Improved catalytic and stereoselective glycosylation with glycosyl N-trichloroacetylcarbamate: application to various 1-hydroxy sugars

Article abstract of DOI:10.1016/j.carres.2010.01.011

Efficient catalytic and stereoselective glycosylation was achieved by activating a glycosyl N-trichloroacetylcarbamate with a catalytic amount of Lewis acid in the presence of a glycosyl acceptor and 5 ? molecular sieves. Catalytic one-pot dehydrative glycosylation of a 1-hydroxy carbohydrate was achieved stereoselectively by reaction with trichloroacetyl isocyanate, followed by activation with a catalytic amount of activators.

Full text of DOI:10.1016/j.carres.2010.01.011

Carbohydrate Research 345 (2010) 740–749
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Improved catalytic and stereoselective glycosylation with glycosyl
N-trichloroacetylcarbamate: application to various 1-hydroxy sugars
Tatsuya Shirahata a, Jun-ichi Matsuo b, , Satoko Teruya c, Nozomu Hirata c, Taku Kurimoto c,
a
d,e,
*
Nanao Akimoto c, Toshiaki Sunazuka d,e, Eisuke Kaji , Satoshi Omura
¯
a School of Pharmacy, Kitasato University 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan
b Center for Basic Research, The Kitasato Institute, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8642, Japan
c Department of Chemistry, School of Science, Kitasato University, S-401, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan
d Kitasato Institute for Life Sciences, Kitasato University 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan
e Graduate School of Infection Control Sciences, Kitasato University 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Efficient catalytic and stereoselective glycosylation was achieved by activating a glycosyl N-trichloroace-
0
Received 12 September 2009
Received in revised form 13 January 2010
Accepted 20 January 2010
tylcarbamate with a catalytic amount of Lewis acid in the presence of a glycosyl acceptor and 5 AÅ molec-
ular sieves. Catalytic one-pot dehydrative glycosylation of a 1-hydroxy carbohydrate was achieved
stereoselectively by reaction with trichloroacetyl isocyanate, followed by activation with a catalytic
amount of activators.
Available online 4 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Glycosylation
Lewis acids
Solvent effects
Synthetic methods
1. Introduction
tion reactions employing glycosyl carbamates as a glycosyl donor
have been reported, and these are activated by using a stoichiom-
O-Glycosylation is a crucial method for the construction of
O-glycosyl bonds, which are found in natural products and biolog-
ically active compounds.1 Many O-glycosylation methods have
been disclosed2 since the emergence of the Koenigs–Knorr proce-
dure. For example, Schmidt and Kinzy have reviewed the glycosyl-
ation with trichloroacetimidate derivatives,2c which has two
attractive features. One is the smooth promotion of the reaction
by catalytic amounts of Lewis acid under mild conditions, and
the other is the easy preparation of the glycosyl donor by treating
a 1-hydroxy carbohydrate with trichloroacetonitrile in the pres-
ence of a base such as NaH or DBU.
A more convenient method for preparing glycosyl donors would
be useful for generating the O-glycosyl bond. The high reactivity of
trichloroacetyl isocyanate, which usually reacts with alcohols
under neutral conditions to generate the corresponding N-trichlo-
roacetyl carbamate, is an attractive approach. We were also inter-
ested in knowing whether the N-trichloroacetyl carbamate group
would be a good leaving group for glycosylation. Some glycosyla-
etric amount of activators. Kunz and Zimmer reported the first
example of employing a glycosyl carbamate for glycosylation, uti-
lizing glycosyl N-allylcarbamates by activation of the allylic double
bond with a soft electrophile, dimethylmethylthiosulfonium tri-
flate (DMTST).3 Lacombe and co-workers reported glycosylation
using glycosyl N-phenylcarbamates and a stoichiometric amount
of BF3ꢀEt2O.4 Although Kiessling reported that glycosyl N-alkyl-
N-p-toluenesulfonylcarbamates were activated with a catalytic
amount of Me3SiOTf, N-unalkylated sulfonylcarbamates were not
activated under these conditions, and they required N-methylation
or N-cyanomethylation for catalytic activation.5
Redlich and co-workers6 were the first to report glycosylation
using glycosyl N-trichloroacetyl carbamate, activated with a stoi-
chiometric amount of Lewis acid. Jayakanthan and Vankar7
reported catalytic glycosylation with glycosyl N-trichloroacetyl car-
bamate, but the a:b selectivity was low.
We believed that a more efficient and stereoselective glycosyl-
ation could be achieved using a glycosyl trichloroacetyl carbamate
and by varying experimented conditions already reported by
Redlich and co-workers6 and Jayakanthan and Vankar.7 Reaction
conditions for catalytic and stereoselective glycosylation with gly-
cosyl trichloroacetyl carbamate have been devised in our labora-
tory.8 In this paper, we describe in detail catalytic and
stereoselective glycosylation using a glycosyl N-trichloroacetylcar-
* Corresponding author.
E-mail address: omuras@insti.kitasato-u.ac.jp (S. Omura).
¯
Present address: Division of Pharmaceutical Sciences, Graduate School of Natural
Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192,
Japan.
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.01.011

T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
741
Table 1
bamate and the catalytic one-pot dehydrative glycosylation of a 1-
hydroxy carbohydrate.
Effect of Lewis acids in glycosylation with glycosyl donor 2a
OBn
OH
O
O
BnO
BnO
2. Results and discussion
BzO
BzO
H
+
BnO
O
N
CCl3
BzO
OMe
O
O
2.1. Preparation of glycosyl N-trichloroacetylcarbamate
2 (1.2 equiv)
3 (1.0 equiv)
A glycosyl N-trichloroacetylcarbamate donor 2 was prepared
OBn
O
Activator
(1.0 equiv)
BnO
from 2,3,4,6-tetra-O-benzyl-D-glucopyranose 1 (a:b = 86:14, ano-
BnO
meric ratio determined by 1H NMR spectroscopy in C6D6) by the
reaction of 1.1 equiv of trichloroacetyl isocyanate in dry CH2Cl2
at room temperature (Scheme 1). The reaction was complete after
30 min, and evaporation of CH2Cl2 in vacuo gave 2 quantitatively
O
BnO
CH2Cl2
MS5A
O
BzO
BzO
BzO
4
OMe
Entry
Activator
Temp. (°C)
Time
Yield (%)
a
:bb
as a mixture of anomers (a:b = 89:11, anomeric ratio determined
by 1H NMR spectroscopy in CDCl3). Donor 2 was employed in the
1
2
3
4
5
6
7
8
9
Zn(OTf)2
TfOH
rt
rt
rt
rt
rt
0
0
0
0
2 days
2 h
0
40
49
73
84
95
92
61
84
—
71:29
40:60
73:27
74:26
61:39
70:30
47:53
44:56
next glycosylation reaction without purification and could be
Sc(OTf)3
Mg(ClO4)2
Cu(OTf)2
1.5 h
2.5 h
1.5 h
20 min
1 h
stored in a refrigerator for several months. The
a-anomer of 2
could be isolated in 72% yield by column chromatography on silica
gel.
c
TMSOTf
TMSOTf
d
SnCl4
SnCl4
20 min
2 h
2.2. Glycosylation of 2,3,4,6-tetra-O-benzyl-D-glycosyl donors
a
b
c
The donor 2 (a:b = 89:11) was used unless otherwise noted.
2.2.1. Optimization of reaction conditions
With glycosyl donor 2 in hand, activation conditions for the gly-
cosylation of 2 with methyl 2,3,4-tri-O-benzoyl- -glucopyranoside
Determined by 1H NMR spectroscopy (500 MHz) and HPLC.
TMSOTf (1.2 equiv) was employed.
d
D
TMSOTf (0.2 equiv) was employed.
(3)9 (1.0 equiv) were screened in CH2Cl2 over 5 Å molecular sieves
(5 Å MS). Although Zn(OTf)2 did not activate donor 2 (Table 1, entry
1), glycosylation proceeded moderately using TfOH and Sc(OTf)3
(entries 2 and 3). The same reaction proceeded slowly using other
Lewis acids such as Mg(ClO4)2 and Cu(OTf)2, even at room temper-
ature (entries 4 and 5). It was found that 1.2 equiv of TMSOTf
smoothly activated the glycosylation process at 0 °C to afford
the disaccharide 410 in 95% yield as a mixture of anomers
Table 2
a
-Selective glycosylation with glycosyl donor 2a
OBn
OH
O
O
BnO
BnO
BzO
BzO
H
N
+
BnO
O
CCl3
BzO
OMe
O
O
(a
:b = 61:39, anomeric ratio determined by 1H NMR spectroscopy
2 (1.2 equiv)
3 (1.0 equiv)
in CDCl3 and HPLC) (entry 6). The use of a catalytic amount of
TMSOTf (0.2 equiv) promoted glycosylation in a yield similar to
that obtained using stoichiometric conditions (92% yield, entry
7). Glycosylation using SnCl4 as a promoter gave 4 in lower yield
than when using either catalytic or stoichiometric amounts of
TMSOTf (entries 8 and 9).
OBn
O
Activator
BnO
BnO
Et2O
BnO
MS5A
0 oC
O
O
BzO
BzO
BzO
OMe
4a
Entry
Activator (equiv)
Time (h)
Yield (%)
a
:bb
Next, we investigated the combination of solvent and Lewis
acid for
ity ( :b = 87:13) was observed for TMSOTf-catalyzed glycosyla-
tion in Et2O (Table 2, entry 1). The -selectivity ratio was
a-selective glycosylation with 2 and 3. Good a-selectiv-
1
2
TMSOTf (1.2)
TMSClO4 (1.2)
TMSClO4 (0.2)
TMSClO4 (0.1)
8
1
3
98
99
97
98
87:13
93:7
94:6
93:7
a
a
3
4c
18
further improved (a:b = 93:7) by changing the activator to TMS-
ClO4 (entry 2).11 When a catalytic amount (20 mol %) of TMSClO4
a
b
c
The donor 2 (a:b = 89:11) was used unless otherwise noted.
Determined by 1H NMR spectroscopy (500 MHz) and HPLC.
was employed, the reaction proceeded smoothly to give 4 in 97%
The
a isomer of 2 was employed.
yield and high
a-selectivity (a:b = 94:6, entry 3). Even 10 mol %
of TMSClO4 catalyzed the glycosylation efficiently (
a:b = 93:7,
entry 4).
tative yields of disaccharides 4 were obtained from both the stoi-
chiometric and catalytic glycosylation reactions. Interestingly,
catalytic glycosylation required the presence of 5 Å MS, since the
TMSClO4-catalyzed glycosylation did not proceed in the presence
of 4 Å MS or 3 Å MS. The reasons for the outstanding effects of
5 Å MS are not clear, but similar effects of 5 Å MS have been ob-
served in the catalytic glycosylation of glycosyl fluorides.12
Subsequently, we turned to b-selective glycosylation
Purified
tion with TMSClO4 (Table 2, entry 4), provided the same
tivity as using an ,b-mixture of 2 (Table 2, entry 3). These results
suggested that TMSClO4 effectively activates the carbamate car-
bonyl group of 2, resulting in the formation of an oxonium cation
intermediate. Catalytic glycosylation required longer reaction
times compared to stoichiometric glycosylation, but nearly quanti-
a
isomer of 2, used in catalytic
a
-selective glycosyla-
a
,b-selec-
a
(a
:b = 6:94) performed in MeCN13 containing a stoichiometric
amount of TMSOTf14 (Table 3, entry 1) with 2 and 3. The reaction
-selective
OBn
O
OBn
O
O
proceeded at a lower temperature (ꢁ40 °C) than the
a
BnO
BnO
BnO
BnO
OCN
CCl3
H
reaction in Et2O. When a catalytic amount of TMSOf was employed
in MeCN, the desired glycoside was obtained with lower b-selectiv-
ity (13:87) and in lower yield (51%, entry 3). Efficient catalytic b-
selective glycosylation was realized by using 20 mol % of TMSOTf
in EtCN to afford disaccharide 4 in 99% yield, with a ratio of
BnO
O
N
CCl3
BnO
(1.1 equiv)
OH
1 (α/β = 86/14)
CH2Cl2
O
O
0 °C ~ r.t., 0.5 h
(1.0 equiv)
2 (quant., α/β = 89/11)
Scheme 1. Preparation of glycosyl donor 2.

742
T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
Table 3
previous procedure (entry 4). The procedure for the one-pot cata-
b-Selective glycosylation with glycosyl donor 2a
lytic glycosylation was slightly modified to put 5 Å MS into the
reaction medium after preparing the glycosyl donor. The catalytic
one-pot dehydrative glycosylation proceeded stereoselectively in
the presence of 5 Å MS (entries 2 and 5). We believe that the
one-pot catalytic glycosylation might require 5 Å MS. The presence
of 5 Å MS in catalytic reactions prevents the hydrolysis of Lewis
acids by trace amounts of H2O in the reaction medium. The ease
of the present glycosylation method, especially for one-pot dehyd-
rative glycosylation, will be useful in the synthesis of oligosaccha-
rides or bioactive compounds having carbohydrate moieties.
OBn
OH
O
O
BnO
BnO
BzO
BzO
H
N
+
BnO
O
CCl3
BzO
OMe
O
O
2 (1.2 equiv)
3 (1.0 equiv)
OBn
O
TMSOTf
Solvent
BnO
BnO
O
BnO
O
BzO
MS5A
BzO
–40 oC
4b
BzO
OMe
Entry Activator
(equiv)
Solvent Temp.
Time
Yield
(%)
a
:bb
2.2.3. Scope of stereoselective glycosylation with
N-trichloroacetylcarbamate
(°C)
1
2
3
1.2
0.2
0.2
MeCN
MeCN
MeCN
ꢁ40
—
0
40 min 93
6:94
—
13:87
Next, the scope and limitations of catalytic and stereoselective
glycosylation with 2 were investigated by using various glycosyl
—
0
12 h
2.5 h
51
acceptors under
(Table 5).
a- and b selective glycosylation conditions
then rt
ꢁ40
4c
0.2
EtCN
40 min 93
1 h
7:93
The glycosylation of 2,3,4-tri-O-benzylated acceptor 516 bearing
then ꢁ23
a primary hydroxy group proceeded smoothly to afford the corre-
a
b
c
The donor 2 (
Determined by 1H NMR spectroscopy (500 MHz) and HPLC.
The isomer of 2 was employed.
a:b = 89:11) was used unless otherwise noted.
sponding disaccharides 11.17 The
a and b selectivities were similar
to those obtained using 3 as the glycosyl acceptor (entries 1 and 2).
a
Glycosyl donors 6 and 7,13 which have a secondary hydroxy group,
reacted similar to 3 and 5 under a-selective conditions (TMSClO4 in
a
:b = 7:93 (entry 4). The use of EtCN as the solvent therefore
Et2O) (entries 3 and 5), whereas they reacted slowly in b-selective
glycosylation conditions (TMSOTf in EtCN) and the observed b-
selectivities were slightly lower (entries 4 and 6). Cholesterol (8),
which does not have a sugar moiety, is also a good acceptor for
greatly improved both b-selectivity and chemical yield.
2.2.2. One-pot dehydrative glycosylation
Most conventional glycosylation reactions have been conducted
in two steps: (1) isolation of a glycosyl donor having a latent-leav-
ing group at the anomeric position and (2) activation of the leaving
group in the presence of a glycosyl acceptor. When glycosyl donors
are unstable and difficult to isolate, it is desirable to perform the
glycosylation by derivatizing a stable 1-hydroxy carbohydrate with
a reactive glycosyl donor in situ, followed by activation in a one-
pot manner. Since there are no side-products in the preparation
of 2, one-pot glycosylation (i.e., dehydrative glycosylation)15 of
the 1-hydroxy sugar 1 was investigated (Table 4). In this dehydra-
tive glycosylation starting from 1, CH2Cl2 was used as the co-sol-
vent in the preparation of the carbamate donor 2 because of the
low solubility of 1 in Et2O and EtCN. Before adding TMSClO4 or
TMSOTf to the reaction mixture, acceptor 3 was added in either
Et2O or EtCN. By following this procedure, the stoichiometric
one-pot glycosylation proceeded smoothly using 1.5 equiv of TMS-
a
- and b-selective glycosylation (entries 7 and 8). Glycosylation
with protected serine derivatives 918 afforded the corresponding
isomer 15a and b isomer 15b19 in high yields (entries 9 and
a
10). These results suggest that the present glycosylation method
can be employed in glycoprotein research. When the acceptor
has a tertiary hydroxy group, as in the case of tert-BuOH (10),
the
a-selective reaction proceeds efficiently, given a sufficiently
long reaction time (entry 11). On the other hand, the b-selective
reaction proceeds slowly to afford the corresponding glycoside in
low yield and with only moderate b selectivity (entry 12).
2.3. Glycosylation of various glycosyl
N-trichloroacetylcarbamates
2,3,4,6-Tetra-O-benzyl-
D
-galactosyl 18, 2,3,4,6-tetra-O-benzyl-
-mannnosyl donors
D-mannnosyl 20 and 2,3-di-O-benzyidene-
D
ClO4 in Et2O or TMSOTf in EtCN to afford the
respectively, in high yields (entries 1 and 3). One-pot catalytic gly-
a- or b-glycoside,
22 were prepared from the corresponding 1-hydroxy sugars,
17,20 1921 and 2122 according to standard procedures (Scheme 2).
cosylation in the absence of 5 Å MS did not proceed when using the
The
a- and b-selective glycosylations with galactosyl donor 18
Table 4
One-pot dehydrative glycosylationa
OBn
O
O
BnO
OBn
O
OCN CCl3
(1.5 equiv)
CH2Cl2
BnO
3 (1.0 equiv)
Activator
BnO
BnO
BnO
O
O
BzO
BzO
BnO
Solvent
MS5A
OH
BzO
r.t., 1 h
1 (1.0 equiv)
4
OMe
Entry
Activator (equiv)
Solventb
Reaction conditions
Yield (%)
a
:bc
1d
2
TMSClO4 (1.5)
TMSClO4 (0.2)
TMSOTf (1.5)
TMSOTf (0.2)
TMSOTf (0.2)
Et2O
Et2O
EtCN
EtCN
EtCN
0 °C, 0.5 h
0 °C, 0.5 h
ꢁ40 °C, 0.5 h then ꢁ23 °C, 0.5 h
ꢁ40 °C, 0.5 h then ꢁ23 °C, 0.5 h
ꢁ40 °C, 1 h then –23 °C, 1 h
99
88
88
0
93:7
91:9
8:92
—
3d
4d
5
85
12:88
a
b
c
The donor 2 (a:b = 89:11) was used unless otherwise noted.
Solvent/CH2Cl2 = 5:1.
Determined by 1H NMR spectroscopy (500 MHz) and HPLC.
5 Å MS was not used.
d

T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
743
Table 5
Stereoselective glycosylation of 2 with acceptor alcohola
TMSClO4
OBn
O
or
OBn
O
BnO
BnO
TMSOTf
(20 mol%)
BnO
BnO
H
+
ROH
BnO
O
N
CCl3
(1.0 equiv)
BnO
OR
Solvent
MS5A
2 (1.2 equiv)
O
O
Entry
Acceptor
Activator
Solvent
Temp. (°C)
Time (h)
Product
Yield (%)
a
:bb
OH
O
OBn
O
1
2
TMSCl4
TMSOTf
Et2O
EtCN
0
4
0.5
3
98
99
94:6
7:93
ꢁ40
BnO
BnO
BnO
BnO
then ꢁ23
BnO
OMe
BnO
O
O
5
BnO
BnO
BnO
11
OMe
OBn
O
OBn
O
3
4
TMSClO4
TMSOTf
Et2O
EtCN
0
5
1.5
16
93
83
90:10
15:85
ꢁ40
HO
BnO
BnO
OBn
O
BnO
then ꢁ23
BnO
BnO
O
OMe
BnO
12
OBn
6
BnO
OMe
Ph
O
5
6
TMSClO4
TMSOTf
Et2O
EtCN
0
ꢁ20
3
1
86
74
96:4
17:83
O
O
O
BnO
BnO
HO
OMe
BnO
BnO
OMe
BnO
O
7
O
O
Ph
O
13
7
8
TMSClO4
TMSOTf
Et2O
EtCN
0
0
4
2
93
88
94:6
21:79
then rt
1
H
H
H
OBn
O
BnO
BnO
H
H
H
8
BnO
HO
HO
O
O
14
NHCbz
COOMe
OBn
O
9
10
TMSClO4
TMSOTf
Et2O
EtCN
0
3
0.5
4.5
90
88
92:8
20:80
ꢁ40
BnO
BnO
NHCbz
COOMe
then ꢁ23
BnO
9
15
OBn
O
11
TMSClO4
TMSOTf
Et2O
EtCN
0
rt
19
96
89
38
86:14
39:61
HO
12c
BnO
BnO
BnO
16
O
10
a
b
c
The donor 2 (
Determined by 1H NMR spectroscopy (500 MHz) and HPLC.
Glycosyl donor 2 (1.0 equiv) and acceptor 10 (2.0 equiv) were employed.
a:b = 89:11) was used unless otherwise noted.
Glycosylation of mannosyl donor 20 with acceptor 24 using
TMSOTf in MeCN proceeded smoothly, but the glycoside was ob-
O
BnO
BnO
OBn
O
BnO
BnO
OBn
O
a
OCN
CCl3
H
(1.0 equiv)
tained as the major product (entry 4). In order to prepare the b gly-
coside more selectively, we employed the O-benzylidene-
protected donor 22.24a As expected, b selectivity was enhanced,
but the yield was low when the reaction was carried out at
ꢁ20 °C (entry 5). The same glycosylation at room temperature gave
the desired glycosides in low yield because of the deprotection of
the benzylidene acetal with TMSOTf (entry 6).
BnO
O
N
CCl3
CH2Cl2
r.t., 0.25 h
BnO
OH
O
O
17
18 (quant., α/β = 85/15)
O
BnO
BnO
OBn
O
BnO
BnO
OBn
O
OCN
CCl3
(1.0 equiv)
BnO
H
BnO
O
N
CCl3
CH2Cl2
r.t., 1.5 h
OH
O
O
19
2.4. Model study for the construction of the glycosyl bond in
natural products
20 (99%, α/β = 90/10)
O
OBn
O
Ph
CCl3
OBn
O
O
O
We are interested in the synthesis of irumamycin (27) (Fig. 1),
initially isolated from culture broth of Streptomyces subflavus
subsp., Irumaensis nov. subsp. AM-3603, and which exhibits high
activity against phytopathogenic fungi.25 The sugar moiety of iru-
Ph
O
OCN
BnO
O
H
(1.0 equiv)
BnO
O
N
CCl3
CH2Cl2
r.t., 1 h
OH
21
O
O
22 (95%, α/β = 88/12)
mamycin, 2-deoxy-D-rhamnose, is connected to the aglycon of iru-
Scheme 2. Preparation of various glycosyl donors.
mamycin by a b-glycosidic bond. Roush and co-workers have
already reported that the stereoselective construction of the
2-deoxy-D-rhamnose moiety was achieved by glycosylation with
2-SPh, 6-bromoglucose derivatives, followed by reduction of bro-
mine and the thiophenyl group.26 The selective glycosylation of
2-deoxysugars is still a challenging topic in synthetic organic
gave good yields and selectivities (Table 6, entries 1 and 2). The a-
selective reaction between the mannosyl donor 20 and the accep-
tor 2423 smoothly proceeded in good yield and selectivity (entry 3).

744
T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
Table 6
Glycosylation of various glycosyl N-trichloroacetylcarbamates
TMSClO4
or
TMSOTf
(20 mol%)
ROH
N-Trichloroacetylcarbamate
+
Product
Donor
(1.2 equiv)
Acceptor
(1.0 equiv)
Solvent
MS5A
Entry
Donor
Acceptor
Activator
Solvent
Temp. (°C)
Time (h)
Product
Yield (%)
a
:ba
18b
3
TMSClO4
TMSOTf
Et2O
EtCN
0
ꢁ40
1
20
90
96
87:13
19:81
BnO
1
2
OBn
O
BnO
BnO
BzO
O
O
BzO
BzO
23
OMe
20c
TMSOTf
TMSOTf
Et2O
MeCN
rt
ꢁ40
0.25
0.5
99
99
94:6
76:24
OH
O
BnO
BnO
OBn
O
3
4
AcO
AcO
BnO
AcO
O
OMe
O
AcO
24
AcO
AcO
25
OMe
22d
TMSOTfe
TMSOTfe
CH2Cl2
CH2Cl2
ꢁ20
4
1.5
25
34
27:73
22:78
OH
O
OBn
O
5
6
Ph
O
rt
AcO
AcO
O
BnO
AcO
O
OMe
O
24
AcO
AcO
AcO
26
OMe
a
b
c
Determined by 1H NMR spectroscopy (500 MHz) and HPLC.
Donor 18 (
Donor 20 (
Donor 22 (
a
a
a
:b = 85:15) was used.
:b = 90:10) was used.
:b = 88:12) was used.
d
e
TMSOTf (1.2 equiv) was employed.
Table 7
O
O
HO
O
O
Model study for the construction of the glycosyl-bond of irumamycinb
H2N
O
OH
O
O
O
Br
O
HO
Br
O
AcO
TBSO
O
30 (4.0 equiv)
AcO
TBSO
H
O
PhS
OH
O
N
CCl3
TMSOTf
(0.3 equiv)
PhS
O
O
31
Solvent
MS5A
29 (1.0 equiv)
27
Entry
Solvent
Temp. (°C)
Time (h)
Yield (%)
a
:ba
Figure 1. The structure of irumamycin (27).
1
2
3
CH2Cl2
CH2Cl2
1,2-Dichloroethane
ꢁ5
14
19.5
0.25
19
56
70
78:22
20:80
19:81
rt
chemistry. The glycosyl donor 29 was synthesized from 1-hydroxy
sugar 2826 with N-trichloracetylisocyanate in CH2Cl2 in quantita-
tive yield using our general procedure (Scheme 3). The model
study for the stereoselective construction of the b-glycosylic bond
of irumamycin was performed using 2-propanol (30) as an accep-
40
Determined by 1H NMR spectroscopy (500 MHz) and HPLC.
The donor 29 (a:b = 90:10) was used.
a
b
tor. Undesired a-selectivity was observed when glycosylation was
to form intermediate 34, which collapses to an oxocarbenium cat-
ion intermediate along with trimethylsilyl N-trichloroacetyl carba-
mate (35). A glycosyl acceptor then reacts with intermediate 35 to
give glycoside 36 and N-trichloroacetyl carbamic acid (37). The low
reactivity and b selectivity obtained in the glycosylation of benzyl-
idene-protected mannosyl donor 22 might be explained by the
interaction of trimethylsilyl N-trichloroacetyl carbamate or N-tri-
chloroacetyl carbamic acid.
conducted at ꢁ5 °C (Table 7, entry 1), while the same glycosylation
reaction at room temperature gave the product in improved yield
as well as with the desired b selectivity (entry 2). Glycosylation
at higher temperature (40 °C) using 1,2-dichlorethane as a solvent
resulted in acceptable yield and b selectivity (entry 3).
2.5. Plausible reaction mechanism
A mechanism for glycosylation with glycosyl N-trichloroacetylc-
arbamate by TMSOTf as an activator is proposed in Scheme 4. The
carbonyl group of the glycosyl donor 33 is activated with TMSOTf
3. Conclusions
The
a- or b-selective glycosylation using glycosyl N-trichloro-
acetylcarbamate 2 as a glycosyl donor proceeded efficiently by
activating the donor with a catalytic amount of TMSClO4 in Et2O
or TMSOTf in EtCN in the presence of 5 Å MS. Preparation of 2 from
a 1-hydroxy carbohydrate 1 and successive stereoselective and cat-
alytic glycosylations were also realized in a one-pot manner, and
O
Br
O
Br
O
AcO
TBSO
OCN
CCl3
AcO
TBSO
H
N
(1.0 equiv)
PhS
O
CCl3
PhS
CH2Cl2
r.t., 1.5 h
OH
O
O
28
29 (quant., α/β = 90/10)
the desired
a or b glycoside was obtained directly from 1. The ease
of the present glycosylation approach, especially for the one-pot
Scheme 3. The synthesis of glycosyl donor 31.

T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
745
OBn
O
H
OBn
O
O
N
CCl3
BnO
BnO
+
BnO
BnO
H
OH
O
37
OR
BnO
BnO
O
N
CCl3
36
33
O
O
Me3SiOTf
ROH
OBn
O
OBn
O
OTf
BnO
BnO
BnO
BnO
H
H
BnO
O
N
CCl3
BnO
N
O
CCl3
OTf
O
O
O
O
35
34
Me3Si
Me3Si
Scheme 4. Plausible reaction mechanism of TMSOTf-catalyzed glycosylation of 33.
dehydrative glycosylation, will be useful in the synthesis of oligo-
saccharides or other bioactive compounds having carbohydrate
moieties.
4.2. Preparation of the glycosyl N-trichloroacetylcarbamate
4.2.1. 2,3,4,6-Tetra-O-benzyl- -glucopyranosyl N-
D
trichloroacetylcarbamate (2a and 2b)
To the stirred solution of 2,3,4,6-tetra-O-benzyl-D-glucopyra-
4. Experimental
nose (1) (1.00 g, 1.85 mmol) in dry CH2Cl2 was added trichloroace-
tyl isocyanate (0.24 mL, 2.01 mmol) at 0 °C. After the reaction
mixture was stirred at room temperature for 0.5 h, the solvent
was evaporated in vacuo to give a mixture of 2a and 2b as colorless
4.1. General methods
1H NMR spectra were measured on a Varian VXR-300 (300 MHz)
or on a JEOL JNM-ECP500 (500 MHz) spectrometer; chemical shifts
(d) are reported in parts per million relative to internal tetrameth-
ylsilane. Splitting patterns are designated as s, singlet; d, doublet; t,
triplet; m, multiplet; br, broad. 13C NMR spectra were measured on
a Varian VXR-300 (75 MHz) or on a JEOL JNM-ECP500 (125 MHz)
spectrometer with complete proton decoupling. Chemical shifts
are reported in parts per million relative to tetramethylsilane, using
the residual solvent resonance as the internal standard (CDCl3;
77.0 ppm, C6D6; 128.0 ppm). High-performance liquid chromatog-
raphy (HPLC) was carried out using a Senshu UV–vis Detector
(SSC-5410) and Senshu HPLC-pump (SSC-3461) with Senshu Pak
PEGASIL Silica Gel 60-5 (normal phase: 4.6 ø ꢂ 250 mm). Analytical
TLC was done on precoated (0.25 mm) Silica Gel 60 F254 plates
(E. Merck). Thin-layer chromatography (TLC) was performed on
Wakogel B-5F (Wako). Column chromatography was performed
on Silica Gel 60 (Kanto Chemical Co., Inc. Silica Gel 60 N (63–
210 mm)). All reactions were carried out under an argon atmo-
sphere in dried glassware, unless otherwise noted. All reagents
were purchased from Tokyo Kasei Kogyo, Kanto Chemical, Fluka
or Sigma–Aldrich Chemical Co. and used without further purifica-
tion, unless otherwise noted. Acetonitrile and propionitrile were
distilled from P2O5 and then from CaH2, and were stored over 4 ÅA
molecular sieves. Dichloromethane was freshly distilled from
CaH2. Powdered and pre-dried molecular sieves 4 ÅA, and 5 ÅA were
used in glycosylation. A 0.1 M solution of TMSClO4 in Et2O was pre-
pared as follows: To a solution of AgClO4 (38.4 mg, 185
Et2O (1.85 mL) at 0 °C was added TMSCl (20.5 mg, 189
this mixture was stirred. After the mixture was left standing for
10 min without stirring, the supernatant was used for glycosylation
as a catalyst. [Caution: Explosive reagent!]
syrup (quant.,
copy). If necessary, the
and the b isomer 2b (Rf 0.34, 3:1 hexanes–AcOEt) were separated,
and the isomer was isolated in 72% yield by column chromato-
graphy on silica gel (7:1 hexanes–AcOEt).
Isomer (2a): 1H NMR (300 MHz, C6D6): d 8.11 (s, 1H, N–H),
a
:b = 87:11, as determined by 1H NMR spectros-
a
isomer 2a (Rf 0.40, 3:1 hexanes–AcOEt)
a
a
7.05–6.75 (m, 20H, Ph–H), 6.33 (d, J1,2 3.5 Hz, 1H, H-1), 4.65 (d, J
11.4 Hz, 1H, CH2Ph), 4.64 (d, J 11.1 Hz, 1H, CH2Ph), 4.53 (d, J
11.4 Hz, 1H, CH2Ph), 4.37 (d, J 11.1 Hz, 1H, CH2Ph), 4.23 (d, J
11.4 Hz, 1H, CH2Ph), 4.13 (d, J 11.4 Hz, 1H, CH2Ph), 4.12 (d, J
12.0 Hz, 1H, CH2Ph), 4.00 (d, J 11.1 Hz, 1H, CH2Ph), 3.96 (m, 2H,
H-3, H-5), 3.62 (dd, J 9.7, 9.5 Hz, 1H, H-4), 3.44 (dd, J6a,6b 11.0,
J5,6a 3.2 Hz, 1H, H-6a), 3.29 (dd, J6a,6b 11.0, J5,6b 1.5 Hz, 1H, H-6b),
3.29 (dd, J2,3 9.5, J1,2 3.5 Hz, 1H, H-2). 13C NMR (75 MHz); d 158.0
(C@O), 150.0(C@O), 140.0, 138.4, 129.1, 129.0, 128.9, 128.84,
128.84, 128.81, 128.80, 128.79, 128.55, 128.54, 128.54, 128.49,
128.45, 128.23, 128.23, 128.1, 128.0, 95.0 (C-1), 92.5 (CCl3), 82.3
(C-3), 79.7 (C-2), 77.6 (C-4), 76.0, 75.7, 74.9 (C-5), 73.98, 73.97,
68.9 (C-6).
b Isomer (2b): 1H NMR (300 MHz, C6D6): d 7.76 (s, 1H, N–H),
7.04–6.72 (m, 20H, Ph–H), 5.54 (d, J1,2 7.5 Hz, 1H, H-1), 4.58 (d, J
11.3 Hz, 1H, CH2Ph), 4.54 (d, J 11.3 Hz, 1H, CH2Ph), 4.51 (d, J
11.3 Hz, 1H, CH2Ph), 4.47 (m, 2H, CH2Ph), 4.30 (d, J 11.3 Hz, 1H,
CH2Ph), 4.10 (d, J 12.0 Hz, 1H, CH2Ph), 3.95 (d, J 11.3 Hz, 1H,
CH2Ph), 3.59 (dd, J4,5 9.8, J3,4 9.4 Hz, 1H, H-4), 3.40–3.35 (m, 2H,
H-2, H-3), 3.33 (dd, J6a,6b 10.8, J5,6a 3.1 Hz, 1H, H-6a), 3.28 (dd,
J6a,6b 10.8, J5,6b 2.1 Hz, 1H, H-6b), 3.06 (ddd, J4,5 9.8, J5,6a 3.1, J5,6b
2.1 Hz, 1H, H-5). 13C NMR (75 MHz): d 157.7 (C@O), 149.1 (C@O),
139.4, 139.3, 139.1, 138.9, 129.00, 128.96, 128.91, 128.5, 128.41,
128.41, 128.2, 97.1 (C-1), 92.4 (CCl3), 97.1 (C-3), 81.1 (C-2), 77.7
(C-4), 76.3 (C-5), 76.0, 75.3, 75.2, 74.0, 68.9 (C-6).
0
0
0
l
mol) in
mol) and
l

746
T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
4.3. Glycosylation with 2,3,4,6-tetra-O-benzyl-
D-glycosyl donors
4.3.2.2. Procedure for b-selective, one-pot dehydrative glyco-
sylation with 2,3,4,6-tetra-O-benzyl- -glucopyranose (Table 4,
entry 5). To the stirred solution of 2,3,4,6-tetra-O-benzyl- -glu-
D
4.3.1. Reaction optimization
D
4.3.1.1. Typical procedure for glycosylation with 2,3,4,6-tetra-O-
benzyl- -glucopyranosyl N-trichloroacetylcarbamate (2a and
2b): methyl 2,3,4,6-tetra-O-benzyl- ,b- -glucopyranosyl-(1?6)-
2,3,4-tri-O-benzoyl- -glucopyranoside (Table 1, entry 7). To
a stirred suspension of 5 Å MS (118.1 mg, 5 Å MS:acceptor = 3 g/
1 mmol), (34.9 mg, 47.8 mol) and acceptor (20.1 mg,
mol) in dry CH2Cl2 (2.5 mL) was added TMSOTf (1.4 L,
mol) at 0 °C. After the reaction mixture was stirred at 0 °C
for 1 h, the reaction was quenched by adding satd NaHCO3 solution,
andthemixturewasfilteredthroughaCelitepad. Thefiltratewasex-
tracted with AcOEt and the combined organic extracts were washed
with H2O and brine, dried over anhyd Na2SO4, and concentrated. The
crude product was purified by preparative TLC (silica gel, 10:1 ben-
zene–AcOEt) to afford known disaccharide 410 (a colorless oil,
copyranose (1) (20.4 mg, 37.7 mmol) in dry CH2Cl2 (0.25 mL) was
added trichloroacetyl isocyanate (6.6 mL, 56.3 mmol) at room
temperature. The reaction mixture was stirred at room tempera-
ture for 0.5 h. 5 Å MS (114 mg) and a solution of acceptor 3
(28.3 mg, 55.9 mmol) in dry EtCN (1.25 mL) were added to the
reaction mixture, followed by cooling to ꢁ40 °C. To the resulting
suspension was added TMSOTf (1.3 mL, 7.5 mmol). After the reac-
tion mixture was stirred at ꢁ40 °C for 1 h and ꢁ20 °C for 1 h, the
reaction was quenched by adding satd NaHCO3 solution and the
mixture was filtered through a Celite pad. The filtrate was ex-
tracted with AcOEt, and the combined organic extracts were
washed with H2O and brine and dried over anhyd Na2SO4. The
crude product was purified by preparative TLC (silica gel, 10:1
benzene–AcOEt) to afford known disaccharide 410 (a colorless oil,
D
a
D
a-D
2
l
3
39.7
7.93
l
l
l
37.6 mg, 36.5
determined by 1H NMR spectroscopy (500 MHz).
Isomer (4a): 1H NMR (300 MHz, CDCl3): d 7.99–7.93 (m, 4H,
l
mol, 92%) as a mixture of anomers (
a
:b = 70:30 as
32.9 mg, 85%) as a mixture of anomers (
a:b = 12:88), as deter-
mined by 1H NMR spectroscopy (500 MHz).
a
Ph–H), 7.88–7.84 (m, 2H, Ph–H), 7.54–7.11 (m, 29H, Ph–H), 6.14
(t, J2,3, J3,4 9.7 Hz, 1H, H-3), 5.52 (dd, J4,5 10.4 Hz, J3,4 9.7 Hz, 1H,
H-4), 5.24–5.19 (m, 2H, 1-H, H-2), 4.91 (d, J 11.0 Hz, 1H, –CH2Ph),
4.82 (d, J 11.0 Hz, 1H, –CH2Ph), 4.77 (d, J 11.0 Hz, 1H, –CH2Ph),
4.3.3. Scope of the stereoselective glycosylation with N-
trichloroacetylcarbamate
4.3.3.1. Methyl 2,3,4,6-tetra-O-benzyl-
(1?6)-2,3,4-tri-O-benzyl- -glucopyranoside (11a) (Table 5,
entry 1). The glycosylation was performed according to the
typical procedure employing carbamate donor (34.5 mg,
47.3 mol), acceptor (18.5 mg, 39.8 mol) and TMSClO4
(80.0 L, 0.2 M solution in Et2O, 8.0 mmol) in Et2O (3.0 mL) at
0 °C for 4 h. An anomeric mixture of the known disaccharide
1117 (38.8 mg, 99%,
:b = 94:6) was obtained as a colorless oil
a,b-D-glucopyranosyl-
a
-D
4.76 (d, J 12.3 Hz, 1H, –CH2Ph), 4.74 (d, J1 ,2 3.5 Hz, 1H, H-10),
4.62 (d, J 12.3 Hz, 1H, –CH2Ph), 4.54 (d, J 12.0 Hz, 1H, –CH2Ph),
4.45 (d, J 11.0 Hz, 1H, –CH2Ph), 4.37 (d, J 12.0 Hz, 1H, –CH2Ph),
4.32 (ddd, J4,5 10.4 Hz, J5,6a 6.7 Hz, J5,6b 2.1 Hz, 1H, H-5), 3.96 (t,
J2,3, J3,4 9.2 Hz, 1H, H-3), 3.88–3.83 (m, 2H, H-6), 3.66–3.61 (m,
0
0
2
l
5
l
l
2H, H-40, H-50), 3.58 (dd, J6 a,6 b 11.0 Hz, J5 ,6 a 2.5 Hz, 1H, H-60a),
a
0
0
0
0
3.53 (dd, J1 ,2 9.7 Hz, 3.5 Hz, 1H, H-20), 3.50 (dd J6 a,6 b 11.0 Hz,
after the purification by preparative TLC (silica gel, 10:1 ben-
zene–AcOEt). The NMR data for 11a matched those previously
reported.17 The anomeric ratio of 11 was determined by HPLC
analysis [eluent, 4:1 hexanes–AcOEt; flow rate, 1.0 mL/min; tR
0
0
0
0
J5 ,6 b 2.1 Hz, 1H, H-60b), 3.43 (s, 3H, –OCH3).
0
0
b Isomer (4b): 1H NMR (300 MHz, CDCl3): d 7.99–7.91 (m, 4H,
Ph–H), 7.86–7.83 (m, 2H, Ph–H), 7.54–7.12 (m, 29H, Ph–H), 6.17
(t, J2,3, J3,4 9.7 Hz, 1H, H-3), 5.47 (t, J3,4, J4,5 9.7 Hz, 1H, H-4), 5.25
(dd, J2,3 9.7, J1,2 3.5 Hz, 1H, H-1), 5.20 (d, J1,2 3.5 Hz, 1H, H-1),
5.06 (d, J 10.8 Hz, 1H, –CH2Ph), 4.91 (d, J 11.0 Hz, 1H, –CH2Ph),
4.80 (d, J 11.0 Hz, 1H, –CH2Ph), 4.76 (d, J 11.0 Hz, 1H, –CH2Ph),
4.68 (d, J 10.8 Hz, 1H, –CH2Ph), 4.53 (d, J 12.3 Hz, 1H, –CH2Ph),
(11b,
b
disaccharide) = 14.8 min, tR (11a, a disaccharide)
17.2 min].
4.3.3.2. Methyl 2,3,4,6-tetra-O-benzyl-
(1?6)-2,3,4-tri-O-benzyl-b- -glucopyranoside (11b) (Table 5,
entry 2). The glycosylation was performed according to the typ-
ical procedure employing carbamate donor 2 (34.9 mg, 47.6 mol),
acceptor 5 (18.5 mg, 39.6 mol) and TMSOTf (1.4 L, 7.7 mol) in
a,b-D-glucopyranosyl-
D
4.51 (d, J 11.0 Hz, 1H, –CH2Ph), 4.47 (d, J1 ,2 7.8 Hz, 1H, H-10),
4.43 (d, J 12.3 Hz, 1H, –CH2Ph), 4.41–4.34 (m, 1H, H-50), 4.12 (dd,
J6a,6b 11.0, J5,6a 2.1 Hz, H-6a), 3.81 (dd, J6a,6b 11.0, J5,6ab 7.5 Hz, H-
6b), 3.67–3.56 (m, 4H, H-20, H-30, H-40, H-50), 3.48–3.43 (m, 2H,
H-60), 3.37 (s, 3H, –OCH3).
0
0
l
l
l
l
EtCN (3.0 mL) at ꢁ40 °C for 30 min then at ꢁ23 °C for 3 h. The ano-
meric mixture of the known disaccharide 1125 (38.0 mg, 97%,
a:b = 7:93) was obtained as a colorless oil after purification by pre-
parative TLC (silica gel, 10:1 benzene–AcOEt). The NMR data for
11b matched those previously reported.17 The anomeric ratio of
11 was determined by HPLC analysis [eluent, 4:1 hexanes–AcOEt;
4.3.2. One-pot dehydrative glycosylation
4.3.2.1. Procedure for the
glycosylation with 2,3,4,6-tetra-O-benzyl-
(Table 4, entry 2). To a stirred solution of 2,3,4,6-tetra-O-ben-
zyl- -glucopyranose (1) (20.3 mg, 37.5 mol) in dry CH2Cl2
(0.25 mL) was added trichloroacetyl isocyanate (6.6 L, 56.3 mol)
a-selective, one-pot dehydrative
D
-glucopyranose
flow rate, 1.0 mL/min; tR (11b, b disaccharide) 14.8 min, tR (11a,
a
disaccharide) 17.2 min].
D
l
l
l
at room temperature. The reaction mixture was stirred at room
temperature for 0.5 h. 5 Å MS (113 mg) and a solution of acceptor
4.3.3.3. Methyl 2,3,4,6-tetra-O-benzyl-
(1?4)-2,3,6-tri-O-benzyl-a- -glucopyranoside (12a) (Table 5,
entry 3). The glycosylation was performed according to the
a,b-D-glucopyranosyl-
D
3 (28.4 mg, 56.0
reaction mixture, followed by cooling to 0 °C. To the resulting sus-
pension was added TMSClO4 (37.0 L, 0.2 M solution in Et2O,
7.5 mol). After the reaction mixture was stirred at 0 °C for 3 h,
lmol) in dry Et2O (1.25 mL) were added to the
typical procedure employing carbamate donor
2 (35.2 mg,
l
48.2 mmol), acceptor 627 (18.5 mg, 39.8 mmol) and TMSClO4
(80.0 mL, 0.2 M solution in Et2O, 8.0 mmol) in Et2O (3.0 mL) at
0 °C for 5 h. The anomeric mixture of the known disaccharide
l
the reaction was quenched by adding satd NaHCO3 solution, and
the mixture was filtered through a Celite pad. The filtrate was ex-
tracted with AcOEt, and the combined organic extracts were
washed with H2O and brine, dried over anhyd Na2SO4. The crude
product was purified by preparative TLC (silica gel, 10:1 ben-
zene–AcOEt) to afford known disaccharide 410 (a colorless oil,
1228 (36.7 mg, 93%,
a:b = 90:10) was obtained as a colorless
oil after the purification by preparative TLC (silica gel, 10:1 ben-
zene–AcOEt). The NMR data for 12a matched those previously
reported.28 The anomeric ratio of 12 was determined by HPLC
analysis [eluent, 4:1 hexanes–AcOEt; flow rate, 1.0 mL/min; tR
34.0 mg, 88%) as a mixture of anomers (
a:b = 91:9), as determined
(12b,
12.4 min].
b
disaccharide) 12.0 min, tR (12a, a disaccharide)
by 1H NMR spectroscopy (500 MHz).

T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
747
4.3.3.4. Methyl 2,3,4,6-tetra-O-benzyl-
2,3,4-tri-O-benzyl- -glucopyranoside (12b) (Table 5, entry
4). The glycosylation was performed according to the typical
procedure employing carbamate donor 2 (35.7 mg, 49.0 mol),
acceptor 627 (18.3 mg, 39.5
mol) and TMSOTf (2.1 L in toluene
D
-glucopyranosyl-(1?4)-
acceptor 9 (10.5 mg, 41.5
tion in Et2O, 8.0
mixture of the known disaccharide 1519 (29.0 mg, 90%,
as a colorless oil after the purification by preparative TLC (silica gel,
7:1 benzene–AcOEt). The NMR data for 15 matched those previ-
ously reported.19 The anomeric ratio of 15 was determined by 1H
NMR spectroscopy (500 MHz).
l
mol) and TMSClO4 (80.0
l
L, 0.2 M solu-
a-
D
l
mol) in Et2O (3.0 mL) at 0 °C for 3 h. An anomeric
a:b = 92:8)
l
l
l
(0.15 mL), 11.6 mmol) in EtCN (3.0 mL) at 0 °C for 1.5 h. The ano-
meric mixture of the known disaccharide 1228 (32.3 mg, 83%,
a:b = 15:85) was obtained as a colorless oil after purification by
preparative TLC (silica gel, 10:1 benzene–AcOEt). The NMR data
for 11 matched those previously reported.28 The anomeric ratio
of 12 was determined by HPLC analysis [eluent, 4:1 hexanes–
AcOEt; flow rate, 1.0 mL/min; tR (12b, b disaccharide) 12.0 min, tR
4.3.3.10. Methyl (S)-2-((benzyloxycarbonyl)amino)-3-O-(2,3,4, 6-
tetra-O-benzyl-
entry 10). The glycosylation was performed according to the
typical procedure employing carbamate donor (34.4 mg,
47.3 mol), acceptor 9 (10.0 mg, 39.5 mol) and TMSOTf (1.4
in toluene (0.1 mL), 7.7
mol) in EtCN (3.0 mL) at ꢁ40 °C for
30 min then at ꢁ20 °C for 4.5 h. An anomeric mixture of the known
disaccharide 1519 (27.0 mg, 88%,
:b = 20:80) was obtained as a
a,b-D-glucopyranosyl)propanoate (15b) (Table 5,
2
(12a,
a
disaccharide) 12.4 min].
l
l
lL
l
4.3.3.5. Methyl 2,3,4,6-tetra-O-benzyl-
(1?3)-2-O-benzyl-4,6-O-benzylidene- -glucopyranoside (13a);
(Table 5, entry 5). The glycosylation was performed according
to the typical procedure employing carbamate donor 2 (35.2 mg,
48.2 mol) and TMSClO4
mol), acceptor 729 (14.8 mg, 39.7
(80.0 L, 0.2 M solution in Et2O, 8.0 mol) in Et2O (3.0 mL) at
0 °C for 3 h. An anomeric mixture of the known disaccharide 1330
(30.7 mg, 86%, :b = 96:4) was obtained as a colorless oil after puri-
a,b-D-glucopyranosyl-
a-D
a
colorless oil after the purification by preparative TLC (silica gel,
7:1 benzene–AcOEt). The NMR data for 15 matched those previ-
ously reported.19 The anomeric ratio of 15 was determined by 1H
NMR spectroscopy (500 MHz).
l
l
l
l
a
4.3.3.11. tert-Butyl 2,3,4,6-tetra-O-benzyl-
(16a) (Table 5, entry 11). The glycosylation was performed
according to the typical procedure employing carbamate donor 2
(34.8 mg, 47.9 mol), acceptor 10 (7.0 mg, 95.7 mol) and TMS-
ClO4 (80.0 L, 0.2 M solution in Et2O, 8.0 mol) in Et2O (3.0 mL)
at 0 °C for 19 h. An anomeric mixture of the known glycoside
1617 (25.2 mg, 89%,
:b = 87:13) was obtained as a colorless oil
a,b-D-glucopyranoside
fication by preparative TLC (silica gel, 10:1 benzene–AcOEt). The
NMR data for 13 matched those previously reported.30 The ano-
meric ratio of 13 was determined by 1H NMR spectroscopy
(500 MHz).
l
l
l
l
4.3.3.6. Methyl 2,3,4,6-tetra-O-benzyl-
2-O-benzyl-4,6-O-benzylidene-b- -glucopyranoside (13b)
(Table 5, entry 6). The glycosylation was performed according to
the typical procedure employing carbamate donor 2 (34.5 mg,
47.3 mol) and TMSOTf (1.4
mol), acceptor 729 (14.8 mg, 39.5
in toluene (0.1 mL), 7.7 mol) in EtCN (3.0 mL) at 0 °C for 1.5 h. An
anomeric mixture of the known disaccharide 1330 (26.1 mg, 74%,
:b = 17:83) was obtained as a colorless oil after purification by pre-
D
- glucopyranosyl-(1?3)-
a
D
after the purification by preparative TLC (silica gel, 10:1 hex-
anes–AcOEt). The NMR data for 16 matched those previously re-
ported.17a The anomeric ratio of 16 was determined by HPLC
analysis [eluent, 10:1 hexanes–AcOEt; flow rate, 1.0 mL/min; tR
l
l
lL
l
(16b, b-saccharide) = 10.6 min, tR (16a, a-saccharide) = 11.6 min].
a
4.3.3.12. tert-Butyl 2,3,4,6-tetra-O-benzyl-
(Table 5, entry 12). The glycosylation was performed according
to the typical procedure employing carbamate donor 2 (34.7 mg,
47.6 mol), acceptor 10 (7.0 mg, 94.4 mol) and TMSOTf (1.7
in toluene (0.1 mL), 9.5
D-glucopyranoside (16b)
parative TLC (silica gel, 10:1 benzene–AcOEt). The NMR data for 13
matched those previously reported.30 The anomeric ratio of 13 was
determined by 1H NMR spectroscopy (500 MHz).
l
l
lL
l
mol) in EtCN (3.0 mL) at ꢁ20 °C for
4.3.3.7. 3-O-(2,3,4,6-Tetra-O-benzyl-
a
,b-
D
-glucopyranosyl)cho-
30 min, at 0 °C for 2.5 h, and then at room temperature for 96 h.
lesterol (14a) (Table 5, entry 7).
The glycosylation was per-
An anomeric mixture of the known disaccharide 1617a (10.8 mg,
formed according to the typical procedure employing carbamate
donor 2 (34.3 mg, 47.0 mol), acceptor 8 (15.3 mg, 39.6 mol)
and TMSClO4 (80.0 L, 0.2 M solution in Et2O, 8.0 mol) in Et2O
(3.0 mL) at 0 °C for 4 h. An anomeric mixture of the known glyco-
side 1431 (33.8 mg, 93%,
:b = 94:6) was obtained as a colorless oil
38%, a:b = 39:61) was obtained as a colorless oil after the purifica-
l
l
tion by preparative TLC (silica gel, 10:1 benzene–AcOEt). The NMR
data for 16 matched those previously reported.17a The anomeric ra-
tio of 16 was determined by 1H NMR spectroscopy (500 MHz).
l
l
a
after the purification by preparative TLC (silica gel, 10:1 benzene–
AcOEt). The NMR data for 14 matched those previously reported.31
The anomeric ratio of 14 was determined by 1H NMR spectroscopy
(500 MHz).
4.4. Glycosylation with various glycosyl N-
trichloroacetylcarbamates
4.4.1. Preparation of various glycosyl carbamates
4.4.1.1. 2,3,4,6-Tetra-O-benzyl-
trichloroacetylcarbamate (18a and 18b).
of 2,3,4,6-tetra-O-benzyl-
a
- and b-
D
-galactopyranosyl N-
To a stirred solution
4.3.3.8. 3-O-(2,3,4,6-Tetra-O-benzyl-
terol (14b) (Table 5, entry 8). The glycosylation was performed
according to the typical procedure employing carbamate donor 2
(34.3 mg, 47.3 mol), acceptor 7 (15.3 mg, 39.6 mol) and TMSOTf
(1.4 L in toluene (0.1 mL), 7.7 mol) in EtCN (3.0 mL) at 0 °C for
2 h. The anomeric mixture of the known glycoside 1431 (31.7 mg,
88%, :b = 21:79) as a colorless oil after the purification by pre-
parative TLC (silica gel, 10:1 benzene–AcOEt). The NMR data for
14 matched those previously reported.31 The anomeric ratio of
14 was determined by 1H NMR spectroscopy (500 MHz).
a
,b-
D
-glucopyraosyl)choles-
D
-galactopyranose
(17)
(1.06 g,
1.85 mmol) in dry CH2Cl2 (10 mL) was added trichloroacetyl isocy-
anate (0.23 mL, 1.91 mmol) at 0 °C. The reaction mixture was stir-
red at room temperature for 0.25 h, and the solvent was
evaporated in vacuo to give a mixture of 18a and 18b as colorless
l
l
l
l
a
syrup (quant.,
spectroscopy). If necessary, the
a
:b = 85:15, as determined by 500 MHz 1H NMR
a isomer 18a (Rf 0.40, 3:1 hex-
anes–AcOEt) and the b isomer 18b (Rf 0.34, 3:1 hexanes–AcOEt)
were separated by column chromatography on silica gel (7:1 hex-
anes–AcOEt). Data for the
a
isomer (18a): 1H NMR (500 MHz,
4.3.3.9. Methyl (S)-2-((benzyloxycarbonyl)amino)-3-O-(2,3,4,6-
CDCl3): d 8.45 (s, 1H, –CONHCOCl3), 7.38–7.25 (m, 20H, Ph–H),
6.42 (d, J1,2 3.7 Hz, 1H, H-1), 4.94 (d, J 11.5 Hz, 1H, –CH2Ph),
4.81–4.73 (m, 4H, –CH2Ph), 4.56 (d, J 11.5 Hz, 1H, –CH2Ph), 4.47,
4.41 (d, J 11.9 Hz, 1H each, –CH2Ph), 4.21 (dd, J2,3 10.1, J3,4 3.7 Hz,
tetra-O-benzyl-
entry 9). The glycosylation was performed according to the typ-
ical procedure employing carbamate donor 2 (36.6 mg, 50.2 mol),
a,b-D-glucopyranosyl)propanoate (15a) (Table 5,
l

748
T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
1H, H-2), 4.11 (m, 1H, H-5), 4.06 (m, 1H, H-4), 3.97 (dd, J2,3 10.1, J2,3
2.3 Hz, 1H, H-3), 3.55 (m, 2H, H-6); 13C NMR (125 MHz, CDCl3): d
157.4 (–OCONHCOCCl3), 148.9 (–OCONHCOCCl3), 138.3, 138.3,
137.6, 137.6, 128.4, 128.4, 128.3, 128.1, 128.1, 127.9, 127.8,
127.7, 127.6, 127.5, 95.0 (C-1), 91.8, 78.4 (C-3), 75.0 (–CH2Ph),
75.0 (–CH2Ph), 74.2 (C-2), 73.7 (C-4), 73.5 (–CH2Ph), 73.0 (–CH2Ph),
72.6 (C-5), 68.2 (C-6). Data for the b isomer (18b): 1H NMR
(500 MHz, CDCl3): d 8.18 (s, 1H, CONHCOCl3), 7.36–7.25 (m, 20H,
Ph–H), 5.59 (d, J1,2 8.3 Hz, 1H, H-1), 4.93 (d, J 11.0 Hz, 1H, –CH2Ph),
4.89 (d, J 11.5 Hz, 1H, –CH2Ph), 4.76–4.69 (m, 3H, –CH2Ph), 4.62 (d,
J 11.0 Hz, 1H, –CH2Ph), 4.44, 4.39 (d, J 11.9 Hz, 1H each, –CH2Ph),
3.99 (m, 1H, H-4), 3.96 (dd, J2,3 9.6, J1,2 8.3 Hz, 1H, H-2), 3.71 (m,
1H, H-5), 3.65 (dd, J2,3 9.6, J3,4 2.3 Hz, 1H, H-3), 3.60–3.54 (m, 2H,
H-6); 13C NMR (125 MHz, CDCl3): d 157.4 (–OCONHCOCCl3),
147.7 (–OCONHCOCCl3), 138.2, 138.1, 137.9, 137.5, 128.5, 128.5,
128.4, 128.3, 128.2, 128.0, 127.9, 127.9, 127.8, 127.7, 127.6, 96.3
(C-1), 91.5, 82.4 (C-3), 77.6, 77.5, 77.1, 76.5, 75.2 (–CH2Ph), 74.7
(–CH2Ph), 74.2 (C-5), 73.5 (–CH2Ph), 72.8 (–CH2Ph), 72.7 (C-4),
67.7 (C-6).
(80.0
An anomeric mixture of the known disaccharide 2332 (36.6 mg,
90%, :b = 87:13) was obtained as a colorless oil after purification
lL, 0.2 M solution in Et2O, 8.0 mmol) in Et2O at 0 °C for 3 h.
a
by preparative TLC (silica gel, 10:1 benzene–AcOEt). The NMR data
for 23 matched those previously reported.32
4.4.2.2. Methyl 2,3,4,6-tetra-O-benzyl-
(1?6)-2,3,4-tri-O-benzoyl-a- -glucopyranoside (23b) (Table 6,
entry 2). The glycosylation was performed according to the typ-
ical procedure employing carbamate donor 18 (30.6 mg,
41.2 mmol), acceptor (17.5 mg, 34.3 mmol) and TMSOTf
a,b-D-galactopyranosyl)-
D
3
(2.0 mL, 8.0 mmol) in EtCN (1.5 mL) at ꢁ40 °C for 20 h. An anomer-
ic mixture of the known disaccharide 2332 (33.8 mg, 96%,
a:b = 19:81) was obtained as a colorless oil after purification by
preparative TLC (silica gel, 10:1 benzene–AcOEt). The NMR data
for 23 matched those previously reported.32
4.4.2.3. Methyl
(1?6)-2,3,6-tri-O-acetyl-
entry 3). The glycosylation was performed according to the typ-
ical procedure employing carbamate donor 20 (54.6 mg,
2,3,4,6-tetra-O-benzyl-a,b-D-mannopyraosyl)-
a-D-glucopyranoside (25a) (Table 6,
4.4.1.2. 2,3,4,6-Tetra-O-benzyl-
trichloroacetylcarbamate (20a and 20b).
of 2,3,4,6-tetra-O-benzyl- -mannopyranose
a
- and b-
D
-mannopyranosyl N-
To a stirred solution
74.9
(2.3
l
l
mol), acceptor 24 (20.0 mg, 62.4
L, 12.5 mol) in Et2O (1.5 mL) at rt for 15 min. The anomeric
:b = 94:6)
lmol) and TMSOTf
D
(19)
(0.36 g,
l
0.67 mmol) in dry CH2Cl2 (3 mL) was added trichloroacetyl isocya-
nate (0.078 mL, 0.69 mmol) at 0 °C. The reaction mixture was stir-
red at room temperature for 0.25 h, and the solvent was
evaporated in vacuo to give a mixture of 20a and 20b as colorless
mixture of the known disaccharide 2524 (52.0 mg, 93%,
a
was obtained as a colorless oil after purification by preparative TLC
(silica gel, 10:1 benzene–AcOEt). The NMR data for 25 matched
those previously reported.24
syrup (quant.,
troscopy). If necessary, the
a
:b = 85:15, determined by 500 MHz 1H NMR spec-
a
isomer 20a (Rf 0.40, 3:1 hexanes–
4.4.2.4. Methyl 2,3,4,6-tetra-O-benzyl-
2,3,4-tri-O-acetyl-a- -glucopyranoside (25b); (Table 5, entry
4). The glycosylation was performed according to the typical
procedure employing carbamate donor 20 (54.6 mg, 74.9 mmol),
acceptor 24 (20.0 mg, 62.4 mmol) and TMSOTf (13.6 L, 74.9 mol)
in EtCN (3.0 mL) at ꢁ40 °C for 30 min. An anomeric mixture of the
known disaccharide 2524 (52.2 mg, 99%,
:b = 76:24) was obtained
D-mannopyranosyl-(1?6)-
AcOEt) and the b isomer 20b (Rf 0.34, 3:1 hexanes–AcOEt) were
D
separated by column chromatography on silica gel (7:1 hexanes–
AcOEt). Data for
a
isomer (20a): 1H NMR (300 MHz, C6D6): d 8.59
(s, 1H, N–H), 7.44–6.98 (m, 20H, Ph–H), 5.56 (m, 1H, H-1), 4.82
(d, J 12.0 Hz, 1H, CH2Ph), 4.80 (d, J 11.4 Hz, 1H, CH2Ph), 4.74–4.71
(br m, 2H, CH2Ph), 4.47 (d, J 11.6 Hz, 1H, CH2Ph), 4.43–4.37 (br
m, 2H, CH2Ph), 4.28 (d, J 11.9 Hz, 1H, CH2Ph), 4.17 (dd, J3,4 9.4,
J4,5 8.8 Hz, 1H, H-4), 3.73- 3.61 (m, 3H, H-2, H-6), 3.44 (ddd, J4,5
8.8, J5,6a 4.4, J5,6b 2.3 Hz, 1H, H-5), 3.44 (m, 1H, H-3). 13C NMR
(75 MHz, C6D6): d 157.9 (C@O), 148.6 (C@O), 139.2, 139.1, 138.8,
128.8, 128.6, 128.5, 128.08, 128.00, 127.97, 127.86, 127.8, 95.4
(C-1), 92.2 (CCl3), 82.1 (C-3), 76.7 (C-5), 75.0, 74.8, 74.7 (C-2),
74.4 (C-4), 73.6, 72.4, 69.2 (C-6).
l
l
a
as a colorless oil after purification by preparative TLC (silica gel,
10:1 benzene–AcOEt).
4.4.2.5. Methyl 2,3-di-O-benzyl-4,6-O-benzylidene-
nopyranosyl-(1?6)-2,3,4-tri-O-acetyl- -glucopyranoside (26)
(Table 6, entry 5). The glycosylation was performed according
a,b-D-man-
a-D
to the typical procedure employing carbamate donor 22
(52.2 mg, 74.9 mmol), acceptor 24 (20.0 mg, 62.4 mmol) and
4.4.1.3. 2,3-Di-O-benzyl-4,6-O-benzylidene-
N-trichloroacetyl carbamate (22a and 22b).
tion of 2,3-di-O-benzyl-4,6-benzylidene-
D
-mannopyranosyl
To a stirred solu-
TMSOTf (13.6
An anomeric mixture of the known disaccharide 2624 (15.9 mg,
34%, :b = 22:78) was obtained as a colorless oil after purification
lL, 74.9 lmol) in CH2Cl2 (3.0 mL) at 0 °C for 1.5 h.
D
-mannopyranose (21)
a
(1.00 g, 2.23 mmol) in dry CH2Cl2 (10 mL) was added trichloroace-
tyl isocyanate (0.29 mL, 2.30 mmol) at 0 °C. The reaction mixture
was stirred at room temperature for 0.25 h, and the solvent was
evaporated in vacuo to give a mixture of 22a and 22b as colorless
by preparative TLC (silica gel, 10:1 benzene–AcOEt). The NMR data
for 26 matched those previously reported.24
4.5. Model study for the construction of a glycosyl bond in a
natural product
syrup (quant.,
troscopy). If necessary, the
a
:b = 85:15, determined by 500 MHz 1H NMR spec-
a
isomer 22a (Rf 0.40, 3:1 hexanes–
AcOEt) and the b isomer 22b (Rf 0.34, 3:1 hexanes–AcOEt) were
4.5.1. Preparation of the glycosyl carbamate
separated by column chromatography on silica gel (7:1 hexanes–
4.5.1.1. 4-O-Acetyl-3-O-(tert-butyldimethylsilyl)-6-bromo-6-
AcOEt): Data for
a
isomer (22a): 1H NMR (300 MHz, CDCl3): d
deoxy-2-S-phenyl-2-thio-
a
- and b-D-glucopyranosyl N-trichlo-
8.32 (s, 1H, N–H), 7.44–6.98 (m, 15H, Ph–H), 6.19 (d, J1,2 1.4 Hz,
1H, H-1), 5.66 (s, 1H, PhCH–), 5.02–4.66 (m, 4H, CH2Ph), 4.80 (d, J
11.4 Hz, 1H, CH2Ph), 4.74–4.71(br m, 2H, CH2Ph), 4.47 (d, J
11.6 Hz, 1H, CH2Ph), 4.36–4.25 (m, 2H), 4.03–3.84 (m, 3H).
roacetylcarbamates (29).
To the stirred solution of 4-O-acetyl-
3-O-(tert-butyldimethylsilyl)-6-bromo-6-deoxy-2-S-phenyl-2-
thio- -glucopyranose (28) (187.0 mg, 38.1 mol) in dry CH2Cl2
(5 mL) was added trichloroacetyl isocyanate (68.0 L, 57.2 mol)
D
l
l
l
at 0 °C. The reaction mixture was stirred at room temperature for
4.4.2. Glycosylation with various glycosyl carbamates
1.5 h, and the solvent was evaporated in vacuo to give a mixture of
4.4.2.1. Methyl 2,3,4,6-tetra-O-benzyl-
(1?6)-2,3,6-tri-O-benzoyl- -glucopyranoside (23a) (Table 6,
entry 1). The glycosylation was performed according to the typ-
ical procedure employing carbamate donor 18 (34.8 mg,
47.7 mol), acceptor (20.1 mg, 39.7 mol) and TMSClO4
a
,b-
D
-galactopyranosyl)-
29a and 29b as colorless syrup (quant.,
was determined by 1H NMR spectroscopy (300 MHz)). If necessary,
the isomer 29a (Rf 0.40, 3:1 hexanes–AcOEt) and the b isomer
29b (Rf 0.34, 3:1 hexanes–AcOEt) were separated by column
chromatography on silica gel (10:1 benzene–AcOEt). Data for iso-
a:b = 90:10, anomeric ratio
a-D
a
l
3
l
a

T. Shirahata et al. / Carbohydrate Research 345 (2010) 740–749
749
mer (29a): 1H NMR (300 MHz,CDCl3): d 8.45 (s, 1H, N–H), 7.50–7.43
(m, 2H, SPh–H), 7.36–7.25 (m, 3H, SPh–H), 6.33 (d, J1,2 3.1 Hz, 1H, H-
1), 5.02 (dd, J4,5 9.8, J3,4 8.6 Hz, 1H, 4-H), 4.14 (dd, J2,3 10.7, J3,4 8.6 Hz,
1H, H-3), 4.08 (ddd, J4,5 9.8, J5,6a 6.2 Hz, J5,6b 3.1 Hz, 1H, H-5), 3.42 (dd,
J6a,6b 11.3, J5,6b 3.1 Hz, 1H, H-6b), 3.34 (dd, J2,3 10.7, J1,2 3.1 Hz, 1H, H-
2), 3.30 (dd, J6a,6b 11.3, J5,6a 6.2 Hz, 1H, H-6a), 2.16 (s, 3H, –OCOCH3),
0.90 (s, 9H, –SiC(CH3)3), 0.22 (s, 3H, –Si(CH3)2C–), 0.13 (s, 3H, –
Si(CH3)2C–). 13C NMR (75 MHz, C6D6): d 169.6 (C@O), 157.4 (C@O),
148.8 (C@O), 136.6, 132.1 (2C), 129.3 (2C), 127.9, 127.5, 95.5 (C-1),
74.2 (C-4), 72.4 (C-3), 70.1 (C-5), 55.9 (C-2), 31.0 (C-6), 25.9 (3C, –
SiC(CH3)3), 21.5 (–OCOCH3), 18.1 (–SiC(CH3)3), –3.5 (–Si(CH3)2C–),
–4.1 (–Si(CH3)2C–).
Kinzy, W. Adv. Carbohydr. Chem. Biochem. 1994, 50, 21–123; (d) Toshima, K.;
Tatsuta, K. Chem. Rev. 1993, 93, 1503–1531; (e) Sinaÿ, P. Pure Appl. Chem. 1991,
63, 519–528.
3. Kunz, H.; Zimmer, J. Tetrahedron Lett. 1993, 34, 2907–2910.
4. Prata, C.; Mora, N.; Lacombe, J.-M.; Maurizis, J. C.; Pucci, B. Tetrahedron Lett.
1997, 38, 8859–8862.
5. Hinklin, R. J.; Kiessling, L. L. J. Am. Chem. Soc. 2001, 123, 3379–3380.
6. Knoben, H.-P.; Schlueter, U.; Redlich, H. Carbohydr. Res. 2004, 339, 2821–2833.
7. Jayakanthan, K.; Vankar, Y. D. Carbohydr. Res. 2005, 340, 2688–2692.
¯
8. Matsuo, J.; Shirahata, T.; Omura, S. Tetrahedron Lett. 2006, 47, 267–271.
9. Hashimoto, S.; Hayashi, M.; Noyori, R. Tetrahedron Lett. 1984, 25, 1379–1382.
10. Nagai, H.; Sasaki, K.; Matsumura, S.; Toshima, K. Carbohydr. Res. 2005, 340,
337–353.
11. Nakarahra, Y.; Ogawa, T. Carbohydr. Res. 1990, 200, 363–375.
12. (a) Jona, H.; Mandai, H.; Chavasiri, W.; Takeuchi, K.; Mukaiyama, T. Bull. Chem.
Soc. Jpn. 2002, 75, 291–309; (b) Toshima, K.; Kasumi, K.; Matsumura, S. Synlett
1998, 643–645.
13. Kreuzer, M.; Thiem, J. Carbohydr. Res. 1986, 149, 347–361.
14. (a) Inaba, S.; Yamada, M.; Yoshino, T.; Ishido, Y. J. Am. Chem. Soc. 1973, 95,
2062–2063; (b) Ishido, Y.; Inaba, S.; Matsuno, A.; Yoshino, T.; Umezawa, H. J.
Chem. Soc., Perkin Trans. 1 1977, 1382–1390; (c) Ishido, Y.; Inaba, S.; Komura,
H.; Matsuno, A. J. Chem. Soc., Chem. Commun. 1977, 90–91.
15. Garcia, B. A.; Gin, D. Y. J. Am. Chem. Soc. 2000, 122, 4269–4279. and references
cited therein.
16. Umemura, K.; Matsuyama, H.; Kobayashi, M.; Kamigata, N. Bull. Chem. Soc. Jpn.
1989, 62, 3026–3028.
17. Chiba, H.; Funasaka, S.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 2003, 76, 1629–
1644.
4.5.2. Glycosylation
4.5.2.1. Isopropyl
bromo-6-deoxy-2-S-phenyl-2-thio-
glycosylation was performed according to the typical procedure
employing carbamate donor 29 (31.0 mg, 45.6 mol), acceptor 30
(14.0 mL, 183.0 mol) and TMSOTf (2.5 L, 13.8 mol) in 1,2-
dichloroethane (1.0 mL) at 40 °C for 15 min. An anomeric mixture
of the known glycoside 3126b (17.0 mg, 70%,
:b = 19:81) was ob-
4-O-acetyl-3-O-(tert-butyldimethylsilyl)-6-
a
,b- -glucopyranose (31). The
D
l
l
l
l
a
tained as a colorless oil after purification by preparative TLC (silica
gel, 70:1 benzene–AcOEt): 1H NMR (300 MHz,CDCl3) 31a: d 7.47–
7.41 (m, 2H, SPh–H), 7.28–7.15 (m, 3H, SPh–H), 4.80 (dd, J4,5
9.4 Hz, J3,4 8.2 Hz 1H, H-4), 4.48 (d, J1,2 8.6 Hz, 1H, H-1), 3.93 (t, J
6.2 Hz, 1H, –OCH(CH3)2), 3.72 (dd, J2,3 10.1, J3,4 8.2 Hz 1H, H-3),
3.53 (ddd, J4,5 9.4, J5,6a 6.4, J5,6b 4.1 Hz 1H, H-5), 3.35 (m, 2H, H-
6), 3.16 (dd, J2,3 10.1, J1,2 8.6 Hz, 1H, H-2), 2.13 (s, 3H, –OCOCH3),
1.16 (d, J 6.2 Hz, 3H, –OCH(CH3)2), 1.01 (d, J 6.2 Hz, 3H, –
OCH(CH3)2), 0.85 (s, 9H, –SiC(CH3)3), 0.19 (s, 3H, –Si(CH3)2C–),
0.07 (s, 3H, –Si(CH3)2C–).
18. Chhabra, S. R.; Mahajan, A.; Chan, W. C. J. Org. Chem. 2002, 67, 4017–4029.
19. Grayson, E. J.; Ward, S. J.; Hall, A. L.; Rendle, P. M.; Gamblin, D. P.; Batsanov, A.
S.; Davis, B. G. J. Org. Chem. 2005, 70, 9740–9754.
20. Motawia, M. S.; Olsen, C. E.; Denyer, K.; Smith, A. M.; Moller, B. L. Carbohydr.
Res. 2001, 330, 309–318.
21. Hu, Y.-J.; Dominique, R.; Das, S. K.; Roy, R. Can. J. Chem. 2000, 78, 838–845.
22. Oshitari, T.; Tomita, M.; Kobayashi, S. Tetrahedron Lett. 1994, 35, 6493–6494.
23. Chen, M.-Y.; Patkar, L. N.; Lu, K.-C.; Lee, A. S.-Y.; Lin, C.-C. Tetrahedron 2004, 60,
11465–11475.
24. (a) Crich, D.; Sun, S. Tetrahedron 1998, 54, 8321–8348; (b) Wuiff, G.;
Wichelhaus, J. Chem. Ber. 1979, 112, 2847–2853.
¯
25. (a) Omura, S.; Tanaka, Y.; Nakagawa, A.; Iwai, Y.; Inoue, M.; Tanaka, H. J.
Antibiot. 1982, 35, 256–257; (b) Omura, S.; Nakagawa, A.; Tanaka, Y. J. Org.
Chem. 1982, 47, 5413–5415; (c) Omura, S.; Tanaka, Y.; Takahashi, Y.; Chia, I.;
Inoue, M.; Iwai, Y. J. Antibiot. 1984, 37, 1572–1578; (d) Hirose, T.; Sunazuka, T.;
Yamamoto, D.; Mouri, M.; Hagiwara, Y.; Matsumaru, T.; Kaji, E.; Omura, S.
Tetrahedron Lett. 2006, 48, 413–416.
Acknowledgments
A part of this work was supported by KAKENHI, Grant-in-Aid for
Young Scientists (B) (20790017) from the Ministry of Education,
Culture, Sports, Science and Technology (MEXT), Japan, and Kitasa-
to University Research Grant for Young Researchers.
26. (a) Roush, W. R.; Sebesta, D. P.; Bennett, C. E. Tetrahedron 1997, 53, 8825–8836;
(b) Roush, W. R.; Sebesta, D. P.; James, R. A. Tetrahedron 1997, 53, 8837–8852;
(c) Roush, W. R.; Briner, K.; Kesler, B. S.; Murphy, M.; Gustin, D. J. J. Org. Chem.
1996, 61, 6098–6099; (d) Roush, W. R.; Hartz, R. A.; Gustin, D. J. J. Am. Chem.
Soc. 1999, 121, 1990–1991.
27. Garegg, P. J.; Hultberg, H. Carbohydr. Res. 1981, 93, C10.
28. (a) Garcia, B. A.; Gin, D. Y. J. Am. Chem. Soc. 2000, 122, 4269–4279; (b) Kim, W.-S.;
Hosono, S.; Sasai, H.; Shibasaki, M. Heterocycles 1996, 42, 795–809; (c) Fukase,
K.; Hasuoka, A.; Kinoshita, I.; Aoki, Y.; Kusumoto, S. Tetrahedron 1995, 51, 4923;
(d) Koide, K.; Ohno, M.; Kobayashi, S. Tetrahedron Lett. 1991, 48, 7065–7068.
29. (a) Wang, C.-C.; Lee, J.-C.; Luo, S.-Y.; Kulkarni, S. S.; Huang, Y.-W.; Lee, C.-C.;
Chang, K.-L.; Hung, S.-C. Nature 2007, 446, 896–899; (b) Dasgupta, F.; Garegg, P.
Synthesis 1994, 1121–1123; (c) Boons, G. J.; Castle, G. H.; Clase, J. A.; Grice, P.;
Ley, S. V.; Pinel, C. Synlett 1993, 913–914.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.01.011.
References
30. Dasgupta, F.; Garegg, P. J. Carbohydr. Res. 1988, 177, C13.
31. Vankayalapati, H.; Singh, G.; Tranoy, I. Tetrahedron: Asymmetry 2001, 12, 1371–
1. (a) Seeberger, P. H.; Werz, D. B. Nature 2007, 446, 1046–1051; (b)Handbook of
Chemical Glycosylation; Demchenko, A. V., Ed.; Wiley-VCH: Weinheim, 2008.
2. (a) Boons, G. J. Tetrahedron 1996, 52, 1095–1121; (b) Danishefsky, S. J.;
Bilodeau, M. T. Angew. Chem., Int. Ed. 1996, 35, 1380–1419; (c) Schmidt, R. R.;
1381.
32. (a) Uchiro, H.; Kurusu, N.; Mukaiyama, T. Isr. J. Chem 1997, 37, 87–96; (b)
Uchiro, H.; Miyazaki, K.; Mukaiyama, T. Chem. Lett. 1997, 403–404.