Microwave irradiation for accelerating the synthesis of thioglycosides

Article abstract of DOI:10.1080/00397910600767314

A simple and efficient procedure for the synthesis of thioglycosides has been achieved from the reaction of glycosylisothiouronium salts with alkyl or heteroaryl halides under microwave irradiation, in much shorter times and in yields comparable with conventional methods. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600767314

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Microwave Irradiation for Accelerating the
Synthesis of Thioglycosides
E. S. H. El Ashry a , L. F. Awad a , H. M. Abdel Hamid a & A. I. Atta a
a Chemistry Department, Faculty of Science, Alexandria University,
Alexandria, Egypt
Published online: 16 Feb 2007.
To cite this article: E. S. H. El Ashry , L. F. Awad , H. M. Abdel Hamid & A. I. Atta (2006): Microwave
Irradiation for Accelerating the Synthesis of Thioglycosides, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 36:19, 2769-2785
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Synthetic Communicationsw, 36: 2769–2785, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600767314
Microwave Irradiation for Accelerating
the Synthesis of Thioglycosides
E. S. H. El Ashry, L. F. Awad, H. M. Abdel Hamid,
and A. I. Atta
Chemistry Department, Faculty of Science, Alexandria University,
Alexandria, Egypt
Abstract: A simple and efficient procedure for the synthesis of thioglycosides has been
achieved from the reaction of glycosylisothiouronium salts with alkyl or heteroaryl
halides under microwave irradiation, in much shorter times and in yields comparable
with conventional methods.
Keywords: Alkylating agents, microwave irradiation, pyridine, quinoxaline,
thioglycosides
Thioglycosides are important class of carbohydrate derivatives.[1–5] Their
importance in biological investigations, particularly as candidates for
enzyme inhibition studies,[6] is due to their chemical and enzymatic
stability, which is greater than their O-analogues. They are widely
employed as inducers and ligands for affinity chromatography of carbo-
hydrate-processing enzymes and proteins.[7] Moreover, thioglycosides have
attracted much attention as versatile glycosyl donors because they can be
activated with appropriate thiophilic reagents;[8–11] in the meantime they
are stable under conditions suitable for a variety of chemical transformations,
which make them useful compounds as acceptors for subsequent steps in
oligosacchoride synthesis.
Received in the U.K. September 26, 2005
Address correspondence to E. S. H. El Ashry, Chemistry Department, Faculty of
Science, Alexandria University, Alexandria, Egypt. E-mail: eelashry60@hotmail.
com or eelashry60@link.net
2769

2770
E. S. H. El Ashry et al.
Several methods have been published for the synthesis of thioglycosides;
the most common one included a reaction of glycosyl halide with thiolate
anion.[12] Other methods are based on Lewis acid–catalyzed glycosylation
of thiols with 1,2-trans glycosylesters,[13] trichloroacetimidates,[14] 1-O-tri-
methylsilylglycosides,[15] and glycopyranoses.[16] A convenient and simple
approach for the stereoselective synthesis of 1,2-trans thioglycosides is
based on utilization of glycosyl isothiourea derivatives as precursors.[17]
Recently they were successfully used for the synthesis of thio-oligosacchar-
ides.[18] The chemoselectivity in glycosidation reactions and the adjustment
of reactivity and/or stability of glycosyl donors by varying the electronic
properties and steric factors of the substituent on the anomeric center has
directed our protocol for a comparative study of using microwave (MW)
versus conventional methods for the synthesis of thioglycosides.
Microwave irradiation (MWI) has been utilized for effecting a sequence
of reactions leading to the synthesis of thioglycosides 6–13, each bearing
a flexible armed methylene group, by starting with 2,3,4,6-tetra-O-acetyl-b-
D-glucopyranosyl isothiouronium bromide (3) and 2-acetamido-3,4,6-tri-
O-acetyl-2-deoxy-b-D-glucopyranosyl isothiouronium chloride (4). The
thiouronium salts were prepared[19] by the reaction of the glycosyl halides
2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bromide (1) or 2-acetamido-
3,4,6-tri-O-acetyl-2-deoxy-a-D-glucopyranosyl chloride[20] (2) with thiourea
in dry acetone under MWI for 3 min to give 3 and 4, respectively; conven-
tional synthesis gave 3 and 4 in 80–82 % yield within 15–30 min.[21,22]
Coupling reaction of isothiouronium salts 3 and 4 with alkyl halides 5a–d
in acetonitrile as a solvent and triethylamine as a catalyst was achieved under
MWI to give the thioglycosides 6–13, respectively, within 2–3 min, in
moderate to high yield (50–94%). On the other hand, when the reactions
were carried out under conventional conditions, 3–11 h were required to
give 40–78% yield. The reaction may have taken place through the respective
thiolate anion formed from 3 or 4 by the nucleophilic attack of triethylamine
on the imine carbon of the isothiouronium salt, leading to a C-S bond
cleavage. Spontaneous attack of the thiolate anion on the alkyl halides
5a–d gave the b-thioglycosides 6–13, respectively (Scheme 1).
Along with other expected signals in 1H NMR spectra of compounds 11–
13 measured in CDCl3, the SCH2 protons were assigned as either two doublet
of doublets for 11 or two doublets for 12 and 13 at dH 3.22–3.40 and 3.56–
3.78 with Jgem 13.0–14.7 Hz. The assignment of the sugar protons of
1
compound 12 was based on its H-1H Double-quantum filtered correlation
spectroscopy (DQFCOSY) experiment, which showed H-30 resonating at dH
5.15 and correlated with both of the doublets of doublets of H-20 and H-40,
which resonated at dH 5.03 and 5.00, respectively. H-10 resonated at dH 4.46
0
0
as a doublet with J1 ,2 10.0 Hz, in agreement with the 1,2-trans relationship.
The 13C NMR spectrum of 12 exhibited, in addition to the signals correspond-
ing to sugar and pyran moieties, a signal characteristic to SCH2 at the lower
frequency region at dC 30.2 (Experimental).

MW Irradiation in Thioglycoside Synthesis
2771
Scheme 1.
When the isothiouronium salts 3 and 4 were coupled with (+) epichloro-
hydrin 5e under the same reaction conditions for 3 min, the racemic products
14 and 15, respectively, were obtained. Although the 13C NMR spectra for
both compounds showed two signals for each carbon of the enantiomers of
1
the racemate (Experimental), the H NMR spectra showed only one signal
with a multiplet splitting pattern. The assignments of both proton and carbon
signals were based on the 1H-1H DQFCOSY and 1H-13C Heteronuclear
multiple-quantum correlation (HMQC) experiments. Thus, the signals

2772
E. S. H. El Ashry et al.
corresponding to the SCH2 protons appeared as three doublets of doublets at dH
2.68–2.83 and 2.73–2.88 and two doublet of doublets at dH 2.95–3.06 and
3.03–3.14, respectively, with Jgem 14.5–14.7 Hz, whereas their coupling
constant with the neighboring proton varied from 2.8 to 7.7 Hz. Both of
SCH2 protons were correlated with the multiplet of the oxiran ring H-2 at d
3.94–4.09, which in turn correlated with H-3a, H-3b, which that resonated
as doublets of doublets at dH 3.59 or at dH 3.61 with J2,3cis 5.3–5.4 Hz,
J2,3trans 2.0–2.3 Hz, and Jgem 6.9–7.4 Hz. Correlation of the carbon signals
with those of the attached protons led to their assignment. The anomeric
0
protons of 14 and 15 were assigned as doublets (J1 ,2 10.1 Hz) and triplets
0
0
0
(J1 ,2 10.7 Hz), respectively, which were correlated with their corresponding
carbons at dC 83.04, 83.1 and 85.1, 85.13. The other sugar protons and
carbons are in accordance with their structures (Experimental) (Scheme 2).
The simplicity and versatility of the proposed procedure for the synthesis
of 1,2-trans thioglycosides have caused us to apply it to the synthesis of thio-
disaccharides. Hutson[23] has synthesized the thiodisaccharide 16 in 19%
yields from the coupling reaction of 2,3,4,6-tetra-O-acetyl-1-thio-b-D-gluco-
pyranose with methyl 6-O-p-tolylsulfonyl-a-D-glucopyranoside in acetone
and in the presence of aqueous K2CO3 or in 55% yield by reacting the
sodium salt of methyl 6-thio-a-D-glucopyranoside with 1, followed by acety-
lation. Herein the disaccharides 16 and 17 were prepared in 70 and 73 % yield,
respectively, when the isothiouronium salts 3 and 4 were coupled with methyl
2,3,4-tri-O-acetyl-6-iodo-a-D-glucopyranoside in acetonitrile and in presence
1
of triethylamine under MWI for 3 min. The H and 13C NMR spectra of
compounds 16 and 17 confirmed the assigned structure. As a result of the
shielding effect exerted by the thio linkage, an upfield shift of both of
the C-6a protons and carbon was observed. The SCH2 protons of 16 were
assigned as multiplet at dH 2.72–2.77 whereas that of 17 were resonated as
two doublets of doublets at dH 2.76–2.98. Their respective carbons were
resonated at dC 30.9 and 31.2, respectively. The anomeric protons H-10a
0
0
were assigned as doublets at dH 4.87 and 4.99 with J1 a,2 a 3.6 Hz and
3.5 Hz, respectively whereas those of H-10b were assigned at the lower
0
frequency region at dH 4.64 and 4.60 with J1 b,2 b 10.1 Hz and 10.4 Hz,
0
Scheme 2.

MW Irradiation in Thioglycoside Synthesis
2773
respectively. Their carbons were resonated at dC 96.4, 96.0 (C-10a) and 83.8,
85.1 (C-10b), respectively. The other sugar protons and carbons are in their
appropriate positions (Experimental).
Disarmed thioglycosides have been also successfully synthesized under
the MWI technique. Thus, thioglycosides 18–21, with a pyridyl moiety
having a nitro group at position 3 or 5, have been synthesized when isothiour-
onium salts 3 and 4 were treated with 2-choloro-3-nitropyridine or 2-chloro-5-
nitropyridine in acetonitrile and in the presence of triethylamine under MWI
for 2–3 min in moderate to good yields. On the other hand, compounds 18–21
were obtained using the traditional method within 6–8 h in less yield.
The 1H NMR spectra of compounds 18–21 showed characteristic signals
corresponding to 3- or 5-nitropyridyl moieties. The anomeric protons of 18–
0
0
21 were assigned as doublets at dH 5.85–6.06 with J1 ,2 10.0–11.7 Hz, con-
firming the b-configuration. The 2-D NMR spectra (1H-1H DQFCOSY and
1H-13C HMQC) facilitated the spectral assignment of the sugar and 5-nitropyr-
idyl moieties of compound 21. Thus, the anomeric proton H-10 was resonated
as a doublet at dH 5.85, correlated with the quartet of H-20 at dH 4.43, whereas
their respective carbons were assigned at dC 82.5 and 52.4 (Scheme 3).
Under the same reaction conditions, the isothiouronium salts 3 and 4 were
coupled with 2-chloro-3-methylquinoxaline to give the respective thioglyco-
sides 22 and 23 in 60 and 66% yields within 3 min. Similarly, 2,3-dichloroqui-
noxaline was reacted with 3 and 4 to afforded the monothioglycosides 24 and 25
in 48 to 50% yield within 3 min. Under conventional conditions, compounds
22–25 were obtained in 40–48% yield within 10 h. The formation of the thio-
glycosides 24 and 25 was deduced from their 1H NMR spectra, which showed
characteristic signals corresponding to only one sugar moiety. The anomeric
0
0
proton appeared at dH 5.87 as a doublet with J1 ,2 10.7 Hz, correlated with dC
82.4 for C-10, which is characteristic of a b anomer (Scheme 4).
Increasing the molar ratio of 3 or 4 to two equivalents in their coupling
under MWI for 7 min with 2,3-dichloroquinoxaline resulted in the
formation of the bisthioglycosides 26 and 27 (59–61% yield) together with
the mono derivatives, 24 and 25 (13% yield). Alternatively, the conventional
Scheme 3.

2774
E. S. H. El Ashry et al.
Scheme 4.
method required 48 h to give both compounds in comparable yields. The
1
structures of compounds 26 and 27 can be established by H NMR spectra.
As a result of symmetry exited in both compounds, the sugar protons were
assigned as a single signals for each protons but with double intensities, in
agreement with the introduction of two sugar moieties. The two anomeric
protons H-10 of 26 and 27 were resonated at dH 6.06–6.1 as doubles.
In conclusion, the use of MWI for accelerating organic reactions has
provided a facile approach for the synthesis of thioglycosides by the nucleoph-
lic displacement of the halide from alkyl, aryl, and heterocyclic compounds
with 1-thioglycosyl O-acetates.
A comparison of the results of MWI with those of conventional con-
ditions revealed that higher yields were obtained in a shorter time (Table 1).
Thus, economical and environmental impacts have been achieved.
EXPERIMENTAL
General Methods
Melting points were determined on a Mel-temp apparatus and are uncorrected.
1H NMR and 13C NMR spectra were recorded on Jeol spectrometer

MW Irradiation in Thioglycoside Synthesis
2775
Table 1. Comparison of the yield (%) and reaction time of con-
ventional and microwave methods for the synthesis of 6–27
Conventional
MWI
Compound
Yield (%) Time (h) Yield (%) Time (min)
6
7
75
78
71
76
40
40
44
48
42
45
61
61
40
60
68
68
46
48
40
42
57
58
3
3
90
92
90
94
50
50
64
73
55
65
70
73
60
85
80
88
60
66
48
50
59
61
2
2
2
2
2
2
3
3
3
3
3
3
3
3
2
2
3
3
3
3
7
7
8
3
9
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
3
3
11
10
7
7
8
8
8
8
7
6
10
10
10
10
48
48
(500 MHz) and a Bruker Advance 300-MHz spectrometer. The chemical shifts
are expressed on the d scale using Me4Si as a standard, and coupling constant
1
values are given in Hz. The assignments of H NMR spectra were based on
chemical-shift correlation DQFCOSY spectra, whereas the assignment of
13C NMR spectra were based on HMQC experiments. TLC was preformed
on Merck silica gel 60F254 with detection by charring in sulfuric acid and
by UV light. Irradiation was achieved using a domestic microwave oven
EM-230 M (800-W output power). Microanalyses were preformed in the
Microanalysis Unit at the Faculty of Science, Cairo University, Egypt.
Synthesis of Thioglycosides 6–15
Method A
A suspension of the glycosyl isothiouronium salts 3 or 4 (1 mmol), the respect-
ive alkylating agent 5a–e (1 mmol) and triethylamine (5 mmol) in acetonitrile

2776
E. S. H. El Ashry et al.
(5 mL) was allowed to react under MWI for 2–3 min. The reaction mixtures
were left to cool. The solid products were washed with water and dried,
whereas the syrup ones were dissolved in methylene chloride (20 mL) and
washed with water (3 ꢀ 10 mL), dried over anhydrous sodium sulfate, and
evaporated.
Method B
To a stirred suspension of 3 or 4 (1 mmol) in acetonitrile (15 mL), Et3N
(5 mmol), and the alkylating agent 5a–e (1 mmol) were added at room temp-
erature. The reaction mixture was further stirred at room temperature for
3–11 h, and then concentrated under reduced pressure. The residue was
dissolved in CH2Cl2 (20 mL), then washed with water (3 ꢀ 10 mL), dried
(Na2SO4), and concentrated (see Table 1 for yield).
Data
Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (6). It was recrys-
tallized from ethanol as colorless crystals, mp 83–858C, lit.[24] mp 828C.
Ethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-b-D-glucopyrano-
side (7). It was recrystallized from methanol as colorless crystals, mp 186–
1888C, lit.[25] mp 184–1868C.
Benzyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (8). It was
recrystallized from ethanol as colorless needles, mp 101–1038C, lit.[24] mp
1018C.
Benzyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-b-D-glucopyrano-
side (9). It was recrystallized from ethanol, mp 204–2068C, lit.[26] mp 2028C.
Allyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (10). The residue
was purified by column chromatography using ethyl acetate–petroleum
ether (1:5) to give 10, mp 51–538C, lit.[24] mp 53–558C.
Allyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-b-D-glucopyranoside
(11). It was recrystallized from chloroform ether to give 11 as pale yellow
crystals, mp 178–1808C; 1H NMR (CDCl3, 500 MHz) d: 1.93 (s, 3 H,
NHAc), 2.00, 2.01, 2.06 (3 s, 9 H, 3 ꢀ OAc), 3.22 and 3.40 (2 dd, 2 H,
0
Jgem ¼ 13.0 Hz, J2,3allyl ¼ 6.1 Hz, J2,3 allyl ¼ 8.4 Hz, SCH2), 3.61–3.62
(m, 1 H, H-5), 4.10–4.19 (m, 3 H, H-6, H-60, H-2), 4.53 (d, 1 H,
J1,2 ¼ 10.7 Hz, H-1), 4.99–5.15 (m, 4 H, H-3, H-4, CH2 allyl), 5.68 (d, 1
H, J2,NH ¼ 9.2 Hz, NH), 5.76–5.78 (m, 1 H, CH allyl); anal. calcd. for
C17H25NO8S: C, 50.61; H, 6.25; N, 3.47; S, 7.95. Found: C, 49.91; H, 6.29;
N, 3.54; S, 7.85.

MW Irradiation in Thioglycoside Synthesis
2777
2-(20,30,40,60-Tetra-O-acetyl-10-thio-b-D-glucopyranosyl)methyl-5-hydroxy-
4H-pyran-4-one (12). The residue was purified by column chromatography
using ethyl acetate–petroleum ether (1:1) to give 12, mp 142–1448C;
1H NMR (CDCl3 þ H2O, 300 MHz) d: 1.94, 1.96, 1.98, 2.03 (4 s, 12 H,
4 ꢀ OAc), 3.56 (d, 1 H, Jgem ¼ 14.7 Hz, SCH), 3.60–3.64 (m, 1 H, H-50),
0
0
3.78 (d, 1 H, Jgem ¼ 14.7 Hz, SCH), 4.05 (dd, 1 H, J6 ,5 ¼ 3.2 Hz,
J6 ,6 ¼ 12.4 Hz, H-60), 4.18 (dd, 1 H, J6 ,5 ¼ 4.6 Hz, J6 ,6 ¼ 12.4 Hz,
0
00
00
0
0
00
H-600), 4.46 (d, 1 H, J1 ,2 ¼ 10.0 Hz, H-10), 5.00 (dd, 1 H, J4 ,5 ¼ 9.7 Hz,
0
0
0
0
J4 ,3 ¼ 9.3 Hz, H-40), 5.03 (dd, 1 H, J2 ,1 ¼ 10.0 Hz, J2 ,3 ¼ 9.3 Hz, H-20),
0
0
0
0
0
0
5.15 (t, 1 H, J3 ,4 ¼ J3 ,2 ¼ 9.3 Hz, H-30), 6.38 (s, 1 H, H-3), 7.77 (s, 1 H,
0
0
0
0
13
H-6); C NMR (CDCl3) d: 19.8, 19.9 (4 ꢀ Ac), 30.2 (SCH2), 61.2 (C-60),
67.2, 68.8, 72.7 (C-20, C-40, C-30), 75.5 (C-50), 81.2 (C-10), 110.8 (C-2),
137.1 (C-3), 144.8 (C-6), 164.2 (C-5), 168.6, 168.7, 169.3, 169.8
(4 ꢀ CH3CO), 173.03 (C-4); anal. calcd. for C20H24O12S: C, 49.18; H,
4.95; S, 6.56. Found: C, 48.97; H, 4.97; S, 6.69.
2-(20-Acetamido-30,40,60-tri-O-acetyl-20-deoxy-10-thio-b-D-glucopyranosyl)-
methyl-5-hydroxy-4H-pyran-4-one (13). Thecrudeproduct was recrystallized
1
from methanol, to give 13 as colorless crystals, mp 230–2328C; H NMR
(DMSO-d6, 500 MHz) d: 1.72 (s, 3 H, NHAc), 1.88, 1.93, 1.98 (3 s, 9 H,
3 ꢀ OAc), 3.36–3.39 (m, 1 H, H-50), 3.68 (d, 1 H, Jgem ¼ 14.5 Hz, SCH), 3.78
0
0
0
00
(d, 1 H, Jgem ¼ 14.5 Hz, SCH), 3.94 (dd, 1 H, J6 ,5 ¼ 1.5 Hz, J6 ,6 ¼ 12.3 Hz,
H-60), 4.10 (dd, 1 H, J6 ,5 ¼ 4.6 Hz, J6 ,6 ¼ 12.3 Hz, H-600), 4.68 (d, 1 H,
00
0
0
00
J1 ,2 ¼ 10.7 Hz, H-10), 4.81 (dd, 1 H, J3 ,4 ¼ 9.2 Hz, J4 ,5 ¼ 9.9 Hz H-40), 5.05
0
0
0
0
0
0
(dd, 1 H, J2 ,3 ¼ 9.9 Hz, J3 ,4 ¼ 9.2 Hz, H-30), 6.36 (s, 1 H, H-3), 8.0 (s, 1 H,
H-6), 9.10 (s, 1 H, OH); anal. calcd. for C20H25NO11S: C, 49.28; H, 5.17; N,
2.87. Found: C, 48.96; H, 4.77; N, 3.08.
0
0
0
0
2,3-Epoxypropyl
20,30,40,60-tetra-O-acetyl-10-thio-b-D-glucopyranoside
(14). The residue was purified by column chromatography using ethyl
acetate–petroleum ether (1: 4) to give 14 as syrup; 1H NMR (CDCl3,
300 MHz) d: 1.97, 1.98, 2.02, 2.05 (4 s, 12 H, 4 ꢀ OAc), 2.68–2.83 (3dd, 1
H, JSCH,1 ¼ 4.2 Hz. JSCH,2 ¼ 7.1 Hz, Jgem ¼ 14.7 Hz, SCH), 2.95–3.06 (2dd,
1 H, J
¼ 4.1 Hz, JSCH,2 ¼ 7.4 Hz, Jgem ¼ 14.7 Hz, SCH), 3.59 (dd, 2 H,
SCH,1
J2,3cis ¼ 5.4 Hz, J2,3trans ¼ 2.0 Hz, Jgem ¼ 7.4 Hz, H-3), 3.71–3.76 (m, 1 H,
H-50), 3.94–3.96 (m, 1 H, H-2), 4.13 (d, 2 H, J ¼ 3.7 Hz, H-60,600), 4.54 (d, 1
H, J1 ,2 ¼ 10.1 Hz, H-10), 5.05 (ddd, 2 H, J3 ,4 ¼ 9.4 Hz, J1 ,2 ¼ 10.1 Hz,
0
0
0
0
0
0
H-40, H-20), 5.19 (t, 1 H, J3 ,4 ¼ J2 ,3 ¼ 9.4 Hz, H-30); 13C NMR (CDCl3) d:
19.6, 19.7, 19.8 (CH3CO), 34.38, 34.41 (SCH2), 46.0, 46.3 (C-3), 60.93, 60.96
(C-60), 67.09, 67.1 (C-20), 68.8, 68.6 (C-40), 69.7, 69.8 (H-2), 72.55, 72.56
(C-30), 74.9 (C-50), 83.04, 83.1 (C-10), 168.4, 168.9, 169.1, 169.7 (4 ꢀ CH3CO).
0
0
0
0
2,3-Epoxypropyl 20-acetamido-30,40,60-tri-O-acetyl-20-deoxy-10-thio-b-D-
glucopyranoside (15). The crude product was recrystallized from methanol
to give 15 as colorless crystals, mp 146–1488C; 1H NMR (CDCl3,

2778
E. S. H. El Ashry et al.
500 MHz) d: 1.95, 2.01, 2.02, 2.05 (4 s, 12 H, 3 ꢀ OAc, NHAc), 2.73–2.88
(3dd, 1 H, JSCH,1 ¼ 3.9 Hz, J ¼ 4.6 Hz, JSCH,2 ¼ 7.7 Hz, Jgem ¼ 14.5 Hz,
SCH), 3.03–3.14 (2dd,
1
H, JSCH,1 ¼ 3.8 Hz, JSCH,2 ¼ 6.9 Hz,
Jgem ¼ 14.5 Hz, SCH), 3.61 (dd, 2 H, J2,3cis ¼ 5.3 Hz, J2,3trans ¼ 2.3 Hz,
J2,3 cis ¼ 5.4 Hz, J2,3 trans ¼ 1.5 Hz Jgem ¼ 6.9 Hz, H-3,30), 3.75–3.78 (m, 1
0
0
H, H-50), 4.09 (m, 1 H, H-2), 4.11–4.15 (m, 3 H, H-20, H-60,600), 4.70 (t, 1
H, J1 ,2 ¼ 10.7 Hz, H-10), 5.07 (dd, 1 H, J3 ,4 ¼ 10.0 Hz, J4 ,5 ¼ 10.0 Hz,
0
0
0
0
0
0
H-40), 5.20 (ddd, 1 H, J3 ,2 ¼ 9.9 Hz, J3 ,4 ¼ 10.0 Hz, H-30), 6.23 (d, 1 H,
0
0
0
0
D2O exchangeable, JNH,2 8.4 Hz, NH); 13C NMR (CDCl3) d: 20.7, 20.8
0
(CH3CO), 23.4 (NHAc), 35.4, 35.5 (SCH2), 47.1, 47.5 (C-3), 53.3, 53.5
(C-20), 62.24 (C-60), 68.31, 68.34 (C-2), 70.8, 70.9 (C-40), 73.5, 73.6 (C-30),
75.0, 75.0 (C-50), 85.10, 85.13 (C-10), 169.4, 170.7, 170.8, 171.1
(4 ꢀ CH3CO); anal. calcd. for C17H25NO9S: C, 48.68; H, 6.01; N, 3.34; S,
7.64. Found: C, 48.98; H, 5.84; N, 3.18; S, 7.07.
Reaction of Glycosyl Isothiouronium Salts with Methyl 2,3,4-Tri-O-
acetyl-6-iodo-a-D-glucopyranoside
Method A
A suspension of the glycosyl isothiouronium salts 3 or 4 (1 mmol), methyl
2,3,4-tri-O-acetyl-6-iodo-a-D-glucopyranoside (1 mmol), and triethylamine
(5 mmol) in acetonitrile (10 mL) was irradiated under microwaves, for
3 min. The reaction mixture was left to cool.
Method B
A suspension of 3 or 4 (1 mmol), Et3N (5 mmol), and methyl 2,3,4-tri-O-
acetyl-6-iodo-a-D-glucopyranoside (1 mmol) in acetonitrile (30 mL) was
stirred at room temperature for 6 h. Then concentrated under reduce
pressure. The residue was dissolved in CH2Cl2 (20 mL); the solution was
washed with H2O (3 ꢀ 15 mL), dried (Na2SO4), and concentrated.
Data
Methyl 2,3,4-Tri-O-acetyl-6-S-(2,3,4,6-tetra-O-acetyl-b-glucpyranosyl)-
6-thio-a-D-glucopyranoside (16). The residue was purified by column
chromatography using ethylacetate–petroleum ether (1:4) to give 16 as
colorless white crystal, mp 153–1558C, lit.[22] mp 156.58C; 1H NMR
(CDCl3, 600 MHz) d: 1.96, 1.97, 1.98, 2.02, 2.03, 2.07 (6s, 21 H, 7 ꢀ OAc),
2.72–2.77 (m, 2 H, H-6a, H-60a), 3.39 (s, 3 H, OCH3), 3.69 (m, 1 H, H-5b),
0
00
3.94 (ddd, 1 H, J5a,4a ¼ 9.0 Hz, J5a,6 a ¼ 3.2 Hz, J5a,6 a ¼ 4.6 Hz, H-5a), 4.1
0
(dd, 1 H, J6b,5b ¼ 2.3 Hz, J6b,6 b ¼ 12.4 Hz, H-6b), 4.22 (dd, 1 H,
J6 b,5b ¼ 5.2 Hz, J6 b,6b ¼ 12.4 Hz, H-60b), 4.64 (d, 1 H, J1b,2b ¼ 10.1 Hz,
0
0

MW Irradiation in Thioglycoside Synthesis
2779
H-1b), 4.82 (dd, 1 H, J2a,1a ¼ 3.7 Hz, J2a,3a ¼ 10.2 Hz, H-2a), 4.85 (d, 1 H,
J4a,3a ¼ 9.6 Hz, H-4a), 4.87 (d, 1 H, J1a,2a ¼ 3.6 Hz, H-1a), 4.94 (t, 1 H,
J2b,3b ¼ 9.8 Hz, H-2b), 5.02 (t, 1 H, J4b,5b ¼ J4b,3b ¼ 9.8 Hz, H-4b), 5.17 (t, 1
H, J3b,4b ¼ J3b,2b ¼ 9.4 Hz, H-3b), 5.39 (t, 1 H, J3a,2a ¼ J3a,4a ¼ 9.7 Hz,
H-3a); 13C NMR (CDCl3) d: 20.4, 20.5, 20.6 (7 ꢀ CH3CO), 30.9 (C-6a), 55.2
(OCH3), 62.1 (C-6b), 68.2 (C-4b), 69.5 (C-5a), 69.8 (C-3a), 70.0 (C-2b), 70.7
(C-2a), 71.8 (C-4a), 73.7 (C-3b), 75.8 (C-5b), 83.8 (C-1b), 96.4 (C-1a),
169.5, 169.6, 170.0, 170.1, 170.2, (7 ꢀ 4 ꢀ CH3CO).
Methyl 2,3,4-tri-O-acetyl-6-S-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
glucpyranosyl)-6-thio-a-D-glucopyranoside (17). The residue was purified
by column chromatography using ethyl acetate–toluene (2 : 4) to give 17 as
colorless crystals mp 147–1498C; 1H NMR (CDCl3, 300 MHz) d: 1.95,
2.00, 2.03, 2.07, 2.11 (5 s, 21 H, 6 ꢀ OAc, NHAc), 2.76 (dd, 1 H,
0
J6a,5a ¼ 8.0 Hz, J6a,6 a ¼ 13.7 Hz, H-6a), 2.98 (dd, 1 H, J6’a,5a ¼ 2.5 Hz, J
¼ 13.7 Hz, H-60a), 3.41 (s, 3 H, OCH3), 3.67–3.69 (m, 1 H, H-5b),
0
6 a,6a
3.99–4.04 (m, 1 H, H-5a), 4.07–4.14 (m, 2 H, H-2b, H-6b), 4.21–4.25
(m, 1 H, H-60b), 4.60 (d, 1 H, J1b,2b ¼ 10.4 Hz, H-1b), 4.89 (dd, 1 H,
J2a,1a ¼ 3.5 Hz, J2a,3a ¼ 9.9 Hz, H-2a), 4.99 (d, 1 H, J1a,2a ¼ 3.5 Hz, H-1a),
5.07 (t, 1 H, J4a,3a ¼ 9.6 Hz, J4a,5a ¼ 9.6 Hz, H-4a), 5.10 (t, 2 H,
J3b,2b ¼ 9.8 Hz, J3b,4b ¼ 9.8 Hz, H-3b, H-4b), 5.44 (t, 1 H, J3a,2a ¼ 9.6 Hz,
J3a,4a ¼ 9.6 Hz, H-3a), 5.73 (d, 1 H, JNH,2b ¼ 9.3 Hz, NH); 13C NMR
(CDCl3) d: 19.4, 19.9, 19.96, 20.01, 20.04 (6 ꢀ CH3CO, NAc), 31.3
(C-6a), 52.7 (C-2b), 54.7 (OCH3), 61.6 (C-6b), 67.6 (C-4b), 67.9 (C-5a),
69.3 (C-3a), 70.1 (C-2a), 70.9 (C-4a), 73.1 (C-3b), 75.2 (C-5b), 85.1 (C-1b),
96.0 (C-1a), 169.3, 169.4, 169.44, 170.1, 170.4, (6 ꢀ 4 ꢀ CH3CO, NCO).
Synthesis of Hetar-2-yl 20,30,40,60-Tetra-O-acetyl-10-thio-b-D-
glycopyranosides (18–25)
Method A
A suspension of the glycosyl isothiouronium salts 3 or 4 (1 mmol), 2-chloro-3-
nitropyridine, 2-chloro-5-nitropyridine, 2-chloro-3-methylquinoxaline or 2,3-
dichloro quinoxaline (1 mmol), and triethylamine (5 mmol) in acetonitrile
(5 mL) was irradiated under MWI for 2–3 min, and then it was left to cool
at room temperature. The solid product was washed with water and dried,
whereas the syrup was dissolved in chloroform (25 mL), washed with
water, dried over anhydrous sodium sulfate, and evaporated.
Method B
A suspension of 3 or 4 (1 mmol), 2-chloro-3-nitropyridine, 2-chloro-5-nitro-
pyridine, 2-chloro-3-methylquinoxaline or 2,3-dichloro quinoxaline

2780
E. S. H. El Ashry et al.
(1 mmol), and triethylamine (5 mmol) in acetonitrile (5 mL) was stirred at
room temperature for 6–10 h and then concentrated under reduce pressure.
The residue was dissolved in CH2Cl2 (20 mL); the solution washed with
H2O (3 ꢀ 15 mL), dried (Na2SO4), and concentrated.
Data
(3-Nitropyrid-2-yl)20,30,40,60-tetra-O-acetyl-10-thio-b-D-glucopyranoside
(18). The residue was purified by column chromatography using ethyl
acetate–petroleum ether (1:4) to give as pale yellow crystals; mp 62–648C;
1H NMR (CDCl3, 500 MHz) d: 2.02, 2.03 (2 s, 12 H, 4 ꢀ OAc), 3.92
(dddd, 1 H, J5 ,6 ¼ 2.3 Hz, J5 ,6 ¼ 4.6 Hz, J5 ,4 ¼ 9.5 Hz, H-50), 4.08 (dd, 1
0
0
0
00
0
0
H, J6 ,5 ¼ 2.3 Hz, J6 ,6 ¼ 12.3 Hz, H-60), 4.24 (dd, 1 H, J6 ,5 ¼ 4.6 Hz,
0
0
0
00
00
0
J6 ,6 ¼ 12.3 Hz, H-600), 5.17 (dd, 1 H, J4 ,3 ¼ 9.2 Hz, J4 ,5 ¼ 9.5 Hz, H-40),
00
0
0
0
0
0
5.39 (ddd, 2 H, J1 ,2 ¼ 10.0 Hz, J2 ,3 ¼ 9.2 Hz, J3 ,4 ¼ 9.2 Hz, H-20, H-30),
0
0
0
0
0
0
6.06 (d, 1 H, J1 ,2 ¼ 10.0 Hz, H-10), 7.32 (dd, 1 H, J5,6 ¼ 4.6 Hz,
J5,4 ¼ 8.4 Hz, H-5), 8.54 (dd, 1 H, J4,6 ¼ 1.6 Hz, J4,5 ¼ 8.4 Hz, H-4), 8.72
(dd, 1 H, J6,4 ¼ 1.6 Hz, J6,5 ¼ 4.6 Hz, H-6); anal. calcd. for C19H22N2O11S:
C, 46.91; H, 4.56; N, 5.76. Found: C, 46.34; H, 4.94; N, 5.57.
0
0
(3-Nitropyrid-2-yl) 20-acetamido-30,40,60-tri-O-acetyl-20-deoxy-10-thio-b-
D-glucopyanoside (19). The crude product was recrystallized from
methanol to give 19 as pale yellow crystals, mp 195–1978C; 1H NMR
(CDCl3, 500 MHz) d: 1.89 (s, 3 H, NHAc), 2.01, 2.03, 2.05 (3 s, 9 H,
0
0
0
00
0
0
3 ꢀ OAc), 3.87 (dddd, 1 H, J5 ,6 ¼ 2.3 Hz, J5 ,6 ¼ 4.6 Hz, J5 ,4 ¼ 9.9 Hz,
H-50), 4.06 (dd, 1 H, J6 ,5 ¼ 2.3 Hz, J6 ,6 ¼ 12.3 Hz, H-60), 4.22 (dd, 1 H,
0
0
0
00
J6 ,5 ¼ 4.6 Hz, J6 ,6 ¼ 12.3 Hz, H-600), 4.43 (dd, 1 H, J2 ,1 ¼ 10.7 Hz, J2 ,
00
0
00
0
0
0
0
¼ 10.0 Hz, H-20), 5.19 (dd, 1 H, J4 ,3 ¼ 9.2 Hz, J4 ,5 ¼ 9.9 Hz, H-40),
0
0
0
0
30
5.32 (dd, 2 H, J3 ,2 ¼ 10.0 Hz, J3 ,4 ¼ 9.2, H-30), 5.74 (d, J2 ,NH ¼ 8.4 Hz,
0
0
0
0
0
NH), 6.06 (d, 1H, J1 ,2 ¼ 10.7 Hz, H-10), 7.30 (dd, 1 H, J5,6 ¼ 4.6 Hz,
J5,4 ¼ 8.4 Hz, H-5), 8.52 (dd, 1 H, J4,6 ¼ 1.6 Hz, J4,5 ¼ 7.7 Hz, H-4), 8.69
(dd, 1 H, J6,4 ¼ 1.6 Hz, J6,5 ¼ 4.6 Hz, H-6); anal. calcd. for C19H23N3O10S:
C, 47.01; H, 4.78; N, 8.66; S, 6.61. Found: C, 46.56; H, 5.12; N, 8.22; S, 6.44.
0
0
(5-Nitropyrid-2-yl) 20,30,40,60-tetra-O-acetyl-10-thio-b-D-glucopyranoside
(20). The crude product was recrystallized from methanol, to give 20 as
1
needles, mp 188–1908C; H NMR (CDCl3, 500 MHz) d: 2.02, 2.03, 2.04,
0
0
0
0
2.08 (4 s, 12 H, 4 ꢀ OAc), 3.92 (ddd, 1 H, J5 ,4 ¼ 9.5 Hz, J5 ,6 ¼ 1.9 Hz,
J5 ,6 ¼ 3.8 Hz, H-50), 4.10 (dd, 1 H, J6 ,5 ¼ 1.9 Hz, J6 ,6 ¼ 12.4 Hz, H-60),
0
00
0
0
0
00
4.28 (dd, 1 H, J6 ,5 ¼ 3.8 Hz, J6 ,6 ¼ 12.4 Hz, H-600), 5.18 (t, 1 H,
00
0
00
0
J4 ,3 ¼ J4 ,5 ¼ 9.5 Hz, H-40), 5.27 (dd, 1 H, J2 ,1 ¼ 10.5 Hz, J2 ,3 ¼ 9.5 Hz,
0
0
0
0
0
0
0
0
H-20), 5.38 (t,
1
H, J3 ,2 ¼ J3 ,4 ¼ 9.5 Hz, H-30), 5.92 (d,
1 H,
0
0
0
0
J1 ,2 ¼ 10.5 Hz, H-10), 7.33 (d, 1 H, J3,4 ¼ 8.6 Hz, H-3), 8.31 (dd, 1 H,
0
0
J4,3 ¼ 8.6 Hz, J4,6 ¼ 2.8 Hz, H-4), 9.26 (d, 1 H, J6,4 ¼ 2.8 Hz, H-6);

MW Irradiation in Thioglycoside Synthesis
2781
anal. calcd. for C19H22N2O11S: C, 46.91; H, 4.56; N, 5.76. Found: C, 46.85; H,
4.63; N, 5.76.
(5-Nitropyrid-2-yl) 2-acetamido-30,40,60-tri-O-acetyl-20-deoxy-10-thio-b-
D-glucopyanoside (21). The crude product was recrystallized from
methanol to give 21 as pale yellow crystals, mp 225–2278C; 1H NMR
(CDCl3, 500 MHz) d: 1.91 (s, 3 H, NHAc), 2.03, 2.04, 2.05 (3 s, 9 H,
0
0
0
0
0
00
3 ꢀ OAc), 3.87 (4dd, 1 H, J5 ,4 ¼ 9.9 Hz, J5 ,6 ¼ 1.8 Hz, J5 ,6 ¼ 4.6 Hz,
H-50), 4.09 (dd, 1H, J6 ,5 ¼ 1.8 Hz, J6 ,6 ¼ 13.0 Hz, H-60), 4.26 (dd, 1 H,
0
0
0
00
J6 ,5 ¼ 4.6 Hz, J6 ,6 ¼ 13.0 Hz, H-600), 4.43 (q, 1 H, J2 ,1 ¼ 9.9 Hz,
00
0
00
0
0
0
J2 ,3 ¼ 9.9 Hz, H-20), 5.12 (dd, 1 H, J4 ,3 ¼ 9.9 Hz, J4 ,5 ¼ 9.2 Hz, H-40),
0
0
0
0
0
0
5.24 (t, 1 H, J3 ,4 ¼ 9.9 Hz, J3 ,2 ¼ 9.9 Hz, H-30), 5.85 (d,
1
H,
0
0
0
0
J1 ,2 ¼ 11.4 Hz, H-10), 6.03 (d, 1 H, J2 ,NH ¼ 9.2 Hz, NH), 7.32 (d, 1 H
J3,4 ¼ 9.2 Hz, H-3), 8.27 (dd, 1 H, J4,3 ¼ 9.2 Hz, J4,6 ¼ 3.1 Hz, H-4), 9.20
(d, 1 H, J6,5 ¼ 2.3 Hz, H-6); 13C NMR (CDCl3) d: 20.7, 20.8, 20.9 (CH3CO),
23.4 (NHAc), 52.4 (C-20), 62.0 (C-60), 68.0 (C-40), 73.9 (C-30), 76.4 (C-50),
82.5 (C-10), 122.5 (C-3), 131.2 (C-4), 141.9 (C-2), 144.9 (C-6), 164.6 (C-5),
169.3, 170.4, 170.7, 171.3 (4 ꢀ CH3CO); anal. calcd. for C19H23N3O11S: C,
47.01; H, 4.78; N, 8.66; S, 6.61. Found: C, 46.95; H, 4.76; N, 8.66; S, 6.73.
0
0
0
(3-Methylquinoxalin-2-yl) 20,30,40,60-tetra-O-acetyl-10-thio-b-D-glucopyr-
anoside (22). The crude product was stirred with water, filtered, and recrystal-
lized from methanol to give 22 as yellow crystals, mp 173–1758C; 1H NMR
(CDCl3, 500 MHz) d: 1.9, 2.03, 2.05, 2.09 (4 s, 12 H, 4 ꢀ OAc), 2.65 (s, 3 H,
CH3), 4.06 (dddd, 1 H, J5 ,4 ¼ 9.9 Hz, J5 ,6 ¼ 2.3 Hz, J5 ,6 ¼ 4.6 Hz,H-50),
0
0
0
0
0
00
4.13 (dd, 1 H, J6 ,5 ¼ 2.3 Hz, J6 ,6 ¼ 12.3 Hz, H-60), 4.24 (dd, 1 H,
0
0
0
00
J6 ,5 ¼ 4.6 Hz, J6 ,6 ¼ 12.3 Hz, H-600), 5.20 (dd, 1 H, J4 ,3 ¼ 9.2 Hz,
00
0
00
0
0
0
J4 ,5 ¼ 9.9 Hz, H-40), 5.38 (dd, 1 H, J2 ,1 ¼ 10.7 Hz, J2 ,3 ¼ 9.2 Hz, H-20),
0
0
0
0
0
0
5.46 (t, 1 H, J3 ,2 ¼ J3 ,4 ¼ 9.2 Hz, H-30), 6.10 (d, 1 H, J1 ,2 ¼ 10.7 Hz,
H-10), 7.63–7.69 (m, 2 H, H-6, H-7), 7.9 (dd, 1 H, J5,7 ¼ 1.5 Hz,
J5,6 ¼ 9.2 Hz, H-5), 7.97 (dd, 1 H, J6,8 ¼ 1.5 Hz, J7,8 ¼ 8.5 Hz, H-8); anal.
calcd. for C23H26N2O9S: C, 54.54; H, 5.17; N, 5.53; S, 6.33. Found: C,
54.00; H, 5.19; N, 5.41; S, 7.00.
0
0
0
0
0
0
(3-Methylquinoxalin-2-yl) 20-acetamido-30,40,60-tri-O-acetyl-20-deoxy-10-
thio-b-D-glucopyranside (23). The product obtained was recrystallized
1
from ether to give 23 as yellow crystals, mp 212–2148C; H NMR (CDCl3,
500 MHz) d: 1.88 (s, 3 H, NHAc), 1.94, 2.07, 2.09 (3 s, 9 H, 3 ꢀ OAc),
2.69 (s, 3 H, CH3), 3.95–3.97 (m, 1 H, H-50), 4.12 (dd, 1 H, J6 ,5 ¼ 2.3 Hz,
0
0
J6 ,6 ¼ 12.2 Hz, H-60), 4.22 (dd, 1 H, J6 ,5 ¼ 5.3 Hz, J6 ,6 ¼ 12.2 Hz,
0
00
00
0
00
0
H-600), 4.59 (dd, 1 H, J2 ,NH ¼ 9.9 Hz, J2 ,3 ¼ 9.9 Hz, H-20), 5.22 (dd, 1 H,
0
0
0
J4 ,3 ¼ 9.2 Hz, J4 ,5 ¼ 9.9 Hz, H-40), 5.29 (dd, 1 H, J3 ,2 ¼ 9.9 Hz,
0
0
0
0
0
0
J3 ,4 ¼ 9.2 Hz, H-30), 5.87 (d, 1 H, J2 ,NH ¼ 9.9 Hz, NH), 5.97 (d, 1 H,
0
0
0
J1 ,2 ¼ 10.7 Hz, H-10), 7.63–7.69 (m, 2 H, H-6, H-7), 7.89 (dd, 1 H,
0
0
J5,7 ¼ 1.5 Hz, J5,6 ¼ 8.4 Hz, H-5), 7.97 (dd,
1
H, J6,8 ¼ 1.5 Hz,

2782
E. S. H. El Ashry et al.
J7,8 ¼ 7.7 Hz, H-8); anal. calcd. for C23H27N3O8S: C, 54.64; H, 5.38; N, 8.31;
S, 6.34. Found: C, 54.57; H, 5.40; N, 8.29; S, 6.50.
(3-Chloroquinoxalin-2-yl) 20,30,40,60-tetra-O-acetyl-10-thio-b-D-glucopyr-
anoside (24). The residue was purified by column chromatography using
ethyl acetate–petroleum ether (1:4) to give 24 as yellow crystal, mp 182–
1848C; 1H NMR (CDCl3, 500 MHz) d: 1.91, 2.04, 2.07 (3 s, 12 H, 4 ꢀ OAc),
4.02–4.09 (m, 1 H, H-50), 4.13 (d, 1 H, J6 ,6 ¼ 12.2 Hz, H-60), 4.24 (dd, 1 H,
0
00
J6 ,5 ¼ 5.4 Hz, J6 ,6 ¼ 12.3 Hz, H-600), 5.20 (dd, 1 H, J4 ,3 ¼ 9.2 Hz,
00
0
00
0
0
0
J4 ,5 ¼ 9.9 Hz, H-40), 5.38 (dd, 1 H, J2 ,1 ¼ 10.0 Hz, J2 ,3 ¼ 9.2 Hz, H-20),
0
0
0
0
0
0
5.45 (dd, 1 H, J3 ,4 ¼ 9.2 Hz, J3 ,2 ¼ 9.2 Hz, H-30), 5.95 (d, 1 H,
0
0
0
0
J1 ,2 ¼ 10.0 Hz, H-10), 7.72, 7.77 (2 t, 2 H, J6,7 ¼ 7.7 Hz, H-6, H-7), 7.98 (dd,
2 H, J5,7 ¼ 1.5 Hz, J5,6 ¼ 8.4, J7,8 ¼ 8.5 Hz, H-5, H-8); anal. calcd. for
C22H23ClN2O9S: C, 50.14; H, 4.40; N, 5.32. Found: C, 49.69; H, 4.46; N, 5.33.
0
0
(3-Chloroquinoxalin-2-yl) 20-acetamido-30,40,60-tri-O-acetyl-20-deoxy-10-
thio-b-D-glucopyranside (25). The residue was purified by column chrom-
atography using ethyl acetate–petroleum ether (2:4) to give 25 as yellow
1
crystal, mp 192–1948C; H NMR (CDCl3, 500 MHz) d: 1.88, 1.92, 2.05,
0
0
2.06 (4 s, 12 H, 3 ꢀ OAc, NHAc), 3.98 (ddd, 1 H, J5 ,6 ¼ 2.3 Hz,
J5 ,6 ¼ 5.3 Hz, J5 ,4 ¼ 9.9 Hz, H-50), 4.10 (dd, 1 H, J6 ,5 ¼ 2.3 Hz,
0
00
0
0
0
0
J6 ,6 ¼ 12.9 Hz, H-60), 4.18 (dd, 1 H, J6 ,5 ¼ 5.3 Hz, J6 ,6 ¼ 12.9 Hz,
0
00
00
0
00
0
H-600), 4.53 (dd, 1 H, J2 ,1 ¼ 10.7 Hz, J2 ,3 ¼ 9.9 Hz, H-20), 5.18 (dd, 1 H,
0
0
0
0
J4 ,3 ¼ 9.2 Hz, J4 ,5 ¼ 9.9 Hz, H-40), 5.33 (dd, 1 H, J3 ,2 ¼ 9.9 Hz,
0
0
0
0
0
0
J3 ,4 ¼ 9.2 Hz, H-30), 5.87 (d, 1 H, J1 ,2 ¼ 10.7 Hz, H-10), 5.93 (d, 1 H,
0
0
0
0
0
JNH,2 ¼ 9.2 Hz, NHAc), 7.67, 7.70, 7.73 (3 dd, 2 H, J6,7 ¼ 7.7 Hz, H-6,
H-7), 7.89 (dd, 1 H, J8,5 ¼ 1.5 Hz, J8,6 ¼ 8.4, J7,8 ¼ 8.5 Hz, H-8), 7.95 (dd,
1 H, J5,8 ¼ 1.5 Hz, J5,6 ¼ 8.4, J5,7 ¼ 6.9 Hz, H-5); 13C NMR (CDCl3) d:
20.7, 20.8, 20.9 (3 ꢀ OAc), 23.4 (NHAC), 52.4 (C-20), 62.3 (C-60), 68.3
(C-40), 74.2 (C-30), 76.5 (C-50), 82.4 (C-10), 127.6 (C-5), 128.5 (C-8), 129.8
(C-6), 130.7 (C-7), 139.7 (C-8b), 140.9 (C-5a), 145.1 (C-2), 152.9 (C-3),
169.4, 170.4, 170.8, 171.5 (4 ꢀ CH3CO); anal. calcd. for C23H27N3O8S: C,
50.24; H, 4.60; N, 7.99. Found: C, 49.71; H, 5.16; N, 7.69.
Synthesis of Bisthioglycosidequinoxaline (26, 27)
Method A
A suspension of the glycosyl isothiouronium salts 3 or 4 (2 mmol), 2,3-
dichloroquinoxaline (1 mmol), and triethylamine (10 mmol) in acetonitrile
(10 mL) was irradiated under MWI for 7 min, and then it was left to cool at
room temperature. The solvent was evaporated under reduced pressure; the
product was dissolved in chloroform (25 mL), washed with water, dried
over anhydrous sodium sulfate and then evaporated under reduced pressure.

MW Irradiation in Thioglycoside Synthesis
2783
Method B
A suspension of 3 or 4 (2 mmol), 2,3-dichloroquinoxaline (1 mmol), and tri-
ethylamine (10 mmol) in acetonitrile (20 mL) was stirred at room temperature
for 48 h, and then concentrated under reduced pressure. The residue was
dissolved in chloroform (20 mL); the solution washed with H2O
(3 ꢀ 15 mL) and dried over anhydrous sodium sulfate.
Data
2,3-bis(20,30,40,60-Tetra-O-acetyl-10-thio-b-D-glucopyranoside)quinoxa-
line (26). The residue was purified by column chromatography using ethyl
acetate–petroleum ether (1:4) to afford 13% of 24 and 57% of 26 as white
crystals, mp 167–1698C lit.[27] mp 169–1708C; 1H NMR (CD3OD,
500 MHz) d: 1.84, 2.02, 2.03, 2.05 (4 s, 24 H, 8 ꢀ OAc), 4.09 (d, 2 H,
J6 ,6 ¼ 12.6 Hz, H-60a,b), 4.11–4.18 (m, 2 H, H-50a,b), 4.26 (dd, 2 H,
0
00
J6 ,5 ¼ 5.7 Hz, J6 ,6 ¼ 12.6 Hz, H-600a,b), 5.15 (dd, 2 H, J4 ,3 ¼ 9.2 Hz,
00
0
00
0
0
0
J4 ,5 ¼ 9.8 Hz, H-40a,b), 5.32 (dd, 2 H, J2 ,1 ¼ 10.3 Hz, J2 ,3 ¼ 9.2 Hz,
0
0
0
0
0
0
H-20a,b), 5.50 (dd, 2 H, J3 ,4 ¼ 9.2 Hz, J3 ,2 ¼ 9.2 Hz, H-30a,b), 6.09 (d, 2
0
0
0
0
H, J1 ,2 ¼ 10.3 Hz, H-10a,b), 7.71 (dd, 2 H, J6,5 ¼ 6.3 Hz, H-6, H-7), 7.97
0
0
(dd, 2 H, J5,7 ¼ 3.4 Hz, J5,6 ¼ 6.3 Hz, H-5, H-8).
2,3-bis(20-Acetamido-30,40,60-tri-O-acetyl-20-deoxy-10-thio-b-D-glucopyr-
anside)quinoxaline (27). The residue was purified by column chromato-
graphy using ethyl acetate–petroleum ether (2:4) to afford 13% of 25 and
1
58% of 27 as yellow crystals, mp 192–1948C; H NMR (CD3OD þ D2O,
500 MHz) d: 1.80, 1.89, 2.01, 2.04 (4 s, 24 H, 6 ꢀ OAc, 2 ꢀ NHAc), 4.04–
00
0
4.06 (m,
00
4
H, H-50a,b,H-60a,b), 4.22 (dd,
2
H, J6 ,5 ¼ 3.5 Hz,
J6 ,6 ¼ 9.2 Hz, H-600a,b), 4.31 (dd, 2 H, J2 ,1 ¼ 10.8 Hz, J2 ,3 ¼ 9.7 Hz,
0
0
0
0 0
H-20), 5.08 (dd, 2 H, J4 ,3 ¼ 9.2 Hz, J4 ,5 ¼ 9.7 Hz, H-40), 5.40 (dd, 2 H,
0
0
0
0
J3 ,2 ¼ 9.7 Hz, J3 ,4 ¼ 9.2 Hz, H-30), 6.10 (d, 2 H, J1 ,2 ¼ 10.8 Hz, H-10),
7.72 (dd, 2 H, J6,5 ¼ 6.3 Hz, J6,8 ¼ 3.4 Hz, H-6, H-7), 7.98 (dd, 2 H,
J8,7 ¼ 6.3 Hz, J5,7 ¼ 3.4 Hz, H-5, H-8); anal. calcd. for C36H44N4O16S2: C,
50.70; H, 5.20; N, 6.57. Found: C, 50.61; H, 5.60; N, 6.23.
0
0
0
0
0
0
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