A catalytic Koenigs-Knorr glycosylation based on acceptor activation with In(NTf2)3

Article abstract of DOI:10.1016/j.tet.2018.05.080

The development of efficient glycosylation methods is important for gaining better insight into biological processes of significance to medicinal chemistry. Herein, we describe an In(NTf₂)₃ -catalyzed Koenigs-Knorr glycosylation based on the activation of an alcoholic hydroxyl group. A catalytic amount of In(NTf₂)₃ enables effective glycosylation of diverse alcohols with peracylated aldosyl bromides as donors, leading to the stereoselective formation of a series of glycosides in satisfactory yields. The protocol is characterized by mild reaction conditions and good functional-group tolerance, while obviating any need for any additive. Moreover, the potential utility of this transformation is demonstrated by the convenient syntheses of key building blocks for biomolecules of medicinal relevance.

Full text of DOI:10.1016/j.tet.2018.05.080

Accepted Manuscript
A catalytic Koenigs-Knorr glycosylation based on acceptor activation with In(NTf )
2
3
Changwei Li, Haijing Liang, Zhan-xin Zhang, Zhaoyan Wang, Lan Yu, Huanxiang Liu,
Fengli An, Shaohua Wang, Lixia Ma, Weihua Xue
PII:
S0040-4020(18)30639-2
10.1016/j.tet.2018.05.080
TET 29587
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 9 April 2018
Revised Date: 23 May 2018
Accepted Date: 28 May 2018
Please cite this article as: Li C, Liang H, Zhang Z-x, Wang Z, Yu L, Liu H, An F, Wang S, Ma L, Xue W,
A catalytic Koenigs-Knorr glycosylation based on acceptor activation with In(NTf ) , Tetrahedron (2018),
2
3
doi: 10.1016/j.tet.2018.05.080.
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A catalytic Koenigs-Knorr glycosylation
based on acceptor activation with In(NTf2)3
Leave this area blank for abstract info.
Changwei Li, Haijing Liang, Zhan-xin Zhang, Zhaoyan Wang, Lan Yu, Huanxiang Liu, Fengli An, Shaohua
*
Wang, Lixia Ma, Weihua Xue
School of Pharmacy, Lanzhou University

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
A catalytic Koenigs-Knorr glycosylation based on acceptor activation with
In(NTf2)3
Changwei Li, Haijing Liang, Zhan-xin Zhang, Zhaoyan Wang, Lan Yu, Huanxiang Liu, Fengli An,
*
Shaohua Wang, Lixia Ma, Weihua Xue
School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The development of efficient glycosylation methods is important for gaining better insight into
biological processes of significance to medicinal chemistry. Herein, we describe an In(NTf
catalyzed Koenigs-Knorr glycosylation based on the activation of an alcoholic hydroxyl group.
A catalytic amount of In(NTf enables effective glycosylation of diverse alcohols with
2 3
) -
2 3
)
Available online
peracylated aldosyl bromides as donors, leading to the stereoselective formation of a series of
glycosides in satisfactory yields. The protocol is characterized by mild reaction conditions and
good functional-group tolerance, while obviating any need for any additive. Moreover, the
potential utility of this transformation is demonstrated by the convenient syntheses of key
building blocks for biomolecules of medicinal relevance.
Keywords:
Koenigs-Knorr Glycosylation
Acceptor activation
In(NTf
catalytic
stereoselective
2 3
)
2
009 Elsevier Ltd. All rights reserved.
—
——
∗
Corresponding author. Tel: +86 0536 8915682; E-mail address: xuewh2018@sina.com

2
Tetrahedron
1
. Introduction
isolated yield in the presence of catalytic In(OTf) (0.1 equiv)
ACCEPTED MANUSCRIPT
3
(
Entry 4, Table1 ), which increased to 62% when InI was used
3
Glycosides and polysaccharides are broadly prevalent in
as the catalyst (Entry 5, Table 1). We eventually discovered that
the reaction was most efficient in the presence of In(NTf ) (0.01
organisms. Their carbohydrate components are well known to be
closely associated with many physiological processes relevant to
human life. Synthetic access to ample O-glycosidically linked
carbohydrate units is often necessary to gain better insight in2
their involvement into biologically significant processes.
Chemical glycosylation is a common strategy for glycosidic-
bond formation.
2
3
mmol) in CH Cl for 4h, which facilitated the isolation of G1 in
1
2
2
9
6% yield (Entry 6, Table 1). We were able to decrease the
catalyst loading to 0.05 equiv. with longer reaction times or
under reflux with minimal effect on the yield (94-97%, Entries 7
and 8, Table 1). Hence, the conditions listed in Entry 6 were
taken as optimal.
Currently the development of methods for accessing the
glycosidic linkages has grown into a topic of intensive research
interest in the field of glycochemistry. The generation of complex
and diverse scaffolds from structurally simple glycosyl donors
affords the advantages of operational simplicity and atom
Table1. Optimizing the indium-catalyzed Koenigs-Knorr
reaction
a
3
economy. The Koenigs-Knorr reaction provides an attractive
pathway to glycosides because aldosyl halides are a useful
category of building blocks, a consequence of their low costs and
ready accessibilities. Moreover, glycosyl bromides are prone to
exist as single isomers, which make them relatively easily isolate
and purify. Unfortunately, this named reaction relies on the use
Indium salt
equiv.)
InBr (0.1)
InBr (0.1)
Isolated
yield (%)
Entry
T(ꢀ)
Time(h)
b
(
1
2
3
4
5
6
7
3
23
40
23
23
23
23
23
40
24
24
24
24
2
4
10
1
43
45
17
51
62
96
94
97
3
4
5
of stoichiometric halophilic reagents such as Hg(CN) , AgNO ,
InCl
In(OTf)
InI (0.1)
In(NTf (0.1)
3
(0.1)
2
3
6
7
8
9
AgOTf, AgClO4, and Ag O, as well as others. Recently a
3
(0.1)
2
remarkably modified version of the Koenigs-Knorr reaction was
3
10
2
)
3
reported by Ye and co-workers, who found that a wide range of
alcohols could be converted into glycosides through an
interactive process involving glycosyl chloride donors and a
catalytic amount of thiourea. In spite of these encouraging
results, large excess of additives in combination with the reflux
conditions required to achieve the good yields is a major
drawback of the method. Hence, the development of a novel
catalyst that facilitates the easy formation of glycosides under
mild condition is still important for continued advancements in
this area.
In(NTf
In(NTf
2
)
)
3
(0.05)
(0.05)
8
2
3
a
Reaction conditions: D1 (0.1 mmol), epiandrosterone (0.12
mmol), and 4Å molecular sieves, with stirring in CH Cl (2 mL)
2
2
b
under Ar. Isolated yield based on D1.
Having established the optimal reaction conditions, we turned
our attention to the scope of the reaction using known donors D1-
7 (Figure 1) and acceptors. We first investigated glycosylation
with readily accessible aldosyl bromides D1-5 including fully
acylated glucosyl (D1, D5), galactosyl(D2), mannosyl(D3), and
rhamnosyl(D4) donors, which they were successively treated
with a series of alcohols to construct glycosidic bonds.
We also paid significant attention to substantial advances
made in the transition-metal-catalyzed syntheses of glycosides. In
general, the use of a transition-metal catalyst provides a mild and
orthogonal alternative approach to traditional glycosylation
1
1-15
chemistry.
Recently,1 we reported the InBr -catalyzed
3
6
syntheses of thioaldoses through reactions of peracetylated
aldoses with arylthiols, and subsequently discovered InI to be an
3
17
effective glucosidation catalyst with a glucosyl fluoride donor.
Taking into account on the above advances about
glycochemistry, we wondered whether or not Koenigs-Knorr
glycosylation would proceed under indium catalysis. Although
several glycosylation protocols 18using indium halides as
promoters have been reported,
they suffer from narrow
substrate scope and relatively high promoter dosage. Herein we
describe a new advance in the indium-catalyzed synthesis of
glycoside.
Figure 1. Glycosyl donors in In(NTf ) -catalyzed glycosylation
2
3
As shown in Figure 1, primary, secondary, and tertiary
alcohols were readily accommodated in this transformation to
produce in corresponding glycosides G2-18 in good yields and
with 1, 2-trans stereocontrol. For instance, sterically bulky 1-
adamantanol was effectively glucosidated, with the
corresponding product G2 obtained in a good yield (89%).
Especially interestingly, an intermediate of significance to
potential pharmaceutical molecules was examined to demonstrate
the synthetic potential of this protocol. Tyrosol underwent the
regioselective glucosidation to provide G4 in a 90% yield; this
glucoside, bearing a free phenolic hydroxyl group, is a direct
precursor of salidroside, which is a significant bioactive
2
. Result and discussion
To test reaction conditions, perbenzoylated glucosyl bromide
(D1) was initially exposed to with epiandrosterone (1.2 equiv)
and catalytic InBr (0.1 equiv) in CH Cl at 23ꢀ under argon
3
2
2
(Table 1). To our delight, our hypothesis was validated, with G1
obtained in 43% isolated yield after 24 h (Entry 1, Table 1).
However, the subsequent use of the reflux conditions did not help
to further increase the yield (45%, Entry 2, Table 1), and the use
of InCl instead of InBr resulted in a much lower yield (17%,
3
3
Entry 3, Table 1).These results, together with our recent study on
the indium-catalyzed (thio)glycosidations suggest that the
activity of catalyst is significantly influenced by the counterions,
consequently we further examine the effects of other
commercially available indium salts. G1 was formed in 51%
19
component isolated from Rhodiola sachalinensis. Consequently,
the natural product, which was cumbersome to prepare
20
previously using other methodologies, are now economically
obtained using our protocol and subsequent routine deprotection.

Remarkably, this method was also applicable to 2-
acceptor was sluggish and provided an unsatisfactory yield (46%)
of the desired product G23 even after 24 h. These results
demonstrated the hydroxyl groups of sugar are less nucleophilic
than those of the simple alcohols. Therefore, we were required to
slightly modify the reaction conditions in order to efficiently
glycosylating the alcohol moieties of sugars. In our attempts to
improve the yields, In(NTf ) and A1 dosages were screened.
An increase in the dosage of A1 to only1.5 equiv led to a slightly
higher yield (52%; Entry 1, Table 2) after stirring for 24h at room
temperature. Notably, when the catalyst loading was increased to
0.15 equiv. and 1.5 equiv of A1 was used, a good conversion of
D1 was observed (76%; Entry 2, Table 2); further increasing the
amount of A1 to 2.0 equiv led to a yield of 85% (Entry 3, Table
2), while subjecting the reaction to the reflux conditions resulted
in no significant change in yield (Entry 4, Table 2).
ACCEPTED MANUSCRIPT
azidogalactosyl bromide (D6). D6 and bulky acceptors were
rapidly coupled to provide azide derivatives G19 and 20 in high
yields. In the case of a typical amino acid, the coupling of N-
Fmoc threonine ester with D6 delivered the glycosylation product
G21 (88%, α/β = 6:1), which often serves as a pivotal synthon in
the syntheses of biologically important glycoproteins carrying N-
acetylgalactosamine units α-O-glycosidically linked to threonine
residues. Furthermore, 2-deoxyglycoside G22 could be
efficiently and α-selectively prepared when 2-deoxy sugar
bromide (D7) was used as the donor. Our results also showed
2
3
that the
In(NTf ) -promoted glycosylation reactions with
2 3
glycosyl bromide donors tolerated a wide range of functional
substituents, including azido(G3, G19), phenolic hydroxyl(G4),
ketal(G6), halide(G7, G8), silyl(G10), ester(G17),
and
carbamate (G14, G21) groups; these coupling reactions
proceeded smoothly within about 4 h.
Significantly, the yield dropped sharply when other solvents
were used instead of CH Cl (Entries 5-7, Table2). Using these
2
2
modified conditions (Entry 3, Table 2), some other disaccharides
G 24-29 (Figure 2) were obtained in synthetically useful yields
that ranged from 75 to 92%. Disaccharides G23-28 were
obtained with uniform 1, 2-trans stereoselectivity when donors
D1-5 were employed, whereas glycosyl donor D6 afforded
exclusively the disaccharide G29 as an α- anomer.
Table2. Optimization for the In(NTf ) -catalyzed Koenigs-
2
3
a
Knorr reaction for disaccharide synthesis
In(NTf
2
)
3
Isolated
yields (%)
Entry
A1(equiv)
Solvent
b
b
(equiv)
1
2
3
0.1
1.5
1.5
2.0
2.0
2.0
2.0
2.0
CH
CH
CH
CH
toluene
THF
2
2
2
2
CH
CH
CH
CH
2
2
2
2
52
76
85
87
61
47
40
0.15
0.15
0.15
0.15
0.15
0.15
c
4
5
6
7
3
CH CN
a
Reactions were run with D1 (0.1 mmol), A1 and 4Å MS in the
b
stirred solvent (2 mL) under Ar for 24 h. Isolated yields based
on D1. The reaction was carried out under reflux.
c
Donors D1-5 bearing acyl groups at their C-2 position benefit
from neighboring -group participation effect, and reacted to
generate only the 1, 2-trans glycosides G1-18, 23-28. In contrast,
D6 benefits from the anomeric effect, resulting the α-selectivity
during 2-azidogalactosylation. In addition, an acetyl group at C-6
of D6 becomes involved in remote neighboring-group
participation, which is also helpful for the formation of
glycosides with the high α-anomeric selectivities; hence, D6
exhibits the strong preference of the formation of products G19-
2
1, 29 in a 1, 2-cis-selective manner. As for 2-deoxysugar donor
D7, the anomeric effect of 2-deoxyglycosides favors the
formation of G22 as a single α-isomer. All of the synthesized O-
1
13
glycosides were structurally characterized by H and C NMR
spectroscopies. Additionally, the α-anomeric configuration of
mannosides was further confirmed by NOE-based NMR
spectroscopy (see Supporting Information). NMR analyses
confirmed that except G21 other glycosylation products were
formed as single anomers in these reactions. These favorable
results are encouraging, as they demonstrate the feasibility of
facilitating Koenigs-Knorr reaction with catalytic amounts of
indium and bode well for future synthetic applications in
carbohydrate chemistry.
Figure 2. List of glycosides accessed by the In(NTf ) -catalyzed
2
3
glycosylation of common alcohols with donor D1-6. Reagents
and conditions: donor (0.1 mmol), acceptor (0.12 mmol),
In(NTf ) (0.01 mmol), CH Cl (2 mL) at room temperature
2
3
2
2
under Ar. Isolated yields based on the donor molar equivalent
and anomeric linkage as determined using the NMR spectra
Given the efficiencies of the indium-catalyzed glycosylations
of ordinary nucleophiles we decided to investigate the extension
of this methodology to the synthesis of disaccharides from
alcohol containing carbohydrate motifs. Unexpectedly,
glycosylation using compound D1 as the donor and A1 as the

4
Tetrahedron
ACCEPTED MAad
N
di
U
tiv
S
e i
C
s r
R
eq
I
uired, which is an important feature of this method.
P
T
Finally, mechanistic investigations using NMR spectroscopy
suggest that the reaction proceeds via the formation of an alkoxy-
indium adduct that displays enhanced oxygen-centered
nucleophilicity relative to a free alcohol. This represents an
interesting example of a Koenigs-Knorr glycosylation process
mediated by acceptor activation. Further investigations into the
application of indium catalysts to glycosidation reactions are
underway in our laboratory.
4
. Experimental section
4
.1 General inforamation
All operations were carried out in a nitrogen-filled glove box
or by using standard high vacuum and Schlenk techniques unless
otherwise noted. Dichloromethane was dried over calcium
hydride prior to use. In(NTf ) was purchased from Aldrich. All
2
3
other reagents, obtained from commercial sources, were used
without further purification. Flash column chromatography was
carried out on Silica Gel 60 (230-400 mesh). The reactions were
monitored by TLC. Spots were visualized by irradiation with a
UV lamp at 280 nm or by spraying with 10% H SO in ethanol
2
4
and subsequently heating on a hot plate. NMR spectra were
obtained on a Bruker AVANCE DMX 400 spectrometer
Figure 3. List of disaccharides accessed by the In(NTf ) -
1
2
3
operating at 400 MHz for H-NMR and NOE spectra, 100 MHz
catalyzed glycosylation of sugar alcohols with donor D1-6.
Reagents and conditions: donor (0.1 mmol), acceptor (0.2 mmol),
In(NTf ) (0.015 mmol), CH Cl (2 ml) at room temperature
13
for C-NMR. The following abbreviations were used to describe
peak splitting patterns when appropriate: s = singlet, d = doublet,
t = triplet, q=quatet, dd = doublet of doublets, m = multiplet.
Coupling constants J were reported in hertz unit (Hz). Chemical
shifts (in ppm) were referenced to tetramethylsilane (δ = 0 ppm)
2
3
2
2
under Ar, isolated yields based on the donor molar equivalent
and anomeric linkage as determined using the NMR spectra
To gain direct insight into the progress of the reaction, we
in CDCl as an internal standard. HRMS determinations were
3
1
elected to perform control H NMR experiments in CDCl . First,
made with the use of JOEL MStation (JMS-700) Mass
Spectrometer. Optical rotations were acquired on a JASCO DIP-
370 digital polarimeter. Analytical and spectral data of all the
known compounds are consistent with the reported values.
3
D1 was dissolved in CDCl at room temperature and treated with
3
an equimolar amount of In(NTf ) . No changes in the chemical
2
3
shifts of signals of the mixture relative to those of D1 alone were
detected by NMR spectroscopy (see Figure 4 in the Supporting
Information), and D1 was almost quantitatively recovered by the
chromatography. Schmidt et al. showed that AuCl3 catalyst
4
.2 Procedures for the In(NTf ) -catalyzed glycosidation of the
2 3
common alcohols
interacts with 2-propanol as an acceptor to give RO-AuCl -H
To a solution of glycosyl bromide (0.1 mmol) in anhydrous
CH Cl (2 mL) containing In(NTf (9 mg, 0.01mmol ) and 4 Å
3
[
9d]
adduct during glycosylation.
In a similar manner, we also
2
2
)
2 3
found In(NTf2)3 interacted with 2-propanol, as evidenced by
NMR spectroscopy. Our spectrum (Figure 5 in the Supporting
Information) fully corresponded with that of Schmidt. The
presence of In(NTf ) in CDCl caused the chemical shift of the
molecular sieves (5 mg), alcohol (0.12mmol) was added under
Ar. The mixture was allowed to stir for 2 h at room temperature.
The reaction mixture was evaporated under reduced pressure.
The resultant residue was rapidly eluted through chromatograph
on silica gel with toluene or hexane in EtOAc to yield the title
compound.
2
3
3
OH group in isopropanol to the downfield. It is worth
mentioning that in addition to Au, In and Pd are also able to
interact with alcohols to initiate glycosylation. In the study
reported by Galan the glycosylation reaction proceeded via an
alkoxy-palladium intermediate that increased the proton acidity
4
.2.1 Pregnenolonyl 2, 3, 4, 6-tetra-O-Bz-β-D-glucopyranoside
(G1)
21
23
[α ]D
of the alcohol and the nucleophilicity of its oxygen. Therefore,
we reasonably surmise that a shift in the OH signal was
ascribable to an adduct formed by the bonding of In(NTf ) to an
Yield 96% (83mg); White solid; mp 221-223 ꢀ ;
+63.7(c=1.0, CHCl ); R =0.30(Ethyl acetate/toluene, 1/10).
3
f
2
3
1
H NMR (400 MHz, CDCl ) δ 8.01 (d, J = 7.6 Hz, 2H), 7.96 (d, J
3
alcoholic hydroxyl. The above results clearly corroborate the
indium-mediated acceptor activation mechanism of our novel
Koenigs-Knorr glycosylation system, which is different to the
donor activation mechanism involved in thiourea-catalyzed
Koenigs-Knorr reaction recently reported by Ye and co-workers.
=
7.6 Hz, 2H), 7.91(d, J = 7.6 Hz, 2H), 7.83 (d, J = 7.6 Hz, 2H),
.56-7.46 (m, 3H), 7.39 (ddd, J = 11.9, 7.9, 4.1 Hz, 6H), 7.33 (d,
J = 7.8 Hz, 1H), 7.29 (d, J = 7.8 Hz, 2H), 5.90 (t, J = 9.6 Hz,
H), 5.63 (t, J = 9.7 Hz, 1H), 5.52-5.45 (m, 1H), 4.94 (d, J = 7.9
7
1
[
8]
Hz, 1H), 4.64-4.50 (m, 2H), 4.16 (s, 1H), 3.60 (dt, J = 11.2, 6.2
Hz, 1H), 2.48-2.31 (m, 2H), 2.05 (dt, J = 18.9, 9.0 Hz, 1H), 1.90
(s, 2H), 1.80-1.66 (m, 3H), 1.58 (d, J = 13.8 Hz, 2H), 1.48 (d, J =
3
. Conclusion
1
2.1 Hz, 2H), 1.24-1.15 (m, 5H), 0.98 (s, 2H), 0.83 (s, 3H), 0.71
13
An efficient glycosylation protocol has been developed that
employs indium-promoted Koenigs-Knorr reaction with
(s, 3H), 0.61 (d, J = 10.6 Hz, 1H). C NMR (100 MHz, CDCl ) δ
3
1
66.0, 165.8, 165.2, 165.0, 133.4, 133.2, 133.1, 133.0, 129.8,
In(NTf2) at low catalytic loadings. The reactions proceeded
3
129.7, 129.7, 129.6, 129.5, 129.0, 128.8, 128.8, 128.4, 128.3,
1
6
smoothly at room temperature to afford a variety of glycosides in
the satisfactory yields and with the good stereocontrol. An
28.3, 128.2, 128.2, 125.3, 100.0, 79.9, 73.0, 72.1, 72.0, 70.1,
3.4, 51.4, 47.7, 44.6, 36.7, 35.8, 35.6, 34.9, 34.5, 31.5, 30.8,

+
2
9.2, 28.2, 21.7, 20.4, 13.8, 12.1. HRMS (ESI): m/z [M +H]
4.42 (dd, J = 11.3, 6.3 Hz, 1H), 4.29 (t, J = 6.5 Hz, 1H), 3.48 (td,
J = 10.7, 4.2 Hz, 1H), 2.36 (s, 0H), 1.94 (d, J = 12.0 Hz, 1H),
ACCEPTED MANUSCRIPT
calcd for C H O 867.3744; found: 867.3750.
53
55 11
1
0
.59 (s, 3H), 1.24 (d, J = 13.9 Hz, 3H), 0.87 (d, J = 7.1 Hz, 3H),
4
.2.2 Adamantyl 2, 3, 4, 6-tetra-O-Bz-β-D-glucopyranoside (G2)
13
.74 (dd, J = 11.9, 6.7 Hz, 7H). C NMR (100 MHz, CDCl ) δ
3
2
3
Yield 89% (65 mg); White solid; mp 206-208 ꢀ ; [α ]
+
NMR (400 MHz, CDCl ) δ 8.02 (d, J = 7.5 Hz, 2H), 7.94 (dd, J =
1
7
1
1
7
1
1
1
1
166.1, 165.7, 165.6, 165.2, 133.5, 133.2, 133.1, 130.0, 129.8,
129.8, 129.7, 129.6, 129.5, 129.2, 128.9, 128.6, 128.4, 128.3,
99.9, 79.9, 72.1, 71.2, 70.0, 68.4, 62.3, 47.3, 41.2, 34.1, 31.4,
25.1, 23.0, 22.0, 20.9, 15.7. HRMS (ESI): m/z [M +H] calcd for
C
D
1
57.4(c=1.0, CHCl ); R =0.18(Ethyl acetate/toluene, 1/60). H
3 f
3
+
5.7, 7.6 Hz, 4H), 7.83 (d, J = 7.3 Hz, 2H), 7.55-7.47 (m, 3H),
.44-7.32 (m, 8H), 7.29 (d, J = 7.7 Hz, 1H), 5.93 (t, J = 9.6 Hz,
H), 5.59-5.47 (m, 2H), 5.13 (d, J = 7.9 Hz, 1H), 4.59 (dd, J =
1.9, 3.0 Hz, 1H), 4.49 (dd, J = 11.9, 7.1 Hz, 1H), 4.18 (d, J =
.0 Hz, 1H), 2.02 (s, 3H), 1.82 (d, J = 11.3 Hz, 3H), 1.66 (d, J =
H
47
O10 735.3169; found: 735.3165.
44
4
.2.6 Diosgenyl 2, 3, 4, 6-tetra-O-Bz-α-D-galactopyranoside
(G6)
13
23
1.5 Hz, 3H), 1.58-1.46 (m, 6H). C NMR (100 MHz, CDCl ) δ
Yield 89% (87mg); Colorless oil;1
=0.36 (Ethyl acetate/toluene1/20). H NMR (400 MHz, CDCl ) δ
[α
]D +40.9(c=1.5, CHCl ); R
3
3
f
66.0, 165.8, 165.3, 164.9, 133.4, 133.1, 133.0, 129.8, 129.7,
29.7, 129.6, 129.5, 129.0, 128.9, 128.8, 128.4, 128.3, 128.3,
28.2, 128.2, 94.3, 75.8, 73.2, 72.1, 71.9, 70.3, 63.7, 42.3, 36.0,
3
8.10 (d, J = 7.5 Hz, 2H), 8.02 (d, J = 7.5 Hz, 2H), 7.96 (d, J = 7.6
Hz, 2H), 7.79 (d, J = 7.2 Hz, 2H), 7.60 (d, J = 7.5 Hz, 1H), 7.56
(s, 2H), 7.52-7.47 (m, 3H), 7.40 (dt, J = 15.5, 7.6 Hz, 6H), 5.98
(d, J = 3.0 Hz, 1H), 5.77 (dd, J = 10.2, 8.0 Hz, 1H), 5.59 (dd, J =
10.4, 3.4 Hz, 1H), 5.22 (s, 1H), 4.91 (d, J = 8.0 Hz, 1H), 4.68
+
3
0.5. HRMS (ESI): m/z [M +H] calcd for C H O 731.2856;
44
43 10
found: 731.2859.
’
4
.2.3 2 -Azidoethyl 2, 3, 4, 6-tetra-O- Bz -β-D-glucopyranoside
(dd, J = 11.2, 6.8 Hz, 1H), 4.46-4.38 (m, 2H), 4.32 (t, J = 6.6 Hz,
(G3)
1
H), 3.56 (s, 1H), 3.48 (d, J = 10.1 Hz, 1H), 3.37 (t, J = 10.9 Hz,
2
D
3
Yield 88% (59 mg); Colorless oil; [α ] +10.2(c=1.0, CHCl ); Rf
=
1H), 2.19 (s, 2H), 1.97 (s, 2H), 1.89-1.84 (m, 1H), 1.74 (dd, J =
14.8, 5.1 Hz, 4H), 1.66-1.59 (m, 4H), 1.46 (s, 3H), 1.26 (s,
3H),1.08 (s,1H), 0.97 (d, J = 6.9 Hz, 4H), 0.93 (s, 4H), 0.80- 0.76
(m, 6H).
3
1
0.21(Ethyl acetate/hexane, 1/4). H NMR (400 MHz, CDCl ) δ
3
8
.03 (d, J = 7.8 Hz, 2H), 7.96 (d, J = 7.8 Hz, 2H), 7.91 (d, J = 7.8
Hz, 2H), 7.83 (d, J = 7.8 Hz, 2H), 7.59 -7.46 (m, 3H), 7.44 -7.38
m, 4H), 7.38-7.33 (m, 3H), 7.28 (d, J = 7.7 Hz, 2H), 5.92 (t, J =
.6 Hz, 1H), 5.69 (t, J = 9.7 Hz, 1H), 5.56 (t, J=9.6, 1H), 4.94 (d,
(
9
13
C NMR (100 MHz, CDCl ) δ 166.0, 165.6, 165.6, 165.2, 140.3,
3
1
1
1
5
33.5, 133.2, 133.1, 130.2, 130.1, 129.8, 129.6, 129.5, 129.5,
29.0, 128.8, 128.7, 128.6, 128.4, 128.4, 128.3, 128.3, 121.7,
09.3, 100.7, 80.8, 80.7, 71.9, 71.3, 67.0, 68.1, 66.8, 62.1, 56.5,
0.0, 41.6, 40.2, 39.7, 38.9, 37.1, 36.8, 32.0, 31.8, 31.4, 30.3,
J = 7.8 Hz, 1H), 4.67 (dd, J = 12.1, 3.0 Hz, 1H), 4.51 (dd,
J=12.1, 5.1Hz,1H), 4.18 (dt, J = 9.1, 4.0 Hz, 1H), 4.05 (dt, J =
1
0.4, 4.5 Hz, 1H), 3.75 (ddd, J = 11.2, 7.9, 3.7 Hz, 1H), 3.44
(
ddd, J = 11.8, 7.8, 3.8 Hz, 1H), 3.30 (dt, J = 13.2, 4.3 Hz, 1H).
1
3
29.6, 28.8, 20.8, 19.3, 17.1, 16.2, 14.5. HRMS (ESI): m/z [M
+
C NMR (101 MHz, CDCl ) δ 166.1, 165.8, 165.1, 165.1, 133.4,
+
3
H] calcd for C H O 979.4633; found: 979.4635.
60 67 12
1
1
6
6
33.2, 133.2, 133.2, 129.8, 129.8, 129.7, 129.7, 129.5, 129.2,
28.7, 128.4, 128.3, 128.2, 101.2, 72.8, 72.4, 71.7, 69.6, 68.4,
4.2.7Bromoethyl 2, 3, 4, 6-tetra-O-Bz-β-D-galactopyranoside
(G7)
+
3.0, 50.6.HRMS (ESI): m/z [M +H] calcd for C H N O
36
32
3
10
66.2088; found: 666.2084.
2
D
3
[α
]
-15.4(c=1.0, CHCl ); R
3
f
’
Yield 90% (63mg); Colorless oil;1
4
.2.4 (4 -hydroxyphenyl)ethyl 2, 3, 4, 6-tetra-O-Bz-β-D-
=0.48(Ethyl acetate/hexane, 1/3). H NMR (400 MHz, CDCl ) δ
3
glucopyranoside (G4)
8.09 (d, J = 7.5 Hz, 2H), 8.03 (d, J = 7.5 Hz, 2H), 7.98 (d, J = 7.5
Hz, 2H), 7.79 (d, J = 7.5 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.56
(t, J = 7.4 Hz, 1H), 7.49 (d, J = 7.7 Hz, 2H), 7.47-7.41 (m, 4H),
2
3
[α ]
3
Yield 90% (64mg); Colorless oil; +27.1(c=1.0, CHCl ); Rf
D
1
=
0.33 (Ethyl acetate/hexane, 1/4). H NMR (400 MHz, CDCl ) δ
3
7
1
1
4
.38 (t, J = 7.7 Hz, 2H), 7.27-7.22 (m, 2H), 6.00 (d, J = 3.4 Hz,
H), 5.82 (dd, J = 10.4, 7.9 Hz, 1H), 5.62 (dd, J = 10.4, 3.4 Hz,
H), 4.92 (d, J = 7.9 Hz, 1H), 4.67 (dd, J = 11.3, 6.7 Hz, 1H),
.44 (dd, J = 11.3, 6.4 Hz, 1H), 4.35 (t, J = 6.5 Hz, 1H), 4.23 (dt,
8
2
7
8
5
1
1
.03 (d, J = 7.4 Hz, 2H), 7.98-7.92 (m, 4H), 7.87 (d, J = 7.4 Hz,
H), 7.54 (dd, J = 13.1, 5.7 Hz, 2H), 7.48 (d, J = 7.5 Hz, 1H),
.43-7.35 (m, 6H), 7.28 (dd, J = 14.2, 6.6 Hz, 3H), 7.07 (d, J =
.3 Hz, 2H), 6.65 (d, J = 8.4 Hz, 2H), 6.15 (t, J = 9.8 Hz, 1H),
.63 (t, J = 9.9 Hz, 1H), 5.32 (d, J = 3.5 Hz, 1H), 5.27 (dd, J =
0.1, 3.6 Hz, 1H), 4.49 (dd, J = 12.2, 2.5 Hz, 1H), 4.33 (dd, J =
2.2, 5.0 Hz, 1H), 3.99 (ddd, J = 9.6, 4.5, 2.7 Hz, 1H), 3.95-3.88
J = 11.6, 5.9 Hz, 1H), 3.93 (dt, J = 11.2, 7.1 Hz, 1H), 3.49-3.42
13
(
m, 2H). C NMR (100 MHz, CDCl ) δ 166.0, 165.5, 165.5,
3
1
1
65.3, 133.6, 133.3, 133.3, 133.2, 123.0, 129.8, 129.7, 129.3,
28.9, 128.7, 128.6, 128.5, 128.3, 128.3, 101.8, 71.6, 71.5, 69.9,
(
m, 1H), 3.69 (dt, J = 9.4, 6.1 Hz, 1H), 2.86 (t, J = 6.4 Hz, 2H).
C NMR (100 MHz, CDCl ) δ 166.2, 165.9, 165.8, 165.3, 154.2,
+
1
3
69.5, 68.0, 62.0, 29.6. HRMS (ESI): m/z [M +H] calcd for
C H BrO 703.1179; found 703.1173.
3
36
32
10
1
1
7
33.4, 133.4, 133.1, 130.7, 130.2, 129.9, 129.9, 129.7, 129.7,
29.6, 129.1, 129.0, 128.8, 128.4, 128.4, 128.3, 115.2, 95.5, 72.0,
0.5, 69.4, 68.9, 67.6, 62.9, 35.0.
4.2.8 Chloroethyl 2, 3, 4, 6-tetra-O-Bz-α-D-mannopyranoside
(G8)
+
23
HRMS (ESI): m/z [M +H] calcd for C H O 717.2336; found:
[α
3 f
Yield 94% (67mg); Colorless oil;1 ]D +61.7(c=1.0, CHCl ); R
42
37 11
7
17.2340.
=0.34(Ethyl acetate/hexane, 1/4). H NMR (400 MHz, CDCl ) δ
3
8
.11 (d, J = 7.6 Hz, 2H), 8.05 (d, J = 7.7 Hz, 2H), 7.97 (d, J = 7.6
Hz, 2H), 7.84 (d, J = 7.6 Hz, 2H), 7.62-7.55 (m, 2H), 7.51 (t, J =
.4 Hz, 1H), 7.45-7.34 (m, 8H), 7.28 (d, J = 7.7 Hz, 1H), 6.13 (t,
4
.2.5 (L)-Mentyl 2, 3, 4, 6-tetra-O-Bz-α-D-galactopyranoside
(
G5)
7
2
D
3
Yield 91% (67mg); Colorless oil;
=
8
[
α
]
+46.5(c=1.0, CHCl ); Rf
J = 10.1 Hz, 1H), 5.93 (dd, J = 10.1, 3.2 Hz, 1H), 5.75 (s, 1H),
5.16 (s, 1H), 4.71 (dd, J = 12.0, 2.0 Hz, 1H), 4.57 (d, J = 10.1 Hz,
1H), 4.50 (dd, J = 12.0, 4.4 Hz, 1H), 4.07 (dt, J = 11.6, 5.9 Hz,
3
1
0.47(Ethyl acetate/hexane, 1/5). H NMR (400 MHz, CDCl ) δ
.09 (d, J = 7.2 Hz, 2H), 8.02 (d, J = 7.2 Hz, 2H), 7.97 (d, J = 7.3
3
13
Hz, 2H), 7.80 (d, J = 7.3 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.58-
1H), 3.94 (dt, J = 10.9, 5.3 Hz, 1H), 3.78 (t, J = 5.6 Hz, 2H). C
NMR (100 MHz, CDCl ) δ 166.1, 165.5, 165.4, 133.5, 133.4,
133.2, 133.0, 129.8, 129.7, 129.3, 129.1, 129.0, 128.6, 128.4,
7
1
1
.46 (m, 5H), 7.40 (dt, J = 18.7, 7.7 Hz, 6H), 5.98 (d, J = 2.8 Hz,
H), 5.74 (dd, J = 10.3, 8.0 Hz, 1H), 5.58 (dd, J = 10.4, 3.4 Hz,
H), 4.87 (d, J = 7.9 Hz, 1H), 4.62 (dd, J = 11.2, 6.7 Hz, 1H),
3

6
Tetrahedron
MA(m
1
28.3, 97.9, 70.4,70.0, 69.3, 68.8, 66.8, 6
A
2.8
C
,
C
42
E
.5
P
.
T
HR
E
M
D
S
N
, 8
U
H
S
),
C
7.
R
28
I
(
P
d, J = 7.7 Hz, 1H), 6.13 (t, J = 10.1 Hz, 1H), 5.94
T
+
(ESI): m/z [M +H] calcd for C H ClO 659.1684; found:
(dd, J = 10.2, 3.2 Hz, 1H), 5.74 (s, 1H), 5.17 (s, 1H), 4.71 (dd, J
= 12.1, 2.2 Hz, 1H), 4.59 (d, J = 10.1 Hz, 1H), 4.51 (dd, J = 12.1,
36
32
10
6
59.1689.
4
5
.4 Hz, 1H), 4.13 (dt, J = 12.6, 6.3 Hz, 1H), 4.01 (dt, J = 11.3,
.7 Hz, 1H), 3.61 (t, J = 6.0 Hz, 2H). C NMR (100 MHz,
4
.2.9 Cholesteryl 2, 3, 4, 6-tetra-O-Bz-α-D-mannopyranoside
13
(G9)
CDCl ) δ 166.1, 165.4, 165.4, 133.5, 133.5, 133.2, 133.1, 130.1,
129.9, 129.8, 129.8, 129.7, 129.2, 129.0, 128.9, 128.8, 128.6,
128.6, 128.4, 128.4, 128.3, 97.8, 70.3, 69.9, 69.4, 68.6, 66.7,
3
2
D
3
Yield 88% (85mg); Colorless oil;
=
8
[α
]
-29.9(c=1.0, CHCl ); Rf
3
1
0.56(Ethyl acetate/hexane, 1/6). H NMR (400 MHz, CDCl ) δ
3
+
.08 (t, J = 7.5 Hz, 4H), 7.98 (d, J = 7.8 Hz, 2H), 7.84 (d, J = 7.8
62.8, 29.7. HRMS (ESI): m/z [M +H]
32BrO10703.1179; found : 703.1175.
calcd for
Hz, 2H), 7.62-7.54 (m, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.39 (dt, J =
C H
36
1
5
7.4, 8.2 Hz, 7H), 7.29-7.24 (m, 2H), 6.05 (t, J = 9.9 Hz, 1H),
.95 (dd, J = 10.1, 3.1 Hz, 1H), 5.66 (s, 1H), 5.26 (s, 2H), 4.68
4
.2.13 Stigmasterol 2, 3, 4-tri-O-Bz-α-D-rhamnoside (G13)
2
3
(d, J = 11.7 Hz, 1H), 4.58-4.46 (m, 2H), 3.63 (s, 1H), 2.47 (d, J =
Yield 92% (80mg); Colorless oil;1
=0.56(Ethyl acetate/hexane, 1/8). H NMR (400 MHz, CDCl ) δ
[α
]
+70.4(c=1.0, CHCl ); R
3
f
D
6
.1 Hz, 2H), 2.06-1.80 (m, 6H), 1.60 (s, 3H), 1.49 (d, J = 10.6
3
Hz, 4H), 1.35 (d, J = 8.1 Hz, 3H), 1.26 (s, 2H), 1.13 (d, J = 6.3
Hz, 5H), 1.02 (d, J = 8.8 Hz, 5H), 0.93 (d, J = 6.4 Hz, 4H), 0.87
8.11 (d, J = 7.7 Hz, 2H), 7.98 (d, J = 7.8 Hz, 2H), 7.83 (d, J = 7.8
Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.49 (q, J = 7.9 Hz, 4H), 7.39
(dt, J = 15.3, 7.6 Hz, 4H), 5.87 (dd, J = 10.1, 3.3 Hz, 1H), 5.67 (t,
J = 10.0 Hz, 1H), 5.63 (s, 1H), 5.38 (s, 1H), 5.20-5.13 (m, 2H),
5.02 (dd, J = 15.1, 8.6 Hz, 1H), 4.28 (dd, J = 9.6, 6.3 Hz, 1H),
3.59 (s, 1H), 2.44 (d, J = 10.1 Hz, 1H), 2.35 (t, J = 12.0 Hz, 1H),
2.01 (d, J = 11.9 Hz, 5H), 1.91 (d, J = 13.3 Hz, 1H), 1.74 (d, J =
14.6 Hz, 3H), 1.57-1.49 (m, 6H), 1.35 (d, J = 6.2 Hz, 3H), 1.26
(t, J = 11.3 Hz, 3H), 1.19 (s, 1H), 1.16 (d, J = 9.3 Hz, 2H), 1.12
13
(
d, J = 6.6 Hz, 6H), 0.69 (s, 3H). C NMR (100 MHz, CDCl ) δ
3
1
1
9
4
2
66.2, 165.6, 165.5, 140.2, 133.4, 133.1, 133.0, 129.8, 129.8,
29.7, 129.4, 129.1, 129.0, 128.6, 128.4, 128.4, 128.3, 122.2,
6.0, 78.6, 71.2, 70.1, 68.9, 67.2, 63.3, 56.8, 56.2, 50.1, 42.3,
0.0, 39.8, 39.5, 36.9, 36.7, 36.2, 32.0, 31.9, 28.2, 28.0, 27.8,
4.3, 23.8, 22.8, 22.6, 21.0, 19.3, 18.7, 11.9. HRMS (ESI): m/z
+
[
M +H] calcd for C H O 965.5204; found: 965.5213.
61
73 10
(
s, 1H), 1.07 (s, 3H), 1.03 (d, J = 6.5 Hz, 3H), 0.85 (d, J = 6.2
4
.2.10 (2-Trimethylsilyl) ethyl 2, 3, 4, 6-tetra-O-Bz-α-D-
13
Hz, 3H), 0.83 (s, 1H), 0.80 (d, J = 6.6 Hz, 6H), 0.72 (s, 3H). C
NMR (100 MHz, CDCl ) δ 165.8, 165.6, 165.5, 140.1, 138.3,
133.4, 133.2, 133.0, 129.9, 129.7, 129.7, 129.5, 129.3, 129.3,
129.2, 128.5, 128.4, 128.2, 122.1, 95.8, 78.0, 72.1, 71.5, 70.1,
66.7, 56.8, 55.9, 51.2, 50.2, 42.2, 40.5, 39.7, 38.5, 37.3, 36.7,
31.9, 31.9, 29.5, 28.9, 25.4, 24.3, 21.2, 21.1, 21.1, 19.4, 19.0,
17.7, 12.2, 12.0. HRMS (ESI): m/z [M +H] calcd for C56
871.5149; found : 871.5153.
mannopyranoside (G10)
3
2
D
3
Yield 71% (49mg); Colorless oil;
=
8
2
8
[α
]
+14.5(c=1.5, CHCl ); Rf
3
1
0.55(Ethyl acetate/hexane, 1/4). H NMR (400 MHz, CDCl ) δ
3
.12 -8.05 (m, 4H), 7.97 (d, J = 7.8 Hz, 2H), 7.84 (d, J = 7.8 Hz,
H), 7.62-7.54 (m, 2H), 7.51 (t, J = 7.4 Hz, 1H), 7.47-7.30 (m,
H), 7.26 (t, J = 7.7 Hz, 2H), 6.09 (t, J = 9.9 Hz, 1H), 5.94 (dd, J
+
H O
71 8
=
10.1, 3.2 Hz, 1H), 5.67 (s, 1H), 5.13 (s, 1H), 4.69 (d, J = 10.1
Hz, 1H), 4.54-4.43 (m, 2H), 3.94 (td, J = 10.2, 6.2 Hz, 1H), 3.68
4
.2.14 O-(2, 3, 4-tri-O-Bz-α-D-rhamosyl)- N-Cbz-L-threonine
(
td, J = 10.3, 6.2 Hz, 1H), 1.09 (tq, J = 13.8, 7.7 Hz, 2H), 0.07 (s,
13
methyl ester(G14)
9
1
1
H). C NMR (101 MHz, CDCl ) δ 166.2, 165.5, 160.7, 133.4,
3
2
D
3
33.1, 133.0, 129.8, 129.8, 129.7, 129.4, 129.1, 129.0, 128.6,
Yield 92% (67mg); Colorless oil; 1
=0.31 (Ethyl acetate/hexane, 1/2). H NMR (400 MHz, CDCl ) δ
8.09 (d, J = 7.2 Hz, 2H), 7.95 (d, J = 7.2 Hz, 2H), 7.81 (d, J = 7.2
Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.50 (dt, J = 15.4, 7.5 Hz, 4H),
[α
]
+38.9(c=1.0, CHCl ); R
3
f
28.4, 128.3, 97.1, 70.8, 70.1, 68.8, 67.1, 66.1, 63.1, 18.0, -1.4.
3
+
HRMS (ESI): m/z [M +H] calcd for C H O Si 697.2469;
39
41 10
found: 697.2476.
7
.39 (dq, J = 12.7, 7.5 Hz, 8H), 7.32 (d, J = 7.0 Hz, 1H), 5.79 (d,
J = 8.5 Hz, 1H), 5.66 (q, J = 10.5 Hz, 4H), 5.18 (s, 2H), 5.02 (s,
H), 4.69 (d, J = 8.5 Hz, 1H), 4.28 (d, J = 7.2 Hz, 1H), 4.06-4.00
4
.2.11 Epiandrosteronyl 2, 3, 4, 6-tetra-O-Bz-α-D-
mannopyranoside (G11)
1
1
3
2
3
Yield 82% (67mg); White solid; mp 105-107 ꢀ ;
[α
]
(m, 1H), 3.91-3.80 (m, 5H), 1.36 (d, J = 6.2 Hz, 3H). C NMR
(100 MHz, CDCl ) δ 170.2, 165.7, 165.5, 165.4, 155.9, 136.1,
D
1
+
35.4(c=1.0, CHCl ); R =0.39(Ethyl acetate/hexane, 1/4). H
3
3
f
NMR (400 MHz, CDCl ) δ 8.08 (t, J = 8.0 Hz, 4H), 7.98 (d, J =
133.5, 133.3, 133.1, 129.9, 129.6, 129.2, 129.2, 129.1, 128.6,
128.5, 128.4, 128.2, 128.2, 128.1, 128.1, 97.5, 71.5, 70.4, 69.7,
68.1, 67.2, 67.1, 54.2, 52.7, 17.6. HRMS (ESI): m/z [M +H]
3
7
.3 Hz, 2H), 7.84 (d, J = 7.3 Hz, 2H), 7.63-7.54 (m, 2H), 7.51 (t,
+
J = 7.4 Hz, 1H), 7.40 (h, J = 8.4, 7.1 Hz, 7H), 7.30-7.24 (m, 2H),
6
1
1
.06 (t, J = 10.0 Hz, 1H), 5.95 (dd, J = 10.1, 3.2 Hz, 1H), 5.65 (s,
H), 5.26 (s, 2H), 4.68 (d, J = 10.1 Hz, 1H), 4.52 (dd, J = 18.0,
1.6 Hz, 2H), 3.62 (s, 1H), 2.59-2.43 (m, 3H), 2.20 (d, J = 10.9
calcd for C40
H40NO12 726.2551; found: 726.2549.
4
.2.15Epiandrosteronyl 2, 3, 4-tri-O-Bz-α-D-rhamnoside (G15)
2
D
3
Hz, 1H), 2.13 (s, 2H), 2.07 (d, J = 9.8 Hz, 1H), 2.02-1.85 (m,
Yield 95% (71mg); Colorless oil;1
[α
]
+59.1(c=1.0, CHCl ); R
3
f
4
3
2
1
1
4
1
H), 1.66 (dd, J = 21.7, 10.5 Hz, 4H), 1.52-1.43 (m, 3H), 1.26 (s,
=0.53(Ethyl acetate/hexane, 1/3). H NMR (400 MHz, CDCl ) δ
3
13
H), 1.04 (s, 5H), 0.65 (s, 3H). C NMR (100 MHz, CDCl ) δ
8.11 (d, J = 7.2 Hz, 2H), 7.98 (d, J = 7.2 Hz, 2H), 7.83 (d, J = 7.2
Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.50 (q, J = 8.2, 7.7 Hz, 3H),
7.40 (dt, J = 15.2, 7.5 Hz, 3H), 7.27-7.23 (m, 2H), 5.86 (dd, J =
10.1, 3.3 Hz, 1H), 5.67 (t, J = 10.0 Hz, 1H), 5.59 (s, 1H), 5.18 (s,
1H), 4.26 (dd, J = 9.7, 6.3 Hz, 1H), 3.66 (s, 1H), 2.44 (dd, J =
19.2, 8.7 Hz, 1H), 2.07 (dt, J = 18.9, 9.0 Hz, 1H), 1.92 (s, 2H),
1.81 (d, J = 12.1 Hz, 2H), 1.77-1.75 (m, 1H), 1.68 (d, J = 9.6 Hz,
3
09.5, 166.2, 165.6, 165.5, 140.2, 133.4, 133.1, 133.0, 129.8,
29.8, 129.7, 129.4, 129.1, 129.0, 128.6, 128.4, 128.4, 128.3,
21.9, 96.1, 78.6, 71.2, 70.1, 69.0, 67.2, 63.7, 63.2, 56.9, 49.9,
4.0, 40.0, 38.8, 36.9, 36.7, 31.8, 31.5, 27.8, 24.5, 22.8, 21.0,
+
9.3, 13.2. HRMS (ESI): m/z [M +H]
calcd for
C H O 895.4057; found: 895.4069.
55
59 11
2
1
1
H), 1.60 (dd, J = 10.6, 3.6 Hz, 1H), 1.54 (dd, J = 8.6, 3.2 Hz,
H), 1.49 (dd, J = 9.4, 3.1 Hz, 1H), 1.44 (d, J = 12.8 Hz, 1H),
.35 (d, J = 6.2 Hz, 4H), 1.29 (d, J = 5.4 Hz, 1H), 1.25 (d, J = 3.8
4
.2.12 Bromoethyl 2, 3, 4, 6-tetra-O-Bz-α-D-galactopyranoside
(G12)
2
D
3
Yield 87% (61mg); Colorless oil;
=
[
α
]
+42.4(c=1.0, CHCl ); Rf
Hz, 1H), 1.14 (d, J = 12.4 Hz, 1H), 1.03 (td, J = 13.4, 4.1 Hz,
2H), 0.88 (d, J = 7.8 Hz, 6H), 0.75-0.67 (m, 1H). C NMR (100
3
1
13
0.59(Ethyl acetate/hexane, 1/3). H NMR (400 MHz, CDCl )
3
δ8.13-8.03 (m, 4H), 7.97 (d, J = 7.7 Hz, 2H), 7.85 (d, J = 7.7 Hz,
H), 7.59 (q, J = 7.4 Hz, 2H), 7.51 (t, J = 7.4 Hz, 1H), 7.47-7.33
MHz, CDCl
3
) δ 165.8, 165.7, 165.5, 133.4, 133.2, 133.0, 129.8,
2
129.7, 129.6, 129.5, 129.3, 129.2, 128.5, 128.4, 128.2, 95.6,

7
3
1
7.15, 72.01, 71.6, 70.1, 66.6, 54.4, 51.4, 47.8, 44.8, 37.0, 35.8,
5.9, 35.0, 34.0, 31.5, 30.9, 29.2, 28.4, 21.7, 20.5, 17.7, 13.8,
36.0, 28.1, 26.7, 20.7, 20.6, 19.8, 18.9, 13.4. HRMS (ESI): m/z
+
ACCEPTED MANUSCRIPT
[M +H] calcd for C H N O 468.2346; found: 468.2350.
22 34 3 8
+
2.3. HRMS (ESI): m/z [M+H] calcd for C H O 747.3533;
46
51
9
4
.2.20 (L)-Mentyl 3, 4, 6-tri-O-acetyl-2-deoxy-2-azido-α-D-
found: 747.3528.
galactopyranoside (G20)
4
.2.16 Borneolyl 3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-
2
3
[α ]
3 f
Yield 81% (40mg); Colorless oil; +102.5(c=1.0, CHCl ); R
D
1
glucopyranoside (G16)
=
0.55(Ethyl acetate/hexane, 1/3). H NMR (400 MHz, CDCl ) δ
3
2
D
3
Yield 92% (53mg); Colorless oil;
=
[α
]
+9.8(c=1.0, CHCl ); Rf
5.31 (d, J = 2.9 Hz, 1H), 4.76 (dd, J = 10.9, 3.3 Hz, 1H), 4.42 (d,
J = 8.0 Hz, 1H), 4.13 (dd, J = 11.1, 6.8 Hz, 1H), 4.06 (dd, J =
11.2, 6.7 Hz, 1H), 3.82 (t, J = 6.6 Hz, 1H), 3.62 (dd, J = 10.7, 8.1
Hz, 1H), 3.47 (td, J = 10.7, 4.2 Hz, 1H), 2.32-2.26 (m, 1H), 2.16
(s, 3H), 2.04 (d, J = 9.9 Hz, 6H), 1.67 (d, J = 11.2 Hz, 2H), 1.33-
1.24 (m, 2H), 1.11-1.02 (m, 2H), 0.93 (dd, J = 15.0, 6.8 Hz, 8H),
0.75 (d, J = 6.8 Hz, 3H). C NMR (100 MHz, CDCl ) δ 170.4,
170.2, 169.9, 100.0, 79.2, 71.2, 70.4, 66.5, 61.5, 60.8, 47.6, 40.2,
34.2, 31.5, 25.1, 23.0, 22.2, 20.9, 20.7, 20.6, 15.5. HRMS (ESI):
3
1
0.63(Ethyl acetate/hexane, 1/2). H NMR (400 MHz, CDCl ) δ
3
7
5
5
3
2
1
0
.87 (dd, J = 5.4, 3.0 Hz, 2H), 7.75 (dd, J = 5.4, 3.1 Hz, 2H),
.86 (dd, J = 10.8, 9.1 Hz, 1H), 5.29 (d, J = 8.4 Hz, 1H), 5.21-
.14 (m, 1H), 4.38-4.30 (m, 2H), 4.16 (dd, J = 12.1, 2.4 Hz, 1H),
.95 (d, J = 8.7 Hz, 1H), 3.84 (d, J = 8.0 Hz, 1H), 2.11 (s, 3H),
.04 (s, 4H), 1.88 (s, 3H), 1.66 (d, J = 13.3 Hz, 1H), 1.45 (s, 2H),
.04 (d, J = 12.3 Hz, 1H), 0.82 (s, 3H), 0.76 (d, J = 7.7 Hz, 6H),
13
3
13
.59 (dd, J = 13.2, 2.9 Hz, 1H), 0.52 (s, 1H). C NMR (100
+
MHz, CDCl ) δ 170.7, 170.2, 169.5, 134.3, 131.4, 123.5, 96.9,
m/z [M +H] calcd for C H N O 470.2502; found: 470.2495.
3
22 36
3
8
8
2
+
3.6, 71.7, 70.7, 69.4, 62.2, 54.9, 49.1, 47.7, 44.7, 35.8, 27.9,
4
.2.21
O-(2-deoxy-2-azido-
3,
4,
6-tri-O-Ac-α-D-
6.3, 20.7, 20.6, 20.5, 19.6, 18.8, 13.2. HRMS (ESI): m/z [M
+
galactopyranosyl)- N-Fmoc-L-threonine methyl ester (G21-α)
H] calcd for C H NO 572.2496; found: 572.2502.
30
38
10
2
3
[α ]
3 f
Yield 75% (50mg); Colorless oil; +11.2(c=1.0, CHCl ); R
D
1
=
7
4
.2.17 Ethyl O- (3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-
0.64(Ethyl acetate/hexane, 1/1). H NMR (400 MHz, CDCl ) δ
3
.77 (d, J = 7.4 Hz, 2H), 7.67-7.62 (m, 2H), 7.41 (t, J = 7.3 Hz,
glucopyranosyl)-L-lactate (G17)
2
D
3
Yield 80% (43mg); Colorless oil;
=
7
5
J = 9.6 Hz, 1H), 4.40-4.29 (m, 3H), 4.17 (dd, J = 12.3, 2.1 Hz,
1
1
MHz, CDCl ) δ 171.8, 170.7, 170.1, 169.5, 134.1, 123.4, 97.2,
7
[
α
]
-19.3(c=1.0, CHCl ); Rf
2H), 7.34 (dd, J = 6.8, 3.5 Hz, 2H), 5.64 (d, J = 9.5 Hz, 1H), 5.46
(s, 1H), 5.29 (dd, J = 11.1, 3.1 Hz, 1H), 5.04 (d, J = 3.5 Hz, 1H),
4.46 (d, J = 10.1 Hz, 3H), 4.42-4.34 (m, 2H), 4.32-4.24 (m, 2H),
4.10 (d, J = 6.4 Hz, 2H), 3.81 (s, 2H), 3.69 (dd, J = 11.2, 3.6 Hz,
1H), 2.15 (s, 3H), 2.06 (d, J = 12.2 Hz, 6H), 1.35 (d, J = 6.3 Hz,
3H). C NMR (100 MHz, CDCl ) δ 170.6, 170.3, 170.0, 169.8,
156.7, 143.8, 143.8, 141.3, 127.7, 127.1, 125.2, 120.0, 99.4, 68.2,
67.6, 67.5, 67.1, 61.8, 58.7, 57.8, 52.7, 47.1, 20.6, 20.6, 20.6,
3
1
0.26(Ethyl acetate/hexane, 1/2). H NMR (400 MHz, CDCl ) δ
3
.87 (dd, J = 5.4, 3.1 Hz, 2H), 7.74 (dd, J = 5.4, 3.0 Hz, 2H),
.90 (dd, J = 10.6, 9.2 Hz, 1H), 5.35 (d, J = 8.5 Hz, 1H), 5.17 (t,
13
H), 4.02-3.83 (m, 3H), 2.12 (s, 3H), 2.03 (s, 3H), 1.88 (s, 3H),
3
13
.35 (d, J = 6.9 Hz, 3H), 1.02 (t, J = 7.1 Hz, 3H). C NMR (100
3
+
2.7, 71.7, 70.4, 69.0, 62.0, 60.9, 54.5, 20.7, 20.6, 20.5, 18.6,
18.5. HRMS (ESI): m/z [M +H] calcd for C H N O
669.2408; found: 669.2413.
3
2
37
4
12
+
1
3.9. HRMS (ESI): m/z [M +H] calcd for C H NO 536.1768;
25
30
12
found: 536.1772.
4
.2.21O-(2-deoxy-2-azido-
3,
4,
6-tri-O-Ac-β-D-
4
.2.18 Cholesteryl 3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-β-
galactopyranosyl)- N-Fmoc-L-threonine methyl ester (G21-β)
D-glucopyranoside (G18)
2
D
3
Yield 13% (9mg); Colorless oil;1
[
α
]
-31.4(c=1.0, CHCl ); R
3
f
2
3
Yield 93% (75mg); White solid; mp 85-87 ꢀ ;
125.5(c=1.0, CHCl ); R =0.49(Ethyl acetate/hexane, 1/2). H
[
α
]
=0.53(Ethyl acetate/hexane, 1/1). H NMR (400 MHz, CDCl ) δ
3
D
1
+
7.77 (d, J = 7.5 Hz, 2H), 7.62 (t, J = 7.3 Hz, 2H), 7.40 (t, J = 7.4
Hz, 2H), 7.31 (t, J = 7.4 Hz, 2H), 5.60 (d, J = 9.4 Hz, 1H), 5.32-
5.29 (m, 1H), 4.75 (dd, J = 10.9, 3.2 Hz, 1H), 4.53 (d, J = 6.3 Hz,
1H), 4.46 (d, J = 9.5 Hz, 1H), 4.41 (t, J = 6.6 Hz, 3H), 4.28 (q, J
= 7.2 Hz, 2H), 4.09 (dd, J = 6.6, 2.6 Hz, 2H), 3.81 (t, J = 6.6 Hz,
1H), 3.77 (s, 2H), 3.66 (dd, J = 10.7, 8.1 Hz, 1H), 2.15 (s, 3H),
3
f
NMR (400 MHz, CDCl ) δ 7.87 (dd, J = 5.2, 3.0 Hz, 2H), 7.75
3
(dd, J = 5.4, 3.0 Hz, 2H), 5.83-5.74 (m, 1H), 5.48 (d, J = 8.5 Hz,
1
2
1
1
4
1
H), 5.23 (s, 1H), 5.17 (t, J = 9.6 Hz, 1H), 4.30 (d, J = 10.7 Hz,
H), 4.15 (d, J = 12.1 Hz, 1H), 3.87 (d, J = 12.2 Hz, 1H), 3.48 (s,
H), 2.11 (s, 3H), 2.03 (s, 3H), 2.00-1.91 (m, 3H), 1.86 (s, 3H),
.79 (d, J = 10.1 Hz, 2H), 1.54-1.40 (m, 6H), 1.32 (d, J = 8.0 Hz,
H), 1.24 (d, J = 13.0 Hz, 2H), 1.09 (dd, J = 18.3, 8.8 Hz, 6H),
.00 (dd, J = 19.5, 7.0 Hz, 5H), 0.90 (d, J = 6.5 Hz, 3H), 0.86 (d,
13
2.07-2.04 (m, 6H), 1.35 (d, J = 6.3 Hz, 3H). C NMR (100 MHz,
CDCl ) δ 170.5, 170.4, 170.0, 169.8, 156.6, 143.9, 143.7, 141.3,
3
141.3, 127.7, 127.1, 125.2, 125.1, 120.0, 100.3, 75.2, 70.6, 67.3,
66.1, 61.7, 60.9, 60.6, 58.4, 58.0; 52.6, 47.1, 20.7, 20.6, 20.6,
13
J = 7.4 Hz, 9H), 0.63 (s, 3H). C NMR (100 MHz, CDCl ) δ
3
+
1
7
3
2
70.7, 170.2, 169.5, 140.2, 134.2, 131.4, 123.6, 122.1, 96.8, 79.5,
1.7, 70.9, 69.2, 62.2, 56.7, 56.1, 54.9, 50.1, 42.3, 39.7, 39.5,
8.6, 37.1, 36.6, 36.2, 35.7, 31.9, 31.8, 29.3, 28.2, 28.0, 24.2,
16.8. HRMS (ESI): m/z [M +H] calcd for C H N O
3
2
37
4
12
669.2408; found: 669.2410.
4
.2.22 Borneolyl 3, 4, 6-tri-O-Bz-2-deoxy-α-D-glucopyranoside
3.8, 22.8, 22.5, 21.0, 20.8, 20.6, 20.4, 19.3, 18.7, 11.8. HRMS
+
(G22)
(ESI): m/z [M +H] calcd for C H NO 804.4687; found:
47
66
10
2
3
8
04.4690.
Yield 91% (39mg); Colorless oil;
+37.4(c=1.0, CHCl ); R
[α
]
3 f
D
1
=
0.55(Ethyl acetate/hexane, 1/5). H NMR (400 MHz, CDCl ) δ
.05 (d, J = 7.2 Hz, 2H), 7.99 (d, J = 7.2 Hz, 2H), 7.95 (d, J = 7.2
3
4
.2.19 Borneolyl 3, 4, 6-tri-O-acetyl-2-deoxy-2-azido-α-D-
8
galactopyranoside (G19)
Hz, 2H), 7.53 (d, J = 7.5 Hz, 1H), 7.48 (dd, J = 7.4, 3.5 Hz, 2H),
7.41 (d, J = 7.8 Hz ,2H), 7.39-7.34 (m, 4H), 5.81-5.72 (m, 2H),
5.55 (t, J = 9.5 Hz, 1H), 5.08 (d, J = 2.9 Hz, 1H), 4.56 (t, J = 7.1
Hz, 1H), 4.48-4.41 (m, 1H), 3.89 (d, J = 8.7 Hz, 1H), 2.55 (dd, J
= 12.6, 5.1 Hz, 1H), 2.25-2.15 (m, 1H), 2.14–2.06 (m, 1H), 2.01
(td, J = 12.5, 3.8 Hz, 1H), 1.77–1.69 (m, 1H), 1.59 (t, J = 4.3 Hz,
1H), 1.37-1.31 (m, 1H), 1.23 (td, J = 14.3, 13.4, 4.6 Hz, 2H),
0.86 (d, J = 7.9 Hz, 6H), 0.81 (s, 3H). C NMR (100 MHz,
CDCl ) δ 166.2, 165.8, 165.6, 133.3, 133.0, 133.0, 129.8, 129.8,
129.7, 129.6, 129.6, 129.2, 128.4, 128.3, 128.3, 128.2, 98.6, 84.9,
2
3
[α ]
3
Yield 82% (38mg); Colorless oil; +88.1(c=1.0, CHCl ); Rf
D
1
=
0.56(Ethyl acetate/hexane, 1/3). H NMR (400 MHz, CDCl ) δ
3
5
.31 (d, J = 2.8 Hz, 1H), 4.73 (dd, J = 10.9, 3.3 Hz, 1H), 4.34 (d,
J = 8.0 Hz, 1H), 4.19 (dd, J = 11.1, 6.4 Hz, 1H), 4.06 (dd, J =
7.8, 6.9 Hz, 2H), 3.80 (t, J = 6.7 Hz, 1H), 3.66 (dd, J = 10.8, 8.0
1
Hz, 1H), 2.16 (s, 3H), 2.04 (d, J = 6.8 Hz, 6H), 1.69 (d, J = 4.4
Hz, 3H), 1.27 (d, J = 9.5 Hz, 3H), 1.14 (dd, J = 13.2, 2.9 Hz, 1H),
13
1
3
0
1
.90-0.85 (m, 9H). C NMR (100 MHz, CDCl ) δ 170.4, 170.2,
3
3
69.8, 101.4, 85.0, 70.8, 70.5, 66.4, 61.3, 61.2, 49.1, 48.1, 44.8,

8
Tetrahedron
13
7
0.5, 70.2, 68.5, 63.7, 49.5, 47.5, 45.0, 37.0
A
, 3
C
5.
C
7,
E
28
P
.3
T
, 2
E
6
D
.7, MA1H
NU
),
2
S
.08
C
(
R
d,IP
J = 10.7 Hz, 6H), 2.02 (s, 3H). C NMR (100
T
+
1
6
9.7, 18.7, 13.9. HRMS (ESI): m/z [M +H] calcd for C H O
13.2801; found: 613.2802.
MHz, CDCl ) δ 170.1, 169.5, 169.3, 166.0, 165.4, 165.3, 133.5,
37
41
8
3
133.3, 133.2, 133.0, 132.9, 131.6, 129.8, 129.8, 129.8, 129.7,
1
1
6
29.3, 129.2, 129.1, 128.8, 128.6, 128.5, 128.4, 128.3, 128.3,
28.1, 97.4, 86.2, 76.41, 73.9, 70.1, 69.9, 69.0, 68.9, 67.1, 66.5,
2.6, 20.8, 20.6, 20.6. HRMS (ESI): m/z [M +H] calcd for
4
.3 Procedures for the In(NTf ) -catalyzed synthesis of
2
3
disaccharide
+
To a solution of glycosyl bromide (0.1 mmol) in anhydrous
CH Cl (2 mL) containing In(NTf ) (14 mg, 0.015mmol ) and
C
52
H
49
O
17S 977.2690; found: 977.2687.
2
2
2 3
4
.3.4 Methyl 4-O-(2, 3, 4-tri-O-Bz-α-D-rhamosyl)-(1→4)-2, 3, 6-
4
Å molecular sieves(5 mg), alcohol (0.12mmol) was added under
tri-O-Bn-α-D-glucopyranoside (G26)
Ar. The mixture was allowed to stir for 12h at room temperature.
The suspension was filtered through a pad of Celite and
concentrated in vacuo. The crude product was purified by flash
column chromatography to yield the product.
2
3
[α ]
Yield 82% (76mg); White solid; mp 68-70ꢀ; +63.8(c=1.2,
D
1
CHCl ); R =0.55(Ethyl acetate/toluene, 1/10). H NMR (400
MHz, CDCl ) δ 8.06 (d, J = 7.3 Hz, 2H), 7.87 (dd, J = 16.0, 7.3
3
f
3
Hz, 4H), 7.59 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H), 7.49-
4
.3.1 Phenyl 6-O-(2, 3, 4, 6-tetra-O-Bz-β-D-glucopyranosyl)-
7
7
.44 (m, 2H), 7.40 (q, J = 7.7, 7.1 Hz, 5H), 7.32 (s, 3H), 7.30-
.26 (m, 6H), 7.21-7.16 (m, 3H), 7.16-7.11 (m, 3H), 5.78 (dd, J =
(1→6)-2, 3, 4-tri-O-Ac-β-D-thioglucopyranoside (G23)
2
D
3
Yield 83% (67mg); White solid; mp 79-81ꢀ;
CHCl ); R =0.13(Ethyl acetate/toluene, 1/10). H NMR (400
MHz, CDCl ) δ 8.04 (d, J = 7.6 Hz, 2H), 7.97-7.87 (m, 4H), 7.83
[α
]
+12.9(c=1.0,
10.2, 3.3 Hz, 1H), 5.63-5.54 (m, 2H), 5.21 (d, J = 11.7 Hz, 2H),
4.85 (d, J = 11.1 Hz, 1H), 4.76 (d, J = 12.1 Hz, 1H), 4.66-4.60
(m, 2H), 4.59 -4.51 (m, 2H), 4.37 (dd, J = 9.9, 6.1 Hz, 1H), 3.99
(q, J = 8.9 Hz, 2H), 3.92-3.87 (m, 1H), 3.84 (d, J = 9.1 Hz, 1H),
3.73 (d, J = 10.9 Hz, 1H), 3.65 (dd, J = 9.0, 3.5 Hz, 1H), 3.41 (s,
1
3
f
3
(d, J = 7.6 Hz, 2H), 7.59-7.47 (m, 4H), 7.43 (t, J = 7.6 Hz, 5H),
7
1
.36 (d, J = 4.2 Hz, 5H), 7.32-7.28 (m, 2H), 7.17 (d, J = 7.0 Hz,
H), 5.84 (t, J = 9.6 Hz, 1H), 5.63 (t, J = 9.7 Hz, 1H), 5.53-5.44
13
3H), 0.89 (d, J = 6.1 Hz, 3H). C NMR (100 MHz, CDCl ) δ
3
(
m, 1H), 5.13 (t, J = 9.3 Hz, 1H), 4.84 (ddd, J = 39.7, 20.6, 8.8
165.7, 165.7, 138.7, 137.9, 137.7, 133.4, 133.2, 133.1, 129.7,
129.7, 129.6, 129.4, 129.2, 128.5, 128.5, 128.4, 128.3, 128.2,
128.2, 128.1, 128.1, 128.0, 127.6, 127.4, 127.4, 127.3, 98.0, 97.0,
Hz, 3H), 4.67-4.58 (m, 2H), 4.46 (dd, J = 12.2, 5.4 Hz, 1H), 4.06
(
s, 1H), 3.79 (dd, J = 16.4, 9.4 Hz, 2H), 3.73-3.65 (m, 1H), 2.05
13
(s, 3H), 1.94 (d, J = 8.6 Hz, 6H). C NMR (100 MHz, CDCl ) δ
80.3, 79.7, 75.5, 74.8, 73.3, 73.3, 71.7, 71.3, 70.0, 70.0, 68.3,
3
+
1
1
1
7
70.0, 169.5, 169.2, 166.1, 165.7, 165.2, 165.1, 133.5, 133.2,
32.9, 131.6, 129.8, 129.8, 129.7, 129.5, 129.2, 129.0, 128.8,
28.8, 128.5, 128.4, 128.4, 128.3, 128.3, 128.2, 100.8, 85.4, 77.9,
3.8, 72.9, 72.3, 71.7, 69.9, 69.6, 68.8, 68.0, 63.0, 20.7, 20.5,
67.0, 55.3, 17.1. HRMS (ESI): m/z [M +H] calcd for C55
923.3643; found: 923.3639.
H O
55 13
4
.3.5 6-O- (3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-
+
glucopyranosyl)- (1→6)-1, 2: 3, 4-di-O-isopropylidene-α-D-
galactopyranose (G27)
2
0.5. HRMS (ESI): m/z [M +H] calcd for C H O S 977.2690;
52
49 17
found: 977.2694.
23
Yield92% (62mg); White solid; mp 220-222 ꢀ ;
113.2(c=1.0, CHCl ); R =0.45(Ethyl acetate/hexane, 1/1). H
[α ]
D
1
4
.3.2 Methyl 4-O-(2, 3, 4, 6-tetra-O-Bz-β-D-glucopyranosyl)-
+
3
f
(1→4)-2, 3, 6-tri-O-Bz-α-D-mannopyranoside (G24)
NMR (400 MHz, CDCl ) δ 7.84 (s, 2H), 7.71 (dd, J = 5.3, 3.0
3
2
D
3
Yield 79% (85mg); Colorless oil;
=
[
α
]
+58.1(c=1.0, CHCl ); Rf
Hz, 2H), 5.84 (t, J = 9.9 Hz, 1H), 5.45 (d, J = 8.5 Hz, 1H), 5.16
(t, J = 9.6 Hz, 1H), 5.10 (d, J = 5.0 Hz, 1H), 4.40 (dd, J = 7.9, 2.1
Hz, 1H), 4.37-4.28 (m, 2H), 4.20-4.14 (m, 1H), 4.09 (dd, J = 4.9,
2.2 Hz, 1H), 3.99 (d, J = 8.0 Hz, 1H), 3.94 (d, J = 8.1 Hz, 1H),
3.89 (d, J = 10.1 Hz, 1H), 3.69 (d, J = 7.8 Hz, 2H), 2.11 (s, 3H),
2.03 (s, 3H), 1.86 (s, 3H), 1.39 (s, 3H), 1.23 (s, 3H), 1.03 (d, J =
3
1
0.42 (Ethyl acetate/toluene, 1/10). H NMR (300 MHz, CDCl ) δ
3
8
.03 (d, J = 7.2 Hz, 2H), 7.93 (dd, J = 12.7, 7.2 Hz, 4H), 7.80 (d,
J = 7.2 Hz, 4H), 7.74 (d, J = 7.2 Hz, 2H), 7.54 (q, J = 7.4 Hz,
H), 7.48-7.43 (m, 5H), 7.41-7.36 (m, 5H), 7.32 (dd, J = 8.2, 3.6
Hz, 4H), 7.22 (d, J = 7.5 Hz, 2H), 7.16 (td, J = 7.8, 2.6 Hz, 4H),
.76 (dd, J = 9.7, 3.4 Hz, 1H), 5.67 (t, J = 9.7 Hz, 1H), 5.56 (dd,
J = 3.3, 1.9 Hz, 1H), 5.49-5.40 (m, 2H), 4.88-4.79 (m, 3H), 4.62
t, J = 9.7 Hz, 1H), 4.40 (d, J = 12.1 Hz, 1H), 4.09 (d, J = 3.7 Hz,
3
13
5
3.1 Hz, 6H). C NMR (100 MHz, CDCl ) δ 170.7, 170.1, 169.5,
3
133.7, 123.4, 109.3, 108.0, 99.3, 95.9, 71.6, 70.8, 70.7, 70.6,
(
70.1, 69.4, 69.0, 67.4, 62.0, 54.5, 25.8, 25.3, 24.6, 24.2, 20.8,
+
2
3
H), 3.87 (dd, J = 10.9, 2.5 Hz, 1H), 3.80 (d, J = 9.7 Hz, 1H),
.72 (d, J = 9.9 Hz, 1H), 3.58 (d, J = 11.3 Hz, 1H), 3.37 (s, 3H).
20.6, 20.5. HRMS (ESI): m/z [M +H] calcd for C32
678.2398; found: 678.2393.
H40NO15
13
C NMR (100 MHz, CDCl ) δ 165.8, 165.7, 165.4, 165.1, 164.9,
3
4
.3.6 Methyl 3-O- (3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-β-
1
1
1
7
64.7, 138.4, 133.3, 133.3, 133.1, 133.0, 132.8, 129.8, 129.7,
29.7, 129.6, 129.6, 129.5, 129.3, 129.1, 128.8, 128.7, 128.7,
28.5, 128.4, 128.3, 128.2, 128.1, 128.0,127.7, 100.7, 98.5,
D-glucopyranosyl)- (1→6)- 4, 6-benzylidene-2-O- Bz-α-D-
glucopyranoside (G28)
2
3
3.49, 73.2, 72.9, 72.0, 71.0, 70.7, 69.8, 69.6, 67.9, 63.0, 55.3.
[α ]
3 f
Yield 75% (60mg); Colorless oil;1 +22.1(c=1.0, CHCl ); R
D
+
HRMS (ESI): m/z [M +H] calcd for C H O 1071.3439;
found: 1070.3442.
=0.24(Ethyl acetate/hexane, 1/2). H NMR (400 MHz, CDCl3) δ
7.83 (d, J = 7.3 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.49-7.41 (m,
62
55 17
5
(
1
H), 7.36 (t, J = 7.8 Hz, 3H), 7.31 (d, J = 6.9 Hz, 3H), 5.73-5.67
m, 1H), 5.62 (d, J = 8.4 Hz, 1H), 5.55 (s, 1H), 5.13-5.07 (m,
H), 5.02 (dd, J = 9.8, 3.9 Hz, 1H), 4.90 (d, J = 3.9 Hz, 1H), 4.41
4
.3.3 Phenyl 6-O-(2, 3, 4, 6-tetra-O-Bz-α-D-mannopyranosyl)-
(1→6)-2, 3, 4-tri-O-Ac-β-D-thioglucopyranoside (G25)
2
D
3
Yield 87% (85mg); Colorless oil;
=
8
[
α
]
-39.31(c=2.0, CHCl ); Rf
(t, J = 9.4 Hz, 1H), 4.30 (dd, J = 10.6, 8.5 Hz, 1H), 4.24 (dd, J =
9.4, 3.8 Hz, 1H), 4.11 (dd, J = 12.2, 3.6 Hz, 1H), 3.92 (dd, J =
12.3, 2.1 Hz, 1H), 3.87-3.81 (m, 1H), 3.77 (dd, J = 17.4, 8.4 Hz,
2H), 3.67 (d, J = 9.9 Hz, 1H), 3.29 (s, 3H), 1.94 (d, J = 11.2 Hz,
6H), 1.75 (s, 3H). C NMR (100 MHz, CDCl3) δ 170.7, 170.0,
169.4, 165.6, 137.2, 133.9, 133.1, 130.8, 130.0, 129.1, 129.0,
128.3, 128.2, 126.0, 123.2, 101.3, 97.3, 96.9, 79.0, 75.8, 72.7,
71.4, 70.6, 68.9, 68.6, 62.2, 61.6, 55.3, 54.7, 20.6, 20.6, 20.3.
HRMS (ESI): m/z [M +H] calcd for C41
found: 804.2508.
3
1
0.38(Ethyl acetate/hexane, 1/2). H NMR (400 MHz, CDCl ) δ
3
.11 (d, J = 7.7 Hz, 2H), 8.04 (d, J = 7.7 Hz, 2H), 7.87 (d, J = 7.7
Hz, 2H), 7.77 (d, J = 7.7 Hz, 2H), 7.62-7.54 (m, 4H), 7.44 (t, J =
13
7
1
5
1
4
4
.0 Hz, 4H), 7.39 (td, J = 7.8, 3.0 Hz, 4H), 7.30 (d, J = 7.7 Hz,
H), 7.24 (dd, J = 11.6, 3.7 Hz, 4H), 6.11 (t, J = 10.1 Hz, 1H),
.91 (dd, J = 10.1, 3.3 Hz, 1H), 5.75 (s, 1H), 5.29 (t, J = 9.3 Hz,
H), 5.10 (s, 1H), 5.03-4.94 (m, 2H), 4.82 (d, J = 10.2 Hz, 1H),
.71-4.66 (m, 1H), 4.54 (d, J = 10.3 Hz, 1H), 4.45 (dd, J = 12.1,
.4 Hz, 1H), 3.94 (dq, J = 16.8, 7.5 Hz, 2H), 3.67 (d, J = 10.2 Hz,
+
H42NO16 804.2504;

4
.3.7 Methyl 4-O-(2-deoxy-2-azido- 3, 4, 6-tri-O-Ac -β-D-
8.
(a) Gouliaras C, Lee D, Chan L, Taylor M S. J Am Chem Soc. 2011;
133: 13926-13929; (b) Muramatsu W, Yoshimatsu H. Adv Synth
Catal. 2013; 355: 2518-2524.
Kaeothip S, Pornsuriyasak P, Demchenko A V. Tetrahedron Lett. 2008;
49: 1542-1545.
ACCEPTED MANUSCRIPT
galactopyranosyl)-
glucopyranoside (G29)
(1→4)-
2,
3-di-O-Bz-6-O-Bn-α-D-
9
.
2
3
Yield 83% (67mg); White solid; mp 75-77ꢀ; +50.2(c=1.0,
CHCl ); R =0.4(Ethyl acetate/hexane, 1/4). H NMR (400 MHz,
CDCl ) δ 7.98 (d, J = 7.5 Hz, 4H), 7.49 (t, J = 7.3 Hz, 2H), 7.41-
[α ]
D
1
3
f
10. Sun L, Wu X, Xiong DC, Ye XS. Angew Chem Int Ed. 2016; 55: 8041-
8045.
3
7
3
4
1
3
3
.35 (m, 9H), 6.07 (t, J = 9.6 Hz, 1H), 5.32 (s, 1H), 5.25 (d, J =
.5 Hz, 1H), 5.21-5.14 (m, 2H), 5.10 (dd, J = 10.2, 3.6 Hz, 1H),
.68 (d, J = 4.9 Hz, 2H), 4.20 (d, J = 9.5 Hz, 1H), 4.14 (dd, J =
2.4, 6.1 Hz, 1H), 4.06-3.98 (m, 1H), 3.92 (dt, J = 10.0, 4.1 Hz,
H), 3.79 (d, J = 11.1 Hz,1H), 3.53 (dd, J = 11.2, 3.6 Hz, 1H),
11. For selective references on Au-catalyzed glycosylation, see: (a) Li Y,
Yang X., Liu Y, Zhu C, Yang Y, Yu B. Chem Eur J. 2010; 16: 1871-
1
882; (b) Zhu Y, Yu B. Angew Chem Int Ed. 2011; 50: 8329-8332; (c)
Zhang Q, Sun J, Zhu Y, Zhang F, Yu B. Angew Chem Int Ed. 2011;
0: 4933-4936; (d) Peng P, Schmidt RR. J Am Chem Soc. 2015; 137:
5
13
12653-12659.
.44 (s, 3H).2.07 (s, 3H), 1.99 (d, J = 13.3 Hz, 6H). C NMR
1
1
2. For glycosylation protocol using Cu as a catalyst, see: Wang HY,
Simmons CJ, Blaszczyk SA, Balzer PG, Luo R, Duan X., Tang W.
Angew Chem Int Ed. 2017; 56: 15698-15702.
3. For a reference on Pd-catalyzed glycosylation, see: Ji L, Xiang
SH, Leng WL, Hoang Kle M, Liu XW. Org. Lett. 2015; 17: 1357-
1360.
(100 MHz, CDCl ) δ 170.2, 169.8, 169.5, 166.0, 165.3, 138.0,
3
1
1
7
33.2, 132.9, 130.0, 129.9, 129.9, 129.6, 129.5, 129.1, 128.7,
28.5, 128.4, 128.3, 128.1, 127.8, 127.5, 98.8, 96.8, 75.7, 73.3,
2.3, 69.5, 68.7, 68.4, 67.2, 61.4, 57.4, 55.5, 20.5. HRMS (ESI):
+
m/z [M +H] calcd for C H N O 806.2772; found: 806.2776.
40
44
3
15
1
1
4. For a reference on Ni-catalyzed glycosylation, see: Mensah EA, Yu
F, Nguyen HM. J Am Chem Soc. 2010; 132: 14288-14302.
5. For representative reviews on metal-catalyzed glycosylation, see (a)
McKay MJ, Nguyen HM. ACS Catal. 2012; 2: 1563-1595; (b) Yu B.
Acc Chem Res. 2018; 51: 507-516.
6. Ma T, Li C, Liang H, Zhang Z,Wang Z, Yu L, Xue W.
Synlett 2017; 28: 2311-2314.
7. Ma T, Li C, Zhang Z, Wang Z, Yu L, Xue W. Synlett 2017; 28: 2633-
Acknowledgments
The work was supported by the National Science Foundation
of China (51501080, 21772071, 21675070, 21405067 and
1
1
1
3
1670350) and the Fundamental Research Funds for the Central
Universities, Lanzhou University (lzujbky-2017-207, lzujbky-
017-k24, and lzujbky-2017-k25). We gratefully acknowledge
2
2
636.
the financial support from the Fundamental Research Funds for
the Central Universities, Lanzhou University (lzujbky-2017-207,
lzujbky-2017-k24, and lzujbky-2017-k25).
8.
(a)Mukherjee D, Yousuf SK, Taneja SC. Tetrahedron lett. 2008; 49:
4
944-4948; (b) Mukherjee D, Ray PK, Chowdhury US. Tetrahedron,
2
001; 57: 7701-7704; (c) Chandra S, Yadav RN, Paniagua A., Banik
BK. Tetrahedron lett. 2016; 57: 1425-1429.
19. Saratikov A S. Die Pharmazie, 1968; 69: 394-398.
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