A new approach for the N- and S-galactosylation of 5-arylidene-2-thioxo-4- thiazolidinones

Article abstract of DOI:10.1016/j.carres.2011.09.035

N- and S-galactosylation was carried out via the reaction of 5-((Z)-arylidene)-2-thioxo-4-thiazolidinones with 2,3,4,6-tetra-O-acetyl- α-d-galactopyranosyl bromide under alkaline conditions or under silylation conditions. Deacetylation of the N-galactosyl

Full text of DOI:10.1016/j.carres.2011.09.035

Carbohydrate Research 346 (2011) 2831–2837
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
A new approach for the N- and S-galactosylation of
5-arylidene-2-thioxo-4-thiazolidinones
Ahmed I. Khodair a, , Jean-Pierre Gesson b
⇑
a Chemistry Department, Faculty Science, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt
b Laboratoire Synthèse et Réactivité des Substances Naturelles, Université de Poitiers, CNRS-UMR 6514, 40 Avenue du Recteur Pineau, Poitiers F-86022, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 June 2011
Received in revised form 7 September 2011
Accepted 14 September 2011
Available online 18 October 2011
N- and S-galactosylation was carried out via the reaction of 5-((Z)-arylidene)-2-thioxo-4-thiazolidinones
with 2,3,4,6-tetra-O-acetyl-a-D-galactopyranosyl bromide under alkaline conditions or under silylation
conditions. Deacetylation of the N-galactosylation products was performed with concentrated hydrochlo-
ric acid in methanol (3.5%) or sodium methoxide in methanol without cleavage of the 2-thioxo-4-thaizo-
lidinone ring by means of acid hydrolysis. The anomers were separated by flash column chromatography,
and their configurations were assigned by NMR spectroscopy. The deprotected nucleosides were
screened against leukemia L-1210 and were found inactive.
Keywords:
2-Thioxo-4-thiazolidinone
2,3,4,6-Tetra-O-acetyl-
Ó 2011 Elsevier Ltd. All rights reserved.
a-D-galactopyranosyl
bromide
N-galactosylation
S-galactosylation
Antileukemic activity
1. Introduction
S-galactosyl derivatives of 2-thioxo-4-thiazolidinones have been
prepared via new synthetic strategies. The previous work of
The chemistry of 2-thioxo-4-thiazolidinone and its derivatives
has been studied for over half a century because of its important
chemical and biological applications. Derivatives of 2-thoxo-4-
thiazolidinone have been demonstrated to possess antibacterial,1–4
antifungal,5,6 anticonvulsant,7 anticancer,8 antituberculosis,9 anti-
human immunodeficiency virus type 1 (HIV-1),10–12 antimicro-
Metwally et al.13 was successful in preparing N-glycosyl deriva-
tives of 2-thioxo-4-thiazolidinones without the S-glycosylation of
2-thioxo-4-thiazolidinone. At the same time, they did not succeed
in the synthesis of the corresponding deprotected N-glycosyl deriv-
atives of 2-thioxo-4-thiazolidinone.
bial,13
antidiabetic,14
antitubercular,15,16
antiparasitic,17
2. Results and discussion
hypnotic,18 and anthelmintic activities.19 2-Thioxo-4-thiazolidi-
nones also act as analogs of purine bases in nucleic acid synthesis.20
During the last decade thiazole nucleoside analogs have been recog-
nized as potent and increasingly important antimetabolite
agents.21,22 N-Galactosyl derivatives of 2-thioxo-4-thiazolidinones
2-Thioxo-4-thiazolidinone (1) was condensed with the appro-
priate aromatic aldehydes (2a–f) in ethanol in the presence of
piperidine as catalyst at room temperature to afford the corre-
sponding
5-((Z)-arylidene)-2-thioxo-4-thiazolidinones
(3a–f)
are not very well known, but N-(b-D-glucopyranosyl)-5-(4-nitro-
(Scheme 1).
benzylidene)-2-thioxo-4-thiazolidinone showed antiviral activity
by inhibition of viral RNA synthesis.23 Glycosyl derivatives of struc-
turally similar heterocyclic systems have been reported before.24–28
In continuation of our work on the synthesis of novel nucleosides
as potential antiviral and antitumor agents, and keeping in mind
the biological significance of 2-thioxo-4-thiazolidinones,29–37 we
hereby report the synthesis, antitumor screening, and spectros-
copy of a series of N- and S-galactosylated analogs bearing 2-
thioxo-4-thiazolidinone bases. This is the first time that N- and
Treatment of 3a–f with 1.1 equiv of NaH in anhyd acetonitrile
furnished the sodium salts of 2-thioxo-4-thiazolidinones (4a–f),
which in turn were treated with 2,3,4,6-tetra-O-acetyl-a-D-galac-
topyranosyl bromide (6) to afford nitrogen protected nucleosides
8a–f and sulfur protected nucleosides 9a–f, respectively. The N-
isomers and S-isomers were isolated by silica gel column chroma-
tography. The protected nucleosides 8a and 9a were independently
synthesized through another pathway. The silylation of 3a was
accomplished with bis(trimethylsilyl)acetamide (BSA) in anhyd
acetonitrile at 70–80 °C. Similar conditions furnished the trimeth-
ylsilylated derivative 5a. This derivative 5a was condensed with
⇑
Corresponding author. Tel.: +20 403 35 58 18; fax: +20 473 21 51 75.
E-mail address: khodair_2005@yahoo.com (A.I. Khodair).
1,2,3,4,6-penta-O-acetyl-a-D-galactopyaranose (7) in the presence
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.09.035

2832
A. I. Khodair, J.-P. Gesson / Carbohydrate Research 346 (2011) 2831–2837
O
O
Ar
i
NH
S
NH
S
S
1
S
3a-f
2,3 Ar
2,3 Ar
a
b
c
Phenyl
d
e
f
3,4-Ethylenedioxphenyl
2-Thienyl
2-Hydroxy-3-methoxyphenyl
3,4-Methylenedioxphenyl
5-Bromo-2-thienyl
Scheme 1. Reagents and condition: (i) Ar-CHO (2a–f), piperidine, EtOH, rt.
of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as catalyst at
70–80 °C for 60 min. The protected nucleosides 8a and 9a were iso-
lated by silica gel column chromatography in 32% and 26% yields,
respectively.
In conclusion, we have carried out the successful synthesis
of hitherto unreported 5-((Z)-arylidene)-3-(20,30,40,60-tetra-O-
acetyl-b-
5-((Z)-arylidene)-2-(20,30,40,60-tetra-O-acetyl-b-
2-thioxo-4-thiazolidinones (9a–f), and
(b- -galactopyranosyl)-2-thioxo-4-thiazolidinones (10a–f). The
D-galactopyranosyl)-2-thioxo-4-thiazolidinones
(8a–f),
D-galactopyranosyl)-
The structures of 8a–f and 9a–f were established and confirmed
by elemental analyses and spectral data (IR, 1H NMR, 13C NMR and
MS). The absence of a signal for NH and the presence of signal for
the thiocarbonyl group at vmax 1210–1240 cmꢀ1 were characteristic
of the IR absorption spectra of 8a–f, while the IR absorption spectra
of 9a–f were characterized by the absence of signals for the NH and
CS groups. The 1H NMR (CDCl3) spectrum of compound 8d showed a
singlet at dH 7.62 assigned to the vinyl proton, indicating the pres-
ence of a Z-configuration for the exocyclic double bond and subse-
quent N-glycosylation. This is in agreement with the 1H NMR
(CDCl3) spectrum of 5-((Z)-benzylidene)-3-methyl-2-thioxo-4-
thiazolidinone whose vinyl proton appears at dH 7.75.38 The ano-
meric proton appears as a doublet at dH 6.30 (J = 9.4 Hz), indicating
5-((Z)-arylidene)-3-
D
conformational analyses of their most stable configurations were
established by NMR spectroscopy. Compounds 10a–f were screened
against leukemia-1210 and were found to be inactive.41,42 The antivi-
ral and further antitumor activities of the new prepared compounds
are under investigation and will be reported in due time.
3. Experimental
3.1. General procedures
Melting points were determined on a Büchi apparatus and are
uncorrected. TLC was carried out on aluminum backed Silica Gel
60 F254 (E. Merck) plates and detected by shortwave UV light. IR
spectra were obtained as potassium bromide pellets using a Pye
Unicam spectrometer 1000. 1H NMR and 13C NMR spectra were
measured on a Bruker Avance DPX 300 MHz spectrometer in
DMSO-d6 or CDCl3 using TMS as the internal standard. Chemical
shifts are given in d units (ppm) and J values in Hz. Analytical data
were obtained using a Carlo Erba 1106 C,H,N elemental analyzer.
Mass spectra were recorded by EI on a Varian MAT 112 spectrom-
eter and FAB on a Kratos MS spectrometer.
the presence of the b-D-galactopyranose moiety and N-glycosyla-
tion. The 13C NMR (CDCl3) spectrum of 8d showed a singlet at dC
166.36 and 194.4 assigned to the carbonyl carbon at C-4 and the
thiocarbonyl group at C-2, respectively. These data are also in
agreement with the 13C NMR (CDCl3) spectrum of 5-((Z)-hexylid-
ene-4-oxo-2-thioxo-thiazolidinyl)acetic acid,39 since the carbonyl
at C-4 appears at dC 165.7 and the thiocarbonyl group at C-2 appears
at dC 194.8, indicating the presence of N-glycosylation. The 1H NMR
(CDCl3) spectrum of compound 9d showed a singlet at dH 7.78 as-
signed to the vinyl proton, indicating the presence of a Z-configura-
tion for the exocyclic double bond and S-glycosylation. This is in
agreement with the 1H NMR (CDCl3) spectrum of 5-((Z)-benzyli-
dene)-2-allylmercapto-4-thiazolidinone whose vinyl proton ap-
pears at dH 7.84.40 The anomeric proton appears as a doublet at dH
3.2. 5-((Z)-Arylidene)-2-thioxo-4-thiazolidinones (3a–f).
General procedure
5.98 (J = 10.4 Hz), indicating the presence of the b-D-galactopyran-
To a mixture of 2-thioxo-4-thiazolidinone (1) (1.33 g, 10 mmol),
anhyd piperidine (0.9 g, 10 mmol) and anhyd EtOH (30 mL) were
added the appropriate aromatic aldehydes (2a–f) (11 mmol). The
mixture was stirred until the starting material was consumed
(12 h; TLC). The reaction mixture was diluted with water and neu-
tralized with dilute hydrochloric acid. The yellow solid that sepa-
rated was collected by filtration and recrystallized from ethanol
to give the products 3a–f in quantitative yields.
osyl moiety and S-glycosylation. The 13C NMR (CDCl3) spectrum
of 9d showed a singlet at dC 179.1 and 188.6 assigned to the car-
bonyl at C-4 and the thiocarbonyl group at C-2, respectively. These
data are also in agreement with the 13C NMR (CDCl3) spectrum of 5-
((Z)-benzylidene)-2-allylmercapto-4-thiazolidinone,40 since the
carbonyl at C-4 appears at dC 179.8 and the thiocarbonyl group at
C-2 appears at dC 191.8, indicating the presence of S-glycosylation.
Removal of the acetyl groups from the glycon moiety of 8a–f
with a solution of concd HCl–MeOH (2%) at 50 °C for 2 h or
NaOMe–MeOH at room temperature furnished 5-((Z)-arylidene)-
3.2.1. Preparation of 5-((Z)-benzylidene)-2-thioxo-4-
thiazolidinone (3a)
Yield 2.00 g (90%); mp 205–206 °C (lit.40 yield 95%, mp 208–
3-(b-D-galactopyranosyl)-2-thioxo-4-thiazolidinones (10a–f), indi-
210 °C); IR:
m ;
3190 (NH), 1726 (C@O) cmꢀ1 1H NMR (300 MHz,
cating the presence of N-glycosylation. Correspondingly, when the
protected nucleoside 9c was treated with concd HCl–MeOH (10%)
at 50 °C or NaOMe–MeOH at room temperature. 5-((Z)-Methylene-
dioxy-benzylidene)-2,4-thazolidinedione (11) was obtained, indi-
cating the presence of S-glycosylation. This type of cleavage
explains why we were not successful in the preparation of the cor-
responding deprotected nucleosides of 9a–f (Scheme 2). The nucle-
oside bases 1 and 3 can be utilized as starting materials for the
synthesis of other carbohydrate derivatives such as deoxy, amino,
and azido nucleosides.
DMSO-d6): d 7.49–7.59 (m, 5H, Ar-H), 7.62 (s, 1H, @CH), 13.85 (s,
1H, NH); 13C NMR (300 MHz, DMSO-d6): d 125.90 (@CH), 129.84,
130.90, 131.14, 132.05, 133.36 (C-5, C-Ar), 169.76 (C-4), 196.07
(C-2).
3.2.2. Preparation of 5-((Z)-(2-hydroxy-3-methoxybenzylidene)-
2-thioxo-4-thiazolidinone (3b)
Yield 2.25 g (84%); mp 197–198 °C (lit.40 yield 86%, mp 194–
196 °C); IR:
m ;
3190 (NH), 1728 (C@O) cmꢀ1 1H NMR (300 MHz,

A. I. Khodair, J.-P. Gesson / Carbohydrate Research 346 (2011) 2831–2837
2833
O
O
O
Ar
Ar
Ph
iii
i
N
S
NH
N
S
S
S
S
S
Na
SiMe3
3a-f
4a-f
ii
5a
iv
Ar
O
Ar
N
S
S
OAc
OAc
AcO
S
O
+
S
N
OAc
OAc
AcO
O
O
OAc
9a-f
OAc
8a-f
v or vi
Ar
v or vi
S
O
O
O
S
O
N
NH
S
OH
OH
HO
O
O
OH
10a-f
11
3-10 Ar
3-10 Ar
a
b
c
Phenyl
d
e
f
3,4-Ethylenedioxphenyl
2-Thienyl
2-Hydroxy-3-methoxyphenyl
3,4-Methylenedioxphenyl
5-Bromo-2-thienyl
Scheme 2. Reagents and conditions: (i) CH3CN, NaH; (ii) 1,2,3,4,6-penta-O-acetyl-
a
-
D-galactopyranosyl bromide (6); (iii) CH3CN, BSA, 70–80 °C, 30 min; (iv) 1,2,3,4,6-penta-
O-acetyl-a-D-galactopyranose (7), TMSOTf, 70–80 °C, 60 min; (v), concd HCl–MeOH (3.5%), 0–50 °C, 2 h; (vi) NaOMe–MeOH, 0 °C, rt, 2 h.
DMSO-d6): d 3.86 (s, 3H, OMe), 6.86–7.15 (m, 3H, Ar-H), 7.94 (s, 1H,
@CH), 9.89 (s, 1H, OH), 13.72 (s, 1H, NH); 13C NMR (300 MHz,
DMSO-d6): d 56.23 (OMe), 114.43, 119.99, 120.50, 124.70, 127.19,
147.19, 148.26 (@CH, C-5, C-Ar), 170.10 (C-4), 196.42 (C-2).
(300 MHz, DMSO-d6): d 7.27 (d, J = 3.83 Hz, 1H, 40-H), 7.68 (t,
J = 3.70 Hz, 1H, 30-H), 7.90 (d, J = 3.78 Hz, 1H, 50-H), 8.05 (s, 1H,
@CH), 13.77 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6):
d
123.11, 124.86, 129.37, 134.37, 135.44, 137.56 (@CH, C-5, C-Ar),
169.11 (C-4), 194.68 (C-2).
3.2.3. Preparation of 5-((Z)-3,4-methylenedioxybenzylidene)-2-
thioxo-4-thiazolidinone (3c)
3.2.6. 5-[(Z)-(5-Bromo-2-thienylidene)]-2-thioxo-4-
thiazolidinone (3f)
Yield 2.45 g (92%); mp 211–212 °C (lit.43 yield 71%, mp 278–
279 °C); IR (KBr)
m
3194 (NH), 1732 (C@O) cmꢀ1
;
1H NMR
Yield 2.72 g (89%); mp 220–221 °C; IR (KBr)
m 3196 (NH), 1727
(300 MHz, DMSO-d6): d 6.13 (s, 2H, OCH2O), 7.12 (m, 3H, Ar-H),
7.56 (s, 1H, @CH) 13.67 (s, 1H, NH).
(C@O) cmꢀ1 1H NMR (300 MHz, DMSO-d6): d 7.12–7.37 (m, 2H,
;
Ar-H), 7.73 (s, 1H, @CH), 13.56 (s, 1H, NH); 13C NMR (300 MHz,
DMSO-d6): d 119.79 (@CH), 123.24 (C-5), 124.04, 132.14, 134.76,
139.25 (C-Ar), 168.91 (C-4), 193.77 (C-2); MS, m/z 306 (M+); Anal.
Calcd for C8H4BrNOS3 (306.23): C, 31.38; H, 1.32; N, 4.57. Found: C,
31.46; H, 1.60; N, 4.28.
3.2.4. 5-((Z)-3,4-Ethylenedioxybenzylidene)-2-thioxo-4-
thiazolidinone (3d)
Yield 2.62 g (94%); mp 207–208 °C; IR (KBr)
m 3196 (NH), 1736
(C@O) cmꢀ1 1H NMR (300 MHz, DMSO-d6): d 4.26 (m, 4H,
;
2 ꢁ OCH2), 6.94 (m, 3H, Ar-H), 7.38 (s, 1H, @CH) 13.65 (s, 1H,
NH); 13C NMR (300 MHz, DMSO-d6) d 64.14, 64.71 (2 ꢁ OCH2),
118.19, 119.35, 122.99, 124.57, 125.69, 126.40, 131.79, 143.89,
146.15 (C-Ar, @CH, C-5), 169.52 (C-4), 195.46 (C-2); MS, m/z 279
(M+); Anal. Calcd for C12H9NO3S2 (279.34): C, 51.60; H, 3.25; N,
5.01. Found: C, 51.86; H, 3.39; N, 4.76.
3.3. 5-((Z)-Benzylidene)-3-(20,30,40,60-tetra-O-acetyl-b-
galactopyranosyl)-2-thioxo-4-thiazolidinone (8a) and 5-((Z)-
benzylidene)-2-(20,30,40,60-tetra-O-acetyl-b-
-galactopyranosyl)-
D-
D
2-thioxo-4-thiazolidinone (9a). General procedures
3.3.1. Method A
3.2.5. Preparation of 5-((Z)-2-thienylidene)-2-thioxo-4-
thiazolidinone (3e)
5-((Z)-Benzylidene)-2-thioxo-4-thiazolidinone (3a) (1.10 g,
5.0 mmol) was suspended in anhyd MeCN (5 mL) at room temper-
ature. To this suspension was added NaH (50%, 0.26 g, 5 mmol),
and the mixture was stirred at room temperature for 30 min. The
Yield 2.15 g (95%); mp 220–221 °C; (lit.40 yield 89% mp 218–
220 °C); IR (KBr)
m ;
3198 (NH), 1727 (C@O) cmꢀ1 1H NMR

2834
A. I. Khodair, J.-P. Gesson / Carbohydrate Research 346 (2011) 2831–2837
mixture became clear after 15 min. 2,3,4,6-Tetra-O-acetyl-
a
-
D
-
3.3.3.1. Data for 8b.
IR (KBr) m ;
1750 (C@O), 1744 (C@O) cmꢀ1
galactopyranosyl bromide (6, 2.26 g, 5.50 mmol) was added, and
the mixture was stirred at room temperature for 12 h until the
starting material was consumed (TLC). The reaction mixture was
diluted with CH2Cl2 (200 mL), washed with cold satd aq NaHCO3
(200 mL) and water (2 ꢁ 100 mL), and dried over anhyd Na2SO4.
The mixture was concentrated in vacuo, and the residue was puri-
fied by flash chromatography (eluent 30–50% Et2O–petroleum
ether, bp 40–60 °C) to afford, respectively, 1.00 g (36%) of 8a and
0.85 g (31%) of 9a as yellow solids.
1H NMR (300 MHz, CDCl3): d 1.98 (s, 3H, Ac), 2.04 (s, 3H, Ac), 2.06
(s, 3H, Ac), 2.28 (s, 3H, Ac), 3.93 (s, 3H, OCH3), 4.10–4.26 (m, 3H, 50-
H, 60-H, 600-H), 5.24 (dd, J = 3.36, 9.90 Hz, 1H, 40-H), 5.52 (d,
J = 3.26 Hz, 1H, 30-H), 6.29 (t, J = 9.20 Hz, 1H, 20-H), 6.33 (d,
J = 9.60 Hz, 1H, 10-H), 6.47 (s, 1H, OH), 6.92 (m, 3H, Ar-H), 8.18 (s,
1H, @CH); 13C NMR (300 MHz, CDCl3): d 20.48, 20.61, 20.70,
20.73 (4Ac), 56.22 (OCH3), 61.47 (C-60), 65.68 (C-20), 66.79 (C-30),
71.63 (C-40), 73.53 (C-50), 81.16 (C-10), 112.91, 119.79, 120.07,
120.12, 121.02, 125.90, 146.32, 146.91 (C-Ar, @CH, C-5), 166.01
(C-4), 169.88, 170.10, 170.45, 170.53 (4Ac), 194.85 (C-2); MS: m/
z 597 (M+); Anal. Calcd for C25H27NO12S2 (597.60): C, 50.24; H,
4.55; N, 2.34. Found: C, 50.16; H, 4.90; N, 2.08.
3.3.2. Method B
5-((Z)-Benzylidene)-2-thioxo-4-thiazolidinone (3a) (1.10 g,
5 mmol) was suspended in anhyd acetonitrile (25 mL) and BSA
(1.25 mL, 5 mmol) was added, and the reaction mixture was heated
3.3.3.2. Data for 9b.
IR (KBr) m ;
1752 (C@O) cmꢀ1 1H NMR
(300 MHz, CDCl3): d 2.01 (s, 3H, Ac), 2.04 (s, 3H, Ac), 2.07 (s, 3H,
Ac), 2.18 (s, 3H, Ac), 3.94 (s, 3H, OCH3), 4.09–4.21 (m, 3H, 50-H,
60-H, 600-H), 5.16 (dd, J = 3.34, 9.91 Hz, 1H, 40-H), 5.41 (t,
J = 10.14 Hz, 1H, 20-H), 5.50 (d, J = 3.16 Hz, 1H, 30-H), 5.98 (d,
J = 10.40 Hz, 1H, 10-H), 6.32 (s, 1H, OH), 6.92–7.05 (m, 3H, Ar-H),
8.36 (s, 1H, @CH); MS: m/z 597 (M+); Anal. Calcd for C25H27NO12S2
(597.60): C, 50.24; H, 4.55; N, 2.34. Found: C, 50.33; H, 4.78; N,
2.14.
at 70–80 °C for 30 min. The 1,2,3,4,6-penta-O-acetyl-a-D-galacto-
pyranose (7,1.87 g, 5 mmol) dissolved in anhyd acetonitrile
(25 mL) was added to the reaction mixture via a cannula. Finally
TMSOTf (1.00 mL, 5 mmol) was added, and the reaction mixture
was heated at 70–80 °C for 60 min. Then satd NaHCO3 was added
to quench the reaction, and the resulting mixture was extracted
with CH2Cl2. The combined organic fractions were washed with
satd NaCl solution, dried over MgSO4, filtered, and evaporated to
dryness. The solid obtained was purified by flash chromatography
(eluent 10–50% Et2O–petroleum ether, bp 40–60 °C) to give,
respectively, 0.87 g (32%) of 8a and 0.71 g (26%) of 9a as yellow
solids.
3.3.4. 5-((Z)-3,4-Methylenedioxybenzylidene)-3-(20,30,40,60-tetra-
O-acetyl-b-
and 5-((Z)-3,4-methylenedioxybenzylidene)-2-(20,30,40,60-tetra-
O-acetyl-b- -galactopyranosyl)-2-thioxo-4-thiazolidinone (9c)
D-galactopyranosyl)-2-thioxo-4-thiazolidinone (8c)
D
Method A described for the synthesis of 8a was utilized using
1.32 g (5 mmol) of 3c instead of 3a as the starting material. The
product was purified by flash chromatography (eluent 30–50%,
Et2O–petroleum ether, bp 40–60 °C) to afford, respectively 1.80 g
(60%) of 8c and 0.90 g (30%) of 9c as yellow foams.
3.3.2.1. Data for 8a.
Mp 103–105 °C; IR (KBr) v 1749 (C@O)
cmꢀ1 1H NMR (300 MHz, CDCl3): d 1.92 (s, 3H, Ac), 1.99 (s, 3H,
;
Ac), 2.01 (s, 3H, Ac), 2.22 (s, 3H, Ac), 4.07–4.21 (m, 3H, 50-H, 60-H,
600-H), 5.20 (dd, J = 3.26, 9.14 Hz, 1H, 40-H), 5.48 (d, J = 3.17 Hz,
1H, 30-H), 6.23 (t, J = 9.21 Hz, 1H, 20-H), 6.30 (d, J = 9.15 Hz, 1H,
10-H), 7.43 (m, 5H, Ar-H), 7.71 (s, 1H, @CH); 13C NMR (300 MHz,
CDCl3): d 20.33, 20.47, 20.58 (4Ac), 61.31 (C-60), 65.54 (C-20),
66.65 (C-30), 71.42 (C-40), 73.44 (C-50), 82.06 (C-10), 120.54 (@CH),
130.80 (C-5), 129.24, 130.58, 133.04, 133.73 (C-Ar), 165.90 (C-4),
169.80 169.87, 170.25, 170.29 (4Ac), 194.03 (C-2); MS: m/z 551
(M+); Anal. Calcd for C24H25NO10S2 (551.59): C, 52.26; H, 4.57; N,
2.54. Found: C, 52.14; H, 4.80; N, 2.46.
3.3.4.1. Data for 8c.
IR (KBr) m ;
1750 (C@O), 1746 (C@O) cmꢀ1
1H NMR (300 MHz, CDCl3): d 1.97 (s, 3H, Ac), 2.03 (s, 3H, Ac), 2.06
(s, 3H, Ac), 2.27 (s, 3H, Ac), 4.10–4.24 (m, 3H, 50-H, 60-H, 600-H), 5.23
(dd, J = 3.36, 9.42 Hz, 1H, 40-H), 5.51 (d, J = 3.24 Hz, 1H, 30-H), 6.07
(s, 2H, OCH2O), 6.26 (t, J = 9.36 Hz, 1H, 20-H), 6.32 (d, J = 9.20 Hz,
1H, 10-H), 6.89–7.04 (m, 3H, Ar-H), 7.64 (s, 1H, @CH); 13C NMR
(300 MHz, CDCl3): d 20.48, 20.61, 20.72 (4Ac), 61.43 (C-60), 65.64
(C-20), 66.76 (C-30), 71.57 (C-40), 73.54 (C-50), 82.17 (C-10), 102.09
(OCH2O), 109.23, 109.36, 118.11, 127.51, 127.58, 133.93, 148.74,
150.21 (C-Ar, @CH, C-5), 166.15 (C-4), 170.04, 170.43 (4Ac),
193.88 (C-2); MS: m/z 595 (M+); Anal. Calcd for C25H25NO12S2
(595.60): C, 50.41; H, 4.23; N, 2.35. Found: C, 50.27; H, 4.35; N,
2.30.
3.3.2.2. Data for 9a.
Mp 180–182 °C; IR (KBr) m 1750 (C@O)
cmꢀ1 1H NMR (300 MHz, CDCl3): d 2.01 (s, 3H, Ac), 2.03 (s, 3H,
;
Ac), 2.08 (s, 3H, Ac), 2.18 (s, 3H, Ac), 4.10–4.23 (m, 3H, 50-H, 60-H,
600-H), 5.20 (dd, J = 3.36, 9.92 Hz, 1H, 40-H), 5.42 (t, J = 10.17 Hz,
20-H), 5.50 (d, J = 3.32 Hz, 1H, 30-H), 5.98 (d, J = 10.35 Hz, 1H, 10-
H), 7.42 (m, 5H, Ar-H), 7.70 (s, 1H, @CH); 13C NMR (300 MHz,
CDCl3): d 20.32, 20.45, 20.60 (4Ac), 61.11 (C-60), 66.44 (C-20),
66.94 (C-30), 71.40 (C-40), 75.12 (C-50), 82.40 (C-10), 120.50 (@CH),
130.82 (C-5), 129.26, 130.58, 133.05, 133.76 (C-Ar), 169.80
169.86, 170.27, 170.30 (4Ac), 179.30 (C-4), 188.40 (C-2); MS, m/z
551 (M+); Anal. Calcd for C24H25NO10S2 (551.58): C, 52.26; H,
4.57; N, 2.54. Found: C, 52.07; H, 4.72; N, 2.50.
3.3.4.2. Data for 9c.
IR (KBr) m
1748 (C@O) cmꢀ1; MS: m/z 595
(M+); Anal. Calcd for C25H25NO12S2 (595.60): C, 50.41; H, 4.23; N,
2.35. Found: C, 50.32; H, 4.44; N, 2.18.
3.3.5. 5-((Z)-3,4-Ethylenedioxybenzylidene)-3-(20,30,40,60-tetra-
O-acetyl-b-
and 5-((Z)-3,4-ethylenedioxybenzylidene)-2-(20,30,40,60-tetra-O-
acetyl-b- -galactopyranosyl)-2-thioxo-4-thiazolidinone (9d)
D-galactopyranosyl)-2-thioxo-4-thiazolidinone (8d)
D
3.3.3. 5-((Z)-(2-Hydroxy-3-methoxybenzylidene)-3-(20,30,40,60-
tetra-O-acetyl-b-D-galactopyranosyl)-2-thioxo-4-thiazolidinone
Method A described for the synthesis of 8a was utilized using
1.40 g (5 mmol) of 3d instead of 3a as the starting material. The
product was purified by flash chromatography (eluent 30–50%
Et2O–petroleum ether, bp 40–60 °C) to afford 1.80 g (58%) of 8d
and 0.80 g (26%) of 9d as yellow foams.
(8b) and 5-((Z)-(2-hydroxy-3-methoxybenzylidene)-2-
(20,30,40,60-tetra-O-acetyl-b-
D-galactopyranosyl)-2-thioxo-4-
thiazolidinone (9b)
Method A described for the synthesis of 8a was utilized using
1.33 g (5 mmol) of 3b instead of 3a as the starting material. The
product was purified by flash chromatography (eluent 30–50%,
Et2O–petroleum ether, 40–60 °C) to afford, respectively, 1.44 g
(48%) of 8b and 0.92 g (31%) of 9b as yellow foams.
3.3.5.1. Data for 8d.
IR (KBr) m ;
1750 (C@O), 1746 (C@O) cmꢀ1
1H NMR (300 MHz, CDCl3): d 1.95 (s, 3H, Ac), 2.02 (s, 3H, Ac), 2.05
(s, 3H, Ac), 2.26 (s, 3H, Ac), 4.10–4.33 (m, 7H, 50-H, 60-H, 600-H,
2 ꢁ OCH2), 5.22 (dd, J = 3.36, 8.67 Hz, 1H, 40-H), 5.50 (d,

A. I. Khodair, J.-P. Gesson / Carbohydrate Research 346 (2011) 2831–2837
2835
J = 3.24 Hz, 1H, 30-H), 6.26 (t, J = 9.20 Hz, 1H, 20-H), 6.30 (d,
J = 9.40 Hz, 1H, 10-H), 6.92–7.01 (m, 3H, Ar-H), 7.62 (s, 1H, @CH);
13C NMR (300 MHz, CDCl3): d 20.67, 20.81, 20.92, 20.97 (4Ac),
61.65 (C-60), 64.36, 64.92 (2 OCH2), 65.85 (C-20), 67.00 (C-30),
71.82 (C-40), 73.76 (C-50), 82.39 (C-10), 118.45, 118.50, 119.68,
125.39, 126.95, 134.06, 144.25, 146.65 (C-Ar, @CH, C-5), 166.36
(C-4), 170.07, 170.23, 170.60, 170.66 (4Ac), 194.40 (C-2); MS: m/z
609 (M+); Anal. Calcd for C26H27NO12S2 (609.62): C, 51.22; H, 4.46;
N, 2.30. Found: C, 51.12; H, 4.68; N, 2.37.
60), 65.80 (C-20), 67.01 (C-30), 71.68 (C-40), 73.73 (C-50), 82.42 (C-
10), 119.35 (@CH), 121.43 (C-5), 124.98, 132.18, 134.52, 139.57
(C-Ar), 165.74 (C-4), 170.09, 170.12, 170.51, 170.54 (4Ac), 192.77
(C-2); MS: m/z 636 (M+); Anal. Calcd for C22H22BrNO10S3
(636.51): C, 41.51; H, 3.48; N, 2.20. Found: C, 41.42; H, 3.75; N,
2.08.
3.3.7.2. Data for 9f.
IR (KBr) m
1750 cmꢀ1 (C@O); 1H NMR
(300 MHz, CDCl3): d 2.01 (s, 3H, Ac), 2.04 (s, 3H, Ac), 2.05 (s, 3H,
Ac), 2.08 (s, 3H, Ac), 4.08–4.22 (m, 3H, 50-H, 60-H, 600-H), 5.20 (dd,
J = 3.35, 9.90 Hz, 1H, 40-H), 5.42 (t, J = 10.18 Hz, 1H, 20-H), 5.50 (d,
J = 3.24 Hz, 1H, 30-H), 5.95 (d, J = 10.37 Hz, 1H, 10-H), 7.16–7.31
(m, 2H, Ar-H), 7.93 (s, 1H, @CH); MS: m/z 636 (M+); Anal. Calcd
for C22H22BrNO10S3 (636.51): C, 41.51; H, 3.48; N, 2.20. Found: C,
41.36; H, 3.80; N, 2.27.
3.3.5.2. Data for 9d.
IR (KBr) m ;
1750 (C@O) cmꢀ1 1H NMR
(300 MHz, CDCl3): d 2.02 (s, 3H, Ac), 2.05 (s, 3H, Ac), 2.08 (s, 3H,
Ac), 2.20 (s, 3H, Ac), 4.10–4.34 (m, 7H, 50-H, 60-H, 600-H, 2 ꢁ OCH2),
5.28 (dd, J = 3.36, 9.92 Hz, 1H, 40-H), 5.42 (t, J = 10.15 Hz, 1H, 20-H),
5.50 (d, J = 3.26 Hz, 1H, 30-H), 5.98 (d, J = 10.40 Hz, 1H, 10-H), 6.90–
7.10 (m, 3H, Ar-H), 7.78 (s, 1H, @CH); 13C NMR (300 MHz, CDCl3): d
20.22, 20.33, 20.37 (4Ac), 60.99 (C-60), 63.87 (OCH2), 64.44 (OCH2),
66.30 (C-20), 66.88 (C-30), 71.28 (C-40), 75.03 (C-50), 82.25 (C-10),
117.96, 118.98, 122.90, 124.81, 126.44, 136.95, 143.75, 146.35
(C-Ar, @CH, C-5), 169.37, 169.41, 169.78, 170.06 (4Ac), 179.14 (C-
4), 188.58 (C-2); MS: m/z 609 (M+); Anal. Calcd for C26H27NO12S2
(609.62): C, 51.22; H, 4.46; N, 2.30. Found: C, 51.07; H, 4.72; N,
2.26.
3.4. 5-((Z)-Benzylidene)-3-b-D-galactopyranosyl-2-thioxo-4-
thiazolidinone (10a). General procedures
3.4.1. Method A
The protected nucleoside 8a (551 mg, 1 mmol) was suspended
in MeOH (15 mL), and concd HCl (0.5 mL) was added. The reaction
mixture was stirred at 50 °C for 2 h, then cooled to room tempera-
ture. To the resulting solution was added an ion-exchange resin
(Amberlite IR-120, HOꢀ-form), previously washed with MeOH.
After stirring for 5 min., the solution was filtered and evaporated
in vacuo and the residue was purified by flash chromatography
(eluent 0–5%, CHCl3–MeOH) to afford 340 mg (89%) of 10a as yel-
3.3.6. 5-((Z)-2-Thienylidene)-3-(20,30,40,60-tetra-O-acetyl-b-
D-
galactopyranosyl)-2-thioxo-4-thiazolidinone (8e) and 5-((Z)-2-
thienylidene)-2-(20,30,40,60-tetra-O-acetyl-b-
D-galactopy-
ranosyl)-2-thioxo-4-thiazolidinone (9e)
Method A described for the synthesis of 8a was utilized using
1.13 g (5 mmol) of 3g instead of 3a as the starting material. The
product was purified by flash chromatography (eluent 30–50%,
Et2O–petroleum ether, bp 40–60 °C) to afford, respectively, 1.17 g
(42%) of 8e and 0.89 g (32%) of 9e as yellow foams.
low solid: mp 203–205 °C; IR (KBr)
m ;
3400 (OH), 1719 (C@O) cmꢀ1
1H NMR (300 MHz, DMSO-d6): d 3.32–3.74 (m, 5H, 40-H, 50-H, 60-H,
600-H, 30-H), 4.51 (m, 1H, 20-H), 4.71 (t, J = 5.00 Hz, 1H, 60-OH), 5.00
(d, J = 5.12 Hz, 1H, 40-OH), 5.26 (d, J = 3.62 Hz, 1H, 30-OH), 5.33 (d,
J = 3.63 Hz, 1H, 20-OH), 5.80 (d, J = 9.00 Hz, 1H, 10-H), 7.52–7.80
13
3.3.6.1. Data for 8e.
IR (KBr)
m
1752 (C@O), 1747 (C@O) cmꢀ1
;
(m, 5H, Ar-H); C NMR (300 MHz, DMSO-d6): d 60.74 (C-60),
1H NMR (300 MHz, CDCl3): d 1.96 (s, 3H, Ac), 2.03 (s, 3H, Ac), 2.04
(s, 3H, Ac), 2.26 (s, 3H, Ac), 4.14–4.24 (m, 3H, 50-H, 60-H, 600-H),
5.22–5.52 (m, 2H, 40-H, 30-H), 6.26–6.30 (m, 2H, 20-H, 10-H), 7.18–
7.90 (m, 4H, Ar-H, @CH); 13C NMR (300 MHz, CDCl3): d 20.66,
20.79, 20.89 (4Ac), 61.66 (C-60), 65.82 (C-20), 67.01 (C-30), 71.74
(C-40), 73.74 (C-50), 82.43 (C-10), 118.79 (@CH), 126.30 (C-5),
129.19, 133.48, 134.55, 138.03 (C-Ar), 165.93 (C-4), 170.06,
170.15, 170.53 (4Ac), 193.54 (C-2); MS, m/z 557 (M+); Anal. Calcd
for C22H23NO10S3 (557.62): C, 47.39; H, 4.16; N, 2.51. Found: C,
47.25; H, 4.31; N, 2.39.
65.29 (C-20), 68.64 (C-30), 74.56 (C-40), 79.32 (C-50), 85.79 (C-10),
121.10 (@CH), 132.93 (C-5), 125.67, 129.80, 130.85, 133.18 (C-
Ar), 166.01 (C-4), 195.82 (C-2); MS: m/z 383 (M+); Anal. Calcd for
C16H17NO6S2 (383.44): C, 50.12; H, 4.47; N, 3.65. Found: C, 49.94;
H, 4.82; N, 3.57.
3.4.2. Method B
To a stirred suspension of the protected nucleoside 8a (551 mg,
1 mmol) in anhyd MeOH (15 mL) was added portionwise NaOMe
(0.06 g, 1.1 mmol) in anhyd MeOH (15 mL) at 0 °C. Then the reac-
tion mixture was stirred for 2 h at room temperature. To the result-
ing solution was added an ion-exchange resin (Amberlite IR-120,
H+-form), previously washed with MeOH. After stirring for 5 min,
the solution was filtered and evaporated in vacuo, and the residue
was purified by flash chromatography (eluent 0–5%, CHCl3–MeOH)
to afford 330 mg (86%) of 10a as yellow solid.
3.3.6.2. Data for 9e.
IR (KBr) m
1750 cmꢀ1 (C@O); MS: m/z 557
(M+); Anal. Calcd for C22H23NO10S3 (557.62): C, 47.39; H, 4.16; N,
2.51. Found: C, 47.30; H, 4.35; N, 2.46.
3.3.7. 5-[(Z)-(5-Bromo-2-thienylidene)]-3-(20,30,40,60-tetra-O-
acetyl-b-
and 5-[(Z)-(5-bromo-2-thienylidene)]-2-(20,30,40,60-tetra-O-
acetyl-b- -galactopyranosyl)-2-thioxo-4-thiazolidinone (9f)
D-galactopyranosyl)-2-thioxo-4-thiazoli-dinone (8f)
3.4.3. 5-((Z)-(2-Hydroxy-3-methoxybenzylidene)-3-b-D-
galactopyranosyl-2-thioxo-4-thiazolidinone (10b)
D
Method A described for the synthesis of 8a was utilized using
1.53 g (5 mmol) of 3f instead of 3a as the starting material. The
product was purified by flash chromatography (eluent 30–50%,
Et2O–petroleum ether, bp 40–60 °C) to afford, respectively, 1.87 g
(60%) of 8f and 0.62 g (20%) of 9f as yellow foams.
Method A described for the synthesis of 10a was utilized using
597 mg (1 mmol) of 8b instead of 8a as the starting material. The
product was purified by flash chromatography (eluent 0–5%,
CHCl3–MeOH) to afford 334 mg (78%) of 10b as yellow solid: mp
155–157 °C; IR (KBr)
m ;
3398 (OH), 1714 (C@O) cmꢀ1 1H NMR
(300 MHz, DMSO-d6 + D2O): d 3.16–3.72 (m, 5H, 40-H, 50-H, 60-H,
30-H), 3.85 (s, 3H, OCH3), 4.41 (t, J = 8.96 Hz, 1H, 20-H), 5.86 (d,
J = 9.33 Hz, 1H, 10-H), 6.91–7.15 (m, 3H, Ar-H), 7.98 (s, 1H, @CH);
13C NMR (300 MHz, DMSO-d6): d 55.96 (OCH3), 60.88 (C-60),
67.50 (C-20), 69.72 (C-30), 77.33 (C-40), 80.64 (C-50), 84.81 (C-10),
114.40, 119.41, 119.80, 120.04, 120.54, 128.30, 146.84, 148.01
(@CH, C-5, C-Ar), 165.98 (C-4), 195.80 (C-2); MS: m/z 429 (M+);
3.3.7.1. Data for 8f.
IR (KBr) m ;
1750 (C@O), 1746 (C@O) cmꢀ1
1H NMR (300 MHz, CDCl3): d 1.97 (s, 3H, Ac), 2.04 (s, 3H, Ac), 2.06
(s, 3H, Ac), 2.27 (s, 3H, Ac), 4.11–4.27 (m, 3H, 50-H, 60-H, 600-H), 5.26
(dd, J = 3.31, 9.05, 1H, 40-H), 5.53 (d, J = 3.23 Hz, 1H, 30-H), 6.25–
6.30 (m, 2H, 20-H, 10-H), 7.16 (m, 2H, Ar-H), 7.75 (s, 1H, @CH);
13C NMR (300 MHz, CDCl3): d 20.65, 20.76, 20.87 (4Ac), 61.67 (C-

2836
A. I. Khodair, J.-P. Gesson / Carbohydrate Research 346 (2011) 2831–2837
Anal. Calcd for C17H19NO8S2 (429.47): C, 47.54; H, 4.46; N, 3.26.
Found: C, 47.33; H, 4.75; N, 3.13.
1H, 10-H), 7.33–7.55 (m, 2H, H-400, H-300), 7.89 (s, 1H, @CH); 13C
NMR (300 MHz, DMSO-d6): d 60.49 (C-60), 65.11 (C-20), 68.42 (C-
30), 74.49 (C-40), 78.92 (C-50), 85.58 (C-10), 119.34, 120.20, 124.07,
132.43, 135.43, 139.11 (@CH, C-5, C-Ar), 165.51 (C-4), 193.72 (C-
2); MS: m/z 468 (M+); Anal. Calcd for C14H14BrNO6S3 (468.37): C,
35.90; H, 3.01; N, 2.99. Found: C, 35.76; H, 3.13; N, 2.78.
3.4.4. 5-((Z)-3,4-Methylenedioxybenzylidene)-3-b-D-
galactopyranosyl-2-thioxo-4-thiazolidinone (10c)
Method A described for the synthesis of 8a was utilized using
595 mg (1 mmol) of 8c instead of 8a as the starting material. The
product was purified by flash chromatography (eluent 0–5%,
CHCl3–MeOH) to afford 350 mg (82%) of 10c as yellow solid: mp
3.5. 5-((Z)-(3,4-Methylenedioxybenzylidene)-2,4-
thiazolidindione (11)
186–188 °C; IR (KBr)
m ;
3400 (OH), 1710 (C@O) cmꢀ1 1H NMR
(300 MHz, DMSO-d6): d 3.14–3.82 (m, 5H, 40-H, 50-H, 60-H, 600H,
30-H), 4.32 (m, 1H, 20-H), 4.63 (m, 1H, 60-OH), 4.77 (d, J = 4.23 Hz,
1H, 40-OH), 4.86 (m, 1H, 30-OH), 5.22 (d, J = 4.32 Hz, 1H, 20-OH),
5.84 (d, J = 9.00 Hz, 1H, 10-H), 6.13 (s, 2H, OCH2O), 7.01–7.17 (m,
3H, Ar-H), 7.67 (s, 1H, @CH); 13C NMR (300 MHz, DMSO-d6): d
60.56 (C-60), 65.22 (C-20), 68.50 (C-30), 74.59 (C-40), 78.94 (C-50),
84.80 (C-10), 102.07 (OCH2O), 109.15, 109.30, 118.03, 126.88,
127.18, 132.44, 148.47, 149.84 (@CH, C-5, C-Ar), 165.99 (C-4),
194.640 (C-2); MS: m/z 427 (M+); Anal. Calcd for C17H17NO8S2
(427.45): C, 47.77; H, 4.01; N, 3.28. Found: C, 47.61; H, 4.15; N,
3.22.
The protected nucleoside 9c (595 mg, 1 mmol) was suspended
in MeOH (15 mL), and concd HCl (2 mL) was added. The reaction
mixture was heated under reflux for 2 h until the starting material
was consumed (TLC), then it was cooled to room temperature, and
the separated yellow solid was collected by filtration and recrystal-
lized from EtOH to give 212 mg (90%) of product 11: mp 245–
247 °C; IR (KBr)
m ;
3200 (NH), 1755 (CO), 1710 (CO) cmꢀ1 1H
NMR (300 MHz, DMSO-d6): d 6.15 (s, 2H, OCH2O), 7.05–7.18 (m,
3H, Ar-H), 7.72 (s, 1H, @CH), 12.56 (s, 1H, NH); 13C NMR
(300 MHz, DMSO-d6): d 102.10, 109.12, 109.34, 118.06, 126.90,
127.26, 132.50, 148.60, 149.98 (C-Ar, C-5, @CH), 167.40 (C-4),
167.86 (C-2); MS: m/z 249 (M+); Anal. Calcd for C11H7NO4S
(249.24): C, 53.01; H, 2.83; N, 5.62. Found: C, 53.32; H, 3.04; N,
5.48.
3.4.5. 5-((Z)-3,4-Ethylenedioxybenzylidene)-3-b-D-
galactopyranosyl-2-thioxo-4-thiazolidinone (10d)
Method A described for the synthesis of 10a was utilized using
609 mg (1 mmol) of 8d instead of 8a as the starting material. The
product was purified by flash chromatography (eluent 0–5%,
CHCl3–MeOH) to afford 379 mg (86%) of 10d as yellow solid: mp
Acknowledgements
ADIR (Groupe Servier, Paris) are thanked for carrying out the
antitumor testing of the new deprotected nucleosides. Ahmed I.
Khodair is grateful for an Alexander von Humboldt-Fellowship.
194–196 °C; IR (KBr)
m ;
3398 (OH), 1709 (C@O) cmꢀ1 1H NMR
(300 MHz, DMSO-d6): d 3.25–3.75 (m, 5H, 40-H, 50-H, 60-H, 30-H),
4.26–4.48 (m, 6H, 2 ꢁ OCH2, 20-H, 60-OH), 4.60 (d, J = 5.38 Hz, 1H,
40-OH), 5.00 (d, J = 4.50 Hz, 1H, 30-OH), 5.20 (d, J = 4.83 Hz, 1H, 20-
OH), 5.78 (d, J = 9.30 Hz, 1H, 10-H), 7.04–7.2 (m, 3H, Ar-H), 7.68
References
13
(s, 1H, @CH); C NMR (300 MHz, DMSO-d6): d 60.68 (C-60), 64.17
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3.4.6. 5-((Z)-2-Thienylidene)-3-b-D-galactopyranosyl-2-thioxo-
4-thiazolidinones (10e)
Method A described for the synthesis of 10a was utilized using
557 mg (1 mmol) of 8e instead of 8a as the starting material. The
product was purified by flash chromatography (eluent 0–5%,
CHCl3–MeOH) to afford 318 mg (82%) of 10e as yellow solid: mp
180–182 °C; IR (KBr)
m ;
3400 (OH), 1710 (C@O) cmꢀ1 1H NMR
(300 MHz, CD3OD-d4): d 3.29–3.94 (m, 6H, 40-H, 50-H, 60-H, 30-H,
20-H), 6.00 (d, J = 9.34 Hz, 1H, 10-H), 7.24–7.94 (m, 4H, H-400, H-300,
13
@CH, H-500); C NMR (300 MHz, CD3OD): d 62.40 (C-60), 67.16
(C-20), 70.63 (C-30), 76.28 (C-40), 80.22 (C-50), 86.74 (C-10), 120.36,
126.48, 130.15, 134.60, 135.80, 139.28 (@CH, C-5, C-Ar), 168.00
(C-4), 196.10 (C-2); MS: m/z 389 (M+); Anal. Calcd for C14H15NO6S3
(389.47): C, 43.17; H, 3.88; N, 3.60. Found: C, 43.04; H, 4.11; N,
3.53.
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3.4.7. 5-[(Z)-(5-Bromo-2-thienylidene)]-3-b-D-galactopyranosyl-
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Method A described for the synthesis of 10a was utilized using
636 mg (1 mmol) of 8f instead of 8a as the starting material. The
product was purified by flash chromatography (eluent 0–5%,
CHCl3–MeOH) to afford 360 mg (77%) of 10f as yellow solid: mp
178–180 °C; IR (KBr)
m ;
3398 (OH), 1702 (C@O) cmꢀ1 1H NMR
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4.40 (m, 2H, 20-H, 60-OH), 4.71 (t, J = 9.06 Hz, 1H, 40-OH), 4.94 (t,
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