Effective synthesis of nucleosides with glycosyl trifluoroacetimidates as donors

Article abstract of DOI:10.1016/j.tetlet.2008.06.042

Glycosyl trifluoroacetimidates have been disclosed to be effective glycosyl donors for the synthesis of nucleosides; the present N-glycosylation protocol requires only a catalytic amount of TMSOTf as promoter and proceeds smoothly at room temperature.

Full text of DOI:10.1016/j.tetlet.2008.06.042

Tetrahedron Letters 49 (2008) 5036–5038
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Tetrahedron Letters
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Effective synthesis of nucleosides with glycosyl trifluoroacetimidates as donors
a,
Jinxi Liao b, Jiansong Sun a, , Biao Yu
*
*
a State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
b Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Glycosyl trifluoroacetimidates have been disclosed to be effective glycosyl donors for the synthesis
of nucleosides; the present N-glycosylation protocol requires only a catalytic amount of TMSOTf as
promoter and proceeds smoothly at room temperature.
Received 16 April 2008
Revised 4 June 2008
Accepted 10 June 2008
Available online 13 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Glycosyl trifluoroacetimidates
Nucleosides
N-Glycosylation
Since the introduction of the silyl variation of the Hilbert-John-
son reaction1 by Iwai and Nishimura in 1964,2 many types of gly-
cosyl donors have been applied in the synthesis of a large variety of
the nucleosides. Among them, 1-O-acetyl sugars, in the presence of
a strong Lewis acid, are the most frequently used glycosyl donors.3
However, in all these methods, either stoichiometric amount of the
promoter or high temperature is required to secure high-yielding
of the N-glycosylation. Glycosyl trichloroacetimidates,4 one of the
most favorable types of glycosyl donors for O-glycosylation, which
require a catalytic amount of Lewis acid (e.g., TMSOTf and
BF3ꢀOEt2) at low temperature for activation, have rarely been em-
ployed in the nucleosides synthesis.5 Recently, glycosyl trifluoro-
acetimidates have been found to be valuable alternatives to the
trichloroacetimidates as glycosylation donors,6 showing advanta-
ges especially in the sialylation,7 glycosylation of hydroxamic
acids,8 and N-glycosylation of amides.9 Herein, we report effective
glycosylation of nucleobases employing glycosyl trifluoroacetimi-
dates as donors under mild conditions.
of the solvent.11 As shown in Scheme 1 and Table 1, glycosylation
of the silylated uracil and thymine with the ribofuranosyl trifluoro-
acetimidates 1a and 1b proceeded smoothly in the presence of
0.1 equiv of TMSOTf at room temperature, providing the corre-
sponding b-nucleosides (3aa,12 3ab,13 3ba,12 and 3bb14
) in
88–98% yields (entries 1, 2, 4, and 5). Glycosylation of the pyr-
idin-2-one (2c) with the tri-O-benzoyl-ribofuranosyl trifluoroace-
timidate 1a gave the b-nucleoside 3ac15 in 98% yield (entry 3),
however, with the tri-O-acetyl-ribofuranosyl trifluoroacetimidate
1b led to the desired nucleoside 3bc in only 64% yield (entry 6).
N-Trimethylsilylacetamide, resulting from the silylation reagent
BSA, competed for the N-glycosylation to afford the 1-N-acetyl-b-
ribofuranosylamine 4b in a remarkable 30% yield. Glycosylation
of the nucleobases with the tetra-O-acetyl- and -benzoyl-D-gluco-
pyranosyl trifluoroacetimidates 1c and 1d under similar conditions
was found unsuccessful. While coupling of 1c with uracil gave the
O
O
The tri-O-benzoyl- and -acetyl-
D
-ribofuranosyl trifluoroacetim-
N
idates 1a19 and 1b,8 tetra-O-acetyl-, -benzoyl-, and -benzyl-
D-glu-
N
H
O
H
copyranosyl trifluoroacetimidates 1c,6 1d,6 and 1e6 were readily
prepared by condensation of the corresponding 1-OH sugars and
N-phenyl trifluoroacetimidoyl chloride in the presence of K2CO3
in acetone.6,8 Uracil, thymine, and pyridin-2-one (2a–c) were
chosen as the nucleobases. These nucleobases were treated with
N,O-bis(trimethylsilyl)acetamide (BSA)10 in dry acetonitrile to
provide the corresponding silylated bases, which are sensitive
toward moisture, and therefore were used directly after removal
4
2a c
-
OTMS
NTMS
BSA
O
NHTMS
NPh
+
TMSOTf (0.1 eq)
ClCH2CH2Cl, rt
O
O
+
CF3
N
O
O
N
OTMS
1a-e
3
* Corresponding authors. Tel.: +86 21 54925131; fax: +86 21 64166128 (B.Y.).
E-mail address: byu@mail.sioc.ac.cn (B. Yu).
Scheme 1. Nucleoside synthesis employing glycosyl trifluoroacetimidates as
donors and BSA as a silylation reagent.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.06.042

J. Liao et al. / Tetrahedron Letters 49 (2008) 5036–5038
5037
Table 1
OR
O
2a c
-
H
N
OTMS
NTMS
BSTFA
Nucleoside synthesis employing glycosyl trifluoroacetimidates as donors and BSA as a
RO
RO
silylation reagenta
O
F3C
O
OR
F3C
O
O
OR
O
5c R = Ac, 5d R = Bz
F3C
O
NHTMS
NPh
NPh
R
RO
HN
RO
RO
O
CF3
NPh
O
O
TMSOTf (0.1 eq)
OTMS
ClCH2CH2Cl, rt
O
N
H
N
H
O
OR
1c R = Ac
+
N
O
CF3
N
N
RO
OR
2a R = H
2b
2c
3
O
1c-e
1a R = Bz
1d
R = Bz
R = Me
1b
R = Ac
O
1e R = Bn
or
O
N
N
O
O
NH
NH
O
5
O
O
O
TMS
N
O
N
RO
RO
RO
RO
O
O
Scheme 2. Nucleoside synthesis employing glucopyranosyl trifluoroacetimidates
3aa R = Bz
3ab R = Bz
3ac R = Bz
3bc
as donors and BSTFA as a silylation reagent.
RO
3ba
RO
3bb
RO
OR
R = Ac
OR
R = Ac
OR
R = Ac
OR
OR
O
O
NH
O
O
NH
O
OR
methylsilyl)trifluoroacetamide (BSTFA)17 was used instead. The
O
O
RO
RO
RO
RO
N
N
N
resultant N-trimethylsilyltrifluoroacetamide,
a much weaker
RO
OR
nucleophile, could hardly compete with the nucleobases for glycos-
ylation. Thus, the previously unsuccessful coupling reactions with
BSA were examined with BSTFA as the silylation reagent. The
results are listed in Scheme 2 and Table 2.
OR
O
OR
3ca R = Ac
3cb R = Ac
3cc R = Ac
3da
3db
R = Bz
R = Bz
3dc
R = Bz
3ea R = Bn
3eb R = Bn
3ec R = Bn
O
OAc
AcO
Expectedly, glycosylation of uracil and thymine with the tetra-
acetyl-glucopyranosyl trifluoroacetimidate 1c provided the corre-
sponding b-nucleosides 3ca16 and 3cb18 in excellent 87% and 91%
yields, respectively (entries 1 and 2). However, under similar con-
ditions, coupling of 1c with pyridin-2-one provided the O-glycosyl-
ation product 5c19 (C1 at 93.2 ppm) dominantly (80%, entry 4).
When the silylation time was prolonged (from the original 0.5 h
to 12 h), the otherwise similar coupling procedure afforded the
N-glycosylation product 3cc19 (C1 at 79.0 ppm) as the major prod-
uct (86%, entry 3). The glycosylation of uracil with the tetra-
benzoyl-glucopyranosyl trifluoroacetimidate 1d again led to a
complex mixture (entry 5). Nevertheless, glycosylation of thymine
with 1d proceeded smoothly, providing the nucleoside 3db19 in an
excellent 91% yield (entry 6). Glycosylation of pyridin-2-one with
1d led to the O-glycosylation product 5d19 in good yield, regardless
of the variation of the silylation time (entry 7). Finally, glycosyl-
ation of pyridin-2-one with 1e took place under the present condi-
tions, furnishing the nucleoside 3ec19 as a pair of the anomers in
63% yield (entry 8).
In summary, glycosyl trifluoroacetimidates have been disclosed
to be effective glycosyl donors for the synthesis of nucleosides. The
present N-glycosylation protocol requires only a catalytic amount
of TMSOTf as promoter and proceeds smoothly at room tempera-
ture. The procedure for the silylation of the bases also affects the
subsequent glycosylation reaction. BSTFA has been shown to be
superior to BSA for the subsequent glycosylation with pyranosyl
donors.
HN
O
H
N
O
AcO
AcO
OAc
4c
4b
O
AcO OAc
Entry
Donor
Acceptor
Product
Yieldb (%)
a
:bc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a
2a
2b
2c
2a
2b
2c
2a
2b
2c
2a
2b
2c
2a
2b
2c
3aa
3ab
3ac
98
88
98
98
88
64 + 30
45
60
—
—
—
—
87
84
—
b
b
b
b
b
b
b
b
1b
1c
1d
1e
3ba
3bb
3bc + 4b
3ca
4c
4c
NR
NR
NR
3ea
—
—
—
—
1:2
1:2.5
—
3eb
Complex
a
A typical procedure: To a stirred suspension of the nucleobase (1.5 equiv) in dry
acetonitrile was added BSA (2 equiv for 2a and 2b, 1 equiv for 2c). The mixture was
stirred at rt for 30 min, leading to a clear solution. The solvent was removed under
reduced pressure to provide a clear oil. Under argon atmosphere, the resulting oil
was dissolved in dry 1,2-dichloroethane, followed by addition of the activated 4 Å
MS and the glycosyl trifluoroacetimidate (1.0 equiv). After subsequent addition of
TMSOTf (0.1 equiv), the mixture was stirred at rt until the imidate was consumed
completely (12–48 h), as monitored by TLC.
b
Isolated yield.
c
Determined by 1H NMR.
Table 2
nucleoside 3ca16 in a moderate 45% yield, coupling of 1c with thy-
mine and pyridin-2-one led to the 1-N-acetyl-b-glucosylamine 4c
Nucleoside synthesis employing glucopyranosyl trifluoroacetimidates as donors and
BSTFA as a silylation reagenta
Yieldb (%)
a
:bc
as the major product (entries 7–9). The tetra-O-benzoyl-D-gluco-
Entry
Donor
Acceptor
Product
pyranosyl trifluoroacetimidate 1d remained intact under these
conditions (entries 10–12). The glycosylation of uracil and thymine
with the ‘armed’ tetra-benzyl-glucopyranosyl trifluoroacetimidate
1e afforded the desired nucleosides 3ea19 and 3eb19 in 87% and
84% yields, respectively; albeit each in a pair of the anomers, in
the absence of a neighboring participating group in the donors
(entries 13 and 14). The reaction of 1e with pyridin-2-one failed,
leading to a complex mixture (entry 15).
1
2
3d
4
5
6
7
8
1c
2a
2b
2c
2c
2a
2b
2c
2c
3ca
3cb
3cc
5c
NR
3db
5d
87
91
86
80
—
91
86
63
b
b
b
b
—
b
1d
1e
b
1:3
3ec
a
A similar procedure as that described in Table 1 was used.
Isolated yield.
The unsuccessful glycosylation encountered above are partially
due to the competing glycosylation of the N-trimethylsilylacet-
amide resulting from the silylation reagent BSA. Thus, N,O-bis(tri-
b
c
Determined by 1H NMR.
d
The silylation time was prolonged from the standard 0.5–12 h.

5038
J. Liao et al. / Tetrahedron Letters 49 (2008) 5036–5038
(d, J = 8.7 Hz, 1H), 5.28 (d, J = 8.4 Hz, 1H), 4.87–4.42 (m, 8H), 3.80–3.40 (m, 6H);
Acknowledgments
13C NMR (75 MHz, CDCl3) d 162.8, 150.3, 137.9, 137.6, 136.8, 128.7, 128.5,
128.4, 128.4, 128.3, 127.83, 127.82,127.7, 127.7, 102.8, 85.7, 78.3, 77.4, 77.3,
75.8, 75.0, 74.5, 73.3, 68.1. HRMS (ESI) calcd for C38H38N2O7Na [M+Na]+:
657.2571. Found: 657.2556.
Financial support from the National Natural Science Foundation
of China (20621062) and the Committee of Science and Technology
of Shanghai (06XD14026 and 07DZ22001) is gratefully
acknowledged.
1-(2,3,4,6-Tetra-O-benzyl-b-D-glucopyranosyl)thymine (3eb): For the a isomer:
½
a 2D5
ꢁ
ꢂ21.4 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3) d 8.20 (s, 1H), 7.38–7.06
(m, 21H), 5.98 (s, 1H), 4.53–4.22 (m, 9H), 3.98 (s, 1H), 3.77 (s, 1H), 3.69–3.60
(m, 3H), 1.74 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 164.1, 149.8, 138.0, 137.8,
137.5, 137.2, 136.6, 128.5, 128.43, 128.39, 128.3, 128.2, 128.1, 128.0, 127.7,
109.0, 78.8, 76.6, 76.0, 75.0, 74.1, 73.5, 73.1, 72.3, 71.9, 69.4, 12.3. For the b
References and notes
isomer: ½a 2D5
ꢁ
ꢂ42.9 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3) d 8.21 (s, 1H),
1. Nishimura, T.; Iwai, I. Chem. Pharm. Bull. (Tokyo) 1964, 12, 352.
2. Hilbert, G. E.; Johnson, T. B. J. Am. Chem. Soc. 1930, 52, 4489.
3. (a) Vorbrüggen, H.; Ruh-Pohlenz, C. Org. React. 2000, 55, 1; (b) Vorbrüggen, H.
Acc. Chem. Res. 1995, 28, 509.
4. Schmidt, R. R.; Michel, J. Angew. Chem., Int. Ed. Engl. 1980, 19, 731.
5. (a) Chanteloup, L.; Thuong, N. T. Tetrahedron Lett. 1994, 35, 877; (b) Shohda, K.;
Wada, T.; Sekine, M. Nucleosides Nucleotides 1998, 17, 2199.
6. (a) Yu, B.; Tao, H. Tetrahedron Lett. 2001, 42, 2405; (b) Yu, B.; Tao, H. J. Org.
Chem. 2002, 67, 9099; (c) Adinolfi, M.; Barone, G.; Iadonisi, A.; Schiattarella, M.
Synlett 2002, 269.
7.37–7.16 (m, 20H), 6.65 (s, 1H), 5.59 (d, J = 9.0 Hz, 1H), 4.86 (s, 2H), 4.95–4.45
(m, 6H), 3.87 (t, J = 8.7 Hz, 1H), 3.74–3.58 (m, 4H), 3.46 (t, J = 8.7 Hz, 1H), 1.67
(s, 3H); 13C NMR (75 MHz, CDCl3) d 163.4, 150.5, 138.0, 137.61, 137.56, 136.9,
128.6, 128.43, 128.40, 128.36, 128.3, 128.1, 127.8, 127.7, 110.9, 85.9, 77.8, 77.4,
75.7, 75.0, 74.2, 73.2, 68.0. HRMS (ESI) calcd for C39H40N2O7Na [M+Na]+:
671.2728. Found: 671.2709.
1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dihydropyridin-2-one ( 3cc):
1H NMR (300 MHz, CDCl3) d 7.39 (d, J = 6.6 Hz, 1H), 7.34 (dd, J = 8.7, 6.9 Hz,
1H), 6.53 (d, J = 9.0 Hz, 1H), 6.34 (d, J = 9.3 Hz, 1H), 6.28 (t, J = 6.9 Hz, 1H), 5.46
(t, J = 9.3 Hz, 1H), 5.24 (m, 2H), 4.30 (dd, J = 4.8, 12.6 Hz, 1H), 4.13 (d,
J = 11.1 Hz, 1H), 3.96 (dd, J = 3.3, 9.9 Hz, 1H), 2.05, 2.03, 2.00, 1.91 (s each, 3H
each); 13C NMR (75 MHz, CDCl3) d 170.2, 169.4, 169.3, 169.1, 161.5, 139.9,
132.5, 120.1, 106.4, 79.0, 74.6, 72.5, 70.3, 67.7, 61.5, 20.4, 20.3, 20.2, 19.9.
HRMS (ESI) calcd for C19H23NO10Na [M+Na]+: 448.1214. Found: 448.1214.
7. Cai, S.; Yu, B. Org. Lett. 2003, 21, 3827.
8. Thomas, M.; Gesson, J. P.; Papot, S. J. Org. Chem. 2007, 72, 4262.
9. Tanaka, H.; Iwata, Y.; Takahashi, D.; Adachi, M.; Takahashi, T. J. Am. Chem. Soc.
2005, 127, 1630.
10. (a) Klebe, J. F. Acc. Chem. Res. 1970, 3, 299; (b) Sell, T. B.; Nair, V. Tetrahedron
1994, 50, 117; (c) Caplar, V.; Zinic, M. Tetrahedron Lett. 1995, 36, 4455.
11. (a) Dudycz, L. W.; Wright, G. E. Nucleosides Nucleotides 1984, 3, 34; (b) Matulic-
Adamic, J.; Gonzalez, C.; Usman, N.; Beigelman, L. Bioorg. Med. Chem. Lett. 1996,
6, 373.
2-[(2,3,4,6-Tetra-O-acetyl-b-D
-glucopyranosyl)-oxy]pyridine (5c): 1H NMR
(300 MHz, CDCl3) d 8.16 (d, J = 4.2 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.00 (t,
J = 6 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 6.21 (d,J = 7.2 Hz, 1H), 5.34–5.30 (m, 2H),
5.23 (t, J = 8.7 Hz, 1H), 4.34 (dd, J = 3.9, 12.3 Hz, 1H), 4.13 (d, J = 12.3 Hz, 1H),
3.96 (d, J = 9.3, 1H), 2.04, 2.02, 1.98 (s each, 3H each); 13C NMR (75 MHz, CDCl3)
d 170.5, 170.1, 169.32, 169.28, 161.1, 146.6, 139.2, 118.7, 111.6, 93.2, 72.9,
71.9, 70.6, 67.9, 61.5, 20.5, 20.44, 20.39. HRMS (ESI) calcd for C19H23NO10Na
[M+Na]+: 448.1214. Found: 448.1214.
12. Nowal, I.; Robins, M. J. Org. Lett. 2005, 7, 4903.
13. Sheng, J.; Jiang, J.-S.; Salon, J.; Huang, Z. Org. Lett. 2007, 9, 749.
14. Chow, K.; Danishefsky, S. J. Org. Chem. 1990, 55, 4211.
15. Matulic-Adamic, J.; Gonale, C.; Usman, N.; Beigelman, L. Bioorg. Med. Chem. Lett.
1996, 6, 373.
16. Haeckel, R.; Weber, K.; Germann, C.; Haberkorn, V.; Zeisler, S.; Eisenbarth, J.;
Wiessler, M.; Oberdor, F. J. Labbel. Compds. Radiopharm. 1996, 38, 1061.
17. (a) Johnson, F.; Pillai, K. M. R.; Grollman, A-P.; Tseng, L.; Takeshita, M. J. Med.
Chem. 1984, 27, 954; (b) Siddiqui, A. P.; Driscoll, J. S.; Marquez, V. E.; Roth, J. S.;
Shirasaka, T.; Mitsuya, H.; Barchi, J. J.; Kelley, J. A. J. Med. Chem. 1992, 35, 2195.
18. Ermolinsky, B-S.; Fomitcheva, M-V.; Efimtseva, E-V.; Meshkov, S-V.; Mikhailov,
S-N. Nucleosides Nucleotides 1996, 15, 1619.
1-(2,3,4,6-Tetra-O-benzoyl-b-
D
-glucopyranosyl)thymine ( 3db): ½a D25
ꢁ
5.0 (c 1.0,
CHCl3); 1H NMR (300 MHz, CDCl3) d 8.47 (s, 1H), 8.05–7.74 (m, 8H), 7.62–7.22
(m, 13H), 6.27 (d, J = 9.3 Hz, 1H), 6.11 (dd, J = 9.6, 9.9 Hz, 1H), 5.81 (dd, J = 9.6,
10.2 Hz, 1H), 5.71 (dd, J = 9.9, 9.3 Hz, 1H), 4.69 (dd, J = 2.4, 12.6 Hz, 1H), 4.51–
4.39 (m, 2H), 1.94 (s, 3H); 13C NMR (75 MHz, CDCl3) d 165.9, 165.3, 165.09,
165.07, 163.4, 150.5, 134.4, 133.6, 133.5, 133.2, 133.1, 129.8, 129.7, 129.6,
129.5, 129.1, 128.33, 128.26, 128.21, 128.17, 127.7, 112.1, 80.2, 74.9, 72.8, 69.9,
68.7, 62.6, 12.4; HRMS (ESI) calcd for C39H32N2O11Na [M+Na]+: 727.1898.
Found: 727.1907.
-glucopyranosyl)-oxy]pyridine (5d): ½a D25
ꢁ
56.2 (c
19. Selected data for new compounds: 2,3,5-Tri-O-benzoyl-D-ribofuranosyl(N-
2-[(2,3,4,6-Tetra-O-benzoyl-b-
D
phenyl)trifluoroacetimidate ( 1a): 1H NMR (300 MHz, CDCl3) d 8.12–7.82 (m,
6H), 7.62–7.23 (m, 11H), 7.12 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 8.1 Hz, 2H), 6.60 (s,
1H), 6.01–5.92 (m, 2H), 4.90–4.85 (m, 1H), 4.78 (dd, J = 3.9, 12.0 Hz, 1H), 4.65
(dd, J = 5.4, 12.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 166.0, 165.2, 164.9,
143.2, 133.7, 133.5, 133.2, 129.8, 129.7, 129.6, 129.3, 128.6, 128.5 (2C), 128.4
(2C), 128.3 (2C), 124.3, 119.3, 101.4, 80.5, 74.8, 71.4, 63.8. HRMS (ESI) calcd for
1.0, CHCl3); 1H NMR (300 MHz, CDCl3) d 8.12 (d, J = 4.2 Hz, 1H), 8.00–7.85 (m,
8H), 7.60–7.23 (m, 13H), 6.96 (dd, J = 6.3, 5.7 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H),
6.57 (d, J = 8.1 Hz, 1H), 6.08 (t, J = 9.6 Hz, 1H), 5.88–5.75 (m, 2H), 4.68–4.36 (m,
J = 8.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 166.0, 165.7, 165.12, 165.08, 161.1,
146.5, 139.2, 133.4, 133.2, 132.9, 129.64, 129.60, 129.58, 129.57, 129.4, 128.8,
128.53, 128.51, 128.33, 128.26, 128.1, 118.7, 111.6, 93.8, 73.1, 72.4, 71.3, 69.4,
C
39H31NO10Na [M+Na]+: 696.1840. Found:
C
38H38N2O7Na [M+Na]+: 656.1503. Found: 656.1506.
1-(2,3,5-Tri-O-acetyl-b- -ribofuranosyl)-1,2-dihydropyridin-2-one (3bc):
62.8; HRMS (ESI) calcd for
696.1843.
D
½ ꢁ
a 2D5
110.1 (c 0.45, CHCl3); 1H NMR (300 MHz, CDCl3) d 7.54 (dd, J = 1.2, 7.2 Hz,
1H), 7.36 (dt, J = 1.8, 9.0 Hz, 1H), 6.53 (d, J = 9.0 Hz, 1H), 6.30 (d, J = 4.2 Hz, 1H),
6.24 (dt, J = 6.0, 1.2 Hz, 1H), 5.41–5.29 (m, 2H), 4.35–4.33 (m, 3H), 2.14, 2.11,
2.08 (s each, 3H each); 13C NMR (75 MHz, CDCl3) d 170.1, 169.5, 169.3, 162.0,
139.8, 132.0, 121.0, 106.2, 88.0, 79.2, 73.8, 69.5, 62.6, 20.6, 20.4. HRMS (ESI)
calcd for C16H19NO8Na [M+Na]+: 376.1003. Found: 376.1005.
1-(2,3,4,6-Tetra-O-benzyl-D-glucopyranosyl)-1,4-dihydropyridin-2-one (3ec): For
the
a
isomer: ½a 2D5
ꢁ
ꢂ89.0 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3) d 7.80 (s,
1H), 7.42–7.13 (m, 19H), 7.09–7.06 (m, 2H), 6.53 (d, J = 9.3 Hz, 1H), 6.41 (d,
J = 2.7 Hz, 1H), 6.21 (dd,J = 6.9, 6.3 Hz, 1H), 4.63–4.29 (m, 10H), 3.83–3.63 (m,
4H); 13C NMR (CDCl3, 75 MHz) d 162.0, 139.6, 138.0, 137.7, 137.3, 137.2, 134.9,
128.44, 128.38, 128.30, 128.27, 128.1, 128.0, 127.9, 127.82, 127.81, 127.7,
127.6, 127.5, 119.6, 105.1, 79.8, 76.6, 74.8, 73.4, 73.3, 72.9, 71.9, 71.7, 69.8. For
1-(2,3,4,6-Tetra-O-benzyl-
D
-glucopyranosyl)uracil (3ea): For the
a
isomer: ½a 2D5
ꢁ
ꢂ30.4 (c 0.45, CHCl3); 1H NMR (300 MHz, CDCl3) d 8.16 (s, 1H), 7.53 (d,
J = 8.1 Hz, 1H), 7.27–7.07 (m, 20H), 5.96 (s, 1H), 5.54 (d, J = 7.5 Hz, 1H), 4.52–
4.21 (m, 9H), 3.98 (s, 1H), 3.76 (s, 1H), 3.67–3.60 (m, 3H); 13C NMR (75 MHz,
CDCl3) d 164.0, 149.8, 142.1, 137.8, 137.5, 137.1, 136.4, 128.6, 128.5, 128.40,
128.36, 128.3, 128.1, 128.1, 127.8, 127.7, 127.6, 100.8, 79.3, 76.6, 76.2, 74.9,
the b isomer: ½a 2D5
ꢁ
69.9 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3) d 7.38–7.12
(m, 20H), 7.09–7.06 (m, 1H), 6.60 (d, J = 10.2 Hz, 1H), 6.21 (d, J = 9.3 Hz, 1H),
6.09 (dd, J = 6.6, 6.9 Hz, 1H), 4.90–4.84 (m, 3H), 4.62–4.31 (m, 5H), 3.95–3.59
(m, 6H); 13C NMR (75 MHz, CDCl3) d 161.9, 139.2, 138.0, 137.68, 137.66, 137.0,
132.5, 128.2, 128.1, 127.9, 127.7, 127.6, 127.53, 127.49, 127.47, 120.7, 106.1,
85.3, 80.6, 77.4, 75.4, 74.8, 74.2, 73.1, 68.1. HRMS (ESI) calcd for C39H39NO6Na
[M+Na]+: 640.2670. Found: 640.2661.
73.7, 73.4, 73.0, 72.2, 71.9, 69.3. For the b isomer: ½a D25
ꢁ
ꢂ22.7 (c 0.9, CHCl3); 1
H
NMR (300 MHz, CDCl3) d 7.28–7.11 (m, 20H), 6.81 (dd, J = 3.6, 8.4 Hz, 1H), 5.52