Stereoselectivity investigation on glycosylation of oxazolidinone protected 2-amino-2-deoxy-d-glucose donors based on pre-activation protocol

Article abstract of DOI:10.1016/j.tet.2008.03.103

Diverse 2,3-oxazolidinone protected 2-amino-2-deoxy-d-glucose thioglycosides were prepared and studied as glycosyl donors at low temperature by BSM/Tf₂O pre-activation protocol before the addition of glycosyl acceptors. The stereochemistry outc

Full text of DOI:10.1016/j.tet.2008.03.103

Tetrahedron 64 (2008) 4949–4958
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselectivity investigation on glycosylation of oxazolidinone protected
2-amino-2-deoxy-D-glucose donors based on pre-activation protocol
*
Yiqun Geng, Li-He Zhang, Xin-Shan Ye
The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd #38, Beijing 100083, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Diverse 2,3-oxazolidinone protected 2-amino-2-deoxy-D-glucose thioglycosides were prepared and
Received 25 December 2007
Received in revised form 25 March 2008
Accepted 28 March 2008
Available online 3 April 2008
studied as glycosyl donors at low temperature by BSM/Tf2O pre-activation protocol before the addition of
glycosyl acceptors. The stereochemistry outcomes of a series of glycosylations were investigated. Dif-
ferent stereoselectivities of the coupling reactions were obtained, arising from the different protecting
groups in the oxazolidinone donors. 4,6-Di-O-benzyl-N-benzyl-oxazolidinone protected thioglycoside
donor 1c underwent glycosylation with general
also affected by glycosylation conditions.
b
-anomeric selectivity and the stereoselectivity could be
Keywords:
Oxazolidinone
Pre-activation
Glycosylation
Stereoselectivity
Carbohydrate
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
donor 1a afforded either excellent b-stereoselectivity or excellent
a
-stereoselectivity toward glycosylations simply by means of the
Stereoselective glycosylation for 2-amino-2-deoxy sugars is
critical to the assembly of numerous aminosugar-containing oli-
gosaccharides and glycoconjugates with biologically important
roles.1,2 In particular, formation of 1,2-cis glycosidic bond, requiring
the use of a non-participating group such as an azido group at C-2,3
is still a challenge to synthetic chemists.4 In 2001, Kerns and co-
workers reported 2,3-trans-oxazolidinone as an effective protective
addition of hindered base 2,4,6-tri-tert-butylpyrimidine (TTBP)11 or
the absence of base (Fig. 1).
Our initial success suggested that pre-activation protocol could
greatly influence the stereochemistry outcomes of glycosylations.
Meanwhile, under the conditions of non-preactivation, change and
uncertainty in stereochemistry of glycosylations by the use of
oxazolidinone and its derivatives as glycosyl donors reported
by different research groups5–7 sparked our curiosity. To explore
the scope of pre-activation protocol and investigate the influence of
protecting groups at the 4,6-OH and/or 2-NH positions on stereo-
chemistry outcomes toward glycosylations, our attention was paid
to stereoselective glycosylations with various oxazolidinone-con-
taining glycosyl donors by pre-activation manner, and our findings
are reported here.
group possessing high
a
-selectivity toward glycosylations.5a Un-
fortunately, this glycosyl donor has several drawbacks such as the
undesired glycosylation and sulfenylation of the nitrogen atom.
Later, Kerns and co-workers5b,c and Oscarson and co-workers6
modified the oxazolidinone group to its N-acetyl analog, leading
to significant reduction of
observed in some cases. Recently, Ito and co-workers disclosed
N-benzyl-2,3-trans-oxazolidinone as a highly
-directing donor,7
a-selectivity, and b-selectivity was
a
but the coupling yields are generally not high and the origin of
selectivity is not clear. To tackle these problems, a new efficient
AcO
O
AcO
ROH
ROH
O
BSM,Tf2O
strategy for both
a- and b-stereoselective glycosylations of glu-
N
Ac
OR
O
AcO
AcO
cosamine donors based on pre-activation protocol was developed
by us very recently.8 By virtue of the pre-activation strategy,9,10 that
is, a glycosyl donor was pre-activated in the absence of an acceptor,
the known 4,6-di-O-acetyl-N-acetyl-oxazolidinone protected
O
CH2Cl2,-73 °C
BSM,TTBP,Tf2O
STol
N Ac
O
AcO
AcO
O
1a
O
OR
O
CH2Cl2,-73 °C
NAc
O
* Corresponding author. Tel.: þ86 10 62014949; fax: þ86 10 82802724.
E-mail address: xinshan@bjmu.edu.cn (X.-S. Ye).
Figure 1. Stereoselectivity-controllable glycosylation of donor 1a.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.103

4950
Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
2. Results and discussions
by BSM/Tf2O at low temperature in anhydrous CH2Cl2, the acceptor
6a was then added to the reaction mixture after the complete
consumption of donor by TLC monitoring. As shown in Table 1,
glycosyl donors 1b, 1c, 1e and 1g successfully afforded the coupling
products in good isolated yields,14 but interestingly, the stereo-
selectivities varied with the glycosyl donors equipped with differ-
ent protecting groups. Among them, the tri-benzyl substituted
2.1. Preparation of glycosyl donors 1b–1g
A series of oxazolidinone protected glucosamine thioglycosides
1b–1g were designed and synthesized. In these glycosyl donors, the
4,6-OH and 2-NH functional groups were protected by two kinds of
groups: the electron-donating benzyl group (or benzylidene group)
and the electron-withdrawing acetyl group. Among them, 1b is
known and was prepared according to the literature.5c
donor 1c exhibited complete b-selectivity (entry 2). Compared with
4,6-di-O-acetyl-N-acetyl-oxazolidinone protected donor 1a repor-
ted in our previous work, glycosyl donor 1c afforded the completely
opposite stereochemistry outcomes under the same glycosylation
conditions. It showed that the stereoselectivities of glycosylations
by pre-activation protocol can be modulated by suitably protected
glycosyl donors.
AcO
O
AcO
STol
O
NH
1b
O
The different stereoselectivities might arise from the variety of
intermediates. After being activated, the oxazolidinone protected
donors turned into the oxacarbenium ion, which could be trapped
The synthesis of N-benzyl-oxazolidinone protected glycosyl do-
nors 1c, 1f and 1g, N-acetyl-oxazolidinone protected glycosyl donor
1e and N-unsubstituted-oxazolidinone protected glycosyl donor 1d
all started from the same glucosamine derivative 212 (Scheme 1).
Removal of the acetyl groups in 2 with 30% MeONa afforded the
intermediate 3 in quantitative yield. Compound 3 was treated with
sodium hydride (NaH) and benzyl bromide (BnBr) to provide 4,6-
di-O-benzyl-N-benzyl-2N,3O-oxazolidinone protected donor 1c
and 4,6-di-O-benzyl-2N,3O-oxazolidinone protected donor 1d,
respectively, just by using different amount of the benzylation
reagents (6.0 equiv of NaH and 4.5 equiv of BnBr for 1c; 4.5 equiv
of NaH and 2.5 equiv of BnBr for 1d). The reaction outcomes can
be modulated because the O-benzylation occurs ahead of the
N-benzylation. The N-acetyl donor 1e was easily prepared via
acetylation of donor 1d. On the other hand, compound 3 was sub-
jected to 4,6-O-benzylidene protection to afford 4, which was treated
again with NaH and BnBr, yielding the N-benzyl donor 1f in good
isolated yield. Subsequently, 1f was smoothly converted to 1g via
selective deprotection followed by re-acetylation.
by triflate anion to give either
pre-activation conditions, there are three types of intermediate:
oxacarbenium ion, -triflate and -triflate. Oxacarbenium ion
a-triflate or b
-triflate.15 Thus, under
a
b
intermediate may participate in an SN1-like process with the ac-
ceptor, while triflate intermediate may participate in an SN2-like
process. The electronic property of protecting groups may influence
the major form of intermediate during the glycosylation reactions.
Pre-activation of 4,6-O-benzyl protected donors 1c and 1e (entries
2 and 4, Table 1) produced oxacarbenium ions, which could be the
major form existed instead of the glycosyl triflate presumably due
to the stabilization effect of electron-donating benzyl groups.
Attacked by acceptor 6a via an SN1-like process, the disaccharides
7c and 7e were gained. The only discrimination between 1c and 1e
is the protecting group at 2-N-position. N-Benzyl group affords
steric hindrance to
results in excellent
a
-face attack by hindered nucleophiles, and
b
-selectivity. This steric hindrance is removed in
the case of N-acetyl substituent, so there is no selectivity for donor
1e. Pre-activation of 4,6-O-acetyl protected donors 1b and 1g
(entries 1 and 6, Table 1) could afford glycosyl triflates by contrast.
The equilibrium might favor the formation of covalent anomeric
triflates in this case because the oxacarbenium ion could be very
unstable and be trapped easily by triflate anion, arising from the
2.2. Glycosylations of various 2,3-oxazolidinone protected
glycosyl donors with unalterable acceptor 6a
With glycosyl donors 1b–1g in hand, we firstly investigated the
influence of protecting groups at the 4,6-OH and/or 2-NH positions
on stereochemistry outcomes toward glycosylations. A series of
couplings of the unalterable acceptor 6a with diverse donors 1b–1g
by pre-activation protocol were checked (Table 1). Identical to
our previous work,8 a combination of benzenesulfinyl morpholine
(BSM)13 and triflic anhydride (Tf2O) acted as the promoter system.
Since the use of hindered base is not necessary in our routine pre-
activation protocol,9,13 the glycosylation reactions were conducted
in the absence of hindered base TTBP. Each donor was pre-activated
electron-withdrawing effect of acetyl groups. Both
-triflate may exist, so the coupling products are
mixtures.
a
a
-triflate and
-anomeric
b
/b
2.3. Stereoselective couplings of donor 1c with various
glycosyl acceptors
Based on the excellent b-stereoselectivity of coupling between
donor 1c and acceptor 6a, we then focused on performing
BnO
O
BnO
STol
O
N Bn
O
1c
b
BnO
BnO
BnO
HO
HO
AcO
AcO
a
O
O
c
d
O
O
BnO
STol
STol
STol
NHTrOC
STol
NHTrOC
O
O
HO
AcO
N Ac
1e
NH
1d
O
O
3
2
e
AcO
AcO
O
HO
HO
Ph
Ph
O
O
O
f
O
O
g
O
d
STol
N Bn
STol
N Bn
1g
O
STol
N Bn
STol
NHTrOC
O
O
O
HO
O
O
O
4
1f
5
Scheme 1. Preparation of donors 1c–1g. Reagents and conditions: (a) MeONa, MeOH, 100%; (b) 4.5 equiv BnBr, 6.0 equiv NaH, DMF, 80%; (c) 2.5 equiv BnBr, 4.5 equiv NaH, DMF,
65%; (d) Ac2O, Py, 95% for 1e, 90% for 1g; (e) PhCH(OMe)2, CSA, CH3CN, 85%; (f) 1.5 equiv BnBr, 2.5 equiv NaH, DMF, 90%; (g) TsOH, MeOH, 85%.

Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
4951
Table 1
The couplings of various 2,3-oxazolidinone protected glycosyl donors with unalterable acceptor 6a
Ph
O
O
O
HO
6a
R1O
R1O
Ph
O
O
R1O
R1O
BnO
O
O
O
O
OMe
BSM,Tf2O
STol
N R2
O
O
BnO
N R2
CH2Cl2, -73 °C
OMe
O
7b, 7c, 7e, 7g
O
1b-1g
Entry
1
Donor
T (ꢀC)
ꢁ73
Product
O Ph
Yield (%)
87
a/b
AcO
AcO
O
O
AcO
O
AcO
STol
O
O
O
O
1:2
NH
NH
BnO
O
O
OMe
1b
7b
Ph
O
O
O
BnO
BnO
BnO
O
O
O
BnO
STol
O
O
BnO
2
3
ꢁ73
ꢁ73
ꢁ60
85
84
94
b
only
N Bn
N Bn
OMe
O
O
O
O
1c
1d
1e
7c
BnO
O
BnO
STol
O
No coupling product
NH
BnO
BnO
Ph
O
O
O
O
BnO
BnO
STol
O
O
O
4
5
1:1a
O
N Ac
NAc
BnO
O
OMe
7e
O
Ph
O
O
STol
O
No activation
N Bn
O
1f
AcO
AcO
AcO
O Ph
O
O
O
AcO
O
STol
N Bn
O
O
O
6
ꢁ50
3:1
N Bn
BnO
O
O
OMe
1g
7g
a
Anomeric ratio was determined by the integration of 1H NMR spectrum of the anomeric mixture.
glycosylations of 1c with a series of acceptors by pre-activation
2.4. Stereochemistry under different glycosylation conditions
manner to illustrate the generality of the stereoselectivity, and the
results are listed in Table 2. As shown, donor 1c was
b
-selective
Next we turned our attention to the influence on stereo-
chemistry outcomes arising from different glycosylation condi-
tions such as solvent, temperature and promoter system. The
representative reaction was performed as exemplified by the
coupling of donor 1c and acceptor 6a (Table 3). In contrast to our
published work,8 addition of the hindered base TTBP to the
reaction system gave rise to the same stereoselectivity in a little
higher yield (entry 1). Under pre-activation conditions, using
benzenesulfinyl piperidine/triflic anhydride (BSP/Tf2O)16 or
diphenyl sulfoxide/triflic anhydride (Ph2SO/Tf2O)17 instead of our
BSM/Tf2O promoter system, the coupling afforded almost the same
results (entry 2). However, activation of thioglycoside 1c by
toward glycosylations with a wide range of glycosyl acceptors
except for acceptor 6m (entry 13) and the coupling yields were
generally high. And a clear trend that the stereochemistry out-
comes of the glycosylations correlated to acceptors was observed.
Acceptors 6a–6e equipped with 4,6-O-benzylidene protecting
group displayed excellent
reactive acceptors 6i and 6j with primary hydroxyl group also led
to good -selectivity (entries 9 and 10). In contrast to the recently
b-selectivity (entries 1–5), and more
b
reported similar donor N-benzyl-2,3-trans oxazolidinone de-
rivative,7 our donor 1c provided opposite stereoselectivity under
pre-activated conditions. It is again verified that pre-activation
protocol can influence the stereoselectivity of glycosylations.
According to the results displayed in Table 2, the glycosylation
might be an SN1-like process via the intermediate of oxacarbenium
ion. The benzyl group on nitrogen atom affords steric hindrance to
employing N-(phenylthio)-
led to non-stereoselective glycosylation, providing both
-linked products (entries 3–6). The quotient of -anomer in-
3
-caprolactam/Tf2O18 or NIS/AgOTf19
- and
a
b
a
creased along with rise of temperature (entry 3 vs entry 4). Change
of solvent from CH2Cl2 to toluene also led to the increase of
a
-face attack by hindered nucleophiles. Thus the glycosylation
reaction is -selective, more hindered acceptors equipped with the
b
a-anomer (entry 3 vs entry 5). It was exhibited that stereochem-
4,6-O-benzylidene protecting group afford better stereoselectivity.
In comparison with donor 1a,8 the opposite stereoselectivity of
donor 1c may arise from the different intermediates produced after
pre-activation, which could be influenced by the electronic prop-
erty of protecting groups at the 4,6-OH and 2-NH positions.
istry outcomes of glycosylations can be modulated by reaction
conditions such as promoter, temperature, solvent and activation
manner. The rise of temperature and the use of non-polar solvent
resulted in the increase of the thermodynamic-controlled product
a-anomer.

4952
Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
Table 2 (continued)
Table 2
Entry
Acceptor
(ROH)
Product
IsolatedAnomeric
yield ratio
Glycosylations of donor 1c with a series of acceptors by BSM/Tf2O pre-activation
BnO
BnO
BnO
BnO
O
(%)
(a/b)
O
STol
N Bn
BSM,Tf2O
R-OH
6a-6m
O
OR
O
N Bn
BnO
BnO
CH2Cl2, -73 °C
O
O
7c, 8b-8m
O
1c
HO
BnO
O
O
O
N Bn
BnO
BnO
BnO
1:6a
O
10
85
O
BnO
OMe
BnO
Entry
Acceptor
(ROH)
Product
IsolatedAnomeric
yield ratio
OMe
6j
8j
(%)
(a/b)
BnO
O
Ph
O
O
BnO
BnO
BnO
Ph
Ph
O
HO
O
CH3(CH2)7OH
O
O
O
O
O
11
12
95
98
1:3.5
1:3a
N Bn
O(CH2)7CH3
O
BnO
1
85
b
b
only
only
BnO
6k
O
N Bn
OMe
OMe
O
8k
6a
7c
BnO
O
O
O
H
H2
BnO
Ph
O
HO C
CH C OMe
NHCbz
6l
O
O
O
OMe
C C
O C
O
O
N Bn
8l
H2
BnO
O
NHCbz
BnO
BnO
O
O
O
O
BnO
OMe
2
83
HO
O
OMe
N Bn
BnO
O
O
6b
BnO
BnO
O
BnO
O
HO
8b
O
BnO
N Bn
O
13
82
2.5:1a
BnO
OMe
6m
BnO
Ph
BnO
O
Ph
OMe
O
O
8m
BnO
O
O
O
BnO
a
Anomeric ratio was determined by the integration of 1H NMR spectrum of the
O
O
O
3
83
b
only
BnO
N Bn
HO
anomeric mixture.
OMe
BnO
O
OMe
8c
6c
2.5. Deprotection of disaccharide 8d
Ph
O
Ph
O
The formed disaccharides can be fully deprotected. For example,
as shown in Scheme 2, disaccharide 8d was deprotected under
basic conditions (t-BuOK/DMSO).20 The ring-fused oxazolidinone
was thus opened in several minutes in excellent yield affording
9, followed by the concomitant removal of the O-, N-benzyl groups
and O-benzylidene group over hydrogenolysis to obtain di-
saccharide 10.
O
O
O
O
BnO
BnO
O
O
BnO
4
5
6
84
87
85
b
b
only
only
O
OMe
BnO
N Bn
HO
O
OMe
8d
6d
Ph
O
BnO
BnO
O
Ph
Ph
O
O
O
OMe
O
O
O
OMe
O
OBn
HO
N Bn
OBn
O
3. Conclusion
6e
8e
We have demonstrated that diverse 2,3-oxazolidinone pro-
tected 2-deoxy-2-amino-D-glucose thioglycosides show different
Ph
O
BnO
O
O
O
O
OMe
O
BnO
BnO
O
O
OMe
even opposite stereoselectivities in glycosylations conducted by the
BSM/Tf2O pre-activation protocol at low temperature in dichloro-
methane. The stereochemistry outcomes of coupling reactions
are strongly influenced by the protecting groups in oxazolidinone
protected glycosyl donors and the activation manner of donors. In
contrast to the tri-acetyl protected donor 1a reported previously,
4,6-di-O-benzyl-N-benzyl-oxazolidinone protected thioglycoside
a
BnO
1:2
O
OH
N Bn
6f
O
8f
N3
N3
O
Ph
O
O
O
Ph
O
BnO
BnO
O
O
O
HO
7
8
O
83
91
1:1.5
OMe
N Bn
8g
OMe
donor 1c affords moderate to excellent b-selectivity toward glyco-
sylations. Moreover, in the case of donor 1c, the stereoselectivity
O
6g
Ph
O
O
O
Table 3
Ph
O
N3
O
BnO
BnO
O
The coupling of donor 1c and acceptor 6a under different conditions
O
O
N3
OMe
1:2
HO
O
Entry Promoter
system
Solvent Temperature Isolated Anomeric ratio
OMe
N Bn
(ꢀC)
yield (%)
(a/b)
O
6h
1
2
3
BSM, TTBP, Tf2O
BSP (or Ph2SO), Tf2O CH2Cl2
CH2Cl2
ꢁ73
ꢁ73
15
88
85–87
86
b
b
only
only
8h
BnO
BnO
1:1.5a
O
N-(Phenylthio)-
caprolactam, Tf2O
N-(Phenylthio)-
caprolactam, Tf2O
N-(Phenylthio)-
3
-
CH2Cl2
CH2Cl2
Toluene
CH2Cl2
O
OH
O
O
O
O
N Bn
4
5
6
3
-
45
15
75
87
86
1:1a
O
O
O
O
O
9
96
1:11a
O
1:1a
O
3
-
O
caprolactam, Tf2O
NIS/AgOTf
6i
ꢁ10
1:2.5a
8i
a
Anomeric ratio was determined by the integration of 1H NMR spectrum of the
anomeric mixture.

Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
4953
Ph
Ph
O
O
OH
O
O
OH
O
a
b
O
O
O
O
HO
HO
HO
BnO
BnO
BnO
BnO
O
BnO
BnO
O
O
O
HO
OMe
O
HO
OMe
OMe
NH2
N Bn
8d
NHBn
9
O
10
Scheme 2. Deprotection of disaccharide 8d. Reagents and conditions: (a) t-BuOK, DMSO, 90%; (b) H2, Pd/C, 95%.
cannot be affected by the addition of TTBP, but can be modulated
by changing reaction conditions such as solvent, temperature and
promoter system. In summary, based on our BSM/Tf2O pre-activa-
tion strategy, using 2,3-oxazolidinone protected thioglycoside
room temperature and stirred for 4 h. The mixture was directly
concentrated under reduced pressure, and the residue was purified
by column chromatography (petroleum ether/ethyl acetate,12:1) to
give 1c (1.51 g, 80%) as a white solid: 1H NMR (500 MHz, CDCl3)
donors, either
a
- or
b
-glycosidic linkage can be formed. The ste-
d
7.24–7.41 (m, 17H), 7.00 (d, 2H, J¼8.0 Hz), 4.88 (d, 1H, J¼11.5 Hz),
reoselectivity can be greatly affected by modulating protective
groups of the glycosyl donors. The mechanistic understandings
await further investigation.
4.78 (d, 1H, J¼15.0 Hz), 4.74 (d, 1H, J¼15.0 Hz), 4.69 (d, 1H, J¼9.5 Hz,
H-1), 4.55 (d, 1H, J¼11.5 Hz), 4.54 (d, 1H, J¼11.5 Hz), 4.48 (d, 1H,
J¼12.0 Hz), 4.16 (dd,1H, J¼10.0,11.0 Hz), 3.86 (dd,1H, J¼8.5, 9.5 Hz),
3.75 (dd, 1H, J¼2.0, 11.0 Hz), 3.69 (dd, 1H, J¼5.0, 11.0 Hz), 3.54–3.57
(m, 1H), 3.44 (dd, 1H, J¼9.5, 11.0 Hz), 2.29 (s, 3H); 13C NMR
4. Experimental
(125 MHz, CDCl3)
d 159.27, 138.61, 138.06, 137.32, 136.36, 132.93,
129.80, 128.63, 128.48, 128.39, 128.33,128.16,128.00,127.93, 127.70,
127.62, 127.57, 86.64, 83.45, 79.91, 73.74, 73.38, 73.16, 68.53, 60.30,
47.46, 21.10; MS (FAB) 581 [M]þ; Anal. Calcd for C35H35NO5S: C,
72.26; H, 6.06; N, 2.41. Found: C, 72.37; H, 6.15; N, 2.31.
4.1. General procedures
All chemicals were purchased as reagent grade and used with-
out further purification, unless otherwise noted. Dichloromethane
(CH2Cl2), pyridine, toluene and acetonitrile (CH3CN) were distilled
over calcium hydride (CaH2). Methanol was distilled from magne-
sium. DMF was stirred with CaH2 and distilled under reduced
pressure. All reactions were carried out under anhydrous condi-
tions with freshly distilled solvents, unless otherwise noted. Re-
actions were monitored by analytical thin-layer chromatography
on silica gel 60 F254 precoated on aluminum plates (E. Merck).
Spots were detected under UV (254 nm) and/or by staining with
acidic ceric ammonium molybdate. Solvents were evaporated un-
der reduced pressure and below 40 ꢀC (bath). Organic solutions of
crude products were dried over anhydrous Na2SO4. Column chro-
matography was performed on silica gel (200–300 mesh). 1H NMR
spectra were recorded on a JEOL AL-300, Varian INOVA-500,
or Advance DRX Bruker-500 spectrometers at 25 ꢀC. Chemical shifts
4.2.3. p-Tolyl 2-amino-2,3-N,O-carbonyl-4,6-O-dibenzyl-2-deoxy-
1-thio-b-D-glucopyranoside (1d)
Compound 3 (1.50 g, 3.26 mmol, 1 equiv) was dissolved in dry
DMF (30 mL) and stirred at ꢁ15 ꢀC, and NaH (0.59 g, 14.67 mmol,
4.5 equiv, 60% in mineral oil) was added, followed by the addition
of benzyl bromide (0.97 mL, 8.15 mmol, 2.5 equiv). After stirring for
30 min on the ice-water bath, the reaction mixture was warmed to
room temperature and stirred for 2 h. The mixture was directly
concentrated under reduced pressure, and the residue was purified
by column chromatography (petroleum ether/ethyl acetate, 5:1) to
give the major product 1d (1.04 g, 65%) as a white solid: 1H NMR
(500 MHz, CDCl3) d 7.28–7.41 (m, 10H), 7.15–7.17 (m, 2H), 7.07–7.09
(m, 2H), 4.91 (d, 1H, J¼11.5 Hz), 4.78 (s, 2H), 4.72 (d, 1H, J¼9.5 Hz,
H-1), 4.61 (d, 1H, J¼11.0 Hz), 4.18 (dd, 1H, J¼10.0, 11.0 Hz), 3.80–
3.85 (m, 2H), 3.69–3.74 (m, 1H), 3.45–3.48 (m, 1H), 3.36 (dd, 1H,
(in ppm) were referenced to tetramethylsilane (
deuterated chloroform. 13C NMR spectra were obtained by using
the same NMR spectrometers and were calibrated with CDCl3
77.00 ppm). Mass spectra were recorded using a PE SCLEX QSTAR
spectrometer. Elemental analysis data were recorded on a Vario
EL-III elemental analyzer.
d
¼0 ppm) in
J¼9.5, 11.5 Hz), 2.32 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 159.21,
(d
¼
139.03, 137.20, 136.21, 133.06, 129.94, 128.70, 128.50, 128.15, 128.05,
127.65, 86.70, 83.19, 80.19, 73.49, 73.22, 61.60, 60.43, 47.52, 21.12;
HRMS (ESI) calcd for C28H30NO5S [MþH]þ: 492.1839, found:
492.1826.
4.2. Preparation of oxazolidinone protected glycosyl donors
4.2.4. p-Tolyl N-acetyl-2-amino-2,3-N,O-carbonyl-4,6-O-dibenzyl-
4.2.1. p-Tolyl N-2,2,2-trichloroethyloxycarbonyl-2-amino-2-deoxy-
2-deoxy-1-thio-b-D-glucopyranoside (1e)
1-thio-
b
-
D
-glucopyranoside (3)
To a stirred solution of the compound 1d (0.50 g, 1.02 mmol,
1 equiv) in pyridine (10 mL), was added acetic anhydride (0.29 mL,
3.05 mmol, 3 equiv). The reaction mixture was stirred at room
temperature for 2 h, quenched by the addition of saturated aqueous
NaHCO3 (15 mL) and extracted with CH2Cl2 (2ꢂ15 mL). The com-
bined organic layer was dried, filtered and concentrated under
reduced pressure. The residue was purified by column chroma-
tography (petroleum ether/ethyl acetate, 5:1) to give 1e (0.51 g,
Trichloroethyl carbamate protected glucosamine
2
(2.00 g,
3.41 mmol, 1 equiv) in 100 mL methanol containing a catalytic
amount of NaOMe (30% in MeOH) under pH 8–9 was stirred for
1.5 h. The reaction mixture was neutralized with cation exchange
resin (Hþ), filtered and concentrated to dryness under reduced
pressure to give compound 3 (1.50 g, 95%) as a white solid. Rf¼0.7
(ethyl acetate/methanol, 10:1). Compound 3 was used for the next
reaction directly.
95%) as a white solid: 1H NMR (500 MHz, CDCl3)
d 7.28–7.42 (m,
10H), 7.21–7.23 (m, 2H), 7.07 (d, 2H, J¼8.0 Hz), 4.90 (d, 1H,
J¼11.5 Hz), 4.49 (d, 1H, J¼15.5 Hz), 4.75 (d, 1H, J¼16.0 Hz), 4.66 (d,
1H, J¼9.5 Hz, H-1), 4.59 (d, 1H, J¼11.5 Hz), 4.30 (dd, 1H, J¼2.5,
12.0 Hz), 4.25 (dd, 1H, J¼5.0, 12.0 Hz), 4.16 (dd, 1H, J¼9.5, 11.0 Hz),
3.74 (t, 1H, J¼9.5 Hz), 3.58–3.61 (m, 1H), 3.40 (dd, 1H, J¼9.5,
11.5 Hz), 2.33 (s, 3H), 1.96 (s, 3H); 13C NMR (125 MHz, CDCl3)
4.2.2. p-Tolyl N-benzyl-2-amino-2,3-N,O-carbonyl-4,6-O-dibenzyl-
2-deoxy-1-thio-b-D-glucopyranoside (1c)
Compound 3 (1.50 g, 3.26 mmol, 1 equiv) was dissolved in dry
DMF (40 mL) and stirred at ꢁ15 ꢀC, and NaH (0.78 g, 19.57 mmol,
6 equiv, 60% in mineral oil) was added, followed by the addition of
benzyl bromide (1.75 mL, 14.67 mmol, 4.5 equiv). After stirring for
30 min on the ice-water bath, the reaction mixture was warmed to
d
170.49, 159.08, 138.91, 136.93, 136.29, 133.24, 129.78, 128.67,
128.51, 128.28, 128.19, 128.14, 127.63, 86.69, 83.37, 77.76, 73.05,

4954
Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
72.96, 62.74, 60.30, 47.49, 21.13, 20.75; HRMS (ESI) calcd for
C
(15.9 mg, 0.075 mol, 1.4 equiv) and activated 4 Å molecular sieves
(400 mg) in CH2Cl2 (5.0 mL) at low temperature under nitrogen
atmosphere. The reaction mixture was stirred for 5–20 min, after
loss of donor detected by TLC, a solution of the acceptor alcohol 6a
(20.0 mg, 0.054 mmol, 1.0 equiv) in CH2Cl2 (0.5 mL) was added
dropwise to the pre-activated system. The mixture was stirred and
warmed to room temperature slowly, and then quenched by 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 to give 7b, 7c, 7e and 7g.
30H31NO6SNa [MþNa]þ: 572.1504, found: 572.1506.
4.2.5. p-Tolyl N-2,2,2-trichloroethyloxycarbonyl-2-amino-4,6-O-
benzylidene-2-deoxy-1-thio- -glucopyranoside (4)
b-D
Compound 3 (1.50 g, 3.26 mmol, 1 equiv) in CH3CN (40 mL)
containing a catalytic amount of camphorsulfonic acid under PH 2–
3 was stirred, followed by the addition of benzaldehyde dimethyl
acetyl (0.59 mL, 3.91 mmol, 1.2 equiv). The mixture was stirred for
5 h, then neutralized with Et3N and concentrated to dryness under
reduced pressure. The crystalline residue was crystallized from
EtOAc to give 4 (1.52 g, 85%) as a white solid. The NMR data of 4 was
identical to that reported previously.9b
4.3.1. Coupling of 1b with 6a to give methyl (2-amino-2,3-N,O-
carbonyl-4,6-diacetyl-2-deoxy-
a
- and
b-D-glucopyranosyl)-(1/3)-
2-O-benzyl-4,6-O-benzylidene-
a
-D-glucopyranosides
4.2.6. p-Tolyl N-benzyl-2-amino-4,6-O-benzylidene-2,3-N,O-
(7ba) and (7bb)
carbonyl-2-deoxy-1-thio-
b-
D-glucopyranoside (1f)
Donor 1b was pre-activated at ꢁ73 ꢀC, and then the reaction
Compound 4 (1.00 g, 1.82 mmol, 1 equiv) was dissolved in dry
DMF (15 mL) and stirred at ꢁ15 ꢀC, and NaH (0.18 g, 4.56 mmol,
2.5 equiv, 60% in mineral oil) was added, followed by the addition of
benzyl bromide (0.33 mL, 2.74 mmol, 1.5 equiv). After stirring for
30 min on the ice-water bath, the reaction mixture was warmed to
room temperature and stirred for 2 h. The mixture was directly
concentrated under reduced pressure, and the residue was purified
by column chromatography (petroleum ether/ethyl acetate,10:1) to
give the main product 1f (0.89 g, 90%) as a white solid: 1H NMR
mixture was quenched by Et3N at ꢁ60 ꢀC. The crude product was
purified by column chromatography (petroleum ether/ethyl ace-
tate, 3:1 to 1.5:1) to give 7b, yield¼87% (
mer)¼0.25, Rf -isomer)¼0.20 (petroleum ether/ethyl acetate,
1:1); compound 7b 7.36–7.41 (m,
1H NMR (500 MHz, CDCl3)
a
/b
¼1:2). Rf
(a-iso-
(
b
a
:
d
10H), 5.49 (s, 1H), 5.44 (d, 1H, J¼2.5 Hz, H-10), 5.23 (t, 1H,
J¼10.0 Hz), 4.83 (s, 1H), 4.73 (d, 1H, J¼3.5 Hz, H-1), 4.59–4.66 (m,
3H), 4.27 (t, 1H, J¼9.5 Hz), 4.26 (dd, 1H, J¼4.5, 10.5 Hz), 4.12–4.15
(m, 1H), 4.00 (dd, 1H, J¼2.0, 12.5 Hz), 3.94 (dd, 1H, J¼4.0, 12.5 Hz),
3.83 (dt, 1H, J¼5.0, 10.0 Hz), 3.71 (t, 1H, J¼10.5 Hz), 3.56–3.63 (m,
(500 MHz, CDCl3)
d 7.43–7.26 (m, 10H), 7.11–7.07 (m, 4H), 5.73 (s,
1H), 5.28 (d, J¼9.5 Hz, 1H), 4.71–4.66 (m, 2H), 4.59 (d, J¼11.5 Hz,
1H), 4.25–4.20 (m, 2H), 3.86 (t, J¼10.5 Hz, 1H), 3.74–3.69 (m, 1H),
3.67 (t, J¼10.5 Hz, 1H), 2.26 (s, 3H); 13C NMR (125 MHz, CDCl3)
3H), 3.41 (s, 3H), 2.06 (s, 6H); 13C NMR (125 MHz, CDCl3)
d 170.63,
169.15, 158.47, 137.35, 136.95, 129.50, 128.61, 128.57, 128.32, 126.09,
101.92, 98.28, 95.29, 82.20, 77.67, 76.08, 74.41, 72.84, 70.04, 69.00,
68.10, 61.90, 61.26, 58.47, 55.40, 20.68 (2C); HRMS (ESI) calcd for
d
158.6,137.7,17.4, 137.0,131.4,129.8,129.1, 128.6,128.4,128.2,127.0,
100.2, 85.8, 77.5, 71.5, 67.4, 61.3, 47.4, 20.6; HRMS (ESI) calcd for
C
32H37NO13Na [MþNa]þ: 666.2157, found: 666.2155. Compound
C
28H28NO5S [MþH]þ: 490.1683, found: 490.1682.
7bb: d 7.33–7.47 (m, 10H), 5.52 (s, 1H),
1H NMR (500 MHz, CDCl3)
5.30 (s,1H), 5.24 (dd,1H, J¼9.0,10.0 Hz), 4.88 (d,1H, J¼8.0 Hz, H-10),
4.67 (d, 1H, J¼11.5 Hz), 4.66 (d, 1H, J¼4.0 Hz, H-1), 4.64 (d, 1H,
J¼11.5 Hz), 4.25 (dd, 1H, J¼5.0, 10.0 Hz), 4.09–4.19 (m, 3H), 4.04 (dd,
1H, J¼10.5, 12.0 Hz), 3.79 (dt, 1H, J¼4.5, 10.0 Hz), 3.71 (t, 1H,
J¼10.0 Hz), 3.62–3.66 (m, 1H), 3.58 (dd, 1H, J¼3.5, 9.5 Hz), 3.56 (t,
1H, J¼9.5 Hz), 3.43 (dd, 1H, J¼7.5, 12.0 Hz), 3.39 (s, 3H), 2.08 (s, 3H),
4.2.7. p-Tolyl N-benzyl-2-amino-2,3-N,O-carbonyl-2-deoxy-1-thio-
b-
D-glucopyranoside (5)
Compound 1f (0.50 g, 1.02 mmol, 1 equiv) was dissolved in
methanol (15 mL) and stirred, then TsOH (0.10 g, 0.51 mmol,
0.5 equiv) was added. The reaction mixture was stirred over night,
then neutralized with Et3N and concentrated to dryness under
reduced pressure to give compound 5 (0.35 g, 86%) as a white solid.
Rf¼0.1 (petroleum ether/ethyl acetate, 10:1). Compound 5 was used
for the next reaction directly.
1.98 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 170.63, 169.15, 158.22,
137.11, 137.03, 129.06, 128.83, 128.69, 128.33, 128.18, 125.92, 101.85,
101.19, 98.27, 79.79, 79.26, 78.95, 76.62, 74.76, 73.53, 68.80, 67.49,
62.40, 62.18, 59.93, 55.41, 20.67, 20.63; MS (FAB) 644 [MþH]þ; Anal.
Calcd for C32H37NO13: C, 59.71; H, 5.79; N, 2.18. Found: C, 60.06; H,
5.66; N, 1.99.
4.2.8. p-Tolyl N-benzyl-2-amino-2,3-N,O-carbonyl-4,6-O-diacetyl-
2-deoxy-1-thio-b-D-glucopyranoside (1g)
To a stirred solution of compound 5 (0.35 g, 0.87 mmol, 1 equiv)
in pyridine (10 mL), was added acetic anhydride (0.82 mL,
8.71 mmol, 10 equiv). The reaction mixture was stirred at room
temperature for 3 h, quenched by the addition of saturated aqueous
NaHCO3 (15 mL) and extracted with CH2Cl2 (2ꢂ15 mL). The com-
bined organic layer was dried, filtered and concentrated under
reduced pressure. The residue was purified by column chroma-
tography (petroleum ether/ethyl acetate, 3:1) to give 1g (0.38 g,
4.3.2. Coupling of 1c with 6a to give methyl (N-benzyl-2-amino-
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy-b-D-glucopyranosyl)-(1/
3)-2-O-benzyl-4,6-O-benzylidene- -glucopyranoside (7c)
a-D
Donor 1c was pre-activated at ꢁ73 ꢀC. The crude product was
purified by column chromatography (petroleum ether/ethyl ace-
tate, 6:1) to give 7c, yield¼85%. Rf¼0.40 (petroleum ether/ethyl
acetate, 2:1); 1H NMR (500 MHz, CDCl3)
d 7.39–7.46 (m, 4H), 7.13–
7.34 (m, 21H), 5.48 (s, 1H), 5.11 (d, 1H, J¼8.0 Hz, H-10), 4.77 (d, 1H,
J¼11.5 Hz), 4.69 (d, 1H, J¼3.5 Hz, H-1), 4.54 (d, 1H, J¼15.0 Hz), 4.49
(s, 2H), 4.45 (d, 1H, J¼11.0 Hz), 4.37 (d, 1H, J¼14.5 Hz), 4.36 (d, 1H,
J¼12.0 Hz), 4.36 (t, 1H, J¼9.0 Hz), 4.31 (d, 1H, J¼12.0 Hz), 4.26 (dd,
1H, J¼4.5, 10.0 Hz), 3.98 (dd, 1H, J¼10.0, 12.0 Hz), 3.82 (dd, 1H,
J¼4.5, 10.0 Hz), 3.78 (dd, 1H, J¼8.5, 9.5 Hz), 3.72 (t, 1H, J¼10.0 Hz),
3.60–3.65 (m, 2H), 3.58 (dd, 1H, J¼4.0, 11.0 Hz), 3.54 (dd, 1H, J¼2.0,
11.0 Hz), 3.39–3.42 (m, 1H), 3.36 (s, 3H), 3.27 (dd, 1H, J¼8.0,
90%) as a white solid: 1H NMR (300 MHz, CDCl3)
d 7.23–7.41 (m,
7H), 7.09 (d, 2H, J¼8.0 Hz), 5.24 (dd, 1H, J¼9.0, 10.0 Hz), 4.76 (s, 2H),
4.71 (d, 1H, J¼9.6 Hz, H-1), 4.10–4.26 (m, 3H), 3.67–3.73 (m, 1H),
3.50 (dd, 1H, J¼9.6, 11.0 Hz), 2.34 (s, 3H), 2.10 (s, 3H), 2.07 (s, 3H);
13C NMR (125 MHz, CDCl3)
d 170.45, 169.18, 158.52, 139.10, 135.98,
133.41, 129.83, 128.72, 128.20, 127.86, 127.73, 86.89, 79.82, 77.17,
67.42, 62.22, 60.19, 47.52, 21.14, 20.71, 20.62; HRMS (ESI) calcd for
C
25H28NO7S [MþH]þ: 486.1581, found: 486.1571.
12.0 Hz); 13C NMR (125 MHz, CDCl3)
d 159.23, 138.24, 137.41, 137.24,
137.17, 135.73, 129.49, 128.98, 128.59, 128.50, 128.32, 128.20, 128.14,
127.94, 127.81, 127.43, 126.14, 101.66, 100.96, 97.86, 80.74, 80.58,
79.69, 77.16, 74.76, 74.19, 73.46, 72.94, 72.61, 68.97, 68.19, 62.28,
4.3. Glycosylations of donors 1b–1g with acceptor 6a
General procedure: Triflic anhydride (11.8
mL, 0.070 mmol,
60.41, 55.28, 47.84; MS (FAB) 829 [M]þ; Anal. Calcd for C49H51NO11
C, 70.91; H, 6.19; N, 1.69. Found: C, 70.80; H, 6.25; N, 1.64.
:
1.3 equiv) was added to a stirred solution of 1b–1g (1.2 equiv), BSM

Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
4955
4.3.3. Coupling of 1e with 6a to give methyl (N-acetyl-2-amino-
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy- -glucopyranosyl)-(1/3)-
2-O-benzyl-4,6-O-benzylidene- -glucopyranoside (7e)
Donor 1e was pre-activated at ꢁ60 ꢀC. The crude product
was purified by column chromatography (petroleum ether/ethyl
acetate, 4:1) to give 7e as an inseparable anomeric mixture, and
anomeric ratio was determined by integration of the 1H NMR
disappearance of 1c detected by TLC, a solution of the acceptor alcohol
6a (25.0 mg, 0.054 mmol, 1.0 equiv) or 6b–6m in CH2Cl2 (0.5 mL) was
added dropwise to the pre-activated system. The mixture was stirred
and slowly warmed to room temperature, and then quenched by Et3N
(0.1 mL). The precipitate was filtered off and the filtrate was concen-
trated. The crude product was purified by column chromatography on
silica gel to give 7c and 8b–8m.
D
a-D
spectrum of the reaction mixture, yield¼84% (
(petroleum ether/ethyl acetate, 1.5:1); 1H NMR (500 MHz, CDCl3)
7.40–7.46 (m, 4H), 7.25–7.36 (m, 20H), 7.14 (t,1H, J¼7.0 Hz), 7.00 (t,
2H, J¼7.5 Hz), 6.65 (d, 2H, J¼7.5 Hz), 5.52 (s, 0.8H), 5.40 (s, 1H), 5.36
), 4.84 (d, 1H,
J¼12.0 Hz), 4.81 (d, 0.8H, J¼12.0 Hz), 4.72 (d, 1.7H, J¼4.0 Hz, H-1),
4.49–4.67 (m, 8H), 4.23–4.34 (m, 4H), 4.13–4.15 (m, 2H), 4.03 (d, 2H,
J¼4.0 Hz), 4.00 (dd, 0.8H, J¼10.0, 12.0 Hz), 3.80–3.88 (m, 1.8H),
3.53–3.77 (m, 8H), 3.44–3.48 (m, 1H), 3.41 (s, 3H), 3.36 (s, 2.2H),
a
/
b
¼1:1). Rf¼0.30
4.4.1. Coupling of 1c with 6b to give methyl (N-benzyl-2-amino-
d
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy-b-D-glucopyranosyl)-(1/
2)-3-O-benzyl-4,6-O-benzylidene- -glucopyranoside (8b)
a-D
(d, 1H, J¼3.0 Hz, H-10
a
), 5.08 (d, 0.7H, J¼7.5 Hz, H-10
b
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 7:1) to give 8b, yield¼83%. Rf¼0.50
(petroleum ether/ethyl acetate, 2:1); 1H NMR (500 MHz, CDCl3)
d
7.58–7.60 (m, 2H), 7.48–7.50 (m, 2H), 7.24–7.40 (m, 19H), 7.18–7.20
(m, 2H), 5.59 (s, 1H), 5.04 (d, 1H, J¼8.0 Hz, H-10), 5.00 (d, 1H,
J¼11.0 Hz), 4.85 (d, 1H, J¼3.5 Hz, H-1), 4.80 (d, 1H, J¼11.5 Hz), 4.63
(d, 1H, J¼14.5 Hz), 4.56 (d, 1H, J¼11.0 Hz), 4.52 (d, 1H, J¼12.5 Hz),
4.45 (d, 1H, J¼12.5 Hz), 4.44 (d, 1H, J¼11.5 Hz), 4.34 (dd, 1H, J¼5.0,
10.5 Hz), 4.20 (t,1H, J¼9.5 Hz), 4.18 (d,1H, J¼14.5 Hz), 3.88–3.97 (m,
3H), 3.78 (t, 1H, J¼10.0 Hz), 3.71 (dd, 1H, J¼3.0, 9.0 Hz), 3.60–3.68
(m, 3H), 3.49 (s, 3H), 3.45–3.48 (m,1H), 3.14 (dd,1H, J¼7.5, 12.0 Hz);
3.25 (dd, 0.7H, J¼7.5, 11.5 Hz, H-20 ), 3.01 (dd, 1H, J¼3.0, 12.0 Hz, H-
b
20
a), 1.88 (s, 3H), 1.80 (s, 2H); HRMS (ESI) calcd for C44H47NO12Na
[MþNa]þ: 804.2990, found: 804.2994.
4.3.4. Coupling of 1g with 6a to give methyl (N-benzyl-2-amino-
2,3-N,O-carbonyl-4,6-diacetyl-2-deoxy-a- and b-D-
glucopyranosyl)-(1/3)-2-O-benzyl-4,6-O-benzylidene-
a-D
-
13C NMR (125 MHz, CDCl3)
d 158.91, 137.93, 137.82, 137.25 (2C),
glucopyranosides (7g
a
) and (7g
b
)
135.24,130.47,129.02,128.50,128.40,128.37,128.28,128.04,128.00,
127.94, 127.91, 127.74, 127.71, 125.95, 102.06, 101.40, 100.09, 83.19,
80.62, 78.43, 76.69, 76.17, 75.18, 73.93, 73.36, 73.00, 69.16, 68.31,
62.20, 59.63, 55.45, 47.68; MS (FAB) 829 [M]þ, 830 [MþH]þ; Anal.
Calcd for C49H51NO11: C, 70.91; H, 6.19; N, 1.69. Found: C, 71.11; H,
6.32; N, 1.50.
Donor 1g was pre-activated at ꢁ50 ꢀC. The crude product was
purified by column chromatography (petroleum ether/ethyl ace-
tate, 7:1) to give 7g, yield¼94% (
isomer)¼0.40 (petroleum ether/ethyl acetate, 1:1); compound 7g
1H NMR (500 MHz, CDCl3)
7.42–7.44 (m, 2H), 7.31–7.39 (m, 8H),
a
/
b
¼3:1). Rf (
a
-isomer)¼0.45, Rf (
b-
a
:
d
7.13–7.16 (m, 1H), 6.97–7.00 (m, 2H), 6.61–6.63 (m, 2H), 5.44 (s, 1H),
5.38 (d, 1H, J¼3.0 Hz, H-10), 5.06 (t, 1H, J¼10.0 Hz), 4.78 (d, 1H,
J¼4.0 Hz, H-1), 4.67 (d, 1H, J¼15.0 Hz), 4.65 (d, 1H, J¼11.0 Hz), 4.57
(d, 1H, J¼11.0 Hz), 4.50 (dd, 1H, J¼10.0, 12.0 Hz), 4.29 (t, 1H,
J¼9.5 Hz), 4.26 (dd, 1H, J¼5.0, 10.5 Hz), 4.15–4.18 (m, 1H), 3.92 (dd,
1H, J¼2.0, 12.5 Hz), 3.86–3.90 (m, 1H), 3.83 (dd, 1H, J¼4.0, 12.5 Hz),
3.71 (t, 1H, J¼10.5 Hz), 3.64 (d, 1H, J¼15.0 Hz), 3.60 (t, 1H, J¼9.5 Hz),
3.58 (dd, 1H, J¼3.5, 9.5 Hz), 3.44 (s, 3H), 3.09 (dd, 1H, J¼3.0,
12.0 Hz), 2.03 (s, 3H), 2.01 (s, 3H); 13C NMR (125 MHz, CDCl3)
4.4.2. Coupling of 1c with 6c to give methyl (N-benzyl-2-amino-
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy-b-D-glucopyranosyl)-(1/
3)-2-O-benzyl-4,6-O-benzylidene- -galactopyranoside (8c)
a-D
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 3:1) to give 8c, yield¼83%. Rf¼0.20
(petroleum ether/ethyl acetate, 2:1); 1H NMR (500 MHz, CDCl3)
d
7.56–7.58 (m, 2H), 7.42–7.43 (m, 2H), 7.24–7.38 (m,16H), 7.18–7.20
(m, 2H), 7.10 (t,1H, J¼7.5 Hz), 6.85 (t, 2H, J¼7.5 Hz), 5.55 (s,1H), 5.08
(d, 1H, J¼8.0 Hz, H-10), 4.89 (d, 1H, J¼3.5 Hz, H-1), 4.80 (d, 1H,
J¼11.0 Hz), 4.59 (d, 2H, J¼12.5 Hz), 4.55 (d, 1H, J¼12.0 Hz), 4.53 (d,
1H, J¼11.5 Hz), 4.44 (d, 1H, J¼12.0 Hz), 4.43 (d, 1H, J¼11.5 Hz), 4.34
(d, 1H, J¼3.5 Hz), 4.28 (dd, 1H, J¼3.5, 10.0 Hz), 4.21–4.26 (m, 2H),
4.19 (dd, 1H, J¼3.5, 10.5 Hz), 4.00 (dd, 1H, J¼1.5, 12.5 Hz), 3.98 (dd,
1H, J¼10.0, 12.0 Hz), 3.72 (dd,1H, J¼9.0, 10.0 Hz), 3.64–3.67 (m, 3H),
3.53–3.56 (m, 1H), 3.38 (s, 3H), 3.18 (dd, 1H, J¼8.0, 12.0 Hz); 13C
d
170.58, 169.09, 158.09, 137.13, 136.85, 134.34, 129.80, 128.64,
128.58, 128.46, 128.36, 128.30, 127.78, 126.66, 102.75, 98.04, 94.52,
82.19, 77.58, 73.73, 73.54, 72.55, 70.15, 69.01, 68.00, 61.93, 61.06,
59.23, 55.39, 46.86, 20.62 (2C); HRMS (ESI) calcd for C39H43NO13Na
[MþNa]þ: 756.2627, found: 756.2629. Compound 7g
b:
1H NMR
(500 MHz, CDCl3)
d 7.45–7.47 (m, 2H), 7.41–7.43 (m, 2H), 7.28–7.37
(m, 11H), 5.54 (s, 1H), 5.13 (dd, 1H, J¼8.5, 10.5 Hz), 5.10 (d, 1H,
J¼7.5 Hz, H-10), 4.74 (d, 1H, J¼3.5 Hz, H-1), 4.56 (d, 1H, J¼14.5 Hz),
4.53 (s, 2H), 4.32 (t, 1H, J¼9.5 Hz), 4.30 (d, 1H, J¼14.5 Hz), 4.27 (dd,
1H, J¼4.5, 10.0 Hz), 4.08 (dd, 1H, J¼5.0, 12.5 Hz), 4.01 (dd, 1H, J¼2.5,
12.5 Hz), 3.96 (dd, 1H, J¼10.0, 12.0 Hz), 3.84 (dt, 1H, J¼4.5, 10.0 Hz),
3.76 (t, 1H, J¼10.0 Hz), 3.68 (dd, 1H, J¼3.5, 9.5 Hz), 3.58 (t, 1H,
J¼9.5 Hz), 3.52–3.55 (m, 1H), 3.33–3.38 (m, 1H), 3.36 (s, 3H), 2.05 (s,
NMR (125 MHz, CDCl3)
d 158.98, 137.96, 137.89, 137.50, 137.28,
135.10, 130.20, 129.11, 128.56, 128.36, 128.32, 128.23, 128.04, 128.02,
127.89, 127.68, 126.46, 102.75, 101.34, 98.16, 80.71, 76.75, 76.60,
76.59, 74.04, 73.76, 73.35, 72.97, 72.76, 69.23, 68.48, 62.54, 59.70,
55.47, 47.69; MS (FAB) 852 [MþNa]þ; Anal. Calcd for C49H51NO11: C,
70.91; H, 6.19; N, 1.69. Found: C, 71.05; H, 6.66; N, 1.49.
3H), 1.93 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 170.58, 169.15,158.39,
137.14, 135.22, 129.52, 129.10, 128.64, 128.42, 128.18, 128.12, 128.02,
126.04, 101.63, 101.34, 97.79, 80.42, 79.37, 75.86, 74.26, 72.60, 68.90,
67.68, 62.35, 62.10, 60.37, 60.03, 55.30, 47.84, 21.03, 20.64; HRMS
(ESI) calcd for C39H43NO13þNH4 [MþNH4]þ: 751.3073, found:
751.3074.
4.4.3. Coupling of 1c with 6d to give methyl (N-benzyl-2-amino-
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy-b-D-glucopyranosyl)-(1/
2)-3-O-benzyl-4,6-O-benzylidene- -galactopyranoside (8d)
a-D
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 5:1) to give 8d, yield¼83%. Rf¼0.3
(petroleum ether/ethyl acetate, 2:1); 1H NMR (500 MHz, CDCl3)
4.4. Glycosylations of 1c with 6a–6m by means of BSM/Tf2O
pre-activation
d 7.53–7.59 (m, 4H), 7.23–7.36 (m, 18H), 7.17–7.19 (m, 2H), 5.46 (s,
1H), 5.02 (d, 1H, J¼3.5 Hz, H-1), 4.97 (d, 1H, J¼7.5 Hz, H-10), 4.79 (d,
1H, J¼11.5 Hz), 4.59 (d, 1H, J¼15.0 Hz), 4.54 (d, 1H, J¼11.5 Hz), 4.52
(d, 1H, J¼12.0 Hz), 4.43 (d, 1H, J¼10.0 Hz), 4.42 (d, 1H, J¼12.5 Hz),
4.28–4.31 (m, 3H), 4.27 (d, 1H, J¼14.5 Hz), 4.12 (dd, 1H, J¼3.5,
10.0 Hz), 4.05 (dd, 1H, J¼1.5, 12.5 Hz), 3.97 (dd, 1H, J¼10.0, 12.0 Hz),
3.76 (t, 1H, J¼9.5 Hz), 3.69 (s, 1H), 3.66 (dd, 1H, J¼4.5, 11.5 Hz), 3.61
(dd, 1H, J¼1.5, 10.5 Hz), 3.47–3.50 (m, 1H), 3.46 (s, 3H), 3.21 (dd, 1H,
General procedure: Triflicanhydride (11.8 mL, 0.070 mmol,1.3 equiv)
was added to a stirred solution of 1c (37.6 mg, 0.065 mmol,1.2 equiv),
BSM (15.9 mg, 0.075 mmol, 1.4 equiv) and activated 4 Å molecular
sieves (500 mg) in CH2Cl2 (6.0 mL) at ꢁ73 ꢀC under nitrogen atmo-
sphere. The reaction mixture was stirred for 3–5 min, after

4956
Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
J¼8.0, 11.5 Hz); 13C NMR (125 MHz, CDCl3)
d
158.86, 137.86, 137.64,
67.97, 63.80, 63.70, 59.06, 55.13, 46.62; MS (FAB) 764 [M]þ, 765
137.60, 137.36, 135.36, 130.40, 128.92, 128.40, 128.33, 128.29, 128.13,
128.02, 127.93, 127.90, 128.81, 127.77, 127.71, 127.63, 126.20, 102.44,
101.10, 100.19, 80.73, 76.51, 75.94, 74.38, 73.82, 73.42, 73.25, 72.90,
70.89, 69.49, 68.17, 62.25, 59.54, 55.71, 47.31; MS (FAB) 852
[MþNa]þ, 868 [MþK]þ; Anal. Calcd for C49H51NO11: C, 70.91; H,
6.19; N, 1.69. Found: C, 70.73; H, 6.18; N, 1.53.
[MþH]þ; Anal. Calcd for C42H44N4O10: C, 65.96; H, 5.80; N, 7.33.
Found: C, 65.69; H, 6.04; N, 7.09. Compound 8gb:
1H NMR
(500 MHz, CDCl3)
d 7.21–7.38 (m, 20H), 5.44 (s, 1H), 4.84 (d, 1H,
J¼8.0 Hz, H-10), 4.81 (d, 1H, J¼11.5 Hz), 4.69 (d, 1H, J¼1.5 Hz, H-1),
4.48–4.56 (m, 3H), 4.43 (s, 2H), 4.16–4.18 (m, 1H), 4.13 (dd, 1H,
J¼4.0, 9.5 Hz), 4.03–4.09 (m, 2H), 3.70–3.79 (m, 4H), 3.50–3.55 (m,
2H), 3.37–3.41 (m, 1H), 3.35 (s, 3H), 3.32 (dd, 1H, J¼4.0,12.0 Hz); 13
C
4.4.4. Coupling of 1c with 6e to give methyl (N-benzyl-2-amino-
NMR (125 MHz, CDCl3) d 159.05, 138.07, 137.30, 137.16, 136.23,
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy-
b
-
D
-glucopyranosyl)-(1/
129.22, 128.63, 128.36, 128.29, 128.17, 128.00, 127.90, 127.76, 127.64,
126.17, 102.04, 99.61, 98.70, 80.36, 77.54, 77.26, 74.01, 73.26, 73.17,
72.85, 68.62, 68.39, 63.54, 61.44, 60.96, 55.09, 47.90; MS (FAB) 764
[M]þ, 765 [MþH]þ; Anal. Calcd for C42H44N4O10: C, 65.96; H, 5.80;
N, 7.33. Found: C, 65.69; H, 6.08; N, 7.10.
3)-2-O-benzyl-4,6-O-benzylidene- -glucopyranoside (8e)
b-D
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 8:1) to give 8e, yield¼87%. Rf¼0.30
(petroleum ether/ethyl acetate, 3:1); 1H NMR (500 MHz, CDCl3)
d
7.40–7.43 (m, 4H), 7.16–7.32 (m, 21H), 5.49 (s, 1H), 5.04 (d, 1H,
J¼7.5 Hz, H-10), 4.85 (d, 1H, J¼11.5 Hz), 4.78 (d, 1H, J¼11.0 Hz), 4.49
(d, 1H, J¼14.5 Hz), 4.45 (d, 1H, J¼11.5 Hz), 4.40 (d, 1H, J¼7.5 Hz, H-
1), 4.39 (d, 1H, J¼11.0 Hz), 4.31–4.37 (m, 4H), 4.09 (t, 1H, J¼9.5 Hz),
3.88 (dd, 1H, J¼9.5, 12.0 Hz), 3.77 (t, 1H, J¼10.5 Hz), 3.72 (dd, 1H,
J¼8.5, 9.5 Hz), 3.66 (t, 1H, J¼9.5 Hz), 3.57–3.59 (m, 1H), 3.56 (s, 3H),
3.54 (dd, 1H, J¼4.5, 11.0 Hz), 3.49 (dd, 1H, J¼7.5, 8.0 Hz), 3.35–3.43
(m, 2H), 3.23 (dd, 1H, J¼7.5, 11.5 Hz); 13C NMR (125 MHz, CDCl3)
4.4.7. Coupling of 1c with 6h to give methyl (N-benzyl-2-amino-
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy-
glucopyranosyl)-(1/2)-3-azide-4,6-O-benzylidene-3-deoxy-
glucopyranosides (8h ) and (8h
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 4:1) to give 8h, yield¼83% (
¼1:2). Rf ( -isomer)¼0.40, Rf ( -isomer)¼0.25 (petroleum ether/
ethyl acetate, 2:1); compound 8h
1H NMR (500 MHz, CDCl3)
7.48–7.50 (m, 2H), 7.21–7.38 (m, 18H), 5.56 (s, 1H), 5.09 (d, 1H,
a- and b-D-
a-D-
a
b)
a
/
b
b
a
d
159.20, 138.17, 137.87, 137.36, 137.12, 135.81, 129.32, 129.01, 128.50,
a:
128.36, 128.26, 128.17, 127.97, 127.89, 127.85, 127.78, 127.51, 126.14,
105.08, 101.49, 100.34, 82.61, 80.61, 78.98, 77.17, 74.44, 74.21, 73.43,
72.90, 68.74, 68.47, 66.15, 60.51, 57.28, 47.90; MS (FAB) 853
[MþNaþH]þ; Anal. Calcd for C49H51NO11: C, 70.91; H, 6.19; N, 1.69.
Found: C, 71.11; H, 6.29; N, 1.42.
d
J¼3.0 Hz, H-10), 4.93 (d, 1H, J¼15.0 Hz), 4.89 (d, 1H, J¼3.5 Hz, H-1),
4.87 (d, 1H, J¼11.0 Hz), 4.68–4.72 (m, 1H), 4.56 (d, 1H, J¼12.5 Hz),
4.48 (d, 1H, J¼11.5 Hz), 4.42 (d, 1H, J¼12.0 Hz), 4.32 (dd, 1H, J¼5.0,
10.5 Hz), 4.01 (t, 1H, J¼10.0 Hz), 3.98 (d, 1H, J¼15.0 Hz), 3.91–3.94
(m, 2H), 3.85 (dt, 1H, J¼5.0, 10.0 Hz), 3.75 (dd, 1H, J¼2.5, 10.5 Hz),
3.73 (t, 1H, J¼10.5 Hz), 3.59–3.63 (m, 2H), 3.50 (s, 3H), 3.46 (t, 1H,
J¼10.0 Hz), 3.30 (dd, 1H, J¼3.0, 12.0 Hz); 13C NMR (125 MHz, CDCl3)
4.4.5. Coupling of 1c with 6f to give methyl (N-benzyl-2-amino-2,3-
N,O-carbonyl-4,6-dibenzyl-2-deoxy-
D-glucopyranosyl)-(1/2)-3-
O-benzyl-4,6-O-benzylidene- -glucopyranoside (8f)
b-
D
d 158.48, 137.64, 137.44, 136.65, 134.95, 129.16, 128.41, 128.37,
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 4:1) to give 8f as an inseparable
anomeric mixture, and anomeric ratio was determined by in-
tegration of the 1H NMR spectrum of the reaction mixture,
128.32, 128.07, 127.91, 127.82, 125.98, 101.59, 96.38, 91.84, 80.01,
77.39, 74.41, 73.80, 73.45, 73.38, 72.97, 68.81, 67.43, 62.48, 61.04,
59.05, 55.11, 47.12; HRMS (ESI) calcd for C42H48N4O10 [MþNH4]þ:
782.3396, found: 728.3381. Compound 8hb:
1H NMR (500 MHz,
yield¼85% (
a
/
b
¼1:2). Rf¼0.30 (petroleum ether/ethyl acetate, 2:1);
CDCl3) d 7.48–7.54 (m, 4H), 7.21–7.40 (m, 16H), 5.60 (s, 1H), 4.92 (d,
1H NMR (500 MHz, CDCl3)
d
7.46–7.49 (m, 3H), 7.11–7.40 (m, 33H),
1H, J¼7.5 Hz, H-10), 4.84 (d, 1H, J¼12.5 Hz), 4.83 (d, 1H, J¼4.0 Hz, H-
1), 4.79 (d, 1H, J¼15.0 Hz), 4.52 (d, 1H, J¼12.0 Hz), 4.48 (d, 1H,
J¼12.0 Hz), 4.46 (d, 1H, J¼12.5 Hz), 4.34 (d, 1H, J¼14.5 Hz), 4.33 (dd,
1H, J¼5.0, 10.0 Hz), 4.09–4.14 (m, 2H), 3.92 (dt, 1H, J¼5.0, 10.0 Hz),
3.56–3.77 (m, 7H), 3.43 (s, 3H), 3.24 (dd, 1H, J¼7.5, 11.5 Hz); 13C
7.03–7.06 (m, 2H), 5.59 (s, 0.5H), 5.58 (s,1H), 5.52 (d, 0.6H, J¼3.0 Hz,
H-1a0), 5.06 (d, 1H, J¼7.5 Hz, H-1b0), 4.96 (d, 1H, J¼11.0 Hz), 4.93 (d,
0.6H, J¼10.5 Hz), 4.81–4.87 (m, 2H), 4.59 (d, 1H, J¼10.5 Hz), 4.57 (d,
1H, J¼12.0 Hz), 4.44–4.51 (m, 5.5H), 4.37–4.41 (m, 2H), 4.33 (d,
0.7H, J¼7.0 Hz, H-1a), 4.27 (d, 1H, J¼14.5 Hz), 4.18 (d, 0.6H,
J¼12.0 Hz), 3.67–4.02 (m,12H), 3.53 (s,1.7H), 3.46 (s, 3H), 3.43–3.49
(m, 2H), 3.20–3.26 (m, 2H), 3.13 (dd, 0.7H); MS (FAB) 853
[MþNaþH]þ; Anal. Calcd for C49H51NO11: C, 70.91; H, 6.19; N, 1.69.
Found: C, 71.65; H, 6.66; N, 1.44.
NMR (125 MHz, CDCl3)
d 158.85, 137.74, 137.19, 136.71, 135.32,
129.85, 129.07, 128.47, 128.42, 128.28, 128.06, 127.96, 127.89, 127.81,
127.71, 125.89, 102.24, 101.46, 99.60, 80.90, 80.42, 76.91, 76.60,
73.80, 73.38, 72.98, 69.06, 68.53, 62.37, 61.44, 59.89, 55.64, 47.67;
HRMS (ESI) calcd for C42H48N5O10 [MþNH4]þ: 782.3396, found:
782.3384.
4.4.6. Coupling of 1c with 6g to give methyl (N-benzyl-2-amino-
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy-
glucopyranosyl)-(1/3)-2-azide-4,6-O-benzylidene-2-deoxy-
mannopyranosides (8g ) and (8g
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 7:1) to give 8g, yield¼83% (
¼1:1.5). Rf ( -isomer)¼0.45, Rf ( -isomer)¼0.40 (petroleum ether/
ethyl acetate, 2:1); compound 8g
1H NMR (500 MHz, CDCl3)
7.44–7.46 (m, 2H), 7.25–7.34 (m, 11H), 7.15–7.21 (m, 3H), 7.06 (t,
a
- and
b
-
D
-
4.4.8. Coupling of 1c with 6i to give N-benzyl-2-amino-2,3-N,O-
a-D
-
carbonyl-4,6-dibenzyl-2-deoxy-D-glucopyranosyl-(1/6)-1,2:3,4-
a
b
)
di-O-isopropylidene- -galactopyranoside (8i)
a-D
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 5:1) to give 8i as an inseparable
anomeric mixture, and anomeric ratio was determined by in-
tegration of the 1H NMR spectrum of the reaction mixture,
a
/
b
a
b
a
:
d
yield¼96% (
a
/
b
¼1:11). Rf¼0.35 (petroleum ether/ethyl acetate, 2:1);
2H, J¼8.0 Hz), 6.72 (d, 2H, J¼7.5 Hz), 5.49 (s, 1H), 5.29 (d, 1H,
J¼2.5 Hz, H-10), 4.85 (d, 1H, J¼11.5 Hz), 4.59–4.65 (m, 3H), 4.53 (d,
1H, J¼12.0 Hz), 4.45 (d, 1H, J¼11.0 Hz), 4.43 (d, 1H, J¼12.5 Hz), 4.42
(dd, 1H, J¼3.5, 10.0 Hz), 4.23–4.25 (m, 1H), 4.05 (t, 1H, J¼9.0 Hz),
3.94 (dd, 1H, J¼1.5, 3.5 Hz), 3.74–3.84 (m, 5H), 3.68 (d, 2H,
J¼2.5 Hz), 3.37 (s, 3H), 3.13 (dd, 1H, J¼3.0, 12.5 Hz); 13C NMR
major isomer 8i
b:
1H NMR (500 MHz, CDCl3)
d
7.54–7.55 (m, 2H),
7.25–7.53 (m, 11H), 7.17–7.19 (m, 2H), 5.58 (d, 1H, J¼5.0 Hz, H-1),
4.81 (d, 1H, J¼11.0 Hz), 4.71 (d, 1H, J¼14.5 Hz), 4.70 (d, 1H, J¼8.0 Hz,
H-10), 4.61 (d, 1H, J¼5.0, 8.0 Hz), 4.57 (d, 1H, J¼12.5 Hz), 4.46 (d, 1H,
J¼11.0 Hz), 4.43 (d, 1H, J¼11.0 Hz), 4.41 (d, 1H, J¼12.5 Hz), 4.22 (dd,
1H, J¼2.0, 5.0 Hz), 4.19 (dd, 1H, J¼2.0, 8.0 Hz), 4.15 (dd, 1H, J¼2.0,
11.0 Hz), 4.08–4.13 (m, 2H), 4.07 (dd, 1H, J¼9.5, 12.0 Hz), 3.79 (dd,
1H, J¼8.5, 9.5 Hz), 3.72–3.76 (m, 1H), 3.69 (dd, 1H, J¼3.0, 11.5 Hz),
3.53–3.56 (m, 1H), 3.22 (dd, 1H, J¼8.0, 12.0 Hz), 1.48 (s, 3H), 1.47 (s,
(125 MHz, CDCl3)
d 158.61, 137.72, 137.40, 136.95, 134.80, 129.73,
128.63, 128.55, 128.36, 128.14, 128.02, 127.81, 127.74, 126.56, 102.93,
99.89, 96.16, 78.56, 76.90, 74.56, 74.28, 73.53, 73.48, 72.81, 68.71,

Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
4957
3H), 1.32 (s, 3H), 1.29 (s, 3H); MS (FAB) 718 [MþH]þ; Anal. Calcd for
integration of the 1H NMR spectrum of the reaction mixture,
yield¼98% ( ¼1:3). Rf¼0.25 (petroleum ether/ethyl acetate, 1:1);
major isomer 8l 7.21–7.35 (m, 20H),
: 1H NMR (500 MHz, CDCl3)
C
40H47NO11: C, 66.93; H, 6.60; N, 1.95. Found: C, 67.02; H, 6.72; N,
a/b
1.91.
b
d
5.53 (d,1H, J¼7.5 Hz), 5.10 (d,1H, J¼15.5 Hz), 5.09 (d,1H, J¼15.5 Hz),
4.83 (d, 1H, J¼11.0 Hz), 4.51 (d, 1H, J¼8.0 Hz, H-1), 4.40–4.49 (m,
5H), 4.03–4.09 (m, 2H), 3.73–3.82 (m, 2H), 3.70 (s, 3H), 3.63–3.65
(m, 3H), 3.50–3.52 (m, 1H), 3.21 (dd,1H, J¼8.0, 12.0 Hz); HRMS (ESI)
calcd for C40H43N2O10 [MþH]þ: 711.2912, found: 711.2976.
4.4.9. Coupling of 1c with 6j to give methyl (N-benzyl-2-amino-2,3-
N,O-carbonyl-4,6-dibenzyl-2-deoxy-D-glucopyranosyl)-(1/6)-
2,3,4-tri-O-benzyl- -glucopyranoside (8j)
a-D
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 4:1) to give 8j as an inseparable
anomeric mixture, and anomeric ratio was determined by in-
tegration of the 1H NMR spectrum of the reaction mixture, yield¼
4.4.12. Coupling of 1c with 6m to give methyl (N-benzyl-2-amino-
2,3-N,O-carbonyl-4,6-dibenzyl-2-deoxy-D-glucopyranosyl)-(1/4)-
85% (
isomer 8j
a
/
b
¼1:6). Rf¼0.25 (petroleum ether/ethyl acetate, 2:1); major
2,3,6-tri-O-benzyl- -glucopyranoside (8m)
a-D
b
:
1H NMR (500 MHz, CDCl3)
d
7.42–7.44 (m, 2H), 7.17–
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 5:1) to give 8m as an inseparable
anomeric mixture, and anomeric ratio was determined by in-
7.35 (m, 28H), 4.98 (d, 1H, J¼11.0 Hz), 4.85 (d, 1H, J¼11.5 Hz), 4.81
(d, 1H, J¼11.5 Hz), 4.80 (d, 1H, J¼10.5 Hz), 4.78 (d, 1H, J¼11.0 Hz),
4.62 (d, 1H, J¼12.0 Hz), 4.58 (d,1H, J¼15.0 Hz), 4.55 (d,1H, J¼3.5 Hz,
H-1), 4.54 (d, 1H, J¼10.5 Hz), 4.52 (d, 1H, J¼10.0 Hz), 4.48 (d, 1H,
J¼15.0 Hz), 4.45 (d, 1H, J¼11.0 Hz), 4.38 (d, 1H, J¼7.5 Hz, H-10), 4.31
(d, 1H, J¼14.5 Hz), 4.01 (t, 1H, J¼12.0 Hz), 3.99–4.04 (m, 2H), 3.82–
3.85 (m, 1H), 3.73 (dd, 1H, J¼8.5, 9.5 Hz), 3.62–3.66 (m, 2H), 3.51
(dd, 1H, J¼5.5, 11.0 Hz), 3.46 (dd, 1H, J¼3.5, 10.0 Hz), 3.47–3.50 (m,
1H), 3.34 (dd, 1H, J¼9.0, 10.0 Hz), 3.33 (s, 3H), 3.22 (dd, 1H, J¼7.5,
12.0 Hz); MS (ESI) 939 [MþNH4]þ, 944 [MþNa]þ, 960 [MþK]þ;
Anal. Calcd for C56H59NO11: C, 72.94; H, 6.45; N, 1.52. Found: C,
72.67; H, 6.44; N, 1.55.
tegration of the 1H NMR spectrum of the mixture, yield¼82% (
a
/b
¼
2.5:1). Rf¼0.3 (petroleum ether/ethyl acetate, 2:1); 1H NMR
(500 MHz, CDCl3)
10a), 5.08 (d, 1H, J¼12.0 Hz), 5.02 (d, 0.7H, J¼12.0 Hz), 3.87–4.05 (m,
d
7.03–7.35 (m, 56H), 5.54 (d, 1H, J¼3.0 Hz, H-
6H), 3.73–3.84 (m, 4H), 3.67–3.70 (m, 1H), 3.41–3.63 (m, 8H), 3.38
(s, 3H), 3.35 (s, 3H), 3.27–3.30 (m, 1H), 3.17 (dd, 0.9H, J¼3.0, 12.0 Hz,
H-20
a
), 3.01 (dd, 0.4H, J¼7.5, 12.0 Hz, H-20
b
); MS (FAB) 921 [M]þ;
Anal. Calcd for C56H59NO11: C, 72.94; H, 6.45; N, 1.52. Found: C,
72.75; H, 6.29; N, 1.43.
4.5. Deprotection of disaccharide 8d
4.4.10. Coupling of 1c with 6k to give N-benzyl-2-amino-2,3-N,O-
carbonyl-4,6-dibenzyl-1-O-octyl-2-deoxy-
a- and
b-
D-
4.5.1. Methyl (N-benzyl-2-amino-4,6-O-dibenzyl-2-deoxy-b-D-
glucopyranosides (8k ) and (8k
a
b
)
glucopyranosyl)-(1/2)-3-O-benzyl-4,6-O-benzylidene-
a-D-
The crude product was purified by column chromatography
galactopyranoside (9)
(petroleum ether/ethyl acetate, 11:1 to 9:1) to give 8k, yield¼95%
Compound 8d (50.0 mg, 0.066 mmol, 1.0 equiv) was dissolved in
DMSO (2.0 mL) and stirred, and then t-BuOK (34.0 mg, 0.30 mmol,
5.0 equiv) was added. The reaction mixture was stirred at room
temperature for 20 min, diluted with ethyl acetate and washed
with water. The aqueous layer was extracted with ethyl acetate
(3ꢂ2 mL). The combined organic layer was dried, filtered and
concentrated under reduced pressure. The residue was purified by
column chromatography (petroleum ether/ethyl acetate, 1:1) to
give 9 (44 mg, 90%) as a white solid: 1H NMR (500 MHz, CDCl3)
(a
/b
¼1:3.5). Rf (
b
-isomer)¼0.7, Rf ( -isomer)¼0.5 (petroleum ether/
a
ethyl acetate, 2:1); compound 8ka:
1H NMR (500 MHz, CDCl3)
d
7.20–7.35 (m, 14H), 4.86 (d, 1H, J¼11.0 Hz), 4.68 (d, 1H, J¼3.0 Hz,
H-1), 4.64 (dd, 1H, J¼10.0, 12.0 Hz), 4.56 (d, 1H, J¼12.5 Hz), 4.47 (d,
1H, J¼11.0 Hz), 4.42 (d, 1H, J¼12.0 Hz), 4.41 (s, 2H), 3.90 (t, 1H,
J¼9.0 Hz), 3.72 (dd, 1H, J¼3.5, 10.5 Hz), 3.65–3.67 (m, 1H), 3.59 (dd,
1H, J¼1.5, 10.5 Hz), 3.46–3.51 (m, 1H), 3.31 (dd, 1H, J¼3.0, 12.0 Hz),
3.00–3.05 (m, 1H), 1.46 (s, 2H), 1.26–1.32 (m, 10H), 0.88 (t, 3H,
J¼6.5 Hz); 13C NMR (125 MHz, CDCl3)
d
159.14, 137.78, 137.45,
d 7.55–7.57 (m, 2H), 7.23–7.37 (m, 20H), 7.18–7.20 (m, 3H), 5.54 (s,
135.31, 128.75, 128.63, 128.36, 128.13, 128.04, 127.84, 127.75, 95.17,
77.38, 74.88, 73.46, 73.00, 72.42, 68.65, 67.72, 61.24, 48.64, 31.80,
29.31, 29.17, 26.06, 22.62, 14.07; MS (ESI) 588 [MþH]þ, 605
[MþNH4]þ, 610 [MþNa]þ; Anal. Calcd for C36H45NO6: C, 73.57; H,
1H), 4.84 (d, 1H, J¼11.0 Hz), 4.77 (d, 1H, J¼3.5 Hz, H-1), 4.71 (d, 1H,
J¼8.0 Hz, H-10), 4.49–4.61 (m, 5H), 4.38 (d, 1H, J¼3.5 Hz), 4.23 (dd,
1H, J¼3.5, 10.5 Hz), 4.20 (dd, 1H, J¼1.0, 12.5 Hz), 4.12 (dd, 1H, J¼3.0,
10.0 Hz), 4.07 (d, 1H, J¼13.0 Hz), 3.99 (d, 1H, J¼13.0 Hz), 3.96 (dd,
1H, J¼1.5, 12.5 Hz), 3.73 (dd, 1H, J¼2.0, 11.0 Hz), 3.68 (dd, 1H, J¼5.0,
11.0 Hz), 3.61 (s, 1H), 3.38–3.50 (m, 3H), 3.36 (s, 3H), 3.22 (br, 1H),
2.53 (dd, 1H, J¼8.0, 9.0 Hz), 1.67 (br.s, 1H); 13C NMR (125 MHz,
7.72; N, 2.38. Found: C, 73.41; H, 7.47; N, 2.36. Compound 8kb
: 1H
NMR (500 MHz, CDCl3)
d 7.39–7.41 (m, 2H), 7.25–7.34 (m, 11H),
7.21–7.23 (m, 2H), 4.84 (d, 1H, J¼11.0 Hz), 4.57 (d, 1H, J¼12.0 Hz),
4.56 (d, 1H, J¼7.5 Hz, H-1), 4.51 (d, 1H, J¼15.0 Hz), 4.50 (d, 1H,
J¼12.5 Hz), 4.49 (d, 1H, J¼15.0 Hz), 4.46 (d, 1H, J¼12.0 Hz), 4.11 (dd,
1H, J¼9.5, 12.0 Hz), 3.81–3.86 (m, 1H), 3.79 (dd, 1H, J¼8.0, 9.5 Hz),
3.71 (dd, 1H, J¼2.0, 11.0 Hz), 3.67 (dd, 1H, J¼5.0, 11.0 Hz), 3.55–3.58
(m, 1H), 3.28–3.33 (m, 1H), 3.26 (dd, 1H, J¼7.0, 12.0 Hz), 1.55–1.57
(m, 2H), 1.26–1.30 (m, 10H), 0.88 (t, 3H, J¼7.0 Hz); 13C NMR
CDCl3)
d 140.27, 138.37, 138.23, 138.03, 137.98, 128.72, 128.51,
128.33, 128.18, 128.02, 127.93, 127.76, 127.68, 127.62, 126.88, 126.18,
104.86, 100.60, 98.54, 78.10, 76.82, 75.73, 74.61, 74.24, 73.90, 73.37,
72.94, 69.26, 69.19, 62.70, 62.37, 55.43, 51.56, 42.65; HRMS (ESI)
calcd for C48H54NO10 [MþH]þ: 804.3742, found: 804.3759.
(125 MHz, CDCl3)
d
159.13, 137.98, 137.33, 136.15, 128.80, 128.47,
4.5.2. Methyl (2-amino-2-deoxy-b-D-glucopyranosyl)-(1/2)-a-D-
128.39, 128.01, 127.91, 127.74, 127.68, 101.59, 80.85, 76.75, 74.17,
73.45, 73.00, 69.78, 68.52, 60.72, 47.84, 31.78, 29.47, 29.32, 29.21,
26.04, 22.63,14.08; MS (FAB) 587 [M]þ, 588 [MþH]þ; Anal. Calcd for
galactopyranoside (10)
Compound 9 (44.0 mg, 0.055 mmol) was dissolved in THF/water
(2:1, 3.0 mL) containing HOAc (0.15 mL), and 10% Pd/C (15.0 mg)
was added. The mixture was hydrogenated under an atmospheric
pressure of hydrogen. After stirring for 24 h, the catalyst was re-
moved by filtration and the filtrate was concentrated. The residue
was subjected to a C-18 reverse phase column chromatography
(H2O) to give 13 (18.0 mg, 95%) as a white solid after lyophilization:
C
36H45NO6: C, 73.57; H, 7.72; N, 2.38. Found: C, 73.79; H, 8.00; N,
2.58.
4.4.11. Coupling of 1c with 6l to give N-benzyl-2-amino-2,3-N,O-
carbonyl-4,6-dibenzyl-1-O-(N-carbobenzyloxy-L-serine methyl
ester)-2-deoxy- -glucopyranoside (8l)
D
1H NMR (300 MHz, D2O)
d
4.89 (d, 1H, J¼3.5 Hz, H-1), 4.49 (d, 1H,
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate, 3:1) to give 8l as an inseparable
anomeric mixture, and anomeric ratio was determined by
J¼8.5 Hz, H-10), 3.72–3.82 (m, 5H), 3.56–3.62 (m, 3H), 3.25–3.31 (m,
3H), 3.23 (s, 3H), 2.65 (t, 1H, J¼9.0 Hz); 13C NMR (125 MHz, D2O)
d
106.11, 101.55, 80.78, 78.61, 77.27, 73.18, 72.19, 71.98, 70.98, 63.77,

4958
Y. Geng et al. / Tetrahedron 64 (2008) 4949–4958
63.26, 59.04, 57.34; HRMS (ESI) calcd for C13H26NO10 [MþH]þ:
9. (a) Huang, X.; Huang, L.; Wang, H.; Ye, X.-S. Angew. Chem., Int. Ed. 2004, 43,
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Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China, ‘973’ and ‘863’ grants from the Min-
istry of Science and Technology of China.
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Supplementary data
12. Zhang, Z.; Ollman, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong, C.-H. J. Am.
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14. Donor 1d did not afford the expected disaccharide after it was absolutely
activated by means of BSM/Tf2O, presumably due to the instability of in-
termediate after the pre-activation. Donor 1f could be activated at a range of
temperatures from ꢁ73 ꢀC to room temperature by the use of promoter sys-
1H and 13C NMR spectra of all new compounds. Supplementary
data associated with this article can be found in the online version,
at doi:10.1016/j.tet.2008.03.103.
tems including BSM (BSP or Ph2SO)/Tf2O, N-(phenylthio)-3-caprolactam/Tf2O
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