Copper-Catalyzed Anomeric O-Arylation of Carbohydrate Derivatives at Room Temperature

Article abstract of DOI:10.1021/acs.joc.9b01218

Direct and practical anomeric O-arylation of sugar lactols with substituted arylboronic acids has been established. Using copper catalysis at room temperature under an air atmosphere, the protocol proved to be general, and a variety of aryl O-glycosides have been prepared in good to excellent yields. Furthermore, this approach was extended successfully to unprotected carbohydrates, including α-mannose, and it was demonstrated here how the interaction between carbohydrates and boronic acids can be combined with copper catalysis to achieve selective anomeric O-arylation.

Full text of DOI:10.1021/acs.joc.9b01218

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Article
Copper-catalyzed anomeric O-arylation of
carbohydrate derivatives at room temperature
Tristan Verdelet, Sara Benmahdjoub, Belkacem Benmerad, Mouad Alami, and Samir Messaoudi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01218 • Publication Date (Web): 24 Jun 2019
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The Journal of Organic Chemistry
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Copper-catalyzed anomeric O-arylation of carbohydrate de-
rivatives at room temperature
Tristan Verdelet,a Sara Benmahdjoub,b Belkacem Benmerad,b Mouad Alami,a,* and Samir Messaoudia,*
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a BioCIS, Univ. Paris-Sud, CNRS, University Paris-Saclay, Châtenay-Malabry, France
b Laboratoire de Physico-Chimie des Matériaux et Catalyse, Faculté des Sciences Exactes, Université de Bejaia, 06000 Be-
jaia, Algeria
Supporting Information Placeholder
ABSTRACT: Direct and practical anomeric O-arylation of sugars lactols with substituted aryl boronic acids has been established.
Using copper catalysis at room temperature under air atmosphere, the protocol proved to be general, and a variety of aryl O-
glycosides have been prepared in good to excellent yields. Furthermore, this approach was extended successfully to unprotected
carbohydrates including α-mannose, and demonstrated here how the interaction between carbohydrates and boronic acids can be
combined with copper catalysis to achieve selective anomeric O-arylation.
donium salts5 (Figure 1-B, path 2). Other anomeric arylation
methods that have been applied to hydroxyl group in protected
INTRODUCTION
O-aryl glycosides are an important class of glycosides that
exhibit promising biological activities, including antibiotic
(e.g., vancomycin and chromomycin), antiviral, and anticancer
sugars include photoredox substitution of aryl bromides under
iridium catalysis6 (Figure 1-B, path 3). Although elegant, this
method is restricted to aryl bromides bearing electron deficient
(e.g., dauxorubucin) properties1 (Figure 1-A). Usually, these
groups. Besides, only per-O-benzylated sugar lactols were
derivatives are prepared by treating phenol derivatives with
used as partners, thus limited the scope of the reaction. An
glycosyl donors through an SN2 type mechanism under basic
conditions or through an SN1 reaction under acidic conditions
(Figure 1-B, path 1).2 Glycosyl acetates, halides, and trichlo-
roacetimidates have been used as donors in the formation of β-
O-aryl glycosides, these later, however, only work well with
specific phenol nucleophiles. For instance, glycosyl acetates
and trichloroacetimidates are preferred for electron-donating
phenol substrates. Glycosyl acetates usually provide the β-O-
aryl glycosides with lower yields than trichloroacetimidates
due to anomerization of both the glycosyl donor and the cou-
pling product.2 Alternative routes to O-glycosidic bond for-
mation consist on the use of phenols as partners in a Mitsuno-
bu coupling glycosylation with sugar hemiacetal.3 However,
the yield is clearly dependent on the acidity of the phenols,
that is, the least acidic phenols give usually low yields. Nucle-
ophilic aromatic substitution (SNAr) reactions have been also
used to generate O-arylglycosides from protected carbohy-
drates and activated fluoroarenes4 or electrophilic diarylio-
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parameters revealed that the use of molecular sieves plays a
critical role in the outcome of the C(Sp2)–O bond formation.
Pleasingly, the yield of 3a was improved up to 73% with
complete retention of the anomeric ratio (α/β = 1:3) when the
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Table 1 Survey of reaction conditions for the O-arylation of Glu-(OAc)4
1a with phenylboronic acid 2aa
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9
entry
[Cu]
Base
yield
(%)b
32
39
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8
Ratio
α:βc
1:1.2
1:1.2
1:2.8
1:3
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Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(acac)2
Cu(OTf)2
CuO
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2
Pyridine
Pyridine
DMAP
2,6-lutidine
Et3N
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
-
-
3:1
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-
73
84
82
β only
-
Figure 1. Example of bioactive O-aryl glycosides, and approaches to
anomeric O-arylation of carbohydrates
1:3d
1:2d,e
1:2d,e
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appealing option to access aryl O-glycosides would be the use
of carbohydrate hemiacetals as nucleophiles in transition
metal-catalyzed reactions. Owing to the biological signifi-
cance and existing restricted synthetic methodologies, there is
an exigent need for a facile and efficient protocol to synthesize
aryl O-glycosides. Since our initial reports on Chan-Lam-
Evans cross coupling of 1-aminosugars with arylboronic acids
under copper catalysis,7 to the best of our knowledge, there is
no report describing the formation of aryl O-glycosides from
carbohydrates hemiacetal and arylboronic acids.8 Consequent-
ly, in continuation of our interest in C-heteroatom bond for-
mation,9 we report herein that O-arylation of sugar hemiace-
tals can be realized efficiently using a catalytic amount of
Cu(OAc)2 at room temperature under air atmosphere (Figure
1-C).
a1a (1 equiv), phenylboronic acid 2a (3 equiv), [Cu] (20 mol %), base (1
b
equiv), 24 h, rt, [0.5M]. Yield of isolated 3a as a mixture of both
c
1
anomers. anomer ratio was measured by H NMR of the crude mixture
and found to be the same when calculated after purification of both α:β
anomers d The reaction performed with molecular sieves as additive.e 30
mol% of Cu(OAc)2.H2O was used and reaction concentration increased to
[0.7M].
reaction was conducted in the presence of molecular sieves
(entry 9). By increasing the amount of Cu-catalyst (from 20
mol% to 30 mol%) and the reaction concentration (from 0.5 M
to 0.7 M), we managed to isolate 84 % of the desired product
3a with a slight erosion of the anomeric purity (from α:β 1:3 to
1:2) (entry 10). One can be noted that the use of anhydrous
Cu(OAc)2 led to 3a in the same yield and same α/β-ratio (1:2,
entry 11). Importantly, the stability of 1a (α/β =1:3) and both
isolated pure anomeres α-3a and β-3a in deuterated dichloro-
RESULTS AND DISCUSSION
In the first set of experiments, we examined the coupling of
2,3,4,6-tetra-O-acetyl-D-glucopyranose 1a (in a mixture of
α/β = 1:3) with phenylboronic acid 2a as a model study under
various source of copper catalysts, bases and solvents. Repre-
sentative results from this study are summarized in Table 1.
The reaction of 1a (1 equiv) with 2a (3 equiv) was first inves-
tigated under our previously reported procedure
[Cu(OAc)2.H2O (20 mol%), pyridine, CH2Cl2, 24 h at 25 °C]
(Table 1, entry 1). Unfortunately, this protocol afforded the
desired aryl O-glycoside 3a in a low 32% yield. Switching
from CH2Cl2 as the solvent to the less volatile dichloroethane
(DCE) furnished 3a in a slightly increased yield (39%, entry
2). However in both cases, a significant erosion of the dia-
stereomeric ratio (α/β ratio from 1:3 to 1:1.2) was observed.
This result indicates clearly that the reactivity of hemiacetal
carbohydrates is far to be similar to those of 1-aminosugars
and are more prone to anomerization than their aminoconge-
ners. To increase the yield of 3a and reduce the erosion of the
diastereomeric ratios, we examined the influence of other
nitrogen bases under otherwise identical conditions. When
DMAP, 2,6-lutidine or Et3N were used instead pyridine, the
yield has never exceed 15% demonstrating that pyridine is the
best choice (compare entries 2 and 3-5). The optimization
reaction conditions was continued with respect to copper
catalyst, however, no significant improvement of the yield of
3a was observed when Cu(acac)2, Cu(OTf)2 or CuO were used
(entries 6-8). Extensive examinations of the other reaction
1
methane (CD2Cl2) was measured by HNMR after 19 h at
room temperature. The results demonstrated that both ano-
meres α-3a and β-3a are completely stable in CD2Cl2 and no
1
anomerization was detected by HNMR. However, analysis of
1
the HNMR of the starting material 1a revealed that the ano-
meric purity was lost and the ratio α/β is 1:1.1. This result
demonstrate cclearly that the erosion observed during the
reaction is due to the anomerization of the starting glycosyl
lactol (see SI, p98).
Motivated by these results, we next explored the scope of the
coupling reaction of glucopyranose 1a (in a mixture of α/β =
1:3) with various arylboronic acids. Gratifyingly, all the aryla-
tions proceeded cleanly to give the substituted aryl O-
glycosides 3a−p as a mixture of β and α anomers in ratios
ranging from 1:2 to 1:7.3 and yields up to 86%. As depicted in
Scheme 1, 1a was readily coupled with aryl boronic acids
having para- and meta-electron-donating or electron-
withdrawing substituents to give aryl O-glycosides 3b-d, 3f-p
in good yields with a retention of the diastereomeric α/β ratio.
Interestingly, this cross-coupling tolerated the presence of
C−halogen bonds (e.g., F, Cl, Br, I) which offers a platform
for further metal-catalyzed cross coupling reactions (com-
pounds 3h, 3i, 3m and 3o). It is well known that substitution
ortho to boron had a dramatic influence on the reaction effi-
cency. Thus, when 2-methylphenylboronic acid was used as
the coupling partner, only traces of product 3e were detected
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Scheme 1 Scope of Arylboronic Acids 2 for Cu-Catalyzed O-Arylation of 1aa
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Reaction conditions: reaction of 1a (1 equiv) with ArB(OH)2 2 (3 equiv) were performed in flask at r.t. in DCE by using Cu(OAc)2.H2O (30
mol %), Pyridine (1 equiv) and molecular sieves. *anomer ratio was calculated after purification and isolation of both α- and β-products from
the crude mixture.** anomer ratio was measured by 1H NMR (and confirmed by HPLC) on the mixture of both anomers.
by LCMS analysis even when a stoichiometric amount of
copper catalyst was used.
reaction with 2a proceeded smoothly giving the desired prod-
uct 4a in 82% yield and 2:1 of anomeric purity. Moving from
D-glucopyranose to O-acetylated α-D-mannose 1c (α/β = 9:1),
and O-acetylated D-galactopyranose 1d (α/β = 1:2.3) resulted
in the isolation of compound 4b and 4c in excellent yields and
a slight loss of anomeric purity (<5%). The synthetic potential
of this protocol was demonstrated by performing a gram scale
process with 1c (5.7 mmol). Delightedly, the reaction pro-
ceeded well to afford phenolic glycoside 4b in 94% yield with
the anomeric purity α/β = 6.1:1. Interestingly, joining of the
phenylboronic acid moiety to α–D-mannofuranose 1e was
In a further set of experiments, we investigated the scope and
generality of the method with respect to mono- di- and poly-
saccharides. As depicted in Scheme 2, this coupling reaction
tolerates a large variety of sugars 1b−h and furnished the
desired aryl O-glycosides in yields up to 90%. At first we
investigated the influence of the stereochemistry of the ano-
meric hydroxyl group on the coupling reaction. Thus, when
the α/β-ratio of tetra-acetoxy-D-glucopyranose was inversed
from 1:3 to 3:1 in favour of the α-anomer 1b, the coupling
Scheme 2 Scope of Sugar Lactols 1b-j for Cu-Catalyzed O-Arylation with phenylboronic Acids 2aa
Reaction conditions: reaction of 1b-j (1 equiv) with PhB(OH)2 2a (3 equiv) were performed in flask at r.t. in DCE by using Cu(OAc)2.H2O
(30 mol %), Pyridine (1 equiv) and molecular sieves. *anomer ratio was calculated after purification and isolation of both α- and β-products
from the crude mixture.** anomer ratio was measured by 1H NMR (and confirmed by HPLC) on the mixture of both anomers.
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effective and resulted in the formation of the desired product 4f were isolated nicely in excellent 89% and 82% yields,
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4d in 76% yield as the only α–anomer.
respectively but the anomeric purity was completely lost in
these cases. These results indicate that the acetyl group at the
C2-position plays a pivotal role in maintaining the stability of
the anomeric purity of glycosyl lactols 1f and 1g under the
reaction conditions.
Next, the scope of the new reaction was investigated by using
two glycosyl partners devoid from the C-2 ester neighboring
participating group: the 2-deoxy glucose 1f and 1g bearing a
benzyl group rather than the acetyl. As we can expect, when
these two substrates where used, the coupling products 4e and
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Scheme 3 Scope of the Cu-Catalyzed O-Arylation with more complex carbohydratesa
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Reaction conditions: reaction of 1i-j (1 equiv) with PhB(OH)2 2a (3 equiv) were performed in flask at r.t. in DCE by using Cu(OAc)2.H2O (30
mol %), Pyridine (1 equiv) and molecular sieves.** anomer ratio was measured by H NMR (and confirmed by HPLC) on the mixture of
both anomers.
1
Having demonstrated the efficacy of our method with various
sugar lactols, we next turned our attention to the validation of
the method with respect to more complex and biologically
relevant saccharides (Scheme 3). We were delighted to find
that di- and trisaccharide derivatives cellobiose 1i (α/β = 1.2:1)
and maltotriose 1j (α/β = 3:1), readily undergo O-arylation
coupling in this transformation. The desired O-aryl glycoside
4i was isolated in 77% (α/β = 1.1:1). Moreover, the O-aryl
trisaccharide 4j which is commonly used in bacterial imag-
ing10 was isolated in 76% yield (α/β = 1.6:1). Importantly, the
stereochemistry of the 1,4′-O-glycosidic bond in the disaccha-
rides 4i and the α-1,4′ in trisaccharide 4j remained intact.
Of note in almost all cases, the β and α anomers were separat-
ed by SiO2 flash chromatography or preparative HPLC and the
NMR of pure single anomers has been reported (see SI).
Scheme 4 Cu-catalyzed O-arylation of unprotected α–Man 1k with
It was well known that arylboronic acids react with non-
protected sugars having erythro-configured OH groups at C-2
phenylboronic acid 2aa
and C-3 (e.g., mannose, allose)11 to favor the formation of
furanosides, with which they form particularly stable chelated
complexes. Thus we were interesting whether this strategy
may be applied to unprotected sugars to perform a selective O-
arylation reaction of the anomeric OH group. In this context,
we were pleased to observe that when the commercially avail-
able α-D-mannose 1k (α/β = 4:1) and phenylboronic acid 2a
(5 equiv) were subjected to our conditions, phenyl O-
furanoside 5a was generated in moderate yield as a single α–
anomer (Scheme 4). After reaction with m-CPBA to cleave
boronic ester groups, 6a could be isolated in a good 80% yield
despite the fact that the conditions were not been optimized.
Based on previous works12 on the mechanistic study of the
Chan-Lam-Evans reaction, we proposed in Figure 2 a mecha-
nistic description of the O-arylation of sugar lactols. At first,
the complex (I) is formed through denucleation of the complex
[Cu(OAc)2]2.2H2O. Engagement of the arylboronic acid leads
to transmetalation via 4-membered transition state (II) to
deliver Cu(II) species (III). Oxidation to Cu(III) via dispropor-
tionation of CuII(OAc)2 to CuI(OAc) gives complex (IV). A
selective C−O reductive elimination liberates the desired O-
arylglycoside and a Cu(I)OAc species (V). Completion of the
catalytic cycle is achieved via oxidation to Cu(II) in the pres-
ence of O2 and AcOH.
CONCLUSION
In summary, we have succeeded in achieving the coupling of
sugar lactols with functionalized arylboronic acid at room
temperature to furnish aryl O-arylglycosides. To the best of
our knowledge the C(sp2)O bond of aryl O-glycosides was
formed, for the first time, directly by using anomeric hydroxyl
group of sugars as nucleophile in the presence of Cu(OAc)2 as
the catalyst system. Because of the mildness of the reaction
conditions, the protocol developed is stereoretentive, function-
al-group tolerant, and proceeds in good to excellent yields.
Given its distinct convenience we expect this method to be
widely adopted within the synthetic and medicinal chemistry
community.
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The Journal of Organic Chemistry
gel chromatography (cyclohexane/EtOAc) afforded the de-
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sired compound. Unless other specified indications, α and β
anomers were isolated separately.
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Description of coupling products 3a-d, 3f-p and 4a-i
1-Phenyl-2,3,4,6-tetra-O-acetyl-D-glucopyranoside 3a.
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The title compound was prepared according to the
general procedure from commercially available 2,3,4,6-tetra-
O-acetyl-D-glucopyranose (174 mg, 0.5 mmol, α:β = 1:3) and
phenylboronic acid (183 mg) and was purified on silica gel
chromatography (cyclohexane/EtOAc, from 90/10 to 70/30) to
afford 59 mg of the α anomer and 115 mg of the β anomer as
amorphous white solids. Global yield: 84 % (0.42 mmol, 178
mg).
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1-Phenyl-2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside.13
1H NMR (300 MHz, CDCl3) δ 7.35-7.28 (m, 2 H), 7.12-7.05
(m, 3 H), 5.75 (d, J = 3.3 Hz, 1 H), 5.72 (app t, J = 9.8 Hz, 1
H), 5.17 (app t, J = 9.8 Hz, 1 H), 5.06 (dd, J = 10.2, 3.7 Hz, 1
H), 4.27 (dd, J = 12.2, 4.5 Hz, 1 H), 4.15 (ddd, J = 10.2, 4.5,
2.1 Hz, 1 H), 4.07 (dd, J = 12.2, 2.2 Hz, 1 H), 2.08 (s, 3 H),
2.07 (s, 3 H), 2.06 (s, 3 H), 2.05 (s, 3 H). 13C NMR (75 MHz,
CDCl3) δ 170.6, 170.2, 169.6, 156.1, 129.7 (2 C), 123.0, 116.6
(2 C), 94.2, 70.5, 70.1, 68.3, 68.0, 61.6, 20.6 (4 C).
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Figure 2. A proposed mechanism to anomeric O-arylation of carbo-
hydrates
EXPERIMENTAL SECTION
General Procedure. Unknown compounds were all iden-
tified by usual physical methods, e.g., 1H NMR, 13C NMR, IR,
1
MS (ESI). H and 13C NMR spectra were measured in deuter-
1
ated solvents with a Bruker Avance‐300. H chemical shifts
1-Phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside.14
are reported in ppm from an internal standard TMS or of re-
sidual solvent peak. 13C chemical shifts are reported in ppm
from the residual solvent peak. IR spectra were measured on a
Bruker Vector 22 spectrophotometer. Analytical TLC was
performed on Merck precoated silica gel 60F plates. Merck
silica gel 60 (0.015–0.040 mm) was used for column chroma-
tography. High pressure liquid chromatography was recorded
with a Waters Alliance 2695 device using a DAD 2996 as UV
detector. High resolution mass spectra (HR‐MS) were record-
ed on a Bruker MicroTOF spectrometer, using ESI with meth-
anol as the carrier solvent. Nominal and exact m/z values are
1H NMR (300 MHz, CDCl3) δ 7.34-7.28 (m, 2 H), 7.11-7.07
(m, 1 H), 7.02-6.99 (m, 2 H), 5.35-5.26 (m, 2 H), 5.22-5.17
(m, 1 H), 5.12-5.09 (m, 1 H), 4.31 (dd, J = 12.2, 5.3 Hz, 1 H),
4.18 (dd, J = 12.3, 2.5 Hz, 1 H), 3.88 (ddd, J = 9.9, 5.3, 2.5
Hz, 1 H), 2.09 (s, 3 H), 2.08 (s, 3H), 2.06 (s, 3 H), 2.05 (s, 3
H). 13C NMR (75 MHz, CDCl3) δ 170.6, 170.2, 169.4, 169.3,
156.8, 129.6 (2 C), 123.4, 117.0 (2 C), 99.1, 72.7, 72.0, 71.2,
68.3, 62.0, 20.7, 20.6 (3 C).
1-(4'-Methoxy)-2,3,4,6-tetra-O-acetyl-D-glucopyranoside
3b.
reported
in
Daltons.
2,3,4,6-Tetra-O-acetyl-β-D-
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
D-glucopyranose (174 mg, 0.5 mmol, α:β = 1:3) and 4-
methoxyphenylboronic acid (228 mg) and was purified on
silica gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/30) to afford 43 mg of the α anomer and 90 mg of the β
anomer as amorphous white solids. Global yield: 59 % (0.29
mmol, 134 mg).
glucopyranose 1a (α:β = 1:3), β-D-glucose pentacetate, β-D-
galactose pentacetate, D-mannose, D-glucosamine, 2,3,4,6-
Tetra-O-benzyl-α-D-glucopyranose 1g, maltotriose, α-D-
cellobiose octaacetate, tri-O-acetyl-D-glucal, 2,3,5,6-di-O-
isopropylidene-α-D-mannofuranose 1e and all boronic acids
were bought from available commercial sources.
General procedure for copper-catalyzed anomeric O-
arylation of carbohydrate derivatives.
1-(4'-Methoxy)-2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside.15
1H NMR (300 MHz, CDCl3) δ 7.04-7.01 (m, 2 H), 6.86-6.83
(m, 2 H), 5.70 (app t, J = 9.8 Hz, 1 H), 5.63 (d, J = 3.7 Hz, 1
H), 5.16 (app t, J = 9.8 Hz, 1 H), 5.03 (dd, J = 10.3, 3.7 Hz, 1
H), 4.27 (dd, J = 12.1, 4.6 Hz, 1 H), 4.18 (ddd, J = 12.0, 4.7,
2.1 Hz, 1 H), 4.09 (dd, J = 12.1, 2.1 Hz, 1 H), 3.79 (s, 3 H),
2.09-2.06 (m, 12 H). 13C NMR (75 MHz, CDCl3) δ 170.5,
170.1 (2 C), 169.6, 155.5, 150.2, 117.9 (2 C), 114.7 (2 C),
95.1, 70.6, 70.1, 68.4, 67.9, 61.7, 55.7, 20.7, 20.6 (3 C).
In a 50 mL round bottom flask, monohydrated cop-
per (II) acetate (30 mg, 0.15 mmol) and pyridine (40 μL, 0.50
mmol) were added on activated 4 Å molecular sieves (200
mg). Dichloroethane (700 μL, c = 0.7 M) was added and the
resulting suspension was stirred for 5 minutes. The boronic
acid (1.50 mmol) was then introduced and the reaction media
was stirred again for 5 minutes. Finally, the carbohydrate
(0.50 mmol) was added and the resulting mixture was stirred
at room temperature and under air atmosphere for 24 hours
(the round bottom flask was capped to prevent the evaporation
of dichloromethane). The media was then diluted with di-
chloromethane and filtered over celite. Purification by silica
1-(4'-Methoxy)-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside.16
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1H NMR (300 MHz, CDCl3) δ 6.98-6.95 (m, 2 H), 6.85-6.82 1H NMR (300 MHz, CDCl3) δ 7.35-7.32 (m, 2 H), 7.04-7.02
1
2
3
4
5
6
7
(m, 2 H), 5.93-5.22 (m, 1 H), 5.17 (t, J = 9.1 Hz, 1 H), 4.97 (d,
J = 7.1 Hz, 1 H), 4.31 (dd, J = 12.3, 5.2 Hz, 1 H), 4.18 (dd, J =
12.3, 2.5 Hz, 1 H), 3.85-3.79 (m, 1 H), 3.79 (s, 3 H), 2.10 (s, 3
H), 2.09 (s, 3 H), 2.06 (s, 3 H), 2.05 (s, 3 H). 13C NMR (75
MHz, CDCl3) δ 170.6, 170.2, 169.4, 169.3, 155.8, 150.9,
118.7 (2 C), 114.6 (2 C), 100.3, 72.8, 72.0, 71.3, 68.3, 62.0,
55.6, 20.7 (2 C), 20.6 (2 C).
(m, 2 H), 6.65 (dd, J = 17.6, 10.9 Hz, 1 H), 5.73-5.60 (m, 3
H), 5.18-5.11 (m, 2 H), 5.03 (dd, J = 10.2, 3.7 Hz, 1 H), 4.13-
4.01 (m, 2 H), 4.23 (dd, J = 12.1, 4.4 Hz, 1 H), 2.05 (s, 3 H),
2.04 (s, 3 H), 2.03 (s, 3 H), 2.02 (s, 3 H). 13C NMR (75 MHz,
CDCl3) δ 170.5, 170.1 (2 C), 169.5, 155.7, 135.8, 132.7, 127.4
(2 C), 116.6 (2 C), 112.9, 94.2, 70.4, 70.0, 68.3, 68.1, 61.6,
20.7, 20.6 (3 C).
8
9
1-(4'-Thiomethyl)-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside 3c.
1-(4'-vinyl)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.17
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
1H NMR (300 MHz, CDCl3) δ 7.34-7.31 (m, 2 H), 6.95-6.92
(m, 2 H), 6.65 (dd, J = 17.6, 10.9 Hz, 1 H), 5.63 (d, J = 17.6
Hz, 1 H), 5.32-5.22 (m, 2 H), 5.22-5.12 (m, 2 H), 5.08-5.06
(m, 1 H), 4.28 (dd, J = 12.3, 5.3 Hz, 1 H), 4.16 (dd, J = 12.3,
2.5 Hz, 1 H), 3.91-3.78 (m, 1 H), 2.06 (s, 3 H), 2.04 (s, 3 H),
2.03 (s, 3 H), 2.02 (s, 3 H). 13C NMR (75 MHz, CDCl3) δ
170.5, 170.2, 169.3, 169.2, 156.5, 135.8, 133.1, 127.4 (2 C),
117.0 (2 C), 113.0, 99.1, 72.7, 72.1, 71.2, 68.3, 61.9, 20.7,
20.6 (3 C).
D-glucopyranose (174 mg, α:β
=
1:3) and 4-
thiomethylphenylboronic acid (250 mg) and was purified on
silica gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/30) to afford 34 mg of the α anomer and 82 mg of the β
anomer as amorphous white solids. Global yield: 49 % (0.24
mmol, 115 mg).
1-(4'-Thiomethyl)-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.
1-(3'-Methoxy)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3f.
1H NMR (300 MHz, CDCl3) δ 7.27-7.24 (m, 2 H), 7.05-7.03
(m, 2 H), 5.73-5.66 (m, 2 H), 5.16 (t, J = 9.7 Hz, 1 H), 5.04
(dd, J = 10.2, 3.7 Hz, 1 H), 4.26 (dd, J = 11.9, 4.2 Hz, 1 H),
4.12 (ddd, J = 10.3, 4.4, 2.2 Hz, 1 H), 4.07 (dd, J = 12.3, 2.3
Hz, 1 H), 2.47 (s, 3 H), 2.07-2.05 (m, 12 H). 13C NMR (75
MHz, CDCl3) δ 170.5, 170.1 (2 C), 169.5, 154.3, 132.1, 129.3
(2 C), 117.3 (2 C), 94.4, 70.4, 70.0, 68.3, 68.0, 61.6, 20.7, 20.6
(3 C), 17.3. HRMS (ESI) calculated for C21H26O10NaS [M +
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
D-glucopyranose (174 mg, α:β
=
1:3) and 3-
methoxyphenylboronic acid (227 mg) and was purified on
silica gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/30) to afford 42 mg of the α anomer and 134 mg of the β
anomer as amorphous white solids. Global yield: 77 % (0.38
mmol, 175 mg).
13
Na]+ 493.1144, found 493.1136. [α]D +160.7° (c 0.28,
MeOH). FT-IR vmax/cm-1 : 1733, 1493, 1368, 1222, 1034, 816,
604, 559.
1-(3'-Methoxy)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.
1-(4'-Thiomethyl)-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.
1H NMR (300 MHz, CDCl3) δ 7.19 (app t, J = 8.1 Hz, 1 H),
6.69-6.60 (m, 3 H), 5.79-5.60 (m, 2 H), 5.14 (app t, J = 9.7
Hz, 1 H), 5.03 (dd, J = 10.3, 3.6 Hz, 1 H), 4.25 (dd, J = 12.1,
4.5 Hz, 1 H), 4.16-4.08 (m, 1 H), 4.05 (dd, J = 12.1, 2.2 Hz, 1
H), 3.79 (s, 3 H), 2.06 (m, 6 H), 2.05 (s, 3 H), 2.04 (s, 5 H).
13C NMR (75 MHz, CDCl3) δ 170.5, 170.1 (2 C), 169.6,
160.8, 157.2, 130.1, 108.7, 108.5, 103.0, 94.2, 70.4, 70.1,
68.4, 68.0, 61.6, 55.4, 20.7, 20.6 (3 C). HRMS (ESI) calculat-
ed for C21H26O11Na [M+Na]+ 477.1373, found 477.1378.
1H NMR (300 MHz, CDCl3) δ 7.26-7.23 (m, 2 H), 6.97-6.94
(m, 2 H), 5.36-5.22 (m, 1 H), 5.17 (app t, J = 9.2 Hz, 1 H),
5.05 (d, J = 7.3 Hz, 1 H), 4.30 (dd, J = 12.3, 5.3 Hz, 1 H), 4.18
(dd, J = 12.3, 2.5 Hz, 1 H), 3.86 (ddd, J = 9.8, 5.3, 2.5 Hz, 1
H), 2.46 (s, 3 H), 2.09 (s, 3 H), 2.07 (s, 3 H), 2.06 (s, 3 H),
2.05 (s, 3 H). 13C NMR (75 MHz, CDCl3) δ 170.5, 170.2,
169.3, 169.2, 155.0, 132.5, 129.2 (2 C), 117.8 (2 C), 99.3,
72.7, 72.1, 71.2, 68.3, 61.9, 20.7, 20.6 (3 C), 17.2. HRMS
(ESI) calculated for C21H26O10NaS [M + Na]+ 493.1144, found
14
[α]D +146.3° (c 0.21, MeOH). FT-IR vmax/cm-1 : 1739, 1593,
13
493.1138. [α]D -21.6° (c 0.37, MeOH). FT-IR vmax/cm-1:
1493, 1368, 1223, 1033, 787, 691, 603.
1740, 1493, 1366, 1218, 1059, 1033, 818, 699, 642.
1-(3'-Methoxy)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.15
1-(4'-vinyl)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3d.
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
1H NMR (300 MHz, CDCl3) δ 7.18 (app t, J = 8.2 Hz, 1 H),
6.67-6.52 (m, 2 H), 5.35-5.21 (m, 2 H), 5.19-5.11 (m, 1 H),
5.07 (app d, J = 7.3 Hz, 1 H), 4.27 (dd, J = 12.3, 5.4 Hz, 1 H),
4.16 (dd, J = 12.3, 2.5 Hz, 1 H), 3.85 (ddd, J = 9.8, 5.4, 2.5
Hz, 1 H), 3.78 (s, 3 H), 2.07 (s, 3 H), 2.05 (s, 3 H), 2.04 (s, 3
H), 2.03 (s, 3 H). 13C NMR (75 MHz, CDCl3) δ 170.6, 170.2,
169.4, 169.3, 160.8, 158.0, 130.0, 110.0, 108.9, 108.6, 103.6,
99.0, 72.8, 72.1, 71.2, 68.4, 62.0, 55.4, 20.6 (4 C).
D-glucopyranose (174 mg, α:β
=
1:3) and 4-
vinylphenylboronic acid (222 mg) and was purified on silica
gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/50) to afford 62 mg of the α anomer and 126 mg of the β
anomer as amorphous white solids. Global yield: 84 % (0.42
mmol, 189 mg).
1-(4'-vinyl)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.17
1-(3’,5’-dimethyl)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3g.
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The Journal of Organic Chemistry
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
D-glucopyranose (174 mg, α:β 1:3) and 3,5-
dimethylphenylboronic acid (225 mg) and was purified on
silica gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/30) to afford 52 mg of the α anomer and 106 mg of the β
anomer as amorphous white solids. Global yield: 70 % (0.35
mmol, 158 mg).
1H NMR (300 MHz, CDCl3) δ 7.40-7.37 (m, 2 H), 6.89-6.86
1
2
3
4
5
6
7
(m, 2 H), 5.34-5.19 (m, 2 H), 5.15 (app t, J = 9.2 Hz, 1 H),
5.03 (d, J = 7.3 Hz, 1 H), 4.27 (dd, J = 12.3, 5.3 Hz, 1 H), 4.15
(dd, J = 12.3, 2.5 Hz, 1 H), 3.84 (ddd, J = 10.0, 5.4, 2.5 Hz, 1
H), 2.07 (s, 3 H), 2.05 (s, 3 H), 2.04 (s, 3 H), 2.02 (s, 3 H). 13C
NMR (75 MHz, CDCl3) δ 170.5, 170.2, 169.3, 169.2, 155.9,
132.5 (2 C), 118.9 (2 C), 115.9, 99.1, 72.6, 72.1, 71.1, 68.2,
61.9, 20.7 (2 C), 20.6 (2 C).
=
8
9
1-(3’,5’-dimethyl)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.
1-(4'-Fluorophenyl)-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3i.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
1H NMR (300 MHz, CDCl3) δ 6.70 (m, 3 H), 5.69 (app t, J =
9.7 Hz, 1 H), 5.70 (d, J = 3.7 Hz, 1 H), 5.15 (app t, J = 9.8 Hz,
1H), 5.02 (dd, J = 10.2, 3.7 Hz, 1 H), 4.26 (dd, J = 12.2, 4.5
Hz, 1 H), 4.13 (ddd, J = 10.1, 4.5, 2.1 Hz, 1 H), 4.05 (dd, J =
12.2, 2.3 Hz, 1 H), 2.29 (s, 6 H), 2.05-2.03 (m, 12 H). 13C
NMR (75 MHz, CDCl3) δ 170.5, 170.1 (2 C), 169.6, 156.1,
139.5, 124.7, 114.2 (2 C), 94.1, 70.5, 70.1, 68.4, 67.9, 61.7,
21.4 (2 C), 20.7, 20.6 (3 C). HRMS (ESI) calculated for
D-glucopyranose (174 mg, α:β
=
1:3) and 4-
fluorophenylboronic acid (210 mg) and was purified on silica
gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/30) to afford 22 mg of the α anomer and 105 mg of the β
anomer as amorphous white solids. Global yield: 58 % (0.29
mmol, 128 mg).
14
C22H28O10Na [M+Na]+ 475.1580, found 475.1574. [α]D
1-(4'-Fluorophenyl)-2,3,4,6-tetra-O-acetyl-α-D-
+160.9° (c 0.23, MeOH). FT-IR vmax/cm-1 : 1743, 1593, 1367,
1214, 1172, 1155, 1033, 839, 600.
glucopyranoside.16
1H NMR (300 MHz, CDCl3) δ 7.06-6.95 (m, 4 H), 5.74-5.57
(m, 2 H), 5.13 (app t, J = 9.6 Hz, 1 H), 5.01 (dd, J = 10.3, 3.7
Hz, 1 H), 4.23 (dd, J = 11.8, 4.4 Hz, 1 H), 4.16-3.99 (m, 2 H),
2.06-2.03 (m, 12 H). 13C NMR (75 MHz, CDCl3) δ 170.5,
170.1 (2 C), 169.6, 158.6 (J13C{F} = 241.4 Hz), 152.2, 118.0
(J13C{F} = 7.9 Hz, 2 C), 116.1 (J13C{F} = 23.1 Hz, 2 C), 94.9,
70.5, 70.0, 68.3, 68.1, 61.6, 20.7, 20.6 (3 C). 19F (188 MHz,
CDCl3) δ -120.6.
1-(3’,5’-dimethyl)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.
1H NMR (300 MHz, CDCl3) δ 6.71 (m, 1 H), 6.61 (m, 2 H),
5.32-5.21 (m, 2 H), 5.14 (app t, J = 9.4 Hz, 1 H), 5.05 (app d,
J = 7.1 Hz, 1 H), 4.26 (dd, J = 12.2, 5.5 Hz, 1 H), 4.18 (dd, J =
12.2, 2.6 Hz, 1 H), 3.87 (ddd, J = 9.9, 5.5, 2.5 Hz, 1 H), 2.28
(s, 6 H), 2.08 (s, 3 H), 2.05 (s, 3 H), 2.04 (s, 3 H), 2.03 (s, 3
H). 13C NMR (75 MHz, CDCl3) δ 170.5, 170.2, 169.4, 169.3,
156.9, 139.4, 125.0, 114.6 (2 C), 99.0, 72.8, 72.0, 71.2, 68.4,
1-(4'-Fluorophenyl)-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.15
62.2, 21.4 (2 C), 20.7, 20.6 (3 C). HRMS (ESI) calculated for
C22H28O10Na [M+Na]+ 475.1580, found 475.1579. [α]D
-
1H NMR (300 MHz, CDCl3) δ 7.00-6.95 (m, 4 H), 5.31-5.20
(m, 2 H), 5.15 (app t, J = 9.2 Hz, 1 H), 4.98 (d, J = 7.0 Hz, 1
H), 4.28 (dd, J = 12.3, 5.3 Hz, 1 H), 4.16 (dd, J = 12.3, 2.5 Hz,
1 H), 3.81 (ddd, J = 10.0, 5.3, 2.5 Hz, 1 H), 2.07 (s, 3 H), 2.06
(s, 3 H), 2.03 (s, 3 H), 2.02 (s, 3 H). 13C NMR (75 MHz,
CDCl3) δ 170.5, 170.2, 169.3, 169.2, 158.8 (J13C{F} = 241.5
Hz), 152.9, 118.8 (J13C{F} = 8.5 Hz, 2 C), 116.0 (J13C{F} = 23.2
Hz, 2 C), 99.9, 72.7, 72.1, 71.2, 68.3, 61.9, 20.7, 20.6 (3 C).
19F (188 MHz, CDCl3) δ -120.1.
14
25.3° (c 0.48, MeOH). FT-IR vmax/cm-1 : 1751, 1595, 1367,
1214, 1136, 1036, 954, 906, 846, 599.
1-(4'-Bromo)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3h.
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
D-glucopyranose (174 mg, α:β
=
1:3) and 4-
bromophenylboronic acid (301 mg) and was purified on silica
gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/30) to afford 40 mg of the α anomer and 139 mg of the β
anomer as amorphous white solids. Global yield: 71 % (0.35
mmol, 178 mg).
1-(4'-Trifluoromethyl)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3j.
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
D-glucopyranose (174 mg, α:β
=
1:3) and 4-
1-(4'-Bromophenyl)-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.16
trifluoromethylphenylboronic acid (286 mg) and was purified
on silica gel chromatography (cyclohexane/EtOAc, from
90/10 to 70/30) to afford 36 mg of the α anomer and 145 mg
of the β anomer as amorphous white solids. Global yield: 74
% (0.29 mmol, 182 mg).
1H NMR (300 MHz, CDCl3) δ 7.42-7.39 (m, 2 H), 6.99-6.96
(m, 2 H), 5.73-5.59 (m, 1 H), 5.14 (app t, J = 9.9 Hz, 1 H),
5.02 (dd, J = 10.3, 3.7 Hz, 1 H), 4.23 (dd, J = 12.3, 4.7 Hz, 1
H), 4.12-3.99 (m, 1 H), 2.06 (s, 3 H), 2.04 (s, 3 H), 2.03 (s, 6
H). 13C NMR (75 MHz, CDCl3) δ 170.5, 170.1 (2 C), 169.5,
155.1, 132.6 (2 C), 118.4 (2 C), 115.6, 94.4, 70.4, 69.9, 68.2,
61.6, 20.7, 20.6 (3 C).
1-(4'-Trifluoromethyl)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.
1H NMR (300 MHz, CDCl3) δ 7.59-7.56 (m, 2 H), 7.19-7.17
(m, 2 H), 5.80 (d, J = 3.7 Hz, 1 H), 5.69 (app t, J = 9.8 Hz, 1
H), 5.15 (app t, J = 9.7 Hz, 1 H), 5.05 (dd, J = 10.3, 3.7 Hz, 1
H), 4.23 (dd, J = 12.8, 5.1 Hz, 1 H), 4.06-4.03 (m, 2 H), 2.06
(s, 3 H), 2.05 (s, 3 H), 2.04 (s, 3H), 2,02 (s, 3 H). 13C NMR
1-(4'-Bromophenyl)-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.18
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The Journal of Organic Chemistry
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(75 MHz, CDCl3) δ 170.4, 170.1 (2 C), 169.5, 158.3, 127.1, acetylphenylboronic acid (245 mg) and was purified on silica
1
2
3
4
5
6
7
8
127.0, 125.3 (q, J13C{F} = 33 Hz), 124.0 (q, J13C{F} = 270 Hz),
116.5 (2 C), 94.0, 70.3, 69.9, 68.4, 68.2, 61.5, 20.6, 20.5 (3 C).
19F (188 MHz, CDCl3) δ -61.9. HRMS (ESI) calculated for
gel chromatography (cyclohexane/EtOAc, from 90/10 to
50/50) to afford 32 mg of the α anomer and 95 mg of the β
anomer as amorphous white solids. Global yield: 74 % (0.37
mmol, 172 mg).
13
C21H23O10NaF3 [M + Na]+ 515.1141, found 515.1143. [α]D
+137.0° (c 0.27, MeOH). FT-IR vmax/cm-1 : 1742, 1330, 1224,
1123, 1032, 844, 687, 608.
1-(4'-acetyl)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.
1-(4'-Trifluoromethyl)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.16
1H NMR (300 MHz, CDCl3) δ 7.95-7.93 (m, 2 H), 7.16-7.13
(m, 2 H), 5.82 (d, J = 3.6 Hz, 1 H), 5.70 (app t, J = 9.8 Hz, 1
H), 5.16 (app t, J = 9.9 Hz, 1 H), 5.06 (dd, J = 10.2, 3.6 Hz, 1
H), 4.24 (dd, J = 12.3, 4.5 Hz, 1 H), 4.09-4.02 (m, 2 H), 2.57
(s, 3 H), 2,06-2.03 (m, 12 H). 13C NMR (75 MHz, CDCl3) δ
196.6, 170.4, 170.1 (2 C), 169.5, 159.6, 132.3, 130.5 (2 C),
116.2 (2 C), 93.9, 70.3, 69.9, 68.4, 68.2, 61.5, 26.4, 20.7, 20.6
(2 C). HRMS (ESI) calculated for C22H26O11Na [M+Na]+
9
1H NMR (300 MHz, CDCl3) δ 7.57-7.55 (m, 2 H), 7.07-7.05
(m, 2 H), 5.34-5.25 (m, 2 H), 5.20-5.14 (m, 2 H), 4.28 (dd, J =
12.3, 5.4 Hz, 1 H), 4.17 (dd, J = 12.3, 2.5 Hz, 1 H), 3.89 (ddd,
J = 9.9, 5.4, 2.5 Hz, 1 H), 2.06 (s, 3 H), 2.05 (s, 6 H), 2.03 (s,
3 H). 13C NMR (75 MHz, CDCl3) δ 170.4, 170.1, 169.3,
169.2, 159.0, 127.0 (2 C), 125.4 (q, J13C{F} = 33 Hz), 124.0 (q,
J13C{F} = 270 Hz), 116.8 (2 C), 98.4, 72.5, 72.2, 71.0, 68.2,
61.9, 20.6 (2 C), 20.5 (2 C). 19F (188 MHz, CDCl3) δ -61.9.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
489.1373, found 489.1365. [α]D +177.8° (c 0.23, MeOH).
FT-IR vmax/cm-1 : 1736, 1677, 1600, 1360, 1223, 1033, 829,
761, 590.
1-(4’-trifluoromethoxy)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3k.
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
1-(4'-acetyl)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.19
1H NMR (300 MHz, CDCl3) δ 7.96-7.93 (m, 2 H), 7.06-7.03
(m, 2 H), 5.37-5.28 (m, 2 H), 5.22-5.16 (m, 2 H), 4.30 (dd, J =
12.3, 5.4 Hz, 1 H), 4.19 (dd, J = 12.3, 2.5 Hz, 1 H), 3.96-3.91
(m, 1 H), 2.58 (s, 3H), 2.09-2.05 (m, 12 H). 13C NMR (75
MHz, CDCl3) δ 196.6, 170.5, 170.1, 169.3, 169.2, 160.2,
132.4, 130.5 (2 C), 116.3 (2 C), 98.2, 72.6, 72.3, 71.1, 68.2,
61.9, 26.4, 20.7, 20.6 (2 C).
D-glucopyranose (174 mg, α:β
=
1:3) and 4-
(trifluoromethoxy)phenylboronic acid (310 mg) and was puri-
fied on silica gel chromatography (cyclohexane/EtOAc, from
90/10 to 60/40) to afford 39 mg of the α anomer and 139 mg
of the β-anomer as amorphous white solids. Global yield: 70
% (0.35 mmol, 178 mg).
1-(4’-trifluoromethoxy)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.
1-(3'-Iodo)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3m.
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
1H NMR (300 MHz, CDCl3) δ 7.24-6.98 (m, 4 H), 5.71-5.64
(m, 2 H), 5.14 (app t, J = 9.9 Hz, 1 H), 5.03 (dd, J = 10.3, 3.7
Hz, 1 H), 4.23 (dd, J = 12.3, 4.8 Hz, 1 H), 4.11-4.05 (m, 2 H),
2.06 (s, 3 H), 2.05 (s, 3 H), 2.03 (s, 3 H), 2.02 (s, 2 H). 13C
NMR (75 MHz, CDCl3) δ 170.4, 170.1 (2 C), 169.5, 154.4,
144.5, 122.5, 122.2 (2 C), 120.5 (q, J13C{F} = 252 Hz), 117.6 (2
C), 94.5, 70.4, 69.9, 68.3, 68.2, 61.6, 20.5 (4 C). 19F (188
D-glucopyranose (174 mg, α:β
=
1:3) and 3-
iodophenylboronic acid (373 mg) and was purified on silica
gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/30) to afford 54 mg of the α anomer and 164 mg of the β
anomer as amorphous white solids. Global yield: 79 % (0.4
mmol, 217 mg).
MHz, CDCl3)
δ -58.4. HRMS (ESI) calculated for
C21H23O11F3Na [M+Na]+ 531.1090, found 531.1082. [α]D
+128.6° (c 0.21, MeOH). FT-IR vmax/cm-1 : 1745, 1505, 1368,
1213, 1192, 1161, 1033, 918, 801, 601.
14
1-(3'-Iodo)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.20
1H NMR (300 MHz, CDCl3) δ 7.47 (m, 1 H), 7.42-7.39 (m, 1
H), 7.07-6.99 (m, 2 H), 5.69 (d, J = 3.4 Hz, 1 H), 5.66 (app t, J
= 9.9 Hz, 1 H), 5.13 (app t, J = 9.9 Hz, 1 H), 5.02 (dd, J =
10.2, 3.7 Hz, 1 H), 4.24 (dd, J = 12.5, 5.1 Hz, 1 H), 4.14-3.88
(m, 2 H), 2.06 (m, 6 H), 2.04 (s, 3 H), 2.03 (s, 3 H). 13C NMR
(75 MHz, CDCl3) δ 170.5, 170.1 (2 C), 169.5, 156.4, 132.3,
131.0, 125.8, 116.0, 94.3, 94.2, 70.3, 69.9, 68.3, 68.2, 61.6,
20.7 (2 C), 20.6 (2 C).
1-(4’-trifluoromethoxy)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.16
1H NMR (300 MHz, CDCl3) δ 7.17-7.14 (m, 2 H), 7.01-6.98
(m, 2 H), 5.33-5.23 (m, 2 H), 5.16 (app t, J = 9.4 Hz, 1 H),
5.06 (d, J = 7.2 Hz, 1 H), 4.28 (dd, J = 12.3, 5.3 Hz, 1 H), 4.17
(dd, J = 12.3, 2.5 Hz, 1 H), 3.85 (ddd, J = 10.0, 5.4, 2.6 Hz, 1
H), 2.06 (m, 6 H), 2.05 (s, 3 H), 2.03 (s, 3 H). 13C NMR (75
MHz, CDCl3) δ 170.4, 170.1, 169.3, 169.2, 155.1, 144.7,
122.4 (2 C), 120.4 (JC-F = 255 Hz), 118.1 (2 C), 99.2, 72.6,
72.2, 71.1, 68.3, 61.9, 20.5 (4 C). 19F (188 MHz, CDCl3) δ -
58.3.
1-(3'-Iodo)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.18
1H NMR (300 MHz, CDCl3) δ 7.45-7.32 (m, 2 H), 7.04-6.93
(m, 2 H), 5.32-5.21 (m, 2 H), 5.12 (app t, J = 9.3 Hz, 1 H),
5.05 (app d, J = 7.1 Hz, 1 H), 4.32-4.13 (m, 2 H), 3.88 (ddd, J
= 10.2, 5.8, 2.7 Hz, 1 H), 2.11 (s, 3 H), 2.05 (s, 3 H), 2.04 (s, 3
H), 2.02 (s, 3 H). 13C NMR (75 MHz, CDCl3) δ 170.6, 170.1,
1-(4'-acetyl)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3l.
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
D-glucopyranose (174 mg, α:β
=
1:3) and 4-
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The Journal of Organic Chemistry
169.4, 169.2, 157.1, 132.5, 130.9, 125.9, 116.6, 98.8, 94.0,
72.6, 72.2, 71.1, 68.3, 62.1, 20.8, 20.6 (3 C).
FT-IR vmax/cm-1 : 1739, 1474, 1383, 1224, 1033, 932, 826,
1
776, 687, 608.
2
3
4
5
6
7
8
9
1-(3'-Nitro)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3n.
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
1-(3’,5’-dichloro)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.
D-glucopyranose (174 mg, α:β
=
1:3) and 3-
1H NMR (300 MHz, CDCl3) δ 7.34 (d, J = 8.8 Hz, 1 H), 7.12
(d, J = 2.8 Hz, 1 H), 6.84 (dd, J = 8.9, 2.8 Hz, 1 H) 5.31-5.20
(m, 2 H), 5.12 (app t, J = 9.3 Hz, 1 H), 5.03 (d, J = 7.1 Hz, 1
H), 4.33-4.07 (m, 2 H), 3.87 (ddd, J = 9.5, 5.8, 2.6 Hz, 1 H),
2.09 (s, 3 H), 2.05 (s, 3 H), 2.04 (s, 3 H), 2.02 (s, 3 H). 13C
NMR (75 MHz, CDCl3) δ 170.5, 170.1, 169.3, 169.2, 155.5,
133.0, 130.8, 126.9, 118.9, 117.0, 99.0, 72.5, 72.3, 71.0, 68.2,
nitrophenylboronic acid (250 mg) and was purified on silica
gel chromatography (cyclohexane/EtOAc, from 90/10 to
50/50) to afford 28 mg of the α anomer and 111 mg of the β
anomer as amorphous solids. Global yield: 59 % (0.29 mmol,
138 mg).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-(3'-Nitro)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.20
62.0, 20.7, 20.6 (3 C). HRMS (ESI) calculated for
C20H22O10NaCl2 [M+Na]+ 515.0488, found 515.0495. [α]D
-
14
22.2° (c 0.23, Me0H). FT-IR vmax/cm-1 : 1749, 1477, 1367,
1H NMR (300 MHz, CDCl3) δ 8.04-7.86 (m, 2 H), 7.56-7.34
(m, 2 H), 5.80 (d, J = 3.6 Hz, 1 H), 5.68 (app t, J = 9.8 Hz, 1
H), 5.15 (app t, J = 9.9 Hz, 1 H), 5.06 (dd, J = 10.3, 3.6 Hz, 1
H), 4.24 (dd, J = 12.6, 5.2 Hz, 1 H), 4.14-3.97 (m, 2 H), 2.07
(s, 3 H), 2.05 (s, 3 H), 2.03 (s, 3 H), 2.02 (s, 3 H).
1211, 913, 873, 825, 711, 600.
1-(2’-naphthyl)-2,3,4,6-tetra-O-acetyl-D-glucopyranoside
3p.
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-acetyl-
D-glucopyranose (174 mg, α:β = 1:3) and naphthalen-2-
ylboronic acid (258 mg) and was purified on silica gel chro-
matography (cyclohexane/EtOAc, from 90/10 to 70/30) to
afford 64 mg of the α anomer and 141 mg of the β anomer as
yellowish solids. Global yield: 86 % (0.43 mmol, 203 mg).
13C NMR (75 MHz, CDCl3) δ 170.4, 170.0 (2 C), 169.4,
156.5, 149.2, 130.3, 122.9, 118.0, 111.9, 94.7, 70.2, 69.7,
68.6, 68.2, 61.6, 20.6, 20.5 (3 C).
1-(3'-Nitro)-phenyl-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranoside.21
1-(2’-naphthyl)-2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside.
1H NMR (300 MHz, CDCl3) δ 7.95 (ddd, J = 8.2, 2.1, 1.0 Hz,
1 H), 7.86 (app t, J = 2.3 Hz, 1 H), 7.47 (app t, J = 8.2 Hz, 1
H), 7.31 (ddd, J = 8.3, 2.4, 1.1 Hz, 1 H), 5.40-5.25 (m, 2 H),
5.24-5.06 (m, 2 H), 4.22 (d, J = 4.2 Hz, 2 H), 4.01-3.88 (m, 1
1H NMR (300 MHz, CDCl3) δ 7.83-7.75 (m, 3 H), 7.50-7.38
(m, 3 H), 7.31-7.28 (m, 1 H), 5.91 (d, J = 3.6 Hz, 1 H), 5.79
(app t, J = 9.8 Hz, 1 H), 5.21 (app t, J = 9.8 Hz, 1 H), 5.13 (dd,
J = 10.2, 3.6 Hz, 1 H), 4.29 (dd, J = 12.2, 4.7 Hz, 1 H), 4.19
(ddd, J = 10.3, 4.8, 2.1 Hz, 1 H), 4.08 (dd, J = 12.2, 2.1 Hz, 1
H), 2.09 (m, 6 H), 2.07 (s, 3 H), 2.00 (s, 3 H). 13C NMR (75
MHz, CDCl3) δ 170.5, 170.2 (2 C), 169.6, 153.7, 134.2, 129.9,
129.7, 127.7, 127.1, 126.7, 124.7, 118.5, 110.9, 94.3, 70.5,
70.1, 68.4, 68.1, 61.6, 20.7, 20.6 (3 C). HRMS (ESI) calculat-
ed for C24H26O10Na [M+Na]+ 497.1424, found 497.1428.
H), 2.09 (s, 3 H), 2.07 (s, 3 H), 2.06 (s, 3 H), 2.04 (s, 3 H). 13
C
NMR (75 MHz, CDCl3) δ 170.6, 170.1, 169.4, 169.2, 157.0,
149.1, 130.2, 123.7, 118.2, 111.3, 98.6, 72.5 (2 C), 71.0, 68.2,
62.0, 20.6 (4 C).
1-(3’,4’-dichloro)-phenyl-2,3,4,6-tetra-O-acetyl-D-
glucopyranoside 3o.
14
[α]D +184.3° (c 0.26, MeOH). FT-IR vmax/cm-1 : 1739, 1227,
The title compound was prepared according to the
general procedure from commercially available 2,3,4,6-tetra-
O-acetyl-D-glucopyranose (174 mg, α:β = 1:3) and 3,4-
dichlorophenylboronic acid (288 mg) and was purified on
silica gel chromatography (cyclohexane/EtOAc, from 90/10 to
70/30) to afford 7 mg of the α anomer and 53 mg of the β
anomer as amorphous white solids. Global yield: 24 % (0.12
mmol, 59 mg).
1213, 1180, 1032, 973, 839, 751, 662, 609.
1-(2’-naphthyl)-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside.22
1H NMR (300 MHz, CDCl3) δ 7.86-7.66 (m, 3 H), 7.52-7.35
(m, 2 H), 7.34 (d, J = 2.5 Hz, 1 H), 7.19 (dd, J = 8.9, 2.5 Hz, 1
H), 5.43-5.28 (m, 2 H), 5.27-5.06 (m, 2 H), 4.31 (dd, J = 12.2,
5.5 Hz, 1 H), 4.21 (dd, J = 12.3, 2.5 Hz, 1 H), 3.94 (ddd, J =
9.9, 5.6, 2.5 Hz, 1 H), 2.08 (m, 6H), 2.06 (s, 3 H), 2.05 (s, 3
H). 13C NMR (75 MHz, CDCl3) δ 170.5, 170.2, 169.4, 169.3,
154.6, 134.1, 130.2, 129.7, 127.7, 127.1, 126.6, 124.7, 118.8,
111.5, 99.2, 72.8, 72.1, 71.3, 68.4, 62.1, 20.7, 20.6 (3 C).
1-(3’,5’-dichloro)-phenyl-2,3,4,6-tetra-O-acetyl-α-D-
glucopyranoside.
1H NMR (300 MHz, CDCl3) δ 7.39 (d, J = 8.9 Hz, 1 H), 7.28
(s, 1 H), 6.98 (dd, J = 8.9, 2.9 Hz, 1 H), 5.70 (d, J = 3.3 Hz, 1
H), 5.67 (app t, J = 9.8 Hz, 1 H), 5.15 (app t, J = 9.7 Hz, 1 H),
5.05 (dd, J = 10.3, 3.7 Hz, 1 H), 4.26 (dd, J = 12.9, 5.6 Hz, 1
H), 4.17-3.97 (m, 2H), 2.09-2.06 (m, 12 H). 13C NMR (75
MHz, CDCl3) δ 170.5, 170.1 (2 C), 169.5, 154.9, 133.2, 130.9,
126.7, 118.8, 116.3, 94.6, 70.3, 69.8, 68.4, 68.2, 61.6, 20.7,
20.6 (3 C). HRMS (ESI) calculated for C20H22O10NaCl2
1-Phenyl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside 4b.
The title compound was prepared according to the general
procedure from 2,3,4,6-tetra-O-acetyl-α-D-mannopyranose 1c
(175 mg, α:β = 9:1) and phenylboronic acid (185 mg) and was
purified on silica gel chromatography (cyclohexane/EtOAc,
from 90/10 to 70/30) to afford 165 mg of the α anomer and 27
mg of the β anomer as amorphous white solids. Global yield:
90 % (0.45 mmol, 191 mg).
14
[M+Na]+ 515.0488, found 515.0483. [α]D +186.7° (c 0.08,
Me0H).
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The Journal of Organic Chemistry
Page 10 of 15
boronic acid (185 mg) and was purified on silica gel chroma-
tography (cyclohexane/EtOAc, from 100/0 to 80/20) to afford
1
1-Phenyl-2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside.
128 mg (76%) of α anomer only as a white amorphous solid.
2
3
4
5
6
7
8
9
1H NMR (300 MHz, CDCl3) δ 7.33-7.28 (m, 2 H), 7.11-7.04
(m, 3 H), 5.57 (dd, J = 10.0, 3.5 Hz, 1 H), 5.53 (d, J = 1.8 Hz,
1 H), 5.45 (dd, J = 3.6, 1.8 Hz, 1 H), 5.37 (app t, J = 10.2 Hz,
1 H), 4.28 (dd, J = 12.4, 5.5 Hz, 1 H), 4.19-4.02 (m, 2 H), 2.20
(s, 3 H), 2.06 (s, 3 H), 2.04 (s, 3 H), 2.02 (s, 3 H). 13C NMR
(75 MHz, CDCl3) δ 170.5, 169.9, 169.9, 169.7, 155.6, 129.6 (2
C), 123.0, 116.5 (2 C), 95.8, 69.4, 69.1, 68.9, 66.0, 62.1, 20.8,
20.7, 20.6 (2 C). HRMS (ESI) calculated for C20H24O10Na
1H NMR (300 MHz, CDCl3) δ 7.44-7.22 (m, 2 H), 7.06-7.01
(m, 3 H), 5.66 (s, 1 H), 4.94 (dd, J = 5.9, 3.4 Hz, 1 H), 4.89 (d,
J = 5.9 Hz, 1 H), 4.45 (ddd, J = 7.9, 6.2, 4.2 Hz, 1 H), 4.21-
4.06 (m, 2 H), 4.01 (dd, J = 8.7, 4.2 Hz, 1 H), 1.54 (s, 3 H),
1.45 (s, 3 H), 1.40 (s, 6 H). 13C NMR (75 MHz, CDCl3) δ
156.3, 129.5 (2 C), 122.2, 116.6 (2 C), 113.0, 109.4, 104.9,
85.5, 81.2, 79.6, 73.0, 66.9, 26.9, 26.0, 25.2, 24.6.
14
[M+Na]+ 447.1267, found 447.1271. [α]D +79.1° (c 0.22,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
MeOH). FT-IR vmax/cm-1 : 1743, 1489, 1366, 1213, 1124,
1036, 975, 915, 757, 692;
1-Phenyl-2-deoxy-,3,4,6-tri-O-acetyl-D-glucopyranoside 4e.
The title compound was prepared according to the general
procedure from 2‐deoxy‐3,4,6‐tri‐O‐acetyl‐α-D‐glucopyranose
1f (145 mg, α:β = 8:1) and phenylboronic acid (185 mg) and
was purified on silica gel chromatography (cyclohex-
ane/EtOAc, from 90/10 to 50/50) to afford 78 mg of the α
anomer and 78 mg of the β anomer as white amorphous solids.
Global yield: 89 % (0.44 mmol, 163 mg).
1-Phenyl-2,3,4,6-tetra-O-acetyl-β-D-mannopyranoside.
1H NMR (300 MHz, CDCl3) δ 7.32-7.27 (m, 2 H), 7.17-6.78
(m, 3 H), 5.69 (d, J = 3.3 Hz, 1 H), 5.33 (app t, J = 9.8 Hz, 1
H), 5.24 (s, 1 H), 5.16 (dd, J = 9.9, 3.3 Hz, 1 H), 4.35 (dd, J =
12.1, 6.2 Hz, 1 H), 4.22 (dd, J = 12.1, 2.8 Hz, 1 H), 3.85 (ddd,
J = 9.4, 6.2, 2.8 Hz, 1 H), 2.26 (s, 3 H), 2.10 (s, 3 H), 2.09 (s,
3 H), 2.04 (s, 3 H). 13C NMR (75 MHz, CDCl3) δ 170.5,
170.3, 169.9, 169.6, 156.6, 129.5 (2 C), 123.2, 116.8 (2 C),
96.9, 72.5, 70.9, 68.8, 66.1, 62.6, 20.8, 20.7 (2 C), 20.6.
HRMS (ESI) calculated for C20H24O10Na [M+Na]+ 447.1267,
found 447.1264. [α]D14 -63.6° (c 0.44, MeOH). FT-IR vmax/cm-
1 : 1735, 1492, 1369, 1214, 1053, 913, 844, 769, 694, 599.
1-Phenyl-2-deoxy-,3,4,6-tri-O-acetyl-α-D-glucopyranoside.25
1H NMR (300 MHz, CDCl3) δ 7.40-7.23 (m, 2 H), 7.19-6.91
(m, 3 H), 5.70 (d, J = 3.5 Hz, 1 H), 5.55 (ddd, J = 11.5, 9.4,
5.4 Hz, 1 H), 5.11 (app t, J = 9.8 Hz, 1 H), 4.31 (dd, J = 12.1,
4.7 Hz, 1 H), 4.08 (ddd, J = 10.1, 4.7, 2.2 Hz, 1 H), 4.01 (dd, J
= 12.2, 2.3 Hz, 1 H), 2.49 (dd, J = 13.1, 5.4 Hz, 1 H), 2.07 (s,
3 H), 2.06 (s, 3 H), 2.03 (s, 3 H), 2.07-1.97 (m, 1 H). 13C NMR
(75 MHz, CDCl3) δ 170.6, 170.2, 169.9, 156.1, 129.5 (2 C),
122.4, 116.4 (2 C), 95.2, 69.1, 68.9, 68.6, 62.1, 35.1, 21.0,
20.7 (2 C).
1-Phenyl-2,3,4,6-tetra-O-acetyl-D-galactopyranoside 4c.
The title compound was prepared according to the general
procedure from 2,3,4,6-tetra-O-acetyl-α-D-galactopyranose 1d
(175 mg, α:β = 2.3:1) and phenylboronic acid (185 mg) and
was purified on silica gel chromatography (cyclohex-
ane/EtOAc, from 90/10 to 70/30) to afford 108 mg of the α
anomer and 57 mg of the β anomer as amorphous white solids.
Global yield: 78 % (0.39 mmol, 165 mg).
1-Phenyl-2-deoxy-,3,4,6-tri-O-acetyl-β-D-glucopyranoside.
1H NMR (300 MHz, CDCl3) δ 7.41-7.24 (m, 2 H), 7.09-7.01
(m, 3 H), 5.22 (dd, J = 9.6, 2.2 Hz, 1 H), 5.19-5.02 (m, 2 H),
4.34 (dd, J = 12.1, 5.6 Hz, 1 H), 4.17 (dd, J = 12.2, 2.6 Hz, 1
H), 3.80 (ddd, J = 8.6, 5.6, 2.5 Hz, 1 H), 2.54 (ddd, J = 13.0,
4.8, 2.2 Hz, 1 H), 2.13-2.02 (m, 10 H). 13C NMR (75 MHz,
CDCl3) δ 170.6, 170.2, 169.7, 156.7, 129.5 (2 C), 122.8, 116.7
(2 C), 97.4, 72.2, 70.3, 68.9, 62.5, 35.9, 20.9, 20.7 (2 C).
HRMS (ESI) calculated for C18H22O8Na [M+Na]+ 389.1212,
found 389.1205. [α]D14 -30.3° (c 0.17, MeOH). FT-IR vmax/cm-
1-Phenyl-2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside.23
1H NMR (300 MHz, CDCl3) δ 7.40-7.22 (m, 2 H), 7.09-7.04
(m, 3 H), 5.79 (d, J = 3.6 Hz, 1 H), 5.59 (dd, J = 10.7, 3.4 Hz,
1 H), 5.56-5.51 (m, 1 H), 5.30 (dd, J = 10.7, 3.6 Hz, 1 H), 4.37
(app t, J = 6.6 Hz, 1 H), 4.17-4.04 (m, 2 H), 2.18 (s, 3 H), 2.08
(s, 3 H), 2.04 (s, 3 H), 1.94 (s, 3 H). 13C NMR (75 MHz,
CDCl3) δ 170.3, 170.2, 170.1, 170.0, 156.3, 129.6 (2 C),
123.0, 116.8 (2 C), 94.9, 67.9, 67.8, 67.5, 67.1, 61.5, 20.7,
20.6 (2 C), 20.5.
1
: 1735, 1494, 1364, 1228, 1115, 1050, 993, 914, 762, 695,
593.
1-Phenyl-2,3,4,6-tetra-O-benzyl-D-glucopyranoside 4f.26
The title compound was prepared according to the general
procedure from commercially available 2,3,4,6-tetra-O-
benzyl-α-D-glucopyranoside (270 mg) and phenylboronic acid
(185 mg) and was purified on silica gel chromatography (cy-
clohexane/EtOAc, from 100/0 to 90/10) to afford 252 mg of
an inseparable mixture of α and β anomers as an amorphous
white solid (82%, α:β = 1.2:1 in NMR, 1.4:1 in HPLC).
1-Phenyl-2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside.22
1H NMR (300 MHz, CDCl3) δ 7.36-7.26 (m, 2 H), 7.13-7.04
(m, 1 H), 7.03-7.00 (m, 2 H), 5.50 (dd, J = 10.5, 8.0 Hz, 1 H),
5.45 (d, J = 3.2 Hz, 1 H), 5.13 (dd, J = 10.3, 3.6 Hz, 1 H), 5.06
(d, J = 7.9 Hz, 1 H), 4.34-3.96 (m, 4 H), 2.19 (s, 3 H), 2.07 (s,
3 H), 2.06 (S, 3 H), 2.02 (s, 3 H). 13C NMR (75 MHz, CDCl3)
δ 170.3, 170.2, 170.1, 169.3, 156.9, 129.5 (2 C), 123.3, 116.9
(2 C), 99.7, 71.0, 70.8, 68.7, 66.9, 61.3, 20.7, 20.6 (3 C).
1H NMR (300 MHz, CDCl3) δ 7.37-7.06 (m, 25 Hα, 25 Hβ),
5.55 (d, J = 3.5 Hz, 1 Hα), 5.14-5.07 (m, 1 Hα, 2 Hβ), 5.04-
4.84 (m, 3 Hα, 4 Hβ), 4.74 (app d, J = 12.0 Hz, 1 Hα), 4.68-
4.55 (m, 2 Hα, 3 Hβ), 4.47 (app d, J = 12.0 Hz, 1 Hα), 4.28
(app t, J = 9.2 Hz, 1 Hα), 3.98-3.62 (m, 5 Hα, 6 Hβ). 13C NMR
(75 MHz, CDCl3) δ 157.4, 156.8, 138.9, 138.6, 138.3, 138.2,
138.1, 137.9, 129.6, 128.5, 128.4, 128.3, 128.2, 128.0, 127.9,
1-Phenyl-2,3,5,6-di-O-isopropylidene-α-D-mannofuranose
4d.24
The title compound was prepared according to the general
procedure from commercially available 2,3,5,6-di-O-
isopropylidene-α-D-mannofuranose (132 mg) and phenyl-
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The title compound was prepared according to the general
127.7, 127.6, 122.7, 122.4, 117.0, 116.9, 101.7, 95.5, 84.7,
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82.1, 79.8, 77.8, 77.5, 75.8, 75.2, 75.1, 73.5, 73.3, 70.9, 68.9,
68.3. HRMS (ESI) calculated for C40H40O6Na [M+Na]+
639.2723, found 639.2737.
procedure from 1j (462 mg) and phenylboronic acid (185 mg)
and was purified on silica gel chromatography (cyclohex-
ane/EtOAc, (50/50) to afford 379 mg of an inseparable mix-
ture of α and β anomers as a white solid (76%, α:β = 1.6:1 in
NMR, 1.6:1 in HPLC).
1-Phenyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-
glucopyranose 4g.
The title compound was prepared according to the general
procedure from 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-
glucopyranose 1h (172 mg, α:β = 19:1) and phenylboronic
acid (185 mg) and was purified on silica gel chromatography
(cyclohexane/EtOAc, from 90/10 to 40/60) to afford 45 mg of
the α anomer and 12 mg of the β anomer as amorphous white
solids. Global yield: 27 % (0.135 mmol, 57 mg).
1-Phenyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-
glucopyranose.27
1H NMR (300 MHz, CDCl3) δ 7.30-7.18 (m, 2 Hα, 2 Hβ),
7.06-6.98 (m, 3 Hα, 1 Hβ), 6.93-6.90 (2 Hβ), 5.68 (app t, J =
9.5 Hz, 1 Hα), 5.55 (d, J = 3.6 Hz, 1 Hα), 5.37-5.22 (m, 4 Hα,
4 Hβ), 5.08-5.95 (m, 1 Hα, 3 Hβ), 4.87-4.75 (m, 2 Hα, 1 Hβ),
4.71-4.67 (m, 1 Hα, 1 Hβ), 4.42-3.83 (m, 11 Hα, 12 Hβ), 2.08-
1.91 (m, 30 Hα, 30 Hβ). 13C NMR (75 MHz, CDCl3) δ 170.7,
170.6, 170.5, 170.4, 170.3, 170.0, 169.7, 169.6, 169.4, 156.7,
156.2, 129.6, 123.3, 123.0, 117.0, 116.9, 98.5, 95.9, 95.7,
95.6, 94.3, 75.2, 73.9, 72.7, 72.5, 72.4, 72.2, 72.0, 71.7, 71.0,
70.5, 70.0, 69.4, 69.0, 68.6, 68.5, 68.0, 63.0, 62.6, 62.3, 61.4,
20.8, 20.7, 20.6, 20.5. HRMS (ESI) calculated for
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26
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60
1H NMR (300 MHz, CDCl3) δ 7.28-7.20 (m, 2 H), 7.03-6.98
(m, 3 H), 5.81 (d, J = 9.4 Hz, 1 H), 5.50 (d, J = 3.6 Hz, 1 H),
5.37 (dd, J = 10.8, 9.4 Hz, 1 H), 5.14 (app t, J = 9.7 Hz, 1 H),
4.45 (ddd, J = 10.8, 9.4, 3.6 Hz, 1 H), 4.14 (dd, J = 12.8, 5.2
Hz, 1 H), 4.00-3.96 (m, 2 H), 2.00 (s, 3 H), 1.97 (s, 3 H), 1.95
(s, 3 H), 1.89 (s, 3 H). 13C NMR (75 MHz, CDCl3) δ 171.5,
170.6, 170.0, 169.3, 155.8, 129.7 (2 C), 123.1, 116.4 (2 C),
95.6, 71.1, 68.4, 67.9, 61.7, 51.9, 23.1, 20.7, 20.6 (2 C).
14
C44H56O26Na [M+Na]+ 1023.2958, found 1023.2950. [α]D
+130.5° (c 0.48, MeOH). FT-IR vmax/cm-1 : 1742, 1368, 1213,
1029, 897, 761, 693, 600.
(3aS,4R,6R,6aR)-4-phenoxy-2-phenyl-6-(2-phenyl-1,3,2-
dioxaborolan-4-yl)tetrahydrofuro[3,4-d][1,3,2]dioxaborole
5a.
Phenylboronic acid (245 mg, 2 mmol) and MgSO4 (2.0 g, 16.6
mmol) were added to a suspension of α-mannose (180 mg, 1.0
mmol) in dioxane (20 mL). The reaction media was then
stirred for three hours at room temperature, filtrated and the
solvent was evaporated. The resulting diboronate was used
without further purification. In a 100 mL round bottom flask,
molecular sieves (350 mg), Cu(OAc)2*H2O (60.0 mg, 0.30
mmol), pyridine (80.0 µL, 1.0 mmol) and dichloroethane (3.0
mL) were introduced successively. The suspension was stirred
5 minutes and phenylboronic acid (365 mg, 3 mmol) was
added, followed by the previous diboronate. This mixture was
stirred under air atmosphere at room temperature for 24 hours.
The media was diluted DCM and filtrated over celite. The
solvent was removed by evaporation and the crude residue
was purified by silica gel chromatographie (DCM) to afford
172 mg (40%) of the title compound as a single α anomer.
1-Phenyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-
glucopyranose.28
1H NMR (300 MHz, CDCl3) δ 7.32-7.13 (m, 2 H), 7.04-6.79
(m, 3 H), 5.61 (d, J = 8.7 Hz, 1 H), 5.34 (dd, J = 10.5, 9.2 Hz,
1 H), 5.20 (d, J = 8.2 Hz, 1 H), 5.07 (app t, J = 9.5 Hz, 1 H),
4.22 (dd, J = 12.2, 5.4 Hz, 1 H), 4.16-3.99 (m, 2 H), 3.90-3.70
(m, 1 H), 2.00 (s, 3 H), 1.99 (s, 3 H), 1.97 (s, 3 H), 1.88 (s, 3
H). 13C NMR (75 MHz, CDCl3) δ 170.8, 170.6, 170.3, 169.4,
157.0, 129.5 (2 C), 123.2, 116.9 (2 C), 99.0, 72.1, 72.0, 68.6,
62.2, 54.8, 23.3, 20.7 (2 C), 20.6.
1-phenyl-2,3,6,2’,3’,4’,6’-Hepta-O-acetylcellobiose 4i.
The title compound was prepared according to the general
procedure from 1i (320 mg) and phenylboronic acid (185 mg)
and was purified on silica gel chromatography (cyclohex-
ane/EtOAc, (50/50) to afford 274 mg of an inseparable mix-
ture of α and β anomers as an amorphous white solid (77%,
α:β = 1.5:1 in NMR, 1.2:1 in HPLC).
1H NMR (400 MHz, CDCl3) δ 7.79-7.73 (m, 4 H), 7.49-7.36
(m, 2 H), 7.36-7.26 (m, 4 H), 7.24-7.16 (m, 2 H), 7.01-6.89
(m, 3 H), 5.72 (s, 1 H), 5.24 (dd, J = 6.2, 3.9 Hz, 1 H), 5.14 (d,
J = 6.1 Hz, 1 H), 4.93 (app dt, J = 8.1, 6.4 Hz, 1 H), 4.41-4.31
(m, 1 H), 4.21 (dd, J = 9.4, 6.6 Hz, 1 H). 13C NMR (100 MHz,
CDCl3) δ 156.0, 135.1 (2 C), 135.0 (2 C), 132.1, 131.6, 129.6
(2 C), 128.0 (2 C), 127.8 (2 C), 122.6, 116.7 (2 C), 105.2,
86.0, 82.3, 80.6, 74.3, 68.0.29 11B NMR (128 MHz, CDCl3) δ
1H NMR (300 MHz, CDCl3) δ 7.26-7.20 (m, 2 Hα, 2 Hβ),
7.02-6.96 (m, 3 Hα, 1 Hβ), 6.91-6.88 (m, 2 Hβ), 5.63 (app t, J
= 9.7 Hz, 1 Hα), 5.57 (d, J = 3.5 Hz, 1 H α), 5.23-4.96 (m, 2
Hα, 5 Hβ), 4.92-4.84 (m, 2 Hα, 1 Hβ), 4.48-4.29 (m, 3 Hα, 3
Hβ), 4.11-3.94 (m, 3 Hα, 2 Hβ), 3.83-3.71 (m, 1 Hα, 2 Hβ),
3.62-3.59 (m, 1 Hα, 1 Hβ), 2.02-1.91 (m, 21 Hα, 21 Hβ). 13C
NMR (75 MHz, CDCl3) δ 170.5, 170.4, 170.2, 169.6, 169.3,
169.0, 156.8, 156.2, 129.6, 129.5, 123.3, 122.9, 116.9, 116.6,
100.8, 98.9, 94.1, 76.5, 76.4, 73.0, 72.9, 72.5, 72.0, 71.6, 71.4,
70.6, 69.5, 68.9, 67.8, 61.9, 61.6, 20.6, 20.5. HRMS (ESI)
14
32.2. [α]D +106.4° (c 0.24, MeOH). FT-IR vmax/cm-1 : 1601,
1369, 1297, 1223, 1097, 982, 754, 692, 634.
1-Phenyl-α-D-mannofuranose 6a.
In a round bottom flask, 5a (693 mg, 1.62 mmol) was sus-
pended in a mixture of EtOH (9.1 mL) and water (4.9 mL). m-
CPBA30 (800 mg, 3.24 mmol) was added and the resulting
mixture was stirred at room temperature for 4 hours. The
solvent was evaporated on a rotavapor and the crude residue
was purified by silica gel chromatography (DCM/MeOH,
from 100/0 to 90/10) to afford 334 mg (80%) of the titled
compound as a colorless oil that solidified over time.
calculated for C32H40O18Na [M+Na]+ 735.2112, found
14
735.2112. [α]D +38.0° (c 0.40, DCM). FT-IR vmax/cm-1
:
1742, 1368, 1218, 1038, 908, 762, 693, 598.
1-Phenyl-(4-O-(4-O-(2,3,4,6-tetra-O-acetyl-α-D-
glucopyranosyl)-2,3,6-tri-O-acetyl-α-D-glucopyranosyl))-
2,3,6-tri-O-acetyl-D-glucopyranose 4j.
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The Journal of Organic Chemistry
1H NMR (300 MHz, CD3OD) δ 7.37-7.18 (m, 2 H), 7.04-6.96
2,3,4,6-Tetra-O-acetyl-D-galactopyranose 1d.
Page 12 of 15
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(m, 3 H), 5.56 (d, J = 3.3 Hz, 1 H),4.39-4.33 (m, 2 H), 4.11
(dd, J = 8.1, 3.1 Hz, 1 H), 4.03-3.97 (m, 1 H), 3.78 (dd, J =
11.5, 3.1 Hz, 1 H), 3.61 (dd, J = 11.5, 6.0 Hz, 1 H). 13C NMR
(75 MHz, CD3OD) δ 158.8, 130.4 (2 C), 123.0, 117.7 (2 C),
107.7, 81.6, 78.9, 72.6, 71.4, 64.7. HRMS (ESI) calculated for
In a round bottom flask, hydrazine acetate (0.26 g, 2.82 mmol)
was added to a solution of β-D-galactose pentaacetate (1.00 g,
2.56 mmol) in DMF (30 mL). The resulting mixture was
stirred at 55 °C for 2 hours. The media was allowed to cool
down at room temperature and was diluted with EtOAc and a
saturated solution of NaHCO3. The aqueous layer was extract-
ed with EtOAc and the combined organic layer was washed
with brine. The solvent was dried over MgSO4, filtrated and
evaporated. The resulting oil was diluted with toluene and the
volatiles were evaporated on a rotavapor. This procedure was
performed until most of the DMF was eliminated. The crude
residue was then purified by silica gel flash chromatography
(cyclohexane/EtOAc, from 80/20 to 40/60) to afford the title
compound as a mixture of two anomers. Amorphous white
solid, 400 mg (45%, α:β = 2.3:1). The NMR data were in good
agreement with the literature.33
14
C12H16O6Na [M+Na]+ 279.0845, found 279.0850. [α]D
+171.4° (c 0.32, MeOH). FT-IR vmax/cm-1 : 3332, 1599, 1494,
1222, 1007, 885, 823, 752, 690.
9
Synthesis of starting material 1b, 1d, 1f, 1h, 1i and 1j.
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2,3,4,6-tetra-α-O-acetyl-D-glucopyranose 1b.
β-D-glucose pentacetate (3.9 g, 10.0 mmol) was introduced in
THF (50.0 mL) and benzylamine (1.2 mL, 11.0 mmol) was
added. The resulting solution was stirred at room temperature
for 18 hours. The media was diluted with Et2O and washed
with a solution of HCl (1 M) and brine, dried over sodium
sulfate and concentrated on a rotavapor. The crude residue
was purified on silica gel chromatography (cyclohexa-
he/EtOAc, from 70/30 to 60/40) to afford the desired product
as an inseparable mixture of two anomers. White foam, 2.9 g
(82%, α:β = 3:1). NMR data were in good agreement with the
literature.31
1H NMR (300 MHz, CDCl3) δ (α anomer) 5.44 (app t, J = 3.6
Hz, 1 H), 5-41-5.40 (m, 1 H), 5.33-5.32 (m, 1 H), 5.07 (dd, J =
10.8, 3.5 Hz, 1 H), 4.41 (app t, J = 6.6 Hz, 1 H), 4.10-4.02 (m,
2 H), 3.93-3.90 (m, 1H), 2.08 (s, 3 H), 2.03 (s, 3 H), 1.99 (s, 3
H), 1.93 (s, 3 H), (β anomer) 5.36 (d, J = 3.4 Hz, 1 H),5.02-
5.00 (m, 2 H), 4.65 (app t, J = 7.5 Hz, 1 H), 4.14 (d, J = 8.5
Hz, 1 H), 4.10-4.02 (m, 2 H), 3.93-3.90 (m, 1 H), 2.10 (s, 3
H), 2.03 (s, 3 H), 1.99 (s, 3 H), 1.93 (s, 3 H). 13C NMR (75
MHz, CDCl3) δ (α anomer) 170.6, 170.5, 170.3, 170.2, 170.1,
90.6, 68.4, 68.2, 67.3, 66.1, 61.8, 20.8, 20.7, 20.6, 20.5, (β
anomer) 170.9, 170.6, 170.2, 170.1, 95.9, 70.9 (2 C), 70.5,
67.2, 61.5, 20.8, 20.7, 20.6, 20.5.
1H NMR (300 MHz, CDCl3) δ (α anomer) 5.54 (app t, J = 9.8
Hz, 1 H), 5.47 (app t, J = 3.7 Hz, 1 H), 5.09 (app t, J = 9.8 Hz,
1 H), 4.93-4.87 (m, 1 H), 4.29-4.22 (m, 2 H), 4.17-4.12 (m, 1
H), 3.52 (d, J = 3.9 Hz, 1H), 2.11-2.03 (m, 12 H), (β anomer)
5.26 (app t, J = 9.5 Hz, 1 H), 5.13-5.06 (m, 1 H), 4.93-4.87
(m, 1 H), 4.75 (app t, J = 8.3 Hz, 1 H), 4.29-4.22 (m, 1 H),
4.17-4.12 (m, 1 H), 3.85 (d, J = 8.7 Hz, 1H), 3.77 (ddd, J =
10.0, 4.8, 2.4 Hz, 1 H), 2.11-2.03 (m, 12 H). 13C NMR (75
MHz, CDCl3) δ 170.8, 170.7 (β), 170.2, 169.6, 169.5 (β), 95.5
(β), 90.1(α), 73.2(β), 72.3(β), 72.1(β), 71.1, 69.9(α), 68.5(α),
68.5(β), 67.2(α), 62.0(α), 20.7, 20.6.
2‐Deoxy‐3,4,6‐tri‐O‐acetyl‐α-D‐glucopyranose 1f.
In a round bottom flask and under inert atmosphere, LiBr
(1.00 g, 11.52 mmol), amberlite IR120 (1.00 g) and water (1.2
ml) were added to a solution of tri-O-acetyl-D-glucal (1.00 g,
3.67 mmol) in MeCN (30 mL). The solution was stirred at
room temperature for 5 h, filtered and neutralized with tri-
ethylamine. The volatiles were removed by evaporation on a
rotavapor . The residue was dissolved in DCM and water. The
organic phase was washed with an ice cold solution of HCl
(1M) and NaHCO3 (sat), dried over Na2SO4, filtered and
evaporated to dryness. Purification by flash column chroma-
tography on silica gel (cyclohexane/EtOAc, 60/40) afforded
the desired product as a mixture of two anomers. White amor-
phous solid, 390 mg (37%, α:β = 8:1). NMR data were in good
agreement with the literature.34
2,3,4,6-Tetra-O-acetyl-α-D-mannopyranose 1c.
In a round bottom flask, D-mannose (3.06 g, 17 mmol) was
dissolved in pyridine (15.0 mL, 186 mmol). Then, acetic an-
hydride (16.0 mL, 170 mmol) was carefully added. The result-
ing mixture was stirred overnight at room temperature. The
media was poured into water and the aqueous layer was ex-
tracted three times with EtOAc. The combined organic layer
was then successively washed with NaHCO3 (sat), water and
brine, dried over sodium sulfate and concentrated under re-
duced pressure to afford a brown foam. This intermediate was
introduced in Et2O (85.0 mL) and benzylamine (2.05 mL, 18.7
mmol) was added. The resulting solution was stirred at room
temperature for 5 hours. The media was then washed with
NH4Cl (sat) and brine, dried over sodium sulfate and concen-
trated on a rotavapor. The crude residue was purified on silica
gel chromatography (cyclohexahe/EtOAc, from 80/20 to
50/50) to afford the desired product as an inseparable mixture
of two anomers. White foam, 4.1 g (70%, α:β = 9:1). NMR
data were in good agreement with the literature.32
1H NMR (300 MHz, CDCl3) δ 5.43-5.34 (m, 2 H), 5.01 (app t,
J = 9.5 Hz, 1 H), 4.30-4.19 (m, 2 H), 4.11-4.07 (m, 1 H), 2.82-
2.80 (m, 1 H), 2.28 (dd, J = 13.3, 5.6 Hz, 1 H), 2.09 (s, 3 H),
1
2.04 (s, 3 H), 2.01 (s, 3 H), 1.86-1.77 (m, 1 H). H NMR (300
MHz, CDCl3) δ 170.8, 170.2, 169.9, 91.6, 69.5, 68.7, 68.0,
62.5, 35.1, 20.9, 20.7(2 C).
2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranose
1h.
In a round bottom flask, glucosamine hydrochloride (2.0 g,
9.3 mmol) was introduced in pyridine (26.0 mL, 322 mmol).
Then, acetic anhydride (13.0 mL, 138 mmol) was carefully
added. The resulting mixture was stirred overnight at room
temperature. The media was poured into water and the aque-
ous layer was extracted three times with EtOAc. The com-
bined organic layer was then successively washed with Na-
HCO3 (sat), water and brine, dried over sodium sulfate and
1H NMR (300 MHz, CDCl3) δ 5.41 (dd, J = 10.1, 3.2 Hz, 1
H), 5.32-5.22 (m, 3 H), 4.27-4.19 (m, 2 H), 4.16-4.11 (m, 1
H), 3.75 (d, J = 4.1 Hz, 1 H), 2.15 (s, 3 H), 2.09 (s, 3 H), 2.04
(s, 3 H), 1.99 (s, 3 H). 13C NMR (75 MHz, CDCl3) δ 170.9,
170.2, 170.1, 169.8, 92.1, 70.1, 68.8, 68.5, 66.2, 62.6, 20.9 (2
C), 20.7 (2 C).
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The Journal of Organic Chemistry
HCl (1 M), NaHCO3 (sat) and brine. The organic layer was
concentrated under reduced pressure. This intermediate was
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dissolved in Et2O (40 mL) and 4.6 mL of a 2 M solution of
methylamine in MeOH (9.2 mmol) was then added. The re-
sulting solution was stirred at room temperature for 4 hours.
The media was then washed with NH4Cl (sat) and brine, dried
over sodium sulfate and concentrated on a rotavapor. The
crude residue was purified on silica gel chromatography
(DCM/MeOH, from 100/0 to 95/5) to afford the desired prod-
uct as a mixture of two anomers. White amorphous solid, 2.4 g
(73%, α:β = 19:1). NMR data were in good agreement with
the literature.35
dried over magnesium sulfate, filtrated and the solvent was
evaporated. Purification by silica gel chromatography (cyclo-
hexane/EtOAc : 60/40) afforded the desired compound as a
mixture of two anomers. White amorphous solid, 3.05 g (55%,
α:β = 1.6:1). NMR data were in good agreement with the
literature.37
1H NMR (300 MHz, CDCl3) δ 5.56 (app t, J = 9.4 Hz, 1 H),
5.42-5.24 (m, 5 Hα, 5 Hβ), 5.08-5.01 (m, 1 Hα, 1 Hβ), 4.85-
4.81 (m, 1 Hα, 1 Hβ), 4.77-4.70 (m, 2 Hα, 2 Hβ), 4.48-4.44
(m, 2 Hα, 2 Hβ), 4.30-3.89 (m, 9 Hα, 10 Hβ), 3.78-3.74 (m, 1
Hα, 1 Hβ), 2.15-1.97 (m, 30 Hα, 30 Hβ). 13C NMR (75 MHz,
CDCl3) δ 170.7, 170.6, 170.5, 170.4, 170.2, 169.9, 169.8,
169.7, 169.4, 95.8, 95.6, 94.9, 90.0, 74.7, 73.8, 73.7, 72.6,
72.5, 72.4, 72.3, 71.8, 71.7, 71.6, 70.4, 70.1, 69.4, 69.0, 68.9,
68.5, 68.0, 67.7, 63.0, 62.4, 62.3, 61.4, 20.9, 20.8, 20.6, 20.5.
HRMS (ESI) calculated for C38H52O26Na [M+Na]+ 947.2645,
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60
1H NMR (300 MHz, CDCl3) δ 6.00 (d, J = 9.3 Hz, 1 H), 5.31-
5.22 (m, 2 H), 5.11 (app t, J = 9.5 Hz, 1 H), 4.67-4.66 (m, 1
H), 4.30-4.07 (m, 4 H), 2.07 (s, 3H), 2.01 (s, 4H), 2.01 (s, 4H),
1.95 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 171.4, 171.0,
170.6, 169.4, 91.5, 71.0, 68.3, 67.5, 62.1, 52.4, 23.1, 20.7 (2
C), 20.6.
found 947.2674.
2,3,6,2’,3’,4’,6’-Hepta-O-acetylcellobiose 1i.
In a round bottom flask, α-D-cellobiose octaacetate (1.36 g,
2.00 mmol) was dissolved in a mixture of THF (15.0 mL) and
acetone (2.0 mL). To this solution was added benzylamine
(660 µL, 6.0 mmol) and the resulting mixture was heated at 50
°C overnight. After cooling, the volatiles were evaporated and
the residue was dissolved in DCM. The organic layer was
successively washed with a solution of HCl( 1 M), NaHCO3
(sat) and brine, dried over magnesium sulfate, filtrated and
evaporated to dryness. Purification by flash column chroma-
tography on silica gel (cyclohexane/EtOAc, 60/40) afforded
the desired product as a mixture of two anomers. White amor-
phous solid, 710 mg (56%, α:β = 1.3:1). NMR data were in
good agreement with the literature.36
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
Full optimization table, NMR spectra of all synthesized com-
pounds and HPLC chromatograms.
AUTHOR INFORMATION
Corresponding Author
* samir.messaoudi@u-psud.fr, mouad.alami@u-psud.fr
Author Contributions
1H NMR (300 MHz, CDCl3) δ 5.48 (app t, J = 9.7 Hz, 1 Hα),
5.34 (app t, J = 3.7 Hz, 1 Hα), 5.22-5.01 (m, 2 Hα, 3 Hβ),
4.93-4.87 (m, 1 Hα, 1 Hβ), 4.82-4.68 (m, 1 Hα, 2 Hβ), 4.53-
4.47 (m, 2 Hα, 2 Hβ), 4.37-4.32 (m, 1 Hα, 1 Hβ), 4.17-3.92
(m, 3 Hα, 3 Hβ), 3.79-3.62 (m, 3 Hα, 3 Hβ), 2.11-1.96 (m, 21
Hα, 21 Hβ). 13C NMR (75 MHz, CDCl3) δ 170.6, 170.4,
170.3, 169.7, 169.3, 169.0, 100.8, 100.6, 95.2, 90.0, 76.5,
73.3, 73.0, 72.9, 71.9, 71.6, 71.3, 69.3, 68.2, 67.9, 67.8, 61.9,
61.8, 61.6, 20.9, 20.7, 20.6, 20.5. HRMS (ESI) calculated for
C26H36O18Na [M+Na]+ 654.2245, found 654.2251.
The manuscript was written through contributions of all authors.
/ All authors have given approval to the final version of the
manuscript.
ACKNOWLEDGMENTS
Authors acknowledge support of this project by CNRS, Universi-
ty Paris-Sud, ANR (ANR-15-CE29- 0002), and by la Ligue Con-
tre le Cancer through an Equipe Labellisée 2014 grant. We also
thank the Algerian Ministry of Education and Research for a
fellowship (PNE) to Sara Benmahdjoub. Our laboratory is a
member of the Laboratory of Excellence LERMIT supported by a
grant (ANR-10-LABX-33)
4-O-(4-O-(2,3,4,6-Tetra-O-acetyl-α-D-glucopyranosyl)-
2,3,6-tri-O-acetyl-α-D-glucopyranosyl)-2,3,6-tri-O-acetyl-
D-glucopyranose 1j.
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