Immunoactive ionic liquids based on 2-hydroxyethylamines and 1-R-indol-3-ylsulfanylacetic acids. Crystal and molecular structure of immunodepressant tris-(2-hydroxyethyl)ammonium indol-3-ylsulfanylacetate

Article abstract of DOI:10.1515/chem-2015-0018

A base catalyzed sequential one-pot protocol for an effective preparation of 3-(substitutedphenyl) -6,6-dimethyl-2-(substitutedphenylcarbonyl)-3,5,6,7-tetrahydro-1-benzofuran-4(2H)-one derivatives have been described. One-pot reaction of aromatic aldehyde

Full text of DOI:10.1515/chem-2015-0018

Open Chem., 2015; 13: 149–155
Research Article
Open Access
AImnnamN. uMinrskoovaa,cSteirgveey Ni. oAdnamiocviclhi,qRuudiodlf Gs. Mbirasksove, Odlga P. Kolesnikova, Uwe Schilde*
on 2-hydroxyethylamines and 1-R-indol-3-
ylsulfanylacetic acids. Crystal
and molecular structure of immunodepressant
tris-(2-hydroxyethyl)ammonium
indol-3-ylsulfanylacetate
Abstract: Immunoactive ionic liquids (2-hydroxyethyl)
1 Introduction
+
∙
ammonium 1-R-indol-3-ylsulfanyl-acetates HN R1R2(CH2CH2OH)
-O(O)CCH2S-Ind-R3-1 (1-5), were synthesized by the reaction
Over the last decade, the synthesis and investigation
of (2-hydroxyethyl)amines with indol-3-ylsulfanylacetic-
of biologically active ionic liquids (ILs) is progressing
or 1-benzylindol-3-ylsulfanylacetic acid. 1: R1 = R2
=
intensively. Of great research and practical importance are
the so-called third generation ILs, which are also known
as the biologically active generation [1-10]. However,
among these ILs, there are no immunoactive ones, which
makes for promising materials in drug design.
CH2CH2OH, R3 = H; 2: R1 = СН3,R2=CH2CH2OH, R3 = H; 3: R1
= R2 = CH3, R3 = H; 4: R1 = R2 = CH2CH2OH, R3 = СH2С6Н5;
5: R1 = СН3; R2 = CH2CH2OH; R3 = СH2С6Н5. The structure
1
of each compound was elucidated by IR, NMR H, 13С,
and 15N techniques and their composition was confirmed
by elemental analysis. The crystal structure of tris-(2-
hydroxyethyl) ammonium indol-3-ylsulfanylacetate was
investigated by X-ray diffraction analysis. Immunoactive
properties of the title compounds were screened.
2-Hydroxyalkylammonium salts of aryloxy(sulfanyl)
(sulfonyl)acetic acids, HN+R1R2(CH2CHR3OH)3-n -O(O)
∙
CCH2(O)(S)(SO2)Ar; R1, R2 , R3 = H, Alk; n = 0-2, which
we have synthesized previously [11-12], represent protic
alkanolammoniumionicliquids(PAILs).Beinglow-toxicity
(LD50 = 1300-6000 mg kg-1), these compounds exert high
and diverse biological activities such as antiinflammatory,
Keywords: Protic 2-hydroxyethylammonium ionic liquids,
2-Hydroxyethylammonium 1-R-indol-3-ylsulfanylacetates,
Crystal and molecular structure, Immunoactive properties
antithrombotic,
antioxidant,
adaptogenic,
and
hypocholesterolemic properties [11]. They are also highly
efficient growth-stimulating agents for biotechnological
processes [12]. Indole derivatives are important structural
units of many biologically active natural compounds and
pharmaceuticals. However, indole-containing PAILs were
still not studied as immunoactive substances.
DOI: 10.1515/chem-2015-0018
received April 15, 2014; accepted June 17, 2014.
*Corresponding author: Uwe Schilde: Institute of Chemistry,
University of Potsdam, D-14476 Potsdam, Germany,
E-mail: us@chem.uni-potsdam.de
Anna N. Mirskova, Sergey N. Adamovich, Rudolf G. Mirskov: A. E.
Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian
Academy of Sciences, 664033 Irkutsk, Russia
Olga P. Kolesnikova: Research Institute of Clinical Immunology,
Siberian Branch of the Russian Academy of Medical Sciences,
630099 Novosibirsk, Russia
The present work entails the synthesis of tris-(2-
hydroxyethyl)ammonium indol-3-ylsulfanylacetat 1 and
its analogues 2-5 (earlier we made preliminary study of
methods of synthesis and immunoactivity compounds
of 2-5 [13]), the study of crystal and molecular structure
1 and evaluation of immunomodulating properties of
compounds 1-5.
© 2015 Anna N. Mirskova et al., licensee De Gruyter Open.
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
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2 Experimental procedure
2.1 General
1Н NMR (d4-methanol) δ (ppm) 7.74-7.10 (m, 5Н, Ind), 3.73
(t, J = 5.5 Hz, 4Н, ОСН2), 3.35 (s, 2Н, SCН2), 3.25 (t, J =
5.5 Hz, 4Н, NСН2), 3.10 (s, 3Н, NCН3).
13С NMR (d4-methanol) δ (ppm) 176.37 (С=О), 137.26-
IR spectra (ν, cm–1) were recorded on a Varian 3100 FT- 104.89 (Ind), 58.00 (ОСН2 ), 57.11 (NCH2), 49.91 (SCН2),
IR75 spectrophotometer (KBr). The resolution of the IR 40.56 (NCН3). IR (KBr) ν (cm–1) 1560, 1620 (С=О); 2400-
instrument is 1 cm-1. NMR spectra (δ, ppm) were measured 2550 (H+N), 3310 (ОН). Elemental analysis calcd (%) for
1
on a DPX 400 instrument (400.13 MHz for H; 101.62 MHz С15Н22О4N2S (326.41): C 55.19, H 6.79, N 8.58, S 9.82; found: C
for 13С; 40.53 МHz for 15N) in d4-methanol with TMS as 55.30, H 6.65, N 8.45, S 9.78.
internal standard at 25°С. Reflections were collected
N,N-dimethyl-(2-hydroxyethyl)ammonium
indol-3-
using a STOE Imaging Plate Diffraction System (IPDS- ylsulfanylacetate (3) [13] was prepared from indol-3-
II) at 210 K. The structure was solved by direct methods ylsulfanylacetic acid (2.07 g, 0.01 mol) and N,N-dimethyl-
as implemented in the program SHELXS-97 [14]. The
(2-hydroxyethyl)amine (0.89 g, 0.01 mol). Yield 2.95 g
refinement was carried out using SHELXL-2013 [15]. All (99%), oil-like product.
the non-hydrogen atoms were refined anisotropically. The
1Н NMR (d4-methanol) δ (ppm) 7.70-7.11 (m, 5Н, Ind),
hydrogen atoms were located from the difference Fourier 3.77 (t, J = 5.5 Hz, 2Н, ОСН2), 3.35 (s, 2Н, SCН2), 3.17 (t, J =
map and refined isotropically. For visualization, the 5.5 Hz, 2Н, NСН2), 3.06 (s, 6Н, NCН3).
program DIAMOND [16] was used.
CCDC 971271 contains
13С NMR (d4-methanol) δ (ppm) 177.17 (С=О), 135.96-
the
supplementary 106.99 (Ind), 58.09 (ОСН2 ), 57.19 (NCH2), 48.41 (SCН2), 39.66
crystallographic data for the compound 1. These (NCН3). IR (KBr) ν (cm–1) 1563, 1616 (С=О); 2410-2540 (H+N),
data can be obtained free of charge from Cambridge 3305 (ОН). Elemental analysis calcd (%) for С14Н20О3N2S
Crystallographic Data Centre via www.ccdc.cam.ac.uk/ (296.38): С 56.73, H 6.80, N 9.45, S 10.82; found: С 56.95, H
data_request/cif.
6.88, N 9.40, S 10.86.
Indol-3-ylsulfanylacetic
and
1-benzylindol-3-
Tris-(2-hydroxyethyl)ammonium
1-benzylindol-3-
ylsulfanylacetic acids were prepared according to protocol ylsulfanylacetate (4) [13] was prepared from 1-benzylindol-
[17], constants of the acids were in agreement with 3-ylsulfanylacetic acid (2.97 g, 0.01 mol) and tris-(2-
literature data.
hydroxy-ethyl)amine (1.49 g, 0.01 mol). Yield 4.32 g
Tris-(2-hydroxyethyl)ammonium indol-3-ylsulfanylace- (97%), m.p. 92оС. Н NMR (d4-methanol) δ (ppm) 7.68-
1
tate (1).
7.09 (m, 10H, Ind, С6Н5), 5.41 (s, 2H, С6Н5-СН2), 3.67 (t, J =
Methanol solution (75 mL) of indol-3-ylsulfanylacetic 5.5 Hz, 6H, OCH2), 3.38 (2H, s, SCH2), 3.16 (6H, t, J = 5.5
acid (20.72 g, 0.1 mol) and tris-(2-hydroxyethyl)amine (14.92 g, Hz, NCH2). 13С NMR (d4-methanol) δ (ppm) 178.65 (С=О),
0.1 mol) were stirred and heated up to 50оС for 15 min. The 138.15-108.88 (Ind, С6Н5), 57.11 (ОСН2 ), 56.26 (NCH2), 47.99
cooled reaction mixture was added dropwise to 250 mL dry (SCН2). IR (KBr) ν (cm–1) 1560, 1590 (C=O); 2420-2550 (H+N),
diethyl ether (stirring). The residue was filtered off and dried 3306 (ОН). Elemental analysis calcd (%) for C23H30N2О5S
over P2O5 in vacuum at 0.01Torr (24 h). Colorless powder, mp (446.56): C 61.86, H 6.77, N 6.27, S 7.18; found: C 61.71, H
93оС.Yield33.96g(95.3%).1НNMR(d4-methanol)δ(ppm)7.70- 6.78, N 6.33, S 7.25.
7.11(m, 5Н, Ind), 3.77(t, J=5.5Hz, 6Н, ОСН2), 3.37(s, 2Н, SCН2),
N-methyl-bis-(2-hydroxyethyl)ammoniu 1-benzylindol-
3.19 (t, J = 5.5 Hz, 6Н, NСН2). 13С NMR (d4-methanol) δ (ppm) 3-ylsulfanylacetate(5)[13]waspreparedfrom1-benzylindol-
177.27 (С=О), 138.96-105.88 (Ind), 57.37 (ОСН2 ), 57.11 (SCH2), 3-ylsulfanylacetic acid (2.97 g, 0.01 mol) and N-methyl-
50.91 (NCН2). 15N NMR (d4-methanol, ref. CH3NO2) δ (ppm) bis-(2-hydroxy-ethyl)amine (1.19 g, 0.01 mol). Yield 3.01 g
-339.20 [for H+N(CH2CH2OH)3], -355.00 [for N(CH2CH2OH)3]; (72%), oil-like product.
∆δN = 15.80. IR (KBr) ν(cm–1) 1591 (С=О); 2420-2555 (H+N); 3308
1Н NMR (d4-methanol) δ (ppm) 7.75-7.11 (m, 10Н, Ind,
С6Н5), 5.22 (s, 2Н, С6Н5-СН2), 3.77 (t, J = 5.5 Hz, 4Н, ОСН2),
(ОН).
Elemental analysis calcd (%) for С16Н24О5N2S (356.43): 3.42 (2Н, s, SCН2), 3.06 (t, J = 5.5 Hz, 4Н, NСН2), 2.89 (3Н, s,
С 53.91, Н 6.78, N 7.86, S 8.99; found: С 54.01, Н 6.77, N 7.80, NCН3). 13С NMR (d4-methanol) δ (ppm) 176.75 (С=О),137.75-
S 9.09.
N-methyl-bis-(2-hydroxyethyl)ammonium
ylsulfanylacetate (2) [13] was prepared similarly from indol-
3-ylsulfanylacetic acid (2.07 g, 0.01 mol) and N-methyl-bis- (ОН). Elemental analysis calcd (%) for С22Н28О4N2S (416,53):
(2-hydroxyethyl)amine (1.19 g, 0.01 mol). Yield 3.0 g (92%), C 63.44, H 6.78, N 6.73, S 7.70; found: C 63.30, H 6.72, N 6.59,
oil-like product.
104.98 (BzInd), 58.10 (ОСН2 ), 56.17 (NCH2), 49.73 (SCН2),
indol-3- 40.58 (NCН3).
IR ν (cm–1) 1558, 1600 (С=О); 2460-2550 (H+N), 3322
S 7.76 .
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Immunoactive ionic liquids based on 2-hydroxyethylamines and 1-R-indol-3-ylsulfanylacetic acidsꢀ
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R1
HO(O)CCH2S
OH
+
N
R2
N
R3
R1
O
OH
H N
R2
CCH2S
O
N
R3
1: R1 = R2 = CH2CH2OH; R3 = H;
2: R1 = СН3; R2 = CH2CH2OH; R3 = H;
3: R1 = R2 = CH3; R3 = H;
4: R1 = R2 = CH2CH2OH; R3 = СH2С6Н5;
5: R1 = СН3; R2 = CH2CH2OH; R3 = СH2С6Н5.
Scheme 1: Synthesis of compounds 1-5.
The crystalline structure of 1 was investigated using X-ray Protection of Animals (Strasbourg, 1986) and approved
diffraction analysis. Crystals suitable for X-ray diffraction by the Committee on Biomedical Ethics of the Research
were obtained by recrystallization of compound 1 from Institute of Clinical Immunology of the Russian Academy
methanol (20oC).
of Medical Sciences.
Spleen cells in mice were cultured in round bottom
trays for immunologic reaction (Linbro) at 37оС under СО2
2.2 Biological activity: studies of the (5%) and air (95%) atmosphere. The absolute number of
cells introduced into a well was 200 000. The cells were
stimulated by mitogens, namely concanavalin A (Con
spontaneous and Con A-induced
proliferation of spleen cells
A, Sigma). The mitogen concentration was selected by
Results of preliminary screening of anti-proliferative preliminary titration and used in the optimal dose, being
activity of compounds 2-5 were shown in [13]. To expand for Con A 2 µg mL–1. The compounds in three doses (3, 30,
this study we examined the immunodeppressive action and300µgmL–1)wereintroducedintowellssimultaneously
of compounds 1-5 in a consistent approach and their with mitogens. The proliferative activity of the cells was
toxicity. Screening of the immunoactive properties of estimated by the inclusion of Н3-thymidine into DNA of
compounds 1-5 was carried out in the culture in vitro. dividing cells.
The ability of these compounds to affect the spontaneous
A label was introduced 16 h before the end of
and mitogen-stimulated proliferation of splenocytes cultivation; an amount of 1 µCi into each well of the tray.
in mice was estimated. Healthy pubescent mice, viz., For this purpose, the basic solution of Н3-thymidine was
hybrids (CBAхC57BL/6)F1 (CBF1), both male and female, first dissolved in RPMI-1640 medium to a concentration of
-1
8-10 weeks age, with body weight of 18-20 g were used. The 100 µCi mL , and then 10 µL of the solution was added
scatter in groups by the initial weight of the body did not to each well of the tray. Afer the end of incubation,
exceed 10%. Reference and tested animals of the same the cells were collected on glass fiber filters (Flow Lab)
age were obtained simultaneously from one breeding using a Harvester apparatus (“Titertek”). The filters were
nursery. Before and during experiments, the reference and dried and placed into vials for scintillation counting;
tested animals were contained in a vivarium on a standard radioactivity was counted in a toluene scintillator (4 g of
food allowance. All tests were carried out at the same diphenyloxazole, 0.1 g of diphenyloxazolylbenzene per
time (in the morning). Tests were carried out according 1 liter of toluene) in a Delta liquid scintillation counter
to the rules accepted by the European Convention for the (USA). The results were expressed in pulse min–1 of
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included thymidine per 2×105 cells. The data averaged over that is still not involved, and to the nitrogen atom of the
triplet are presented.
indole ring system. These intermolecular hydrogen bonds
form a chain structure along the crystallographic a axis.
For symmetry operators see legend of Fig. 2.
3 Results and discussion
Table 1: Crystal data and details of the structure solution and
refinement of 1.
Compound 1 and its congeners 2, 3 were synthesized by
the reaction of indol-3-yl-sulfanylacetic acid with tris-
(2-hydroxyethyl)amine (TEA), N-methyl-bis-(2-hydroxy-
ethyl)amine (MDEA) and N,N-dimethyl-(2-hydroxyethyl)
amine (1:1 molar ratio) in methanol at 60оС. Compounds
4, 5 were prepared similarly by the interaction of
1-benzylindol-3-yl-sulfanylacetic acid with TEA and MDEA
(Scheme 1).
Empirical formula
Formula weight
C16H24N2O5S
356.43
Temperature
210(2) K
Wavelength
0.71073 Å
Crystal system space group
Orthorhombic, Pbca
Compounds 1, 4 are powders, compounds 2, 3, 5 are
oily liquids soluble in water. Salts 1, 4 qualified as PAILs
because their melting points were below 100oC, and
possess high electroconductivity in 1N water solutions
(close to the electroconductivity of KCl solutions).
a = 12.4194(5) Å
b = 10.4075(6) Å
c = 27.6272(12) Å
3571.0(3) Å3
8, 1.326 g cm-3
0.209 mm-1
Unit cell dimensions
Volume
Z, Calculated density
Absorption coefficient
F(000)
Crystal and experimental data of 1 are summarized in
Table 1. The molecular structure with the atom-labeling
scheme is given in Fig. 1. The packing diagram is shown in
Fig. 2. Selected bond lengths (Å), bond angles (°) as well
as torsion angles (°) are listed in Table 2, and hydrogen
bonds in Table 3. The bond lengths and angles are in
the expected ranges. Trifurcated hydrogen bonds can be
observed in the HN+(CH2CH2OH)3 cation between H2 and
the oxygen atoms of the hydroxyl groups. Cations and
anions are linked via strong hydrogen bonds between the
carboxylate oxygen atoms and two hydroxyl oxygen atoms
(O3 and O4). Additionally, H bonds are formed between
the carboxylate oxygen atoms and that oxygen atom (O5)
1520
Crystal size
0.7×0.6×0.25 mm
1.47 to 24.96°
Θ range for data collection
Reflections collected / unique
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
R indices [I > 2s(I)]
16486 / 2962
Full-matrix least-squares on F2
2962 / 0 / 290
1.042
R1 = 0.0443, wR2 = 0.1199
R1 = 0.0599, wR2 = 0.1329
0.209 and -0.392 e Å-3
R indices (all data)
Largest diff. peak and hole
Figure 1: Molecular structure of 1 with the atom labeling scheme; hydrogen bonds as dotted lines.
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Immunoactive ionic liquids based on 2-hydroxyethylamines and 1-R-indol-3-ylsulfanylacetic acidsꢀ
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Figure 2: Crystal packing of 1, illustrating hydrogen bonds (dashed lines). Symmetry operators: ‘0.5-x, y-0.5, z; ‘‘-x, y-0.5, 0.5-z.
Table 2: Selected bond lengths (Å), bond angles (°), and torsion angles (°).
Table 3: Hydrogen bond geometry (Å, °).
C2-S1
1.746(2)
1.802(2)
1.256(2)
1.413(3)
1.413(3)
1.415(3)
125.3(2)
130.9(2)
109.3(2)
116.1(2)
110.3(2)
111.4(2)
110.0(2)
-176.7(2)
-177.6(2)
178.1(2)
34.9(3)
C9-C10
C10-O2
C11-N2
C13-N2
C15-N2
1.525(3)
1.242(2)
1.492(3)
1.499(3)
1.504(3)
D-H…A
D-H
H…A
D…A
D-H…A
C9-S1
N1-H1A∙∙∙O2‘
N2-H2∙∙∙O3
N2-H2∙∙∙O4
N2-H2∙∙∙O5
O3-H3A∙∙∙O1‘
O4-H4A∙∙∙O2‘
O5-H5A∙∙∙O1‘‘
0.87(3)
0.81(3)
0.81(3)
0.81(2)
0.83(3)
0.80(3)
0.92(4)
2.01(3)
2.39(2)
2.23(2)
2.28(2)
1.90(3)
1.91(3)
1.70(4)
2.799(3)
2.824(2)
2.732(2)
2.717(2)
2.731(2)
2.709(2)
2.623(2)
150(3)
114(2)
121(2)
114(2)
171(3)
173(3)
176(3)
C10-O1
C12-O3
C14-O4
C16-O5
C1-C2-S1
N1-C8-C6
C1-N1-C8
C10-C9-S1
N2-C11-C12
O3-C12-C11
N2-C15-C16
N1-C1-C2-S1
C1-C2-C7-C3
C3-C7-C8-N1
S1-C9-C10-O2
C7-C2-S1
127.8(2)
107.3(2)
100.6(1)
124.0(2)
109.8(2)
107.4(2)
106.5(2)
179.2(2)
-1.3(3)
N1-C8-C7
C2-S1-C9
O2-C10-O1
N2-C13-C14
O4-C14-C13
O5-C16-C15
C4-C3-C7-C2
S1-C2-C7-C3
S1-C9-C10-O1
Toxicity of compounds 1-5, determined on scrum mice
using intraperitoneal introduction, was LD50 = 1300-
3000 mg kg–1. Immunoactive properties of compounds
1-5 were screened. For example, the ability to impact on
spontaneous and mitogen-stimulated (Con A, Sigma,
2 µg mL–1) proliferation of splenocytes in mice in vitro in the
dosage of 3-300 µg mL–1 were evaluated. The test showed
compounds 1-5 as having immunoactive properties of
varying severity (Table 4). Tris-(2-hydroxyethyl)amine
derivatives 1 and 4 were found to possess the most
pronounced antiproliferative properties and therefore can
be considered as immunodepressants.
-146.4(2)
N2-C11-C12-O3 54.1(2)
N2-C15-C16-O5 53.4(3)
N2-C13-C14-O4 52.3(3)
C6-C8-N1-C1 179.6(2)
C1-C2-S1-C9
-101.4(2)
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Table 4: Effect of compounds 1-5 on the spontaneous and mitogen-stimulated proliferation of spleen cells of intact mice in vitro.
Compound
Control
1
Dose, (µg mL–1)
Spontaneous proliferation (pulse min–1)
Con A-proliferation (pulse min–1)
4150
-
179
3
116 (-35.2%)
60 (-66.5%)
52 (-70.9%)
2906
2756 (-33.6%)
2079 (-49.9%)
264 (-93.6%)
44304
30
300
-
Control
2
3
5033 (+73%)
3656 (+26%)
1512 (-48%)
2906
42915 (-3%)
46562 (+5%)
33936 (-23.4%)
44304
30
300
-
Control
3
3
3156 (+8.6%)
2063 (-29%)
478 (-83%)
179
51247 (+15.7%)
38067 (-26%)
27633 (-46%)
4150
30
300
-
Control
115 (-35.7%)
4
3
3399 (-18.1%)
30
300
-
48 (-73.2%)
19 (-89.4%)
6992
2954 (-28.8%)
30 (-99.3%)
47972
Control
5
3
6183 (-11.6%)
2671 (-61.8%)
320 (-95.4%)
48330
30
300
66644 (+38.9%)
306 (-99.4%)
In preliminary experiments on mice in the experimental tris-(2-hydroxyethyl)ammonium indol-3-ylsulfanylacetate
model of the autoimmune disease immunocomplex 1 was established by X-ray diffraction analysis.
glomerulonephritis, it exhibits a pronounced clinical
Immunoactive properties of compounds 1-5 were
effect comparable with cyclosporine A and azathioprine. investigated. They manifested the high dose-dependent
However, unlike the latter, compound 1, 4 do not exert activity relative to the spontaneous and stimulated
nephrotoxic and hepatotoxic action. The detailed results proliferation of splenocytes. Tris-(2-hydroxyethyl)amine
of these experiments will be published subsequently.
derivatives 1 and 4 were found to possess the most
pronounced antiproliferative properties. This fact is
probably caused by the compact tricyclic structure of a
cation in these compounds that favors the penetration of
matter through cell membranes.
4 Conclusions
Compound 1 and its analogues 2, 3 were prepared by
Thus, the tests of antiproliferative activity of the
the reaction of indol-3-yl-sulfanylacetic acid with tris-(2- new compounds indicate that the search for selective
hydroxyethyl)amine, N-methyl-bis-(2-hydroxyethyl)-amine immunomodulators in the series of (2-hydroxyethyl)
and N,N-dimethyl-(2-hydroxyethyl)amine, respectively, ammonium 1-R-indol-3-yl-sulfanylacetates is promising.
in 1:1 molar ratio, the yields being 92-99%. Compounds
4, 5 were synthesized by the interaction of 1-benzylindol- Acknowledgement: The authors acknowledge financial
3-ylsulfanyl-acetic acid with tris-(2-hydroxyethyl)amine, support from the Presidium of the Russian Academy of
N-methyl-bis-(2-hydroxyethyl)amine.
Sciences.
The structures of compounds 1-5 were proved by IR, 1H,
13С, and 15N NMR techniques and their compositions were Supplementary data:
confirmed by elemental analysis. The crystal structure of Contains all relevant crystallographic information.
Crystallographic data of 1.
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