N-acyliminium reagents of 3,4-dihydro-β-carboline and acyl chlorides in the reaction of intermolecular α-amidoalkylation toward heteroaromatics

Article abstract of DOI:10.1081/SCC-200026238

N-Acyliminium reagents formed from 3,4-dihydro-β-carboline and acyl chlorides were used for amidoalkylation of indole, pyrrole, and thiophene.

Full text of DOI:10.1081/SCC-200026238

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 15, pp. 2813–2821, 2004
N-Acyliminium Reagents of 3,4-Dihydro-
b-carboline and Acyl Chlorides
in the Reaction of Intermolecular
a-Amidoalkylation Toward
Heteroaromatics#
*
Atanaska K. Donova, Stela M. Statkova-Abeghe,
Atanas P. Venkov, and Iliyan I. Ivanov
Department of Organic Chemistry, University of Plovdiv,
Plovdiv, Bulgaria
ABSTRACT
N-Acyliminium reagents formed from 3,4-dihydro-b-carboline and
acyl chlorides were used for amidoalkylation of indole, pyrrole, and
thiophene.
Key Words: N-Acyliminium reagents; b-Carbolines; a-Amidoalkylation
reaction; Heteroaromatics; Alkaloids.
#This paper is dedicated to the memory of Professor Atanas Venkov.
*
Correspondence: Atanaska K. Donova, Department of Organic Chemistry, University
of Plovdiv, 24 Tsar Asen St., 4000 , Plovdiv, Bulgaria; E-mail: donova@argon.acad.bg.
2813
DOI: 10.1081/SCC-200026238
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Donova et al.
INTRODUCTION
The chemistry of b-carbolines is currently of great interest due to their
biological activity.[1] Besides the classical methods, the Pictet–Spengler
and the Bischler–Napieralski reactions, some new synthetic routes to
a-substituted b-carbolines have been developed.[2] In the last several years,
Eudistoma alkaloids and the bengacarboline from marine organisms are
objects of extensive research because of their antitumor, antiviral, and antibac-
terial properties.[3]
Recently, we have reported the utilization of 3,4-dihydroisoquinoline
for preparation of 1-heteroaryl-2-acyl-1,2,3,4-tetrahydroisoquinolines via
intermolecular a-amidoalkylation.[4] In this paper, we continue our research
with another cyclic imine—3,4-dihydro-b-carboline 1. The obtained
N-acyliminium reagents 3 are successfully used in a reaction of intermolecular
a-amidoalkylation toward heteroaromatic compounds.
There are a number of publications regarding the synthetic applications
of N-acyliminium reagents, obtained from acid chlorides and various
N-heterocycles like pyridine, quinoline, isoquinoline, and acridine.[5] So far,
however, there are no reports for utilization of 3,4-b-dihydrocarbolines for
the formation of N-acyliminium intermediates. That is why, we investigated
the reaction between 3,4-dihydro-b-carboline 1 and acyl chlorides. When
dichloromethane solution of imine 1 and acetyl or benzoyl chloride were
mixed at room temperature, a precipitate quickly formed and in 30 min
decomposed giving a complex mixture of products. Therefore, we continued
our research at lower temperature, in an ice bath. To a cooled solution of
3,4-dihydro-b-carboline, equimolar amount of acyl chloride was added. All
attempts for isolation, purification, and characterization of the formed
N-acyliminium intermediates were failed, because of their high reactivity
and instability. We found that after leaving the mixture at 4–58C for about
24 hr, the N-acyliminium reagents converted to the corresponding 1-oxo-2-
acyl-2,3,4,9-tetrahydro-b-carbolines. The mechanism of this process is
unclear and will be subject of further studies. The presence of N-acyliminium
intermediates could be proven only indirectly by trapping them with suitable
nucleophiles.
Initially, we examined the reaction between the N-acyliminium inter-
mediate 3b (R¼OEt) and the indole. To the obtained in situ reagent 3b,
an equivalent amount of an ice-cooled solution of indole was added dropwise.
As a result, the expected product of a-amidoalkylation, ethyl 1-(1H-
3-indolyl)-2,3,4,9-tetrahydro-1H-b-carboline-2-carboxylate 4b, was isolated
in 20% yield. The formation of this product is an indirect evidence for the
existence of the N-acyliminium intermediate 3b in the reaction mixture. We
found that the product is instable in acidic media. On the other hand, nearly

Reagents of 3,4-Dihydro-b-carboline and Acyl Chlorides
2815
20% of starting imine 1 was recovered from the reaction mixture. This led us
to the assumption that under the reaction conditions a part of the 3,4-dihydro-
b-carboline is blocked by the evolved HCl. Thus, the reaction was carried out
in the presence of Et3N as HCl scavenger. When indole and Et3N were added
consecutively to the reaction mixture, the product 4b was obtained in signifi-
cantly better yield250%. The order of addition of indole and Et3N is of
importance—if these reagents are added simultaneously to 3b, then along
with the main product 4b (40% yield), a minor product 4d is obtained in
10% yield. The spectral data show that 4d is a product of second acylation
in the carboline moiety.
These results prompted us to broaden the studies of the reaction with
the use of acetyl and benzoyl chlorides (R¼CH3, C6H5). In all cases, the
N-acyliminium reagents 3 were obtained by adding the corresponding
acyl chloride 2 to an ice-cooled solution of 3,4-dihydro-b-carboline 1 in
dichloromethane and stirring the reaction mixture for 30 min at 08C. The N-
acyliminium reagents prepared in this way were successfully used for ami-
doalkylation of indole according to the above procedure. The only difference
is that here the order of addition of Et3N and indole does not affect the
outcome of the reactions. The yields of obtained products 4a–c and the reac-
tion conditions are displayed in Table 1.
The studies were continued with the utilization of pyrrole and thiophene
as nucleophiles. The results from these experiments are summarized in Schs. 1
and 2 and in Table 1.
Table 1. Reaction conditions, yields and melting points of the
compounds 4, 5, and 7.
Conditions
[hr; T(8C)]
Yield
(%)
Mp
(8C)
Entry
4a
4b
4c
5a
5b
5c
5d
5e
7
1.5; 0
1.5; 0
1.5; 0
1; 0
67
50
70
25
43
35
27
30
25
238–240a
236–238a
179–181a
198–200a,b
133–134a
243–244a,c
221–222d
174–176
1; 0
1.5; 0
12; 5–10
2; 50
2; 50
170–172
aWith decomposition.
bMp 233–2358C in Ref.[6]
.
cMp 262–2638C in Ref.[6]
.
dMp 251–2528C in Ref.[6]
.

2816
Donova et al.
Scheme 1. Synthesis of 1,2-disubstituted tetrahydro-b-carbolines 4 and 5.
The reactions with pyrrole were carried out under the reaction conditions
shown in Table 1, in the presence of Et3N. As a result, the corresponding pro-
1
ducts 5a–c were obtained in good yields. The signals in H-NMR spectra of
compounds 5a–c indicate that only mono a-substitution in the pyrrole ring
takes place. Diamidoalkylation was not observed, in spite of the ratio of 3
and pyrrole.
With ethyl chloroformate, along with the main product 5b, a minor
product 5f in 27% yield was isolated. That could be explained with oxidation
of N-acyliminium reagent 3b under the reaction conditions.
We continued our work with amidoalkylation of thiophene and the initial
experiments were carried out in the absence of HCl scavenger. When ethyl
chloroformate was used, the reaction to the corresponding product of amido-
alkylation failed and only product 5f was isolated from the reaction mixture.
When acetyl or benzoyl chlorides were used, the amidoalkylation of thiophene
was successful and the corresponding products 5d and 5e were obtained
with 27% and 30% yield, respectively. Upon work-up of the reaction
mixtures, 50% and 25% of the starting 3,4-dihydro-b-carboline was recov-
ered, respectively. Most likely it had been blocked by the evolved HCl in
the course of the reaction. That is why, to increase the yields, we tried
Scheme 2. Structural representation of 4d, 5f, and 7.

Reagents of 3,4-Dihydro-b-carboline and Acyl Chlorides
2817
again to carry out the reaction in the presence of Et3N. This strategy, however,
proved unsuccessful and no amidoalkylation of thiophene was observed in the
presence of Et3N, regardless of the applied various reaction conditions.
Finally, we tried to carry out the reaction of amidoalkylation with 1,2-
dimethoxybenzene, as a representative of benzene aromatics. For this
purpose, we used the N-benzoyl iminium reagent 3c (R¼C6H5), because of
its relatively higher stability at elevated temperatures. As a result of the reac-
tion, after 2 hr at 508C, the product 7 was obtained in 25%; and once again
20% of the starting imine was blocked by the evolved HCl. All attempts to
increase the yield of 7 were failed.
As the reactivity of the acyliminium reagents is often improved in the pre-
.
sence of the Lewis acids, we carried out some experiments with BF3 Et2O and
AlCl3. The acyliminium reagents 3, obtained from 3,4-dihydro-b-carboline,
proved highly unstable and were decomposed by the Lewis acids.
As a conclusion, we report for the first time an application of N-acylimi-
nium reagents of 3,4-dihydro-b-carboline. We demonstrate that the obtained
in situ N-acyliminium intermediates are good electrophilic reagents in
intermolecular a-amidoalkylation toward heteroaromatics as indole, pyrrole,
and thiophene. This represents a new and a convenient route to 1-
heteroaryl-2-acyl-2,3,4,9-tetrahydro-b-carbolines. Some of the synthesized
products are analogs of known biologically active substances like Eudistoma
alkaloids.
EXPERIMENTAL
Melting points were determined on a Boetius hotstage apparatus and are
uncorrected. Unless otherwise noted, NMR spectra were recorded on a Bruker
250 MHz device by using [D6]DMSO as solvent. Chemical shifts (d, ppm) are
downfield from TMS as an internal standard and coupling constants are in Hz.
Mass spectra were recorded on a Jeol JMS-D300 spectrometer (70 eV). All
new compounds had correct parent ion peaks by mass spectrometry.
General Procedure for Preparation
of Products 4, 5, and 7 (Table 1)
The starting 3,4-dihydro-b-carboline 1 was obtained by known
procedure.[7]
Acyl chloride (3 mmol) was added dropwise to a stirred and an ice-cooled
solution of 3,4-dihydro-b-carboline (3 mmol) in dry dichloromethane (5 mL).
The mixture was stirred 30 min in order to obtain N-acyliminium intermediate

2818
Donova et al.
3. For preparation of products 4 and 5a–c, an ice-cooled solution of indole
(3 mmol) or pyrrole (3 mmol) and Et3N (3 mmol) in dichloromethane
(1 mL) was added dropwise. Similarly, ice-cooled solutions of thiophene
and 1,2-dimethoxybenzene were added to the dichloroethane solution of 3
for the preparation of 5d, e and 7. The reaction mixtures were stirred for
the time and the temperatures given in Table 1, then were treated with 6%
CH3COOH (10 mL) and rapidly extracted with CH2Cl2 (3 Â 10 mL).
The combined extract was washed with aq. NaHCO3 (2 Â 10 mL), dried
(Na2SO4) and the solvent was removed by vacuum distillation. The products
were separated and purified by recrystallization or column chromatography on
a neutral Al2O3.
1-[1-(1H-3-Indolyl)-2,3,4,9-tetrahydro-1H-b-carbolin-2-yl]-1-ethanone
1
4a: (recrystallization: MeOH). H-NMR: 2.13 (s, 3H), 2.76–2.96 (m, 2H),
3.87–3.93 (m, 2H), 5.76 (s, 1H), 6.80 (s, 1H), 6.92–7.12 (m, 4H), 7.24–7.60
(m, 4H), 10.95 (s, 1H), 11.01 (s, 1H); 13C-NMR: 21.60, 21.80, 24.30, 42.60,
105.16, 110.18, 111.06, 112.70, 118.60, 118.80, 121.40, 123.26, 124.00,
127.18, 129.60, 135.78, 137.40, 170.06 (CO); C21H19N3O (329.40): calcd. C
76.57, H 5.81, N 12.76%; found C 76.63, H 5.93, N 12.84%.
Ethyl 1-(1H-3-indolyl)-2,3,4,9-tetrahydro-1H-b-carboline-2-carboxy-
late 4b: (eluent: Et2O). 1H-NMR: 1.24 (t, 3H, J ¼ 6), 2.80–2.90 (m, 2H),
3.14–3.25 (m, 2H), 4.17 (q, 2H, J ¼ 7), 6.72 (s, 1H), 6.90–7.14 (m, 5H),
7.28–7.60 (m, 4H), 10.95 (s, 1H), 11.09 (s, 1H); 13C-NMR: 13.80, 21.30,
25.70, 43.60, 65.18, 107.30, 108.10, 110.50, 112.80, 116.70, 118.80, 119.20,
119.70, 120.00, 121.20, 128.30, 132.30, 136.20, 137.80, 154.40 (CO);
C22H21N3O (359.43): calcd. C 73.52, H 5.89, N 11.69%; found C 73.60, H
5.97, N 11.84%.
1-(1H-3-Indolyl)-2,3,4,9-tetrahydro-1H-b-carbolin-2-yl-phenyl-
methanone 4c: (eluent: mixture p.ether/ether, 1/1). 1H-NMR: 3.26–3.37
(m, 2H), 3.52-3.60 (m, 2H), 7.09 (t, 2H, J ¼ 2), 7.32–7.51 (m, 7H), 7.75–7.84
(m, 5H), 8.63 (t, 1H, J ¼ 2), 9.96 (s, 1H), 11.67 (s, 1H); 13C-NMR: 23.80,
37.30, 57.60, 110.20, 111.20, 111.60, 114.60, 115.70, 118.60, 120.60, 121.30,
123.80, 126.40, 128.50, 129.30, 130.40, 134.60, 135.60, 136.90, 137.40,
170.90 (CO), C26H21N3O (391.47): calcd. C 79.77, H 5.41, N 10.73%;
found C 80.06, H 5.56, N 10.83%.
Diethyl 1-(1H-3-indolyl)-2,3,4,9-tetrahydro-1H-b-carboline-2,9-dicar-
1
boxylate 4d: (eluent: mixture p.ether/ether, 4/1). H-NMR (CDCl3):
0.70–1.00 (m, 3H), 1.17–1.50 (m, 3H), 2.70–3.00 (m, 2H), 3.05–3.33
(m, 2H), 4.18 (q, 4H, J ¼ 6), 6.58 (s, 1H), 7.15–7.50 (m, 8H), 7.55 (s, 1H),
8.13–8.45 (m, 1H); 13C-NMR: 13.80, 23.55, 32.95, 41.40, 65.80, 106.70,
109.80, 112.60, 116.70, 118.40, 120.60, 121.30, 122.30, 124.10, 125.40,
126.30, 135.60, 140.50, 147.60 (CO), 150.60 (CO); C25H25N3O4 (431.49):
calcd. C 69.59, H 5.84, N 9.74%; found C 69.80, H 5.97, N 9.92%.

Reagents of 3,4-Dihydro-b-carboline and Acyl Chlorides
2819
1-[1-(1H-2-Pyrrolyl)-2,3,4,9-tetrahydro-1H-b-carbolin-2-yl]-1-etha-
none 5a: (eluent: Et2O). 1H-NMR (CDCl3): 2.19 (s, 3H), 3.35–3.54
(m, 2H), 3.85–3.93 (m, 2H), 5.82 (s, 1H), 6.05 (s, 1H), 6.80 (s, 2H),
7.16–7.32 (m, 4H), 8.04 (s, 1H), 9.21 (s, 1H); 13C-NMR: 19.80, 20.60,
31.78, 39.50, 107.60, 108.90, 112.60, 114.60, 117.96, 119.63, 123.54,
126.30, 132.70, 134.15, 140.33, 169.80 (CO); C17H17N3O (279.30): calcd.
C 73.10, H 6.13, N 15.04%; found C 73.23, H 6.23, N 15.25%.
Ethyl 1-(1H-2-pyrrolyl)-2,3,4,9-tetrahydro-1H-b-carboline-2-carbox-
ylate 5b: (eluent: mixture p. ether/ether, 4/1). 1H-NMR (CDCl3): 1.33
(t, 3H, J ¼ 5), 2.90 (t, 2H, J ¼ 5), 3.23 (t, 2H, J ¼ 6), 4.30 (q, 2H, J ¼ 5),
5.95 (s, 1H), 6.15 (t, 1H, J ¼ 3), 6.50 (s, 1H), 6.88 (s, 1H), 7.15–7.43
(m, 3H), 7.58–7.78 (m, 1H), 8.10 (s, 1H), 9.15 (s, 1H); 13C-NMR: 13.60,
19.80, 38.34, 54.18, 62.17, 102.50, 109.70, 113.40, 116.50, 118.52,
120.63, 123.40, 125.43, 134.80, 135.70, 149.75 (CO); C18H19N3O2
(309.36): calcd. C 69.88, H 6.19, N 13.58%; found C 70.03, H 6.27, N
13.78%.
Phenyl-1-(1H-2-pyrrolyl)-2,3,4,9-tetrahydro-1H-b-carbolin-2-ylmetha-
1
none 5c: (eluent: mixture p.ether/ether, 1/1). H-NMR: 2.70–2.90 (m, 2H),
3.36–3.45 (m, 1H), 3.64–3.68 (m, 1H), 5.77 (s, 1H), 5.95 (s, 1H), 6.71 (s, 1H),
6.83 (s, 1H), 6.95–7.11 (m, 3H), 7.30 (d, 1H, J ¼ 8), 7.47 (s, 5H), 10.69 (s, 1H),
11.06 (s, 1H); 13C-NMR: 20.18, 34.12, 59.17, 105.40, 112.80, 114.70, 115.35,
118.60, 120.95, 123.65, 125.18, 126.96, 129.16, 131.50, 132.63, 134.85,
140.16, 169.87 (CO); C22H19N3O (341.41): calcd. C 77.40, H 5.61, N
12.31%; found C 77.15, H 5.73, N 12.45%.
1-[1-(2-Thienyl)-2,3,4,9-tetrahydro-1H-b-carbolin-2-yl]-1-ethanone
5d: (eluent: CHCl3). 1H-NMR: 1.74 (s, 3H), 3.15 (m, 2H), 3.27–3.37
(m, 2H), 7.05–7.12 (m, 2H), 7.28–7.34 (m, 1H), 7.39 (s, 1H), 7.75 (d, 2H,
J ¼ 8), 7.99 (t, 2H, J ¼ 5), 11.72 (s, 1H); 13C-NMR: 19.18, 20.80, 34.83,
56.30, 108.30, 112.63, 116.45, 118.34, 121.34, 124.80, 126.80, 127.30,
132.64, 136.50, 139.73, 172.80 (CO); C17H16N2OS (296.38): calcd. C
68.89, H 5.44, N 9.45%; found C 68.95, H 5.54, N 9.53%.
Phenyl-1-(2-thienyl)-2,3,4,9-tetrahydro-1H-b-carbolin-2-ylmetha-
none 5e: (eluent: Et2O). 1H-NMR: 3.30–3.37 (m, 2H), 3.52–3.60 (m, 2H),
7.05–7.11 (m, 2H), 7.31–7.35 (m, 2H), 7.38–7.50 (m, 4H), 7.74–7.84
(m, 5H), 11.66 (s, 1H); 13C-NMR: 20.84, 35.43, 58.40, 108.60, 110.30,
115.38, 118.63, 120.34, 123.78, 126.23, 127.10, 127.65, 129.54, 131.27,
134.37, 134.83, 139.65, 142.43, 168.89 (CO); C22H18N2OS (358.45): calcd.
C 73.72, H 5.06, N 7.82%; found C 73.94, H 5.28, N 7.97%.
Ethyl1-oxo-2,3,4,9-tetrahydro-1H-b-carboline-2-carboxylate5f:(eluent:
Et2O). 1H-NMR (CDCl3): 1.25 (t, 3H, J ¼ 6), 3.35–3.68 (m, 4H), 4.20
(q, 2H, J ¼ 6), 7.30–7.60 (m, 2H), 8.00–8.20 (m, 2H), 9.50 (s, 1H); 13C-
NMR: 12.65, 19.34, 36.58, 54.15, 110.58, 118.64, 119.53, 121.80, 123.75,

2820
Donova et al.
124.03, 124.15, 129.65, 149.50 (CO), 158.63 (CO); C14H14N2O3 (258.27):
calcd. C 65.11, H 5.46, N 10.85%; found C 65.23, H 5.58, N 10.94%.
1-(3,4-Dimethoxyphenyl)-2,3,4,9-tetrahydro-1H-b-carbolin-2-yl-
phenylmethanone 7: (eluent: Et2O). 1H-NMR (CDCl3): 3.28–3.38 (m, 2H),
3.51–3.59 (m, 8H), 5.73 (s, 1H), 7.05–7.11 (m, 1H), 7.28–7.34 (m, 2H),
7.39–7.50 (m, 4H), 7.73–7.83 (m, 5H), 11.65 (s, 1H); 13C-NMR: (CO),
158.63 (CO); C26H24N2O3 (412.48): calcd. C 75.71, H 5.86, N 6.79%;
found C 75.84, H 5.93, N 6.90%.
REFERENCES
1. (a) Dulenko, V.I.; Comissarov, I.V.; Doljenko, A.T.; Nikolukin, U.A.
b-Carbolines, Chemistry and Neurobiology; Andronati, C.A., Ed.;
Naukova Dumka: Kiev, 1992; 88–188; (b) Ho, B.T. Current Develop-
ments in Psychopharmacology; Essman, W.B., Valzelli, L., Eds.; Spec-
trum Publications: New York, 1977; Vol. 4, 151; (c) Agarwal, D.P.;
Goedde, H.W. Alcohol Metabolism, Alcohol Intolerance and Alcoholism;
Springer-Verlag: Berlin, 1990; 99.
2. (a) Rocca, P.; Marsais, F.; Godard, A.; Queguiner, G. A new convergent
synthesis of a-substituted-b-carbolines. Tetrahedron 1993, 49 (16),
3325–3342; (b) Love, B.E.; Raje, P.S. Preparation of 1-aryl-b-carbolines.
J. Org. Chem. 1994, 59 (11), 3219–3222.
3. (a) Kobayashi, J.; Nakamura, H.; Ohizumi, Y. Eudistomidin-A, a novel
calmodulin antagonist from the Okinawan tunicate Eudistoma glaucus.
Tetrahedron Lett. 1986, 27 (10), 1191–1194; (b) Rinehart, K.L., Jr.;
Kobayashi, J.; Harbour, G.C.; Gilmore, J.; Mascal, M.; Holt, T.G.;
Shield, L.S.; Lafargue, F. Eudistomins, A.-Q, b-carbolines from the
antiviral Caribbean tunicate Eudistoma olivaceum. J. Am. Chem. Soc.
1987, 109 (11), 3378–3387; (c) Debitus, C.; Laurent, D. Alcaloides
d’une ascidie neocaledonienne, Eudistoma fragum. J. Nat. Prod. 1988,
51 (4), 799–801; (d) Kobayashi, J.; Cheng, J.; Ohta, T.; Nozoe, S.;
Ohizumi, Y.; Sasaki, T. Eudistomidins, B, C and D: novel antileukemic
alkaloids from okinawan marine tunicate Eudistoma glaucus. J. Org.
Chem. 1990, 55 (11), 3666–3670; (e) Badre, A.; Boulanger, A.; Abou-
Mansour, E.; Banaigs, B.; Combaut, G.; Francisco, C. Eudistomin U and
isoeudistomine U, new alkaloids from the Caribean ascidian Lissoclinum
fragile. J. Nat. Prod. 1994, 57 (4), 528–533; (f) Foderaro, T.A.;
Barrows, L.R.; Lassota, P.; Ireland, C.M. Bengacarboline, a new b-
carboline from a marine ascidian Didemnum sp. J. Org. Chem. 1997,
62 (17), 6064–6065.

Reagents of 3,4-Dihydro-b-carboline and Acyl Chlorides
2821
4. Venkov, A.P.; Statkova-Abeghe, S.M.; Donova, K.A. Amidoalkylation
of heteroaromatic compounds with adducts of acyl chlorides and
3,4-dihydroisoquinoline and isoquinoline. Cent. Eur. J. Chem. 2004,
2 (1), 234–246. www.cesj.com.
5. (a) Sheinkman, A.K. Heteroarylation of organic compounds. Khimia
Heterocycl. Soedin. 1974, 1, 3–18; (b) Sheinkman, A.K.; Deikalo, A.A.
Reactions of cyclammonium cations XV. Hetarylation of pyrroles by
N-acyl salts of isoquinolinium and acridinium. Khimia Heterocycl.
Soedin. 1971, 7 (12), 1654–1659. (Chem. Abstr. 1972, 77, 5310a);
(c) Dobeneck, H.; Goltzsche, W. Reactionen von N-Acyl-cyclimmonium-
salzen mit nucleophilen verbindungen. Chem. Ber. 1962, 95, 1484–1492.
6. Analgesics. Brit. Patent 6,512,087, March 17, 1966, ICI Ltd. (Chem.
Absrt. 1966, 65, 3844c).
7. Bertrand, M.; Poissonnet, G.; Theret-Bettiol, M.; Gaspard, C.;
Werner, G.H.; Pfeiffer, B.; Renard, P.; Leonce, S.; Dodd, R.H. Cytotoxic
activities of novel hexahydroindolizino[8,7-b]indole derivatives prepared
by 1,3-dipolar cycloaddition reactions of 3,4-dihydro-b-carboline ylides.
Bioorg. Med. Chem. 2001, 9, 2155–2164.
Received in Poland March 31, 2004

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