Versatile acetylation of carbohydrate substrates with bench-top sulfonic acids and application to one-pot syntheses of peracetylated thioglycosides

Article abstract of DOI:10.1016/j.carres.2008.01.014

Inexpensive and readily available sulfonic acids, p-toluenesulfonic acid, and sulfuric acid are versatile and efficient catalysts for the peracetylation of a broad spectrum of carbohydrate substrates in good yield and in a practical time frame. Three appealing features in sulfonic acid-catalyzed acetylation of free sugars were explored including (1) suppression of furanosyl acetate formation for d-galactose and l-fucose; (2) high yielding chemoselective acetylation of sialic acid under appropriate conditions; and (3) peracetylation of amino sugars with different amino protecting functions. Simple one-pot two step acetylation-thioglycosidation methods for the expeditious synthesis of p-tolyl per-O-acetyl thioglycosides were also delineated.

Full text of DOI:10.1016/j.carres.2008.01.014

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 957–964
Note
Versatile acetylation of carbohydrate substrates with bench-top
sulfonic acids and application to one-pot syntheses
of peracetylated thioglycosides
Chin-Sheng Chao, Min-Chun Chen, Shih-Che Lin and Kwok-Kong T. Mong*
Department of Applied Chemistry, National Chiao Tung University, 1001, Ta-Hsueh Road, Hsinchu 300, Taiwan, ROC
Received 20 November 2007; received in revised form 9 January 2008; accepted 16 January 2008
Available online 26 January 2008
Abstract—Inexpensive and readily available sulfonic acids, p-toluenesulfonic acid, and sulfuric acid are versatile and efficient cata-
lysts for the peracetylation of a broad spectrum of carbohydrate substrates in good yield and in a practical time frame. Three appeal-
ing features in sulfonic acid-catalyzed acetylation of free sugars were explored including (1) suppression of furanosyl acetate
formation for D-galactose and L-fucose; (2) high yielding chemoselective acetylation of sialic acid under appropriate conditions;
and (3) peracetylation of amino sugars with different amino protecting functions. Simple one-pot two step acetylation–thioglycos-
idation methods for the expeditious synthesis of p-tolyl per-O-acetyl thioglycosides were also delineated.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: p-Toluenesulfonic acid; Acid-catalyzed acetylation; Amino sugars; One-pot protecting group manipulation
Chemical synthesis of oligosaccharides is a two-stage
process that comprises the preparation of glycosyl build-
ing blocks followed by their assemblage. Different syn-
peracetylation is an acid-catalyzed process, which is
compatible to the second thioglycosidation; a one-pot
acetylation–thioglycosidation is foreseeable. Thus, vari-
ous one-pot strategies for the preparation of per-O-acetyl
thioglycosides have been developed, although most of
the existing methods have pitfalls originating from the
1
thetic strategies have emerged to speed up the
assembling process, which include the armed-disarmed
2
3
approach, orthogonal glycosylation, reactivity-based
4
10
one-pot glycosylation, sequential iterative glycosyl-
ation, and automated solid phase oligosaccharide syn-
thesis. The implementation of these strategies relies
peracetylation process. For example, the formation
5
of undesired furanosyl acetates for some sugars in
acid-catalyzed acetylation compromises the yield in the
6
1
0c,e,11
heavily on the facile synthesis of glycosyl building
blocks. Thioglycoside derivatives constitute a major
class of glycosyl building blocks for oligosaccharide syn-
subsequent thioglycosidation.
The strong Lewis
acid character of some acids makes them less suitable
for the peracetylation of N-protected amino sugars
and thus limits the scope of application to carbohydrate
7
thesis, which are mainly derived from per-O-acetyl
1
0d,e,12–14
thioglycosides.
substrates without amino functions.
Herein, we
Conventional preparation of per-O-acetyl thioglyc-
osides involves peracetylation and subsequent thioglyc-
osidation. However, classical carbohydrate acetylation
report a versatile and high yielding (75–95%) carbohy-
drate peracetylation protocol that can overcome the
above drawbacks by using common sulfonic acids in
the appropriate reaction conditions. Subsequent develo-
pment of the simple one-pot two step acetylation–thio-
glycosidation protocols for the expeditious syntheses
of p-tolyl per-O-acetyl thioglycosides was also delineated.
8
uses excess pyridine; not only is pyridine highly toxic,
but the presence of excess basic reagent makes the
9
one-pot operation impossible. Provided that the first
1
5
*
Corresponding author. Tel.: +886 3 5131204; fax: +886 3 5723764;
e-mail: tonymong@cc.nctu.edu.tw
p-Toluenesulfonic acid monohydrate (TsOH) and
1
6,17
sulfuric acid (H SO )
are known catalysts for
2
4
0
008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.01.014

958
C.-S. Chao et al. / Carbohydrate Research 343 (2008) 957–964
hydroxyl acetylation in the presence of excess acetic
anhydride, however their efficiency with near stoichio-
metric acetic anhydride has not been explored. In addi-
tion, TsOH has never been used for the acetylation of
free sugar substrates. Although silica-supported H SO
ride synthesis, it would be worthy knowing the
compatibility of our protocol to such protecting func-
tions. To this end, D-glucosamines with trichloroethoxy-
carbonyl (Troc), trichloroacetyl (TCA), acetyl (Ac),
azido (N ), and benzylethoxycarbonyl (Cbz) functions
2
4
3
and HClO have been used for carbohydrate acetyla-
were prepared and acetylated with the standard TsOH-
4
1
8
tion, the additional immobilization step makes these
protocols less convenient and the use of potentially
catalyzed protocol (Table 1, entries f–j). To our
delight, the desired peracetylated products 6–10 were
furnished within 3–6 h in respectable 85–94% yield.
For the acetylation of N-acetyl neuraminic acid methyl
ester (NANA methyl ester), 4,7,8,9-tetra-O-acetyl
NANA methyl ester 11 was obtained exclusively in
90% yield without any trace of the pentaacetylated
product (Table 1, entry k). Such chemoselectivity is
1
4a,b
explosive HClO4 is also discouraged.
Our initial
observations showed that both neat H SO and TsOH
2
4
exhibited sufficient catalytic efficiency (1 mol % per OH
group of the sugar) for the acetylation of D-glucose with
a near stoichiometric amount of Ac O. Peracetylation of
2
D-glucose with H SO was completed in 0.2 h while with
2
4
TsOH the reaction needed 8 h; such a difference should
be useful for the selective peracetylation of sugars under
different reaction conditions.
superior to the conventional HClO -catalyzed proto-
col. To obtain the pentaacetyl product, a higher reac-
4
1
9
tion temperature (45 °C) and excess Ac O were required,
2
In the standard protocol, TsOH (1 or 2 mol % per OH
and 2,4,7,8,9-pentacetyl NANA methyl ester 12 was
furnished in 80% yield along with 5% elimination
product (Table 2, entry l). As 11 and 12 are valuable
precursors for the synthesis of sialic acid-containing
oligosaccharides, our new procedure should provide a
more convenient alternative.
group of the sugar) in Ac O (Table 1, entries a–c, h, and
2
m) or in a mixture of Ac O and acetonitrile (CH CN)
2
3
(
Table 1, entries d–g, i–l, and n–o) was added to the
carbohydrate substrate with stirring at 0 °C for 1 h.
Subsequently, the reaction mixture was warmed to the
optimal reaction temperature; detailed experimental
conditions are given in Table S1 of Supplementary data.
It should also be mentioned that the facile acetylation
of amino sugars with the TsOH-catalyzed protocol was
1
2
In general, a near stoichiometric amount of Ac O
in sharp contrast to the reaction using I2. As a com-
parison, the amount of acid catalyst (in mol % per OH
group), reaction time, and product yield for the acetyl-
ation of N-Troc glucosamine, N-acetyl glucosamine,
2
(
1.2 mol equiv per OH group of the sugar) was em-
ployed. For carbohydrate substrates without amino
functions, the desired peracetylated glycosyl acetates
were furnished in good to excellent (75–95%) yield
and NANA methyl ester with I -catalyzed and TsOH-
2
(
Table 1, entries a, b, c, m, n, and o).
catalyzed protocols are provided in Table 1 (entries f,
Acetylation of D-galactose and L-fucose requires
h, k and l). For the acetylation of N-Troc glucosamine
special attention as both are prone to form undesired
furanosyl acetates. Such furanosyl isomers were also
formed from the sugars with our standard TsOH-cata-
lyzed acetylation protocol (30% relative to total perace-
tyl acetates for D-galactose, 26% relative to total
with I , the reported experimental procedure was fol-
2
lowed and 250 mg I2 per g of N-Troc glucosamine
1
2
(9 mol % per OH group) was used. For the I -cata-
2
lyzed acetylation of GlcNAc and NANA methyl ester,
a much higher catalyst loading was applied (either 5 or
1
0c,e,11
peracetyl acetates for L-fucose).
Gratifyingly, the
13 mol % per OH group for the I -catalyzed acetylation
2
furanosyl isomer derived from D-galactose was gradu-
ally reduced by decreasing the reaction temperatures
and nearly complete elimination was accomplished at
versus 2 mol % per OH group for the TsOH-catalyzed
acetylation) (Table 1, entries, h, k, and l). Even at such
a high I concentration, it still took two days for the
2
1
0e,15b
0
°C.
At such low reaction temperature, the more
complete acetylation of N-acetyl glucosamine (Table 1,
entry h). In addition, no significant acetylation was
reactive H SO was needed. However for the acetylation
2
4
of L-fucose, 7% of furanosyl isomer was formed at 0 °C
and thus further decrease in the temperature to ꢀ20 °C
was required. Under the optimal reaction conditions,
the formation of furanosyl isomer was reduced to less
than 2% (see spectroscopic in Supplementary data page
S23).
observed for N-Troc glucosamine when I catalyst was
used (Table 1, entry f).
2
Regarding the a-/b-selectivity of the process, a-glyc-
osyl acetates were formed preferentially in majority of
the cases, which can be explained by thermodynamics
(Table 1, entries a–e, g–h, and m). Nevertheless, for
the acetylation of N-Troc and 2-azido-2-deoxy-glucos-
amines, b-glycosyl acetates were the major anomers
obtained (Table 1, entries f and i). Apparently, the
strong participatory effect of trichloroethoxylcarbamyl
function outweighed the anomeric effect in N-Troc
glucosamine, while the reason for b-selectivity in
2-azido-2-dexoy-glucosoamine is not clear.
After examining the simple carbohydrate substrates,
we turned to the amino sugars, which occur in the
majority of natural oligosaccharides. Although pyr-
idine-catalyzed acetylation works well for the acetylation
of amino sugars, the less toxic TsOH-catalyzed protocol
9
should provide a desirable alternative. As different ami-
no protecting functions have been used in oligosaccha-

C.-S. Chao et al. / Carbohydrate Research 343 (2008) 957–964
959
Table 1. Sulfonic acid-catalyzed acetylation for carbohydrate substrates with different complexities
Entry Carbohydrate substrate
Per-O-acetyl glycosyl acetate
Acid (mol % per OH) Temp (°C)
Time (h) Yield % (a:b)
OAc
AcO
AcO
O
a
b
c
D-Glucose
OAc
TsOH (2)
TsOH (2)
TsOH (2)
0–27
0–27
0–27
6
5
4
95 (71:29)
94 (45:11)
92 (58:42)
OAc
1
2
OAc
OAc
O
D-Mannose
L-RhamnoseꢁH
AcO
AcO
OAc
OAc
O
AcO
2
O
AcO
OAc
3
AcO OAc
O
a
d
D-Galactose
L-Fucose
OAc
H
2
2
SO
4
4
(2)
(2)
ꢀ20 to 0
18
8
92 (76:24)
AcO
OAc
4
OAc
OAc
O
a
e
f
H
SO
ꢀ30 to ꢀ20
93 (9:1)
OAc
AcO
AcO
5
OAc
O
a
2-Trichloroethoxy
carbamyl-2-deoxy-D-
glucopyranose
TsOH (2)
(9)
0–27
0–27
6
>24
90 (27:73)
OAc
NHTroc
AcO
b
I
2
No reaction
6
OAc
a
g
2-Trichloroacetamido-
AcO
O
TsOH (2)
TsOH (2)
0–55
5
93 (77:23)
OAc
NHTCA
AcO
2-deoxy-D-glucopyranose
7
OAc
AcO
AcO
O
0–50
0–27
5
48
90 (61:39)
h
2-Acetamido-2-deoxy-
D-glucopyranose
OAc
b,c
I
2
(5)
98 (2.5:1)
NHAc
8
OAc
O
a
i
2-Azido-2-deoxy-
D-glucopyranose
AcO
AcO
TsOH (2)
TsOH (2)
TsOH (2)
0–27
0–40
4
3
4
85 (23:77)
OAc
N3
9
OAc
O
AcO
AcO
a
j
2-Benzyloxycarbamyl-2-
deoxy-D-glucopyranose
94 (not determined)
OAc
OH
NHCbz
10
AcO
AcO
OAc
a
k
N-Acetyl neuraminic
acid methyl ester
0–27
0–27
0–27
90 (1:4)
O
CO Me
2
AcHN
b,c
I
I
2
(6.5)
(13)
Sluggish Not determined
AcO
OAc
b,c
1
1
2
20 min
70 (not determined)
AcO
AcO
OAc
a,b
l
N-Acetyl neuraminic
acid methyl ester
TsOH (2)
(13)
0–45
0–35
12
60 min
80 (b only)
O
CO Me
2
AcHN
b,c
I
2
90 (1:3.5)
AcO
12
OAc
O
AcO
AcO
OAc
O
m
D-LactoseꢁH
2
O
O
TsOH (2)
0–40
4
90 (3:2)
AcO
OAc
OAc
OAc
13
(continued on next page)

960
C.-S. Chao et al. / Carbohydrate Research 343 (2008) 957–964
Table 1 (continued)
Entry
Carbohydrate substrate
Per-O-acetyl glycosyl acetate
per-O-acetyl-b-cylcodextrin 14
Acid (mol % per OH)
TsOH (1)
Temp (°C)
Time (h)
Yield % (a:b)
a
n
o
b-Cylcodextrin
0–40
0–30
10
6
90
a
D(+)-MelezitoseꢁH
2
O
per-O-acetyl-D(+)-Melezitose 15 TsOH (1)
75
a
b
c
3
CH CN was added to the reaction mixture.
2
Excess Ac O was used.
Ref. 12.
Table 2. One-pot syntheses of per-O-acetyl thioglycosides
O
One-pot [Ac
O, cat. sulfonic acid
Tol-SH, Lewis acid]
O
2
HO
+
AcO
STol
OH
OH (or -protected)
N
OAc (or N-protected)
1
−2 d
Entry
a
Carbohydrate substrate
D-Glucose
Thioglycoside
Yield % (a:b)
OAc
AcO
AcO
O
a
STol
75 (b only)
OAc
1
6
OAc
OAc
O
a
b
c
d
e
f
D-Mannose
AcO
80 (a only)
AcO
1
7
STol
STol
AcO
a
L-RhamnoseꢁH
D-Galactose
L-Fucose
2
O
84 (5:1)
AcO
OAc
1
8
AcO OAc
O
a
STol
68 (b only)
AcO
OAc
1
9
O
STol
OAc
a
75 (b only)
OAc
2
AcO
AcO
0
OAc
O
a
2-Trichloroethoxy carbamyl-2-deoxy-D-glucopyranose
2-Trichloroacetamido-deoxy-D-glucopyranose
2-Acetamido-2-deoxy-D-glucopyranose
72 (b only)
STol
AcO
NHTroc
21
OAc
O
a
AcO
AcO
g
h
i
65 (b only)
STol
NHTCA
2
2
OAc
O
b
AcO
AcO
65 (b only)
STol
NHAc
23
AcO
AcO
OAc
STol
a
N-Acetyl neuraminic acid methyl ester
72 (b only)
O
CO Me
AcHN
2
AcO
24
OAc
O
AcO
OAc
O
a
k
D-LactoseꢁH
2
O
75 (b only)
AcO
O
STol
AcO
OAc
5 OAc
2
a
BF
3
ꢁEt
2
O was used for thioglycosidation.
b
SnCl was used for thioglycosidation.
4
With the sulfonic acid-catalyzed acetylation protocols
in hand, we next explored a simple one-pot two step
acetylation–thioglycosidation approach for the prepara-
tion of per-O-acetyl thioglycosides. In the one-pot
TsOH-catalyzed acetylation–thioglycosidation, the
sugar substrate was firstly peracetylated with the

C.-S. Chao et al. / Carbohydrate Research 343 (2008) 957–964
961
described TsOH-catalyzed acetylation, followed by the
hydride under N before use. Flash column chromato-
2
solvent removal, and the addition of p-thiocresol
graphy was performed on silica gel 60 (70–230 mesh,
1
13
(
1.5 mol equiv) in dichloromethane (CH Cl ) and the
E. Merck). H and C NMR spectra of the prepared
compounds were recorded with 300 MHz and 75 MHz
Bruker spectrometers. Chemical shift (d ppm) was
measured against TMS, generated from the residual
2
2
appropriate Lewis acid catalyst (BF ꢁEt O or SnCl )
3
2
4
(
Table 2, entries a–c and f–k). The optimal reaction con-
ditions and exact amount of reagents used are detailed
in Table S2 of Supplementary data. In the one-pot
H SO -catalyzed acetylation–thioglycosidation of D-gal-
CHCl lock signal at d 7.26 ppm against the residual
3
1
3
proton signal of deuterated chloroform, and the
resonance signal is calibrated against the C signal of
deuterated chloroform. Coupling constant(s) in Hertz
C
2
4
1
3
actose and L-fucose, complete removal of solvent led to
undesired dehydration; thus 1.2 equiv of methanol was
1
added to quench the remaining Ac O, followed by the
(Hz) were obtained from H NMR spectra.
2
addition of thiocresol (2 mol equiv) in CH Cl2 and
2
BF ꢁEt O (2 mol equiv). Simple hexopyranoses (Table
1.2. TsOH-catalyzed acetylation procedure for the pre-
paration of per-O-acetyl glycosyl acetates 1–3 and 6–15
3
2
2
, entries a–e), glucosamines with different amino pro-
tecting functions (Table 2, entries f–h), NANA methyl
ester (Table 2, entry i), and lactose (Table 2, entry k)
were smoothly converted to the expected per-O-acetyl
thioglycosides 15–25 in respectable yields (65–84%)
To 0.5 g of mono-, di-, tri-, or hepta-saccharides was
added Ac O (or a mixture of Ac O and CH CN) in
which a catalytic amount of TsOH was dissolved. The
2
2
3
within 1–2 days. Both N-Cbz and N protecting func-
mixture was firstly stirred at 0 °C for 1 h and then stirred
3
1
9
tions were dismantled under these thioglycosidation
conditions. Due to the participation of the group at
C2, the 1,2-trans thioglycosidic bond was formed exclu-
sively in most cases, whereas for L-rhamnose, a 5:1 a- to
b-thioglycosides mixture was furnished, which also
agreed with previous finding (Table 2, entry c). For
NANA methyl ester, the b-thioglycoside 24 was formed
exclusively, which could be attributed to the anomeric
effect (Table 2, entry i).
at the optimal reaction temperature. Upon complete
acetylation, the mixture was diluted with EtOAc
(20 mL), which was washed with cold satd NaHCO3
(20 mL ꢂ 2), water (20 mL ꢂ 1), brine (20 mL ꢂ 1),
dried over MgSO , filtered, and then concentrated.
4
1
0e
Except for melezitose and N-protected amino sugars,
the crude concentrate after work-up was directly charac-
terized with NMR spectroscopy. For the peracetylated
products of melezitose and N-protected amino sugars,
flash chromatography purification with EtOAc–hexane
elution was performed.
In conclusion, cheap and readily available sulfonic
acids, TsOH, and H SO are versatile and efficient cata-
2
4
lysts for the acetylation of carbohydrates. Contrary to
most acid catalysts, which are mainly restricted to the
acetylation of simple carbohydrates without amino
1.3. H SO -catalyzed acetylation procedure for the
2
4
preparation of per-O-acetyl glycosyl acetates 4 and 5
1
0d,e,12–14
functions,
our versatile protocol can be applied
to different carbohydrate substrates including mono-,
di-, tri-, and hepta-saccharides, amino sugars with differ-
ent amino protecting functions, and oligosaccharides
containing fragile furanosyl glycosidic bonds. Addi-
tional features include the chemoselective formation of
tetra-O-acetyl- and penta-O-acetyl-NANA esters. In
addition, the simple one-pot two step acetylation–thio-
glycosidation protocols were also developed for the
direct access of a panel of p-tolyl per-O-acetyl thioglycos-
ides including the first one-pot preparation of a sialyl
thioglycoside.
To a suspension of 0.5 g of D-galactose in a mixture of
Ac O–CH CN at ꢀ20 °C (or ꢀ30 °C for L-fucose) was
2
3
added catalytic amount of H SO in CH CN (neat
2
4
3
H SO was diluted with CH CN to a 10% v/v solution).
2
4
3
The exact amount of reagents used and specific reaction
19
conditions were detailed in Supplementary data. After
stirring for 1 h at ꢀ20 °C (or ꢀ30 °C for L-fucose), the
temperature was gradually warmed up to 0 °C (ꢀ20 °C
for L-fucose) and the stirring was continued till the
end of the reaction. The workup procedure was pro-
cessed as described above.
1.4. One-pot TsOH-catalyzed acetylation–thioglycosida-
tion procedure for the preparation of per-O-acetyl thio-
glycosides of 16–18 and 21–25
1. Experimental
1
.1. General methods
The peracetylation procedure was performed at 0.5 g
sugar substrate scale as described above. Upon complete
acetylation, the reaction solvent was removed and
co-evaporated twice with an equal volume of toluene
on a rotary evaporator. Thiocresol (1.5 mol equiv) in
CH Cl was added to the crude residue at 0 °C, followed
All chemicals were purchased as reagent grade and used
without further purification. TsOH was dried over P O
2
5
4
under vacuum and stored in desiccators. 99.99% H SO
2
used was purchased from a known chemical vendor.
CH CN and CH Cl were distillated over calcium
3
2
2
2
2

962
C.-S. Chao et al. / Carbohydrate Research 343 (2008) 957–964
1
3
by the addition of Lewis acid (either 2 mol equiv of
(s, 3H, Ac); C NMR (75 MHz, CDCl ) d: 171.0, 170.3,
3
BF ꢁEt O or 1.1 mol equiv of SnCl ), and the mixture
170.22, 170.16, 138.8, 122.0, 130.4, 129.2, 86.4, 69.8,
69.7, 66.8, 62.9, 21.52, 21.27, 21.09, 21.03.
3
2
4
was stirred initially at 0 °C under N . After the addition
2
of the reagents, the reaction temperature was raised to
2
7 °C and the reaction mixture stirred until the end of
1.8. p-Tolyl 2,3,4-tri-O-acetyl-1-thio-a-L-rhamnopyrano-
side (18)
the reaction, except for N-acetyl-D-glucosamine 8, in
which the reaction mixture was warmed up to 40 °C.
Upon completion of the reaction, the mixture was
diluted with cold EtOAc (50 mL), which was sequen-
tially washed with cold satd NaHCO3 (30 mL ꢂ 2),
1
H NMR (300 MHz, CDCl ) d: 7.36 (d, J = 8.1 Hz, 2H,
3
ArH), 7.11 (d, J = 8.1 Hz, 2H, ArH), 5.48 (dd, J = 3.3,
1.5 Hz, 1H, H-2), 5.32 (d, J = 1.5 Hz, 1H, H-1), 5.27
(dd, J = 3.3, 9.9 Hz, 1H, H-2), 5.13 (t, J = 9.9 Hz, 1H,
brine (30 mL ꢂ 1), dried over MgSO , filtered, and then
4
concentrated for flash column chromatography to
H-4), 4.41–4.32 (m, H-5), 2.32 (s, 3H, STol CH ), 2.14
3
furnish the per-O-acetyl thioglycosides 16–18 and 21–25.
(s, 3H, Ac), 2.07 (s, 3H, Ac), 2.00 (s, 3H, Ac), 1.24 (s,
1
3
3
H, CH -R); C NMR (75 MHz, CDCl ) d: 170.4,
3 3
1.5. One-pot H SO -catalyzed acetylation–thioglycos-
idation procedure for the preparation of per-O-acetyl
170.3, 138.6, 132.8, 130.4, 130.3, 129.7, 86.4, 71.6 ꢂ 2,
2
4
69.7, 68.1, 21.52, 21.30, 21.21, 21.08, 17.7.
thioglycosides 19 and 20
1
ranoside (19)
.9. p-Tolyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-galactopy-
The peracetylation procedure of D-galactose or L-fucose
was performed at 0.5 g scale as described above. Upon
complete acetylation, 1.2 equiv of methanol was added
and the mixture was stirred for 1 h at 0 °C; subsequent
addition of thiocresol (1.5 mol equiv) in CH Cl and
1
H NMR (300 MHz, CDCl ) d: 7.39 (d, J = 8.1 Hz, 2H,
3
ArH), 7.10 (d, J = 7.8 Hz, 2H, ArH), 5.4 (dd, J = 1.0,
3.3 Hz, 1H, H-4), 5.22 (t, J = 9.9 Hz, 1H, H-2), 5.03
(dd, J = 3.3, 10.0 Hz, H-3), 4.64 (d, J = 10.0 Hz, H-1),
4.19 (dd, J = 7.0, 11.3 Hz, 1H, H-6), 4.11 (dd, J = 6.3,
11.3 Hz, H-6), 3.92 (dt, J = 1.0, 6.1 Hz, H-5), 2.34 (s,
2
2
BF ꢁEt O followed. The mixture was stirred initially at
3
2
0
°C and then gradually warmed to room temperature
(
27 °C) under N . Upon completion of the reaction,
2
the mixture was diluted with cold EtOAc (50 mL), which
3H, STol CH ), 2.12 (s, 3H, Ac), 2.10 (s, 3H, Ac), 2.04
(s, 3H, Ac), 1.97 (s, 3H, Ac); C NMR (75 MHz,
3
1
3
was washed with cold satd NaHCO (30 mL ꢂ 2), brine
3
(
30 mL ꢂ 1), dried over MgSO , filtered, and then con-
CDCl ) d: 170.8, 170.62, 170.48, 169.84, 138.8, 133.5,
4
3
centrated for flash column chromatography to furnish
130.0, 129.0, 87.3, 72.4, 67.7, 67.6, 61.9, 21.56, 21.27,
21.07, 21.04, 20.99.
the per-O-acetyl thioglycosides 19 and 20.
1.6. p-Tolyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-gluco-
pyranoside (16)
1.10. p-Tolyl 2,3,4-tri-O-acetyl-1-thio-b-L-fucopyranoside
(20)
1
1
H NMR (300 MHz, CDCl ) d: 7.39 (d, J = 8.1 Hz, 2H,
H NMR (300 MHz, CDCl ) d: 7.42 (d, J = 8.1 Hz, 2H,
3
3
ArH), 7.10 (d, J = 7.9 Hz, 2H, ArH), 5.20 (dd, J = 9.3,
ArH), 7.13 (d, J = 7.9 Hz, 2H, ArH), 5.25 (dd, J = 0.7,
3.2 Hz, 1H, H-4), 5.19 (t, J = 9.9 Hz, 1H, 1H, H-2), 5.03
(dd, J = 3.3, 9.9 Hz, 1H, H-3), 4.64 (d, J = 9.8 Hz, 1H,
H-1), 3.80 (q, J = 6.4 Hz, 1H, H-5), 2.33 (s, 3H, STol
9
4
.4 Hz, 1H, H-3), 5.01 (dd, J = 9.3, 9.9 Hz, 1H, H-4),
.92 (dd, J = 9.3, 10.0 Hz, 1H, H-2), 4.63 (d,
J = 9.9 Hz, 1H, H-1), 4.20–4.14 (m, 2H, H-6, H-6),
.70 (ddd, J = 2.6, 4.7, 10.1 Hz, 1H, H-5), 2.33 (s, 3H,
STol CH ), 2.09 (s, 3H, Ac), 2.08 (s, 3H, Ac), 2.01 (s,
3
CH ), 2.14 (s, 3H, Ac), 2.10 (s, 3H, Ac), 1.98 (s, 3H,
3
1
3
Ac), 1.24 (d, J = 6.4 Hz, 3H, CH -R); C NMR
3
3
1
3
3
H, Ac), 1.98 (s, 3H, Ac); C NMR (75 MHz, CDCl3)
(75 MHz, CDCl ) d: 171.1, 170.6, 169.9, 138.6, 133.3,
3
d: 170.97, 170.58, 169.78, 169.63, 139.2, 134.2, 130.2,
130.3, 130.0, 129.5, 8.2, 72.8, 70.7, 67.8, 21.6, 21.3,
21.09, 21.06, 16.8.
1
2
30.1, 127.9, 86.2, 76.1, 70.3, 68.6, 62.5, 21.58, 21.16,
1.12, 20.97.
1
.11. p-Tolyl 3,4,6-tri-O-acetyl-2-deoxy-1-thio-2-tri-
1
pyranoside (17)
.7. p-Tolyl 2,3,4,6-tetra-O-acetyl-1-thio-a-D-manno-
chloroethoxycarbamyl-b-D-glucopyranoside (21)
1
H NMR (300 MHz, CDCl ) d: 7.42 (d, J = 8.1 Hz, 2H,
3
1
H NMR (300 MHz, CDCl ) d: 7.40 (d, J = 8.1 Hz, 2H,
ArH), 7.13 (d, J = 7.8 Hz, 2H, ArH), 5.29–5.26 (m, 2H),
5.03 (t, J = 9.8 Hz, 1H, H-4), 4.79 (d, J = 10.8 Hz, 1H),
4.75 (d, J = 10.9 Hz, 1H), 4.23–4.17 (m, 2H), 3.74–3.65
3
ArH), 7.12 (d, J = 8.1 Hz, 2H, ArH), 5.50 (dd, J = 1.5,
2.5 Hz, 1H), 5.42 (d, J = 1.0 Hz, 1H, H-1), 5.34–5.32 (m,
2H), 4.57–4.56 (m, 1H), 4.30 (dd, J = 12.3, 6.0 Hz, 1H),
4.10 (dd, J = 12.5, 2.6 Hz, 1H), 2.34 (s, 3H, STol CH3),
2.15 (s, 3H, Ac), 2.11 (s, 3H, Ac), 2.08 (s, 3H, Ac), 1.99
(m, 2H), 2.36 (s, 3H, STol CH ), 2.10 (s, 3H, Ac), 2.06
3
1
3
(s, 3H, Ac), 2.01 (s, 3H, Ac); C NMR (75 MHz,
CDCl ) d: 171.4, 171.0, 170.5, 169.8, 154.7, 139.0,
3

C.-S. Chao et al. / Carbohydrate Research 343 (2008) 957–964
963
1
6
38.7, 134.1, 133.2, 130.3, 130.2, 95.8, 86.7, 75.1, 71.4,
3.8, 63.5, 55.7, 52.6, 21.5, 21.1, 21.07, 20.95.
9.4 Hz), 5.03 (dd, J = 9.3, 9.9 Hz, 1H), 4.93 (dd, J = 3.3,
10.0 Hz, 1H), 4.82 (dd, J = 9.3, 10.0 Hz, 1H), 4.57 (d,
J = 10.0 Hz), 4.47–4.43 (m, 2H), 4.09–4.03 (m, 3H),
3.84 (t, J = 6.3 Hz, 1H), 3.70 (t, J = 7.7 Hz, 1H), 3.64
1
.12. p-Tolyl 3,4,6-tri-O-acetyl-2-deoxy-2-trichloro-
acetamido-1-thio-b-D-glucopyranoside (22)
(m, 1H), 2.29 (s, 3H, STol CH ), 2.13–1.92 (m, 21H,
3
1
3
7
ꢂ Ac);
C NMR (75 MHz, CDCl ) d: 170.69,
3
1
H NMR (300 MHz, CDCl ) d: 7.50 (br m, 1H, N–H),
170.64, 170.52, 170.42, 170.09, 169.92, 169.41, 138.9,
134.1, 132.8, 130.3, 130.0, 128.1, 101.3, 85.9, 77.0,
74.3, 71.3, 71.2, 71.1, 70.0, 66.9, 62.4, 61.2, 21.55,
21.22, 21.17, 21.01, 20.99, 20.88.
3
7
.39 (d, J = 8.1 Hz, 2H, ArH), 7.10 (d, J = 7.9 Hz, 2H,
ArH), 5.41 (dd, J = 9.3, 11 Hz, 1H, H-3), 5.03 (t,
J = 9.6 Hz, 1H, H-4), 4.75 (d, J = 9.8 Hz, 1H, H-1),
4
1
3
.23–4.01 (m, 3H, H-6, H-2), 3.76 (ddd, J = 2.5, 4.6,
0.0 Hz, 1H, H-5), 2.32 (s, 3H, STol CH ), 2.06 (s,
3
1
3
H, Ac), 1.98 (s, 3H, Ac), 1.78 (s, 3H, Ac); C NMR
Acknowledgments
(
75 MHz, CDCl ) d: 171.8, 171.0, 170.0, 162.2, 139.4,
3
1
5
34.5, 130.1, 128.2, 92.8, 87.2, 76.2, 73.9, 68.9, 62.8,
4.5, 21.6, 21.1, 21.0, 20.6.
We thank Professor H.-F. Chow of Chinese University
of Hong Kong for advice in manuscript preparation,
Professor Y. C. Chen for performing MALDI TOF
MS analysis of per-O-acetyl-b-D-cyclodextrin and we
are indebted to Professor C.-Y. Wu of Academic Sinica
in Taiwan for providing N-acetyl neuraminic acid as gift
for the study. This work was supported by the National
Science Council of Taiwan ROC (NSC 94-2119-M-009-
002).
1
.13. p-Tolyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-
thio-b-D-glucopyranoside (23)
1
H NMR (300 MHz, CDCl ) d: 7.39 (d, J = 8.1 Hz, 2H,
3
ArH), 7.10 (d, J = 7.9 Hz, 2H, ArH), 5.92 (br d,
J = 12 Hz, 1H, N–H), 5.23 (dd, J = 9.3, 10.9 Hz, 1H,
H-3), 5.03 (dd, J = 9.3, 9.9 Hz, 1H, H-4), 4.79 (d,
0
J = 9.9 Hz, 1H, H-1), 4.20–4.17 (m, 2H, H-6, H-6 ),
4
.00 (dd, J = 9.3, 10.0 Hz, 1H, H-2), 3.71 (ddd,
J = 2.6, 4.7, 10.1 Hz, 1H, H-5), 2.34 (s, 3H, STol
CH ), 2.09 (s, 3H, Ac), 2.01 (s, 3H, Ac), 1.99 (s, 3H,
Supplementary data
3
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.carres.
1
3
Ac); C NMR (75 MHz, CDCl ) d: 171.4, 171.0,
3
1
7
70.5, 169.8, 162.4, 139.4, 134.5, 130.1, 128.2, 87.2,
6.2, 73.9, 68.9, 62.8, 54.5, 21.5, 21.1, 21.07, 20.95.
2008.01.014.
1
.14. p-Tolyl 2-thio-b-D-N-acetyl-neuraminic acid methyl
ester (24)
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