Y. Wang, X.-S. Ye / Tetrahedron Letters 50 (2009) 3823–3826
3825
OMe
OMe
BnO
BnO
O
BnO
BnO
BnO
BnO
O
i
OH
OBz
O
O
HO
BzO
Ac(Bz)N
O
COOR2
COOMe
O
R1HN
OH
HO
BzO
OBz
11β
14
R1 = Ac, R2 = Me
15 R1 = Bz, R2 = Me
16 R1 = Ac, R2 = H
ii, iii
Scheme 3. Reagents and conditions: (i) NaOMe, MeOH, room temperature, 2 h, 84% (14: 15 = 2.7: 1); (ii) Ba(OH)2ꢁ8H2O, EtOH–H2O (v/v 1:1), reflux, 18 h; (iii) Ac2O, MeOH,
NaOH, room temperature, 12 h, 54% over two steps.
AW-300 molecular sieves for the reaction was more efficient
than using 4 Å molecular sieves.21 Thus, in the absence of partic-
ipant solvents, coupling product disaccharide 1122 was obtained
as an unnatural b anomer in 90% isolated yield (Table 1, entry 1).
Acknowledgments
This work was financially supported by the National Natural
Science Foundation of China, and the ‘973’ grant from the Ministry
of Science and Technology of China.
To gain the
a-selectivity, Ph2SO–Tf2O promoter system reported
by Crich23 was attempted. Unfortunately, unnatural b anomer
was still a dominant product though an excess of Ph2SO stabi-
lized the intermediate oxacarbenium ion efficiently and the cou-
pling reaction occurred under the donor pre-activation
conditions24,25 (Table 1, entry 2). Coupling with another C-6 hy-
droxyl-exposed acceptor 926 afforded a similar result: higher b
anomeric selectivity was also achieved when NIS–TfOH instead
of Ph2SO–Tf2O system was used as promoter (Table 1, entries
3 and 4). To apply donor 1 to the construction of 2,3-sialyl link-
ages, partially protected galactoside acceptor 1027 was selected.
As expected, the coupling product 13 was obtained in 53% iso-
lated yield. It was noteworthy that the good b selectivity was
kept although the secondary hydroxyl acceptor was employed
(Table 1, entry 5).
As an example, deprotection of disaccharide 11b is illustrated in
Scheme 3. Fully protected disaccharide 11b was treated with
NaOMe to provide separable compound 14 containing the acetami-
no group and compound 15 containing the benzamido group in
62% and 22% yields, respectively. Compound 15 was further treated
with Ba(OH)2 followed by selective N-reacetylation to give product
16 in acceptable yield.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
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Wien–New York, 1982.
2. Boons, G.; Demchenko, A. V. Chem. Rev. 2000, 100, 4539.
3. Takahashi, T.; Tsukamoto, H.; Yamada, H. Tetrahedron Lett. 1997, 38, 8223.
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8. Demchenko, A. V.; Boons, G. J. Tetrahedron Lett. 1998, 39, 3065.
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10. Crich, D.; Li, W. J. Org. Chem. 2007, 72, 2387.
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[13]. Oscarson, S.. 2000. In Carbohydrates in Chemistry and Biology; Ernst, B., Hart, G.
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Marel, G. A. Chem. Soc. Rev. 2005, 34, 769.
All structures of new compounds were identified by their NMR
and mass spectroscopic analyses. The 1H NMR spectra of com-
pounds 11, 12, and 13 at room temperature showed two groups
of signals due to the hindrance of bond rotation around C5–N, so
clear spectra were recorded at 80 °C. The stereochemistry of newly
formed glycosidic linkages in 11 and 12 was assigned on the basis
of the chemical shifts of sialic acid H-3 equiv as both anomers were
obtained. However, the anomeric configuration of disaccharide 13
had to be determined based on its deprotected product. In addi-
tion, the JC-1,H-3a coupling constants were also used to confirm
the glycosidic bond configurations of deprotected products of
disaccharides 11b and 13.2 The regioselectivity to form disaccha-
ride 13 was confirmed by heteronuclear multiple-bond correlation
(HMBC) experiment of its deprotected product.
In conclusion, N,N-acetyl, benzoyl-O-perbenzoyl-protected
sialyl donor was prepared and its sialylation reactions with three
acceptors using NIS–TfOH and Ph2SO–Tf2O as promotor systems
were investigated. The new sialyl donor showed good b-anomeric
selectivity by using NIS–TfOH as promotor and dichloromethane
as solvent. The N,N-acetyl, benzoyl protective group was deprotec-
ted under basic conditions. The disclosed sialyl donor may find
applications in the construction of unnatural b-linked sialosides
with potential biological importance.
15. Ehara, T.; Kameyama, A.; Yamada, Y.; Ishida, H.; Kiso, M.; Hasegawa, A.
Carbohydr. Res. 1996, 281, 237.
16. Tsvetkov, Y. E.; Nifantiev, N. E. Synlett 2005, 1375.
17. Ikeda, K.; Miyamoto, K.; Sato, M. Tetrahedron Lett. 2007, 48, 7431.
18. Meo, C. D.; Demchenko, A. V.; Boons, G. J. J. Org. Chem. 2001, 66, 5490.
19. Methyl [p-methylphenyl 5-acetamido-4,7,8,9-tetra-O-benzoyl-5-N-benzoyl-3,5-
dideoxy-2-thio-D-glycero-b-D
-galacto-non-2-ulopyranoside]-onate (1): 1H NMR
(500 MHz, DMSO-d6, 80 °C) d 8.01 (d, J = 8.0 Hz, 2H; Ar), 7.84–7.79 (m, 6H; Ar),
7.68 (t, J1 = 7.5 Hz, J2 = 7.0 Hz, 1H; Ar), 7.60–7.50 (m, 8H; Ar), 7.44–7.40 (m, 8H;
Ar), 7.29 (t, J1 = 8.0 Hz, J2 = 7.5 Hz, 2H; Ar), 7.15 (d, J = 7.5 Hz, 2H; Ar), 6.15 (dt,
J3e,4 = 5.0 Hz, J3a,4 = J4,5 = 10.0 Hz, 1H; H-4), 5.89 (dd, J6,7 = 1.5Hz, J7,8 = 3.0 Hz,
1H; H-7), 5.76 (dd, J5,6 = 10.0 Hz, J6,7 = 1.5 Hz, 1H; H-6), 5.50 (m, 1H; H-8), 4.91
(t, J4,5 = J5,6 = 10.0 Hz, 1H; H-5), 4.82 (dd, J8,9a = 3.0 Hz, J9a,9b = 12.5 Hz, 1H; H-
9a), 4.55 (dd, J8,9b = 7.0 Hz, J9a,9b = 12.5 Hz, 1H; H-9b), 3.62 (s, 3H; OMe), 2.91
(dd, J3a,3e = 14.0 Hz, J3e,4 = 4.5 Hz, 1H; H-3e), 2.43 (dd, J3a,3e = 14.0 Hz, J3a,4 = 10.5
Hz, 1H; H-3a), 2.13 (s, 3H; PhMe), 1.71 (s, 3H; Ac). 13C NMR (125 MHz, DMSO-
d6, 80 °C) d 173.38, 172.59, 167.26, 164.82, 164.72, 164.69, 164.30, 139.32,
135.25, 135.14, 133.10, 132.91, 132.69, 132.51, 129.36, 129.05, 128.98, 128.94,
128.74, 128.66, 128.53, 128.30, 128.27, 128.15, 128.04, 127.95, 124.89, 88.31,
72.07, 69.73, 69.10, 67.96, 61.76, 55.80, 51.97, 37.45, 26.84, 20.08. HRMS (ESI)
calcd for C54H47NO13S [M+Na]+ 972.2660; found: 972.2663.
20. Chambers, D. J.; Evans, G. R.; Fairbanks, A. J. Tetrahedron 2005, 61, 7184.
21. Crich, D.; Wu, B. Org. Lett. 2008, 10, 4033.
22. Selected data for methyl 5-acetamido-4,7,8,9-tetra-O-benzoyl-5-N-benzoyl-
3,5-dideoxy-
2,3,4-tri-O-benzyl-
D
-glycero-b-
D-galacto-non-2-ulopyranosylonate-(2?6)-methyl
a-D
-galactopyranoside (11b). 1H NMR (500 MHz, DMSO-d6,
80 °C) d 8.06 (d, J = 7.5 Hz, 2H; Ar), 7.83–7.19 (m, 38H; Ar), 6.08 (dt, J3e,4 = 5.0
Hz, J3a,4 = J4,5 = 10.0 Hz, 1H; H-4), 5.85 (d, J7,8 = 5.0 Hz, 1H; H-7), 5.78 (m, 1H; H-
8), 5.25 (d, J5,6 = 10.0 Hz, 1H; H-6), 5.06 (dd, J8,9a = 2.5 Hz, J9a,9b = 12.5 Hz, 1H;