A highly α-selective glycosylation for the convenient synthesis of repeating α-(1→4)-linked N-acetyl-galactosamine units

Article abstract of DOI:10.1016/j.carres.2010.05.031

The repeating GalpNAc-α-(1→4)-GalpNAc unit is part of a series of essential structures that can be found in many important biomolecules such as the glycoproteins and the O-antigenic polysaccharides of clinically important bacterial strains. In this paper, we describe an exclusive α-selective glycosylation reaction, using a 4,6-di-O-tert-butyldimethylsilyl-N- acetyloxazolidinone-protected thioglycoside as the glycosyl donor, under pre-activation conditions, with only half amount of the promoter, providing the product GalpNAc-α-(1→4)-GalpNAc in high isolated yield. This reaction can be also applied to increasing the length of the repeating structure, which is of significant use in further synthesis of branched or linear oligosaccharides.

Full text of DOI:10.1016/j.carres.2010.05.031

Carbohydrate Research 345 (2010) 1713–1721
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
A highly
a-selective glycosylation for the convenient synthesis of repeating
a-(1?4)-linked N-acetyl-galactosamine units
*
Lin Yang, Xin-Shan Ye
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Xue Yuan Road 38, Beijing 100191, China
School of Pharmaceutical Sciences, Peking University, Xue Yuan Road 38, Beijing 100191, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The repeating GalpNAc-a-(1?4)-GalpNAc unit is part of a series of essential structures that can be found
Received 18 April 2010
Received in revised form 24 May 2010
Accepted 31 May 2010
in many important biomolecules such as the glycoproteins and the O-antigenic polysaccharides of clin-
ically important bacterial strains. In this paper, we describe an exclusive -selective glycosylation reac-
tion, using 4,6-di-O-tert-butyldimethylsilyl-N-acetyloxazolidinone-protected thioglycoside as the
glycosyl donor, under pre-activation conditions, with only half amount of the promoter, providing the
product GalpNAc- -(1?4)-GalpNAc in high isolated yield. This reaction can be also applied to increasing
a
a
Available online 4 June 2010
a
Keywords:
Glycosylation
the length of the repeating structure, which is of significant use in further synthesis of branched or linear
oligosaccharides.
a-Stereoselectivity
Ó 2010 Elsevier Ltd. All rights reserved.
a-(1?4)-Linked N-acetyl-galactosamine
Oxazolidinone
Thioglycoside
1. Introduction
ical route for the stereoselective construction of the a-(1?4)-Galp-
NAc repeat, utilizing a pentafluoropropionyl (PFP) group as a
The repeating GalpNAc-
a
-(1?4)-GalpNAc unit constitutes
temporary protective group of the C-4 OH group in the GalpNAc gly-
essential structures incorporated in a range of oligosaccharides
and glycoconjugates with biologically important roles. For in-
stance, Campylobacter jejuni, a pathogenic Gram negative bacte-
rium causing gastroenteric disorder and neuromuscular paralysis,
has an antigenic asparagine (Asn)-linked (N-linked) glycoprotein
cosyl donor.11–13 Although the ratio of anomeric isomers (
a
/b) was
-pyranosides required several functional
group transformations, which decreased the synthetic efficiency.
Here, we report a convenient and highly -selective glycosylation
high, the use of 2-azido-
D
a
for the preparation of the repeating GalpNAc-a-(1?4)-GalpNAc
which contains pentameric
a
-(1?4)-linked 2-acetamido-2-
unit.
deoxy-
D
-galactopyranose residues (Fig. 1A).1,2 In addition, the
repeating unit of the O-antigen moiety of the lipopolysaccharide
(LPS) from Acinetobacter baumannii strain 9,3 Escherichia coli
O142,4 E. coli O121,5 Providencia alcalifaciens O216 and the sheath
polysaccharide (SPS) of Sphaerotilus natans (Fig. 1B),7 all contain
the important GalpNAc-a-(1?4)-GalpNAc motif.
The synthesis of such glycans can lead the way to synthetic neo-
glycoconjugate vaccines. Obviously, the construction of repeating
2. Results and discussion
Since oxazolidinone-protected glucosamine was first described
by the Kerns group to be an
a
-selective glycosyl donor,14 several
studies had been made subsequently on its N-acetyl analogues,15,16
confirming that the ring-fused oxazolidinone moiety is an effective
non-participating group for the stereoselective synthesis of
a-(1?4)-linked N-acetylgalactosamine residues is one of the most
a-linked glycosides of 2-amino-2-deoxy-D-hexopyranoses. This
significant parts of the synthetic work in the preparation of these
glycans. In previous studies, several efforts have been made to syn-
thesize the N-linked glycan of C. jejuni. Imperiali and co-workers
have reported the chemoenzymatic synthesis of this glycan.8–10
However, the enzymatic approach called for strict control of reac-
tion conditions and could not be performed to provide the target
molecule in large quantity. Ito and co-workers developed a chem-
protective group had been also introduced into acceptors to en-
hance the reactivity of the 4-hydroxy group during the glycosyla-
tion.17,18 The ‘tied-back’ nature of the oxazolidinone can reduce
the hindrance around the nucleophilic oxygen.19 Moreover, the
N-acetyloxazolidinone functionality also decreases the tendency
for amide glycosylation,20 and removes the possibility of problem-
atic hydrogen bonding networks.21
Considering that N-acetyloxazolidinone can serve as a stereose-
lective donor and an effective glycosyl acceptor, and can be easily
removed by chemoselective deprotection,17,18,22 we decided to
* Corresponding author. Tel.: +86 10 8280 5147; fax.: +86 10 62014949.
E-mail address: xinshan@bjmu.edu.cn (X.-S. Ye).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.05.031

1714
L. Yang, X.-S. Ye / Carbohydrate Research 345 (2010) 1713–1721
α-Gal
p
NAc-(1
→
4)-α-Gal
pNAc-(1→4)-[β-Glcp-(1→3)]-α-GalpNAc-(1→4)-α-GalpNAc-(1→4)-α-
Gal NAc-(1
p
→
)-β-Bacp
-Asn-
→4)-β-D-GalpNAc-(1→4)-β-D-Glcp-(1→3)-β-D-GalpNAc-(1→4)-α-D-GalpNAc-(1→4)-α-D-GalpNAc-(1→
Figure 1. Structures of glycans: (A) the structure of the Asn-linked heptasaccharide glycan of Campylobacter jejuni; (B) the structure of the repeating unit from the sheath
polysaccharide of Sphaerotilus natans.
introduce this protecting group into the galactosamine moiety.
Thus, 4,6-protected N-acetyloxazolidinone thioglycosides were
4 was the only one that reacted, owing to its electron-donating
ability which enhances the nucleophilicity of 4-OH. In the consid-
eration of donors, the lack of reaction of 2 might be attributed to
the three-ring structure of the oxocarbenium intermediate, which
could be quite unstable because of the great ring tension.
Acetylated donor 1 also had low reactivity due to the electron-
withdrawing substituents. Therefore, more attention was paid to
donor 3, which should theoretically have higher reactivity
(Scheme 2).
To optimize the coupling yield, we focused on the amount of
the promoter and donor used in the glycosylation (Table 2). As
shown in Table 2, the combination of Ph2SO–Tf2O without the
hindered base 2,4,6-tri-tert-butylpyrimidine (TTBP)37,38 in the
pre-activation protocol gave no disaccharide product (entry 1)
but instead decomposed donor and intact acceptor. The mecha-
nism of this reaction is unclear. One possible reason is that the
indispensable TTBP might act as a stabilizing agent to protect
the highly active oxocarbenium intermediate after the pre-activa-
tion of donor in this glycosylation case.
By reducing the amount of Ph2SO–Tf2O to nearly half that of the
donor (entry 3), it was surprisingly found that not only could donor
3 be pre-activated readily and completely, but also the yield of
disaccharide 9 was increased greatly from 17.4% to 59.0%. None-
theless, when the amount of promoter was raised to 0.8 equiv
the yield was decreased (entry 4). Thus, we presumed that the
optimum number of equivalents of Ph2SO–Tf2O was half that of
the donor. Under these conditions we then raised the amount of
donor 3, trying to reduce the remaining amount of acceptor 4 (en-
tries 5, 6 and 7). The outcomes were good and the best yield, 74.1%,
was obtained by only using 1.5 equiv of donor 3 and almost half
the amount of promoter (entry 6).
In addition, an obvious distinction was found between the pre-
activation protocol and the traditional non-preactivation proce-
dure by comparing entry 3 with 8 and entry 6 with 9, indicating
the obvious advantage of pre-activation. In all conditions, the num-
ber of equivalents of TTBP needed was twice as much as that of the
donor or the yield declined dramatically. Donors 1 and 2 were also
checked again with half amount of promoter. However, donor 1
was too inactive to be pre-activated completely, leading to much
lower yield than the previous method; donor 2 still gave no cou-
pling product although it was able to be entirely pre-activated.
As Wong and co-workers has proposed,39 one possible rational-
ization for this outcome may be that the reaction pathway involves
sulfonium intermediates that can further promote glycosylations
chosen as building blocks to construct
a-(1?4)-linked GalpNAc
fragments. Three glycosyl donors and one acceptor were chosen
(Fig. 2).
The oxazolidinone-containing glycosyl donors and acceptor can
be readily prepared from commercially available D-galactosamine
(5) on large scale, in high yield (Scheme 1). Acetylation of 5 gave
galactosamine pentaacetate (6), which was then treated with
p-toluenethiol and SnCl4 to produce thioglycoside 7. By sequential
deacetylation and oxazolidinone formation, the key synthetic
intermediate 8 was obtained. Following well-established proce-
dure, donors 1, 2 and 3 were prepared smoothly from the common
intermediate 8 under different conditions. The reductive cleavage
of the benzylidene acetal in 2 using Et3SiH and TfOH23 provided
acceptor 4 with a hydroxyl group exposed at the 4-position. Inter-
estingly, the anomeric configuration was changed from b to
a un-
der acidic conditions.16,18,24,25
The ‘pre-activation’ protocol described a method in which a
glycosyl donor is completely activated and consumed (by TLC
detection) prior to the addition of a glycosyl acceptor.26–31 We
adopted this protocol with the belief that a pre-activation protocol
might influence the stereochemistry outcome of the glycosyla-
tions.32 Under the pre-activation conditions, we first coupled
acceptor 4 with donor 1 employing different promoter systems.
The combination of benzenesulfinyl morpholine (BSM)33 and triflic
anhydride (Tf2O) gave similar low yield (around 10%) of the cou-
pling product to the 1-benzenesulfinyl piperidine (BSP)–Tf2O34
system. The combination of p-toluenesulfenyl chloride (p-TolSCl)
and silver triflate (AgOTf) gave no separable coupling product.
The best result was obtained by using diphenyl sulfoxide (Ph2SO)–
Tf2O combination35,36 in 20% isolated yield.
We then took the best promoter system, Ph2SO–Tf2O, to test the
glycosylation of 4 with the two other donors, 2 and 3 (Table 1).
However, the glycosylation of 4 with 2 gave no disaccharide and
the glycosylation of 4 with 3 provided a low yield of disaccharide
with exclusive
a-anomeric selectivity. The major problem of this
glycosylation was the low reactivity of acceptor 4. Compound 4 al-
ways remained in large quantity while donors decomposed. This
difficulty is common to most pyranose acceptors with a 4-OH free,
especially in galactosamine acceptors with the much lower reactiv-
ity of this hydroxyl group.
In the consideration of acceptors, we tried other types of pro-
tecting groups on 6-OH. However, the benzyl-protected acceptor
Ph
O
HO
O
AcO
O
OBn
O
OAc
O
TBDMSO
O
O
OTBDMS
O
O
STol
O
STol
STol
NAc
STol
NAc
NAc
NAc
O
O
O
O
1
2
3
4
Figure 2. Glycosyl building blocks.

L. Yang, X.-S. Ye / Carbohydrate Research 345 (2010) 1713–1721
1715
HO
HO
OH
O
OH
NH2 HCl
OAc
O
OAc
AcO
AcO
AcO
AcO
O
a
b
OAc
STol
NHAc
NHAc
5
6
7
OAc
AcO
O
O
STol
NAc
O
1
Ph
h
O
O
HO
O
HO
OBn
O
OH
O
O
c, d
e, f
g
O
STol
O
STol
NAc
NAc
STol
NH
O
O
O
8
2
4
i, j
OTBDMS
O
TBDMSO
O
STol
NAc
O
3
Scheme 1. Synthesis of monosaccharide blocks. Reagents and conditions: (a) NaOAc, Ac2O, 140 °C. 3 h, 91%; (b) SnCl4, TolSH, CH2Cl2, reflux, overnight, 93%; (c) NaOH, H2O,
reflux, 12 h; (d) triphosgene, NaHCO3, CH3CN/H2O = 2:1, 30 min, 81% for two steps; (e) PhCH(OMe)2, CSA, CH3CN, rt, 10 min; (f) Ac2O, pyridine, DMAP, 12 h, 90% for two steps.
(g) Et3SiH, TfOH, CH2Cl2, ꢀ72 °C, 1 h, 73%; (h) Ac2O, pyridine, DMAP, 3 h, 88%; (i) TBDMSCl, imidazole, DMF, 70 °C, 26 h; (j) Ac2O, pyridine, DMAP, 12 h, 77% for two steps.
Table 1
Subsequently, disaccharide 9 was transformed to acceptor 11 in
order to lengthen the repeating -(1?4)-linked GalpNAc unit.
Glycosylation of 4 with 1, 2 and 3
a
With the method used in the synthesis of monosaccharide building
blocks, compound 9 was readily changed into 11 in high yield
(Scheme 3A). Trisaccharide 12 was obtained as a single a-anomer
by the coupling of 3 and 11 (Scheme 3B). As was done for the disac-
charide, the glycosylation could be greatly improved by changing
the amount of promoter (Table 3).
Donor Acceptor Yield of disaccharide (%)
a
a
/b
only
1
2
3
4
4
4
20
No reaction
17
a
only
Reagents and conditions: Ph2SO, Tf2O, TTBP, CH2CI2, ꢀ72 °C
to r.t.
The relationship between the amount of promoter and the yield
was similar to the disaccharide case. It seemed that using a little
more than half amount of promoter was better (Table 3, entry 3
vs 2 and entry 8 vs 7). Due to the larger sugar fragment and much
lower 4-OH reactivity, the best yield of 12 was 68% using 2.0 equiv
(Fig. 3). If a full equivalent of promoter was provided, half was en-
ough to activate the donor and the other half would remain to acti-
vate the subsequently added acceptor or even the newly formed
disaccharide and destroy them.
OTBDMS
O
TBDMSO
O
OBn
O
HO
O
OTBDMS
O
TBDMSO
O
NAc
O
OBn
O
O
hP2SO, Tf2O, TTBP
CH2Cl2, -72 ºC to r.t.
STol
+
NAc
STol
NAc
O
NAc
STol
O
O
4
3
O
9
Scheme 2. The coupling reaction of 4 and 3.

1716
L. Yang, X.-S. Ye / Carbohydrate Research 345 (2010) 1713–1721
Table 2
Glycosylation of 4 with 3 under different conditions
Entry
Donor (equiv)
Acceptor (equiv)
Promoter system (equiv)
Yield of 9 (%)
a/b
Pre-activation
1
2
3
4
5
6
7
1.1
1.1
1.1
1.1
1.3
1.5
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
Ph2SO (1.1)/Tf2O (1.1)
Trace
17.4
59.0
45.0
64.3
74.1
72.9
Ph2SO (1.1)/Tf2O (1.1)/TTBP(2.2)
Ph2SO (0.6)/Tf2O (0.7)/TTBP (2.2)
Ph2SO (0.8)/Tf2O (0.9)/TTBP (2.2)
Ph2SO (0.7)/Tf2O (0.8)/TTBP (2.6)
Ph2SO (0.8)/Tf2O (0.9)/TTBP (3.0)
Ph2SO (1.0)/Tf2O (1.1)/TTBP (4.0)
a
a
a
a
a
a
only
only
only
only
only
only
Non-pre-activation
8
9
1.1
1.5
1.0
1.0
Ph2SO (0.6)/Tf2O (0.7)/TTBP (2.2)
Ph2SO (0.8)/Tf2O (0.9)/TTBP (3.0)
48.0
54.2
a
a
only
only
TBDMSO
OTBDMS
O
OTf TfO
S
Tf2O
Ph2SO
+
O
STol
NAc
O
3
1.0 equiv
0.5 equiv
TBDMSO
OTBDMS
O
TBDMSO
O
OTBDMS
O
STol
S
TfO
STol
O
+
OTf
+
NAc
NAc
O
O
0.5 equiv
0.5 equiv
0.5 equiv
OBn
O
TBDMSO
OTBDMS
O
HO
O
O
OTf
+
NAc
STol
NAc
O
O
4
1.0 equiv
OTBDMS
O
TBDMSO
O
NAc
O
OBn
O
O
O
NAc
STol
O
9
Figure 3. Proposed reaction pathway for disaccharide formation with substoichiometric amount of Ph2SO–Tf2O.

L. Yang, X.-S. Ye / Carbohydrate Research 345 (2010) 1713–1721
1717
O
Ph
OTBDMS
O
TBDMSO
O
O
HO
O
OBn
O
O
O
a, b
c
NAc
O
NAc
NAc
OBn
O
OBn
O
OBn
O
O
O
O
O
O
O
O
O
NAc
STol
NAc
STol
NAc
STol
O
O
O
9
10
11
(A) Synthesis of disaccharide blocks. Reagents and conditions: (a) TBAF/THF, r.t., 10 min;
(b) PhCH(OMe) 2, CSA, CH3CN, r.t., 10 min, 88% for two steps. (c) Et3SiH, TfOH, CH2Cl2, -72 º C, 50 min, 80%.
TBDMSO
O
OTBDMS
O
HO
O
OBn
NAc
O
O
TBDMSO
O
OTBDMS
O
OBn
O
O
NAc
Ph2SO, Tf2O, TTBP
CH2Cl2, -72 ºC to r.t.
+
O
OBn
O
STol
O
O
O
NAc
NAc
O
OBn
O
O
O
NAc
STol
3
O
O
NAc
STol
11
12
O
(B) Synthesis of trisaccharide
Scheme 3. The synthesis of trisaccharide as an example of increasing the a-(1?4)-linked GalpNAc-repeating unit.
Table 3
Glycosylation of 11 with 3 under different conditions
Entry 1
Donor (equiv)
Acceptor (equiv)
Promoter system (equiv)
Yield of 12 (%)
a/b
Pre-activation
1
2
3
4
5
6a
7
8
9
1.1
1.1
1.1
1.5
1.5
2.0
2.0
2.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
Ph2SO (1.1)/Tf2O (1.1)/TTBP (2.2)
Ph2SO (0.6)/Tf2O (0.7)/TTBP (2.2)
Ph2SO (0.8)/Tf2O (0.9)/TTBP (2.2)
Ph2SO (0.8)/Tf2O (0.9)/TTBP (3.0)
Ph2SO (1.2)/Tf2O (1.2)/TTBP (3.0)
Ph2SO (0.8)/Tf2O (0.9)/TTBP (4.0)
Ph2SO (1.0)/Tf2O (1.1)/TTBP (4.0)
Ph2SO (1.2)/Tf2O (1.3)/TTBP (4.0)
Ph2SO (1.5)/Tf2O (1.6)/TTBP (4.0)
22.7
26.0
33.3
41.0
20.8
38.2
43.8
68.0
20.0
a
a
a
a
a
a
a
a
a
only
only
only
only
only
only
only
only
only
Non-preactivation
10 1.1
1.0
Ph2SO (0.8)/Tf2O (0.9)/TTBP (2.2)
20.8
a
only
a
The donor was not activated completely.
of donor 3 and 1.2 equiv of Ph2SO. Nevertheless, the pre-activation
protocol showed a higher yield than the ordinary non-preactiva-
tion procedure (entry 3 vs 10).
thioglycoside’ glycosylation reaction could be applied to the itera-
tive one-pot oligosaccharide assembly.
In conclusion, an examination of glycosylation reactions for
As donor 3 and acceptor 4 could be easily synthesized on a large
scale, this simple but effective method might be a more convenient
the construction of the repeating GalpNAc-a-(1?4)-GalpNAc unit
was performed. The use of the N-acetyloxazolidinone-protected
way to construct the repeating GalpNAc-
a
-(1?4)-GalpNAc unit for
thioglycosides as the glycosyl donor and acceptor was effective
the synthesis of bioactive oligosaccharides. Meanwhile, the disac-
charide (9), acceptor (11) and trisaccharide (12) products could
be further used as building blocks in the synthesis of branched
and linear glycans with diverse bioactivities. Furthermore, as both
the donor and acceptor are thioglycosides, this ‘thioglycoside-to-
in providing the exclusive a-stereoselective glycosylation. The
greatly increased yield of disaccharide and trisaccharide in the
coupling reaction was achieved by reducing the amount of
Ph2SO–Tf2O promoter. This method may find applications in
the chemical synthesis of various complex oligosaccharides with

1718
L. Yang, X.-S. Ye / Carbohydrate Research 345 (2010) 1713–1721
biological importance. Further extension of this protocol is now
under investigation.
stirred mixture. After 30 min, EtOAc (150 mL) containing ethylene-
diamine (2.1 mL, 30.9 mmol) was added and the stirring was con-
tinued for 15 min. The aqueous layer was separated and extracted
with EtOAc (2 ꢁ 75 mL). The combined organic layers were washed
with brine, dried over Na2SO4, filtered and evaporated. The residue
obtained was purified by column chromatography on silica gel (1:5
hexane–EtOAc) to give 8 (2.8 g, 81%) as a white amorphous solid.
3. Experimental
3.1. General methods
Rf = 0.1 (1:3 hexane–EtOAc): ½a D27
ꢂ
ꢀ51.1 (c 1.0, MeOH); 1H NMR
All chemicals were purchased as reagent grade and used with-
out further purification, unless otherwise noted. Dichloromethane
(CH2Cl2), pyridine and acetonitrile (CH3CN) were distilled over cal-
cium hydride (CaH2). MeOH was distilled from magnesium. DMF
was stirred with CaH2 and distilled under reduced pressure. All
glycosylation reactions were carried out under anhydrous condi-
tions with freshly distilled solvents, unless otherwise noted. Reac-
tions were monitored by analytical thin-layer chromatography on
Silica Gel 60 F254 precoated on aluminium plates (E. Merck). Spots
were detected under UV (254 nm) and/or by staining with acidic
ceric ammonium molybdate. Solvents were evaporated under re-
duced pressure and below 40 °C (bath). Organic solutions of crude
products were dried over anhydrous Na2SO4. Column chromatog-
raphy was performed on silica gel (200–300 mesh). 1H NMR spec-
tra were recorded on a JEOL AL-300, Varian INOVA-500 or Advance
DRX Bruker-400 spectrometers at 25 °C. Chemical shifts (in ppm)
were referenced to tetramethylsilane (d = 0 ppm) in deuterated
chloroform. 13C NMR spectra were obtained by using the same
NMR spectrometers and were calibrated with CDCl3 (d = 77.00
ppm). Mass spectra were recorded using a PE SCLEX QSTAR spec-
trometer. Elemental analysis data were recorded on a Vario EL-I
elemental analyzer.
(400 MHz, CD3COCD3) d 7.50–7.47 (m, 2H, Ar), 7.16 (d, 2H,
J = 8.0 Hz, Ar), 6.73 (s, 1H, NH), 4.87 (d, 1H, J1,2 = 9.6 Hz, H-1),
4.57 (d, 1H, J = 4.4 Hz, 4-OH), 4.37 (d, 1H, J = 4.0 Hz, 6-OH), 4.32
(dd, 1H, J3,2 = 11.2 Hz, J3,4 = 2.0, H-3), 3.94–3.89 (m, 2H, H-2, H-
6a), 3.82–3.78 (m, 3H, H-4, H-5, H-6b), 2.32 (s, 3H, CH3); 13C
NMR (100 MHz, CD3COCD3) d 159.49, 138.79, 133.59, 130.43,
129.47, 86.59, 83.50, 81.06, 65.63, 62.20, 54.70, 21.02. HRMS
(ESI) calcd for
623.1729.
C
28H35N2O10S2 [2M+H]+: 623.1728. Found:
3.4. p-Tolyl 2-acetamino-4,6-O-diacetyl-2,3-N,O-carbonyl-2-
deoxy-1-thio-b- -galactopyranoside (1)
D
4-(Dimethylamino)pyridine (9.8 mg, 0.08 mmol, 0.05 equiv)
was added to stirred solution of compound (500 mg,
a
8
1.61 mmol, 1.0 equiv) in 8 mL of pyridine. The mixture was cooled
to 0 °C and acetic anhydride (Ac2O) (1.64 g, 1.52 mL, 16.1 mmol)
was added dropwise. The resulting solution was gradually warmed
to room temperature and stirred for further 3 h. The crude product
was concentrated and the residue was purified by column chroma-
tography on silica gel (2:1 hexane–EtOAc) to give 1 as a white
amorphous solid (618 mg, 88%): Rf = 0.25 (1.5:1 hexane–EtOAc);
½
a 2D7
ꢂ
ꢀ67.4 (c 1.0, MeOH); 1H NMR (300 MHz, CDCl3) d 7.42 (d,
2H, J = 7.8 Hz, Ar), 7.11 (d, 2H, J = 7.8 Hz, Ar), 5.66 (s, 1H, H-4),
4.81 (d, 1H, J1,2 = 8.7 Hz, H-1), 4.50 (dd, 1H, J2,1 = 8.7 Hz,
J2,3 = 11.7 Hz, H-2), 4.27 (dd, 1H, J3,2 = 11.7 Hz, J3,4 = 2.1 Hz, H-3),
4.20 (dd, 1H, J = 5.7, 11.4 Hz, H-6a), 4.10 (dd, 1H, J = 7.2, 11.4 Hz,
H-6b), 3.95–3.91 (m, 1H, H-5), 2.59 (s, 3H, CH3), 2.34 (s, 3H,
CH3), 2.17 (s, 3H, CH3), 2.00 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d 173.07, 170.21, 169.34, 153.19, 138.34, 133.26, 129.70, 129.52,
88.69, 78.06, 75.60, 64.96, 61.70, 56.40, 24.76, 21.05, 20.54,
20.51. HRMS (ESI) calcd for C20H23NO8SNa [M+Na]+: 460.1037.
Found: 460.1049.
3.2. p-Tolyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-b-D-
galactopyranoside (7)
SnCl4 (6.0 g, 2.7 mL, 23.1 mmol, 0.9 equiv) was added to a stirred
solutionof
-galactosamine pentaacetate(6)40,41 (10.0 g, 25.7 mmol,
D
1.0 equiv) and p-toluenethiol (3.8 g, 30.8 mmol, 1.2 equiv) in dry
CH2Cl2 (200 mL). The reaction mixture was heated at reflux over-
night, then cooled to room temperature and the reaction was
quenched by the addition of satd aq NaHCO3 (250 mL). The aqueous
layer was separated and extracted with CH2Cl2 (2 ꢁ 250 mL). The
combinedorganiclayerswerewashedwithbrine, driedoverNa2SO4,
filtered and evaporated. The residue obtained was recrystallized
from hexane–EtOAc to give 7 (10.8 g, 93%) as a white amorphous so-
3.5. p-Tolyl 2-acetamido-4,6-O-benzylidene-2,3-N,O-carbonyl-2-
deoxy-1-thio-b-D-galactopyranoside (2)
lid. Rf = 0.5 (EtOAc): ½a D27
ꢂ
ꢀ9.4 (c 1.0, MeOH); 1H NMR (400 MHz,
Benzaldehyde dimethyl acetal (1.76 g, 1.74 mL, 11.58 mmol,
2.0 equiv) was added dropwise to a stirred solution of compound
CDCl3) d 7.41 (d, 2H, J = 8.0 Hz Ar), 7.11 (d, 2H, J = 8.0 Hz, Ar), 5.68
(d, 1H, J = 9.2 Hz, NH), 5.37 (d, 1H, J = 2.8 Hz, H-4), 5.20 (dd, 1H,
J3,2 = 10.8 Hz, J3,4 = 3.2 Hz, H-3), 4.86 (d, 1H, J1,2 = 10.4 Hz, H-1),
4.21–4.08 (m, 3H, H-2, H-6a, H-6b), 3.92 (t, 1H, J = 6.4 Hz, H-5),
2.33 (s, 3H, CH3), 2.12 (s, 3H, CH3), 2.02 (s, 3H, CH3), 1.98 (s, 6H,
CH3 ꢁ 2); 13C NMR (75 MHz, CDCl3) d 170.52, 170.39, 170.25,
138.03, 132.59, 129.57, 129.19, 87.42, 74.26, 71.08, 66.90, 61.78,
49.65, 23.38, 21.07, 20.64. HRMS (ESI) calcd for C21H31N2O8S
[M+NH4]+: 471.1796. Found: 471.1794.
8
(1.80 g, 5.79 mmol, 1.0 equiv) and camphorsulfonic acid
(134.40 mg, 0.58 mmol, 0.1 equiv) in dry CH3CN (18 mL) at room
temperature. The pH was about 2–3. The solution was then stirred
for 10 min, at which time TLC showed complete disappearance of
8. The reaction was quenched by the addition of Et3N to pH around
7 and concentrated in vacuo. After the addition of DMAP (35.3 mg,
0.29 mmol, 0.05 equiv), the mixture was dissolved in 18 mL of pyr-
idine. The solution was cooled to 0 °C and Ac2O (5.91 g, 5.5 mL,
57.9 mmol, 10 equiv) was added dropwise. The resulting mixture
was gradually warmed to room temperature and stirred for further
12 h. The crude product was concentrated and the residue was
purified by column chromatography on silica gel (2:1 hexane–
EtOAc) to give 2 as a white amorphous solid (2.29 g, 90%):
3.3. p-Tolyl 2-amino-2,3-N,O-carbonyl-2-deoxy-1-thio-b-D-
galactopyranoside (8)
Compound 7 (5.0 g, 11.0 mmol, 1.0 equiv) was dissolved in 2 N
NaOH (100 mL), and heated at reflux for 24 h, cooled to room tem-
perature and the reaction was quenched by the addition of 2 N HCI
(100 mL). The mixture was evaporated to give the crude product,
which was then dissolved in MeCN (100 mL) and added with satd
aq NaHCO3 (50 mL). The mixture was cooled to 0 °C, and triphos-
gene (1.3 g, 4.4 mmol, 0.4 equiv) was added to the vigorously
Rf = 0.4 (1:1 hexane–EtOAc); ½a D27
ꢂ
ꢀ119.8 (c 1.7, CHCl3); 1H NMR
(CDCl3, 400 MHz): d 7.53–7.47 (m, 4H, Ar), 7.39–7.37 (m, 3H, Ar),
7.10 (d, 2H, J = 8.0 Hz, Ar), 5.60 (s, 1H, PhCH), 4.84 (d, 1H,
J1,2 = 8.8 Hz, H-1), 4.73 (dd, 1H, J2,1 = 8.8 Hz, J2,3 = 11.2 Hz, H-2),
4.60 (s, 1H, H-4), 4,34 (dd, 1H, J = 0.8, 12.8 Hz, H-6a), 4.22 (dd,
1H, J3,2 = 11.2 Hz, J3.4 = 2.0 Hz, H-3), 4.08 (dd, 1H, J = 2.0, 12.8 Hz,

L. Yang, X.-S. Ye / Carbohydrate Research 345 (2010) 1713–1721
1719
H-6b), 3.48 (s, 1H, H-5), 2.56 (s, 3H, CH3), 2.33 (s, 3H, CH3); 13C
3.8. p-Tolyl (2-acetamido-4,6-di-O-tert-butyldimethylsilyl-2,3-
N,O-carbonyl-2-deoxy- -galactopyranosyl)-(1?4)-2-acet-
amido-6-O-benzyl-2,3-N,O-carbonyl-2-deoxy-1-thio-a-D-
NMR (CDCl3, 75 MHz): d 172.94, 153.61, 138.24, 136.85, 133.51,
130.04, 129.53, 129.39, 128.29, 126.38, 100.54, 88.61, 79.26,
70.98, 69.83, 69.64, 55.43, 24.90, 21.15. HRMS (ESI) calcd for
a-D
galactopyranoside (9)
C
C
23H23NO6SK [M+K]+: 480.0872. Found: 480.0867. Anal. Calcd for
23H23NO6S: C, 62.57; H, 5.25; N, 3.17. Found: C, 62.81; H, 5.49;
Tf2O (8.7 mg, 5.1 lL, 0.031 mmol, 0.9 equiv) was added to a stir-
N, 2.98.
red mixture of 3 (29.6 mg, 0.051 mmol, 1.5 equiv), Ph2SO (5.5 mg,
0.027 mmol, 0.8 equiv), TTBP (26 mg, 0.11 mmol, 3.0 equiv) and
activated 4 Å molecular sieves (500 mg, powder) in CH2Cl2 (5 mL)
at ꢀ72 °C under nitrogen atmosphere. The reaction mixture was
stirred for 5 min, after loss of 3 detected by TLC, a solution of the
acceptor 4 (15.0 mg, 0.034 mmol, 1.0 equiv) in CH2Cl2 (1.0 mL)
was added dropwise to the mixture. The mixture was stirred and
warmed up to room temperature slowly and stirred for further
2 h, and the reaction was quenched by the addition of Et3N
(0.1 mL). The precipitate was filtered off and the filtrate was con-
centrated. The residue was purified by column chromatography
on silica gel (10:1 hexane–EtOAc) to give 9 as a syrup (22.6 mg,
3.6. p-Tolyl 2-acetamido-4,6-di-O-tert-butyldimethylsilyl-2,3-
N,O-carbonyl-2-deoxy-1-thio-b-D-galactopyranoside (3)
A mixture of compound 8 (1.5 g, 4.82 mmol, 1.0 equiv), tert-
butyldimethylsilyl chloride (4.4 g, 29.1 mmol, 6.0 equiv) and imid-
azole (1.3 g, 19.11 mmol, 4.0 equiv) in dry DMF (8.8 mL, 0.5 g tert-
butyldimethylsilyl chloride per mL) was heated at 70 °C for 26 h.
After the TLC showed complete disappearance of 8, the reaction
mixture was extracted with EtOAc (90 mL) and the organic layer
was washed with satd aq NH4Cl (30 mL ꢁ 2) and water (30 mL).
The washed organic layer was dried over Na2SO4 and concentrated
in vacuo. After the addition of DMAP (29.4 mg, 0.24 mmol,
0.05 equiv), the mixture was dissolved in 15 mL of pyridine. The
solution was cooled to 0 °C and Ac2O (4.92 g, 4.5 mL, 48.23 mmol,
10 equiv) was added dropwise. The resulting solution was gradu-
ally warmed to room temperature and stirred for further 12 h.
The crude product was concentrated and the residue was purified
by column chromatography on silica gel (10:1 hexane–EtOAc) to
give 3 as a white amorphous solid (2.16 g, 77%): Rf = 0.7 (3:1 hex-
74%): Rf = 0.7 (3:1 hexane–EtOAc); ½a D27
ꢂ
+172.8 (c 2.5, CHCl3); 1H
NMR (CDCl3, 400 MHz): d 7.37–7.31 (m, 7H, Ar), 7.05 (d, 2H,
J = 8.0 Hz, Ar), 6.06 (d, 1H, J1,2 = 4.0 Hz, H-1), 5.81 (d, 1H,
J1 ,2 = 2.8 Hz, H-10), 4.73 (d, 1H, J = 11.6 Hz, PhCH2), 4.61 (dd, 1H,
J3,2 = 12.0 Hz, J3.4 = 2.0 Hz, H-3), 4.59 (s, 1H, H-4), 4.52 (d, 1H,
J = 11.6 Hz, PhCH2), 4.50 (dd, 1H, J2,1 = 4.0 Hz, J2,3 = 12.0 Hz, H-2),
0
0
4.45 (dd, 1H, J3 ,2 = 9.6 Hz, J3 ,4 = 2.0 Hz, H-30), 4.44 (s, 1H, H-40),
0
0
0
0
4.39 (t, 1H, J = 8.0 Hz, H-50), 4.37 (dd, 1H, J2 ,1 = 2.8 Hz, J2 ,3 = 9.6 Hz,
H-20), 3.89 (dd, 1H, J = 6.0, 8.0 Hz, H-6a0), 3.74 (t, 1H, J = 9.6 Hz, H-
5), 3.63–3.59 (m, 2H, H-6b0, H-6a), 3.50 (dd, 1H, J = 6.0, 9.6 Hz, H-
6b), 2.54 (s, 3H, CH3), 2.47 (s, 3H, CH3), 2.31 (s, 3H, CH3), 0.90 (s,
18H, t-Bu ꢁ 2), 0.13 (s, 3H, CH3), 0.10 (s, 3H, CH3), 0.09 (s, 3H,
CH3), 0.08 (s, 3H, CH3); 13C NMR (CDCl3, 75 MHz): d 172.07,
171.37, 152.98, 152.37, 138.53, 137.78, 133.41, 129.90, 128.37,
128.13, 127.69, 96.11, 87.29, 75.29, 74.83, 73.02, 72.96, 70.40,
69.31, 66.81, 65.70, 60.25, 55.64, 54.92, 25.84, 23.88, 21.11,
18.22, ꢀ4.57, ꢀ5.13, ꢀ5.47. HRMS (ESI) Calcd for C44H65N2O12SSi2
[M + H]+: 901.3791. Found: 901.3786.
0
0
0
0
ane–EtOAc); ½a 2D7
ꢂ
ꢀ58.9 (c 1.0, MeOH); 1H NMR (CDCl3, 400 MHz):
d 7.40 (d, 2H, J = 8.0 Hz Ar), 7.08 (d, 2H, J = 8.0 Hz Ar), 4.77 (d, 1H,
J1,2 = 8.7 Hz, H-1), 4.55 (dd, 1H, J2,1 = 8.7 Hz, J2,3 = 11.3 Hz, H-2),
4.39 (s, 1H, H-4), 4,14 (dd, 1H, J3,2 = 11.3 Hz, J3.4 = 1.9 Hz, H-3),
3.78 (dd, 1H, J = 7.1, 10.2 Hz, H-6a), 3.70 (dd, 1H, J = 5.7, 10.2 Hz,
H-6b), 3.54–3.50 (m, 1H, H-5), 2.57 (s, 3H, CH3), 2.32 (s, 3H,
CH3), 0.90 (s, 9H, t-Bu), 0.88 (s, 9H, t-Bu), 0.12 (s, 3H, CH3), 0.09
(s, 3H, CH3), 0.05 (s, 3H, CH3), 0.03 (s, 3H, CH3); 13C NMR (CDCl3,
75 MHz): d 173.22, 153.85, 137.61, 131.99, 130.93, 129.47, 88.57,
81.21, 80.68, 65.72, 61.42, 55.23, 25.84, 24.95, 21.08, 18.21,
ꢀ4.44, ꢀ5.02, ꢀ5.43. MS (ESI) 582 [M+H]+, 604 [M+Na]+, 620
[M+K]+. Anal. Calcd for C28H47NO6SSi2: C, 57.79; H, 8.14; N, 2.41.
Found: C, 57.68; H, 7.95; N, 2.26.
3.9. p-Tolyl (2-acetamido-4,6-O-benzylidene-2,3-N,O-carbonyl-
2-deoxy-a-D-galactopyranosyl)-(1?4)-2-acetamido-6-O-benzyl-
2,3-N,O-carbonyl-2-deoxy-1-thio-a-D-galactopyranoside (10)
The disaccharide 9 (378 mg, 0.42 mmol, 1.0 equiv) was dis-
solved in 4 mL of 1 M TBAF in THF solvent at room temperature
by stirring for about 10 min. The mixture was then extracted with
EtOAc (50 mL) and the organic layer was washed with satd aq
NH4Cl (15 mL ꢁ 2) and water (10 mL). The washed organic layer
was dried over Na2SO4 and concentrated in vacuo. Purification
using a short chromatography column, from which the crude prod-
uct was readily flushed out by EtOAc, was necessary to remove the
large amount of inorganic salts. The crude product, along with
camphorsulfonic acid (9.75 mg, 0.04 mmol, 0.1 equiv), was then
dissolved in dry CH3CN (4 mL) at room temperature. The pH was
3.7. p-Tolyl 2-acetamido-6-O-benzyl-2,3-N,O-carbonyl-2-deoxy-
1-thio-a-D-galactopyranoside (4)
Et3SiH (1.19 g, 1.63 mL, 10.23 mmol, 3.0 equiv) and TfOH
(1.02 g, 0.60 mL, 6.80 mmol, 2.0 equiv) were added to a stirred
mixture of 2 (1.5 g, 3.40 mmol, 1.0 equiv) and activated 4 Å molec-
ular sieves (2.0 g, powder) in CH2Cl2 (60 mL, 25 mg of 2 per mL) at
ꢀ72 °C under nitrogen atmosphere. After being stirred for 1 h at
ꢀ72 °C, Et3N (1 mL) and MeOH (1 mL) were added successively.
The mixture was filtered and the filtrate was concentrated. The res-
idue was purified by column chromatography on silica gel (4:1
hexane–EtOAc) to give white amorphous solids (1.1 g, 73%):
about 2–3. Benzaldehyde dimethyl acetal (127 mg, 125.7 lL,
0.84 mmol, 2.0 equiv) was added dropwise to this stirred solution.
The reaction was finished rapidly in about 10 min and was
quenched by the addition of Et3N to pH of around 7 and concen-
trated in vacuo. The residue was purified by column chromatogra-
phy on silica gel (2:1 hexane–EtOAc) to give white amorphous
Rf = 0.5 (1:1 hexane–EtOAc); ½a D27
ꢂ
+227.4 (c 1.0, MeOH); 1H NMR
(CDCl3, 300 MHz): d 7.36–7.31 (m, 7H, Ar), 7.09 (d, 2H, J = 8.1 Hz,
Ar), 6.17 (d, 1H, J1,2 = 4.5 Hz, H-1), 4.74 (dd, 1H, J2,1 = 4.5 Hz,
J2,3 = 12.3 Hz, H-2), 4.61 (d, 1H, J = 11.4 Hz, PhCH2), 4.55 (d, 1H,
J = 11.1 Hz, PhCH2), 4.53 (s, 1H, H-4), 4,40 (dd, 1H, J3,2 = 12.3 Hz,
J3.4 = 1.8 Hz, H-3), 4.33 (t, 1H, J = 5.1 Hz, H-5), 3.82 (d, 2H,
J = 5.1 Hz, H-6a, H-6b), 3.29 (s, 1H, 4-OH), 2.54 (s, 3H, CH3), 2.33
(s, 3H, CH3); 13C NMR (CDCl3, 100 MHz): d 171.50, 153.00,
138.36, 137.12, 133.02, 129.94, 128.60, 128.12, 127.83, 87.71,
76.54, 73.96, 70.08, 69.91, 66.97, 54.86, 23.93, 21.14. MS (ESI)
444 [M+H]+, 466 [M+Na]+, 482 [M+K]+. Anal. Calcd for C23H25NO6S:
C, 62.29; H, 5.68; N, 3.16. Found: C, 62.44; H, 5.72; N, 3.10.
solids 10 (280 mg, 88%): Rf = 0.5 (1:1 hexane–EtOAc); ½a D27
ꢂ
+306.0
d 7.51 (d, 2H,
(c 0.7, CHCl3); 1H NMR (CDCl3, 400 MHz):
J = 4.8 Hz, Ar), 7.38–7.31 (m, 10H, Ar), 7.06 (d, 2H, J = 8.0 Hz, Ar),
6.07 (d, 1H, J1,2 = 4.0 Hz, H-1), 6.00 (s, 1H, H-10), 5.62 (s, 1H, PhCH),
4.76 (d, 1H, J = 11.6 Hz, PhCH2), 4.71–4.46 (m, 7H, PhCH2, H-2, H-20,
H-3, H-30, H-4, H-40), 4.41 (t, 1H, J = 6.8 Hz, H-5), 4.35 (d, 1H,
J = 12.8 Hz, H-6a0), 4.15 (d, 1H, J = 12.8 Hz, H-6b0), 3.90 (s, 1H,
H-50), 3.59 (t, 1H, J = 8.8 Hz, H-6a), 3.49 (dd, 1H, J = 6.4, 9.6 Hz, H-

1720
L. Yang, X.-S. Ye / Carbohydrate Research 345 (2010) 1713–1721
6b), 2.56 (s, 3H, CH3), 2.47 (s, 3H, CH3), 2.31 (s, 3H, CH3); 13C NMR
(CDCl3, 75 MHz): d 171.90, 171.30, 152.76, 152.69, 138.66, 137.75,
136.89, 133.39, 129.98, 129.32, 128.45, 128.28, 128.04, 127.86,
127.79, 126.17, 100.27, 96.94, 87.20, 75.40, 73.06, 72.38, 71.46,
70.33, 69.82, 69.65, 66.67, 63.70, 55.94, 54.87, 23.96, 23.85,
21.13. HRMS (ESI) calcd for C39H40N2O12SK [M+K]+: 799.1928.
Found: 799.1923.
H-6a0, H-6b0, H-6b00), 2.53 (s, 3H, CH3), 2.47 (s, 3H, CH3), 2.45 (s,
3H, CH3), 2.31 (s, 3H, CH3), 0.90 (s, 9H, t-Bu), 0.89 (s, 9H, t-Bu),
0.12 (s, 3H, CH3), 0.10 (s, 3H, CH3), 0.08 (s, 3H, CH3), 0.07 (s, 3H,
CH3); 13C NMR (CDCl3, 100 MHz): d 172.03, 171.89, 171.35,
153.07, 152.37, 138.59, 137.93, 137.83, 133.42, 131.00, 129.94,
129.29, 128.40, 128.12, 127.75, 127.67, 127.62, 127.58, 124.77,
96.49, 96.06, 87.35, 75.36, 74.89, 73.13, 73.04, 72.97, 72.83,
71.00, 70.44, 70.35, 69.05, 67.21, 66.22, 65.70, 60.14, 55.82,
55.50, 54.98, 25.88, 23.86, 23.80, 21.11, 18.25. 18.21, ꢀ4.53,
ꢀ5.07, ꢀ5.41, ꢀ5.49. HRMS (ESI) calcd for C60H81N3O18SSi2K
[M+K]+: 1258.4400. Found: 1258.4398.
3.10. p-Tolyl (2-acetamido-6-O-benzyl-2,3-N,O-carbonyl-2-
deoxy-
a
-
D
-galactopyranosyl)-(1?4)-2-acetamido-6-O-benzyl-
-galactopyranoside (11)
2,3-N,O-carbonyl-2-deoxy-1-thio-
a-D
Et3SiH (83.8 mg, 115
lL, 0.72 mmol, 6 equiv) and TfOH
Acknowledgements
(71.7 mg, 42 L, 0.48 mmol, 4 equiv) were added to a stirred mix-
l
ture of 10 (91.3 mg, 0.12 mmol, 1.0 equiv) and activated 4 Å molec-
ular sieves (400 mg, powder) in CH2Cl2 (7.3 mL, 12.5 mg of 10 per
mL) at ꢀ72 °C under nitrogen atmosphere. After being stirred for
1 h at ꢀ72 °C, Et3N (1 mL) and MeOH (1 mL) were added succes-
sively. The mixture was filtered and the filtrate was concentrated.
The residue was purified by column chromatography on silica gel
(2:1 hexane–EtOAc) to give white amorphous solids (73.2 mg,
This work was financially supported by the National Natural
Science Foundation of China (Grant No. 20732001) and the grant
(2009ZX09501-011) from the Ministry of Science and Technology
of China.
Supplementary data
80%): Rf = 0.4 (1:1 hexane–EtOAc); ½a D27
ꢂ
+223.5 (c 1.4, CHCl3); 1H
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.05.031.
NMR (CDCl3, 400 MHz): d 7.38–7.32 (m, 12H, Ar), 7.05 (d, 2H,
J = 8.0 Hz, Ar), 6.07 (d, 1H, J1,2 = 3.6 Hz, H-1), 5.90 (s, 1H, H-10),
4.72 (d, 1H, J = 11.6 Hz, PhCH2), 4.62 (d, 1H, J = 12.0 Hz, PhCH2),
4.58–4.51 (m, 8H, PhCH2 ꢁ 2, H-2, H-20, H-3, H-3’,H-4, H-40), 4.41
(t, 1H, J = 7.2 Hz, H-5), 4.03 (t, 1H, J = 4.0 Hz, H-50), 3.81 (d, 2H,
J = 4.0 Hz, H-6a0, H-6b0), 3.59 (dd, 1H, J = 7.2, 11.2 Hz, H-6a), 3.50–
3.46 (m, 2H, H-6b, 4-OH), 2.53 (s, 3H, CH3), 2.46 (s, 3H, CH3),
2.31 (s, 3H, CH3); 13C NMR (CDCl3, 75 MHz): d 172.06, 171.32,
152.98, 152.58, 138.60, 137.79, 137.07, 133.38, 129.94, 128.60,
128.41, 128.07, 127.81, 96.95, 87.24, 75.42, 74.28, 73.89, 73.05,
70.58, 70.43, 69.97, 69.79, 67.09, 67.00, 55.87, 54.56, 23.91,
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3.11. p-Tolyl (2-acetamido-4,6-di-O-tert-butyldimethylsilyl-2,3-
N,O-carbonyl-2-deoxy- -galactopyranosyl)-(1?4)-(2-
acetamido-6-O-benzyl-2,3-N,O-carbonyl-2-deoxy-
galactopyranosyl)-(1?4)-2-acetamido-6-O-benzyl-2,3-N,O-
carbonyl-2-deoxy-1-thio- -galactopyranoside (12)
a
-D
a-D-
a
-D
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Tf2O (27.2 mg, 16
stirred mixture of
l
3
L, 0.096 mmol, 1.3 equiv) was added to a
(85.7 mg, 0.15 mmol, 2.0 equiv), Ph2SO
(17.9 mg, 0.089 mmol, 1.2 equiv), TTBP (75.3 mg, 0.29 mmol,
4.0 equiv) and activated 4 Å molecular sieves (1.5 g, powder) in
CH2Cl2 (15 mL) at ꢀ72 °C under a nitrogen atmosphere. The reac-
tion mixture was stirred for 5 min, after loss of 3 detected by
TLC, a solution of the acceptor 11 (56.2 mg, 0.074 mmol, 1.0 equiv)
in CH2Cl2 (3 mL) was added dropwise to the mixture. The mixture
was stirred and warmed up to room temperature slowly and stir-
red for further 2 h, and the reaction was quenched by the addition
of Et3N (0.1 mL). The precipitate was filtered and the filtrate was
concentrated. The residue was purified by column chromatography
on silica gel (5:1 hexane–EtOAc) to give 12 as a syrup (61.1 mg,
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5224.
68%): Rf = 0.4 (3:1 hexane–EtOAc); ½a D27
ꢂ
+147.1 (c 1.2, CHCl3); 1H
NMR (CDCl3, 500 MHz): d 7.39–7.28 (m, 12H, Ar), 7.05 (d, 2H,
0
0
J = 9.0 Hz, Ar), 6.06 (d, 1H, J1,2 = 3.5 Hz, H-1), 5,83 (d, 1H, J1 ,2
=
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3.0 Hz, H-10), 5.81 (d, 1H, J1 ,2 = 2.5 Hz, H-100), 4.70 (d, 1H,
J = 12.5 Hz, PhCH2), 4.68 (d, 1H, J = 12.0 Hz, PhCH2), 4.62 (dd, 1H,
J3,2 = 12.0 Hz, J3.4 = 2.0 Hz, H-3), 4.59–4.55 (m, 3H, H-30, PhCH2 ꢁ 2),
4.51(s, 1H, H-4), 4.50–4.46 (m, 3H, H-2, H-300, H-40), 4.44 (s, 1H, H-
00 00
400), 4.41 (t, 1H, J = 7.0 Hz, H-5), 4.36 (dd, 1H, J2 ,1 = 2.5 Hz,
00 00
J2 ,3 = 12.0 Hz, H-200), 4.24 (dd, 1H, J2 ,1 = 3.0 Hz, J2 ,3 = 12.5 Hz,
H-20), 4.12 (t, 1H, J = 7.0 Hz, H-50), 3.86 (dd, 1H, J = 5.5, 8.5 Hz,
H-6a00), 3.72 (t, 1H, J = 9.0 Hz, H-500), 5.7–3.45 (m, 5H, H-6a, H-6b,
00 00
0
0
0
0
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L. Yang, X.-S. Ye / Carbohydrate Research 345 (2010) 1713–1721
1721
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