First synthesis of thiophene thioglycosides

Article abstract of DOI:10.1080/07328300902789209

A new method for the preparation of a new class of thiophene thioglycosides via one-pot reaction of the sodium thiophenethiolate salts with 2,3,4,6-tetra-O-acetyl - D-gluco- and galacto-pyranosyl bromides has been studied. The sodium thiophenethiolate sal

Full text of DOI:10.1080/07328300902789209

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First Synthesis of Thiophene
Thioglycosides
Galal H. Elgemeie a , Wafaa A. Zaghary b , Kamelia M. Amin c &
Tamer M. Nasr b
a Department of Chemistry, Faculty of Science, Helwan University,
Ain-Helwan, Cairo, Egypt
b Pharmaceutical Chemistry Department, Faculty of Pharmacy,
Helwan University, Ain-Helwan, Cairo, Egypt
c Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo
University, Cairo, Egypt
Published online: 01 Apr 2009.
To cite this article: Galal H. Elgemeie , Wafaa A. Zaghary , Kamelia M. Amin & Tamer M. Nasr (2009):
First Synthesis of Thiophene Thioglycosides, Journal of Carbohydrate Chemistry, 28:3, 161-178
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Journal of Carbohydrate Chemistry, 28:161–178, 2009
ꢀC
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328300902789209
First Synthesis of Thiophene
Thioglycosides
Galal H. Elgemeie,1 Wafaa A. Zaghary,2 Kamelia M. Amin,3
and Tamer M. Nasr2
1Department of Chemistry, Faculty of Science, Helwan University, Ain-Helwan, Cairo,
Egypt
2Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Ain-
Helwan, Cairo, Egypt
3Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo,
Egypt
A new method for the preparation of a new class of thiophene thioglycosides via one-pot
reaction of the sodium thiophenethiolate salts with 2,3,4,6-tetra-O-acetyl-α-D-gluco-
and galacto-pyranosyl bromides has been studied. The sodium thiophenethiolate salts
are prepared using cyano-di-thioic analogs and their corresponding mono- and dithio-
late salts.
Keywords Thiophene thioglycosides, Sodium thiophenethiolate, Galacto-pyranosyl
bromides
INTRODUCTION
Thio sugars revealed recently biological interest as potential new
therapeutics.[1] Thus, the new developments in the synthetic and medici-
nal chemistry of thio-sugars are important for carbohydrate drug design.[2,3]
In recent reports from our laboratory, we described the preparation of
different novel functionalized pyridine thioglycosides, which revealed antag-
onistic activity.[4,5] In an earlier communication we had already reported the
use of dihydropyridine thioglycosides as substrates or inhibitors of protein
glycosylation.[6] These common features encouraged us to develop a new,
straightforward route for the synthesis of heterocyclic thioglycosides. Here we
describe the synthesis of thiophene thioglycosides by the reaction of sodium
thiophenethiolates with α-halogeno sugars. As far as we know, this is the first
report of a thiophene thioglycoside.
Received July 1, 2008; accepted February 1, 2009.
Address correspondence to Galal H. Elgemeie, Department of Chemistry, Faculty of
Science, Helwan University, Ain-Helwan, Cairo, Egypt. E-mail: Elgemeie@hotmail.com
161

G.H. Elgemeie et al.
162
RESULTS AND DISCUSSION
It has been found that reaction of substituted acetanilide derivatives 1 with
carbon disulfide in the presence of sodium ethoxide gives the sodium dithio-
late salts 2. Compounds 2 are readily monoalkylated with one equivalent of
phenacyl bromide or methyl iodide to give the corresponding sodium salts of
monoalkylated products 3 and 4 in good yields. Upon acidification with hy-
drochloric acid, compounds 3 and4 gave the novel mercapto products 6 and
7, respectively. Compounds 3 and 4 reacted with 2,3,4,6-tetra-O-acetyl-α − D-
gluco- and galacto-pyranosyl bromides 5a,b in ethanol at rt to give in high
yield the corresponding S-glycosides 8a–h and 9a–h. Compounds 8 and 9
could also be prepared by the reaction of the thiols 6 and 7 with 5a,b in
KOH-acetone at rt for 15 h (Sch. 1). It is hypothesized that the cis-(α) sug-
ars react by a simple SN2 reaction to give the β-glycoside products.[7] Struc-
ture 8 h is supported by its mass spectrum, its IR spectrum revealing the
–1
–1
presence of a CN band at 2198 cm and CO band at 1751 cm and its
1H NMR spectrum showing the anomeric proton as a doublet at δ 5.80 ppm
with a spin-spin coupling constant of 10.1 Hz indicating the β-configuration,
as confirmed by the 13C NMR spectrum showing C-1ꢀ at δ 85.2 ppm. The 13C
NMR spectrum of 8 h contained a signal at δ 85.2 ppm corresponding to the
C-1ꢀ atom of the β-configuration. When compounds 2 were subjected to gly-
cosylation with 5a,b followed by neutralization to pH 7, the glycoside thi-
ols 12 were obtained. Compounds 12 could also be prepared by alkylation of
the dithiol derivatives 11 with one equivalent of 5a,b (Sch. 2). Indeed, the
–1
IR spectrum of 12b revealed the presence of a CN band at 2198 cm and a
1
CO band at 1751 cm–1. The H NMR spectrum showed the anomeric proton
as a doublet at δ 6.00 ppm. The 13C NMR spectrum contained a signal at δ
83.6 ppm corresponding to the C-1ꢀ atom of the β-configuration. The sodium α-
cyanoketene thiolates 3 were cyclized by refluxing in sodium ethoxide to give
the corresponding sodium thiophenethiolates 13, and subsequently the novel
2-mercaptothiophenes 14. Upon alkylation with halogenosugars 5, compounds
13 yielded the corresponding 2-(glycopyranosylthio)thiophene derivative 15.
Attempted preparation of 15 through the reaction of thiophene-2-thiols 14
with halogenosugars 5 in KOH-acetone was also successful in our hands (Sch.
3). The mass spectrum of 15d revealed a molecular formula C32H31ClN2S2O11
1
(M+ = 719); in addition, the H NMR spectrum showed the anomeric proton
ꢀ
as a doublet at δ 5.40 ppm (J1ꢀ,2 = 9.8 Hz) indicating the β-configuration, as
confirmed by the 13C NMR spectrum showing a signal at δ 85.2 corresponding
to C-1ꢀ.
In summary, we have achieved a novel synthesis of thiophene thioglyco-
sides by the reaction of the sodium thiophenethiolates with α-glycosyl halides.
These glycosides are excellent starting materials for the synthesis of other car-
bohydrate derivatives and are evaluated for biological activity.

First Synthesis of Thiophene Thioglycosides
163
CN
H
N
Ar
O
1
- +
2 EtONa
CS /
2
EtOH
CN
4
O
CN
H
N
CN
2
CH3 I
PhCOCH2Br
EtOH/ r.t.
H
N
H
N
- +
SNa
SCH3
- +
S Na
S
Ar
Ph
EtOH / r.t.
Ar
Ar
- +
S Na
- +
S Na
O
O
5
O
3
AcO
R1
O
OAc
Br
OAc
R2
EtOH/r.t.
5
EtOH/r.t.
CN
O
CN
H
N
H
N
SCH3
S
Ph
Ar
Ar
S
O
S
O
AcO
R1
AcO
O
R1
O
OAc
9
OAc
R2
R2
OAc
OAc
8
5
5
KOH/acetone
r.t.
KOH/acetone
r.t.
O
CN
CN
H
N
H
N
S
+
SCH3
Ph
Ar
Ar
SH
6
O
SH
7
O
1–4, 6, 7 Ar
a,
b,
c,
C6H5
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
+
H
H
d,
8,9
Ar
R1
H
R2
3
4
a,
b,
c,
d,
e,
f,
OAc
OAc
OAc
OAc
C6H5
H
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
C6H5
H
H
OAc
OAc
OAc
OAc
H
H
H
H
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
g,
h,
Scheme 1.

G.H. Elgemeie et al.
164
-
+
O
SNa
Ar
S
N
H
-
+
CN
O
SNa
5
AcO
Ar
N
-
+
SNa
R1
O
EtOH / r.t.
H
OA c
CN
R2
OAc
2
10
+
+
H (pH= 7)
H
0oC
O
SH
S
O
SH
5
Ar
Ar
SH
N
H
N
H
KOH/ acetone
r.t.
CN
CN
11
AcO
R1
O
OA c
R2
2,11
Ar
OA c
a,
b,
c,
C6H5
12
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
d,
10,12
Ar
R1
H
R2
a,
b,
c,
d,
e,
f,
OAc
OAc
OAc
OAc
H
C6H5
H
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
C6H5
H
H
OAc
OAc
OAc
OAc
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
H
g,
h,
H
H
Scheme 2.

First Synthesis of Thiophene Thioglycosides
165
O
CN
O
NH2
H
ArHN
NaOEt
N
S
+
Ph
Ar
-
-
+
/ 2h
O
SNa
COPh
NaS
S
3
13
5
1)EtOH
/ 2h
EtOH/r.t.
+
2) H
O
NH2
O
ArHN
NH2
ArHN
COPh
5
S
S
AcO
R1
COPh
O
HS
S
KOH/acetone
r.t.
OAc
R2
OAc
14
15
13,14 Ar
a,
b,
c,
C6H5
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
d,
15 Ar
R1
H
R2
OAc
OAc
OAc
OAc
H
a,
b,
c,
d,
e,
f,
C6H5
H
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
C6H5
H
H
OAc
OAc
OAc
OAc
4-H3C-C6H4
4-H3CO-C6H4
4-Cl-C6H4
H
g,
h,
H
H
Scheme 3.
EXPERIMENTAL
All melting points were measured on a Gallenkamp melting point apparatus.
The IR spectra were recorded (KBr disk) on a Perkin Elmer 1650 FT-IR instru-
ment. The 1H NMR spectra were measured on a Varian 400 MHz spectrometer
for solutions DMSO-d6 using Si(CH3)4 as an internal standard. Mass spectra

G.H. Elgemeie et al.
166
were recorded on a Varian MAT 112 spectrometer. Elemental analyses were
obtained from the Microanalytical Data Center at Cairo University, Egypt.
Progress of the reactions was monitored by TLC using aluminum sheets
coated with silica gel F254 (Merck). Viewing under a short-wavelength UV
lamp effected detection. All evaporations were carried out under reduced pres-
sure at 40◦C.
Sodium (2Z)-2-cyano-3-[(2-oxo-2-phenylethyl)thio]-N-
arylacryl-amide-3-thiolates (3a–d)
General procedure
A solution of compounds 2 (0.01 mol) and phenacyl bromide (1.98 g, 0.01
mol) in ethanol (20 mL) was stirred at rt for 2 h, the solution was evaporated,
and the formed solid product was collected by filtration.
Sodium 2-cyano-3-(methylthio)-N-arylacrylamide-3-thiolates
(4a–d)
General procedure
A solution of compounds 2 (0.01 mol) and methyl iodide (1.4 g, 0.01 mol) in
ethanol (30 mL) was stirred at rt for 2 h. The solution was evaporated and the
formed solid product was collected by filtration.
(2E)-2-Cyano-3-mercapto-3-[(2-oxo-2-phenylethyl)thio]-N-
arylacryl-amides (6a–d) and 2-cyano-3-mercapto-
3-(methylthio)-N-arylacryl-amides (7a–d)
General procedure
A solution of compounds 3 or4 in ethanol (20 mL) was poured onto cold
water and treated with hydrochloric acid until just acidic and the formed solid
products 6 or 7 were collected by filtration and recrystallized from ethanol.
(2Z)-N-Aryl-2-cyano-3-[(2-oxo-2-phenylethyl)thio]-3-
(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-β-D-gluco- or
galactopyranosylthio)acrylamides (8a–h)
General procedures
Method A. To a solution of compounds 3 (0.01 mol) in ethanol (30 mL), a
solution of 5a,b (4.10 g, 0.01 mol) in acetone (20 mL) was added. The reaction

First Synthesis of Thiophene Thioglycosides
167
mixture was stirred at rt until completion (TLC, CHCl3:CH3OH, 9:1, 15 h),
then evaporated under reduced pressure, and the residue was washed with
distilled water to remove the formed sodium bromide. The resulting products
were crystallized from ethanol.
Method B. A solution of compounds 6 (0.01 mol) in aq. potassium hydrox-
ide [0.56 g (0.01 mol) in distilled water (6 mL)] was added to a solution of 5a,b
(4.10 g, 0.01 mol) in acetone (30 mL). The reaction mixture was stirred at rt
until completion (TLC, CHCl3:CH3OH, 9:1, 15 h), then evaporated under re-
duced pressure, and the residue was washed with distilled water to remove
the formed potassium bromide. The resulting products were crystallized from
ethanol.
(2Z)-2-Cyano-3-[(2-oxo-2-phenylethyl)thio]-N-phenyl-3-(2ꢀ,3ꢀ,4ꢀ,
6ꢀ-tetra-O-
acetyl-β-D-glucopyranosylthio)acrylamide (8a): yellow crystals, m.p. 180◦C,
–1
80% method A, 75% method B, [α]D+22.5, IR (KBr) νmax/cm 3317 (NH),
2198 (CN), 1751 (CO), 1635 (CO). 1H NMR δ 1.70–2.00 (4s, 12H, 4 ×
CH3CO), 3.50 (s, 2H, CH2), 3.90 (s, 2H, H-6aꢀ, H-6bꢀ), 3.95 (m, 1H, H-5ꢀ),
4.10 (t, 1H, H-4ꢀ), 4.90 (t, 1H, H-3ꢀ), 5.20–5.40 (m, 2H, H-2ꢀ, H-1ꢀ), 7.00–7.80
(m, 10H, 2C6H5), 9.80 (s, 1H, NH). 13C NMR δ 20.4–20.7 (4 × CH3), 52.8
(CH2), 62.2 (CH2, C-6ꢀ), 68.2 (C-4ꢀ), 69.8 (C-2ꢀ), 73.0 (C-3ꢀ), 74.8 (C-5ꢀ),
85.2 (C-1ꢀ), 116.8 (CN), 120.2–141.4 (2C6H5), 154.8 (C-2), 160.8 (C-3),
169.7–187.0 (6 × CO). Anal. Calcd for C32H32N2O11S2 (684.732): C, 56.1; H,
4.7; N, 4.1%. Found: C, 56.0; H, 4.6; N, 4.7%.
(2Z)-2-Cyano-N-(4-methylphenyl)-3-[(2-oxo-2-phenylethyl)thio]-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetra-O-acetyl-β-D-glucopyranosylthio)acrylamide (8b): yellow crystals,
–1
m.p. 188◦C, 84% method A, 77% method B, [α]D+30.5, IR (KBr) νmax/cm
3301 (NH), 2206 (CN), 1751 (CO), 1674 (CO). 1H NMR δ 1.70–1.95 (4s, 12H,
4 × CH3CO), 2.40 (s, 3H, CH3), 3.50 (s, 2H, CH2), 3.80 (s, 2H, H-6aꢀ, H-6bꢀ),
3.95 (m, 1H, H-5ꢀ), 4.10 (t, 1H, H-4ꢀ), 4.90 (t, 1H, H-3ꢀ), 5.20–5.40 (m, 2H,
H-2ꢀ, H-1ꢀ), 7.00–7.80 (m, 9H, C6H5, C6H4), 9.80 (s, 1H, NH). Anal. Calcd
for C33H34N2O11S2 (698.758): C, 56.7; H, 4.9; N, 4.0%. Found: C, 56.8; H,
4.7; N, 4.6%.
(2Z)-2-Cyano-N-(4-methoxyphenyl)-3-[(2-oxo-2-phenylethyl)thio]-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetra-O-acetyl-β-D-glucopyranosylthio)acrylamide (8c): yellow crys-
tals, m.p. 155◦C, 81% method A, 75% method B, [α]D+27.5, IR (KBr)
–1
νmax/cm 3348 (NH), 2198 (CN), 1751 (CO), 1650 (CO). Anal. Calcd for
C33H34N2O12S2 (714.758): C, 55.4; H, 4.8; N, 3.9%. Found: C, 55.3; H, 5.1;
N, 4.3%.
(2Z)-N-(4-Bromophenyl)-2-cyano-3-[(2-oxo-2-phenylethyl)thio]-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetra-O-acetyl-β-D-glucopyranosylthio)acrylamide (8d): yellow crystals,
–1
m.p. 206◦C, 86% method A, 80% method B, [α]D+29.5, IR (KBr) νmax/cm
3325 (NH), 2198 (CN), 1751 (CO), 1643 (CO). 1H NMR δ 1.70–2.00 (4s, 12H,

G.H. Elgemeie et al.
168
4 × CH3CO), 3.40–4.10 (m, 5H, CH2,H-6aꢀ, H-6bꢀ, H-5ꢀ), 4.90 (m, 2H, H-4ꢀ,
H-3ꢀ), 5.30 (m, 2H, H-2ꢀ, H-1ꢀ), 7.40–7.80 (m, 9H, C6H5, C6H4), 10.40 (s, 1H,
NH). Anal. Calcd for C32H31BrN2O11S2 (673.628): C, 50.4; H, 4.1; N, 3.7%.
Found: C, 49.9; H, 4.5; N, 3.4%.
(2Z)-2-Cyano-3-[(2-oxo-2-phenylethyl)thio]-N-phenyl-3-(2ꢀ,3ꢀ,4ꢀ,
6ꢀ-tetra-O-
acetyl-β-D-galactopyranosylthio)acrylamide (8e): yellow crystals, m.p.
177◦C, 79% method A, 73% method B, [α]D+34.5, IR (KBr) νmax/cm–13286
1
(NH), 2214 (CN), 1744 (CO), 1628 (CO). H NMR δ 1.70–2.00 (4s, 12H, 4 ×
CH3CO), 3.50 (s, 2H, CH2), 3.95 (m, 2H, H-6aꢀ, H-6bꢀ), 4.30 (m, 1H, H-5ꢀ),
5.00 (t, 1H, H-4ꢀ), 5.20–5.30 (m, 3H, H-3ꢀ, H-2ꢀ, H-1ꢀ), 7.10–7.80 (m, 9H,
C6H5, C6H4), 10.30 (s, 1H, NH). Anal. Calcd for C32H32N2O11S2 (684.732):
C, 56.1; H, 4.7; N, 4.0%. Found: C, 55.9; H, 4.9; N, 4.2%.
(2Z)-2-Cyano-N-(4-methylphenyl)-3-[(2-oxo-2-phenylethyl)thio]-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetra-O-acetyl-β-D-galactopyranosylthio)acrylamide (8f): yellow crys-
tals, m.p. 170◦C, 84% method A, 78% method B, [α]D+24.5, IR (KBr)
νmax/cm–13325 (NH), 2198 (CN), 1751 (CO), 1627 (CO). 13C NMR δ 20.4–
20.9 (5 × CH3), 52.8 (CH2), 61.9 (CH2, C-6ꢀ), 67.2 (C-4ꢀ), 67.8 (C-2ꢀ),
71.0 (C-3ꢀ), 74.2 (C-5ꢀ), 85.5 (C-1ꢀ), 116.8 (CN), 120.2–141.3 (C6H5and
C6H4), 154.8 (C-2), 160.8 (C-3), 169.7–187.0 (6 × CO). Anal. Calcd for
C33H34N2O11S2 (698.758): C, 56.7; H, 4.9; N, 4.0%. Found: C, 57.1; H, 4.9;
N, 3.3%.
(2Z)-2-Cyano-N-(4-methoxyphenyl)-3-[(2-oxo-2-phenylethyl)thio]-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetra-O-acetyl-β-D-galactopyranosylthio)acrylamide (8g): yellow crys-
tals, m.p. 170◦C, 80% method A, 74% method B, [α]D+32.5, IR (KBr)
νmax/cm–13325 (NH), 2198 (CN), 1751 (CO), 1635 (CO). 1H NMR δ 1.70–2.00
(4s, 12H, 4 × CH3CO), 3.50 (s, 2H, CH2), 3.75 (s, 3H, OCH3), 3.80 (s,
2H, H-6aꢀ, H-6bꢀ), 3.95 (m, 1H, H-5ꢀ), 4.30 (t, 1H, H-4ꢀ), 5.00 (t, 1H, H-3ꢀ),
5.15–5.35 (m, 2H, H-2ꢀ, H-1ꢀ), 7.30–7.80 (m, 9H, C6H5, C6H4), 10.40 (s, 1H,
NH). Anal. Calcd for C33H34N2O12S2 (714.758): C, 55.4; H, 4.8; N, 3.9%.
Found: C, 55.2; H, 5.0; N, 3.3%.
(2Z) − N-(4-Chlorophenyl)-2-cyano-3-[(2-oxo-2-phenylethyl)thio]-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetra-O-acetyl-β-D-galactopyranosylthio)acrylamide (8h): yellow crys-
tals, m.p. 190◦C, 85% method A, 82% method B, [α]D+40.5, IR (KBr)
νmax/cm–13317 (NH), 2198 (CN), 1751 (CO), 1635 (CO). 1H NMR δ 1.70–2.00
(4s, 12H, 4 × CH3CO), 3.45 (s, 2H, CH2), 3.90 (s, 2H, H-6aꢀ, H-6bꢀ), 3.95 (m,
1H, H-5ꢀ), 4.25 (t, 1H, H-4ꢀ), 5.00 (t, 1H, H-3ꢀ), 5.25 (t, 1H, H-2ꢀ), 5.80 (d,
J1 −2 = 9.77, 1H, H-1ꢀ), 7.30–7.80 (m, 9H, C6H5, C6H4), 10.40 (s, 1H, NH).
Anal. Calcd for C33H31ClN2O11S2 (731.188): C, 53.4; H, 4.3; N, 3.9%. Found:
C, 54.1; H, 4.9; N, 4.5%.
ꢀ
ꢀ

First Synthesis of Thiophene Thioglycosides
169
(2Z)−N-Aryl-2-cyano-3-(methylthio)-3-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-
β-D-gluco or galactopyranosylthio)acrylamides
(9a–h)
General procedures
Method A. Compounds 4a–d (0.01 mol) were treated as described for the
preparation of 8a–h.
Method B. Compounds 7a–d (0.01 mol) were treated as described for
the preparation of 8a–h. The reaction was completed within 12 h (TLC,
CHCl3:CH3OH, 9:1).
(2Z)-2-Cyano-3-(methylthio)-N−phenyl-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
glucopyranosylthio)acrylamide (9a): orange crystals, m.p. 156◦C, 68%
–1
method A, 75% method B, [α]D+28.0, IR (KBr) νmax/cm 3332 (NH), 2198
(CN), 1751 (CO of ester), 1666 (CO of amide). 1H NMR δ 1.90–2.10 (4s, 12H,
4 × CH3CO), 2.60 (s, 3H, SCH3), 3.60 (s, 2H, H-6aꢀ, H-6bꢀ), 4.05 (m, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H-5 ), 4.15 (t, 1H, H-4 ), 4.95 (t, 1H, H-3 ), 5.05 (t, 1H, H-2 ), 5.45 (d, J1 ,2
=
9.60, 1H, H-1ꢀ), 7.10–7.50 (m, 5H, C6H5), 10.50 (s, 1H, NH). Anal. Calcd for
C25H28N2O10S2 (580.624): C, 51.7; H, 4.9; N, 4.9%. Found: C, 51.3; H, 5.3;
N, 4.2%.
(2Z)-2-Cyano-N−(4-methylphenyl)-3-(methylthio)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-
β-D-glucopyranosylthio)acrylamide (9b): yellow crystals, m.p. 175◦C, 70%
–1
method A, 87% method B, [α]D+35.0, IR (KBr) νmax/cm 3355 (NH), 2206
(CN), 1743 (CO of ester), 1658 (CO of amide). 1H NMR δ 2.00–2.10 (4s,
12H, 4 × CH3CO), 2.30 (s, 3H, CH3), 2.55 (s, 3H, SCH3), 4.05 (s, 2H, H-6aꢀ,
H-6bꢀ), 4.20 (m, 2H, H-5ꢀ, H-4ꢀ), 5.00 (m, 1H, H-3ꢀ), 5.50 (m, 2H, H-2ꢀ, H-1ꢀ),
7.15–7.50 (d.d, 4H, C6H4), 10.50 (s, 1H, NH). 13C NMR δ 18.6 (SCH3),
20.6–20.8 (5 × CH3), 62.3 (CH2, C-6ꢀ), 68.2 (C-4ꢀ), 69.9 (C-2ꢀ), 73.1 (C-3ꢀ),
75.2 (C-5ꢀ), 85.2 (C-1ꢀ), 111.9 (C-1 enol form), 115.7 (CN), 120.2–135.8
(C6H4), 156.5 (C-2), 161.1 (C-3), 169.5–170.3 (4 × CO). Anal. Calcd for
C26H30N2O10S2 (594.650): C, 52.5; H, 5.1; N, 4.7%. Found: C, 52.5; H, 4.9;
N, 4.8%.
(2Z)-2-Cyano-N−(4-methoxyphenyl)-3-(methylthio)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-
acetyl-β-D-glucopyranosylthio)acrylamide (9c): yellow crystals, m.p. 170◦C,
–1
75% method A, 82% method B, [α]D+37.5, IR (KBr) νmax/cm 3363 (NH),
1
2206 (CN), 1751 (CO of ester), 1658 (CO of amide). H NMR δ 1.90–2.10
(4s, 12H, 4 × CH3CO), 2.60 (s, 3H, CH3), 3.80 (s, 3H, OCH3), 4.10 (m,
3H, H-6aꢀ, H-6bꢀ, H-5ꢀ), 5.05 (m, 2H, H-4ꢀ, H-3ꢀ), 5.40 (m, 2H, H-2ꢀ, H-1ꢀ),
7.00–7.50 (d.d, 4H, C6H4), 10.45 (s, 1H, NH). 13C NMR (DMSO) δ 18.6
(SCH3), 20.6–20.8 (4 × CH3), 55.6 (OCH3), 62.3 (CH2, C-6ꢀ), 68.20 (C-4ꢀ),
69.9 (C-2ꢀ), 73.1 (C-3ꢀ), 75.2 (C-5ꢀ), 85.2 (C-1ꢀ), 112.0 (CN), 114.4–131.3

G.H. Elgemeie et al.
170
(C6H4), 156.5 (C-2), 158.5 (C-3), 161.1 (C-1), 169.5–170.3 (4 × CO). Anal.
Calcd for C26H30N2O11S2 (610.650): C, 51.1; H, 5.0; N, 4.6%. Found: C, 51.2;
H, 5.6; N, 4.7%.
(2Z) − N−(4-Bromophenyl)-2-cyano-3-(methylthio)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-
β-D-glucopyranosylthio)acrylamide (9d): yellow crystals, m.p. 186◦C, 72%
method A, 79% method B, [α]D+39.5, IR (KBr) νmax/cm–13340 (NH), 2206
(CN), 1751 (CO of ester), 1674 (CO of amide). 1H NMR δ 1.90–2.05 (4s, 12H,
4 × CH3CO), 2.60 (s, 3H, CH3), 4.10–4.20 (m, 4H, H-6aꢀ, H-6bꢀ, H-5ꢀ, H-4ꢀ),
ꢀ
ꢀ
4.95–5.10 (m, 2H, H-3 , H-2 ), 5.45 (d, J1 −2 = 9.98, 1H, H-1ꢀ), 7.40–7.50 (dd,
4H, C6H4), 10.70 (s, 1H, NH). 13C NMR δ 18.3 (SCH3), 20.2–20.4 (4 × CH3),
61.7 (CH2, C-6ꢀ), 67.7 (C-4ꢀ), 69.4 (C-2ꢀ), 72.6 (C-3ꢀ), 74.7 (C-5ꢀ), 84.8 (C-1ꢀ),
110.9 (C-1 enol form), 116.2 (CN), 120.1–137.2 (C6H4), 158.5 (C-2), 161.1
(C-3), 169.0–169.4 (4 × CO). Anal. Calcd for C25H27BrN2O10S2 (659.520):
C, 45.5; H, 4.2; N, 4.2%. Found: C, 45.2; H, 4.6; N, 4.1%.
ꢀ
ꢀ
(2Z)-2-Cyano-3-(methylthio)-N−phenyl-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
galactopyranosylthio)acrylamide (9e): yellow crystals, m.p. 160◦C, 65%
–1
method A, [α]D+30.0, 75% method B. IR (KBr) νmax/cm 3332 (NH), 2198
(CN), 1751 (CO of ester), 1666 (CO of amide). 1H NMR δ 1.90–2.20 (4s,
12H, 4 × CH3CO), 2.60 (s, 3H, CH3), 3.60 (s, 2H, H-6aꢀ, H-6bꢀ), 4.10 (m, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H-5 ), 4.15 (t, 1H, H-4 ), 5.00 (t, 1H, H-3 ), 5.05 (t, 1H, H-2 ), 5.50 (d, J1 ,2
=
9.90, 1H, H-1ꢀ), 7.10–7.70 (m, 5H, C6H5), 10.50 (s, 1H, NH). Anal. Calcd for
C25H28N2O10S2 (580.624): C, 51.7; H, 4.9; N, 4.8%. Found: C, 51.2; H, 5.3;
N, 4.2%.
(2Z)-2-Cyano-N−(4-methylphenyl)-3-(methylthio)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-
β-D-galactopyranosylthio)acrylamide (9f): yellow crystals, m.p. 175◦C, 68%
method A, 74% method B, [α]D+25.0, IR (KBr) νmax/cm–13440 (NH), 2198
(CN), 1751 (CO of ester), 1635 (CO of amide).1H NMR δ 1.90–2.20 (4s, 12H,
4 × CH3CO), 2.30 (s, 3H, CH3), 2.60 (s, 3H, SCH3), 4.10 (s, 2H, H-6aꢀ, H-6bꢀ),
4.40 (t, 2H, H-5ꢀ,H-4ꢀ), 5.10 (t, 1H, H-3ꢀ), 5.40 (m, 2H, H-2ꢀ, H-1ꢀ), 7.10–7.70
(m, 4H, C6H4), 10.50 (s, 1H, NH). 13C NMR δ 18.1 (SCH3), 20.2 (Ar-CH3),
20.3–20.4 (4 × CH3), 61.5 (CH2, C-6ꢀ), 67.3 (C-4ꢀ), 67.5 (C-2ꢀ), 70.6 (C-3ꢀ),
74.1 (C-5ꢀ), 85.3 (C-1ꢀ), 114.0 (CN), 119.2–135.0 (C6H4), 156.5 (C-2), 158.5
(C-3), 161.1 (C-1), 169.0–170.3 (4 × CO). Anal. Calcd for C26H30N2O10S2
(594.650): C, 52.5; H, 5.1; N, 4.7%. Found: C, 52.1; H, 5.2; N, 5.2%.
(2Z)-2-Cyano-N−(4-methoxyphenyl)-3-(methylthio)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-
acetyl-β-D-galactopyranosylthio)acrylamide (9g): yellow crystals, m.p.
162◦C, 72% method A, 79% method B, [α]D+40.0, IR (KBr) νmax/cm–13363
(NH), 2206 (CN), 1751 (CO of ester), 1658 (CO of amide).1H NMR δ
1.90–2.10 (4s, 12H, 4 × CH3CO), 2.60 (s, 3H, CH3), 3.80 (s, 3H, OCH3),
4.05–4.20 (m, 3H, H-6aꢀ, H-6bꢀ,H-5ꢀ), 5.00–5.10 (m, 2H, H-4ꢀ, H-3ꢀ), 5.50 (m,
2H, H-2ꢀ, H-1ꢀ), 6.90–7.50 (dd, 4H, C6H4), 10.40 (s, 1H, NH).13C NMR δ 18.2

First Synthesis of Thiophene Thioglycosides
171
(SCH3), 20.2–20.4 (4 × CH3), 55.1 (OCH3), 61.7 (CH2, C-6ꢀ), 67.7 (C-4ꢀ), 69.5
(C-2ꢀ), 72.6 (C-3ꢀ), 75.0 (C-5ꢀ), 84.7 (C-1ꢀ), 114.0 (CN), 115.3–130.9 (C6H4),
156.5 (C-2), 158.5 (C-3), 161.1 (C-1), 169.0–169.9 (4 × CO). Anal. Calcd for
C26H30N2O11S2 (610.650): C, 51.1; H, 5.0; N, 4.6%. Found: C, 50.6; H, 5.2;
N, 4.6%.
(2Z) − N−(4-Chlorophenyl)-2-cyano-3-(methylthio)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl
-β-D-galactopyranosylthio)acrylamide(9h): yellow crystals, m.p. 193◦C, 70%
method A, 78% method B, [α]D+36.5, IR (KBr) νmax/cm–13271 (NH), 2206
(CN), 1751 (CO of ester), 1674 (CO of amide).1H NMR δ 2.00–2.10 (4s, 12H,
4 × CH3CO), 2.60 (s, 3H, CH3), 4.00–4.10 (m, 3H, H-6aꢀ, H-6bꢀ, H-5ꢀ), 4.20
ꢀ
ꢀ
ꢀ
(t, 1H, H-4 ), 5.00 (t, 1H, H-3 ), 5.10 (t, 1H, H-2 ), 5.50 (d, J1 −2 = 9.88, 1H,1ꢀ-
H), 7.40–7.70 (dd, 4H, C6H4), 10.80 (s, 1H, NH). 13C NMR δ 18.3 (SCH3),
20.2–26.7 (4 × CH3), 61.8 (CH2, C-6ꢀ), 67.7 (C-4ꢀ), 69.4 (C-2ꢀ), 72.6 (C-3ꢀ),
74.7 (C-5ꢀ), 84.8 (C-1ꢀ), 115.1 (CN), 119.7–136.8 (C6H4), 156.5 (C-2), 158.5
(C-3), 161.1 (C-1), 169.0–169.9 (4 × CO). Anal. Calcd for C25H27ClN2O10S2
(615.069): C, 48.8; H, 4.4; N, 4.6%. Found: C, 48.1; H, 4.2; N, 4.1%.
ꢀ
ꢀ
Sodium N-aryl-2-cyano-3-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-β-D-gluco or
galactopyranosylthio)acrylamide-3-thiolates (10a–h)
General procedure
Compounds 2 (0.01 mol) were treated as described for the preparation of
8a–h. The reaction was completed within 9 h (TLC, CHCl3:CH3OH, 9:1).
Sodium
2-cyano-N-phenyl-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-gluco-pyranosyl-
thio) acrylamide-3-thiolate (10a): yellow crystals, m.p. <300◦C, 78%,
[α]D+19.5, IR (KBr) νmax/cm–13440 (NH), 2098 (CN), 1751 (CO).
C24H25N2O10S2Na (588.579).
Sodium 2-cyano-N-(4-methylphenyl)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-glucopy-
ranosylthio)acrylamide-3-thiolate (10b): yellow crystals, m.p. <300◦C,
–1
80%, [α]D+25.5, IR (KBr) νmax/cm
3448 (NH), 2183 (CN), 1751 (CO).
C25H27N2O10S2Na (602.606).
Sodium 2-cyano-N-(4-methoxyphenyl)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-gluco-
pyranosylthio)acrylamide-3-thiolate (10c): yellow crystals, m.p. <300◦C,
76%, [α]D+27.0, IR (KBr) νmax/cm–13417 (NH), 2191 (CN), 1751 (CO).
C25H27N2O11S2Na (618.605).
Sodium N-(4-chlorophenyl)-2-cyano-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-glucopy-
ranosylthio)acrylamide-3-thiolate (10d): yellow crystals, m.p. <300◦C,
85%, [α]D+20.5, IR (KBr) νmax/cm–13446 (NH), 2186 (CN), 1751 (CO).
C24H24ClN2O10S2Na (623.024).

G.H. Elgemeie et al.
172
Sodium 2-cyano-N-phenyl-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-galacto-pyranosyl-
thio)acrylamide-3-thiolate (10e): yellow crystals, m.p. <300◦C, 77%,
[α]D+36.0, IR (KBr) νmax/cm–13479 (NH), 2113 (CN), 1750 (CO).
C24H25N2O10S2Na5 (88.579).
Sodium 2-cyano-N-(4-methylphenyl)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-galactop-
yranosylthio)acrylamide-3-thiolate (10f): yellow crystals, m.p. <300◦C,
79%, [α]D+30.0, IR (KBr) νmax/cm–13217 (NH), 2191 (CN), 1751 (CO).
C25H27N2O10S2Na (602.606).
Sodium 2-cyano-N-(4-methoxyphenyl)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-galac-
topyranosylthio)acrylamide-3-thiolate (10g): yellow crystals, m.p. <300◦C,
75%, [α]D+20.5, IR (KBr) νmax/cm–13417 (NH), 2183 (CN), 1751 (CO).
C25H27N2O11S2Na (618.605).
Sodium N-(4-chlorophenyl)-2-cyano-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-galactop-
yranosylthio)acrylamide-3-thiolate (10h): yellow crystals, m.p. <300◦C,
85%, [α]D+29.5, IR (KBr) νmax/cm–13417 (NH), 2183 (CN), 1743 (CO).
C24H24ClN2O10S2Na (623.024).
2-Cyano-3,3-dimercapto-N-arylacrylamides (11a–d)
General procedure
A solution of compounds 2 (0.01 mol) in ethanol (20 mL) was poured onto
cold water and treated with hydrochloric acid until just acidic and the formed
solid products were collected by filtration and recrystallized from ethanol.
N-Aryl-2-cyano-3-mercapto-3-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-β-
D-gluco or galactopyranosylthio)acrylamides (12a–h)
General procedures
Method A. A solution of compounds 10 (0.01 mol) in ethanol (30 mL) was
poured onto cold water and the medium was adjusted to pH 7 using dilute
acetic acid. The formed solid products were collected by filtration and recrys-
tallized from ethanol.
Method B. A solution of compounds 11 (0.01 mol) in aq. potassium
hydroxide [0.56g (0.01 mol) in distilled water (6mL)] was added to a solution of
5a,b (4.10g, 0.01 mol) in acetone (30 mL). The reaction mixture was stirred at
rt until completion (TLC, CHCl3:CH3OH, 9:1, 9 h) and then evaporated under
reduced pressure, and the residue was washed with distilled water to remove
the formed potassium bromide. The resulting products were crystallized from
ethanol.

First Synthesis of Thiophene Thioglycosides
173
2-Cyano-3-mercapto-N-phenyl-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-glucopy-
ranosylthio)acrylamide (12a): yellow crystals, m.p. 231◦C, 73% method A,
80% method B, [α]D+47.5, IR (KBr) νmax/cm–13286 (NH), 2507 (SH), 2183
(CN), 1751 (CO). 1H NMR δ 1.95–2.05 (4s, 12H, 4 × CH3CO), 3.95–4.10
(m, 3H, H-6aꢀ, H-6bꢀ, H-5ꢀ), 4.95 (t, 1H, H-4ꢀ), 5.30–5.40 (m, 2H, H-3ꢀ, H-2ꢀ),
5.90 (d, J1 −2 = 9.80, 1H, H-1ꢀ), 7.00–7.70 (m, 5H, C6H5), 9.60 (s, 1H, NH),
10.40 (s, 1H, SH).Anal. Calcd for C24H26N2O10S2 (566.597): C, 50.9; H, 4.6;
N, 4.9%. Found: C, 51.0; H, 5.1; N, 4.7%.
ꢀ
ꢀ
2-Cyano-3-mercapto-N-(4-methylphenyl)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-ace-tyl-β-D-
glucopyranosylthio)acrylamide (12b): yellow crystals, m.p. 179◦C, 78%
method A, 85% method B, [α]D+19.5, IR (KBr) νmax/cm–13294 (NH), 2499
1
(SH), 2198 (CN), 1751 (CO). H NMR δ 1.95–2.00 (4s, 12H, 4 × CH3CO),
2.30 (s, 3H, CH3), 3.95 (s, 2H, H-6aꢀ, H-6ꢀbꢀ), 4.15 (m, 1H, H-5ꢀ), 4.95 (t, 1H,
ꢀ
ꢀ
H-4 ), 5.10 (t, 1H, H-3 ), 5.35 (t, 1H, H-2 ), 6.00 (d, J1 −2 = 9.65, 1H, H-1ꢀ),
7.10–7.40 (dd, 4H, C6H4), 9.80 (s, 1H, NH), 10.70 (s, 1H, SH). 13C NMR
δ 17.0 (Ar-CH3), 18.0–20.9 (4 × CH3), 62.0 (CH2, C-6ꢀ), 68.4 (C-4ꢀ), 68.8
(C-2ꢀ), 74.1 (C-3ꢀ), 75.1 (C-5ꢀ), 83.6 (C-1ꢀ), 119.5 (CN), 125.0–137.0 (C6H4),
159.8 (C-2), 160.0 (C-3), 162.2 (C-1), 169.5–170.1 (4 × CO). Anal. Calcd for
C25H28N2O10S2 (580.624): C, 51.7; H, 4.9; N, 4.8%. Found: C, 51.2; H, 4.7;
N, 4.8%.
ꢀ
ꢀ
2-Cyano-3-mercapto-N-(4-methoxyphenyl)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
glucopyranosylthio)acrylamide (12c): yellow crystals, m.p. 155◦C, 74%
method A, 79% method B, [α]D+37.5, IR (KBr) νmax/cm–13230 (NH), 2530
1
(SH), 2206 (CN), 1751 (CO). H NMR δ 1.95–2.10 (4s, 12H, 4 × CH3CO),
3.70 (s, 3H, OCH3), 3.80 (s, 2H, H-6aꢀ, H-6bꢀ), 4.15 (m, 1H, H-5ꢀ), 5.00 (t,
ꢀ
ꢀ
ꢀ
1H, H-4 ), 5.10–5.50 (m, 2H, H-3 , H-2 ), 6.00 (d, J1 −2 = 10.00, 1H, H-1ꢀ),
6.90–7.50 (dd, 4H, C6H4).13C NMR δ 13.7–20.9 (4 × CH3), 55.5 (OCH3), 61.8
(CH2, C-6ꢀ), 68.4 (C-4ꢀ), 68.8 (C-2ꢀ), 74.1 (C-3ꢀ), 75.1 (C-5ꢀ), 83.6 (C-1ꢀ), 112.7
(CN), 114.4–128.4 (C6H4), 159.8 (C-2), 160.2 (C-3), 162.2 (C-1), 169.5–170.1
(4 × CO). Anal. Calcd for C25H28N2O11S2 (596.623): C, 50.3; H, 4.7; N, 4.7%.
Found: C, 49.7; H, 4.7; N, 4.2%.
ꢀ
ꢀ
N-(4-Chlorophenyl)-2-cyano-3-mercapto-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-ace-tyl-β-D-
glucopyranosylthio)acrylamide (12d): yellow crystals, m.p. 183◦C, 80%
method A, 84% method B, [α]D+32.5, IR (KBr) νmax/cm–13294 (NH), 2550
(SH), 2198 (CN), 1751 (CO). 13C NMR δ 13.7–20.9 (4 × CH3), 62.0 (CH2,
C-6ꢀ), 68.4 (C-4ꢀ), 68.8 (C-2ꢀ), 74.1 (C-3ꢀ), 75.1 (C-5ꢀ), 83.5 (C-1ꢀ), 119.6 (CN),
120.7–129.0 (C6H4), 159.8 (C-2), 160.2 (C-3), 162.2 (C-1), 169.5–170.1 (4 ×
CO). Anal. Calcd for C24H25ClN2O10S2 (601.042): C, 48.0; H, 4.2; N, 4.7%.
Found: C, 47.8; H, 4.2; N, 4.2%.
2-Cyano-3-mercapto-N-phenyl-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-galactopy-
ranosylthio)acrylamide (12e): yellow crystals, m.p. 246◦C, 71% method

G.H. Elgemeie et al.
174
A, 77% method B, [α]D+46.5, IR (KBr) νmax/cm–13340 (NH), 2600 (SH),
2206 (CN), 1743 (CO). 1H NMR δ 1.90–2.15 (4s, 12H, 4 × CH3CO),
3.30 (s, 2H, H-6aꢀ, H-6bꢀ), 4.0ꢀ0 (m, 1H, H-5ꢀ), 4.25 (t, 1H, H-4ꢀ), 5.20
ꢀ
(t, 1H, H-3 ), 5.35 (t, 1H, H-2 ), 5.80 (d, J1 −2 = 9.70, 1H, H-1ꢀ), 7.70–
7.80 (m, C6H5), 10.30 (s, 1H, NH), 10.70 (s, 1H, SH). Anal. Calcd for
C24H26N2O10S2 (566.597): C, 50.9; H, 4.6; N, 4.9%. Found: C, 50.5; H, 4.9;
N, 4.7%.
ꢀ
ꢀ
2-Cyano-3-mercapto-N-(4-methylphenyl)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
galactopyranosylthio)acrylamide (12f): yellow crystals, m.p. 130◦C, 76%
method A, 82% method B, [α]D+41.0, IR (KBr) νmax/cm–13340 (NH), 2580
1
(SH), 2198 (CN), 1751 (CO). H NMR δ 1.90–2.20 (4s, 12H, 4 × CH3CO),
2.30 (s, 3H, CH3), 3.95 (s, 2H, H-6aꢀ, H-6ꢀbꢀ), 4.25 (m, 1H, H-5ꢀ), 5.10 (t, 1H,
ꢀ
ꢀ
H-4 ), 5.30 (t, 1H, H-3 ), 5.60 (t, 1H, H-2 ), 5.90 (d, J1 −2 = 9.98, 1H, H-1ꢀ),
7.10–7.50 (dd, 4H, C6H4), 9.70 (s, 1H, NH), 10.40 (s, 1H, SH). Anal. Calcd
for C25H28N2O10S2 (580.624): C, 51.7; H, 4.9; N, 4.8%. Found: C, 51.2; H,
5.6; N, 5.4%.
ꢀ
ꢀ
2-Cyano-3-mercapto-N-(4-methoxyphenyl)-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
galactopyranosylthio)acrylamide (12g): yellow crystals, m.p. 120◦C, 72%
method A, 79% method B, [α]D+19.0, IR (KBr) νmax/cm–13294 (NH), 2550
1
(SH), 2198 (CN), 1751 (CO). H NMR δ 1.90–2.20 (4s, 12H, 4 × CH3CO),
3.70 (s, 3H, OCH3), 3.80 (s, 2H, H-6aꢀ, H-6bꢀ), 4.00 (m, 1H, H-5ꢀ), 4.25
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(t, 1H, H-4 ), 4.95 (t, 1H, H-3 ), 5.30 (t, 1H, H-2 ), 5.95 (d, J1 −2 = 9.68,
1H, H-1ꢀ), 6.90–7.60 (dd, 4H, C6H4), 10.00 (s, 1H, NH). Anal. Calcd for
C25H28N2O11S2 (596.623): C, 50.3; H, 4.7; N, 4.7%. Found: C, 49.8; H, 4.9; N,
4.2%.
N-(4-Chlorophenyl)-2-cyano-3-mercapto-3-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
galactopyranosylthio)acrylamide (12h): yellow crystals, m.p. 120◦C, 79%
method A, 82% method B, [α]D+28.5, IR (KBr) νmax/cm–13240 (NH), 2491
(SH), 2198 (CN), 1751 (CO). Anal. Calcd for C24H25ClN2O10S2 (601.042): C,
48.0; H, 4.2; N, 4.7%. Found: C, 47.6; H, 4.1; N, 4.5%.
Sodium 4-amino-5-benzoyl-N-arylthiophene-3-carboxamide-
2-thiolates (13a–e)
General procedure
A solution of compounds 3 (0.01 mol) was refluxed with (0.23g, 0.01 mol)
sodium ethoxide in (20 mL) ethanol for 2 h, the solution was evaporated, and
the formed solid product was collected by filtration.

First Synthesis of Thiophene Thioglycosides
175
4-Amino-5-benzoyl-2-mercapto-N-arylthiophene-
3-carboxamides (14a–e)
General procedure
A solution of compounds 3 (0.01 mol) was refluxed with sodium ethoxide
(0.23 g, 0.01 mol) in ethanol (20 mL) for 2 h, then poured on cold water and
treated with hydrochloric acid until just acidic, and the formed solid products
were collected by filtration and recrystallized from ethanol.
4-Amino-N–aryl-5-benzoyl-2-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-β-D-gluco
or galactopyranosylthio)thiophene-3-carboxamides (15a–h)
General procedures
Method A. To a solution of compounds 13 (0.01 mol) in ethanol (30 mL), a
solution of 5a,b (4.10 g, 0.01 mol) in acetone (20 mL) was added. The reaction
mixture was stirred at rt until completion (TLC, CHCl3:CH3OH, 9:1, 14 h) and
then evaporated under reduced pressure and the residue was washed with
distilled water to remove the sodium bromide formed. The resulting product
was crystallized from ethanol.
Method B. A solution of compounds 14 (0.01 mol) in aq. potassium hy-
droxide [0.56g (0.01 mol) in distilled water (6mL)] was added to a solution of
5a,b (4.10g, 0.01 mol) in acetone (30 mL). The reaction mixture was stirred
at rt until completion (TLC, CHCl3:CH3OH, 9:1, 14 h) and then evaporated
under reduced pressure and the residue was washed with distilled water to
remove the formed potassium bromide salt. The resulting product was crystal-
lized from ethanol.
4-Amino-5-benzoyl-N-phenyl-2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-glu-copyran-
osylthio)thiophene-3-carboxamide (15a): brown crystals, m.p. 230◦C, 61%
method A, 70% method B, [α]D+27.5, IR (KBr) νmax/cm–13440, 3325
(NH2), 1751 (CO), 1680 (CO), 1658 (CO). 1H NMR δ 1.70–1.95 (4s, 12H,
4 × CH3CO), 3.90 (s, 2H, H-6aꢀ, H-6bꢀ), 4.05 (m, 1H, H-5ꢀ), 4.85–4.95
(m, 2H, H-4ꢀ, H-3ꢀ), 5.25–5.35 (m, 2H, H-2ꢀ, H-1ꢀ), 7.10–7.80 (m, 12H, 2
C6H5 and NH2), 10.30 (s, 1H, NH). 13C NMR δ 20.4–20.7 (4 × CH3), 62.2
(CH2, C-6ꢀ), 68.2 (C-4ꢀ), 69.8 (C-2ꢀ), 73.0 (C-3ꢀ), 74.8 (C-5ꢀ), 85.2 (C-1ꢀ),
109.9–154.7 (aromatic carbons), 160.9–187.0 (6 × CO). Anal. Calcd for
C32H32N2O11S2 (684.732): C, 56.1; H, 4.7; N, 4.1%. Found: C, 55.7; H, 5.2;
N, 3.8%.
4-Amino-5-benzoyl-N-(4-methylphenyl)-2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
glucopyranosylthio)thiophene-3-carboxamide (15b): brown crystals, m.p.
216◦C, 65% method A, 73% method B, [α]D+30.5, IR (KBr) νmax/cm–13447,

G.H. Elgemeie et al.
176
3325 (NH2), 1748 (CO), 1685 (CO), 1637 (CO). 1H NMR δ 1.70–2.00 (4s,
12H, 4 × CH3CO), 2.25 (s, 3H, CH3), 3.90 (s, 2H, H-6aꢀ, H-6bꢀ), 4.05 (m, 1H,
H-5ꢀ), 4.85 (m, 2H, H-4ꢀ, H-3ꢀ), 5.30–5.40 (m, 2H, H-2ꢀ, H-1ꢀ), 7.10–8.10 (m,
11H, C6H5, C6H4and NH2), 10.20 (s, 1H, NH). 13C NMR δ 20.1–20.5 (4 ×
CH3), 62.0 (CH2, C-6ꢀ), 67.8 (C-4ꢀ), 69.80 (C-2ꢀ), 73.5 (C-3ꢀ), 74.5 (C-5ꢀ), 84.9
(C-1ꢀ), 110.0–155.0 (aromatic carbons), 159.9–186.0 (6 × CO). Anal. Calcd
for C33H34N2O11S2 (698.758): C, 56.7; H, 4.9; N, 4.0%. Found: C, 57.0; H,
5.2; N, 4.7%.
4-Amino-5-benzoyl-N-(4-methoxyphenyl)-2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
glucopyranosylthio)thiophene-3-carboxamide (15c): brown crystals, m.p.
204◦C, 68% method A, 76% method B, [α]D+40.5, IR (KBr) νmax/cm–13448,
3325 (NH2), 1751 (CO), 1675 (CO), 1635 (CO). 1H NMR δ 1.70–1.95 (4s,
12H, 4 × CH3CO), 3.75 (s, 3H, OCH3), 3.95 (s, 2H, H-6aꢀ, H-6bꢀ), 4.05 (m,
1H, H-5ꢀ), 4.90 (m, 2H, H-4ꢀ, H-3ꢀ), 5.30–5.40 (m, 2H, H-2ꢀ, H-1ꢀ), 6.80–7.80
(m, 11H, C6H5, C6H4 and NH2), 10.10 (s, 1H, NH). 13C NMR δ 19.7–20.9 (4
× CH3), 61.7 (CH2, C-6ꢀ), 66.9 (C-4ꢀ), 68.6 (C-2ꢀ), 74.2 (C-3ꢀ), 75.9 (C-5ꢀ), 86.0
(C-1ꢀ), 108.7–150.0 (aromatic carbons), 161.0–180.0 (6 × CO). Anal. Calcd
for C33H34N2O12S2 (714.758): C, 55.44; H, 4.75; N, 3.91%. Found: C, 55.33;
H, 5.17; N, 3.60%.
4-Amino-5-benzoyl-N-(4-chlorophenyl)-2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
glucopyranosylthio)thiophene-3-carboxamide (15d): brown crystals, m.p.
250◦C, 69% method A, 77% method B, [α]D+40.0, IR (KBr) νmax/cm–13433,
3332 (NH2), 1751 (CO), 1670 (CO), 1651 (CO). 1H NMR δ 1.65–1.95 (4s,
12H, 4 × CH3CO), 3.95 (m, 3H, H-6aꢀ, H-6bꢀ,H-5ꢀ), 4.90 (t, 1H, H-4ꢀ), 5.00
(t, 1H, H-3ꢀ), 5.30–5.35 (m, 2H, H-2ꢀ, H-1ꢀ), 6.90–7.80 (m, 11H, C6H5, C6H4
and NH2), 10.20 (s, 1H, NH).13C NMR δ 20.0–21.6 (4 × CH3), 62.0 (CH2,
C-6ꢀ), 68.0 (C-4ꢀ), 69.3 (C-2ꢀ), 73.5 (C-3ꢀ), 75.8 (C-5ꢀ), 85.0 (C-1ꢀ), 111.0–155.9
(aromatic carbons), 160.0–185.0 (6 × CO). Anal. Calcd for C32H31ClN2O11S2
(719.177): C, 53.4; H, 4.3; N, 3.9%. Found: C, 53.8; H, 4.6; N, 3.4%.
4-Amino-5-benzoyl-N-phenyl-2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-gal-
actopyranosylthio)thiophene-3-carboxamide (15e): brown crystals, m.p.
195◦C, 60% method A, 70% method B, [α]D+32.5, IR (KBr) νmax/cm–13440,
3348 (NH2), 1751 (CO), 1680 (CO), 1658 (CO).1H NMR δ 1.60–2.00 (4s,
12H, 4 × CH3CO), 3.95 (s, 2H, H-6aꢀ, H-6bꢀ), 4.30 (m, 1H, H-5ꢀ), 5.00 (t, 1H,
H-4ꢀ), 5.20–5.30 (m, 3H, H-3ꢀ, H-2ꢀ, H-1ꢀ), 7.10–7.80 (m, 12H, 2 C6H5and
NH2), 10.30 (s, 1H, NH). 13C NMR δ 20.4–20.6 (4 × CH3), 61.9 (CH2, C-6ꢀ),
67.2 (C-4ꢀ), 67.8 (C-2ꢀ), 71.0 (C-3ꢀ), 74.2 (C-5ꢀ), 85.5 (C-1ꢀ), 109.8–154.7 (aro-
matic and carbons), 160.9–187.0 (6 × CO). Anal. Calcd for C32H32N2O11S2
(684.732): C, 56.1; H, 4.7; N, 4.1%. Found: C, 56.5; H, 4.5; N, 3.8%.
4-Amino-5-benzoyl-N-(4-methylphenyl)-2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
galactopyranosylthio)thiophene-3-carboxamide (15f): brown crystals, m.p.

First Synthesis of Thiophene Thioglycosides
177
160◦C, 64% method A, 72% method B, [α]D+45.0, IR (KBr) νmax/cm–13440,
3355 (NH2), 1751 (CO), 1690 (CO), 1658 (CO). 1H NMR δ 1.70–2.00 (4s,
12H, 4 × CH3CO), 2.15 (s, 2H, NH2), 2.30 (s, 3H, CH3), 3.40 (s, 2H, H-6aꢀ,
H-6bꢀ), 3.95 (m, 1H, H-5ꢀ), 4.20 (t, 1H, H-4ꢀ), 4.90 (t, 1H, H-3ꢀ), 5.10–5.30
(m, 2H, H-2ꢀ, H-1ꢀ), 7.00–8.00 (m, 9H, C6H5, C6H4), 10.20 (s, 1H, NH).13C
NMR δ 20.4–20.9 (5 × CH3), 61.9 (CH2, C-6ꢀ), 67.2 (C-4ꢀ), 67.8 (C-2ꢀ), 71.0
(C-3ꢀ), 74.2 (C-5ꢀ), 85.5 (C-1ꢀ), 109.8–154.7 (aromatic carbons), 160.8–187.0
(6 × CO). Anal. Calcd for C33H34N2O11S2 (698.758): C, 56.7; H, 4.9; N, 4.0%.
Found: C, 56.8; H, 4.7; N, 4.1%.
4-Amino-5-benzoyl-N-(4-methoxyphenyl)-2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
galactopyranosylthio)thiophene-3-carboxamide (15g): brown crystals, m.p.
167◦C, 68% method A, 78% method B, [α]D+35.5, IR (KBr) νmax/cm–13440,
3332 (NH2), 1680 (CO), 1751 (CO), 1643 (CO).1H NMR δ 1.70–2.05 (4s,
12H, 4 × CH3CO), 3.75 (s, 3H, OCH3), 3.95 (m, 3H, H-6aꢀ, H-6bꢀ, H-5ꢀ), 4.30
(t, 1H, H-4ꢀ), 5.00 (t, 1H, H-3ꢀ), 5.20–5.30 (m, 2H, H-2ꢀ, H-1ꢀ), 6.95–7.80 (m,
9H, C6H5, C6H4), 10.20 (s, 1H, NH). 13C NMR δ 20.4–20.6 (4 × CH3), 55.6
(OCH3), 61.9 (CH2, C-6ꢀ), 67.2 (C-4ꢀ), 67.8 (C-2ꢀ), 71.1 (C-3ꢀ), 74.2 (C-5ꢀ), 85.5
(C-1ꢀ), 109.7–154.7 (aromatic carbons), 160.7–187.0 (6 × CO). Anal. Calcd
for C33H34N2O12S2 (714.758): C, 55.4; H, 4.8; N, 3.9%. Found: C, 55.6; H,
5.2; N, 3.7%.
4-Amino-5-benzoyl−N-(4-bromophenyl)-2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
galactopyranosylthio)thiophene-3-carboxamide (15h): brown crystals, m.p.
210◦C, 70% method A, 78% method B, [α]D+31.5, IR (KBr) νmax/cm–13440,
3348 (NH2), 1751 (CO), 1665 (CO), 1658 (CO).1H NMR δ 1.64–1.94 (4s, 12H,
4 × CH3CO), 3.91 (s, 2H, H-6aꢀ, H-6bꢀ), 4.06 (m, 1H, H-5ꢀ), 4.80–4.90 (m, 2H,
H-4ꢀ, H-3ꢀ), 5.24–5.35 (m, 2H, H-2ꢀ, H-1ꢀ), 7.38–7.75 (m, 9H, C6H5, C6H4),
10.40 (s, 2H, NH2), 10.67 (s, 1H, NH).13C NMR δ 18.4–19.9 (4 × CH3),
62.0 (CH2, C-6ꢀ), 68.0 (C-4ꢀ), 69.4 (C-2ꢀ), 73.2 (C-3ꢀ), 74.5 (C-5ꢀ), 86.0 (C-1ꢀ),
105.0–150.2 (aromatic carbons), 163.0–181.4 (6 × CO). Anal. Calcd for
C33H31BrN2O11S2 (775.639): C, 50.4; H, 4.1; N, 3.7%. Found: C, 49.7; H, 4.6;
N, 3.1%.
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