P. Ábrányi-Balogh et al. / Tetrahedron Letters 57 (2016) 1953–1957
1955
MW
.5 equiv T3P®
N
N
1
R
N
H
EtOAc
N
H
a-r
RCOOH
a-s
N
2
5
5
5s'
28%
0-95%
NH2
N
H
COOH
COOH
N
N
N
MW
equiv T3P®
N
N
H
Δ, 16 h
Pd/C
dioxane
H
2
1
EtOAc
H
N
H
N
2t
N
5
t'
80%
Scheme 3. Reaction of tryptamine (1) and carboxylic acid derivatives (2a–t) in the presence of T3PÒ.
Table 2
Conditions and yields for the one-pot syntheses of 1-substituted b-carboline derivatives
Entry
5
T (°C)
t (h)
Yield (%)
N
1
a
120
1.5
81
N
H
Ph
N
N
H
2
3
b
c
120
120
1.5
1.5
74
N
N
N
H
85
72
N
H
4
5
d
e
120
120
1.5
1.5
CN
N
N
N
H
94
57
O
N
H
O
6
7
f
120
120
3
4
O
N
g
N
H
O
50
O
(
continued on next page)

1
956
P. Ábrányi-Balogh et al. / Tetrahedron Letters 57 (2016) 1953–1957
Table 2 (continued)
Entry
5
T (°C)
t (h)
Yield (%)
N
N
H
8
9
h
120
1.5
84
O
O
O
N
N
H
i
120
1.5
87
73
55
Cl
N
1
1
0
1
j
N
H
Cl
120
120
2
N
N
H
k
2
NO2
N
N
1
1
2
3
l
120
120
2
2
95
86
N
H
m
N
H
N
N
1
1
4
5
n
o
120
120
2
2
83
80
N
H
N
H
N
N
N
H
1
6
p
150
2
50
NH
S
1
1
1
7
8
9
q
r
N
H
130
130
140
2
2
2
81
N
N
N
H
55
O
0
N
H
28a
s
N
The product was oxidized under the applied reaction conditions to give the aromatic b-carboline derivative (5s ), see Scheme 3.
a
0
yield.16a Our method represents a remarkably efficient one-pot
synthesis of 5l, as the T3P reagent can be handled more easily
than PPA and the yield of the reaction was almost quantitative.
When applying heterocyclic carboxylic acids (Table 2, entries
16–19), the reaction time had to be lengthened (from 1.5 h to 2 h)
and the temperature elevated, which inevitably led to increased
decomposition and lower yields. When reacting indole-3-
carboxylic acid (2p) with tryptamine, the dihydro derivative of
Ò

P. Ábrányi-Balogh et al. / Tetrahedron Letters 57 (2016) 1953–1957
1957
the alkaloid eudistomin U1c,26 (5p) was obtained in 50% yield
Table 2, entry 16). When starting from nicotinic acid (2s), the
Domínguez, G.; Pérez-Castells, J. Targets Heterocycl. Syst. 2008, 12, 212–257; (e)
Domínguez, G.; Pérez-Castells, J. Eur. J. Org. Chem. 2011, 7243–7253; (f) Singh,
V.; Batra, S. Curr. Org. Synth. 2012, 9, 513–528; (g) Laine, A. E.; Lood, C.;
Koskinen, A. M. P. Molecules 2014, 19, 1544–1567.
(
product underwent aromatization at the C ring under the applied
0
reaction conditions, therefore only 1-pyridyl-b-carboline (5s ,
2. (a) Allen, J. R. F.; Holmstedt, B. R. Phytochemistry 1980, 19, 1573–1582; (b)
Buckholtz, N. S. Life Sci. 1980, 27, 893–1011; (c) McNulty, J.; Still, I. W. J. Curr.
Org. Chem. 2000, 4, 121–138.
Scheme 3) could be retrieved from the reaction mixture in 28%
yield. When following the reaction by HPLC–MS, 1-pyridyl-
3
.
(a) Molina, P.; Fresneda, P. M.; Garcia-Zafra, S.; Almendros, P. Tetrahedron Lett.
1994, 35, 8851–8853; (b) Youssef, D. T. A.; Shaala, L. A.; Asfour, H. Z. Mar. Drugs
1
,2,3,4-tetrahydro-b-carboline was also detected in addition to
2
013, 11, 1061–1070.
(a) Winkler, J. D.; Londregan, A. T.; Hamann, M. T. Org. Lett. 2006, 8, 2591–2594;
b) Shilabin, A. G.; Kasanah, N.; Tekwani, B. L.; Hamann, M. T. J. Nat. Prod. 2008,
decomposition products, which could be explained by
4.
disproportionation of the dihydro-b-carboline skeleton to the
(
27
tetrahydro compound and an unsaturated derivative. In the cases
of formic acid, oxalic acid and malonic acid, T3PÒ immediately
scavenged water from the acids after the addition of the reactants,
71, 1218–1221; (c) Gupta, L.; Srivastava, K.; Singh, S.; Puri, S. K.; Chauhan, P. M.
S. Bioorg. Med. Chem. Lett. 2008, 18, 3306–3309.
Lin, N.; Zhao, M.; Wang, C.; Peng, S. Bioorg. Med. Chem. Lett. 2002, 12, 585–587.
Rivas, P.; Cassels, B. K.; Morello, A.; Repetto, Y. Comp. Biochem. Physiol. 1999,
122, 27–31.
(a) Xu, Z.; Chang, F.-R.; Wang, H. K.; Kashiwada, Y.; McPhail, A. T.; Bastow, K. F.;
Tachibana, Y.; Cosentino, M.; Lee, K. H. J. Nat. Prod. 2000, 63, 1712–1715; (b) Yu,
X.; Lin, W.; Li, J.; Yang, M. Bioorg. Med. Chem. Lett. 2004, 14, 3127–3130; (c)
Guan, H.; Chen, H.; Peng, W.; Ma, Y.; Cao, R.; Liu, X.; Xu, A. Eur. J. Med. Chem.
2006, 41, 1167–1179; (d) Tang, J. G.; Wang, Y. H.; Wang, R. R.; Dong, Z. J.; Yang,
L. M.; Zheng, Y. T.; Liu, J. K. Chem. Biodiversity 2008, 5, 447–460; (e) Brahmbhatt,
K. G.; Ahmed, N.; Sabde, S.; Mitra, D. Bioorg. Med. Chem. Lett. 2010, 20, 4416–
5
6
.
.
2
and only the formation of gases (presumably CO and CO ) was
7
.
observed. In the reaction of phenylacetic acid, 1-benzyl-3,4-
dihydro-b-carboline was detected by HPLC–MS analysis of the
reaction mixture showing full conversion, however the product
decomposed during purification. In all cases, the reactions were
followed by TLC and HPLC–MS until full conversion of tryptamine
(1) or until the observation of a significant decomposition.
4419.
The reaction was also extended to terephthalic acid (2t) using
.5 equiv of T3P , giving a mixture of bis b-carboline derivatives
10% unsaturated, 15% dihydro, 30% tetrahydro, 45% hexahydro)
8. Rook, Y.; Schmidtke, K.; Gaube, F.; Schepmann, D.; Wünch, B.; Heilmann, J.;
Ò
Lehmann, J.; Winckler, T. J. Med. Chem. 2010, 53, 3611–3617.
1
(
9.
Soriano-Agatón, F.; Lagoutte, D.; Poupon, E.; Roblot, F.; Fournet, A.; Gantier, J.
C.; Hockuemiller, R. J. Nat. Prod. 2005, 68, 1581–1587.
linked with a phenyl group, which were observed by HPLC–MS.
10. (a) Daugan, A.; Grondin, P.; Ruault, C.; de Gouville, A.-C. M.; Coste, H.;
Kirilovsky, J.; Hyafil, F.; Labaudinière, R. J. Med. Chem. 2003, 46, 4525–4532; (b)
Daugan, A.; Grondin, P.; Ruault, C.; de Gouville, A.-C. M.; Coste, H.; Linget, J. M.;
Kirilovsky, J.; Hyafil, F.; Labaudinière, R. J. Med. Chem. 2003, 46, 4533–4542; (c)
Zhang, Y.; He, Q.; Ding, H.; Wu, X.; Xie, Y. Org. Prep. Proced. Int. 2005, 37, 99–
In this case the amount of the T3PÒ reagent was raised to 2 equiv
and the reaction time to 3.5 h, because of the high steric hindrance
of the formed amides and various intermediates. The large amount
of hexahydro-b-carboline can be explained by thermal dispropor-
102.
2
7
11. (a) Santos, L. S.; Pilli, R. A.; Rawal, V. H. J. Org. Chem. 2004, 69, 1283–1289; (b)
Itoh, T.; Yokoya, M.; Miyauchi, K.; Nagata, K.; Ohsawa, A. Org. Lett. 2006, 8,
1533–1535.
tionation of the carboline C ring during the long reaction time.
In the crude product, the various oxidized derivatives could not
be separated and therefore the mixture was fully oxidized using
1
2. (a) Whaley, W. M.; Govindachari, T. R. Org. React. 1951, 6, 74–150; (b) Whaley,
W. M.; Govindachari, T. R. Org. React. 1951, 6, 151–190; (c) Bondzi c´ , B. P.;
Eilbracht, P. Org. Lett. 2008, 10, 3433–3436; (d) Ohta, Y.; Oishi, S.; Fujii, N.;
Ohno, H. Org. Lett. 2009, 11, 1979–1982; (e) Stöckigt, J.; Antonchick, A. P.; Wu,
F.; Waldmann, H. Angew. Chem., Int. Ed. 2011, 50, 8538–8564; (f) Song, H.; Liu,
Y.; Wang, Q. Org. Lett. 2013, 15, 3274–3277.
0
Pd/C in dioxane to give 1,1 -benzene-1,4-diylbis(9H-b-carboline)
0
(
5t ) which was isolated in an overall yield of 80%.
0
Products 5c,d,g,q,t are new b-carboline derivatives, while com-
0
pounds 5a,b,e,f,h–p,r,s are known in the literature. Nevertheless
the spectral characterization of 5b and 5o was not completely
disclosed.
1
1
3. Bischler, A.; Napieralski, B. Chem. Ber. 1893, 26, 1903–1908.
4. (a) Shankaraiah, N.; Santos, L. S. Tetrahedron Lett. 2009, 50, 520–523; (b)
Ishiyama, H.; Yoshizawa, K.; Kobayashi, J. Tetrahedron 2012, 68, 6186–6192; (c)
García, M. D.; Wilson, A. J.; Emmerson, D. P. G.; Jenkins, P. R.; Mahale, S.;
Chaudhuri, B. Org. Biomol. Chem. 2006, 4, 4478–4484.
Conclusions
15. (a) Hulinská, H.; Taufmann, P.; Frycová, H.; Protiva, M. Collect. Czech. Chem.
Commun. 1988, 53, 373–380; (b) Chen, Z.; Hu, G.; Chen, J.; Li, Y.; Zhou, H.; Xie,
Y. Bioorg. Med. Chem. 2009, 17, 2351–2359.
A new one-pot method has been developed for the cascade acy-
lation between tryptamine and aliphatic or (hetero)aromatic car-
boxylic acids. The primarily formed amide undergoes subsequent
Bischler–Napieralski ring closure to afford 3,4-dihydro-b-carbolines
containing various substituents at position 1. The application of
1
6. for PPA: (a) Ivanov, I.; Nikolova, S.; Statkova-Abeghe, D. Heterocycles 2005, 10,
2483–2492; for PPE: (b) Hino, T.; Lai, Z.; Seki, H.; Hara, R.; Kuramochi, T.;
Nakagawa, M. Chem. Pharm. Bull. 1989, 37, 2596–2600.
1
7. (a) Bhattacharjya, A.; Chattopadhay, P.; Bhaumik, M.; Pakrashi, S. C. J. Chem.
Res. 1989, 228–230; (b) Lingam, Y.; Rao, D. M.; Bhowmik, D. R.; Sarvepalli, S.;
Islam, A. Indian J. Heterocycl. Chem. 2007, 17, 107–108.
Ò
T3P under MW irradiation was beneficial to attain high yields.
18. Banwell, M. G.; Bissett, B. D.; Busato, S.; Cowden, C. J.; Hockless, D. C. R.;
Holman, J. W.; Read, R. W.; Wu, A. W. J. Chem. Soc., Chem. Commun. 1995, 2551–
Additionally, natural products, 1-methyl-3,4-dihydro-b-carboline
2554.
(
harmalan) and dihydro-eudistomin-U have been efficiently syn-
19. Larsen, R. D.; Reamer, R. A.; Corley, E. G.; Davis, P.; Grabowski, E. J. J.; Reider, P.
thesized. The necessity of less than two equivalents of the reagent
for the whole reaction sequence was experimentally explained by
J.; Shinkai, I. J. Org. Chem. 1991, 56, 6034–6038.
2
2
0. Spaggiari, A.; Davoli, P.; Blaszczak, L. C.; Prati, F. Synlett 2005, 661–663.
1. (a) Milen, M.; Ábrányi-Balogh, P.; Dancsó, A.; Frigyes, D.; Pongó, L.; Keglevich,
G. Tetrahedron Lett. 2013, 54, 5430–5433; (b) Milen, M.; Ábrányi-Balogh, P.;
Kangyal, R.; Dancsó, A.; Frigyes, D.; Keglevich, G. Heteroat. Chem. 2014, 25, 245–
Ò
the remaining activity of the adduct of T3P with water which
formed in the reaction of T3PÒ and benzoic acid.
255.
2
2
2
2. Jablonkai, E.; Milen, M.; Drahos, L.; Keglevich, G. Tetrahedron Lett. 2013, 54,
5873–5875.
3. Jablonkai, E.; Henyecz, R.; Milen, M.; Kóti, J.; Keglevich, G. Tetrahedron 2014, 70,
Supplementary data
8
280–8285.
4. Basavaprabhu; Vishwanatha, T. M.; Panguluri, N. R.; Sureshbabu, V. V. Synthesis
013, 1569–1601.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.03.
2
0
67.
25. (a) Glasby, J. S. In Encyclopedia of the Alkaloids; Plenum Press: New York, 1989;
Vol. 1,; pp 659–661; (b) Rommelspacher, H; Brüning, G.; Susilo, R.; Nick, M.;
Hill, R. Eur. J. Pharm. 1985, 109, 363–371.
References and notes
2
6. (a) Badre, A.; Boulanger, A.; Abou-Mansour, E.; Banaigs, B.; Combaut, G.;
Francisco, C. J. Nat. Prod. 1994, 57, 528–533; (b) Roggero, C. M.; Giulietti, J. M.;
Mulcahy, S. P. Bioorg. Med. Chem. Lett. 2014, 24, 3549–3551.
1
.
(a) Torreilles, J.; Guérin, M.-C.; Previero, A. Biochimie 1985, 67, 929–947; (b)
Love, B. E. Org. Prep. Proced. Int. 1996, 28, 1–64; (c) Cao, R.; Peng, W.; Wang, Z.;
Xu, A. Curr. Med. Chem. 2007, 14, 479–500; (d) Rosillo, M.; González-Gómez, A.;
27. Busacca, C. A.; Dong, Y. Synth. Commun. 2000, 30, 501–509.