Synthesis and enantiomeric recognition studies of optically active 5,5-dioxophenothiazine bis(urea) and bis(thiourea) derivatives

Article abstract of DOI:10.1016/j.tetasy.2016.08.002

Novel optically active 5,5-dioxophenothiazine bis(urea) and bis(thiourea) derivatives were synthesized and their enantiomeric recognition abilities toward the enantiomers of tetrabutylammonium salts of α-hydroxy and N-protected α-amino acids were examined in acetonitrile using fluorescence spectroscopy.

Full text of DOI:10.1016/j.tetasy.2016.08.002

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis and enantiomeric recognition studies of optically active
5,5-dioxophenothiazine bis(urea) and bis(thiourea) derivatives
Dávid Pál a, Ildikó Móczár a, Attila Kormos a, Péter Baranyai b, Péter Huszthy a,
⇑
a Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, H-1521 Budapest, Hungary
b ‘Lendület’ Supramolecular Chemistry Research Group, Institute of Organic Chemistry, Research Centre of Natural Sciences, Hungarian Academy of Sciences, PO Box 286,
H-1519 Budapest, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel optically active 5,5-dioxophenothiazine bis(urea) and bis(thiourea) derivatives were synthesized
and their enantiomeric recognition abilities toward the enantiomers of tetrabutylammonium salts of
Received 6 May 2016
Accepted 5 August 2016
Available online xxxx
a-hydroxy and N-protected
a
-amino acids were examined in acetonitrile using fluorescence
spectroscopy.
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
chiral anion sensors possessing two urea or thiourea moieties have
a fluorescent signalling unit, which provide a sensitive tool for the
examination of their anion recognition ability by the use of fluores-
cence spectroscopy.2,24,29–38
Enantiomeric recognition as a special case of molecular recogni-
tion is a widespread and vital phenomenon in Nature. A great num-
ber of biologically important molecules are chiral, and many
biological processes are based on enantioselective reactions. Since
one of the enantiomers of a biologically active chiral compound
may have different toxicological and pharmacological properties
to the other, the determination of the enantiomeric composition
of chiral organic compounds has great significance in drug discov-
ery, the food industry and pesticide chemistry.
The carboxyl group is a very common functional group in amino
acids, enzymes, metabolic intermediates and several physiologi-
cally active molecules. Therefore, the synthesis and studies of sen-
sor and selector molecules, which are able to distinguish between
the enantiomers of chiral carboxylic acids, are of great interest. The
enantiomers of chiral carboxylic acids can be differentiated in their
neutral forms,1,2 and in most cases as their deprotonated forms by
enantioselective anion receptors.2–24 The enantiomeric recognition
of chiral carboxylic acids as carboxylates is advantageous, because
carboxylic acids exist in their dissociated forms under physiologi-
cal conditions.13,21
Neutral anion sensors, which bind anions via hydrogen bonds
for example with their amide, urea or thiourea moieties,39 can also
contain a heterocyclic unit having a slightly acidic NH group such
as pyrrole,40 indole or carbazole41 and in a few cases, acridone24,42–
or 5,5-dioxophenothiazine.45–47 In our research group, achiral
44
bis(amide),45 bis(urea),46 bis(thiourea)46 and chiral bis(thiourea)47
type 5,5-dioxophenothiazine-based sensor molecules (1–5, Fig. 1)
were synthesized, and their anion recognition properties were
studied by UV–vis spectroscopy.
Herein, we report the synthesis of novel 5,5-dioxophenoth-
iazine bis(urea) and bis(thiourea) derivatives containing (S)-1-ary-
lethyl units [(S,S)-6–(S,S)-9, Scheme 1] as well as the UV–vis and
fluorescence studies on their complexation properties and enan-
tiomeric recognition abilities toward the enantiomers of different
optically active tetrabutylammonium carboxylates in acetonitrile.
2. Results and discussion
2.1. Synthesis
The most frequently used chiral motifs in anion receptors are
amino acid, BINOL, steroid and monosaccharide units,2–14,19–22
but among others 1-arylethyl24–29 moieties have also been applied
as sources of chirality. These sensor molecules often contain urea
and thiourea units as receptor parts, which have good hydrogen
bond donating ability therefore high affinity toward anions.2 Some
The synthesis of new 5,5-dioxophenothiazine bis(urea) and bis
(thiourea) derivatives containing (S)-1-arylethyl units [(S,S)-6–(S,S)-
9] was carried out as outlined in Scheme 1. Diamine 1045 was reacted
with the appropriate commercially available optically active iso-
cyanate and isothiocyanate in pyridine to give bis(urea) and bis
(thiourea) derivatives (S,S)-6–(S,S)-9.
⇑
Corresponding author. Tel.: +36 1 463 1071; fax: +36 1 463 3297.
E-mail address: huszthy@mail.bme.hu (P. Huszthy).
http://dx.doi.org/10.1016/j.tetasy.2016.08.002
0957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
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2
D. Pál et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
S
X
O
O
tBu
S
tBu
O
Q =
HN
O
HN
OAc
OAc
R
N
H
AcO
NH
HN
OAc
Q
Q
1: R = Me
: R = Ph
3: X = O
2
4
5
: X = S
Figure 1. Reported 5,5-dioxophenothiazine-based anion sensors.
O
O
tetrabutylammonium salts of mandelic acid (Man), tert-butoxycar-
bonyl-protected phenylglycine (Boc-Phg), tert-butoxycarbonyl-
protected phenylalanine (Boc-Phe) and tert-butoxycarbonyl-pro-
tected alanine (Boc-Ala) were studied in acetonitrile by UV–vis
and fluorescence spectroscopies (Fig. 2).
tBu
X
S
tBu
O
O
S
N
H
tBu
tBu
NH
NH
HN
HN
X
R
N C X
N
H
Since basic anions often cause the deprotonation of neutral
anion sensors, we recorded the UV–vis spectra of the deprotonated
forms of receptors (S,S)-8 and (S,S)-9 using 1,8-diazabicyclo[5.4.0]
undec-7-ene (DBU) as a strong base (Fig. 3).
Upon addition of carboxylate anions to receptors (S,S)-8 and
(S,S)-9, the absorption spectra showed changes due to complexa-
tion, and no spectral changes characteristic of deprotonation could
be observed (Fig. 4).
H2N
NH2
pyridine
R
R
10
6
(S,S)- : X = O, R = phenyl (57%)
(S,S)-7: X = S, R = phenyl (59%)
(S,S)-8: X = O, R = 1-naphthyl (77%)
9
(S,S)- : X = S, R = 1-naphthyl (50%)
Scheme 1. Synthesis of receptors (S,S)-6–(S,S)-9.
2.2. Enantiomeric recognition studies
However, the complex formations with the chiral carboxylates
were almost quantitative at the applied concentration of the sensor
The complexation properties and enantiomeric recognition abil-
ities of receptors (S,S)-8 and (S,S)-9 toward the enantiomers of
molecules (20
lM), and manifested in slight spectral changes in
the case of thiourea receptor (S,S)-9 (Fig. 4). Because of these, it
H
H
N
H
N
HO
COO
N
COO
COO
COO
Bu4N
Bu4N
Bu4N
Bu4N
Boc
Boc
Boc
*
*
*
*
Man
Boc-Phg
Boc-Phe
Boc-Ala
Figure 2. Optically active tetrabutylammonium carboxylates used in the enantiomeric recognition studies.
Figure 3. Absorption spectra of (S,S)-8, (S,S)-9 and their deprotonated forms (20 lM) (A and B) in MeCN.
Figure 4. Series of absorption spectra upon titration of (S,S)-8 (20 lM) with (R)-Boc-Phg (0, 0.2, 0.4, 0.7, 1, 2 equiv) (A) and (S,S)-9 (20 lM) with (R)-Boc-Phg (0, 0.2, 0.5, 1,
2 equiv) (B) in MeCN.
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D. Pál et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
Figure 5. Fluorescence emission spectra of (S,S)-8, (S,S)-9 and their deprotonated forms (20 lM) (A and B) in MeCN, kex = 310 nm.
The fluorescence emission spectra of the neutral and deproto-
nated forms of receptors (S,S)-8 and (S,S)-9 were taken (Fig. 5),
and the fluorescence quantum yields of these species were also
determined (Table 1). Both neutral sensor molecules have low flu-
orescence quantum yields, and comparing them, a considerably
lower value can be observed in the case of thiourea derivative
(S,S)-9. The latter can be attributed to the quenching effect of the
sulfur atoms in the molecule, probably due to a photoinduced elec-
tron transfer (PET) process.24,48–50 In both cases, the deprotonation
significantly decreases the fluorescence quantum yields.
Table 1
Fluorescence quantum yields of (S,S)-8, (S,S)-9 and their deprotonated forms in MeCN,
kex = 325 nm
Uf
Neutral form
Deprotonated form
(S,S)-8
(S,S)-9
0.032
0.0053
0.0037
0.0013
The fluorescence emission spectra of receptors (S,S)-8 and (S,S)-
9 showed 17–32% increases and 33–45% decreases, respectively, at
their maxima upon addition of the carboxylates (Figs. 6 and 7),
which could be fitted satisfactorily (also considering the residual
analysis51) by assuming 1:1 complex formation, and the stability
constants were calculated (Table 2).
In most cases, receptors (S,S)-8 and (S,S)-9 showed slight or no
enantiomeric recognition abilities toward the enantiomers of chiral
carboxylates (Table 2). However, in the case of thiourea receptor
(S,S)-9 and the enantiomers of Boc-Phg, moderate selectivity could
Table 2
Stability constants for complexes of (S,S)-8 and (S,S)-9 with the enantiomers of
optically active tetrabutylammonium carboxylates and the degrees of enantiomeric
recognition in MeCN
Figure 6. Series of fluorescence emission spectra upon titration of (S,S)-8 (5
with (S)-Man (0, 0.2, 0.4, 0.8, 1.2, 1.6, 2.4, 4, 10 equiv) in MeCN, kex = 320 nm.
lM)
(S,S)-8
(S,S)-9
logK
D
logK
logK
DlogK
(R)-Man
(S)-Man
5.50
5.41
5.79
5.76
5.87
5.94
5.94
5.82
0.09
5.16
5.27
5.71
5.47
6.09
5.97
6.01
5.91
ꢀ0.11
0.24
0.12
0.10
was more advantageous to follow the complexation processes by
fluorescence spectroscopy using significantly lower concentrations
of the sensor molecules (5, 3 or 2 lM), which also provided larger
spectral changes in the case of thiourea derivative (S,S)-9 (see
later).
(R)-Boc-Phg
(S)-Boc-Phg
(R)-Boc-Phe
(S)-Boc-Phe
(R)-Boc-Ala
(S)-Boc-Ala
0.03
ꢀ0.07
0.12
Figure 7. Series of fluorescence emission spectra upon titration of (S,S)-9 (5
with (R)-Boc-Phg and (S)-Boc-Phg (0–8 equiv) at 381 nm (B).
lM) with (S)-Boc-Phg (0, 0.2, 0.4, 1, 2, 4, 8, 20 equiv) in MeCN, kex = 340 nm (A). Titration curves
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4
D. Pál et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
be observed, which was the highest among the set. These results
suggest that the enantiomeric differentiation is based on very sub-
tle effects.19 One of these effects is the type of the receptor units
(urea or thiourea) in the anion sensors, which significantly influ-
enced the recognition ability toward the enantiomers of Boc-Phg.
The structure of the guest molecules also affected the enantioselec-
tivity: the presence of a hydroxyl group (in Man) instead of the pro-
tected amino group (in Boc-Phg) and the presence of a benzyl
(aralkyl) group (in Boc-Phe) or a methyl (alkyl) group (in Boc-Ala)
instead of the phenyl group (in Boc-Phg) decreased the recognition
ability of receptor (S,S)-9. This preference of receptor (S,S)-9 is sim-
ilar to that of the reported bis(thiourea) derivative 5 containing glu-
copyranosyl groups, in which case the highest enantioselectivity
was also observed for (R)-Boc-Phg over its (S)-isomer
Avance spectrometer. 1H (300 MHz) and 13C (75.5 MHz) NMR spec-
tra were obtained on a Bruker 300 Avance spectrometer. The sig-
nals of NH protons in the 1H NMR spectra were helped to
identify by shaking the NMR samples with D2O. Mass spectra were
recorded on an Agilent-6120 Single Quadrupole LC/MS instrument
using ESI method. Elemental analyses were performed in the
Microanalytical Laboratory of the Department of Organic Chem-
istry, Institute for Chemistry, L. Eötvös University, Budapest,
Hungary.
UV–vis spectra were taken on a Unicam UV4-100 spectropho-
tometer. Quartz cuvettes with path length of 1 cm were used. Flu-
orescence spectra were recorded on a Perkin–Elmer LS 50B
luminescent spectrometer. Emission spectra were corrected by
the spectrometer software. Quartz cuvettes with path length of
1 cm were used. Fluorescence quantum yields were determined
relative to quinine sulfate (Uf = 0.53 in 0.1 M H2SO4).38 Stability
constants of the complexes were determined by global nonlinear
regression analysis using SPECFIT/32TM software.
The enantiomers of Man and Boc-protected amino acids were
purchased from Sigma–Aldrich Corporation. The tetrabutylammo-
nium salts of the anions were prepared by adding 1 equiv of car-
boxylic acid to 1 equiv of Bu4NOH dissolved in MeOH. After
evaporating MeOH, the salts were dried under reduced pressure
over P2O5. During the fluorescence titrations, the concentrations
of the solutions of receptors (S,S)-6–(S,S)-9 were 2, 3 and 5 lM,
and the concentrations of the titrant solutions of chiral carboxy-
lates were 0.2, 0.5, 1 and 10 mM.
(D
logK = 0.22) among the same chiral carboxylates.47 Another
trend can be observed: the stability constants of complexes with
the enantiomers of Man are lower than those with the enantiomers
of amino acid derivatives (Boc-Phg, Boc-Phe, Boc-Ala) in the cases of
5,5-dioxophenothiazine-based anion sensors 5, (S,S)-8 and (S,S)-9.
The complexation properties of receptors (S,S)-6 and (S,S)-7
toward the chiral carboxylates were also examined. Sensor mole-
cules (S,S)-6 and (S,S)-7 showed similar, but considerably smaller
absorption and fluorescence spectral changes compared to those
of receptors (S,S)-8 and (S,S)-9. These slight changes did not allow
the accurate determination of the stability constants of complexes,
therefore, the enantiomeric recognition abilities of receptors (S,S)-
6 and (S,S)-7 could not be evaluated.
4.2. General procedure for the synthesis of receptors (S,S)-6–
(S,S)-9
3. Conclusion
We synthesized four 5,5-dioxophenothiazine derivatives as
potential enantioselective anion sensors, and their absorption
and fluorescence behaviour in the presence of the enantiomers of
To a stirred solution of diamine 1045 (200 mg, 0.535 mmol) in
pyridine (3 mL) was added the solution of the appropriate (S)-1-
arylethyl isocyanate (1.12 mmol, R = phenyl: 165 mg, R = 1-naph-
thyl: 222 mg) or (S)-1-arylethyl isothiocyanate (1.61 mmol,
R = phenyl: 262 mg, R = 1-naphthyl: 342 mg) in pyridine (2 mL)
under Ar at rt. The mixture was stirred at rt for 1 h (X = O) or 2 days
(X = S) (see Scheme 1). After the reaction was completed, the reac-
tion mixture was poured into a water–ice mixture, and acidified to
pH 2 using concentrated hydrochloric acid. The precipitate was fil-
tered off, washed with water, and the crude product was purified
as described below for each compound.
tetrabutylammonium salts of a-hydroxy and N-protected a-amino
acids were studied. Receptors (S,S)-6 and (S,S)-7 containing phenyl
groups at their stereogenic centres gave considerably small absorp-
tion and fluorescence spectral changes upon addition of the car-
boxylates, which did not allow the accurate determination of the
stability constants of these complexes. However, derivatives (S,
S)-8 and (S,S)-9 containing 1-naphthyl groups at their stereogenic
centres showed larger spectral changes in the presence of the chi-
ral carboxylates, and the enantiomeric recognition abilities were
evaluated based on the fluorescence spectral changes. The highest
enantioselectivity, which is a moderate one, could be observed in
the case of receptor (S,S)-9 and the enantiomers of Boc-Phg.
4.2.1. 1,10-(3,7-Di-tert-butyl-5,5-dioxo-5,10-dihydro-5k6-
phenothiazine-1,9-diyl)bis{3-[(1S)-1-phenylethyl]urea} (S,S)-6
The crude product was triturated with ethanol to give receptor
(S,S)-6 (203 mg, 57%) as off-white crystals. Mp: 216–217 °C; Rf:
4. Experimental
4.1. General
27
0.46 (silica gel TLC, MeOH–CH2Cl2 1:20); [
a
]
27 = +65.2, [
a
]
=
D
578
27
27
+69.5, [
3372, 3085, 3063, 3030, 2965, 2907, 2871, 1665, 1609, 1547,
1495, 1453, 1365, 1240, 1137, 901, 875, 760, 701, 600, 547 cmꢀ1
a]546 = +81.3, [a]436 = +154 (c 1.00, DMF); IR (KBr) mmax
;
Starting materials were purchased from Sigma–Aldrich Corpo-
ration unless otherwise noted. (S)-1-(1-Naphthyl)ethyl isothio-
cyanate was obtained from Alfa Aesar. Silica gel 60 F254 (Merck)
plates were used for TLC. Silica gel 60 F254 (Merck) plates (1 mm)
were used for PLC. Silica gel 60 (70–230 mesh, Merck) was used
for column chromatography. Ratios of solvents for the eluents
are given in volumes (mL/mL). Solvents were dried and purified
according to well established methods.52 Evaporations were car-
ried out under reduced pressure.
1H NMR (500 MHz, DMSO-d6) d 1.30 (s, 18H), 1.39 (d, J = 6 Hz,
6H), 4.82–4.97 (m, 2H), 7.18–7.47 (m, 10H + 2H, NH), 7.51 (s,
2H), 7.98 (s, 2H), 9.08 (br s, 2H, NH), 9.20 (br s, 1H, NH); 13C
NMR (75.5 MHz, DMSO-d6) d 23.55, 30.86, 34.36, 49.08, 111.68,
121.34, 123.88, 125.73, 126.61, 127.64, 128.27, 128.40, 144.25,
145.09, 154.80; MS calcd for C38H45N5O4S: 667.3, found (M+H)+:
668.3; Anal. calcd for C38H45N5O4S: C 68.34, H 6.79, N 10.49, S
4.80, found: C 68.11, H 6.91, N 10.24, S 4.53.
Melting points were taken on a Boetius micro-melting point
apparatus and are uncorrected. Optical rotations were taken on a
Perkin–Elmer 241 polarimeter, which was calibrated by measuring
the optical rotations of both enantiomers of menthol. IR spectra
were recorded on
(500 MHz) NMR spectra were obtained on a Bruker DRX-500
4.2.2. 1,10-(3,7-Di-tert-butyl-5,5-dioxo-5,10-dihydro-5k6-
phenothiazine-1,9-diyl)bis{3-[(1S)-1-phenylethyl]thiourea}
(S,S)-7
The crude product was purified by preparative layer chro-
matography using 1:20 MeOH–CH2Cl2 as an eluent to give receptor
(S,S)-7 (220 mg, 59%) as yellow crystals. Mp: 155–156 °C; Rf: 0.85
a
Bruker Alpha-T FT-IR spectrometer. 1H
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D. Pál et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
32
32 = +34.3, [
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Anzenbacher, P., Jr. Org. Lett. 2014, 16, 1302–1305.
(silica gel TLC, MeOH–CH2Cl2 1:20); [a] a]578 = +35.7,
D
32
32
[
a]
546 = +42.2, [
3085, 3062, 3030, 2965, 2870, 1606, 1494, 1454, 1366, 1286,
1139, 1095, 1024, 901, 884, 756, 700, 552 cm–1 1H NMR
a]436 = +105 (c 0.67, CH2Cl2); IR (KBr) mmax 3346,
;
(500 MHz, CDCl3) d 1.31 (s, 18H), 1.55 (d, J = 7 Hz, 6H), 5.48–5.62
(m, 2H), 6.04–6.32 (br s, 2H, NH), 7.10–7.39 (m, 12H), 8.02 (s,
2H), 8.76 (br s, 1H, NH), 10.07 (br s, 2H, NH); 13C NMR
(75.5 MHz, CDCl3) d 22.53, 31.29, 35.13, 54.72, 119.26, 123.07,
123.49, 126.49, 127.60, 128.81, 129.90, 132.10, 142.76, 146.16,
180.25; MS calcd for C38H45N5O2S3: 699.3, found (M+H)+: 700.3;
Anal. calcd for C38H45N5O2S3: C 65.20, H 6.48, N 10.00, S 13.74,
found: C 64.95, H 6.19, N 9.76, S 13.49.
4.2.3. 1,10-(3,7-Di-tert-butyl-5,5-dioxo-5,10-dihydro-5k6-pheno-
thiazine-1,9-diyl)bis{3-[(1S)-1-(naphthalen-1-yl)ethyl]urea} (S,S)-8
The crude product was triturated with ethanol to give receptor
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(S,S)-8 (318 mg, 77%) as off-white crystals. Mp: 184–187 °C; Rf:
32
0.68 (silica gel TLC, iPrOH–hexane 1:5); [
a
]
31 = +38.9, [
a
]
578
=
D
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32
32
+40.6, [a]546 = +46.6, [a]436 = +96.5 (c 1.04, DMF); IR (KBr) mmax
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75–81.
3369, 3063, 3051, 3012, 2964, 2905, 2870, 1667, 1609, 1544,
1494, 1450, 1396, 1365, 1286, 1239, 1138, 1056, 900, 875, 799,
778, 728, 598, 549 cm–1 1H NMR (500 MHz, DMSO-d6) d 1.28 (s,
;
18H), 1.54 (d, J = 7 Hz, 6H), 5.66–5.75 (m, 2H), 7.14 (d, J = 8 Hz,
2H, NH), 7.45–7.56 (m, 6H), 7.58 (d, J = 2 Hz, 2H), 7.66 (d,
J = 7 Hz, 2H), 7.69 (d, J = 2 Hz, 2H), 7.81 (d, J = 8 Hz, 2H), 7.92 (d,
J = 8 Hz, 2H), 8.15 (d, J = 8 Hz, 2H), 8.60 (s, 2H, NH), 9.72 (s, 1H,
NH); 13C NMR (75.5 MHz, DMSO-d6) d 22.33, 30.85, 34.33, 45.25,
112.93, 121.38, 122.16, 123.10, 125.02, 125.46, 125.60, 126.19,
127.31, 127.52, 128.67, 129.77, 130.19, 133.44, 140.34, 144.21,
155.33; MS calcd for C46H49N5O4S: 767.4, found (M+H)+: 768.4;
Anal. calcd for C46H49N5O4SꢁH2O: C 70.29, H 6.54, N 8.91, S 4.08,
found: C 70.03, H 6.67, N 8.69, S 4.29.
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4.2.4. 1,10-(3,7-Di-tert-butyl-5,5-dioxo-5,10-dihydro-5k6-pheno-
thiazine-1,9-diyl)bis{3-[(1S)-1-(naphthalen-1-yl)ethyl]thiourea}
(S,S)-9
The crude product was purified by column chromatography on
silica gel using 1:15 iPrOH–hexane as an eluent to give receptor
(S,S)-9 (214 mg, 50%) as yellow crystals. Mp: 167–170 °C; Rf: 0.42
(silica gel TLC, iPrOH–hexane 1:7);
546 = +142, [a 29
436 = +297 (c 0.71, CH2Cl2); IR (KBr) mmax 3346,
3098, 3050, 3014, 2963, 2906, 2869, 1605, 1494, 1467, 1366,
1286, 1240, 1138, 900, 884, 798, 777, 734, 648, 556 cm–1 1H NMR
[a]D [ ]578 = +121,
29 = +116, a 29
[
a 29
]
]
;
(300 MHz, CDCl3) d 1.04 (s, 18H), 1.77 (d, J = 6 Hz, 6H), 6.04–6.52
(m, 2H + 2H, NH), 7.15–7.35 (m, 4H), 7.43–7.61 (m, 6H), 7.72 (d,
J = 8 Hz, 2H), 7.85 (d, J = 8 Hz, 2H), 7.90 (s, 2H), 8.20 (d, J = 8 Hz,
2H), 8.64 (br s, 1H, NH), 9.88 (br s, 2H, NH); 13C NMR (75.5 MHz,
CDCl3) d 21.49, 30.99, 34.83, 51.33, 119.12, 122.98, 123.31, 123.41,
125.54, 125.64, 126.10, 127.02, 128.52, 129.17, 129.76, 131.00,
132.08, 134.16, 138.07, 146.24, 180.20; MS calcd for C46H49N5O2S3:
799.3, found (M+H)+: 800.3; Anal. calcd for C46H49N5O2S3: C 69.05, H
6.17, N 8.75, S 12.02, found: C 68.94, H 5.92, N 8.49, S 11.85.
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Financial supports of the Hungarian Scientific Research Fund/
National Research, Development and Innovation Office (OTKA/
NKFIH No. K 112289 and PD 104618), the New Széchenyi Develop-
ment Plan (TÁMOP-4.2.1/B-09/1/KMR-2010-0002) and the
Zsuzsanna Szabó Research Fellowship are gratefully acknowl-
edged. The authors express their appreciation to Dr. György Tibor
Balogh and Dr. Eszter Riethmüller for taking mass spectra.
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Please cite this article in press as: Pál, D.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.08.002