LETTER
New Building Block for Chemical Glycosylation
1503
(3) (a) Pougny, J.-R.; Sinay, P. Tetrahedron Lett. 1976, 17,
4073. (b) Schmidt, R. R.; Michel, J. Angew. Chem., Int. Ed.
Engl. 1980, 19, 731. (c) For a comprehensive review, see:
Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21. (d) See also: Schmidt, R. R.; Jung, K.-H. In
Carbohydrates in Chemistry and Biology; Vol. 1; Ernst, B.;
Hart, G. W.; Sinaÿ, P., Eds.; Wiley-VCH: Weinheim, 2000,
5.
(4) (a) Tao, H.; Yu, B. Tetrahedron Lett. 2001, 42, 2405. (b) For
a comprehensive review, see: Yu, B.; Sun, J. Chem.
Commun. 2010, 46, 4668. (c) Schmidt and co-workers also
pioneered the preparation of glycosyl trifluoroacetimidates,
see: Schmidt, R. R.; Michel, J.; Roos, M. Liebigs Ann. Chem.
1984, 1343.
Table 1 Glycosylations of 2 with 3
Entry
Donor
Acceptor Product
Yield (%) α/β
1
2
2a
2a
2a
2a
2b
2b
2b
2c
2c
2c
2d
2d
2d
2e
2e
2f
3a
3b
3e
3h
3a
3c
3e
3a
3d
3g
3e
3f
4aa
4ab
4ae
4ah
4ba
4bc
4be
4ca
4cd
4cg
4de
4df
4dh
4ee
4ed
4ff
80
94
92
86
84
88
97
95
98
93
57
65
90
74
99
66
96
87
α
α
α
α
α
α
α
β
β
β
β
β
β
β
β
β
β
5:4
3
4a
5
6
(5) Cai, S.; Yu, B. Org. Lett. 2003, 5, 3827.
7
(6) (a) Tanaka, K.; Fujii, Y.; Tokimoto, H.; Mori, Y.; Tanaka,
S.; Bao, G.-m.; Siwu, E. R. O.; Nakayabu, A.; Fukase, K.
Chem.–Asian J. 2009, 4, 574. (b) Tanaka, H.; Iwata, Y.;
Takahashi, D.; Adachi, M.; Takahashi, T. J. Am. Chem. Soc.
2005, 127, 1630. (c) Tanaka, K.; Miyagawa, T.; Fukase, K.
Synlett 2009, 1571.
(7) Papot, S.; Gesson, J.-P.; Thomas, M. J. Org. Chem. 2007,
72, 4262.
(8) Huchel, U.; Tiwari, P.; Schmidt, R. R. J. Carbohydr. Chem.
2010, 29, 61.
8
9
10
11
12
13a
14
15
16
17
18
3h
3e
3d
3f
(9) Fan, L.-Y.; Gao, F.-F.; Jiang, W.-H.; Deng, M.-Z.; Qian,
C.-T. Org. Biomol. Chem. 2008, 6, 2133.
(10) A Typical Procedure for the Preparation of Glycosyl
N-Tosyl Benzimidate
To a solution of mannosyl hemiactal (500 mg, 0.84 mmol) in
acetone (3 mL) was added K2CO3 (290 mg, 2.10 mmol, 2.50
equiv) and N-tosylbenzimidoyl chloride (296 mg, 1.0 mmol,
1.20 equiv) at ambient temperature. After stirring for 2 h the
solid was filtered off, and the filtrate was concentrated under
vacuum, and the residue was purified by silica gel chroma-
tography (EtOAc–PE = 1:4) to give imidate 2a as a white
solid (617 mg, 0.72 mmol, 86%). [α]D20 = –30.1 (c 1.09
CHCl3). 1H NMR (600 MHz, CDCl3): δ = 8.11 (d, J = 7.2 Hz,
2 H), 8.03 (m, 4 H), 7.93 (d, J = 7.14 Hz, 2 H), 7.82 (m, 4 H),
7.68 (t, J = 7.68 Hz, 1 H), 7.59 (m, 4 H), 7.50 (t, J = 7.14 Hz,
1 H), 7.43 (m, 5 H), 7.35 (t, J = 7.74 Hz, 2 H), 7.28 (d, J =
8.28 Hz, 2 H), 7.20 (d, J = 8.28 Hz, 2 H), 6.38 (d, J = 1.62
Hz, 1 H), 6.20 (t, J = 10.44 Hz, 1 H), 5.91 (m, 2 H), 4.73 (dd,
J = 2.16, 12.06 Hz, 1 H), 4.59 (m, 1 H), 4.47 (dd, J = 4.38,
12.12 Hz, 1 H), 2.34 (s, 3 H). 13C NMR (150 MHz,CDCl3):
δ = 166.5, 166.1, 165.6, 165.4, 164.9, 143.5, 138.6, 133.9,
133.8, 133.5, 133.4, 133.3, 130.0, 129.9, 129.8, 129.5,
128.8, 128.7, 128.65, 128.6, 128.5, 127.0, 94.6, 71.8, 69.7,
68.9, 66.0, 62.5, 21.6. ESI-MS: m/z = 876.2 [M + Na]+.
HRMS: m/z calcd for C48H39O12NNaS [M + Na]+: 876.2091;
found: 876.2085.
2f
3g
3d
4fg
2g
4gd
a Conditions: 1.0 equiv of TMSOTf was used in the glycosylation re-
action.
Acknowledgment
We are grateful for the financial support from National Science
Funding of China (21002095), the State Key Laboratory of Bioor-
ganic and Natural Products Chemistry, Chinese Academia of Sci-
ence, PCSIRT (IRT0944), and ‘Young Talent Project’ at Ocean
University of China.
Supporting Information for this article is available online at
data and NMR spectra for compounds 2 and 4.SnoIufproi
m
tgioSrantnugIifoop
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(11) Typical Procedure for the Glycosylation
A solution of 2a (100 mg, 0.12 mmol, 1.40 equiv) and 3a (27
mg, 0.086 mmol) in anhyd CH2Cl2 (2 mL) was stirred for 30
min in the presence of freshly activated 5 Å MS (150 mg)
under argon atmosphere. At this point, the mixture was
cooled to 0 °C, then TMSOTf (1.50 μL, 0.0086 mmol, 0.1
equiv) was added. After the resulting mixture was stirred for
another 2 h, Et3N (1.20 μL, 0.0086 mmol, 0.1 equiv) was
added to quench the reaction. The solid was filtered off, and
the filtrate was concentrated under vacuum, the residue was
applied to silica gel chromatography (EtOAc–PE = 1:9) to
afford the disaccharide 4aa (61 mg, 0.069 mmol, 80%).
[α]D22 –104.5 (c 0.32, CHCl3). 1H NMR (600 MHz, CDCl3):
δ = 8.16 (d, J = 8.22 Hz, 2 H), 8.07 (d, J = 8.28 Hz, 2 H), 8.00
(d, J = 8.28 Hz, 2 H), 7.89 (d, J = 7.74 Hz, 2 H), 7.59 (m, 2
H), 7.52 (t, J = 7.14 Hz, 1 H), 7.42 (m, 8 H), 7.27 (m, 2 H),
References
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(b) Fraser-Reid, B. O.; Tatsuta, K.; Thiem, J. Glycoscience:
Chemistry and Chemical Biology, 2nd ed.; Springer: New
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Ed. 2009, 48, 1934.
(2) (a) Varki, A.; Cummings, R.; Esko, J.; Freeze, H.; Hart, G.;
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© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 1501–1504