Efficient intramolecular β-mannoside formation using m-xylylene and isophthaloyl derivatives as rigid spacers

Article abstract of DOI:10.1016/S0008-6215(01)00306-8

A series of mannosyl donors linked via position 2 to an m-xylylene or an isophthaloyl spacer which was connected to the position 6 of a glucoside acceptor afforded, via intramolecular glycosylation, the corresponding disaccharides with high β anomeric ratio.

Full text of DOI:10.1016/S0008-6215(01)00306-8

Carbohydrate Research 337 (2002) 195–206
www.elsevier.com/locate/carres
Efficient intramolecular b-mannoside formation using m-xylylene
and isophthaloyl derivatives as rigid spacers
Adel A.-H. Abdel-Rahman,a El Sayed H. El Ashry,b Richard R. Schmidta,*
aDepartment of Chemistry, Uni6ersity of Konstanz, Fach M 725, D-78457 Konstanz, Germany
bDepartment of Chemistry, Faculty of Science, Uni6ersity of Alexandria, Alexandria, Egypt
Received 28 July 2001; accepted 15 November 2001
Abstract
A series of mannosyl donors linked via position 2 to an m-xylylene or an isophthaloyl spacer which was connected to the
position 6 of a glucoside acceptor afforded, via intramolecular glycosylation, the corresponding disaccharides with high b
anomeric ratio. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Glycosides; b-Mannopyranosides; Synthesis; Intramolecular glycosidation; Hetaryl thioglycosides
1. Introduction
ing centers. The intramolecular glycosylation approach
by ‘linkage of the accepting atom to the donor via a
bifunctional group’ (‘intramolecular aglycon delivery’,
IAD) was originally developed for the synthesis of
b-mannopyranosides and later extended to the synthesis
of other glycosides. The synthesis of the b-mannosidic
linkage is a difficult task11 because the anomeric effect
favors, thermodynamically, the formation of a-man-
nosides, and participating neighboring groups at 2-O
also lead to a-mannosides (1,2-trans configuration).18,19
The 2-O-isopropenyl ether derivative of thioman-
nosides as a donor was used for the acid-catalyzed
addition of the 6-O or 4-O-unprotected acceptors to
yield the corresponding isopropylidene ketal deriva-
tives. Then, glycosylation by activation of the
thiogroup with N-iodosuccinimide (NIS) yielded exclu-
sively b-mannosides in good yields.20–23 To avoid ketal
formation, the methoxybenzylidene acetal was designed
as a bifunctional group for the attachment of the
acceptor to the glycosyl fluoride donor.24 Further im-
provement was achieved with the help of thioglycoside
donors.25,26 The high performance of the methoxyben-
zylidene acetal method enabled its use for the key step
in the total synthesis of the core pentasaccharide unit of
N-glycoproteins.27,28 It was demonstrated that the
methoxybenzylidene acetal method is also suitable in
polymer-supported synthesis.29 In another approach to
the synthesis of b-mannosides applying the ‘linkage of
As the interest in carbohydrate derivatives with bio-
logically important properties is increasing,1–4 the de-
velopment of selective and efficient methods for the
construction of glycoside bonds is now becoming more
and more important, not only in carbohydrate chem-
istry but also in organic synthesis in general.5–13 The
practical and stereocontrolled synthesis of oligosaccha-
rides is therefore an area of current interest, and partic-
ular attention has recently been paid to the
development of regioselective non-enzymatic glycosyla-
tion methods that would obviate the need for complex
protecting group strategies. Recently, various studies
for anomeric stereocontrol have been reported using the
intramolecular reaction of a glycosyl donor and a gly-
cosyl acceptor which are connected via a suitable
linker.14 The developed methods can be divided into
three classes of spacer-mediated linkages of the accep-
tor to the donor:15–17 (i) Leaving group based accep-
tor–donor linkage; (ii) linkage of the accepting atom
via a bifunctional group to the donor; (iii) spacer
mediated linkage of acceptor and donor via nonreact-
* Corresponding author. Tel.: +49-7531-882538; fax: +
49-7531-883135.
E-mail addresses: eelashry@link.net (E.S.H. El Ashry),
richard.schmidt@uni-konstanz.de (R.R. Schmidt).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00306-8

196
A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
the accepting atom via a bifunctional group’, a silicon-
tethered ‘disaccharide’ was used for intramolecular gly-
cosylations applying sulfoxide activation.30 Further
improvement of the method concerning the preparation
of the silicon-tethered ‘disaccharide’ also enabled the
use of secondary hydroxy groups in the acceptors.31
Variation of the tethering position at the donor and
the acceptor moiety, of the length of the tethering
group, and of the activation method gave a large
number of interesting results [see (iii)].14,32–34 For the
synthesis of Manb(1“4)Gal disaccharides, (6,6%)-teth-
ered glycoside precursors were also used.33 The ‘spacer-
mediated linkage via nonreacting centers’ concept was
also employed for the investigation of the regio- and
stereoselectivity of intramolecular glycosylation reac-
tions using phthaloyl or isophthaloyl spacers.35–37 In
order to obtain the desired close proximity between the
glycosyl donor and acceptor moiety, the rigid spacer
concept was designed.14–17 As this leads to a struc-
turally rigid array, a highly diastereoselective glycosyla-
tion under construction of a large ring should be
enforced. As a powerful example for a rigid spacer, the
m-xylylene moiety and derivatives were chosen. Excel-
lent results in the formation of various glycosidic link-
ages were obtained.14–17
solution of 2 in acetonitrile with 2-mercaptobenzoxa-
zole (3a), 2-mercaptobenzothiazole (3b), 2-mercaptopy-
rimidine (3c) and 2-mercaptopyridine (3d) in the
presence of catalytic amounts of mercury(II) bromide
gave thioglycoside donors 4a–d in 87–93% yields. The
1
protons in the H NMR spectra of 4a–d were assigned
by 1H–1H homonuclear shift correlated (COSY) 2D
NMR spectroscopy. The a configurations of 4a–d were
indicated by the appearance of the anomeric protons as
doublets at l 6.35, 6.33, 6.59 and 6.40 with coupling
constant values of J1,2 1.6, 1.7, 1.7 and 1.7 Hz, respec-
tively. The a configuration at C-1 in the reaction prod-
1
ucts was finally established by H NMR analysis and
comparison with the spectroscopic data recorded in
1
literature.44 The H NMR spectra showed singlets at l
2.21, 2.19, 2.19 and 2.17 corresponding to the acetyl
groups, and the 13C NMR spectra showed signals at l
170.01, 169.98, 170.24, 170.17 (CꢀO), 20.81, 20.99,
21.12 and 21.10 (Me) of the acetyl groups, respectively.
Deacetylation gave the corresponding donors 5a–d in
quantitative yields. The 1H NMR spectra of the
deacetylated products 5a–d showed the disappearance
of the acetyl groups, and the appearance of the hy-
droxyl groups as broad singlets (D2O exchangeable) at
l 2.46, 2.38, 2.52, and 2.76, respectively.
These results prompted us to apply this concept to
b-mannoside formation using m-xylylene and also
isophthaloyl derivatives as rigid spacers.
Isophthaloyl spacer system in the intramolecular gly-
cosylation.—Treatment of 5d with isophthaloyl chlo-
ride (6) in dry toluene and in the presence of a catalytic
amount of dry pyridine under argon at room tempera-
ture afforded 7a which is very sensitive to moisture,
therefore, it was used for the next step without purifica-
tion (Scheme 2). In the case of purification of the acid
chloride derivative 7a by flash-column chromatogra-
phy, the hydrolyzed product 7b was obtained in 78%
yield. The structure of 7b was confirmed by studying its
1H NMR spectrum, which showed a broad singlet (D2O
exchangeable) at l 3.04 corresponding to the OH
group. For the synthesis of the isophthaloyl spacer
connected donor–acceptor system 9, methyl 2,3-di-O-
2. Results and discussion
Synthesis of glycosyl donors.—The known 3,4,6-tri-
O-acetyl-b-
-mannopyranose orthoacetate (1)38–40 was
D
transformed into 3,4,6-tri-O-benzyl-b-D-mannopyran-
ose orthoacetate (2)41–43 (Scheme 1). Treatment of a
benzyl-a-
-glucopyranoside (8)45,46 was treated with
D
dibutyltin oxide in dry toluene at reflux temperature
under azeotropic removal of water, cooled to room
temperature, and then followed by addition of com-
pound 7a and tetrabutylammonium iodide. The reac-
tion was monitored by TLC which gave 77% yield after
purification with flash-column chromatography. Com-
pound 9 could also be synthesized in 70% yield by
dissolving the 4,6-O-unprotected glucoside 8 and 7a in
dry dichloromethane at 0 °C with catalytic amounts of
pyridine. Alternatively, compound 9 could be synthe-
sized in 68% yield by adding diethyl azodicarboxylate
(DEAD) solution in tetrahydrofuran (THF) to the dis-
solved mixture of compound 7b, diol
8
and
triphenylphosphine in dry THF at room temperature.
Activation of the pyridylthio group in 9 with N-iodo-
succinimide (NIS, 1.3 equiv) and trimethylsilyl
Scheme 1. Reagents and conditions: (a) HgBr2, MeCN; (b)
NaOMe, MeOH.

A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
197
Scheme 2. (a) Toluene/Py; (b) Method A, Bu2SnO, Toluene; Method B, CH2Cl2/Py; Method C, Ph3P, THF, DEAD; (c)
NIS/TMSOTf, CH2Cl2; (d) MeONa, MeOH; (e) Pd/C, H2; Ac2O, Py.
trifluoromethanesulfonate†,‡ (TMSOTf, 0.1 equiv)47–50
in dry CH2Cl2 at room temperature afforded the de-
sired (1“4)-linked disaccharide 10, after separation by
flash-column chromatography in an a/b ratio of 1:6
(yield 70%). The a and b configuration could be as-
signed with the help of 13C NMR data of the anomeric
carbon. The b anomer showed a signal at l 101.01 (JCH
158.1 Hz), while the a anomer showed a signal at l
99.71 (JCH 173.1 Hz). The a and b configuration at C-1
in 10 was established by NMR analysis and comparison
with the spectroscopic data recorded in literature.36
Removal of the isophthaloyl spacer was carried out by
treating 10b with a solution of sodium methoxide in
methanol at room temperature to give 11 with 90%
yield. Hydrogenolytic O-debenzylation of 11 and then
O-acetylation afforded 12, which was structurally as-
signed by homo- and heteronuclear NMR spectra.
m-Xylylene spacer system in the intramolecular glyco-
sylation.—For the investigation of this concept, com-
pounds 5a–c were transformed with a,a%-dibromoxyl-
ene (13) in the presence of NaH as base and 15-crown-5
as supporting reagent into 2-O-linked derivatives 14a–c
(Scheme 3). Treatment of the diol 8 with dibutyltin
oxide in dry toluene, and then reaction with 14a–c in
the presence of tetrabutylammonium iodide (TBAI)
afforded the desired 2a,6b-O-linked intermediates 15a–
c in 78–84% yield. Activation of 15a–c with NIS–TM-
SOTf afforded 16 in 78% yield (from 15a, a/b ratio
1:10), 75% yield (from 15b, a/b ratio 1:9) and 76% yield
(from 15c, a/b ratio 1:10). The a and b configuration
could be assigned with the help of 13C NMR data of
the anomeric carbon. The b anomer showed a signal at
l 101.09 (JCH 158.3 Hz), while the a anomer showed a
signal at l 99.97 (JCH 174.0 Hz). Hydrogenolytic O-
debenzylation of 16 and then O-acetylation afforded
again 12.
Synthesis of the disaccharide glycosyl donor.—Treat-
ment of a solution of 241–43 in acetonitrile with 2,5-
dimercapto-1,3,4-thiadiazole (17) by the same method
as described for 4a–d afforded, after chromatographic
purification, 18 in 88% yield (Scheme 4). The protons in
1
1
the H NMR spectrum of 18 were assigned by H–1H
homonuclear shift correlated (COSY) 2D NMR spec-
troscopy. The a configuration of 18 was confirmed by
the appearance of the anomeric proton as a doublet at
l 6.39 with coupling constant value of J1,2 1.7 Hz. The
integration corresponded to two protons due to reac-
† Mercuric, silver, and copper salts, respectively, were also
used for the activation of thioglycosides.49
‡ For the activation of a heterocyclic thioglycoside with
TMSOTf, see Ref. 50.
1
tion with the two available mercapto groups. The H
NMR spectrum showed a singlet at l 2.18 (integration

198
A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
Scheme 3. (a) NaH, 15-Crown-5, CH2Cl2; (b) Bu2SnO, Toluene, TBA; (c) NIS, TMSOTf, CH2Cl2; (d) Pd/C, H2; Ac2O, Py.
derivatives which are useful intermediates for various
applications.
for 6 H) corresponding to the two acetyl groups.
Deacetylation gave the corresponding donor derivative
19 in 97% yield. The H NMR spectrum showed the
1
disappearance of the signal of the acetyl group and the
appearance of a broad singlet (D2O exchangeable) at l
2.79 (integration for 2 H). Compound 19 was trans-
formed with a,a%-dibromoxylene (13) (2 equiv), as de-
scribed for 15a–c, into 20 in 77% yield. Treatment of
844,45 with dibutyltin oxide in dry toluene and then
reaction with 20 afforded the bis(2a,6b-O-linked) inter-
mediate 21 in 70% yield. Activation of 21 with NIS–
TMSOTf afforded 16 in 72% yield in an a/b ratio of
1:6.
In conclusion, we have developed an efficient and
highly regio- and stereoselective protocol for in-
tramolecular b-mannopyranoside synthesis by using 2-
thio derivatives of nitrogen heterocycles as the leaving
group at the anomeric position and m-xylylene and
isophthaloyl derivatives, respectively, as rigid spacers
linked to the 2-hydroxy group of the mannose residue.
The m-xylylene spacer proved to be particularly suit-
able. The method should permit the synthesis of a
variety of differently functionalized b-mannopyranoside
3. Experimental
General methods.—Acetonitrile, CH2Cl2, and pyri-
dine were distilled from CaH2 and stored over molecu-
lar sieves. Tetrahydrofuran (THF) was distilled from
sodium–benzophenone before use. Other solvents were
purified according to the standard procedures. TLC
was performed on plastic plates Silica Gel 60 F254 (E.
Merck, layer thickness 0.2 mm). The detection was
achieved by treatment with a solution of 20 g ammo-
nium molybdate and 0.4 g cerium(IV) sulfate in 400 mL
10% H2SO4 or with 15% H2SO4 in MeOH and heating
at 150 °C. Flash chromatography was carried out on
Silica Gel (Baker, 30–60 mm). Optical rotations were
determined at 23 °C with a Perkin–Elmer 241/MC
polarimeter (1 dm cell). NMR spectra were recorded
with Bruker AC 600 DRX instruments, using tetra-
methylsilane as internal standard. MALDI Mass spec-
tra were recorded on a Kratos Kompact MALDI

A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
199
Scheme 4. (a) HgBr2, MeCN; (b) MeONa, MeOH; (c) 13, NaH, 15-Crown-5, CH2Cl2; (d) 8, Bu2SnO, Toluene; (e) NIS, TMSOTf,
CH2Cl2.
Hz, H-6), 2.21 (s, 3 H, CH3CO). 13C NMR (150.8
instrument, using a 2,5-dihydroxybenzoic acid matrix.
MHz, CDCl3): l 170.01 (CH3CO), 161.90, 152.75,
138.00, 137.99, 137.27, 135.78, 128.45, 128.31, 128.20,
127.90, 127.83, 127.75, 127.66, 126.52, 126.37, 126.21,
125.20, 124.71, 124.39, 122.40, 120.99, 117.91 (Ar-car-
bons), 84.61 (C-1), 78.37 (C-3), 75.30 (CH2Ph), 74.11
(C-5), 74.02 (C-4), 73.37 (2 CH2Ph), 72.08, 69.74 (C-2),
68.33 (C-6), 20.81 (CH3CO). FAB-MS (positive mode,
NBOH–NaI-matrix): m/z 626 [MH+], 648 [MNa+].
Anal. Calcd for C36H35NO7S (625.73): C, 69.10; H,
5.63; N, 2.23. Found: C, 69.00; H, 5.57; N, 2.16.
FAB Mass spectra were recorded on a Finnigan MAT
312/AMD 5000 spectrometer, using a 1:1 (3-nitroben-
zyl)alcohol–glycerol matrix.
General procedure for the synthesis of compounds 4a–
d.—The thioderivatives 3a–d (4 mmol) and HgBr2 (20
mg) were added to a solution of 241–43 (0.50 g, 1.0
mmol) in dry MeCN (5 mL). The mixture was heated
to 60 °C under argon for 3.5–4.0 h, and then concen-
trated. A solution of the residue in CH2Cl2 was washed
with 5% aq NaOH (30 mL), water, dried (MgSO4), and
concentrated. The residue was purified with flash-
column chromatography using 10:1 petroleum ether–
EtOAc to give 4a–d in 87–93% yield. Flash-column
chromatography using 10:1 petroleum ether–EtOAc to
give 4a–d in 87–93% yield.
Benzothiazol-2-yl
2-O-acetyl-3,4,6-tri-O-benzyl-l-
thio-h- -mannopyranoside (4b). Yield 89%, mp 90–
D
92 °C from diethyl ether/petroleum ether; TLC (5:1
petroleum ether–EtOAc): Rf 0.55; [h]D +166° (c 1.4,
1
CHCl3); H NMR (600 MHz, CDCl3): l 7.91 (d, 1 H,
Benzoxazol-2-yl
thio-h- -mannopyranoside (4a). Yield 89% as an oil;
TLC (5:1 petroleum ether–EtOAc): Rf 0.51; [h]D
2-O-acetyl-3,4,6-tri-O-benzyl-1-
J 6.8 Hz, H-7%), 7.73 (t, 1 H, J 7.0 Hz, H-6%), 7.42 (t, 1
H, J 6.9 Hz, H-5%), 7.33–7.24 (m, 15 H, 3 Ph), 7.17 (d,
1 H, J 6.8 Hz, H-4%), 6.33 (d, 1 H, J1,2 1.7 Hz, H-1),
5.66–5.59 (m, 1 H, H-2), 4.75, 4.73 (2 d, 2 H, Jgem 11.2
Hz, CH2Ph), 4.66, 4.57 (2 d, 2 H, Jgem 10.7 Hz,
CH2Ph), 4.52, 4.45 (2 d, 2 H, Jgem 11.1 Hz, CH2Ph),
4.13–4.09 (m, 1 H, H-5), 4.06 (t, 1 H, J3,4 9.5 Hz, H-4),
3.90–3.85 (m, 2 H, H-3, H-6), 3.70 (d, 1 H, Jgem 10.9
Hz, H-6), 2.19 (s, 3 H, CH3CO). 13C NMR (150.8
MHz, CDCl3): l 169.98 (CH3CO), 161.96, 152.74,
138.07, 137.97, 137.27, 135.78, 128.45, 128.30, 128.18,
127.95, 127.80, 127.73, 127.67, 126.51, 126.36, 126.21,
125.22, 124.78, 124.34, 122.30, 120.94, 117.98 (Ar-car-
D
+
1
180° (c 3.0, CHCl3); H NMR (600 MHz, CDCl3): l
7.87 (d, 1 H, J 6.9 Hz, H-7%), 7.80 (t, 1 H, J 7.0 Hz,
H-6%), 7.40 (t, 1 H, J 6.8 Hz, H-5%), 7.32–7.23 (m, 15 H,
3 Ph), 7.19 (d, 1 H, J 6.7 Hz, H-4%), 6.35 (d, 1 H, J1,2 1.6
Hz, H-1), 5.64–5.59 (m, 1 H, H-2), 4.72, 4.67 (2 d, 2 H,
Jgem 11.5 Hz, CH2Ph), 4.65, 4.58 (2 d, 2 H, Jgem 11.9
Hz, CH2Ph), 4.53, 4.43 (2 d, 2 H, Jgem 11.5 Hz,
CH2Ph), 4.11–4.02 (m, 1 H, H-5), 4.08 (t, 1 H, J3,4 9.6
Hz, H-4), 3.89–3.80 (m, 1 H, H-3), 3.84 (dd, 1 H, Jgem
11.0, J5,6 3.0 Hz, H-6), 3.71 (dd, 1 H, Jgem 11.0, J5,6 3.1

200
A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
bons), 84.80 (C-1), 78.21 (C-3), 75.26 (CH2Ph), 74.09
(C-5), 73.97 (C-4), 73.32, 72.00 (2 CH2Ph), 69.71 (C-2),
68.35 (C-6), 20.99 (CH3CO). FAB-MS (positive mode,
NBOH–NaI-matrix): m/z 642 [MH+], 664 [MNa+].
Anal. Calcd for C36H35NO6S2 (641.79): C, 67.37; H,
5.49; N, 2.18. Found: C, 67.17; H, 5.33; N, 2.09.
Pyrimidin-2-yl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-
was added with stirring for 2 h at rt. The reaction
mixture was neutralised with Amberlite IR-120. The
ion-exchange resin was removed and after evaporation
of the solvent under reduced pressure, compounds 5a–d
were obtained in quantitative yield. The products are
pure enough for the next step.
Benzoxazol-2-yl
3,4,6-tri-O-benzyl-1-thio-h-D-
h-
D
-mannopyranoside (4c). Yield 93% as an oil; TLC
mannopyranoside (5a). Yellow oil; TLC (5:1 petroleum
ether–EtOAc): Rf 0.44; [h]D +28° (c 1.0, CHCl3); H
1
(5:1 petroleum ether–EtOAc): Rf 0.50; [h]D +150° (c
2.0, CHCl3); H NMR (600 MHz, CDCl3): l 8.53 (t, 1
1
NMR (600 MHz, CDCl3): l 7.86 (d, 1 H, J 7.0 Hz,
H-7%), 7.79 (t, 1 H, J 7.0 Hz, H-6%), 7.41 (t, 1 H, J 7.2
Hz, H-5%), 7.33–7.24 (m, 15 H, 3 Ph), 7.21 (d, 1 H, J 6.7
Hz, H-4%), 6.71 (d, 1 H, J1,2 1.6 Hz, H-1), 4.81, 4.60 (2
d, 1 H, Jgem 11.5 Hz, CH2Ph), 4.70–4.66 (m, 2 H,
CH2Ph), 4.50, 4.48 (2 d, 2 H, Jgem 10.8 Hz, CH2Ph),
4.31 (d, 1 H, J2,3 1.7 Hz, H-2), 4.10–4.01 (m, 2 H, H-4,
H-5), 3.88–3.83 (m, 1 H, H-3), 3.80 (d, 1 H, Jgem 10.9
Hz, H-6), 3.69 (d, 1 H, Jgem 10.7 Hz, H-6), 2.38 (br.s, 1
H, OH, D2O exchangeable). 13C NMR (150.8 MHz,
CDCl3): l 161.88, 152.71, 138.04, 137.90, 137.25,
135.77, 128.43, 128.32, 128.23, 127.90, 127.80, 127.73,
127.66, 126.52, 126.36, 126.20, 125.21, 124.70, 124.40,
122.40, 120.97, 117.90 (Ar-carbons), 83.52 (C-1), 80.40
(C-3), 75.22 (CH2Ph), 74.71 (C-5), 74.10 (C-4), 73.36,
72.13 (2 CH2Ph), 70.34 (C-2), 68.66 (C-6). FAB-MS
(positive mode, NBOH–NaI-matrix): m/z 584 [MH+],
606 [MNa+]. Anal. Calcd for C34H33NO6S (583.69): C,
69.96; H, 5.69; N, 2.39. Found: C, 69.81; H, 5.48; N,
2.19.
H, J 7.0 Hz, H-5%), 7.34–7.24 (m, 15 H, 3 Ph), 7.16 (d,
1 H, J 6.8 Hz, H-6%), 7.00 (d, 1 H, J3,4 6.9 Hz, H-4%),
6.59 (d, 1 H, J1,2 1.7 Hz, H-1), 5.63–5.60 (m, 1 H, H-2),
4.87, 4.73 (2 d, 2 H, Jgem 11.2 Hz, CH2Ph), 4.63, 4.56 (2
d, 2 H, Jgem 11.1 Hz, CH2Ph), 4.51, 4.45 (2 d, 2 H, Jgem
12.2 Hz, CH2Ph), 4.03–3.98 (m, 2 H, H-4, H-5), 3.91
(dd, 1 H, J2,3 9.1, J3,4 3.3 Hz, H-3), 3.83 (dd, 1 H, Jgem
11.0, J5,6 3.0 Hz, H-6), 3.67 (dd, 1 H, Jgem 11.0, J5,6 3.0
Hz, H-6), 2.19 (s, 3 H, CH3CO). 13C NMR (150.8
MHz, CDCl3): l 170.24 (CH3CO), 157.62, 138.17,
138.15, 137.46, 128.42, 128.29, 128.21, 128.18, 127.87,
127.72, 127.64, 127.47, 117.48 (Ar-carbons), 82.00 (C-
1), 78.77 (C-3), 75.27 (CH2Ph), 74.72 (C-5), 74.13 (C-4),
73.25, 71.85 (2 CH2Ph), 70.57 (C-2), 68.63 (C-6), 21.12
(CH3CO). FAB-MS (positive mode, NBOH–NaI-ma-
trix): m/z 587 [MH+], 609 [MNa+]. Anal. Calcd for
C33H34N2O6S (586.70): C, 67.55; H, 5.84; N, 4.77.
Found: C, 67.38; H, 5.57; N, 4.57.
Pyridin-2-yl 2-O-acetyl-3,4,6-tri-O-benzyl-l-thio-h-
D
-mannopyranoside (4d). Yield 93%, mp 67–68 °C from
Benzothiazol-2-yl
3,4,6-tri-O-benzyl-1-thio-h-D-
diethyl ether/petroleum ether; TLC (5:1 petroleum
ether–EtOAc): Rf 0.54; [h]D +118° (c 1.0, CHCl3); H
mannopyranoside (5b). Mp 105–107 °C from diethyl
ether/petroleum ether; TLC (5:1 petroleum ether–
EtOAc): Rf 0.43; [h]D +12° (c 1.7, CHCl3); H NMR
1
1
NMR (600 MHz, CDCl3): l 8.48 (d, 1 H, J 6.9 Hz,
H-6%), 7.48 (t, 1 H, J 7.0 Hz, H-5%), 7.34–7.29 (m, 15 H,
3 Ph), 7.26 (d, 1 H, J 7.1 Hz, H-4%), 7.17 (d, 1 H, J 7.0
Hz, H-3%), 6.40 (d, 1 H, J1,2 1.7 Hz, H-1), 5.64–5.60 (m,
1 H, H-2), 4.87, 4.74 (2 d, 2 H, Jgem 11.2 Hz, CH2Ph),
4.63, 4.54 (2 d, 2 H, Jgem 11.2 Hz, CH2Ph), 4.52, 4.43 (2
d, 2 H, Jgem 11.9 Hz, CH2Ph), 4.11–4.07 (m, 1 H, H-5),
4.00 (t, 1 H, J3,4 9.6 Hz, H-4), 3.92 (dd, 1 H, J3,4 9.3,
J2,3 3.2 Hz, H-3), 3.83 (dd, 1 H, Jgem 11.1, J5,6 3.0 Hz,
H-6), 3.68 (dd, 1 H, Jgem 11.0, J5,6 3.2 Hz, H-6), 2.17 (s,
3 H, CH3CO). 13C NMR (150.8 MHz, CDCl3): l
170.17 (CH3CO), 155.83, 149.70, 138.29, 138.21,
137.57, 136.64, 128.42, 128.29, 128.21, 128.19, 127.84,
127.71, 127.62, 127.47, 123.47, 123.33, 120.76, 119.43
(Ar-carbons), 82.18 (C-1), 78.80 (C-3), 75.22 (CH2Ph),
74.30 (C-5), 73.91 (C-4), 73.26, 71.82 (2 CH2Ph), 70.54
(C-2), 68.83 (C-6), 21.10 (CH3CO). FAB-MS (positive
mode, NBOH–NaI-matrix): m/z 586 [MH+], 608
[MNa+]. Anal. Calcd for C34H35NO6S (585.71): C,
69.72; H, 6.02; N, 2.39. Found: C, 69.60; H, 5.87; N,
2.22.
(600 MHz, CDCl3): l 7.93 (d, 1 H, J 7.0 Hz, H-7%), 7.71
(d, 1 H, J 7.2 Hz, H-6%), 7.41 (t, 1 H, J 7.1 Hz, H-5%),
7.31–7.22 (m, 15 H, 3 Ph), 7.20 (d, 1 H, J 6.9 Hz, H-4%),
6.77 (d, 1 H, J1,2 1.8 Hz, H-1), 4.83, 4.63 (2 d, 2 H, Jgem
12.1 Hz, CH2Ph), 4.71–4.66 (m, 2 H, CH2Ph), 4.49,
4.41 (2 d, 2 H, Jgem 11.0 Hz, CH2Ph), 4.38 (d, 1 H, J2,3
1.8 Hz, H-2), 4.08–3.99 (m, 2 H, H-4, H-5), 3.85–3.80
(m, 1 H, H-3), 3.78 (d, 1 H, Jgem 10.9 Hz, H-6), 3.72 (d,
1 H, Jgem 10.9 Hz, H-6), 2.46 (br.s, 1 H, OH, D2O
exchangeable). 13C NMR (150.8 MHz, CDCl3): l
161.90, 152.70, 138.09, 137.99, 137.28, 135.77, 128.31,
128.24, 128.13, 127.97, 127.82, 127.77, 127.66, 126.52,
126.33, 126.23, 125.20, 124.76, 124.34, 122.30, 120.95,
118.01 (Ar-carbons), 83.55 (C-1), 80.43 (C-3), 75.26
(CH2Ph), 74.70 (C-5), 74.14 (C-4), 73.38, 72.15 (2
CH2Ph), 70.37 (C-2), 68.65 (C-6). FAB-MS (positive
mode, NBOH–NaI-matrix): m/z 600 [MH+], 622
[MNa+]. Anal. Calcd for C34H33NO5S2 (599.75): C,
68.08; H, 5.54; N, 2.33. Found: C, 67.89; H, 5.55; N,
2.20.
General procedure for the synthesis of compounds 5a–
d.—Compounds 4a–d (1 mmol) were dissolved in dry
MeOH (10 mL) and 1 M sodium methoxide in MeOH
Pyrimidin-2-yl
mannopyranoside (5c). Yellow oil; TLC (5:1 petroleum
ether–EtOAc): Rf 0.39; [h]D +43° (c 1.0, CHCl3); H
3,4,6-tri-O-benzyl-l-thio-h-D-
1

A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
201
1
NMR (600 MHz, CDCl3): l 8.54 (d, 1 H, J 7.1 Hz,
H-5%), 7.36–7.25 (m, 15 H, 3 Ph), 7.18 (d, 1 H, J 6.8 Hz,
H-6%), 7.03 (d, 1 H, J 6.9 Hz, H-4%), 6.60 (d, 1 H, J1,2 1.8
Hz, H-1), 4.83, 4.61 (2 d, 2 H, Jgem 11.2 Hz, CH2Ph),
4.71–4.67 (m, 2 H, CH2Ph), 4.53, 4.45 (2 d, 2 H, Jgem
10.7 Hz, CH2Ph), 4.28 (d, 1 H, J2,3 1.9 Hz, H-2),
4.02–3.98 (m, 2 H, H-4, H-5), 3.87 (m, 1 H, H-3), 3.79
(d, 1 H, Jgem 10.4 Hz, H-6), 3.67 (d, 1 H, Jgem 10.5 Hz,
H-6), 2.52 (br.s, 1 H, OH, D2O exchangeable). 13C
NMR (150.8 MHz, CDCl3): l 157.61, 138.16, 137.56,
128.57, 128.36, 128.26, 128.04, 127.99, 127.95, 127.89,
127.71, 127.52, 117.35 (Ar-carbons), 83.50 (C-1), 80.41
(C-3), 75.21 (CH2Ph), 74.77 (C-5), 74.07 (C-4), 73.33,
72.10 (2 CH2Ph), 70.41 (C-2), 68.61 (C-6). FAB-MS
(positive mode, NBOH–NaI-matrix): m/z 545 [MH+],
567 [MNa+]. Anal. Calcd for C31H32N2O5S (544.66): C,
68.36; H, 5.92; N, 5.14. Found: C, 68.11; H, 5.77; N,
4.98.
ether–EtOAc): Rf 0.68; [h]D +18° (c 1.1, CHCl3); H
NMR (600 MHz, CDCl3): l 8.43 (d, 1 H, J 7.2 Hz,
H-6%), 7.50–7.48 (m, 1 H, H-5%), 7.45–7.40 (m, 3 H,
H-2%%, H-4%%, H-5%%, H-6%%), 7.34–7.19 (m, 15 H, 3 Ph),
7.17–7.10 (m, 1 H, H-4%), 7.02–6.98 (m, 1 H, H-3%),
6.32 (d, 1 H, J1,2 1.8 Hz, H-1), 4.82, 4.62 (2 d, 2 H, Jgem
12.2 Hz, CH2Ph), 4.57–4.53 (m, 2 H, CH2Ph), 4.50,
4.40 (2 d, 2 H, Jgem 10.9 Hz, CH2Ph), 4.29–4.21 (m, 1
H, H-2), 4.12–4.08 (m, 2 H, H-4, H-5), 3.87 (dd, 1 H,
J3,4 3.5, J2,3 1.8 Hz, H-3), 3.75 (d, 1 H, Jgem 10.1 Hz,
H-6), 3.64 (d, 1 H, Jgem 10.0 Hz, H-6), 3.04 (br.s, 1 H,
OH, D2O exchangeable). FAB-MS (positive mode,
NBOH–NaI-matrix): m/z 692 [MH+], 714 [MNa+].
Pyridin-2-yl 3,4,6-tri-O-benzyl-2-O-[3-(methyl-2,3-
di-O-benzyl-h-
D
-glucopyranosid-6-yloxy)carbonylbenzo-
1-yl]-1-thio-h-
D
-mannopyranoside (9)
Method A. Methyl 2,4-di-O-benzyl-a-D-glucopyran-
oside (8)45,46 (0.374 g, 1 mmol) and dibutyltin oxide
(0.270 g, 1.1 mmol) in dry toluene (10 mL) was heated
under reflux with azeotropic removal of water for 3 h.
The reaction mixture was cooled to rt and then 7a
(0.709 g, 1 mmol) and tetrabutylammonium iodide
(0.370 g, 1 mmol) were added. Stirring was continued
for 5 h (TLC) followed by concentration and the purifi-
cation with flash-column chromatography using 6:1
toluene–EtOAc to afford 9 as an oil (0.80 g, 77%).
Method B. A solution of the diol 8 (0.374 g, 1 mmol)
and 7a (0.709 g, 1 mmol) in dry CH2Cl2 (20 mL) was
cooled to 0 °C. Catalytic amounts of dry pyridine were
added and stirring was continued at 0 °C for 8 h (TLC).
The solvent was removed under reduced pressure and
the residue was purified as in method A to give 9 (0.73
g, 70%).
Pyridin-2-yl 3,4,6-tri-O-benzyl-1-thio-h-D-mannopy-
ranoside (5d). Mp 80–83 °C from diethyl ether/
petroleum ether; TLC (5:1 petroleum ether–EtOAc): Rf
1
0.45; [h]D +56° (c 2.3, CHCl3); H NMR (600 MHz,
CDCl3): l 8.46 (d, 1 H, J 7.3 Hz, H-6%), 7.35 (t, 1 H, J
7.1 Hz, H-5%), 7.33–7.24 (m, 15 H, 3 Ph), 7.20 (d, 1 H,
J 7.0 Hz, H-4%), 7.03 (d, 1 H, J 6.9 Hz, H-3%), 6.32 (d,
1 H, J1,2 1.7 Hz, H-1), 4.84, 4.59 (2 d, 2 H, Jgem 10.9
Hz, CH2Ph), 4.71–4.66 (m, 2 H, CH2Ph), 4.53, 4.44 (2
d, 2 H, Jgem 11.1 Hz, CH2Ph), 4.28 (t, 1 H, J2,3 1.9 Hz,
H-2), 3.97–3.91 (m, 1 H, H-4), 3.87 (t, 1 H, J4,5 5.1 Hz,
H-5), 3.77 (dd, 1 H, J3,4 3.5, J2,3 1.9 Hz, H-3), 3.67 (dd,
1 H, Jgem 10.7, J5,6 3.2 Hz, H-6), 3.65 (dd, 1 H, Jgem
10.5, J5,6 3.1 Hz, H-6), 2.76 (br.s, 1 H, OH, D2O
exchangeable). 13C NMR (150.8 MHz, CDCl3): l
156.59, 149.65, 138.24, 138.19, 137.60, 136.68, 128.56,
128.34, 128.24, 128.03, 127.98, 127.90, 127.83, 127.68,
127.49, 123.63, 122.11, 120.70 (Ar-carbons), 83.93 (C-
1), 80.37 (C-3), 75.13 (CH2Ph), 74.32 (C-5), 73.69 (C-4),
73.30, 72.08 (2 CH2Ph), 70.26 (C-2), 68.77 (C-6). FAB-
MS (positive mode, NBOH–NaI-matrix): m/z 544
[MH+], 566 [MNa+]. Anal. Calcd for C32H33NO5S
(543.67): C, 70.69; H, 6.11; N, 2.57. Found: C, 70.51;
H, 5.97; N, 2.46.
Method C. A solution of the diol 8 (0.374 g, 1 mmol),
triphenylphosphine (0.393 g, 1.5 mmol) and 7b (0.691 g,
1 mmol) in dry THF (15 mL) was stirred at rt. A
solution of diethyl azodicarboxylate (DEAD) (0.233
mL, 1.5 mmol) in dry THF (2 mL) was then added.
Stirring was continued overnight and the solvent was
removed under reduced pressure to give 9 (0.71 g, 68%),
after chromatographic purification; TLC (2:1 petroleum
1
ether–EtOAc): Rf 0.47; [h]D +11° (c 2.0, CHCl3); H
Pyridin-2-yl 2-O-(benzo-1-yl-3-chlorocarbonyl)-3,4,
NMR (600 MHz, CDCl3): l 8.44 (d, 1 H, J 7.2 Hz,
H-6%), 7.82–7.55 (m, 1 H, H-5%), 7.51–7.42 (m, 3 H,
H-2%%, H-4%%, H-5%%, H-6%%), 7.33–7.25 (m, 25 H, 5 Ph),
7.21–7.16 (m, 1 H, H-4%), 7.11–7.01 (m, 1 H, H-3%),
6.36–6.32 (m, 1 H, H-1a), 5.13–5.04 (m, 2 H, H-1b,
H-2a), 4.83–4.71 (m, 6 H, 3 CH2Ph), 4.57–4.40 (m, 4
H, 2 CH2Ph), 4.21–4.15 (m, 2 H, H-2b, H-3a), 4.00–
3.94 (m, 2 H, H-4a, H-5a), 3.90–3.84 (m, 2 H, H-4b,
H-5b), 3.76–3.68 (m, 1 H, H-3b), 3.57–3.45 (m, 4 H,
H-6a, H-6b), 3.37 (s, 3 H, OCH3). 13C NMR (150.8
MHz, CDCl3): l 167.11, 166.21 (2 CꢀO), 156.50,
149.60, 138.26, 138.17, 137.57, 136.80, 136.71, 136.66,
128.51, 128.39, 128.27, 128.23, 127.98, 127.93, 127.56,
127.44, 127.19, 123.77, 123.53, 122.19, 120.80 (Ar-car-
6-tri-O-benzyl-1-thio-h- -mannopyranoside (7a).—To
D
a solution of 5d (0.543 g, 1 mmol) and isophthaloyl
chloride (6) (0.203 g, 1 mmol) in dry toluene (10 mL),
dry pyridine (80 mL) was added. The reaction mixture
was stirred at rt under argon for 2.5 h (TLC). The
solvent was evaporated under reduced pressure to give
7a which was very sensitive to the moisture and was
used for the next step without purification.
Pyridin-2-yl 2-O-(benzo-1-yl-3-carboxy)-3,4,6-tri-O-
benzyl-1-thio-h- -mannopyranoside (7b).—Purification
D
of the acid chloride derivative 7a with flash-column
chromatography using 5:1 petroleum ether–EtOAc, af-
forded 7b in 78% yield as an oil; TLC (2:1 petroleum

202
A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
bons), 98.12 (C-1a), 82.20 (C-1b), 81.11 (C-3a), 79.49
(C-2a), 79.01 (C-3b), 76.13, 75.56 (2 CH2Ph), 74.50
(C-5b), 74.38 (CH2Ph), 74.00 (C-4b), 73.21, 71.99 (2
CH2Ph), 70.44 (C-2b), 70.11 (C-4a), 69.27 (C-5a), 68.79
(C-6b), 63.51 (C-6a), 55.22 (OCH3). MALDI-MS: m/z
1071 [MNa+]. Anal. Calcd for C61H61NO13S (1048.21):
C, 69.89; H, 5.86; N, 1.33. Found: C, 69.67; H, 5.59; N,
1.24.
75.58 (2 CH2Ph), 74.99 (C-4b), 74.36, 73.20 (2 CH2Ph),
72.81 (C-5b), 72.02 (CH2Ph), 71.98 (C-5a), 71.36 (C-2a),
70.10 (C-2b, 69.82 (C-4a), 69.73, 69.61 (C-6a, C-6b 55.16
(OCH3). MALDI-MS: m/z 960 [MNa+]. Anal. Calcd
for C56H56O13 (937.05): C, 71.71; H, 6.02. Found: C,
71.58; H, 5.86.
Methyl
(3,4,6-tri-O-benzyl-i-D-mannopyranosyl)-
(1“4)-2,3-di-O-benzyl-h-
D
-glucopyranoside (11).—A
Methyl 6,2%-O-(1,3-isophthaloyl)-(3,4,6-tri-O-benzyl-
stirred solution of 10b (0.234 g, 0.25 mmol) in dry
MeOH to (5 mL) was treated with 1 M sodium methox-
ide (0.10 mL) at rt. The mixture was stirred for further
5 h and then neutralised with Amberlite IR-120. The
ion-exchange resin was removed and after evaporation
of the solvent in vacuo, 11b was obtained (0.181 g,
90%); TLC (5:1 petroleum ether–EtOAc): Rf 0.51; [h]D
h,i-
D
-mannopyranosyl)-(1“4)-2,3-di-O-benzyl-h-D-
glucopyranoside (10).—A stirred solution of 9 (0.52 g,
0.5 mmol) and N-iodosuccinimide (0.145 g, 0.65 mmol)
in dry CH2Cl2 (20 mL) under argon was treated at rt
with trimethylsilyl trifluoromethanesulfonate (50 mL).
The mixture was stirred for 20 min and then neutralised
with triethylamine. The solution was concentrated in
vacuo and then flash chromatography (toluene“10:1
toluene–EtOAc) of the residue afforded 10a (0.046 g,
10%) and 10b (0.278 g, 60%) as colorless oils.
1
+33° (c 0.3, CHCl3); H NMR (600 MHz, CDCl3): l
7.37–7.29 (m, 25 H, 5 Ph), 6.36–6.30 (m, 1 H, H-1a),
5.13–5.08 (m, 2 H, H-1b, H-2a), 4.79–4.68 (m, 6 H, 3
CH2Ph), 4.50–4.40 (m, 4 H, 2 CH2Ph), 4.28–4.20 (m, 2
H, H-2b, H-3a), 4.05–3.97 (m, 2 H, H-4a, H-5a), 3.92–
3.80 (m, 2 H, H-4b, H-5b), 3.71–3.63 (m, 1 H, H-3b),
3.51–3.40 (m, 4 H, H-6a, H-6b), 3.33 (s, 3 H, OCH3),
3.13–3.00 (br.s, 2 H, 2 OH, D2O exchangeable). 13C
NMR (150.8 MHz, CDCl3): l 156.51, 149.64, 138.21,
136.77, 136.70, 136.60, 128.40, 128.29, 128.27, 127.50,
127.13, 123.40, 122.11 (Ar-carbons), 101.00 (JCH 158.0
Hz, C-1b), 97.10 (C-1a), 84.98 (C-3b), 81.31 (C-3a),
76.17, 75.55 (2 CH2Ph), 74.88 (C-4b), 74.34, 73.21 (2
CH2Ph), 72.78 (C-5b), 72.12 (CH2Ph), 72.01 (C-5a),
71.41 (C-2a), 70.30 (C-2b), 70.01 (C-4a), 69.87, 69.79
(C-6a, C-6b,), 55.20 (OCH3). MALDI-MS: m/z 829
[MNa+]. Anal. Calcd for C48H54O11 (806.94): C, 71.44;
H, 6.74. Found: C, 71.31; H, 6.57.
10a: TLC (5:1 petroleum ether–EtOAc): Rf 0.66; [h]D
1
+19° (c 0.5, CHCl3); H NMR (600 MHz, CDCl3): l
8.42 (d, 1 H, J 7.1 Hz, H-6%), 7.61–7.55 (m, 1 H, H-5%),
7.50–7.41 (m, 3 H, H-2%%, H-4%%, H-5%%, H-6%%), 7.33–7.23
(m, 25 H, 5 Ph), 7.18–7.12 (m, 1 H, H-4%), 7.10–7.01
(m, 1 H, H-3%), 6.40–6.33 (m, 1 H, H-1a), 5.12–5.06 (m,
2 H, H-1b, H-2a), 4.80–4.70 (m, 6 H, 3 CH2Ph), 4.55–
4.41 (m, 4 H, 2 CH2Ph), 4.27–4.19 (m, 2 H, H-2b,
H-3a), 4.06–3.97 (m, 2 H, H-4a, H-5a), 3.90–3.80 (m, 2
H, H-4b, H-5b), 3.73–3.65 (m, 1 H, H-3b), 3.52–3.43
(m, 4 H, H-6a, H-6b), 3.39 (s, 3 H, OCH3). 13C NMR
(150.8 MHz, CDC13): l 167.10, 166.15 (2 CꢀO), 156.50,
149.60, 138.26, 138.17, 136.80, 136.71, 136.66, 128.51,
128.39, 128.27, 128.23, 127.93, 127.56, 127.19, 123.77,
123.53, 122.19 (Ar-carbons), 99.71 (JCH 173.1 Hz, C-
1a), 98.12 (C-1b), 82.66 (C-3a), 79.89 (C-3b, C-4a), 76.13,
75.56, 74.38, 73.21, 71.99 (5 CH2Ph), 71.41, 70.98, 70.56
(C-2b, C-5a, C-5b), 70.12 (C-2a), 69.89 (C-4b), 69.77,
69.65 (C-6a, C-6b), 55.13 (OCH3). MALDI-MS: m/z
960 [MNa+]. Anal. Calcd for C56H56O13 (937.05): C,
71.71; H, 6.02. Found: C, 71.60; H, 5.89.
Methyl (2,3,4,6-tetra-O-acetyl-i-D-mannopyranosyl)-
(1“4)-2,3,6tri-O-acetyl-h- -glucopyranoside (12).—A
D
mixture of 11 (0.161 g, 0.2 mmol), and Pd–C (10%, 30
mg) in 1:1 MeOH–EtOAc (8 mL) and formic acid (0.4
mL) was stirred under hydrogen for 24 h. After filtra-
tion and concentration in vacuo, the residue was dis-
solved in 1:1 pyridine–Ac2O (4 mL), and the mixture
was stirred for 20 h. The solution was concentrated in
vacuo and coevaporated with toluene; TLC (5:1
petroleum ether–EtOAc): Rf 0.78; [h]D −44° (c 0.2,
10b: TLC (5:1 petroleum ether–EtOAc): Rf 0.53 [h]D
1
+9° (c 0.4, CHCl3); H NMR (600 MHz, CDCl3): l
8.36 (d, 1 H, J 7.0 Hz, H-6%), 7.70–7.60 (m, 1 H, H-5%),
7.51–7.47 (m, 3 H, H-2%%, H-4%%, H-5%%, H-6%%), 7.31–7.24
(m, 25 H, 5 Ph), 7.20–7.15 (m, 1 H, H-4%), 7.12–7.03
(m, 1 H, H-3%), 6.38–6.31 (m, 1 H, H-1a), 5.14–5.09 (m,
2 H, H-1b, H-2a), 4.80–4.70 (m, 6 H, 3 CH2Ph), 4.52–
4.40 (m, 4 H, 2 CH2Ph), 4.28–4.25 (m, 2 H, H-2b,
H-3a), 4.03–3.90 (m, 2 H, H-4a, H-5a), 3.91–3.82 (m, 2
H, H-4b, H-5b), 3.74–3.60 (m, 1 H, H-3b), 3.47–3.39
(m, 4 H, H-6a, H-6b), 3.36 (s, 3 H, OCH3). 13C NMR
(150.8 MHz, CDCl3): l 167.19, 166.18 (2 CꢀO), 156.52,
149.60, 138.23, 138.19, 136.80, 136.70, 136.61, 128.50,
128.33, 128.22, 128.20, 127.92, 127.59, 127.14, 123.73,
123.50, 122.16 (Ar-carbons), 101.01 (JCH 158.1 Hz,
C-1b), 97.16 (C-1a), 85.09 (C-3b), 81.23 (C-3a), 76.10,
1
CHCl3); H NMR (600 MHz, CDCl3): l 5.50 (d, 1 H,
J3,4 9.6 Hz, H-3a), 5.13 (d, 1 H, J1,2 1.5 Hz, H-1b),
4.85–4.80 (m, 2 H, H-1a, H-2a), 4.48–4.40 (m, 2 H,
H-2b, H-6a), 4.16 (dd, 1 H, Jgem 12.1, J5,6 5.2 Hz, H-6a),
4.10–4.00 (m, 1 H, H-4b), 3.94 (dd, J3,4 9.0, J2,3 3.2 Hz,
H-3b), 3.87 (dd, J5,6 4.7, J4,5 1.9 Hz, H-5a), 3.80–3.77
(m, 1 H, H-5b), 3.75–3.70 (m, 3 H, H-4a, H-6b), 3.39 (s,
3 H, OCH3), 2.19, 2.14, 2.08, 2.07, 2.04, 2.03, 1.98 (7 s,
21 H, CH3CO). 13C NMR (150.8 MHz, CDCl3): l
170.00, 169.70, 169.63, 169.17, 168.90, 168.51, 168.20 (7
CH3CO), 101.08 (JCH 158.1 Hz, C-1b), 97.19 (C-1a),
85.08 (C-3b), 81.45 (C-3a), 74.93 (C-4b), 72.79 (C-5b),
72.19 (C-5a), 71.54 (C-2a), 70.38 (C-2b), 70.14 (C-4a),

A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
203
1
69.89, 69.70 (C-6a, C-6b), 55.13 (OCH3), 20.78, 20.50,
20.15, 20.12, 19.78, 19.33, 19.17 (7 CH3CO). MALDI-
MS: m/z 673 [MNa+]. Anal. Calcd for C27H38O18
(650.57): C, 49.84; H, 5.88. Found: C, 49.67; H, 5.91.
General procedure for the synthesis of compounds
14a–c.—A solution of a,a%-dibromo-m-xylene (0.528 g,
2 mmol) and 5a–c (1 mmol) in dry CH2Cl2 (10 mL)
was cooled to −15 °C. 15-Crown-5 (220 mL, 1.1 mmol)
and NaH (26 mg, 1.1 mmol) were added to the reaction
mixture. Stirring was continued for 16 h (TLC), then
the solvent was removed under reduced pressure. The
residue was purified with flash-column chromatography
using 5:1 petroleum ether–EtOAc to give 14a–c in
74–80% yield.
+21° (c 1.0, CHCl3); H NMR (600 MHz, CDCl3): l
7.66 (d, 1 H, J 7.0, H-6%), 7.40–7.21 (m, 19 H, 3 Ph,
H-2%%, H-4%%, H-5%%, H-6%%), 7.18 (d, 1 H, J 7.1 Hz, H-5%),
7.09 (d, 1 H, J 7.1 Hz, H-4%), 6.51 (d, 1 H, J1,2 1.8 Hz,
H-1), 4.91–4.78 (m, 4 H, 2 CH2Ph), 4.61–4.47 (m, 4 H,
2 CH2Ph), 4.17–4.12 (m, 3 H, H-2, CH2), 4.10–3.91
(m, 2 H, H-4, H-5), 3.80–3.69 (m, 1 H, H-3), 3.60–3.55
(m, 2 H, H-6). 13C NMR (150.8 MHz, CDCl3):l
157.60, 139.25, 138.19, 138.15, 137.46, 128.49, 128.34,
128.29, 128.23, 128.19, 127.86, 127.72, 127.60, 127.41,
117.50 (Ar-carbons), 82.17 (C-1), 78.90 (C-3), 75.24,
75.20 (2 CH2Ph), 74.80 (C-5), 74.11 (C-4), 72.99, 71.90
(2 CH2Ph), 70.51 (C-2), 68.53 (C-6), 33.20 (CH2).
MALDI-MS: m/z 749/751 (bromine isotopes) [MNa+].
General procedure for the synthesis of compounds
Benzoxazol-2-yl 2-O-(h-bromo-m-xylyl)-3,4,6-tri-O-
benzyl-1-thio-h-
an oil; TLC (5:1 petroleum ether–EtOAc): Rf 0.60; [h]D
+10° (c 1.0, CHCl3); H NMR (600 MHz, CDCl3): l
D
-mannopyranoside (14a). Yield 76% as
15a–c.—Methyl 2,4-di-O-benzyl-a-D-glucopyranoside
(8)45,46 (0.374 g, 1 mmol) and dibutyltin oxide (0.270 g,
1.1 mmol) in dry toluene (10 mL) was refluxed under
azeotropic removal of water for 3 h. The reaction
mixture was cooled to rt. Compounds 14a–c (1 mmol)
and tetrabutylammonium iodide (0.370 g, 1 mmol) were
added to the reaction mixture. Stirring was continued
for 10 h (TLC). Removal of the solvent under reduced
pressure and purification with flash-column chromatog-
raphy using 6:1 toluene–EtOAc afforded 15a–c as oils
in 78–84% yield.
1
7.85 (d, 1 H, J 7.2 Hz, H-7%), 7.81 (t, 1 H, J 7.0, H-6%),
7.41 (t, 1 H, J 7.1 Hz, H-5%), 7.33–7.21 (m, 19 H, 3 Ph,
H-2%%, H-4%%, H-5%%, H-6%%), 7.18 (d, 1 H, J 6.9 Hz, H-4%),
6.59 (d, 1 H, J1,2 1.7 Hz, H-1), 4.92–4.71 (m, 4 H, 2
CH2Ph), 4.60–4.45 (m, 4 H, 2 CH2Ph), 4.19–4.12 (m, 3
H, H-2, CH2), 4.10–3.99 (m, 2 H, H-4, H-5), 3.89–3.70
(m, 1 H, H-3), 3.66–3.51 (m, 2 H, H-6). 13C NMR
(150.8 MHz, CDCl3): l 162.23, 152.79, 138.12, 137.90,
137.47, 137.27, 135.74, 128.45, 128.38, 128.24, 127.99,
127.93, 127.83, 127.80, 127.76, 126.59, 126.57, 126.40,
125.20, 124.41, 124.30, 122.30, 121.39, 117.87 (Ar-car-
bons), 85.18 (C-1), 78.47 (C-3), 75.61, 75.37 (2 CH2Ph),
74.35 (C-5), 74.11 (C-4), 73.51, 72.15 (2 CH2Ph), 67.19
(C-2), 68.51 (C-6), 33.15 (CH2). MALDI-MS: m/z 788/
790 (bromine isotopes) [MNa+].
Benzoxazol-2-yl 2-O-[(methyl-2,3-di-O-benzyl-h-
glucopyranosid-6-yloxy)-m-xylyl]-3,4,6-tri-O-benzyl-l-
thio-h- -mannopyranoside (15a).—Yield 81% as an oil;
D-
D
TLC (2:1 petroleum ether–EtOAc): Rf 0.38; [h]D −43°
1
(c 0.4, CHCl3); H NMR (600 MHz, CDCl3): l 7.88 (d,
1 H, J 6.9 Hz, H-7%), 7.84 (t, 1 H, J 7.2 Hz, H-6%), 7.40
(t, 1 H, J 6.9 Hz, H-5%), 7.30–7.23 (m, 29 H, 5 Ph,
H-2%%, H-4%%, H-5%%, H-6%%), 7.21 (d, 1 H, J 6.8 Hz, H-4%),
6.39–6.31 (m, 1 H, H-1a), 5.16–5.04 (m, 2 H, H-1b,
H-2a), 4.99–4.80 (m, 6 H, 3 CH2Ph), 4.77–4.63 (m, 4
H, 2 CH2Ph), 4.58–4.40 (m, 4 H, 2 CH2Ph), 4.29–4.21
(m, 2 H, H-2b, H-3a), 4.09–3.95 (m, 2 H, H-4a, H-5a),
3.92–3.83 (m, 2 H, H-4b, H-5b), 3.78–3.61 (m, 1 H,
H-3b), 3.55–3.43 (m, 4 H, H-6a, H-6b), 3.35 (s, 3 H,
OCH3). 13C NMR (150.8 MHz, CDCl3): l 162.45,
152.89, 138.32, 138.12, 137.91, 137.40, 137.27, 135.70,
128.65, 128.58, 128.44, 128.29, 127.93, 127.84, 127.80,
127.72, 126.69, 126.58, 126.40, 125.20, 124.41, 124.31,
122.32, 121.39, 117.81 (Ar-carbons), 98.00 (C-1a), 85.22
(C-1b), 81.14 (C-3a), 79.53 (C-2a), 78.44 (C-3b), 75.83,
75.77, 75.38 (3 CH2Ph), 74.42 (C-5b), 74.19 (C-4b),
73.66, 73.50, 72.19, 72.13 (4 CH2Ph), 70.15 (C-4a),
69.31 (C-5a), 67.23 (C-2b), 68.50 (C-6b), 64.11 (C-6a),
55.10 (OCH3). MALDI-MS: m/z 1083 [MNa+]. Anal.
Calcd for C63H65NO12S (1060.26): C, 71.36; H, 6.17; N,
1.32. Found: C, 71.21; H, 6.01; N, 1.11.
Benzothiazol-2-yl 2-O-(h-bromo-m-xylyl)-3,4,6-tri-
O-benzyl-1-thio-h- -mannopyranoside (14b). Yield 74%
D
as an oil; TLC (5:1 petroleum ether–EtOAc): Rf 0.69;
[h]D +18° (c 0.7, CHCl3); 1H NMR (600 MHz,
CDCl3): l 7.90 (d, 1 H, J 7.1 Hz, H-7%), 7.70 (t, 1 H, J
7.0 Hz, H-6%), 7.41 (t, 1 H, J 7.1 Hz, H-5%), 7.38–7.22
(m, 19 H, 3 Ph, H-2%%, H-4%%, H-5%%, H-6%%), 7.19 (d, 1 H,
J 7.1 Hz, H-4%), 6.60 (d, 1 H, J1,2 1.7 Hz, H-1),
4.90–4.77 (m, 4 H, 2 CH2Ph), 4.62–4.43 (m, 4 H, 2
CH2Ph), 4.20–4.08 (m, 3 H, H-2, CH2), 3.98–3.89 (m,
2 H, H-4, H-5), 3.81–3.70 (m, 1 H, H-3), 3.61–3.50 (m,
2 H, H-6). 13C NMR (150.8 MHz, CDCl3): l 161.96,
152.94, 152.70, 138.27, 137.94, 137.31, 135.84, 135.78,
128.45, 128.30, 128.23, 127.92, 127.86, 127.73, 127.61,
126.50, 126.51, 126.38, 126.20, 125.22, 124.77, 124.30,
122.40, 120.90, 119.90 (Ar-carbons), 84.90 (C-1), 78.13
(C-3), 75.19, 75.13 (2 CH2Ph), 73.98 (C-5), 73.80 (C-4),
73.27, 72.11 (2 CH2Ph), 69.49 (C-2), 68.20 (C-6), 33.23
(CH2). MALDI-MS: m/z 804/806 (bromine isotopes)
[MNa+].
Benzothiazol-2-yl 2-O-[(methyl-2,3-di-O-benzyl-h-
glucopyranosid-6-yloxy)-m-xylyl]-3,4,6-tri-O-benzyl-1-
thio-h- -mannopyranoside (15b).—Yield 78% as an oil;
TLC (2:1 petroleum ether–EtOAc): Rf 0.41; [h]D −52°
D-
Pyrimidin-2-yl 2-O-(h-bromo-m-xylyl)-3,4,6-tri-O-
benzyl-1-thio-h-
D
-mannopyranoside (14c). Yield 80% as
D
an oil; TLC (5:1 petroleum ether–EtOAc): Rf 0.65; [h]D

204
A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
1
(c 0.2, CHCl3); H NMR (600 MHz, CDCl3): l 7.85 (d,
1 H, J 6.9 Hz, H-7%), 7.80 (t, 1 H, J 7.2 Hz, H-6%), 7.38
(t, 1 H, J 6.9 Hz, H-5%), 7.35–7.23 (m, 29 H, 5 Ph,
H-2%%, H-4%%, H-5%%, H-6%%), 7.17 (d, 1 H, J 6.8 Hz, H-4%),
6.43–6.39 (m, 1 H, H-1a), 5.15–5.06 (m, 2 H, H-1b,
H-2a), 4.82–4.99 (m, 6 H, 3 CH2Ph), 4.74–4.66 (m, 4
H, 2 CH2Ph), 4.48–4.37 (m, 4 H, 2 CH2Ph), 4.33–4.20
(m, 2 H, H-2b, H-3a), 4.06–3.91 (m, 2 H, H-4a, H-5a),
3.90–3.83 (m, 2 H, H-4b, H-5b), 3.74–3.60 (m, 1 H,
H-3b), 3.51–3.43 (m, 4 H, H-6a, H-6b), 3.34 (s, 3 H,
OCH3). 13C NMR (150.8 MHz, CDCl3): l 162.07,
152.99, 152.94, 152.73, 138.29, 137.94, 137.31, 135.80,
135.72, 128.47, 128.35, 128.28, 128.23, 127.92, 127.86,
127.73, 127.61, 126.56, 126.50, 126.33, 126.25, 125.21,
124.72, 124.22, 122.45, 120.91, 119.99, (Ar-carbons),
98.00 (C-1a), 84.94 (C-1b), 81.20 (C-3a), 79.55 (C-2a),
78.19 (C-3b), 75.44, 75.19, 75.15 (3 CH2Ph), 73.90 (C-
5b), 73.85 (C-4b), 73.43, 73.20, 72.17, 72.13 (4 CH2Ph),
70.20 (C-4a), 69.50 (C-5a), 69.46 (C-2b), 68.22 (C-6b),
64.18 (C-6a), 55.16 (OCH3). MALDI-MS: m/z 1099
[MNa+]. Anal. Calcd for C63H65NO11S2 (1076.32): C,
70.30; H, 6.08; N, 1.30. Found: C, 70.11; H, 5.88; N,
1.09.
residue afforded 16 in 78% yield from 15a (a/b ratio,
1:10), in 75% yield from 15b (a/b ratio, 1:9), in 76%
yield from 15c (a/b ratio, 1:10), and from 21 in 72%
yield (a/b ratio, 1:6).
16a: TLC (5:1 petroleum ether–EtOAc): Rf 0.60; [h]D
1
+65° (c 0.4, CHCl3); H NMR (600 MHz, CDCl3): l
7.51–7.23 (m, 29 H, 5 Ph, H-2%%, H-4%%, H-5%%, H-6%%),
6.36–6.31 (m, 1 H, H-1a), 5.12–5.06 (m, 2 H, H-1b,
H-2a), 4.95–4.86 (m, 6 H, 3 CH2Ph), 4.76–4.67 (m, 4
H, 2 CH2Ph), 4.53–4.40 (m, 4 H, 2 CH2Ph), 4.27–4.21
(m, 2 H, H-2b, H-3a), 4.10–3.94 (m, 2 H, H-4a, H-5a),
3.93–3.86 (m, 2 H, H-4b, H-5b), 3.75–3.60 (m, 1 H,
H-3b), 3.52–3.41 (m, 4 H, H-6a, H-6b), 3.34 (s, 3 H,
OCH3). 13C NMR (150.8 MHz, CDCl3): l 156.54,
149.66, 138.34, 138.19, 136.80, 136.75, 136.65, 128.77,
128.60, 128.57, 128.43, 127.90, 127.51, 127.15, 123.77,
123.50, 122.11 (Ar-carbons), 99.77 (JCH 174.0 Hz, C-
1b), 98.10 (C-1a), 82.54 (C-3b), 79.82 (C-3a, C-4b), 75.51,
75.39, 75.26, 74.09, 73.19, 73.15, 71.99 (7 CH2Ph),
71.21, 70.99, 70.63 (C-2a, C-5a, C-5b), 70.14 (C-2b),
69.92 (C-4a), 69.71, 69.64 (C-6a, C-6b), 55.21 (OCH3).
MALDI-MS: m/z 932 [MNa+]. Anal. Calcd for
C56H60O11 (909.08): C, 73.98; H, 6.65. Found: C, 73.83;
H, 6.51.
Pyrimidin-2-yl
glucopyranosid-6-yloxy)-m-xylyl]-3,4,6-tri-O-benzyl-1-
thio-h- -mannopyranoside (15c).—Yield 84% as an oil;
2-O-[(methyl-2,3-di-O-benzyl-h-D-
16b: TLC (5:1 petroleum ether–EtOAc): Rf 0.47; [h]D
1
D
+77° (c 0.3, CHCl3); H NMR (600 MHz, CDCl3): l
TLC (2:1 petroleum ether–EtOAc): Rf 0.40; [h]D −66°
(c 0.1, CHCl3); H NMR (600 MHz, CDCl3): l 8.50 (d,
7.54–7.24 (m, 29 H, 5 Ph, H-2%%, H-4%%, H-5%%, H-6%%),
6.36–6.33 (m, 1 H, H-1a), 5.16–5.06 (m, 2 H, H-1b,
H-2a), 4.93–4.80 (m, 6 H, 3 CH2Ph), 4.71–4.60 (m, 4
H, 2 CH2Ph), 4.48–4.43 (m, 4 H, 2 CH2Ph), 4.22–4.16
(m, 2 H, H-2b, H-3a), 4.00–3.90 (m, 2 H, H-4a, H-5a),
3.86–3.77 (m, 2 H, H-4b, H-5b), 3.68–3.51 (m, 1 H,
H-3b), 3.46–3.38 (m, 4 H, H-6a, H-6b), 3.33 (s, 3 H,
OCH3). 13C NMR (150.8 MHz, CDCl3): l 156.55,
149.69, 138.39, 138.22, 136.81, 136.85, 136.75, 128.73,
128.60, 128.54, 128.40, 127.90, 127.50, 127.19, 123.77,
123.55, 122.14 (Ar-carbons), 101.09 (JCH 158.3 Hz,
C-1b), 97.10 (C-1a), 85.12 (C-3b), 81.31 (C-3a), 75.50,
75.32, 75.23 (3 CH2Ph), 74.90 (C-4b), 74.00, 73.12,
73.10, 72.92 (4 CH2Ph), 72.89 (C-5b), 71.93 (C-5a),
71.56 (C-2a), 70.10 (C-2b), 70.00 (C-4a), 69.72, 69.68
(C-6a, C-6b), 55.23 (OCH3). MALDI-MS: m/z 932
[MNa+]. Anal. Calcd for C56H60O11 (909.08): C, 73.98;
H, 6.65. Found: C, 73.79; H, 6.54.
1
1 H, J 7.1 Hz, H-6%), 7.31–7.20 (m, 29 H, 5 Ph, H-2%%,
H-4%%, H-5%%, H-6%%), 7.14 (d, 1 H, J 7.1 Hz, H-5%), 7.01
(d, 1 H, J 7.2 Hz, H-4%), 6.31–6.27 (m, 1 H, H-1a),
5.15–5.07 (m, 2 H, H-1b, H-2a), 4.96–4.82 (m, 6 H, 3
CH2Ph), 4.73–4.60 (m, 4 H, 2 CH2Ph), 4.55–4.45 (m, 4
H, 2 CH2Ph), 4.27–4.18 (m, 2 H, H-2b, H-3a), 4.16–
4.10 (m, 2 H, H-4a, H-5a), 3.94–3.87 (m, 2 H, H-4b,
H-5b), 3.72–3.65 (m, 1 H, H-3b), 3.59–3.50 (m, 4 H,
H-6a, H-6b), 3.38 (s, 3 H, OCH3).13C NMR (150.8
MHz, CDCl3): l 157.73, 157.65, 139.28, 138.77, 138.19,
138.15, 137.46, 128.79, 128.54, 128.44, 128.29, 128.17,
127.88, 127.70, 127.62, 127.41, 117.54 (Ar-carbons),
97.98 (C-1a), 82.44 (C-1b), 81.34 (C-3a), 79.50 (C-2a),
78.95 (C-3b), 75.31, 75.24, 75.21 (3 CH2Ph), 74.85 (C-
5b), 74.18 (C-4b), 74.00, 73.12, 72.95, 71.93 (4 CH2Ph),
70.55 (C-2b), 70.33 (C-2a), 68.53 (C-6b), 64.47 (C-6a),
55.21 (OCH3). MALDI-MS: m/z 1045 [MNa+]. Anal.
Calcd for C60H65N2O11S (1022.23): C, 70.49; H, 6.40;
N, 2.74. Found: C, 70.30; H, 6.31; N, 2.59.
1,3,4-Thiadiazole-2,5-diyl bis(2-O-acetyl-3,4,6-tri-O-
benzyl-1-thio-h- -mannopyranoside) (18).—2,5-Dimer-
D
capto-1,3,4-thiadiazole (17) (8 mmol) and HgBr2 (40
mg) was added to a solution of 241,42 (0.50 g, 1.0 mmol)
in dry MeCN (10 mL). The mixture was heated to
60 °C under argon for 5 h, and then concentrated. A
solution of the residue in CH2Cl2 was washed with 5%
aq NaOH (50 mL), water, dried (MgSO4), and concen-
trated. The residue was purified by flash-column chro-
matography using 10:1 petroleum ether–EtOAc to give
18 in 88% yield as an oi1; TLC (5:1 petroleum ether–
Methyl 6,2%-O-(m-xylyl)-(3,4,6-tri-O-benzyl-h,i-
D-
mannopyranosyl)-(1“4)-2,3-di-O-benzyl-h- -gluco-
D
pyranoside (16).—Trimethylsilyl trifluoromethanesul-
fonate (50 mL) was added under argon at rt to a
solution of 15a–c (1 mmol) and N-iodosuccinimide
(0.290 g, 1.3 mmol) in dry CH2Cl2 (20 mL); the mixture
was stirred for 20 min. The solution was neutralised
with triethylamine and concentrated in vacuo. Chro-
matography (toluene“10:1 toluene–EtOAc) of the
1
EtOAc): Rf 0.41; [h]D −106° (c 1.0, CHCl3); H NMR

A.A.-H. Abdel-Rahman et al. / Carbohydrate Research 337 (2002) 195–206
205
(600 MHz, CDCl3): l 7.38–7.26 (m, 30 H, 6 Ph), 6.39
(d, 2 H, J1,2 1.7 Hz, H-1), 5.69–5.61 (m, 2 H, H-2,),
4.70–4.43 (m, 12 H, 6 CH2Ph), 4.18–4.12 (m, 2 H,
H-5), 4.00–3.97 (m, 2 H, H-4), 3.94–3.90 (m, 6 H, H-3,
H-6), 3.70 (d, 2 H, Jgem 11.0 Hz, H-6), 2.18 (s, 6 H,
CH3CO). 13C NMR (150.8 MHz, CDCl3): l 170.00 (2
CH3CO), 161.90, 152.70, 138.04, 137.88, 137.34, 135.87,
128.46, 128.31, 128.20, 127.90, 127.75, 127.69, 126.54,
126.39, 124.59, 122.45, 121.19, 117.99 (Ar-carbons),
84.73 (C-1), 78.44 (C-3), 75.39 (CH2Ph), 74.19 (C-5),
74.15 (C-4), 73.45, 72.28 (2 CH2Ph), 69.79 (C-2), 68.39
(C-6), 20.84 (CH3CO). MALDI-MS: m/z 1122 [MNa+].
CH2Ph), 67.23 (C-2), 68.50 (C-6), 33.50 (CH2).
MALDI-MS: m/z 1403/1405 (bromine isotopes)
[MNa+].
1,3,4-Thiadiazole-2,5-diyl bis{[2-O-(methyl-2,3-di-O-
benzyl-h-
O-benzyl-1-thio-h-
2,4-di-O-benzyl-a-
D-glucopyranosid-6-yloxy)-m-xylyl]-(3,4,6-tri-
D
-mannopyranoside)} (21).—Methyl
D
-glucopyranoside (8) (0.748 g, 2
mmol) and dibutyltin oxide (0.540 g, 2.2 mmol) in dry
toluene (20 mL) was refluxed under azeotropic removal
of water for 3 h. The reaction mixture was cooled to rt
and then 20 (1.96 g, 1 mmol) and tetrabutylammonium
iodide (0.740 g, 2 mmol) were added. Stirring was
continued for overnight (TLC). Removal of the solvent
under reduced pressure and purification with flash-
column chromatography using 6:1 toluene–EtOAc af-
forded 21 in 72% yield as an oil; TLC (2:1 petroleum
1,3,4-Thiadiazole-2,5-diyl
bis(3,4,6-tri-O-benzyl-1-
thio-h- -mannopyranoside) (19).—Compound 18 (1.10
D
g, 1 mmol) was dissolved in dry MeOH (10 mL) and 1
M sodium methoxide in MeOH (0.1 mL) was added
with stirring at rt. After 2 h, the reaction mixture was
neutralised with Amberlite IR-120. The ion-exchange
resin was removed and after evaporation of the solvent
under reduced pressure, compound 19 was obtained in
quantitative yield as yellow oil. The product was pure
enough for the next step; TLC (5:1 petroleum ether–
1
ether–EtOAc) Rf 0.30; [h]D −21° (c 0.1, CHCl3); H
NMR (600 MHz, CDCl3): l 7.39–7.23 (m, 38 H, 6 Ph,
H-2%%, H-4%%, H-5%%, H-6%%), 6.36–6.30 (m, 2 H, H-1a),
5.13–5.00 (m, 4 H, H-1b, H-2a), 4.90–4.80 (m, 12 H, 6
CH2Ph), 4.70–4.60 (m, 8 H, 4 CH2Ph), 4.48–4.36 (m, 8
H, 4 CH2Ph), 4.31–4.20 (m, 4 H, H-2b, H-3a), 4.04–
3.93 (m, 4 H, H-4a, H-5a), 3.83–3.73 (m, 4 H, H-4b,
H-5b), 3.73–3.60 (m, 2 H, H-3b), 3.53–3.43 (m, 8 H,
H-6a, H-6b), 3.38 (s, 6 H, OCH3). 13C NMR (150.8
MHz, CDCl3): l 162.45, 152.89, 138.34, 138.11, 137.97,
137.21, 135.73, 128.63, 128.50, 127.94, 127.80, 127.71,
126.79, 126.43, 125.30, 124.53, 124.38, 122.30, 121.43,
117.80 (Ar-carbons), 98.06 (C-1a), 85.27 (C-1b), 81.42
(C-3a), 79.66 (C-2a), 78.42 (C-3b), 75.88, 75.70, 75.30 (3
CH2Ph), 74.45 (C-5b), 74.33 (C-4b), 73.60, 73.44, 72.12,
72.10 (4 CH2Ph), 70.10 (C-4a), 69.39 (C-5a), 68.54 (C-
6b), 67.34 (C-b), 64.14 (C-6a), 55.20 (OCH3). MALDI-
MS: m/z 1990 [MNa+].
1
EtOAc): Rf 0.37; [h]D −87° (c 1.0, CHCl3); H NMR
(600 MHz, CDCl3): l 7.38–7.24 (m, 30 H, 6 Ph), 6.79
(d, 2 H, J1,2, 1.6 Hz, H-1), 4.84–4.43 (m, 12 H, 6
CH2Ph), 4.40 (m, 2 H, H-2), 4.15–4.01 (m, 4 H, H-4,
H-5), 3.87–3.83 (m, 2 H, H-3), 3.80–3.75 (m, 2 H,
H-6), 3.73–3.69 (m, 2 H, H-6), 2.79 (br.s, 2 H, 2 OH,
D2O exchangeable). 13C NMR (150.8 MHz, CDCl3): l
161.80, 152.70, 138.24, 137.93, 137.25, 135.77, 128.30,
128.25, 127.94, 127.80, 127.71, 126.52, 126.36, 125.21,
124.72, 124.41, 120.90, 117.90. (Ar-carbons), 83.66 (C-
1), 80.44 (C-3), 75.32 (CH2Ph), 74.70 (C-5), 74.16 (C-4),
73.41, 72.19 (2 CH2Ph), 70.45 (C-2), 68.69 (C-6).
MALDI-MS: m/z 1038 [MNa+].
1,3,4-Thiadiazole-2,5-diyl
lyl) - 3,4,6 - tri - Obenzyl - 1 - thio - h -
bis[2-O-(h-bromo-m-xy-
- mannopyranoside]
D
Acknowledgements
(20).—A solution of a,a%-dibromo-m-xylene (1.056 g, 4
mmol) and 19 (1.01 g, 1 mmol) in dry CH2Cl2 (20 mL)
was cooled to −15 °C. 15-Crown-5 (440 mL, 2.2 mmol)
and NaH (52 mg, 2.2 mmol) were added to the reaction
mixture. Stirring was continued for overnight (TLC),
and then the solvent was removed under reduced pres-
sure. The residue was purified with flash-column chro-
matography using 5:1 petroleum ether–EtOAc to give
20 in 77% yield as an oil; TLC (2:1 petroleum ether–
This work was supported by the Deutsche
Froschungsgemeinschaft and the Fonds der Chemis-
chen Industrie. A.A.-H.A.-R. is grateful for an Alexan-
der von Humboldt-Fellowship. The continued support
from the Alexander von Humboldt Stiftung for
E.S.H.E.A. is highly appreciated.
1
EtOAc): Rf 0.40; [h]D −77° (c 0.3, CHCl3); H NMR
References
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