A mild method for regioselective de-O-methylation of saccharides by Co2(CO)8/Et3SiH/CO system

Article abstract of DOI:10.1016/j.tet.2016.07.081

A new method for cleaving methyl ethers off protected saccharides using Co₂(CO)₈/Et₃SiH/CO system was developed. The method showed regioselectivity in different protected monosaccharides with various anomeric groups. The p

Full text of DOI:10.1016/j.tet.2016.07.081

Tetrahedron 72 (2016) 5699e5706
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A mild method for regioselective de-O-methylation of saccharides
by Co2(CO)8/Et3SiH/CO system
,b,
Yue-tao Zhao a, Lu-bai Huang a, Qing Li a, Zhong-jun Li a
*
a State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health
Science Center, Beijing 100191, PR China
b National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 June 2016
Received in revised form 25 July 2016
Accepted 30 July 2016
Available online 2 August 2016
A new method for cleaving methyl ethers off protected saccharides using Co2(CO)8/Et3SiH/CO system was
developed. The method showed regioselectivity in different protected monosaccharides with various
anomeric groups. The primary and equatorial secondary methyl ethers were preferentially removed. This
method was successfully applied to the synthesis of the DEF trisaccharide segment of Idraparinux, which
is highly methylated.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
De-O-methylation
Saccharides
Dicobalt octacarbonyl
Regioselectivity
1. Introduction
suitable for regioselective de-O-methylation of saccharides, such
as MeS-SiMe3/ZnI2/n-Bu4NI,7 oxidation-based cleavage of DIB,8
Selective protection and deprotection of hydroxyl groups are
critical transformations in carbohydrate chemistry. Among the
many protecting groups, methyl ether is less frequently used than
other ethers such as benzyl ether because of its harsh cleavage
conditions, despite its simple installation and inherent stability.
On the other hand, methyl group protected saccharides are widely
found in various therapeutic agents and materials, such as idra-
parinux, cyclodextrin, and surfactants, because the protection of
the hydroxyl group with a methyl group may enhance the stability
of saccharides while also maintaining its solubility.1 Compre-
hensive research on the formation and cleavage of methyl ethers
is important for the synthesis of such complex oligosaccharides. In
particular, several methods have been developed to remove
methyl ethers, including acids (HCl, H2SO4, TFA), Lewis acids
(BBr3, BCl3, AlCl3, SiCl4, NbCl5, MgI, TMSI),2 bases (LHDMS, PhSK,
Et2NCH2CH2SH),3 reductive cleavage (LAH,4 DIBAL-H and TIBAL1-
b,5a,b), and ionic liquids.6 However, these methods are some-
times too harsh for saccharide substrates such as thioglycosides
and phenolic glycosides, or not able to remove the methyl ether
regioselectively, which is essential for the synthesis of complex
oligosaccharides. There are only a few reported conditions that are
and engineered cytochrome P450BM3 demethylases.9 However,
the substrate scope of these methods is limited, and development
of a novel method for regioselective de-O-methylation is essential
and a great challenge.
The most famous methylated oligosaccharide, idraparinux, is
a derivative of fondaparinux, which is an efficient and safe anti-
coagulant drug used in the clinic.10 With many hydroxyl groups
protected by methyl ethers, the synthesis of idraparinux is simpler
than that of fondaparinux. Moreover, it has better inhibitory ac-
tivity and much longer half-life. In addition, the dosage and ad-
ministration frequency of idraparinux are also less than those of
fondaparinux. Because of these advantages, idraparinux has been
extensively studied recently.11 However, the synthesis of idrapar-
inux is still a challenge, usually requiring 40 steps, with multiple
protecting group transformations.12 Considering the numerous
methyl ethers in idraparinux, regioselective de-O-methylation may
simplify the total synthesis.
In our previous study, the Co2(CO)8/Et3SiH/CO system was found
to be efficient in the cleavage of benzyl and p-methoxybenzyl
groups in saccharide and non-saccharide substrates.13 This re-
activity was mediated by the strong Lewis acidity and electrophi-
licity of the in situ generated Et3SiþCo(CO)4ꢀ reagent. In this article,
we report a novel method for the regioselective cleavage of methyl
ethers in a wide variety of monosaccharides by the Co2(CO)8/
Et3SiH/CO system (Scheme 1A). Furthermore, we explored the use
* Corresponding author. Fax: þ86 10 8280 5496; e-mail address: zjli@bjmu.edu.
cn (Z.-jun Li).
http://dx.doi.org/10.1016/j.tet.2016.07.081
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

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Y.-tao Zhao et al. / Tetrahedron 72 (2016) 5699e5706
of regioselective de-O-methylation by this system to the synthesis
of the DEF trisaccharide segment of idraparinux, which could be
used as an intermediate for the total synthesis of idraparinux
(Scheme 1B).
with the fact that the actual catalytic reagent Et3SiþCo(CO)4ꢀ
generated by Co2(CO)8/Et3SiH/CO system in situ was sensitive to
the steric hindrance and the hindrance of 6-OMe was smallest.
Increasing the temperature to 70 ꢁC or the reaction time to 72 h
Scheme 1. (A)Regio-selective de-O-methylation of saccharides Co2(CO)8/Et3SiH/CO system; (B) Synthesis of DEF trisaccharides segment of idraparinux by regioselective de-O-
methylation strategy.
2. Results and discussion
did not improve the conversion of 1a (data not shown). With
6.0 equiv of Co2(CO)8, 85% of 1a reacted, generating 52% 1b and
18% de-2, 6-di-O-methylation product 1c (the de-O-methylation
site was confirmed by the chemical shifts and coupling con-
stants of the hydrogen at the acetylation position, Table 1, Entry 2,
and Table 2, Entry 1), indicating that enough amount of Co2(CO)8
is essential for sufficient conversion of 1a. Lowering the temper-
ature to room temperature gave no reaction of 1a (Table 1, Entry
3), indicating that sufficiently high reaction temperatures were
needed. If the solvent was changed to benzene, 40% of 1a
remained unreacted, and the products were a mixture of 1b and
de-2, 6-di-O-methylation products (Table 1, Entry 4). Changing
the silane to PhMe2SiH and reducing the amount used, 1a was
reacted completely but the products were too complex to purify
Recently, our laboratory extended the highly efficient and mild
de-O-benzylation method with the Co2(CO)8/Et3SiH/CO system to
the cleavage of p-methoxybenzyl ethers (PMB).13 We found that
except for the PMB group, a methyl group on PMB in per-p-
methoxybenzylated glucoside was also removed when reacted at
80 ꢁC. We were interested in this observation and hoped to find an
efficient method for selective de-O-methylation of protected
sugars. Therefore, we used per-methylated-b-thioglucoside 1a as
a model substrate to explore and optimize the reaction condition.
To simplify the purification steps and identification of the products,
we further transformed the generated silyl ether to an acetyl group
by treating with TBAF/THF and Ac2O/Py (Table 1).
Table 1
Condition screening of de-O-methylation with per-methylated-b-thioglucoside as model substrate
Entry
Silane
Co2(CO)8 (equiv)
Solvent
T (ꢁC)
Time (h)
Yield (%)a
1
2
3
4
5
6
Et3SiH
Et3SiH
Et3SiH
Et3SiH
PhMe2SiH
PhMe2SiH
3.0
6.0
6.0
6.0
1.0
0.5
Toluene
Toluene
Toluene
Benzene
Toluene
Toluene
50
50
rt.
50
50
50
48
42
48
48
24
24
63b
52þ18c
0
45þ15d
de
de
a
Yield of 3 steps.
37% of 1a was unreacted.
b
c
52% of 1b and 18% of de-2, 6-bi-O-methylation product 1c were obtained, with 15% of 1a unreacted (see Table 2, entry 1 for more details).
45% of 1b and 15% of 1c were obtained, with 40% of 1a unreacted.
1a was completely reacted but the products were rather complex.
d
e
As shown in Table 1, 1a was treated with different equivalents
(Table 1, Entry 5 and 6), indicating that PhMe2SiH was too reactive
and additional methyl ethers were removed. Consequently, our
optimized reaction condition was 6.0 equiv of Co2(CO)8, 20 equiv
of Et3SiH, and CO (1 atm) in toluene at 50 ꢁC, which could convert
the starting materials adequately and gave sufficient product
yield.
of Co2(CO)8, silanes, solvents, and temperatures. When the re-
action was carried out with 3.0 equiv of Co2(CO)8 and 20 equiv of
Et3SiH for 48 h at 50 ꢁC in toluene, 63% of de-6-O-methyltion
product was obtained with 37% of 1a unreacted (Table 1, Entry 1).
The de-O-methylation happened at 6-OMe was in accordance

Y.-tao Zhao et al. / Tetrahedron 72 (2016) 5699e5706
5701
Table 2
Regioselective de-O-methylation of methylated saccarides by Co2(CO)8/Et3SiH/CO system
Entry
1
Substrates
Time (h)
42
Results
1a
1b
1c
52%
18%
2a
48
48
2b
84%
2a
3a
3a
3b
85%
4a
48
48
48
28
4b
87%
4a
5a
6a
5
5b
5c
5d
43%
18%
16%
6
6bb
40%
7
7b b
49%
7c
28%
7d
8%
7a
8a
8
9
48
48
8b b
27%
8c
41%
8d
15%
9b
42%
9c
36%
9a
10
48
10b
30%
10c
27%
10d
8%
10a
(continued on next page)

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Y.-tao Zhao et al. / Tetrahedron 72 (2016) 5699e5706
Table 2 (continued )
Entry
Substrates
Time (h)
Results
11c
12c
18
48
11b
55%
11c
43%
11a
12b
30%
12c
30%
12a
a
The reaction was performed at 70 ꢁC. b the removal of silly ether by TBAF/THF was performed at 50 ꢁC for 2 h c No transformation of hydroxyl group to acetyl group was
performed. d No transformation of silyl group to acetyl group was performed.
Under the established conditions, a wide variety of methylated
saccharide substrates were treated with the Co2(CO)8/Et3SiH/CO
system, and the results are summarized in Table 2. In these sub-
strates, the 6-OMe was preferentially removed. For example, the
cleavage of the equatorial 3-OMe and 4-OMe groups and non-
reactivity of the axial 2-OMe of the per-methylated- -thiomanno-
side 9a and per-methylated- -phenolic mannoside 10a (entry 9,10)
b
b
further confirmed our conclusion. In addition, because mannoses
were more reactive, the main product of 9a and 10a were the de-4,
6-di-O-Me products (9b, 9c, 10b and 10c), and even the de-3, 4, 6-
tri-O-Me product 10d were obtained. Interestingly, the anomic
methyl group could also be removed. Per-methylated glucose 11a
produced 43% of de-1, 6-bi-O-Me products 7c, in addition to 55% of
de-6-O-Me product 11b (entry 11), suggesting that the anomic
methyl group was sensitive to the reaction condition. The de-O-
per-methylated-
thioglucoside 2a, 2, 3, 4-tri-O-Bn-6-O-Me-
2, 3, 4-tri-O-Bn-6-O-Me- -thiomannoside 4a, all gave the de-6-O-
b
-thioglucoside 1a, 2, 3, 4-tri-O-Bn- 6-O-Me-
b-
b-thiogalactoside 3a, and
a
Me products (entry1, 2, 3, 4) as the major product in high yield. This
was attributed to the reduced steric hindrance at 6-O-position,
where the methyl ether could be easily attacked by the
Et3SiþCo(CO)ꢀ4 reagent.
In addition to the cleavage of 6-OMe, another methyl group was
also removed. For 1a, 18% of de-3, 6-di-O-Me product 1c was ob-
tained (Table 2, entry 1). Similar reactivity was observed in the de-
methylation reaction was also carried out with permethylated b-
thiomaltoside 12a, which has two 6-OMe groups, yielding the de-6-
O-methylation product 12b and de-60-O-methylation product 12c
both in 30% yield (entry 12), suggesting that the hindrance of 6-
OMe and 60-OMe were similar.
O-methylation of per-methylated-b-phenolic glucoside 5a, which
yielded 18% of de-2, 6-di-O-Me product 5c and 16% of de-4, 6-di-O-
Me product 5d (entry 5). For the substrates with only one sec-
ondary methyl ether at 2-O-position, such as 2-O-Me-3, 4-O-Bn-6-
After the successful application of the procedure to mono-
saccharides and disaccharides, we investigated the selective de-O-
methylation of trisaccharide 13 in order to synthesize the DEF
segment of Idraparinux. When compound 13 was treated with
Co2(CO)8 (3.0 equiv) and Et3SiH (20 equiv) at 50 ꢁC in toluene for
24 h, the 6-O-Me on sugar D, whose steric hindrance was smaller
the that on sugar E, was removed first and transformed to silyl ether
(14, 48%). The silylated product 14 was then converted to acetylated
compound 15 in 2 steps in 90% yield. When 15 was treated with
Co2(CO)8 (6.0 equiv) and Et3SiH (40 equiv) at 50 ꢁC in toluene for
48 h, the 6-O-Me on sugar E was removed. Because of the high
steric hindrance of 6-O-Me of sugar E, the yield of de-O-
methylation is not very high. Then the TES group was removed
by CSA quantitatively to produce compound 16 (Scheme 2), and the
total yield of two steps is 20%. Compound 16 could be used as the
key intermediate in the synthesis of Idraparinux.
O-TBDPS-b-thioglucoside 6a, the 2-OMe could also be removed
with a yield of 40% (entry 6). These results indicated that unlike the
benzyl ether system, secondary methyl ether may also be removed
by Co2(CO)8/Et3SiH/CO system. This may be due to less steric hin-
drance of the secondary methyl ether compared to that of the
analogous benzyl ether, allowing the Et3SiþCo(CO)4ꢀ reagent to at-
tack on these secondary methyl ethers.
Among the 2-OMe, 3-OMe, 4-OMe groups, the equatorial methyl
ethers were preferentially removed because the equatorial methyl
ethers were less sterically hindered and more electron rich.14 This
could be demonstrated by the de-O-methylation of per-methyl-
ated-b-thiogalactoside 7a, and per-methylated-b-phenolic galac-
toside 8a, whose equatorial 2-OMe and 3-OMe groups were
removed whereas the axial 4-OMe remained (entry 7, 8). The
Scheme 2. Reagents and conditions: (a) Co2(CO)8 (3.0 equiv)/Et3SiH (20equiv)/CO(1 atm), toluene, 50 ꢁC, 48%, 24 h. (b) 1. TBAF, THF, 50 ꢁC, 15 h; 2. Ac2O, Py, 3 h. 90% in 2 steps. (c) 1.
Co2(CO)8 (6equiv)/Et3SiH (40equiv)/CO(1 atm), toluene, 50 ꢁC, 48 h; 2. CSA, CH2Cl2/CH3OH (4/1), 20% in 2 steps.

Y.-tao Zhao et al. / Tetrahedron 72 (2016) 5699e5706
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The proposed mechanism for the deprotection of methyl ethers
4.3. General procedure B for de-O-silylation and acylation
is shown in Scheme 3. Co2(CO)8 reacts with Et3SiH, generating the
active reagent Et3SiþCo(CO)4ꢀ in situ. The Lewis acidic and electro-
philic Et3Siþ combines adds to the oxygen atom and the Co(CO)4ꢀ
attacks the methyl group, leading to the cleavage of the methyl
ether and generating the silyl ether.
TBAF$3H2O (1.2 equiv) was added to a solution of the substrate
in THF, and the mixture was stirred at room temperature for 30 min.
The solvent was removed at reduced pressure and the residue was
purified by flash chromatography.
Scheme 3. Proposed mechanism of de-O-methylation by Co2(CO)8/Et3SiH/CO system.
3. Conclusion
4.4. General procedure C for acylation
In conclusion, a novel regioselective method has been de-
veloped for the cleavage of methyl ethers of saccharides under mild
conditions with the Co2(CO)8/Et3SiH/CO system. This system shows
selectivity for primary and equatorial secondary methyl ether of
various O-methylated saccharides. This de-O-methylation method
provides a powerful tool for accessing an array of methylated sac-
charides with free primary and secondary hydroxyl groups, which
could be used for further synthesis of more complex oligosaccha-
rides. Using this regioselective de-O-methylation strategy, we
achieved a concise synthesis of DEF trisaccharides segment of
Idraparinux.
For acetylation, the de-O-silylation product was dissolved in
pyridine, acetic anhydride (4 equiv) was added slowly, and the
mixture was stirred over 4 h. The reaction was stopped by the
addition of CH3OH in an ice bath. Evaporation of the solvent
afforded a residue, which was purified by flash chromatography.
4.5. p-Methylphenyl 6-O-acetyl-2,3,4-tri-O-methyl-1-thio-
b-
D-glucopyranoside (1b)
General procedure A, B and C, white solid, 52%; 1H NMR
(400 MHz, CDCl3)
d
7.44 (d, 2H, J¼8.1 Hz), 7.10 (d, 2H, J¼8.0 Hz), 4.42
(d, 1H, J¼9.8 Hz), 4.35 (dd, 1H, J¼2.1, 11.8 Hz), 4.19 (dd, 1H, J¼6.1,
11.8 Hz), 3.65 (s, 3H), 3.61 (s, 3H), 3.52 (s, 3H), 3.36e3.40 (m, 1H),
3.22 (t, 1H, J¼8.8 Hz), 2.99e3.08 (m, 2H), 2.33 (s, 3H), 2.09 (s, 3H).
4. Experimental
4.1. General
13C NMR (100 MHz, CDCl3)
d 170.9, 138.0, 132.9, 129.7, 88.7, 87.5,
82.6, 79.8, 76.8, 63.6, 61.1, 61.0, 60.7, 21.3, 21.0.
All chemicals were purchased as reagent grade and used with-
out further purification, unless otherwise noted. Dichloromethane
was distilled over phosphorus pentoxide. Benzene, toluene, tetra-
hydrofuran, and pyridine were distilled over sodium. Analytical TLC
was performed on precoated aluminum sheets with detection by
fluorescence and/or by staining with 5% concentrated sulfuric acid
in EtOH. Column chromatography was performed with silica gel
(230e400 mesh, Merck). Optical rotation was measured using an
Optical Activity AA-10R type polarimeter. 1H NMR spectra were
recorded on Advance DRX Bruker-400 spectrometers at 25 ꢁC.
Chemical shifts (in ppm) were referenced with tetramethylsilane
4.6. p-Methylphenyl 3,6-di-O-acetyl-2,4-di-O-methyl-1-thio-
b-D
-glucopyranoside (1c)
General procedure A, B and C, white solid,18%; 1H NMR (400 MHz,
CDCl3)
d
7.45 (d, 2H, J¼8.1 Hz), 7.12 (d, 2H, J¼8.0 Hz), 5.15 (t, 1H,
J¼9.2 Hz), 4.52 (d,1H, J¼9.8 Hz), 4.36 (dd,1H, J¼2.1,11.9 Hz), 4.22 (dd,
1H, J¼5.9, 11.9 Hz), 3.48e3.54 (m, 4H), 3.40 (s, 3H), 3.21 (t, 3H,
J¼9.5 Hz), 3.13 (t, 3H, J¼9.5 Hz), 2.34 (s, 3H), 2.14 (s, 3H), 2.11 (s, 3H).
4.7. p-Methylphenyl 6-O-acetyl-2,3,4-tri-O-benzyl-1-thio-b-D-
glucopyranoside (2b)
(d
¼0 ppm) in deuterated chloroform. 13C NMR spectra were ob-
tained using the same NMR spectrometers and were calibrated
General procedure A, B and C, white solid, 85%; 1H NMR
(400 MHz, CDCl3)
with CDCl3
(
d
¼77.16 ppm).
d
7.56 (d, 2H, J¼8.1 Hz), 7.50 (d, 2H, J¼8.1 Hz),
7.44e7.33 (m, 13H), 7.19 (d, 2H, J¼8.0 Hz), 5.03e5.00 (dd, 2H,
J¼10.3, 2.2 Hz), 4.95e4.92 (dd, 2H, J¼10.8, 3.2 Hz), 4.84 (d, 1H,
J¼10.3 Hz), 4.69e4.65 (dd, 2H, J¼9.8, 6.2 Hz), 4.47 (d,1H, J¼11.6 Hz),
4.32e4.28 (dd,1H, J¼11.8, 3.7 Hz), 3.82e3.78 (m, 1H), 3.61e3.54 (m,
4.2. General procedure A for de-O-methylation
Co2(CO)8 (3 equiv or 6 equiv, purchased from Alfa Aesar
Chemicals Co. without further purification) was added to a flask
under an atmosphere of CO. Et3SiH (20 equiv, purchased from Alfa
Aesar Chemicals Co. without further purification) was then
added, and the mixture was stirred for 30 min at room temper-
ature. A solution of permethylated saccharides in anhydrous
toluene (2 mmol/5 ml) was degassed and then added using a sy-
ringe. The mixture was heated in an oil bath at 50 ꢁC, and the
reaction was monitored by TLC. After the disappearance of
starting materials, the cobalt complex was precipitated by drop-
wise addition of pyridine and subsequent bubbling of oxygen
through the solution for 20 min. The content of the flask was
filtered through 5 cm of silica gel and eluted with ethyl acetate.
The filtrate was evaporated and the residue was subjected to flash
chromatography.
3H), 2.41 (s, 3H), 2.13 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 170.7,
138.0, 137.9, 137.7, 132.9, 129.7, 128.6, 128.5, 128.1, 128.0, 127.9, 87.8,
86.8, 80.9, 77.6, 76.9, 75.9, 75.5, 75.1, 63.3, 21.2, 21.0.
4.8. p-Methylphenyl 6-O-acetyl-2,3,4-tri-O-benzyl-1-thio-b-D-
galactopyranoside (3b)
General procedure A, B and C, white solid, 85%; 1H NMR
(400 MHz, CDCl3)
d
7.54 (d, 2H, J¼8.1 Hz), 7.47 (d, 2H, J¼8.1 Hz),
7.45e7.28 (m, 13H), 7.08 (d, 2H, J¼8.0 Hz), 5.05 (d, 1H, J¼11.5 Hz),
4.90 (d, 1H, J¼11.2 Hz), 4.84e4.78 (m, 3H), 4.7 (d, 1H, J¼11.6 Hz),
4.63 (d, 1H, J¼9.7 Hz), 4.34e4.30 (dd, 2H, J¼11.2, 7.0 Hz), 4.18e4.14
(dd, 1H, J¼11.3, 5.6 Hz), 3.99e3.95 (t, 1H, J¼9.4 Hz), 3.81e3.77 (m,

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Y.-tao Zhao et al. / Tetrahedron 72 (2016) 5699e5706
1H), 3.66e3.60 (m, 2H), 2.35 (s, 3H), 2.04 (s, 3H). 13C NMR
(100 MHz, CDCl3) 170.6, 138.3, 138.2, 137.4, 132.4, 130.2, 129.6,
4.14. p-Methylphenyl 2,3,4-tri-O-methyl-1-thio-b-D-gal-
actopyranoside (7b)
d
128.4,128.3,128.1,127.8, 127.7, 127.6, 88.1, 84.3, 76.0, 75.7, 74.3, 73.4,
73.2, 68.0, 63.5, 21.1, 20.9.
General procedure A and B, colorless oil, 1H NMR (400 MHz,
CDCl3)
d
7.44 (d, 2H, J¼8.2 Hz), 7.10 (d, 2H, J¼8.0 Hz), 4.46 (d, 1H,
J¼9.6 Hz), 3.88e3.93 (m, 1H), 3.65e3.71 (m, 1H), 3.63 (d, 1H,
J¼2.4 Hz), 3.60 (s, 3H), 3.54 (s, 3H), 3.53 (s, 3H), 3.38e3.43 (m, 2H),
3.20 (dd, 1H, J¼3.0, 9.2 Hz), 2.32 (s, 3H), 2.06 (dd, 1H, J¼3.0, 9.1 Hz).
4.9. p-Methylphenyl 6-O-acetyl-2,3,4-tri-O-benzyl-1-thio-b-D-
mannopyranoside (4b)
13C NMR (100 MHz, CDCl3)
d 137.7,132.5,130.1,129.7, 88.1, 86.1, 79.4,
General procedure A, B and C, white solid, 85%; 1H NMR
(400 MHz, CDCl3)
78.9, 75.9, 62.4, 61.4, 61.3, 58.5, 21.2.
d
7.40e7.28 (m, 17H), 7.14 (d, 2H, J¼8.0 Hz), 5.54
(d, 1H, J¼1.4 Hz), 5.50 (d, 1H, J¼5.50 Hz), 4.76e4.62 (m, 5H),
4.38e4.36 (m, 3H), 4.04e3.98 (m, 2H), 3.94e3.91 (dd, 1H, J¼9.2,
4.15. p-Methylphenyl 2,6-di-O-acetyl-3,4-di-O-methyl-1-thio-
b-D
-galactopyranoside (7c)
3.0 Hz), 2.36 (s, 3H), 2.07 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 170.8,
138.1,138.0,137.9,132.3,130.2,129.8,128.5,128.4,128.1,127.9,127.8,
85.9, 80.1, 76.0, 75.3, 74.7, 72.1, 71.9, 70.9, 63.6, 21.1, 20.9.
General procedure A, B and C, white solid, 28%; 1H NMR
(400 MHz, CDCl3)
d
7.40 (d, 2H, J¼8.1 Hz), 7.09 (d, 2H, J¼8.1 Hz), 5.23
(t, 1H, J¼9.8 Hz), 4.53 (d, 1H, J¼10.0 Hz), 4.23e4.35 (m, 2H), 3.69 (d,
1H, J¼2.6 Hz), 3.63 (t, 1H, J¼6.3 Hz), 3.55 (s, 3H), 3.45 (s, 3H), 3.30
(dd,1H, J¼2.8, 9.6 Hz), 2.33 (s, 3H), 2.13 (s, 3H), 2.08 (s, 3H). 13C NMR
4.10. p-Methoxyphenyl 6-O-acetyl-2,3,4-tri-O-methyl-b-D-
glucopyranoside (5b)
(100 MHz, CDCl3)
d 170.7, 169.6, 137.7, 132.5, 130.1, 129.5, 87.3, 83.7,
General procedure A, B and C, white solid, 43%; 1H NMR
(400 MHz, CDCl3)
76.2, 74.9, 69.7, 63.3, 61.3, 58.2, 21.1, 21.1, 20.8.
d
6.99e7.05 (m, 4H), 4.79 (d, 1H, J¼9.2 Hz), 4.34
(dd,1H, J¼2.2,11.8 Hz), 4.23 (dd,1H, J¼6.1,11.8 Hz), 3.66 (s, 3H), 3.65
(s, 3H), 3.54 (s, 3H), 3.50e3.53 (m, 1H), 3.24e3.31 (m, 2H), 3.16 (t,
1H, J¼9.2 Hz), 2.28 (s, 3H), 2.07 (s, 3H). 13C NMR (100 MHz, CDCl3)
4.16. p-Methylphenyl 3,6-di-O-acetyl-2,4-di-O-methyl-1-thio-
b-D-galactopyranoside (7d)
General procedure A, B and C, white solid, 8%; 1H NMR
(400 MHz, CDCl3)
d
155.0, 122.5, 118.0, 101.9, 86.5, 83.6, 79.6, 73.1, 63.4, 61.1, 60.8, 21.2,
21.0.
d
7.46 (d, 2H, J¼8.1 Hz), 7.10 (d, 2H, J¼8.0 Hz), 4.85
(dd, 1H, J¼3.0, 9.7 Hz), 4.50 (d, 1H, J¼9.7 Hz), 4.31 (dd, 1H, J¼6.9,
11.2 Hz), 4.17 (dd, 1H, J¼6.0, 11.2 Hz), 3.66 (m, 2H), 3.54 (s, 3H), 3.51
4.11. p-Methoxyphenyl 2,6-di-O-acetyl-3,4-di-O-methyl-b-D-
glucopyranoside (5c)
(d, 1H, 9.7 Hz), 3.48 (s, 3H), 2.33 (s, 3H), 2.16 (s, 3H), 2.06 (s, 3H). 13
C
NMR (100 MHz, CDCl3)
d170.7, 170.5, 137.9, 132.7, 130.0, 129.7, 88.3,
General procedure A, B and C, white solid, 18%; 1H NMR
(400 MHz, CDCl3) 6.92e6.94 (m, 2H), 6.79e6.81 (m, 2H), 5.11 (dd,
77.3, 77.3, 76.8, 75.7, 62.7, 61.5, 61.2, 21.3, 21.2, 20.9.
d
4.17. p-Methoxyphenyl 2,3,4-tri-O-methyl-b-D-galactopyrano-
side (8b)
1H, J¼8.0, 9.2 Hz), 4.80 (d, 1H, J¼7.9 Hz), 4.39 (dd, 1H, J¼2.2,
11.8 Hz), 4.25 (dd, 1H, J¼5.6, 11.9 Hz), 3.77 (s, 3H), 3.56 (s, 3H), 3.55
(s, 3H), 3.53e3.54 (m, 1H), 3.29e3.41 (m, 2H), 2.14 (s, 3H), 2.09 (s,
General procedure A and B, colorless oil; 1H NMR (400 MHz,
DMSO) 6.99e7.02 (m, 2H), 6.90e6.93 (m, 2H), 4.88 (d, 1H,
3H). 13C NMR (100 MHz, CDCl3)
d 170.9, 151.4, 118.6, 114.6, 100.4,
d
84.8, 79.4, 73.3, 72.9, 63.1, 60.8, 60.5, 55.8, 21.1, 21.0.
J¼5.2 Hz), 4.84 (d, 1H, J¼7.2 Hz), 3.77 (d, 1H, J¼2.1 Hz), 3.76 (s, 3H),
3.56e3.60 (m, 2H), 3.55 (s, 3H), 3.50 (s, 3H), 3.47 (s, 3H), 3.36 (d, 3H,
J¼14.0 Hz). 13C NMR (100 MHz, CDCl3)
d
155.3, 151.5, 118.5, 114.6,
4.12. p-Methoxyphenyl 3,6-di-O-acetyl-2,4-di-O-methyl-b-D-
glucopyranoside (5d)
102.9, 84.0, 80.6, 75.6, 75.2, 62.2, 61.4, 61.1, 58.7, 55.8.
General procedure A, B and C, white solid, 16%; 1H NMR
(400 MHz, CDCl3) 6.98e7.01 (m, 2H), 6.81e6.84 (m, 2H), 5.16 (t,
4.18. p-Methoxyphenyl 2,6-di-O-acetyl-3,4-di-O-methyl-b-D-
galactopyranoside (8c)
d
1H, J¼9.3 Hz), 4.83 (d, 1H, J¼7.7 Hz), 4.36 (dd, 1H, J¼2.2, 11.9 Hz),
4.27 (dd, 1H, J¼5.7, 11.9 Hz), 3.78 (s, 4H), 3.60 (s, 3H), 3.43 (s, 3H),
3.33 (t, 2H, J¼9.2 Hz), 2.17 (s, 3H), 2.09 (s, 1H). 13C NMR (100 MHz,
General procedure A, B and C, white solid, 41%; 1H NMR
(400 MHz, CDCl3) 6.94e6.96 (m, 2H), 6.78e6.81 (m, 2H), 5.43 (dd,
d
CDCl3)
d 170.7, 170.0, 155.5, 151.1, 118.6, 118.5, 114.5, 102.4, 83.4,
1H, J¼7.9, 10.0 Hz), 4.79 (d, 1H, J¼7.8 Hz), 4.27e4.39 (m, 2H), 3.77 (s,
83.0, 81.2, 77.9, 75.5, 72.7, 63.0, 60.6, 60.0, 55.7, 21.1, 20.9, 20.8,
20.8.
3H), 3.71e3.73 (m, 2H), 3.61 (s, 3H), 3.49 (s, 3H), 3.36 (dd, 1H, J¼2.8,
10.0 Hz), 2.11 (s, 3H), 2.10 (s, 3H). 13C NMR (100 MHz, CDCl3)
d170.8,
155.5, 151.6, 118.8, 114.5, 100.9, 82.5, 74.6, 72.7, 71.1, 63.1, 61.4, 58.4,
55.8, 21.1, 21.0.
4.13. p-Methylphenyl 2,6-di-O-acetyl-3, 4-di-O-benzyl-1-thio-
b-D
-glucopyranoside (6b)
4.19. p-Methoxyphenyl 3,6-di-O-acetyl-2,4-di-O-methyl-b-D-
galactopyranoside (8d)
General procedure A, B and C, white solid, 85%; 1H NMR
(400 MHz, CDCl3)
d
7.43e7.28 (m, 12H), 7.09 (d, 2H, J¼8.0 Hz),
5.45e5.40 (t, 1H, J¼9.8 Hz), 5.0 (d, 1H, J¼11.7 Hz), 4.74 (d, 1H,
J¼12.1 Hz), 4.63e4.54 (m, 3H), 4.31e4.26 (dd, 1H, J¼11.2, 7.0 Hz),
4.14e4.10 (dd, 1H, J¼11.3, 5.4 Hz), 3.88 (d, 1H, J¼2.0 Hz), 3.64e3.57
(m, 2H), 2.33 (s, 3H), 2.09 (s, 3H), 2.01 (s, 3H). 13C NMR (100 MHz,
General procedure A, B and C, white solid, 15%; 1H NMR
(400 MHz, CDCl3) 7.00e7.02 (m, 2H), 6.80e6.82 (m, 2H), 4.87 (dd,
1H, J¼3.1, 10.2 Hz), 4.78 (d, 1H, J¼7.7 Hz), 4.35 (dd, 1H, J¼6.7,
11.1 Hz), 4.20 (dd,1H, J¼6.3,11.1 Hz), 3.77 (s, 3H), 3.67e3.75 (m, 2H),
3.63 (s, 3H), 3.53 (s, 3H), 2.18 (s, 3H), 2.08 (s, 3H). 13C NMR
d
CDCl3)
d 170.6, 169.5, 138.0, 137.7, 132.6, 129.7, 129.5, 128.5, 128.3,
128.2, 127.9, 127.7, 127.5, 87.0, 81.7, 76.2, 74.2, 72.5, 72.4, 69.7, 63.4,
21.1, 21.1, 20.8.
(100 MHz, CDCl3)
76.3, 75.3, 72.1, 62.4, 61.6, 61.1, 55.8, 21.2, 20.9.
d170.7, 170.6, 155.6, 151.4, 118.9, 114.6, 103.0, 78.3,

Y.-tao Zhao et al. / Tetrahedron 72 (2016) 5699e5706
5705
4.20. p-Methylphenyl 3,6-di-O-acetyl-2,4-di-O-methyl-1-thio-
-mannopyranoside (9b)
4.26. Triethyl-silyl 2,3,4-tri-O-methyl-6-O-triethyl-silyl-
copyranoside (11c)
D-glu-
a-D
General procedure A, B and C, white solid, 42%; 1H NMR
(400 MHz, CDCl3)
(d, 1H, J¼1.8 Hz), 5.13 (dd, 1H, J¼3.3, 9.5 Hz), 4.34 (m, 3H), 3.89 (dd,
1H, J¼1.9, 3.2 Hz), 3.61 (t, 1H, J¼9.2 Hz), 3.48 (s, 3H), 3.42 (s, 3H),
2.33 (s, 3H), 2.17 (s, 3H), 2.08 (s, 3H). 13C NMR (100 MHz, CDCl3)
General procedure A, colorless oil, 43%; 1H NMR (400 MHz,
CDCl3)
d
7.39 (d, 2H, J¼8.1 Hz), 7.12 (d, 2H, J¼8.0 Hz), 5.51
d
4.84 (d, 1H, J¼3.6 Hz), 4.56 (d, 1H, J¼3.7 Hz), 3.79e3.86 (m,
5H), 3.61 (s, 3H), 3.40e3.57 (m, 13H), 3.37 (s, 3H), 3.36 (s, 3H),
3.04e3.15 (m, 3H), 0.96e1.00 (m, 36H), 0.60e0.70 (m, 24H). 13C
NMR (100 MHz, CDCl3)
d 100.2, 96.8, 84.4, 82.5, 80.5, 79.6, 74.3,
d
170.8, 170.2, 138.0, 132.3, 129.9, 84.8, 79.5, 75.1, 73.9, 70.5, 63.5,
73.7, 71.5, 71.4, 62.2, 62.1, 61.3, 60.9, 60.4, 58.4, 55.0, 54.9, 7.0, 6.9,
6.8, 5.2, 4.9, 4.6, 4.6.
60.6, 58.4, 21.2, 21.2, 20.9.
4.27. p-Methylphenyl (2,3,4-tri-O-methyl-6-O-triethyl-silyl-
-glucopyranosyl)-(1/4)-2,3,6-tri-O-methyl-1-thiol- -glu-
copyranoside (12b)
a-
4.21. p-Methylphenyl 4,6-di-O-acetyl-2,3-di-O-methyl-1-thio-
a-D-mannopyranoside (9c)
D
b-D
General procedure A,
(400 MHz, CDCl3)
B
and C, white solid; 1H NMR
7.40 (d, 2H, J¼8.1 Hz), 7.14 (d, 2H, J¼8.0 Hz),
General procedure A, colorless oil, 30%; 1H NMR (400 MHz,
CDCl3)
d
d
7.44e7.42 (d, J¼8.1 Hz,1H), 7.11e7.09 (d, J¼8.0 Hz,1H), 5.59
5.60 (d, 1H, J¼1.4 Hz), 5.29 (t, 1H, J¼9.8 Hz), 4.36e4.41 (m, 1H),
4.31 (t, 1H, J¼6.7 Hz), 4.25 (dd, 1H, J¼6.1, 12.2 Hz), 4.10 (dd, 1H,
J¼2.2, 12.1 Hz), 3.89 (dd, 1H, J¼1.8, 2.9 Hz), 3.57 (dd, 1H, J¼3.1,
9.4 Hz), 3.48 (s, 3H), 3.45 (s, 3H), 2.34 (s, 3H), 2.10 (s, 3H), 2.06
(s, 3H).
(d, J¼3.8 Hz, 1H), 4.48e4.46 (d, J¼9.9 Hz, 1H), 3.85e3.75 (m, 4H),
3.65e3.53 (m, 19H), 3.45e3.40 (m, 5H), 3.32e3.24 (m, 5H),
3.19e3.16 (dd, J¼9.8, 3.8 Hz, 1H), 2.33 (s, 3H), 0.98e0.95 (3, 10H),
0.64e0.58 (m, 7H). 13C NMR (100 MHz, CDCl3)
d 137.3, 132.1, 130.3,
129.5, 96.4, 88.7, 87.7, 83.3, 83.1,81.8, 79.2, 79.1, 71.5, 70.8, 62.3, 60.7,
60.5, 60.3, 60.0, 59.7, 59.2, 21.1, 6.8, 4.6.
4.22. p-Methoxyphenyl 3,6-di-O-acetyl-2,4-di-O-methyl-a-D-
mannopyranoside (10b)
4.28. p-Methylphenyl (2,3,4,6-tetra-O-methyl-a-D-glucopyr-
anosyl)-(1/4)-2,3-di-O-methyl-6-O-triethyl-silyl-1-thiol-b-D-
glucopyranoside (12c)
General procedure A, B and C, white solid, 30%; 1H NMR
(400 MHz, CDCl3) 7.02e7.04 (m, 2H), 6.81e6.83 (m, 2H), 5.44 (d,
d
General procedure A, colorless oil, 30%; 1H NMR (400 MHz,
CDCl3)
(d, J¼3.8 Hz, 1H), 4.45e4.43 (d, J¼9.9 Hz, 1H), 3.85e3.74 (m, 4H),
3.64 (s, 3H), 3.62 (s, 3H), 3.60 (m, 4H), 3.56 (m, 7H), 3.53e3.46 (m,
2H), 3.44e3.36 (m, 5H), 3.33e3.25 (m, 5H), 3.16e3.08 (m, 2H), 2.33
(s, 3H), 0.99e0.95 (3, 10H), 0.65e0.60 (m, 7H). 13C NMR (100 MHz,
1H, J¼1.8 Hz), 5.35 (dd, 1H, J¼3.4, 9.5 Hz), 4.28e4.29 (m, 2H),
3.89e3.93 (m, 1H), 3.84 (dd, 1H, J¼2.1, 3.3 Hz), 3.77 (s, 3H), 3.64 (t,
d
7.44e7.42 (d, J¼8.1 Hz,1H), 7.11e7.09 (d, J¼7.9 Hz, 1H), 5.53
1H, J¼9.7 Hz), 3.51 (s, 3H), 3.48 (s, 3H), 2.19 (s, 3H), 2.07 (s, 3H). 13
C
NMR (100 MHz, CDCl3) d 170.8, 170.3, 155.2, 150.2, 117.9, 114.6, 96.3,
78.3, 74.8, 73.6, 70.2, 63.2, 60.5, 59.4, 55.7, 21.3, 20.9.
CDCl3)
d 137.5, 132.3, 131.9, 130.1, 129.6, 129.5, 96.6, 88.7, 87.8, 83.7,
4.23. p-Methoxyphenyl 4,6-di-O-acetyl-2,3-di-O-methyl-a-D-
mannopyranoside (10c)
83.1, 81.9, 78.9, 78.1, 72.0, 71.9, 71.3, 61.4, 60.7, 60.6, 60.4, 60.1, 59.7,
59.1, 21.1, 6.8, 4.5.
General procedure A, B and C, white solid, 27%; 1H NMR
(400 MHz, CDCl3) 7.02e7.04 (m, 2H), 6.83e6.85 (m, 2H), 5.52 (d,
4.29. p-Methylphenyl (2,3,4-tri-O-methyl-6-O-triethyl-silyl-
-glucopyranosyl)-(1/4)-(2,3,6-tri-O-methyl- -glucopyr-
anosyl) -(1/4)-2,3-di-O-benzyl-6-O-tert-butyldiphenyl-silyl-
1-thiol- -glucopyranoside (14)
a-
d
D
b-D
1H, J¼1.7 Hz), 5.31 (t, 1H, J¼9.8 Hz), 4.22 (dd, 1H, J¼5.7, 12.2 Hz),
4.06 (dd, 1H, J¼2.2, 12.2 Hz), 3.93e3.97 (m, 1H), 3.80e3.83 (m, 1H),
3.78 (s, 3H), 3.56 (s, 3H), 3.50 (s, 3H), 2.09 (s, 3H), 2.02 (s, 3H). 13
C
b-D
NMR (100 MHz, CDCl3)
76.8, 69.6, 67.9, 62.8, 59.6, 58.1, 55.8, 21.0, 20.9.
d 169.9, 155.3, 150.3, 117.8, 114.8, 96.8, 78.8,
General procedure A, colorless oil, 48%. 1H NMR (400 MHz,
CDCl3)
d
7.82e7.78 (m, 4H), 7.45e7.23 (m, 22H), 6.98 (d, J¼8.0 Hz,
2H), 5.51 (d, J¼4.0 Hz, 1H), 5.20 (d, J¼11.2 Hz, 1H), 4.77e4.60 (m,
6H), 4.19e4.06 (m, 3H), 3.83e3.71 (m, 4H), 3.68e3.62 (m, 6H), 3.59
(s, 4H), 3.58e3.52 (m, 8H), 3.51e3.39 (m, 11H), 3.34e3.22 (m, 5H),
3.17e3.11 (m, 5H), 2.28 (s, 3H), 1.10 (s, 9H), 0.99e0.93 (t, 12H),
4.24. p-Methoxyphenyl 3,4,6-tri-O-acetyl-2-O-methyl-a-D-
mannopyranoside (10d)
General procedure A, B and C, white solid, 8%; 1H NMR
(400 MHz, CDCl3) 7.03e7.05 (m, 2H), 6.82e6.85 (m, 2H), 5.50 (d,
0.64e0.57 (m, 8H). 13C NMR (100 MHz, CDCl3)
d 139.3, 138.4, 137.3,
d
136.0, 135.7, 133.8, 133.0, 132.3, 130.4, 129.6, 128.3, 128.1, 127.8,
127.7, 127.2, 102.9, 96.5, 87.9, 86.8, 85.5, 84.7, 83.5, 82.0, 80.1, 78.9,
76.9, 75.6, 75.3, 74.2, 72.4, 71.7, 70.8, 61.5, 60.7, 60.4, 60.3, 60.0, 59.2,
58.8, 26.9, 21.1, 19.5, 6.8, 4.5.
1H, J¼1.9 Hz), 5.38e5.47 (m, 2H), 4.27 (dd, 1H, J¼5.5, 12.6 Hz),
4.02e4.07 (m, 2H), 3.83 (dd, 1H, J¼2.0, 2.8 Hz), 3.78 (s, 3H), 3.52 (s,
3H), 2.12 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H).
4.25. Methyl 2,3,4-tri-O-methyl-6-O-triethyl-silyl-
pyranoside (11b)
a
-
D
-gluco-
4.30. p-Methylphenyl (6-O-acetyl-2,3,4-tri-O-methyl-
copyranosyl)-(1/4)-(2,3,6-tri-O-methyl- -glucopyranosyl)-
-glucopyrano-
a-D-glu-
b-D
(1/4)-6-O-acetyl-2,3-di-O-benzyl-1-thiol-b-D
General procedure A, colorless oil, 55%; 1H NMR (400 MHz,
CDCl3)
side (15)
d
4.80 (d, 1H, J¼3.6 Hz), 3.81 (d, 2H, J¼3.1 Hz), 3.63 (s, 3H),
3.55 (s, 3H), 3.45e3.51 (m, 5H), 3.39 (s, 3H), 3.15e3.20 (m, 2H),
TBFA$3H2O (1.2 equiv) was added to a solution of 14 (240 mg,
0.2 mmol) in THF, and the mixture was stirred at room temperature
for 1 h. Then the solvent was removed at reduced pressure and the
residue was purified by column chromatography (PE/acetone¼2/1).
0.98 (t, 10H, J¼8.0 Hz), 0.60e0.66 (m, 6H). 13C NMR (100 MHz,
CDCl3)
4.3.
d 97.1, 83.6, 81.8, 79.0, 71.2, 61.7, 60.5, 60.1, 58.7, 54.6, 6.6,

5706
Y.-tao Zhao et al. / Tetrahedron 72 (2016) 5699e5706
Then the product was dissolved in pyridine (2 ml), then acetic
anhydride (0.5 ml) was added and the mixture was stirred for 3 h.
The reaction was stopped by the addition of CH3OH in ice bath, and
evaporation of the solvent afforded a residue which was purified by
column chromatography, giving 15 as colorless oil (168 mg, 90% in 2
Supplementary data
Supplementary data (Copies of 1H, 13C NMR spectra of relative
compounds) associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2016.07.081.
steps). 1H NMR (400 MHz, CDCl3)
d
7.45 (d, J¼81 Hz, 2H), 7.35e7.34
(d, J¼8.4 Hz, 2H), 7.31e7.24 (m, 9H), 7.09 (d, J¼8.0 Hz, 2H), 5.61 (d,
J¼3.8 Hz, 1H), 5.15 (d, J¼11.4 Hz, 1H), 4.81 (d, J¼10.2 Hz, 1H),
4.72e4.62 (m, 3H), 4.57 (d, J¼9.8 Hz, 1H), 4.32e4.65 (m, 3H),
4.19e4.16(dd, J¼11.9, 1.9 Hz, 1H), 3.83e3.77 (q, J¼9.1 Hz, 2H),
3.67e3.60 (m, 5H), 3.56e3.49 (m, 14H), 3.46e3.30 (m, 6H),
3.18e3.15(dd, J¼9.8, 3.7 Hz, 1H), 3.11e3.07 (m, 4H), 3.01e2.97 (t,
J¼8.0 Hz, 1H), 2.33 (s, 3H), 2.11 (s, 3H), 2.06 (s, 3H). 13C NMR
References and notes
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€
ꢀ
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nori, S.; Shigeru, Ar; Atsushi, N. Eur. J. Org. Chem. 2006, 752e758; (f) Bao, K.;
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67, 6406e6414; (c) Javier, M.; Michael, H. C.; Jerry, D. C.; Thomas, N. J. Org.
Chem. 2006, 71, 7103e7105.
(100 MHz, CDCl3)
d 170.8, 170.5, 139.1, 138.0, 137.9, 133.0, 129.6,
129.5, 128.3, 128.2, 127.8, 127.3, 127.2, 103.4, 95.9, 87.5, 86.8, 84.9,
84.5, 83.4, 81.8, 80.3, 79.5, 78.3, 77.1, 75.4, 75.3, 74.1, 71.4, 70.7, 69.1,
63.0, 62.8, 60.9, 60.6, 60.5, 59.8, 59.5, 58.9, 26.9, 21.0, 20.9.
4.31. p-Methylphenyl (6-O-acetyl-2,3,4-tri-O-methyl-
copyranosyl)-(1/4)-(2,3-di-O-methyl- -glucopyranosyl)-
-glucopyrano-
a-D-glu-
b-D
(1/4)-6-O-acetyl-2,3-di-O-benzyl-1-thiol-b-D
side (16)
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1H), 5.15 (d, J¼11.4 Hz, 1H), 4.81 (d, J¼10.1 Hz, 1H), 4.73e4.62 (m,
3H), 4.58 (d, J¼9.8 Hz, 1H), 4.32e4.21 (m, 4H), 3.88e3.76 (m, 3H),
3.69e3.65 (m, 3H), 3.56e3.52 (m, 14H), 3.49e3.26 (m, 6H),
3.18e3.10 (m, 5H),3.02e2.98 (t, J¼8.0 Hz, 1H), 2.33 (s, 3H), 2.11 (s,
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d 170.8, 170.5, 139.1,
138.0, 137.9, 133.0, 129.6, 129.5, 128.3, 128.2, 127.8, 127.3, 127.2,
103.4, 95.4, 87.6, 86.5, 84.9, 84.4, 81.4, 80.3, 79.1, 78.4, 75.4, 75.3,
74.2, 72.9, 72.1, 70.7, 69.0, 63.1, 62.8, 60.7, 60.5, 59.8, 58.8, 26.9, 21.0,
20.9.
€
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Acknowledgements
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Bioorg. Med. Chem. Lett. 2009, 19, 3875e3879; (c) Herczeg, M.; Mezo, E.; Lazar,
We are grateful for the financial support of the National
Basic Research Program of China (973 Program, Grant No.
2012CB822100), the National Key Technology R&D Program ‘New
Drug Innovation’ of China (No. 2012ZX09502001-001), the Na-
tional Natural Science Foundation of China (NSFC No. 21232002),
the National Research Foundation for the Doctoral Program of
Higher Education of China (No. 20130001110058), and the Open
Project Program of National Research Center for Carbohydrate
Synthesis, Jiangxi Normal University.
ꢀ
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L.; Fekete, A.; Kӧver, K. E.; Antus, S.; Borbas, A. Tetrahedron 2013, 69,
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