Unusually Stable Picoloyl-Protected Trimethylsilyl Glycosides for Nonsymmetrical 1,1′-Glycosylation and Synthesis of 1,1′-Disaccharides with Diverse Configurations

Article abstract of DOI:10.1002/chem.201700785

Nonsymmetrical 1,1′-disaccharides and related derivatives constitute structural components in various glycolipids and natural products. Some of these compounds have been shown to exhibit appealing biological properties. We report a direct yet stereoselective 1,1′-glycosylation strategy for the synthesis of nonsymmetrical 1,1′-disaccharides with diverse configurations and sugar components. The strategy is based on the joined forces of a new class of configurationally stable glycoside acceptors and stereodirecting thioglycoside donors. The new glycoside acceptors feature a picoloyl (Pico) protecting group at the remote C4/C3 position that confers unusual stability on TMS glycosides under acidic conditions.

Full text of DOI:10.1002/chem.201700785

A Journal of
Accepted Article
Title: Unusually Stable Picoloyl-protected Trimethylsilyl Glycosides
for Non-symmetrical 1,1'-Glycosylation and Synthesis of 1,1'-
Disaccharides with Diverse Configurations
Authors: Kwok-Kong Tony Mong, Yen-Chu Luke Lu, and Bhaswati
Ghosh
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201700785
Link to VoR: http://dx.doi.org/10.1002/chem.201700785
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Unusually Stable Picoloyl-protected Trimethylsilyl Glycosides for
Non-symmetrical 1,1-Glycosylation and Synthesis of 1,1-
Disaccharides with Diverse Configurations
Yen-Chu Luke Lu, Bhaswati Ghosh, and Kwok-Kong Tony Mong*
Dedication to Professor Tin Yuen Luk on the occasion of his retirement from National University of Taiwan and 70th Birthday
Abstract: Non-symmetrical 1,1-disaccharides and related
derivatives constitute the structural components in various glycolipids
and natural products. Some of these compounds have been shown to
exhibit appealing biological properties. We report a direct yet
stereoselective 1,1´-glycosylation strategy for the synthesis of non-
symmetrical 1,1-disaccharides with diverse configurations and sugar
components. The strategy is based on the joined forces of a new class
of configurationally stable glycoside acceptors and stereo-directing
thioglycoside donors. The new glycoside acceptors feature a picoloyl
(Pico) protecting group at the remote C4/C3 position that confers
unusual stability on TMS glycosides in acidic conditions.
Conceptually, the stereocontrol in 1,1-glycosylation can be
accomplished by coupling of stereo-directing donors with stereo-
directed or configurationally stable acceptors. Previous
glycosylation studies mainly focused on stereocontrol of glycosyl
donors,[24] whereas studies of glycosyl acceptor have received
much less attention. Glycosyl 1,2-O-stannane acetals have been
exolored as the stable acceptors for synthesis of non-symmetrical
1,1-disaccharides, but the formation of trisaccharide byproduct
was an issue.[22] Peracetyl protected trimethylsilyl (TMS)
glycosides have also been used as acceptors for synthesis of
monosaccharide 1,1-acetals.[2527] The modest stability of the
glycosides severely limited the scope of application.[2628]
Herein we report
a general, yet stereoselective 1,1-
glycosylation strategy for non-symmetrical 1,1-disaccharide
synthesis. In our strategy, a new class of configurationally stable
TMS glycoside acceptors are employed to react with stereo-
directing thioglycosyl donors. These new glycoside acceptors
feature a picoloyl (Pico) protecting group at the remote position to
confer unusual stability on the acceptors in various glycosylation
conditions. Based on the joined forces of the Pico stabilized
acceptors and the stereo-directing donors, synthesis of non-
symmetrical 1,1-disaccharides with diverse configurations and
sugar components is at our disposal. Further studies on the
structure-selectivity relationship and NMR spectroscopy clarify
the stabilization role and mechanism of the Pico-protecting group.
1,1-Disaccharides are non-reducing glycosides linked at
anomeric centres via two glycosidic bonds.[1-3] These
disaccharides are found as the structural units in natural products
such as tunicamycins,[4,5] trehalosamines,[6,7] everninomicins,[8,9]
and avilamycins.[10,11] Trehalose glycolipids contain a 1α1α
disaccharide core that is desymmetrized with fatty acids and, on
some occassions, functionalized with
a
sulfate group.[12]
Examples of these glycolipids include sulfolipids and trehalose
dimycolates of Mycobacterium tuberculosis,[1316] trehalose
dicorynomycolates of Corynebacterium sp.,[17] and maradolipids
of Caenorhabditis elegans.[18] The intriguing structure and
biological relevance of the 1,1-disaccharides and derivatives
have attracted the interest of organic chemists to develop
practical synthetic routes for these compounds.
Although non-symmetrical 1,1-disaccharides can be
constructed by desymmetrizing 1,1-disaccharide substrates, this
approach is limited by substrate availability.[19,20] Alternatively,
these disaccharides can also be acquired by coupling of glycosyl
donors with glycosyl acceptors via so called 1,1-
glycosylation.[2,2123] However the 1,1-glycosylation invokes two
anomeric centres and may produce up to four diastereomers.
Accordingly, it is far more challenging than ordinary glycosylation
in term of stereocontrol and product purification.
[a]
Yen-Chu Luke Lu, Dr. Bhaswati Ghosh, Prof. (Dr.) Kwok-Kong Tony
Mong
Applied Chemistry Department
National Chiao Tung University
Figure 1. Features of New TMS Glycoside Acceptors and their Application to
the Synthesis of 1,1-Disaccharides with Diverse Configurations.
University Road, Hisnchu City, Taiwan, R.O.C.
E-mail: tmong@mail.nctu.edu.tw
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
Results and Discussion
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In the beginning, we tackled the synthesis of a 1α1'α-
disaccharide by glycosylation of 4-O-Pico glucosyl hemiacetal 2
with 4,6-O-benzylidene thiogalactoside 1, N-iodosuccinimide
(NIS) and trimethylsilyl triflate (TMSOTf) as promoters (Scheme
1) (Table 1, entry 1).[29] The reason for using thiogalactoside
donor 1 is that it exhibited high α-selectivity in previous
glycosylation.[30,31] Furthermore, the Pico-protecting group of the
hemiacetal 2 was expected to fix the C1 hydroxyl at the α-
configuration via intramolecular hydrogen bonding.[32,33] But
experimentally, a 3:1 mixture of 1α1'α diastereomer 4aa and
1α1'β diastereomer 4ab was obtained with a yield of ca 73%
yield. The donor 1 did exhibite excellent α-selectivity, but the α-
selectivity for acceptor 2 was just marginal. Though the proposed
hydrogen bonding association did not occur, a marked difference
in polarity between the Pico-containing diastereomers 4aa and
4ab (from thin layer chromatography) was observed, and such a
property facilitated the product purification. Interestingly, a similar
polarity difference was not observed for the benzoyl (Bz)
protected diastereomers 5aa and5ab, which were produced by
the glycosylation of 4-O-Bz glucosyl hemiacetal acceptor 3 with
Table 1. Studies on α-Directing Glycosyl Donors and α-Directing Glucoside
Acceptors for 1,1-Glycosylation.
Entry
Donor
(equiv),
acceptor
Promoter
(equiv)[a]
T (°C),
Time
(h)
Product (%)
Ratio[b]
1
1 (1.2), 2
1 (1.2), 3
1 (1.2), 6
1 (1.2), 7
1 (1.2), 8
10 (1.2), 7
10 (1.2), 7
10 (1.2), 7
10 (1.2), 7
10 (2.0), 7
1 (2.0), 7
10 (1.2), 6
A (1.3)
A (1.3)
A (1.3)
A (1.3)
A (1.3)
A (1.3)
B (1.3)
B (2.0)
B (1.3)
B (1.3)
B (1.3)
B (1.3)
0, 5
4aa, 4ab (73)
5aa, 5ab (70)
9aa only (35)
4aa only (76)
5aa, 5ab (70)
11aa only (10)
11aa only (30)
11aa only (35)
no reaction
2:1
2
0, 6
1:1
3
0, 18
0, 18
0, 6
1:0[c]
1:0
4
5
3:1
6
25, 18
0, 5
1:0
1:0
1:0[d]
ND[e]
1:0
1:0
7
8
0, 6
9
0, 18
0, 18
-20, 7
0, 18
10
11
12
11aa only (65)
4aa only (80)
complex
mixture
ND
13
13 (1.2), 7
B (1.3)
0, 18
14aa,14ba
3:1
(75)
[a] Promoter system A = NIS and TMSOTf. Promoter system B = Me2S2-
Tf2O. [b] Isomer ratio was determined by isolation or NMR spectroscopy. [c]
Compound 9aa was contaminated with an inseparable byproduct stemming
from donor 1. [d] Self-condensation of 7 occurred and the 1,1-disaccharide
12 was obtained as a α/β mixture. [e] 1.3 Equiv. of DTBP (w.r.t to the
acceptor) was added.
galactosyl donor 1 (Entry 2). Structural characterization of the
1,1-disaccharides 4aa, 4ab, 5aa, and 5ab was accomplished by
1D and 2D NMR spectroscopy. Anomeric configuration of the
1
3
diastereomers was determined by the JC1H1 (or JH1H2) coupling
constant at the anomeric centre. For example, the 1JC1H1 values at
C1 and C1 positions of the 1α1'α diastereomer 4aa were 171.3
and 169.6 Hz, respectively; while the corresponding 1JC1H1 values
for the 1α1'β diastereomer 4ab were 169.8 and 160.7 Hz,
1
respectively. These JC1H1 values agreed with the literature
data.[34]
As the proposed hemiacetal acceptor 2 did not work, we
examined the TMS glycoside acceptors. To this end, preparation
of TMS glycoside with a high anomeric purity was required;
therefore, various silylation protocols were evaluated
(unpublished data).[35] Eventually, a α-selective silylation method,
that based on modification of
a known procedure, was
developed.[36] Thus, hemiacetal 2, 3, or 6a in CH2Cl2 (0.08 M) was
treated with 2.0 equiv of TMSOTf at 0 °C, followed by the slow
addition of 1.5 equiv of hexamethyldisilazane (HMDS) (Scheme
2a). Under these reaction conditions, the TMS α-glucosides 6, 7,
and 8 were obtained with α:β ratios spanning from 4:1 to 8:1, and
the desired α-anomers could be isolated by standard
chromatography.[37] For preparation of Pico protected TMS β-
glucoside 7, kinetically controlled conditions were applied. In this
protocol, 1.0 equiv of hemiacetal 2 in THF was treated with 1.5
Scheme 1. 1,1ʹ-Glycosylation studies of glucosyl hemiacetals (2, 3) and TMS
glucosides (6, 7, 8).
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equiv of sodium bis(trimethylsilyl)amide (NaHDMS) at 60 °C,
followed by slow addition of 1.5 equiv of trimethylchlorosilane
(TMSCl). The reaction produced the desired TMS β-glucoside 7
at a yield of 50% with excellent >10:1 α:β ratio. Although ca 45%
of 2 remained, it could be recovered for silylation.[38]
and 11), but was incompatible with peracetyl TMS α-glucoside
acceptor 6 (Entry 12). To compare the stereo-directing effect of
the benzylidene group of donor 10, perbenzyl thioglucoside donor
13 was employed to react with the Pico protected TMS acceptor
7 (Entry 13). The reaction produced a 3:1 mixture of 1α1α and
1β1α disaccharides 14aa and 14ba, confirming the
requirement for the cyclic acetal protection. Taken the results of
Table 1 together suggest that the Pico-protected TMS acceptor
and 4,6-O-benzylidene protected donor constitute the best
donoracceptor pair for the stereoselective 1,1-glycosylation.
Scheme 2. (a) Preparation of TMS α-Glucosides 6-8. (b) Preparation of TMS
β-Glucosides 7.
After the preparation of TMS α-glucoside acceptors 68, the
1,1-glycosylation study was continued. Glycosylation of the
peracetyl TMS α-glucoside acceptor 6 with the galactosyl donor 1
gave a poor yield of 1α1α-disaccharide 9aa (Entry 3). In sharp
contrast, the glycosylation of the Pico-protected TMS α-glucoside
acceptor 7 with 1 produced the diastereomer 9aa as a single
isomer in a high 76% yield (Entry 4). The glycosylation of Bz-
protected TMS α-glucoside acceptor 8 with 1 furnished a 3:1
mixture of 1α1'α disaccharide 5aa and 1α1'β disaccharide
5ab in 70% yield, indicating that anomerization of 8 occurred in
glycosylation (Entry 5). In consideration of the yield and
stereoselectivity, TMS α-glucoside 7 was the acceptor of choice
for further studies.
Next, we investigated the glycosylation of the Pico-protected
acceptor 7 with the 4,6-O-benzylidene thioglucoside donor 10,
which has previously been shown to be α-selective in
glycosylation.[39] However, the glycosylation of 7 with 10 was
sluggish in the presence of NIS and TMSOTf promoters (Entry 6).
After 24 h reaction, the 1α1α disaccharide 11aa was in a low
yield (~10%) and some acceptor 7 still remained. The inferior
result was likely attributed to the poor reactivity of the glucosyl
donor (comparing with galactosyl donor 1).[40] Accordingly, a
sulfonium type promoter that generated in situ from dimethyl
disulfide (Me2S2) and triflic anhydride (Tf2O) was applied.[41] After
optimization (Entries 710), the yield of 1α1α disaccharide
11aa was improved to 65% by glycosylation of 1.0 equiv of the
Pico-protected acceptor 7 with 2.0 equiv of the donor 10 in the
presence of a limited amount (1.3 equiv) of the promoter (Entry
10). Of noted is that excessive amount of the promoter enhanced
the self-condensation of 7 (Entry 8). Addition of di-tertbutylmethyl
pyridine (DTBP) as an acid scavenger completely halted the
reaction, indicating that the glycosylation of the TMS glycoside
acceptor requires an acidic condition.[2528]
Scheme 3. Structure-selectivity Relationship Study for TMS Glycoside
Acceptors 7’, 8, and 15‒17.
Although the Pico-protecting group has been regarded as a
stereo-directing group in other glycosylation studies,[32,33,42] its
role is clearly different in present study. To clarify the role of the
Pico group, we conducted a structure‒selectivity relationship
study. For this purpose, various TMS glucosides with (i) a nicolinyl
(Nico) (15), iso-nicolinyl (iNico) (16), or Bz (8) protecting group at
C4, (ii) a β-TMS acetal at C1 (i.e. 7 and 17), and (ii) with a Pico-
protecting group at C3 (i.e. 17) were prepared for glycosylation
with the donor 10. Preparation of the TMS α-/β-glycosides
followed the protocols shown in Scheme 2.
The optimized conditions also worked in glycosylation of the
Pico-protected acceptor 7 with the galactosyl donor 1 (Entries 4
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Glycosylation of the Nico protected TMS α-acceptor 15 with
the glucosyl donor 10 in the presence of Me2S2‒Tf2O promoter
produced the 1α1α disaccharide 18 at a 55% yield, which is
lower than the yield (~65%) given by the Pico protected acceptor
7 (Scheme 3a). In contrast, glycosylation of the iNico protected
(16) or Bz protected (8) acceptor gave a complex mixture; from
which, no 1,1-disaccharide products could be isolated,
suggesting that both TMS α-acceptors 8 and 16 were inferior the
acceptors 7 and 15 (Schemes 3b and 3c). Among the pyridine
substituted carboxyl protecting groups, the Pico-protecting group
confers the best stability on the TMS glycoside.[43]
picolinium substituent rendered the anomerization (path a) and/or
self-condensation (path b) of the TMS glycoside difficult.
Although TMS β-glycosides are generally considered to be
more reactive than the α-glycosides, the formers are however less
stable in acidic conditions.[27,28] Therefore, it was of interest to
probe the stability of the Pico protected TMS β-glycoside under
the 1,1-glycsoylation conditions. To this end, 4-O-Pico TMS β-
glucoside 7 was prepared for glycosylation with glucosyl donor
10 (Scheme 3d). The glycosylation was conducted at ‒20 °C to
furnish the expected 1α1β-disaccharide 19 as the sole isomer.
The Pico-protecting group could also be placed at the C3 position
as shown by glycosylation of the 3-O-Pico TMS β-glucoside 17
(Scheme 3e).
Figure 2. NMR Spectrum of the Pico-protected TMS α-Glucoside 7 (a) Before
and (b) 24 h After Treatment with TMSOTf.
One may raise a question whether the Pico-protecting group
can be replaced with a structural mimic. This question was
clarified by glycosylation of the Bz protected TMS α-acceptor 8
with donor 10 in the presence of methyl picolinate (Scheme 3f).
Under such conditions, no glycosylation occurred and majority of
the acceptor 8 remained after 24 h reaction. The result is similar
to that given by the addition of DTBP (Table 1, entry 9).
The preceding experiments suggest that the Pico-protecting
group is not merely an acid scavenger. Rather, its presence in the
TMS glycoside acceptor imparts unusual stability during
glycosylation. To compare the stabilization capacities of standard
acyl and Pico protecting groups, the solutions of 4-O-Pico (7) and
4-O-Bz (8) protected TMS α-glucosides in CDCl3 were treated
with 0.5 equiv of TMSOTf at RT. 1H NMR spectroscopy was
performed to monitor the structural change of the TMS glucoside.
Immediately after the addition of TMSOTf, the 1H NMR
spectra of the 4-O-Bz TMS α-glucoside 8 changed dramatically.
Signals corresponding to the anomeric and TMS protons (δ = 5.19
and 0.20 ppm) disappeared, indicating that the acceptor 8 was
unstable in the presence of the acid (see NMR spectra in pp 65
of SI).
Figure 3. Proposed Mechanism of the Stabilization Given by Pico-Protecting
Group.
After elucidating the role of the Pico protecting group, we
explored the substrate scope of the 1,1-glycosylation method. At
start, various non-symmetrical 1α1α-disaccharides were
synthesized from substrates with different protecting groups and
sugar scaffolds (Schemes
4
and 5). Thus, 6-O-tert-
butyldiphenylsilyl (TBDP)-protected TMS α-acceptor 21 and 2-O-
naphthylmethyl (Nap)-protected TMS α-acceptor 22 were
glycosylated with thioglucoside donor 10 and 4,6-O-
naphthylidene (Naph)-protected thiogalactoside donor 23,
respectively (Scheme 4). The reactions furnished the 1α→1α-
disaccharides 29 and 30 as the single isomers at 60% and 76%
yields. Excellent stereocontrol was also observed for the
glycosylation of TMS α-acceptor 7 with thiorhamnosyl donor 24.
Similar to the donors 1, 10, and 23, the donor 24 has a
conformational restrained protecting group at C2 and C3 positions.
In marked contrast, the 1H NMR spectra of the 4-O-Pico TMS
α-glucoside 7 remained largely unchanged in the presence of
TMSOTf as shown by the NMR spectra in Figure 2a and 2b.[44]
A
closer examination revealed the peak broadening and downfield
1
shift (0.10 to 0.40 ppm) of H signals from the pyridine substituent
(Hb, Hc, and Hd) (Figure 2b). A similar NMR pattern has been
observed for pyridine treated with trimethylsilyl perchlorate
(Me3SiClO4).[45] The aforementioned NMR spectrum indicates an
association between TMSOTf and the pyridine nitrogen of the
Pico group.
Based on the structure‒selectivity relationship studies, we
proposed the stabilization mechanism of the Pico protecting
group (Figure 3). Here, glycosylation of the TMS glycoside
acceptor produced the acid by-product TMSOTf, which was
trapped by the pyridine substituent of the Pico to form a picolinium
moiety. The strong electron-withdrawing property of the
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addition to the 2-azido-2-deoxythioglycoside donors, the Pico-
protected TMS α-glucoside acceptor 7 could react with the 2-
deoxythioglycoside donors such as 27 and 28, though a lower
reaction temperature (‒40 C) was needed to avoid the glycal
formation.
The utility of the Pico-protecting group is not limited to the
TMS α-glucosides 7, 21, and 22, but it is also applicable to the
TMS 2-azido-2-deoxy-α-glucoside acceptor 36. For example,
glycosylation of the TMS 2-azido α-acceptor 36 with the
thioglucoside 10, 2-azido-2-deoxythioglucoside 25, and 2-
deoxythioglucoside 28 furnished the 1α1α disaccharides 37,
38, and 39, respectively, at yields of 5872% (Scheme 5). In
addition to D-gluco donors 10, 25, and 28, the TMS 2-azido-2-
deoxy α-acceptor 36 could be coupled with the 2-deoxy-
thiogalactoside donor 27 and thiogalactoside donor 1 to produce
the 1α1α disaccharides 40 and 41, respectively, at yields of 70‒
75% with perfect stereocontrol.
Scheme 4. Synthesis of Non-symmetrical 1α→1α-Disaccharides 29-35 from
Thioglycoside Donors 10 and 23–28, and Pico-protected TMS α-Glucoside
Acceptors 7, 21, and 22.
The applicability of the 1,1-glycosylation method to 2-azido-2-
deoxythioglycoside donors is of interest because 2-azido-2-
deoxythioglycosides are used as the precursors for synthesis of
2-acetamido- or 2-amino-2-deoxy-glycosides, which are present
in some natural 1,1-disaccharide compounds. Therefore, we
studied the glycosylation of TMS α-glucoside acceptor 7 with 2-
Scheme 5. Synthesis of 1α1α-Disaccharides 37‒41 from Thioglycoside
Donors 1, 10, 25, 27, and 28 and TMS 2-Azido-2-Deoxy-α-Glucoside Acceptor
36.
After demonstrating the application of the Pico-protected TMS
glycosides for the synthesis of 1α1α-disaccharides, we
attempted the 1β1α-disaccharide synthesis. Notably, these
disaccharides are found in natural products such as 3,3-diamino-
3,3-dideoxy-β,α-trehalose[46] and tunicamycins.[5] The synthesis
of 1β1α-disaccharide requires the joined forces of a β-directing
glycosyl donor and a Pico protected α-glycoside acceptor.
Regarding the β-directing donor, we applied the concept of
neighbouring group participation (NGP).[47]
azido-2-deoxythioglucoside
25
and
2-azido-2-
deoxythiogalactoside 26. The glycosylations proceeded at 0 °C
and desired 1α1α-disaccharides 32 and 33 were obtained at
65% and 70% yields, respectively, with a perfect stereoselectivity.
Different from the glycosylation with thioglycoside donors 10, 23,
and 24, the glycosylation with the 2-azido-2-deoxy donors
requires a higher stoichiometric amount (1.8 equiv) of Me2S2‒
Tf2O promoter. The requirement of additional promoter may be
due to the less reactive nature of the 2-azido-2-deoxy donors. In
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Accordingly, various participating donors such as N-
trichloroethoxycarbonyl (Troc) protected thioglucosamines 42, 43,
2-O-Bz protected thioglucoside 44, 2-O-Bz protected
thiogalactoside 45, and N-phthalimido (Phth) protected
thiogalactosamine 46 were prepared for glycosylation with the
Pico-protected TMS acceptor 7 (Scheme 6).
It is reasoned that the selectivity of glycosylation may be
modified by adjusting the reaction temperature. Accordingly, the
glycosylation of 7 with 45 was repeated at lower reaction
temperature. To our delight, the desired 1β1α anomer of 50
was obtained in high selectivity at ‒60 °C. Similar reaction
conditions worked fine for glycosylation of TMS α-acceptor 7 with
2-O-Bz protected thiogalactosyl donor 46 and the desired
1β1α-diastereomer of 51 was obtained at a 70% yield with
10:1 1β1α to 1α1α ratio.
Although the 1β1α-disaccharides 47‒51 prepared in above
studies contain 1,2-trans β-glycosidic bonds, some 1β1α-
disaccharides may exist in a 1,2-cis β-configuration such as
everninomicins[8,9,51] and avilamycins.[10,11] For curiosity, we also
investigated the applicability of the Pico-protected TMS glycoside
for coupling with the 1,2-cis β-directing mannosyl donor.[52]
As a proof of concept study, the Pico protected TMS α-
acceptors 7 and 36 were glycosylated with the β-directing
thiomannosyl donor 52 at 0 °C using 1.3 equiv of Me2S2‒Tf2O
(Scheme 7a).[53] The glycosylation reactions produced the
respective β-Man-(11)-α-Glc disaccharide 53 and β-Man-
(11)-α-GlcN3 disaccharide 54 as the single isomers at 52%
and 45% yields. The 1,2-cis β-anomeric configuration of the
mannosides in 53 and 54 was confirmed by 1JC1H1 value of ~154
Hz.
As encouraged by the results in above glycosylation studies,
we challenged the synthesis of 1β1β-disaccharides using Pico-
protected TMS β-glycoside acceptors and 1,2-trans β-directing
glycosyl donors. To avoid the anomerization of the TMS β-
acceptor, the reaction temperature was optimized. A point in case
is the the glycosylation of TMS 4-O-Pico β-glucoside 7 with N-
Troc protected thioglucosamine donor 42. If the reaction was
performed at 0 C in the presence of NIS and TMSOTf promoters,
the 1β1β- and 1β1α diastereomers of 57 were obtained in a
ratio of 7:1 (Scheme 7b).[54] When the reaction was conducted at
–60 C, the 1β1β-disaccharide 57 was produced as a single
isomer and no 1β1α diastereomer was detected. Therefore,
the 1β1α isomer of 57 was likely a consequence of the
anomerization of 7. The β-configuration of the 1β1β-
disaccharide 57 was confirmed by the 3JH1-H2 values of 7.5 and 8.5
Hz. The optimized reaction temperature for glycosylation of 2-O-
Ac and 2-O-Bz protected thioglucoside donors 55 and 56 with
Pico-protected β-glucoside acceptor 7 was ‒50 °C. Under these
conditions, the respective 1β1β-disaccharides 58 and 59 was
furnished at 64‒72% yields with excellent stereoselectivity.
Scheme 6. Synthesis of 1β1α-Disaccharides 47‒51 from 1,2-trans β-
Directing Thioglycoside Donors 42‒46.
Glycosylations of TMS α-glucoside acceptor
7
with
thioglucosamines 42 and 43 and thioglucoside 44 were performed
at 0 °C using Me2S2‒Tf2O as the promoter. The reactions
furnished respective 1β1α-disaccharides 47, 48, and 49 as the
single isomers at 5570% yields. The β- and α-anomeric
configurations of the 1β1α disaccharides 47‒49 were
3
unambiguously confirmed by the JH1H2 values at respective
anomeric centers (8.0–8.5 and 3.5–4.0 Hz).
Conclusions
Unlike the participated thioglycoside donors with a D-gluco
scaffold (i.e. 42‒44), the glycosylation of Pico-protected α-
glucoside acceptor 7 with 2-N-phthalamide (Phth)-2-deoxy-
thiogalactosyl donor 45 at 0 °C produced a 2:1 mixture of 1β1α-
and 1α1α-diastereomers 50. The result might be due to the
competition of the dioxalenium ion[48] and oxacarbenium ion[49] for
coupling with the TMS α-acceptor 7, although another possibility
is the postglycosylation anomerization of the 1β1α- to 1α1α-
anomer. For clarification, pure 1β1α-anomer of 50 in CDCl3
was treated with 0.5 equiv of TMSOTf at 0 °C for 24 h to simulate
the glycosylation conditions. From the proton NMR spectroscopy,
no sight of anomerization of the 1β1α-anomer of 50 occurred,
thus excludes the possibilty of anomerization (see SI).[50]
A general yet stereoselective 1,1-glycosylation strategy has
been developed for the synthesis of non-symmetrical 1,1-
disaccharides with diverse anomeric configurations and sugar
components. The strategy features the joined forces of the Pico
stabilized TMS glycoside acceptors and stereo-directing
thioglycoside donors. The unusual stability of the silyl glycoside
acceptor was confirmed by a structure-selectivity relationship
studies and NMR spectroscopic analysis in acidic conditions.
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10.1002/chem.201700785
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which was concentrated for flash chromatography to obtain the 1,1-
disaccharide. Scheme 7b used the same procedures except that the
NIS/TMSOTf promoters were used.
Preparation
of
TMS
2,3,6-tri-O-benzyl-4-O-picoloyl-1-α-D-
glucopyranoside (7): To a solution of glucosyl hemiacetal 2 (500 mg, 0.90
mmol) (other hemiacetals followed the same protocol) in CH2Cl2 (0.08 M),
TMSOTf (1.8 mmol) was added at 0 °C under N2 and the mixture was
stirred at 0 oC for 10 min. Then, HMDS (1.35 mmol) of CH2Cl2 (2 ml)
solution was slowly added and the reaction mixture was stirred at 0 oC till
completion of the silylation. Workup: the solution was diluted with CH2Cl2
(25 mL), to which, satd. NaHCO3 (20 mL) was added. The organic phase
was separated by separatory funnel, and followed by washed with brine
(20 mL  2), dried over MgSO4, and concentrated for flash chromatography
(Elution: EtOAc/hexanes, 1/3). The desired TMS α-glucoside 7 (570 mg,
76%) was obtained after chromatography. To facilitate the purification (or
if needed), the β-anomer could be selectively hydrolyzed to the hemiacetal
2 by washed with diluted HCl (0.5 M  2). For TMS α-glucoside 7, Rf 0.38
(hexanes/EtOAc, 3/1); [훼]D20 +12.7 (c = 9.0, CHCl3); 1H NMR (400 MHz,
CDCl3): δ = 8.70 (d, J = 4.4 Hz, 1H), 8.59 (bs, 1H), 8.02 (d, J = 7.6 Hz, 1H),
7.74 (dt, J = 1.6, 7.6 Hz, 1H), 7.61 (t, J = 6.4 Hz, 1H), 7.41 (dd, J = 4.8, 6.4
Hz, 1H), 7.34 – 7.22 (m, 7H), 7.17 – 7.03 (m, 6H), 5.49 (t, J = 10.0 Hz, 1H,
H-4), 5.20 (d, J = 3.2 Hz, 1H, H-1), 4.84 (d, J = 11.2 Hz, 1H), 4.74 (d, J =
11.2 Hz, 1H), 4.83 (d, J = 1.2, 11.2 Hz, 2H), 4.48 (d, J = 12.0 Hz, 1H), 4.40
(d, J = 12.0 Hz, 1H), 4.28 (dt, 3.6, 10.0 Hz, 1H), 4.21 (t, J = 9.6 Hz, 1H),
3.61 (dd, J = 2.4, 9.2 Hz, 1H), 3.56 – 3.55 (m, 1H), 0.19 (s, 9H, SiCH3

3); 13C NMR (100 MHz, CDCl3): δ = 164.1 (C=O), 149.7, 147.8, 138.5,
137.2, 137.8, 136.9, 135.9, 128.4, 128.1, 128.0, 127.96, 127.7, 127.3,
127.2, 126.9, 125.6, 91.9 (C-1), 80.6, 78.9, 75.2, 73.5, 73.1, 72.0, 68.8,
68.4, 0.06 (SiCH3); HRMS‒ESI (m/z): [M + H]+ calcd for C36H40NO7Si,
628.2725; found, 628.2734.
Scheme 7. (a) Synthesis of 1β1α Disaccharides 53 and 54 with a 1,2-cis β-
Mannosidic Bond. (b) Synthesis of 1β1β Disaccharides 57‒59.
Preparation
of
TMS
2,3,6-tri-O-benzyl-4-O-picoloyl-1-β-D-
glucopyranoside (7): To prepare β-anomer TMS glycoside 7 (method
B), NaHMDS (0.32 mmol) was added to the glucosyl hemiacetal 2 (120
mg, 0.215 mmol) in THF (0.1 M) under N2 and the mixture was stirred at
Experimental Section
o
60 C for 20 min. Then TMSCl (0.323 mmol) was slowly added to the
mixture at 60 oC. Workup: The solution was diluted with CH2Cl2 (25 mL),
followed by quenching with NH4Cl (30 ml) dried over MgSO4, and
concentrated for flash chromatography (Elution: EtOAc/hexanes, 1/3) to
furnish the desired TMS β-glucoside 7 (67 mg, 50%). For 7, Rf 0.35
(hexanes/EtOAc, 3/1); [훼]D20 11.2 (c = 7.5, CHCl3); 1H NMR (400 MHz,
CDCl3): δ = 8.73 (dd, J = 1.0, 4.0 Hz, 1H, ArH), 7.97 (d, J = 8.0 Hz, 1H,
ArH), 7.77 (dt, J = 2.0, 8.0 Hz, 1H), 7.45 (dd, J = 1.2, 4.8 Hz, 1H, ArH),
7.37 – 7.16 (m, 10H, ArH), 7.10 – 7.05 (m, 5H, ArH), 5.34 (t, J = 9.6 Hz,
1H, H-4), 4.94 (d, J = 11.2 Hz, 1H), 4.81 – 4.73 (m, 3H including H-1), 4.64
(d, J = 11.2 Hz, 1H), 4.48 (s, 2H), 3.87 – 3.83 (m, 2H), ), 3.63 (d, J = 4.8
Hz, 2H), 3.52 (dd, J = 1.2, 9.2 Hz, 1H), 0.24 (s, 9H, SiCH3  3); 13C NMR
(100 MHz, CDCl3): δ = 164.1 (C=O), 149.8, 147.6, 138.4, 138.2, 138.0,
136.9, 128.3, 128.14, 128.11, 128.0, 127.9, 127.7, 127.5, 127.3, 126.9,
125.5, 97.9 (C-1), 83.8, 81.6, 75.2, 74.9, 73.5, 73.2, 72.5, 69.8, 0.02
(SiCH3); HRMS‒ESI (m/z): [M + Na]+ calcd for C36H41NNaO7Si, 650.2545;
found, 650.2544.
General protocol A with NIS and TMSOTf promoter (conventional
procedure) (Table 1, entries 1-6): To a solution of thiogalactosyl donor 1
(260 mg, 0.468 mmol), 4-O-Pico protected glucosyl hemiacetal 2 (or 4-O-
Bz protected glucosyl hemiacetal 3) (200 mg, 0.36 mmol) and freshly
activated 4Å MS (1.0 g) in CH2Cl2 (10 mL) were added and the mixture
was stirred at 0 °C for 30 min under N2. Then, NIS (106 mg, 0.468 mmol)
and TMSOTf (84 µL, 0.468 mmol) were added and the resulting mixture
was stirred at 0 °C until the end of the reaction. Progress of the reaction
was checked by TLC examination. After the completion of the glycosylation,
Na2S2O3(s) and satd. NaHCO3 were added, and the mixture was stirred at
RT for ca 10 min. Then the mixture was filtered over celite and the filtrate
was diluted with CH2Cl2. The resulting CH2Cl2 solution was then washed
with H2O and brine, followed by drying over MgSO4. After removal of the
MgSO4 by filtration, the filtrate was concentrated for flash chromatography
to obtain the desired product (Elution for 4aa and 4ab: EtOAc/hexanes,
1/2; elution for 5aa and 5ab: EtOAc/hexanes, 1/4).
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-galactopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside 4aa: Rf 0.38
General protocol B with Me2S2-Tf2O promoters (Table 1 entries 7-13,
Schemes 1 to 7): To a solution of thioglycosyl donor (2.0 equiv) in CH2Cl2,
TMS glycoside acceptor (1.0 equiv) and activated 4Å MS (10 wt% of the
solvent) were added (final concentration of the acceptor was 50 MM). The
mixture was then stirred at RT for ca. 1 h and then at 0 °C or at optimized
temperature (refer to SI for specific temperature) for additional 15 min. In
another round bottom flask, dimethyldisulfide (Me2S2) (1.3-1.8 equiv) in
CH2Cl2 was treated with triflic anhydride (Tf2O) (1.3-1.8 equiv). After mixing
for 30 min at 0 °C, the Me2S2Tf2O solution was transferred slowly to the
donor and acceptor mixture. The resulting mixture was stirred at 0 °C or at
optimized temperature until the glycosylation was complete. Then the
reaction was diluted with CH2Cl2 followed by quenching with Et3N (1.0
equiv). MS was removed by filtration to give the crude reaction mixture,
(Hexanes/EtOAc 2:1); [훼]2D0 +94.0 (c = 1.50, CHCl3); H NMR (400 MHz,
1
CDCl3): δ= 8.79 (d, J = 4.5 Hz, 1H), 8.05 – 7.96 (m, 1H), 7.81 (t, J = 7.7
Hz, 1H), 7.61 – 7.08 (m, 32H), 5.59 (t, J = 9.8 Hz, 1H, H-4), 5.46 (s, 1H,
benzylidene-H), 5.37 (s, 1H, H-1), 5.31 (d, J = 2.8 Hz, 1H, H-1), 4.95 –
4.70 (m, 7H), 4.64 (d, J = 12.0 Hz, 1H), 4.51 (d, J = 13.2 Hz, 1H, H-5),
4.48 (d, J = 12.4 Hz, 1H), 4.40 (d, J = 12.4 Hz, 1H), 4.24 (broad s, 1H, H-
3), 4.22 (t, J = 9.6 Hz, 1H, H-3), 4.15 (broad s, 2H including H-2 and H-4),
4.04 (d, J = 12.4 Hz, 1H, H-6a), 3.99 (s, 1H, H-5), 3.78 (dd, J = 2.0, 11.2
Hz, 1H, H-2), 3.43 (d, J = 10.8 Hz, 1H, H-6a), 3.36 (dd, J = 2.9, 10.8 Hz,
1H, H-6b); 13C NMR (100 MHz, CDCl3): δ = 164.0 (C=O), 149.78, 147.79,
138.8, 138.6, 138.4, 138.0, 137.9, 137.7, 136.9, 129.8, 128.9, 128.5, 128.4,
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10.1002/chem.201700785
Chemistry - A European Journal
FULL PAPER
128.18, 128.17, 128.14, 127.97, 127.94, 127.8, 127.7, 127.6, 127.5,
69.0, 68.4 (C-6), 62.9; HRMS‒ESI (m/z): [M +
Na]+ calcd for
127.42, 127.40, 127.37, 126.9, 126.3, 125.5, 101.0 (benzylidene-C), 95.9
C60H59NNaO12+, 1008.3929; found, 1008.3939.
1
1
(C-1, JCH 171.3 Hz), 94.4 (C-1, JCH 169.6 Hz), 79.7 (C-2), 79.5 (C-3),
76.0, 75.3, 75.1, 74.3, 73.61, 73.54, 73.50, 71.8 (C-4), 71.7, 69.2 (C-6),
69.1 (C-5), 68.1 (C-6), 63.1 (C-5); HRMS‒ESI (m/z): [M + H]+ calcd for
C60H59NO12, 986.4110; found, 986.4113.
2, 3, 4, 6-Tetra-O-benzyl-α-D-glucopyranosyl-(11)-2,3,6-tri-O-
benzyl-4-O-picoloyl-α-D-glucopyranoside
14aa:
1
Rf
0.4
(Hexanes/EtOAc 2:1); [훼]2D0 +35.4 (c = 1.30, CHCl3); H NMR (500 MHz,
CDCl3): δ = 8.76 (d, J = 4.0 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.78 (td, J =
1.5, 8.0 Hz, 1H), 7.47 (qd, J = 1.5, 5.0 Hz, 1H), 7.42 – 7.04 (m, 35H), 5.47
(t, J = 10.0 Hz, 1H, H-4), 5.27 (d, J = 3.5 Hz, 1H, H-1), 5.25 (d, J = 4.0
Hz, 1H, H-1), 5.07 (d, J = 6.0 Hz, 1H), 4.92 (d, J = 6.6 Hz, 1H), 4.85 (d, J
= 11.0 Hz, 1H), 4.82 (d, J = 10.5 Hz, 1H), 4.73 – 4.63 (m, 4H), 4, .55 (d, J
= 12.0 Hz, 1H), 4.50 – 4.36 (m, 6H), 4.22 (t, J = 9.5 Hz, 1H, H-3), 4.19 –
4.15 (m, 1H, H-5), 4.07 (t, J = 9.0 Hz, 1H, H-3), 3.73 – 3.67 (m, 2H, H-2
and H-4), 3.60 (dd, J = 3.5, 9.5 Hz, 1H, H-2), 3.52 (dd, J = 3.5, 11.0 Hz,
1H, H-6a), 3.43 (dd, J = 3.0, 11.0 Hz, 1H, H-6a), 3.41 – 3.37 (m, 2H, H-
6b and H-6b); 13C NMR (125 MHz, CDCl3): δ =164.0 (C=O), 149.7, 147.8,
139.0, 138.4, 138.35, 138.1, 138.0, 137.8, 137.7, 136.8, 128.5, 128.4,
128.35, 128.3, 128.2, 128.1, 128.08, 128.0, 128.0, 127.95, 127.9, 127.9,
127.87, 127.8, 127.77, 127.7, 127.65, 127.6, 127.59, 127.5, 127.48,
127.45, 127.3, 127.2, 127.2, 126.8, 125.5, 94.4 (C-1, JCH = 171.2 Hz), 94.3
(C-1, JCH = 168.4 Hz), 81.8 (C-3), 79.13 (C-2), 79.12, 79.10 (C-3), 77.7,
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-galactopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-benzoyl-α-D-glucopyranosides 5aa: Rf 0.40
(Hexanes/EtOAc, 4/1); 1H NMR (500 MHz, CDCl3): δ = 7.95 (d, J = 7.8 Hz,
2.0H, ArH), 7.60 (dt, J = 1.0, 7.5 Hz, 1H, ArH), 7.51 (dd, J = 2.0, 9.5 Hz,
2H, ArH), 7.47 –7.43 (m, 4H, ArH), 7.36 – 7.13 (m, 26H, ArH), 5.45 (s, 1H,
benzylidene-H), 5.44 (t, J = 10.0 Hz, 1H, H-4), 5.38 (d, J = 3.6 Hz, 1H, H-
1), 5.25 (d, J = 3.6 Hz, 1H, H-1), 4.84 – 4.82 (m, 3H), 4.78 (d, J = 11.0 Hz,
1H), 4.77 (d, J = 11.5 Hz, 1H), 4.61 (d, J = 11.0 Hz, 1H), 4.60 (d, J = 11.5
Hz, 1H), 4.43 (d, J = 12.0 Hz, 1H), 4.35 (m, 2H including H-5), 4.23 (d, J
= 2.0 Hz, 1H), 4.14 (dd, J = 3.0, 10.0 Hz, 2H), 4.05 (dd, J = 1.8, 10.0 Hz,
1H, H-3), 4.03 (t, J = 9.5 Hz, 1H, H-3), 3.93 (bs, 1H, H-4), 3.74 (dd, J =
1.5, 10.0 Hz, 1H), 3.72 (dd, J = 1.5, 10.0 Hz, 1H, H-2), 3.33 (dd, J = 2.0,
9.0 H, 1H, H-6a), 3.23 (dd, J = 4.0, 11.0 Hz, 1H, H-6b); 13C NMR (125
MHz, CDCl3): δ = 165.1 (C=O), 138.64, 138.55, 138.2, 138.0, 137.7, 133.0,
130.0, 129.8, 128.9, 128.5, 128.4, 128.30, 128.28, 128.2, 128.14, 128.10,
128.0, 127.9, 127.82, 127.78, 127.73, 127.67, 127.61, 127.59, 127.2,
127.45, 127.42, 127.38, 127.37, 126.3, 101.1 (benzylidene-C), 95.0 (C-1,
75.6, 75.3, 75.0, 73.6, 73.5, 73.1, 72.6, 71.9 (C-4), 70.6 (C-5), 69.3, 68.5
+
(C-6), 68.1 (C-6); HRMS‒ESI (m/z): [M + Na]+ calcd for C67H68NNaO12
,
1078.4736; found, 1078.4703.
1JCH 169.5 Hz), 93.8 (C-1, JCH 166.8 Hz), 79.6 (C-2), 79.4 (C-3), 75.6,
1
75.15, 75.10, 74.2, 73.6, 73.5, 73.4, 71.3, 70.6 (C-4), 69.3, 69.2, 68.0 (C-
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl-(11)-
+
6), 63.0 (C-4); HRMS‒ESI (m/z): [M + Na]+ calcd for C61H60NaO12
,
2,3,6-tri-O-benzyl-4-O-nicoloyl-α-D-glucopyranoside (18): Rf 0.3
(Hexanes/EtOAc 3:1); [훼]2D0 +53.3 (c = 0.30, CHCl3); H NMR (500 MHz,
1
1007.3977; found, 1007.3981.
CDCl3): δ = 9.03 (br, 1H), 8.79 (br, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.53 –
7.07 (m, 31H), 5.59 (s, 1H, benzylidene-H), 5.36 (t, J = 10.0 Hz, 1H, H-4),
5.23 (d, J = 3.5 Hz, 1H, H-1), 5.19 (d, J = 3.5 Hz, 1H, H-1), 5.02 (d, J =
11.5 Hz, 1H), 4.90 (d, J = 11.5 Hz, 1H), 4.86 – 4.80 (m, 2H), 4.77 – 4.68
(m, 3H), 4.59 (d, J = 11.0 Hz, 1H), 4.42 (d, J = 12.0 Hz, 1H), 4.32 (d, J =
12.0 Hz, 1H), 4.29 – 4.25 (m, 2H including H-5 and H-5), 4.20 – 4.17 (m,
2H including H-4 and H-6a), 4.07 (t, J = 9.0 Hz, 1H, H-3), 3.73 – 3.71 (m,
2H including H-6b and H-2), 3.69 (t, J = 9.5 Hz, 1H, H-3), 3.65 (dd, J =
4.0, 9.5 Hz, 1H, H-2), 3.29 (dd, J = 2.5, 11.0 Hz, 1H, H-6a), 3.19 (dd, J =
2.5, 11.0 Hz, 1H, H-6b); 13C NMR (125 MHz, CDCl3): δ =163.8 (C=O),
153.4, 150.9, 138.7, 138.10, 138.08, 137.7, 137.5, 137.4, 137.1, 128.9,
128.5, 128.31, 128.26, 128.20, 128.1, 127.89, 127.86, 127.85, 127.8,
127.62, 127.57, 127.54, 127.49, 127.43, 126.1, 101.3 (benzylidene-C),
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-galactopyranosyl-(11)-
2,3,4’,6-tetra-O-acetyl-4-α-D-glucopyranoside
(9aa):
Rf 0.12
(Hexanes/EtOAc 2:1); 1H NMR (500 MHz, CDCl3): δ = 7.55 – 7.15 (m,
15H), 5.52 – 5.45 (m, 2H), 5.27 (d, J = 3.5 Hz, 1H), 5.25 (d, J = 2.5 Hz,
1H), 5.08 (t, J = 10.0 Hz, 1H), 5.00 (dd, J = 4.0, 10.5 Hz, 1H), 4.89 (d, J =
11.5 Hz, 1H), 4.82 (q, J = 8.5 Hz, 2H), 4.78 – 4.70 (m, 1H), 4.62 (d, J =
11.5 Hz, 1H), 4.54 (d, J = 11.5 Hz, 1H), 4.35 (dt, J = 2.5, 10.5 Hz, 1H),
4.27 (s, 1H), 4.21 – 4.09 (m, 4H), 4.03 – 3.90 (m, 3H), 3.75 (s, 1H), 3.69
(dd, J = 2.0, 12.5 Hz, 1H), 2.03 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H), 1.99 (s,
3H); 13C NMR (125 MHz, CDCl3): δ = 170.5, 170.2, 169.4, 169.3, 138.7,
138.4, 138.2, 138.0, 137.8, 137.5, 128.9, 128.8, 128.3, 128.26, 128.2,
128.1, 128.09, 127.8, 127.7, 127.65, 127.6, 127.55, 126.3, 126.2, 101.0,
96.1, 93.3, 76.2, 74.6, 74.4, 74.1, 74.0, 73.9, 72.1, 71.7, 70.4, 70.3, 69.5,
69.0, 68.5, 67.9, 67.4, 63.6, 61.1, 20.7, 20.6, 20.57, 20.5; HRMS‒ESI
(m/z): [M + Na]+ calcd for C41H46NaO15+, 801.2729; found, 801.2738. 9aa
was contaminated with an unidentified side-product (ca 30%) and
therefore no [α]D was given for 9aa.
1
1
94.4 (C-1, JC1H1 =168.8 Hz), 93.8 (C1, JC1 H1 = 166.3 Hz), 82.5 (C-3),


79.1 (C-2), 78.9 (C-2), 78.8 (C-3), 78.5 (C-4), 75.13, 75.10, 73.7, 73.6,
73.4, 70.9 (C-4), 69.2, 69.0 (C-6), 68.1 (C-6), 63.0; HRMS‒ESI (m/z): [M
+ Na]+ calcd for C60H59NNaO12+, 1008.3929; found, 1008.3941.
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-picoloyl-β-D-glucopyranoside 19: Rf 0.2
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside (11aa): Rf 0.3
(Hexanes/EtOAc 2:1); [훼]2D0 +15.0 (c = 0.40, CHCl3); H NMR (500 MHz,
1
(Hexanes/EtOAc 3:1); [훼]2D0 +25.6 (c = 0.16, CHCl3); H NMR (500 MHz,
CDCl3): δ = 8.72 (d, J = 4.0 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.78 (td, J =
2.0, 7.5 Hz, 1H), 7.53 – 7.02 (m, 31H), 5.54 (s, 1H), 5.33 (t, J = 9.5 Hz, 1H,
H-4), 5.12 (d, J = 3.5 Hz, 1H, H-1), 5.09 (d, J = 11.5 Hz, 1H), 4.95 (d, J =
11.0 Hz, 1H), 4.87 – 4.60 (m, 9H), 4.47 (d, J = 2.0 Hz, 1H), 4.29 – 4.21 (m,
2H, including H-3 and H-5), 4.16 (t, J = 9.0 Hz, 1H), 3.88 (t, J = 9.5 Hz,
1
CDCl3): δ = 8.78 (m, 1H), 7.94 (d, J = 7.5 Hz, 1H), 7.79 (td, J = 1.5, 7.5 Hz,
1H), 7.54 – 7.05 (m, 31H), 5.56 (s, 1H, benzylidene-H), 5.48 (t, J = 10.0
Hz, 1H, H-4), 5.21 (d, J = 3.5 Hz, 1H, H-1), 5.20 (d, J = 3.5 Hz, 1H, H-1),
5.01 (d, J = 11.0 Hz, 1H), 4.92 (d, J = 11.0 Hz, 1H), 4.86 (d, J = 11.0 Hz,
1H), 4.77 (dd, J = 6.5, 12.0 Hz, 1H), 4.71 (dd, J = 6.5, 12.0 Hz, 1H), 4.69
(d, J = 11.5 Hz, 1H), 4.48 – 4.46 (m, 1H, H-5), 4.43 (d, J = 12.5 Hz, 1H),
4.39 (d, J = 11.5 Hz, 1H), 4.29 (dt, J = 5.0, 10.0 Hz, 1H), 4.22 (t, J = 9.5
Hz, 1H, H-3), 4.17 (t, J = 9.0 Hz, 1H, H-3), 4.13 (dd, J = 4.0, 10.0 Hz, 1H),
3.73 (dd, J = 4.0, 9.0 Hz, 1H, H-2), 3.70 – 3.63 (m, 2H), 3.61 (dd, J = 4.0,
9.5 Hz, 1H, H-2), 3.43 (dd, J = 3.0, 11.0 Hz, 1H, H-6a), 3.37 (dd, J = 3.0,
11.0 Hz, 1H, H-6b); 13C NMR (125 MHz, CDCl3): δ = 164.0 (C=O), 149.8,
147.8, 138.9, 138.3, 138.1, 137.9, 137.7, 137.5, 136.8, 128.9, 128.5, 128.3,
128.2, 128.16, 128.1, 128.06, 128.0, 127.9, 127.8, 127.7, 127.54, 127.5,
1H), 3.87 – 3.82 (m, 1H), 3.68 – 3.57 (m, 5H, including H-2 and H-2); 13
C
NMR (125 MHz, CDCl3): δ = 164.1, 149.7, 147.5, 138.6, 138.4, 138.1,
138.0, 137.7, 137.6, 136.9, 128.8, 128.3, 128.3, 128.2, 128.1, 128.0,
127.99, 127.9, 127.86, 127.8, 127.7, 127.67, 127.5, 127.4, 127.3, 127.3,
126.9, 126.1, 125.6, 104.1 (C-1), 101.2, 100.1 (C-1), 82.2, 81.6, 81.5, 78.9
(C-2), 78.5 (C-3), 75.2, 75.1, 74.7, 73.7, 73.6, 73.4 (C-5), 72.1 (C-4), 69.6,
+
68.7, 63.3; HRMS‒ESI (m/z): [M + Na]+, calcd for C60H59NNaO12
,
1008.3929; found, 1008.3904.
127.4, 127.3, 126.9, 126.1, 125.5, 101.2 (benzylidene-C), 95.0 (C-1, JCH
172.6 Hz), 94.4 (C-1, JCH = 172.9 Hz), 82.4, 79.2 (C-3), 79.0 (C-2), 78.6
(C-3), 78.5 (C-2), 75.3, 75.26, 73.6, 73.5, 73.4, 71.8 (C-4), 69.3 (C-5),
=
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl-(11)-
2,4,6-tri-O-benzyl-3-O-picoloyl-β-D-glucopyranoside 20: Rf 0.2
(Hexanes/EtOAc 2:1); [훼]D20 +50.0 (c = 1.0, CHCl3); 1H NMR (500 MHz,
CDCl3): δ = 8.70 (d, J = 4.0 Hz, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.71 (td, J =
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10.1002/chem.201700785
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1.5, 7.5 Hz, 1H), 7.46 – 6.83 (m, 28H), 5.50 (s, 1H), 5.47 (t, J = 9.5 Hz, 1H,
H-3), 5.04 (d, J = 3.5 Hz, 1H, H-1), 4.90 (d, J = 11.5 Hz, 1H), 4.80 (d, J =
11.5 Hz, 1H), 4.76 – 4.70 (m, 2H), 4.64 – 4.61 (m, 3H including H-1), 4.54
(d, J = 12.0 Hz, 1H), 4.48 (q, J = 6.0 Hz, 2H), 4.42 (d, J = 11.0 Hz, 1H),
4.22 – 4.17 (m, 2H), 4.09 (t, J = 9.5 Hz, 1H, H-3), 3.79 (t, J = 9.5 Hz, 1H,
H-4), 3.67 – 3.49 (m, 7H including H-2 and H-2); 13C NMR (125 MHz,
CDCl3): δ = 164.2 (C=O), 149.7, 147.8, 138.6, 138.1, 138.0, 137.9, 137.6,
136.8, 128.8, 128.42, 128.4, 128.3, 128.2, 128.12, 128.1, 128.04, 128.0,
127.9, 127.82, 127.8, 127.7, 127.66, 127.62, 127.6, 127.1, 126.4, 126.1,
125.5, 104.4 (C-1, JCH = 173.1 Hz), 101.3, 100.3 (C-1, JCH = 154.6 Hz),
82.2, 79.0, 78.3, 78.2, 77.1 (C-3), 75.7 (C-4), 75.1, 75.0, 74.6, 73.83, 73.8,
10.0 Hz, 1H, H-3), 3.74 (dt, J = 6.5, 16.0 Hz, 1H, H-5), 3.68 (dd, J = 3.5,
9.5 Hz, 1H, H-2), 3.52 – 3.51 (m, 2H, H-6a and H-6b), 3.23 (dd, J = 7.0,
10.0 Hz, 1H, H-4), 1.52 (s, 3H, CH3), 1.42 (s, 3H, CH3), 1.20 (d, J = 6.5 Hz,
3H, H-6); 13C NMR (125 MHz, CDCl3): δ = 164.0 (C=O), 149.8, 147.7,
138.4, 138.3, 137.9, 137.6, 136.8, 128.6, 128.2, 128.1, 128.0, 127.98,
127.8, 127.75, 127.6, 127.31, 127.3, 126.9, 125.6, 109.2, 98.9 (C-1, 1JCH
= 168.0 Hz ), 96.7 (C-1, 1JCH = 167.0), 80.8 (C-4), 79.8 (C-2), 79.2 (C-3),
78.5 (C-3), 75.8 (C-3), 75.3, 73.7, 73.5, 72.9, 71.6, 69.9 (C-5), 68.6 (C-6),
66.1 (C-5), 28.0, 26.5, 17.6 (C-6); HRMS‒ESI (m/z): [M + Na]+ calcd for
C49H53NNaO12+, 870.3460; found, 870.3242.
73.7, 68.82, 68.8, 63.2; HRMS‒ESI (m/z): [M
C60H59NNaO12+, 1008.3929; found, 1008.3954.
+
Na]+ calcd for
2-Azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-α-D-glucopyranosyl-
(11)-2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside 32: Rf
0.2 (Hexanes/EtOAc 3:1); [훼]2D0 +66.7 (c 0.15, CHCl3); 1H NMR (500 MHz,
CDCl3): δ 8.78 – 8.76 (m, 1H), 7.99 (d, J = 7.5 Hz, 1H), 7.79 (td, J = 8, 2
Hz, 1H), 7.52 – 7.09 (m, 26H), 5.60 (s, 1H, benzylidene-H), 5.50 (t, J = 10
Hz, H-4), 5.175 (d, J = 2.5 Hz, 1H, H-1), 5.169 (d, J = 2.5 Hz, 1H, H-1),
5.03 (d, J = 10.5 Hz, 1H), 4.87 (dd, J = 10.5, 14.0 Hz ,2H), 4.77 (d, J = 12.0
Hz, 2H), 4.70 (d , J = 5.0 Hz, 1H), 4.68 (d, J = 4.5 Hz, 1H), 4.49 (q, J =
12.0 Hz, 2H), 4.39 (dt, J = 3.0, 7.5 Hz, 1H, H-5), 4.35 (dt, J = 5.0, 10.0
Hz, 1H, H-5 ), 4.21 (t, J = 9.5 Hz, 1H, H-3), 4.19 (t, J = 9.5 Hz, 1H, H-3),
4.18 – 4.15 (m, 1H, H-6a), 3.78 – 3.71 (m, 3H, including H-2, H-4 and H-
6b), 3.63 – 3.56 (m, 3H, including H-2 and H-6  2);13C NMR (125 MHz,
CDCl3): δ = 163.9 (C=O), 149.9, 147.7, 138.2, 138.0, 137.8, 137.7, 137.3,
136.9, 129.0, 128.6, 128.4, 128.2, 128.18, 128.15, 128.1, 127.93, 127.9,
127.87, 127.8, 127.76, 127.4, 127.3, 126.9, 126.1, 125.5, 101.4, 94.5 (C-
1, JCH = 172.5), 93.7 (C-1, JCH = 171.3), 82.8 (C-4), 79.3 (C-3), 78.9 (C-
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl-(11)-2,3-
di-O-benzyl-4-O-picoloyl-6-O-tertbutyldiphenylsilyl-α-D-
glucopyranoside 29: Rf 0.38 (Hexanes/EtOAc 3:1); [훼]2D0 +66.7 (c = 0.15,
CHCl3); 1H NMR (500 MHz, CDCl3): δ = 8.79 (d, J = 5.0 Hz, 1H), 7.94 (d,
J = 7.5 Hz, 1H), 7.80 (td, J = 2.0, 8.0 Hz, 1H), 7.68 – 6.95 (m, 36H), 5.65
(t, J = 10.0 Hz, 1H, H-4), 5.57 (s, 1H, benzylidene-H), 5.23 (d, J = 4.0 Hz,
1H, H-1), 5.16 (d, J = 4.0 Hz, 1H, H-1), 4.98 (d, J = 11.0 Hz, 1H), 4.88(t, J
= 14.5 Hz, 2H), 4.77 (q, J = 12.0 Hz, 2H), 4.68 (t, J = 11.5 Hz, 2H), 4.57
(d, J = 12.0 Hz, 1H), 4.34 (dt, J = 2.5, 10.0 Hz, 1H, H-5), 4.31 – 4.26 (dt,
J = 6.5, 12.5 Hz, 1H, H-5), 4.23 (t, J = 12.0 Hz, 1H, H-3), 4.158 (t, J =
11.5 Hz, 1H, H-4), 4.150 (dd, J = 4.5, 13.0 Hz, 1H, H-6a), 3.76 (dd, J = 4.0,
10.0 Hz, 1H, H-2), 3.73 – 3.63 (m, 2H including H-3, H-6b), 3.60 – 3.56
(m, 3H, including H-2, H-6a, and H-6b); 13C NMR (125 MHz,CDCl3): δ =
163.7 (C=O), 149.8, 148.0, 138.8, 138.3, 138.0, 137.96, 137.5, 136.8,
135.7, 135.6, 133.4, 133.2, 129.4, 129.3, 128.8, 128.5, 128.3, 128.14,
128.1, 128.0, 127.7, 127.52, 127.5, 127.46, 127.4, 127.39, 127.3, 126.7,
126.1, 125.5, 101.2 (benzylidene-C), 94.8 (H-1, JCH = 168.8 Hz), 94.2 (H-
1, JCH = 167.5 Hz) , 82.5 (C-3), 79.6 (C-2), 79.5 (C-3), 78.8 (C-2), 78.7
(C-4), 75.4, 75.3, 73.6, 73.5, 70.9 (C-4), 70.5 (C-5), 69.0 (C-6), 62.9 (C-
5), 62.0 (C-6) 60.4, 26.7, 19.2. HRMS‒ESI (m/z): [M + Na]+ calcd for
C69H71NNaO12Si+, 1156.4638; found, 1156.4658.
2), 75.4, 75.2, 73.8, 73.5, 71.7, 69.7 (C-5), 68.8 (C-6), 68.4 (C-2), 63.1
+
(C-5), 63.0 (C-6); HRMS‒ESI (m/z): [M + Na]+ calcd for C53H52N4NaO11
,
943.3525; found, 943.3537.
2-Azido-4,6-O-benzylidene-2-deoxy-3-O-naphthylmethyl-α-D-
galactopyranosyl-(11)-2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-
glucopyranoside 33: Rf 0.35 (Hexanes/EtOAc 2:1); [훼]2D0 +168 (c = 1.20,
CHCl3); 1H NMR (600 MHz, CDCl3): δ = 8.77 (d, J = 3.6 Hz, 1H), 8.03 (d,
J = 7.8 Hz, 1H), 7.93 (s, 1H), 7.85 (d, J = 9.6 Hz, 1H), 7.51 (d, J = 7.2 Hz,
2H), 7.46 (dd, J = 4.8, 6.0 Hz, 1H), 7.44 – 7.42 (m, 2H), 7.37 – 7.33 (m,
4H), 7.28 – 7.27 (m, 5H), 5.56 (t, J = 9.9 Hz, 1H, H-4), 5.39 (s, 1H,
benzylidene-H), 5.28 (s, 1H, J = 3.0 Hz, H-1), 5.24 (d, J = 3.0 Hz, 1H, H-
1), 5.00 (d, J = 12.0 Hz, 1H), 4.94 (d, J = 12.0 Hz, 1H), 4.80 (d, J = 11.8
Hz, 1H), 4.76 (d, J = 12.0 Hz, 1H), 4.67 (d, J = 11.4 Hz, 1H), 4.55 (t, J =
12.0 Hz, 2H), 4.47 – 4.45 (m, 2H including H-5), 4.18 – 4.10 (m, 4H
including H-3, H-2, and H-5), 4.01 (d, J = 12.6 Hz, 1H, H-6a), 3.89 (s, 1H,
H-5), 3.74 (dd, J = 3.5, 9.6 Hz, 1H, H-2), 3.66 – 3.63 (m, 2H including H-
6b and H-6a), 3.60 (dd, J = 3.6, 10.8 Hz, 1H, H-6b); 13C NMR (150 MHz,
CDCl3): δ = 164.0 (C=O), 149.8, 147.8, 138.0, 137.9, 137.6, 137.0, 135.5,
133.3, 133.1, 129.0, 128.5, 128.2, 128.1, 128.0, 127.9, 127.84, 127.75,
127.51, 127.46, 127.4, 127.0, 126.4, 126.20, 126.16, 126.0, 125.7, 125.6,
2,3-Di-O-benzyl-4,6-O-naphthylidene-α-D-galactopyranosyl-(11)-
36-di-O-benzyl-2-O-(2-naphthylmethyl)-4-O-picoloyl-α-D-
glucopyranoside 30: Rf 0.35 (Hexanes/EtOAc, 2:1); [훼]2D0 +157.5 (c =
0.80, CHCl3); 1H NMR (600 MHz, CDCl3): δ = 8.00 (d, J = 7.8 Hz, 1H), 7.99
(d, J = 7.8 Hz, 1H), 7.87– 7.76 (m, 7H), 7.70 (s, 1H), 7.61 (d, J = 7.8 Hz,
1H), 7.55 – 7.48 (m, 6H), 7.39 – 7.37 (m, 4H), 7.34 – 7.07 (m, 17H), 5.58
(t, J = 9.9 Hz, 1H, H-4), 5.55 (s, 1H, naphthylidene-H), 5.38 (s, 1H, H-1),
5.34 (d, J = 3.0 Hz, 1H, H-1), 4.98 – 4.74 (m, 7H), 4.71 (d, J = 12.0 Hz,
1H), 4.51 (dt, J = 3.0, 10.2 Hz, 1H, H-5), 4.45 (d, J = 11.9 Hz, 1H), 4.38
(d, J = 11.9 Hz, 1H), 4.27 (s, 1H), 4.24 (t, J = 9.6 Hz, 1H, H-3), 4.17 (s, 2H
including H-2), 4.13 (d, J = 12.6 Hz, 1H), 4.04 (s, 1H), 3.83 (dd, J = 3.5,
9.6 Hz, 1H, H-2), 3.73 (d, J = 11.8 Hz, 1H), 3.42 (dd, J = 2.5, 10.9 Hz, 1H),
3.35 (dd, J = 3.7, 11.0 Hz, 1H); 13C NMR (150 MHz, CDCl3): δ = 164.0
(C=O), 149.8, 147.8, 138.8, 138.6, 138.4, 137.7, 136.9, 135.3, 135.2,
133.7, 133.2, 133.0, 132.9, 128.4, 128.3, 128.2, 128.16, 128.1, 127.9,
127.9, 127.8, 127.8, 127.7, 127.7, 127.6, 127.6, 127.55, 127.4, 127.35,
127.3, 126.9, 126.4, 126.2, 126.18, 125.9, 125.7, 125.5, 125.47, 124.0,
101.1 (naphthylidene-C), 95.9 (C-1), 94.4 (C-1), 79.6 (C-2), 79.5 (C-3),
76.0, 75.3, 75.0, 74.4, 73.7, 73.6, 73.5, 71.8 (C-4), 71.6, 69.4 (C-6), 69.2
(C-5), 68.1 (C-6), 63.2 (C-5); HRMS‒ESI (m/z): [M + H]+ calcd for
C68H63NO12, 1086.4423; found, 1086.4410.
1
1
100.9 (benzylidene-C), 95.3 (C-1, JCH = 172.5 Hz), 94.1 (C-1, JCH
=
169.1 Hz), 79.5 ( 2 including C-2 and C-3), 75.3, 73.8, 73.5, 72.9, 71.8
(C-4), 71.4, 69.5 (C-5), 69.1 (C-6), 68.3 (C-6), 63.1 (C-5), 59.0; HRMS‒
ESI (m/z): [M + H]+ calcd for C57H54N4O11+, 971.3862; found, 971.3883.
3-O-Benzyl-4,6-O-benzylidene-2-deoxy-α-D-galactopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside 34: Rf 0.22
(Hexanes/EtOAc 2:1); [훼]2D0 +57.1 (c = 0.35, CHCl3); H NMR (500 MHz,
1
CDCl3): δ = 8.76 (m, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.82 (td, J = 8.0, 1.5 Hz,
1H), 7.55 – 7.09 (m, 23H), 5.51 (t, J = 9.5 Hz, 1H, H-4), 5.49 (s, 1H,
benzylidene-H), 5.41 (d, J = 2.0 Hz, 1H, H-1), 5.30 (d, J = 3.5 Hz, 1H, H-
1), 4.84 (d, J = 11.5 Hz, 1H), 4.73 (d, J = 12.0 Hz, 1H), 4.72 – 4.67 (m,
3H), 4.60 (d, J = 11.5 Hz, 1H), 4.47 (q, J = 12.0 Hz, 2H), 4.20 (dt, J = 2.8,
9.5 Hz, 1H, H-5), 4.16 (t, J = 9.5 Hz, 1H, H-3), 4.14 (s, 1H, H-5), 4.07 –
4.04 (m, 2H, including H-3 and H-6a), 3.82 (s, 1H, H-4), 3.74 – 3.69 (m,
2H, including H-2 and H-6b), 3.60 (qd, J = 3.0, 10.5 Hz, 2H, H-6a and H-
6b), 2.31 (ddd, J = 3.4, 12.5 Hz, 1H, H-2ax), 1.95 (dd, J = 13, 5 Hz, 1H, H-
2eq); 13C NMR (125 MHz, CDCl3): δ = 164.2 (C=O), 149.7, 147.7, 138.3,
138.2, 138.0, 137.7, 136.9, 128.7, 128.5, 128.4, 128.12, 128.1, 128.0,
4-O-Benzyl-2,3-O-isopropylidene-α-L-rhamnopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside 31: Rf 0.32
(Hexanes/EtOAc, 2/1); [훼]D20 +6.1 (c 1.65, CHCl3); 1H NMR (500 MHz,
CDCl3): δ 8.75 – 8.72 (m, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.78 (td, J = 1.5,
7.5 Hz, 1H), 7.47 – 7.44 (m, 1H), 7.37 – 7.08 (m, 20H), 5.47 (t, J = 10.0
Hz, 1H, H-4), 5.18 (s, 1H, H-1), 5.08 (d, J = 4.0 Hz, 1H, H-1), 4.91 (d, J =
12.0 Hz, 1H), 4.84 (d, J = 12.0 Hz, 1H), 4.79 (d, J = 12.0 Hz, 1H), 4.66 –
4.62 (m, 3H), 4.43 (q, J = 12.0 Hz , 2H), 4.35 (t, J = 5.5 Hz, 1H, H-3), 4.29
(d, J = 6.0 Hz, 1H, H-2), 4.20 (dt, J = 3.5, 10.0 Hz, 1H, H-5), 4.14 (t, J =
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10.1002/chem.201700785
Chemistry - A European Journal
FULL PAPER
127.9, 127.7, 127.7, 127.67, 127.4, 127.39, 126.9, 126.3, 125.7, 100.7,
95.3 (C-1), 93.4 (C-1), 79.6 (C-2), 79.2 (C-3), 75.2, 73.6, 72.8 (C-5), 72.0
(C-4), 71.16, 70.1, 69.8 (C-6), 69.4 (C-5), 68.6 (C-6), 63.2 (C-4), 30.4 (C-
2); HRMS‒ESI (m/z): [M + Na]+ calcd for C53H53NNaO11+, 902.3511; found,
902.3510.
3-O-Benzyl-4,6-O-benzylidene-2-deoxy-α-D-glucopyranosyl-(11)-
2-azido-3,6-tri-O-benzyl-2’-deoxy-4-O-picoloyl-α-D-
glucopyranoside 39: Rf 0.24 (Hexanes/EtOAc, 2/1); [휶]ퟐ퐃ퟎ +46.7 (c = 0.30,
CHCl3); 1H NMR (500 MHz, CDCl3): δ = 8.76 (m, 1H), 8.10 (d, J = 9.5 Hz,
1H), 7.84 (td, J = 9.5, 2 Hz, 1H), 7.58 – 7.08 (m, 21H), 5.65 (s, 1H,
benzylidene-H), 5.52 (t, J = 11.5 Hz, 1H, H-4), 5.245 (d, J = 4.0 Hz, 1H,
H-1), 5.238 (d, J = 3.0 Hz, 1H, H-1), 4.94 (d, J = 14.5 Hz, 1H), 4.83 (d, J
= 13.5 Hz, 1H), 4.77 (d, J = 14.5 Hz, 1H), 4.68 (d, J = 13.5 Hz, 1H), 4.47
(s, 2H), 4.31 (dd, J = 6.0, 13.0 Hz, 1H, H-6a), 4.26 (t, J = 12.0 Hz, 1H, H-
3), 4.19 – 4.05 (m, 3H including H-3 and H-5), 3.80 – 3.71 (m, 2H including
H-4 and H-6b), 3.63 (dd, J = 13, 5 Hz, 1H, H-2), 3.63 – 3.57 (m, 2H, H-6a
and H-6b), 2.31 (dd, J = 6.0, 17.0 Hz, 1H, H-2eq), 1.91 (ddd, J = 5.0, 14.0,
17.5 Hz, 1 H, H-2ax); 13C NMR (125 MHz, CDCl3): δ = 164.1 (C=O), 149.8,
147.4, 138.7, 137.6, 137.55, 137.4, 137.0, 128.9, 128.4, 128.2, 128.19,
128.17, 128.1, 128.0, 127.97, 127.84, 127.8, 127.77, 127.7, 127.68, 127.6,
127.5, 127.2, 126.1, 125.8, 101.3, 93.8 (C-1, JCH = 170.5 Hz), 93.1 (C-1,
JCH = 171.1 Hz), 83.8 (C-4), 77.8 (C-3), 75.1, 73.6, 73.4, 72.8, 72.4 (C-4),
69.7 (C-5), 68.9 (C-6), 68.7 (C-6), 63.8, 62.8, 36.0 (C-2); HRMS‒ESI
(m/z): [M + H]+ calcd for C46H47N4O10+, 815.3287; found, 815.3318.
3-O-Benzyl-4,6-O-benzylidene-2-deoxy-α-D-glucopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside 35: Rf 0.22
(Hexanes/EtOAc 2:1); [훼]D20 +86.2 (c 0.65, CHCl3); 1H NMR (500 MHz,
CDCl3): δ = 8.73 (m, 1H), 8.06 (d, J = 10.0 Hz, 1H), 7.81 (td, J = 9.5, 2 Hz,
1H), 7.54 – 7.03 (m, 26H), 5.63 (s, 1H, benzylidene-H), 5.45 (t, J = 12.0
Hz, 1H, H-4), 5.23 (d, J = 4.0 Hz, 1H, H-1), 5.19 (d, J = 4.5 Hz, 1H, H-1),
4.91 (d, J = 14.5 Hz, 1H), 4.83 (d, J = 14.0 Hz, 1H), 4.77 – 4.60 (m, 4H),
4.44 (d, J = 3.5 Hz, 2H), 4.23 – 4.09 (m, 5H including H-3 and H-3), 3.78
– 3.67 (m, 3H including H-2), 3.60 – 3.50 (m, 2H), 2.30 (dd, J = 6.0, 16.5
Hz, 1H, H-2eq), 1.88 (ddd, J = 5.0, 14.0, 17.0, 1H, H-2ax); 13C NMR (125
MHz, CDCl3): δ = 164.2 (C=O), 149.7, 147.7 138.8 138.3 137.7, 137.7,
136.9, 128.8, 128.5, 128.46, 128.4 128.1, 128.0, 127.97, 127.8, 127.8,
127.6, 127.55, 127.4, 127.3, 128.0, 126.2, 125.7, 101.4, 94.0 (C-1), 93.0
(C-1), 83.9 (C-2), 79.0, 78.9, 75.3, 73.6, 73.5, 73.3, 72.9, 71.9 (C-4), 69.4,
69.0, 68.7, 63.4, 36.2; HRMS‒ESI (m/z): [M
C53H53NNaO11+, 902.3511; found, 902.3532.
+
Na]+ calcd for
3-O-Benzyl-4,6-O-benzylidene-2-deoxy-α-D-galactopyranosyl-(11)-
2-azido-3,6-tri-O-benzyl-2-deoxy-4-O-picoloyl-α-D-
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl-(11)-2-
azido-3,6-di-O-benzyl-2’-deoxy-4-O-picoloyl-α-D-glucopyranoside
37: Rf 0.36 (Hexanes/EtOAc, 2/1); [훼]2D0 +44.4 (c = 0.45, CHCl3); 1H NMR
(500 MHz, CDCl3): δ = 8.77 (m, 1H), 7.97 (d, J = 7.5 Hz, 1H), 7.81 (td, J =
8.0, 2.0 Hz, 1H), 7.55 – 7.11 (m, 26H), 5.58 (s, 1H, benzylidene-H), 5.53
(t, J = 9.5 Hz, 1H, H-4), 5.23 (d, J = 3.5 Hz, 1H, H-1), 5.19 (d, J = 3.5 Hz,
1H, H-1), 5.03 (d, J = 11.5 Hz, 1H), 4.92 (d, J = 11.5 Hz, 1H), 4.83 (d, J =
10.5 Hz, 1H), 4.78 (d, J = 12.0 Hz, 1H), 4.71 (d, J = 11.0 Hz, 2H), 4.47
(ddd, J = 1.0, 4.0, 10.5 Hz, 1H, H-5),4.44 (d, J = 12.0 Hz, 1H), 4.40 (d, J
= 12.0 Hz, 1H), 4.33 (dd, J = 5.0, 10.0 Hz, 1H, H-6a), 4.26 (t, J = 10.0 Hz,
1H, H-3), 4.19 (td, J = 5.0, 10.0 Hz, 1H, H-5), 4.14 (t, J = 9.5 Hz, 1H, H-
3), 3.74 – 3.70 (m, 2H, including H-6b and H-2), 3.65 (t, J = 9.5 Hz, 1H,
H-4), 3.61 (dd, J = 3.5, 14.5 Hz, 1H, H-2), 3.43 (qd, J = 3.0, 11.0 Hz, 2H,
H-6a and H-6b); 13C NMR (125 MHz, CDCl3) δ = 163.9 (C=O), 149.8,
147.5, 138.7, 138.0, 137.6, 137.4, 137.37, 136.9, 128.9, 128.4, 128.3,
128.27, 128.23, 128.2, 128.1, 128.0, 127.83, 127.8, 127.7, 127.6, 127.4,
127.0, 126.0, 125.6, 101.2, 94.7 (C-1, JCH = 169.3 Hz), 94.1 (C-1, JCH
=170.5 Hz), 82.3 (C-4), 78.6 (C-3), 78.3 (C-2), 78.2 (C-3), 75.3, 75.25,
73.64, 73.6, 72.3 (C-4), 69.6 (C-5), 69.0 (C-6), 68.3 (C-6), 63.3 (C-5),
63.2 (C-2); HRMS‒ESI (m/z): [M + H]+ calcd for C53H62N4O11+, 921.3705;
found, 921.3729.
glucospyranoside 40: Rf 0.16 (Hexanes/EtOAc, 3/1); [휶]ퟐ퐃ퟎ +89.6 (c =
5.20, CHCl3); 1H NMR (500 MHz, CDCl3): δ = 8.78 – 8.75 (m, 1H), 8.10 (d,
J = 7.5 Hz, 1H), 7.84 (td, J = 10, 2.5 Hz, 1H), 7.57 – 7.12 (m, 21H), 5.59
(s, 1H, benzylidene-H), 5.54 (t, J = 12.0 Hz, 1H, H-4), 5.44 (d, J = 3.0 Hz,
1H, H-1), 5.29 (d, J = 3.5 Hz, 1H, H-1), 4.82 – 3.63 (m, 4H), 4.49 (dd, J =
15.0, 1H), 4.45 (dd, J = 15.0, 1H), 4.28 (dd, J = 2.0, 14.0 Hz, H-6a), 4.26
(s, 1H, H-5), 4.23 (t, J = 12.0 Hz, 1H, H-3), 4.16 (dt, J = 5.0, 15.0 Hz, 1H,
H-5), 4.10 – 4.02 (m, 2H including H-3 and H-6b), 3.82 (s, 1H, H-4), 3.64
– 3.56 (m, 3H including H-2, H-6a and H-6b), 2.35 (td, J = 4.5, 16.0 Hz,
1H, H-2ax), 1.95 (dd, J = 6.0, 16.5 Hz, 1H, H-2eq); 13C NMR (125 MHz,
CDCl3): δ = 164.1(C=O), 149.8, 147.4, 138.3, 137.9, 137.6, 137.4, 137.0,
128.8, 128.4, 128.2, 128.18, 128.1, 127.96, 127.9, 127.7, 127.65, 127.5,
127.2, 126.3, 125.8, 100.8, 94.2 (C-1, JCH = 170.3), 92.9 (C-1, JCH = 172.3),
77.6 (C-3), 74.9, 73.6, 72.7, 72.5 (C-5), 71.3 (C-4), 70.4 (C-3), 70.0 (C-
6), 69.6 (C-5), 68.6 (C-6), 63.8 (C-4), 62.8 (C-2), 30.6 (C-2); HRMS‒ESI
(m/z): [M + Na]+ calcd for C46H46N4NaO10+, 837.3106; found, 837.3106.
2,3-Di-O-benzyl-4,6-O-benzylidene-α-D-galactopyranosyl-(11)-2-
azido-3,6-di-O-benzyl-2-deoxy-4-O-picoloyl-α-D-glucopyranoside
2-Azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-α-D-glucopyranosyl-
(11)-2-azido-3,6-di-O-benzyl-4-O-picoloyl-α-D-glucopyranoside
41: Rf 0.2 (Hexanes/EtOAc, 3/1); [휶]ퟐ퐃ퟎ +70.9 (c = 3.50, CHCl3); H NMR
1
38: Rf 0.3 (Hexanes/EtOAc, 3/1); [휶]ퟐ퐃ퟎ +27.9 (c = 0.73, CHCl3); H NMR
1
(500 MHz, CDCl3): δ = 8.72 – 8.69 (m, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.73
(td, J = 8, 2 Hz, 1H), 7.48 – 7.39 (m, 5H), 7.32 – 7.02 (m, 21H), 5.48 (t, J
= 9.5 Hz, 1H, H-4), 5.44 (s, 1H, benzylidene-H), 5.28 (d, J = 3.0 Hz, 1H,
H-1), 5.19 (d, J = 3.5 Hz, 1H, H-1), 4.81 – 4.74 (m, 3H), 4.70 (d, J = 10.5
Hz, 1H), 4.65 – 4.58 (m, 2H), 4.39 (ddd, J = 2.0, 4.0, 6.5 Hz, 1H, H-5),
4.37 (d, J = 12.0 Hz, 1H), 4.31 (d, J = 12.0 Hz, 1H), 4.25 (d, J = 2.5 Hz,
1H, H-4), 4.20 (dd, J = 1.5, 12.5 Hz, 1H, H-6a), 4.16 (t, J = 10.0 Hz, 1H, H-
3), 4.06 (qd, J = 3.5, 10.5 Hz, 2H including H-2 and H-3), 3.99 (dd, J = 1.5,
12.5 Hz, 1H, H-6b), 3.86 (s, 1H, H-5), 3.55 (dd, J = 3.0, 10.0 Hz, 1H, H-2),
3.35 (dd, J = 3.0, 11.0 Hz, 2H, H-6a), 3.28 (dd, J = 4.0, 11.0 Hz, 2H, H-
6b); 13C NMR (125 MHz, CDCl3): δ = 163.8 (C=O), 149.8, 147.5, 138.7,
138.5, 137.8, 137.6, 137.4, 136.9, 128.9, 128.3, 128.2, 128.16, 128.11,
128.1, 127.9, 127.8, 127.75, 127.7, 127.67, 127.6, 127.4, 127.3, 127.0,
126.3, 125.5, 101.0, 94.7 (C-1, JCH = 172.8 Hz), 93.5 (C-1, JCH = 168.3
Hz) , 78.0 (C-3), 76.1, 74.9, 74.7, 74.2 (C-4), 73.8, 73.6, 72.2 (C-4), 71.7,
69.4 (C-6), 69.3 (C-5), 68.1 (C-6), 63.6 (C-5), 62.9 (C-2); HRMS‒ESI
(m/z): [M + H]+ calcd for C53H62N4O11+, 921.3705; found, 921.3739.
(500 MHz, CDCl3): δ = 8.78 (d, J = 5.0 Hz, 1H), 8.03 (d, J = 10.0 Hz, 1H),
7.82 (td, J = 10.0, 2.0 Hz, 1H), 7.55 – 7.11 (m, 21H), 5.62 (s, 1H,
benzylidene-H), 5.55 (t, J = 12.5 Hz, 1H, H-4), 5.22 (d, J = 4.5 Hz, 1H, H-
1), 5.16 (d, J = 4.5 Hz, 1H, H-1), 5.05 (d, J = 13.5 Hz, 1H), 4.89 (d, J =
13.5 Hz, 1H), 4.83 (d, J = 13.5 Hz, 1H), 4.71 (d, J = 13.5 Hz, 1H), 4.53 (d,
J = 15.0 Hz, 1H), 4.46 (d, J = 15.0 Hz, 1H),, 4.41 (dt, J = 4.0, 9.0 Hz, 1H,
H-5), 4.34 (dd, J = 6.0, 10.0 Hz, 1H, H-6a), 4.25 (t, J = 12 Hz, 1H, H-3),
4.19 – 4.13 (m, 2H, including H-3 and H-5), 3.77 (t, J = 12.0 Hz, 2H
including H-4 and H-6b), 3.70 (dd, J = 5.0, 13.0 Hz, 1H, H-2), 3.63 – 3.59
(m, 3H including H-2, H-6a, and H-6b); 13C NMR (125 MHz, CDCl3) δ =
163.9 (C=O), 149.9, 147.4, 137.8, 137.6, 137.3, 137.1, 137.0, 129.1, 128.4,
128.3, 128.24, 128.2, 128.17, 128.1, 128.0, 127.7, 127.5, 127.1, 126.0,
125.6, 101.4, 94.1 (C-1), 93.5 (C-1), 82.6 (C-4), 78.1 (C-3), 76.8 (C-3),
75.3, 75.25, 73.5, 72.1 (C-4), 69.9, 68.8 (C-6), 68.3 (C-6), 63.5 (C-5), 62.9
+
(C-2), 62.8 (C-2); HRMS‒ESI (m/z): [M + H]+ calcd for C46H46N7O10
,
856.3301; found, 856.3300.
This article is protected by copyright. All rights reserved.

10.1002/chem.201700785
Chemistry - A European Journal
FULL PAPER
3,4,5-Tri-O-Acetyl-2-N-(2,2,2-trichloroethoxycarbonyl)-β-D-
130.2, 129.7, 128.4, 128.3, 128.27, 128.2, 128.16, 128.03, 128.0, 127.99,
127.96, 127.84, 127.80, 127.75, 127.62, 127.6, 127.54, 127.5, 127.3,
127.1, 126.7, 125.4, 101.7 (C-1, JCH = 158.3 Hz), 99.0 (C-1, JCH = 168.0
Hz) , 82.6 (C-3), 78.9 (C-2), 78.6 (C-3), 77.8 (C-4), 75.5 (C-5), 75.0, 73.7,
73.5, 72.3, 71.2 (C-4), 69.8 (C-5), 68.6 (C-6), 68.1 (C-6). HRMS‒ESI
(m/z): [M + Na]+ calcd for C67H65NNaO13+, 1114.4348; found, 1114.4348.
glucopyranosyl-(11)-2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-
glucopyranoside 47: Rf 0.2 (Hexanes/EtOAc, 2/1); [휶]ퟐ퐃ퟎ +26.7 (c = 1.20,
CHCl3); 1H NMR (500 MHz, CDCl3): δ = 8.78 (d, J = 4.5 Hz, 1H), 8.00 (d,
J = 8.0 Hz, 1H), 7.83 (td, J = 2.0, 10.0 Hz, 1H), 7.52 – 7.48 (m, 1H), 7.37
– 7.18 (m, 10H), 7.12 – 7.04 (m, 5H), 6.70 (d, J = 6.5 Hz, 1H, NH), 5.75 (t,
J = 10.0 Hz, 1H, H-3), 5.51 (d, J = 8.5 Hz, 1H, H-1), 5.47 (d, J = 3.0 Hz, H-
1), 5.19 (t, J = 10.0 Hz, 1H, H-4), 5.00 (t, J = 10.0 Hz, 1H, H-4), 4.88 –
4.69 (m, 4H), 4.65 (d, J = 11.0 Hz, 1H), 4.59 – 4.54 (m, 2H), 4.49 (dt, J =
2.5, 7.5 Hz, 1H, H-5), 4.38 (d, J = 11.5 Hz, 1H), 4.31 (dd, J = 4.5, 12.5 Hz,
1H, H-6a), 4.16 (t, J = 9.5 Hz, 2H, including H-3 and H-6b), 3.86 (broad d,
J = 7.0 Hz, 1H, H-5), 3.65 (dd, J = 3.5, 9.5 Hz, 1H, H-2), 3.62 – 3.53 (m,
2H, H-6a and H-6b), 3.43 (q, J = 9.0 Hz, 1H, H-2), 2.05 (s, 3H, OCH3),
2.02 (s, 3H, OCH3), 1.81 (s,3H, OCH3);13C NMR (125 MHz, CDCl3): δ =
170.6, 169.8, 169.7, 164.0, 153.8, 149.9, 147.2, 138.1, 137.6, 137.0, 128.4,
128.3, 128.1, 128.0, 127.9, 127.8, 127.7, 127.4, 127.1, 125.6, 96.9 (C-1,
JCH = 164.4 Hz), 95.8, 92.5 (C-1, JCH = 172.6 Hz), 78.6 (C-2), 78.5 (C-3),
75.5, 74.0, 73.9, 72.7, 72.3 (C-5), 71.7 (C-4), 70.4 (C-3), 69.9 (C-6), 69.6
6-O-Acetyl-4-O-benzyl-3-O-(2-naphthylmethyl)-2-N-phthalimido-β-D-
galactopyranosyl-(11)-2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-
glucopyranoside 50: Rf = 0.26 (hexanes/CH2Cl2/EtOAc, 3/1/1); [휶]퐃ퟐퟎ
-
26.0 (c = 2.0, CHCl3); 1H NMR (500 MHz, CDCl3): δ = 8.66 (d, J = 4.5 Hz,
1H), 7.80 (d, J = 7.5 Hz, 1H), 7.70 – 6.90 (m, 31H), 6.75 (d, J = 6.5 Hz,
2H), 5.29 (t, J = 10.0 Hz, 1H, H-4), 5.21 (d, J = 8.5 Hz, 1H, H-1), 5.03 (d,
J = 11.5 Hz, 1H), 4.80 (d, J = 12.0 Hz, 1H), 4.77 (dd, J = 2.5, 11.0 Hz, 1H,
H-2), 4.70 (d, J = 3.0 Hz, 1H, H-1), 4.65 (d, J = 11.5 Hz, 1H), 4.46 (d, J =
12.5 Hz, 1H), 4.41 (dd, J = 2.5, 11.5 Hz, 1H, H-3), 4.39 (d, J = 11.0 Hz,
1H), 4.35 (d, J = 11.5 Hz, 1H), 4.30 –4.27 (m, 2H), 4.24 (dt, J = 3.0, 10.0
Hz, 1H, H-5), 4.08 (d, J = 6.5 Hz, 2H), 3.97 (d, J = 12.5 Hz, 1H, H-6a),
3.91 (s, 1H, H-4), 3.89 (t, J = 9.5 Hz, 1H, H-3), 3.71 (t, J = 6.5 Hz, 1H),
3.66 (d, J = 12.5 Hz, 1H, H-6b), 3.42 (dd, J = 2.5, 11.0 Hz, 1H, H-6a), 3.32
(dd, J = 3.0, 11.0 Hz, 1H, H-6b), 3.24 (dd, J = 9.5 Hz, 1H, H-2), 1.82 (s,
3H, CH3); 13C NMR (125 MHz, CDCl3): δ = 170.4, 168.9, 167.7, 163.5,
149.7, 147.6, 138.1, 138.06, 137.7, 137.6, 136.7, 135.0, 133.4, 133.0,
132.7, 131.8, 131.4, 128.5, 128.4, 128.1, 128.06, 128.0, 127.99, 127.9,
127.82, 127.8, 127.77, 127.5, 127.4, 127.3, 127.2, 127.1, 126.6, 126.58,
126.1, 125.8, 125.6, 125.3, 122.8, 122.4, 100.1 (C-1, JCH = 141 Hz), 99.8
(C-1, J = 165.5 Hz), 78.7 (C-3), 78.1 (C-2), 77.1 (C-3), 74.8, 74.6, 73.4,
(C-5), 68.8 (C-4), 62.2 (C-6), 56.0 (C-2), 20.7, 20.6, 20.5; HRMS‒ESI
+
(m/z): [M
+
Na]+ calcd for C48H51Cl3N2NaO16
,
1039.2196; found,
1039.2254.
3,5-Di-O-acetyl-4-O-benzyl-2-N-(2,2,2-trichloroethoxycarbonyl)-β-D-
glucopyranosyl-(11)-2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-
glucopyranoside 48: Rf 0.22 (Hexanes/EtOAc, 3/2); [휶]ퟐ퐃ퟎ +40.0 (c = 0.45,
CHCl3); 1H NMR (500 MHz, CDCl3): δ = 8.76 (d, J = 4.0 Hz, 1H), 8.00 (d,
J = 7.5 Hz, 1H), 7.82 (td, J = 2.0, 8.0 Hz, 1H), 7.51 – 7.47 (m, 1H), 7.36 –
7.17 (m, 17H), 7.12 – 7.05 (m, 4H), 6.23 (d, J = 7.0 Hz, 1H, NH), 5.60 (t, J
= 10.0 Hz, 1H, H-3), 5.36 (d, J = 3.0 Hz, 1H, H-1), 5.28 (t, J = 10.0 Hz, 1H,
H-4), 5.23 (d, J = 5.0 Hz, 1H, H-1), 4.92 (d, J = 12.0 Hz, 1H), 4.84 (d, J =
11.5 Hz, 1H), 4.73 – 4.51 (m, 7H), 4.46 (ddd, J = 2.5, 7.0, 9.5 Hz, 1H, H-
5), 4.41 – 4.35 (m, 3H including H-6a), 4.21 (dd, J = 4.5, 12.0 Hz, 1H, H-
6b), 4.15 (t, J = 9.5 Hz, 1H, H-3), 3.74 –3.68 (m, 1H, H-5), 3.65 (dd, J =
4.0, 10.0 Hz, 1H, H-2), 3.61 – 3.51 (m, 3H, including H-4, H-6a, and H-
6b), 3.44 (q, J = 8.5 Hz, 1H, H-2), 2.00 (s, 3H, OCH3), 1.82 (s, 3H, OCH3);
13C NMR (125 MHz, CDCl3): δ = 170.5, 169.9, 164.0, 153.9, 149.9, 147.3,
138.2, 137.7, 137.24, 137.2, 136.9, 128.53, 128.5, 128.3, 128.1, 128.0,
72.7, 72.4, 72.0, 71.9 (C-4), 70.9 (C-4), 69.6 (C-5), 67.9 (C-6), 63.0, 52.8
+
(C-2), 20.7; HRMS‒ESI (m/z): [M + Na]+ calcd for C67H62N2NaO14
,
1141.4093; found, 1141.4097. For 1α1α anomer of 50: Rf = 0.46
(hexanes/CH2Cl2/EtOAc 3/1/1); 1H NMR (500 MHz, CDCl3): δ = 8.79 (d, J
= 4.0 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H), 7.76 – 7.73 (m, 2H), 7.69 – 7.60
(m, 5H), 7.49 (dd, J = 7.5, 14.5 Hz, 2H), 7.41 – 7.37 (m, 3 H), 7.34 – 7.26
(m, 12 H), 7.21 (dd, J = 1.5, 7.5 Hz, 2H), 7.16 – 7.10 (m, 6H), 7.00 (dd, J
= 2.0, 7.5 Hz, 2H), 5.48 (dd, J = 2.5, 12.5 Hz, 1H, H-3), 5.35 (d, J = 3.5 Hz,
H-1), 5.27 (d, J = 3.5 Hz, H-1), 5.20 (t, J = 10.0 Hz, 1H, H-4), 5.12 (dd, J
= 3.5, 11.5 Hz, 1H, H-2), 5.00 (d, J = 10.5 Hz, 1H), 4.98 (d, J = 10.5 Hz,
1H), 4.92 (d, J = 11.0 Hz, 1H), 4.89 (d, J = 11.0 Hz, 1H), 4.76 – 4.71 (m,
3H), 4.64 (d, J = 11.5 Hz, 1H), 4.43 (t, J = 6.5 Hz, 1H, H-5), 4.221 (t, J =
10.0 Hz, 1H, H-3), 4.216 (dd, J = 3.0, 9.5 Hzz, Hz, 1H, H-6a), 4.15 (d, J =
9.0 Hz, 1H), 4.14 (s, 1H, H-4), 4.10 – 4.07 (m, 2H including H-6b), 3.65
(dd, J = 3.5, 10.0 Hz, 1H, H-2), 3.44 (dt, J = 4.0, 10.0 Hz, 1H, H-5), 2.98
(d, J = 4.0 Hz, H-6  2), 1.89 (s, 3H, CH3); 13C NMR (125 MHz, CDCl3): δ
= 170.2 (C=O), 168.5 (C=O), 168.3 (C=O), 163.5 (C=O), 149.8, 147.7,
138.4, 137.98, 137.94, 137.6, 136.5, 135.5, 133.7, 133.5, 133.2, 132.8,
132.2, 131.1, 128.42, 128.39, 128.3, 128.01, 127.98, 127.96, 127.8,
127.58, 127.56, 127.47, 127.25, 127.24, 126.7, 126.1, 126.0, 125.8, 125.5,
125.0, 94.9 (C-1, JCH = 171.5 Hz), 92.7 (C-1, JCH = 172.0 Hz), 78.8 (C-
2), 78.7 (C-3), 75.3, 74.6, 73.9 (C-3), 73.1, 73.0, 72.2, 71.7 (C-4), 71.5,
69.9, (C-5), 69.2 (C-5), 68.2 (C-6), 62.9 (C-6), 51.7 (C-2), 20.7 (CH3).
127.93, 127.9, 127.85, 127.8, 127.7, 127.4, 127.0, 125.6, 98.2 (C-1, JCH
=
163.5 Hz), 95.8, 94.0 (C-1, JCH = 169.8 Hz), 79.1 (C-2), 78.6 (C-3), 76.0
(C-4), 75.4, 74.3, 74.1, 73.9, 73.4 (C-5), 73.1 (C-3), 72.8, 71.6 (C-4), 69.6
(C-6), 69.5 (C-5), 63.0 (C-6), 56.4 (C-2), 20.8, 20.7; HRMS‒ESI (m/z): [M
+ Na]+ calcd for C53H55Cl3N2NaO15+, 1087.2560; found, 1087.2563.
2-O-Benzoyl-3,4,6-tri-O-benzyl-β-D-glucopyranosyl-(11)-2,3,6-tri-
O-benzyl-4-O-picoloyl-α-D-glucopyranoside
49:
Rf
0.3
(Hexanes/EtOAc, 2/1); [휶]퐃ퟐퟎ +30.0 (c = 0.4, CHCl3); 1H NMR (500 MHz,
CDCl3): δ = 8.68 – 8.65 (m, 1H), 7.95 (d, J = 7.0 Hz, 2H), 7.83 (d, J = 8.0
Hz, 1H), 7.67 (td, J = 1.5, 7.5 Hz, 1H), 7.41 (t, J = 7.5 Hz, 1H), 7.39 – 7.35
(m, 1H), 7.29 – 7.02 (m, 26H), 6.99 – 6.93 (m, 5H), 6.88 (d, J = 6.5 Hz,
2H), 5.35 (t, J = 10.0 Hz, 1H, H-4), 5.34 (t, J = 8.5 Hz, 1H, H-2), 4.90 (d,
J = 3.5 Hz, 1H, H-1), 4.77 (d, J = 10.5 Hz, 1H), 4.70 (d, J = 11.0 Hz), 4.66
(d, J = 8.0 Hz, H-1), 4.64 (d, J = 11.0 Hz, 1H), 4.56 – 4.50 (m, 2H), 4.46
(d, J = 12.0 Hz, 1H), 4.38 (d, J = 11.5 Hz, 2H), 4.27 (q, J = 12.0 Hz, 3H
including H-5), 4.17 (d, J = 12.5 Hz, 1H), 4.06 (d, J = 12.0 Hz, 1H), 4.01
(t, J = 9.5 Hz, 1H, H-3), 3.80 (t, J = 9.0 Hz, 1H, H-3), 3.75 (t, J = 9.5 Hz,
1H, H-4), 3.61 (m, 2H, H-6a and H-6b), 3.47 (td, J = 3.0, 9.5 Hz, 1H, H-5),
3.45 – 3.39 (m, 2H including H-2 and H-6a), 3.32 (dd, J = 3.5, 11.0 Hz,
1H, H-6b); 13C NMR (125 MHz, CDCl3): δ = 164.9 (C=O), 163.7 (C=O),
149.8, 147.7, 138.3, 138.1, 138.0, 137.9, 137.8, 137.79, 136.7, 132.9,
2-O-Benzoyl-3,4,6-tri-O-benzyl-β-D-galactopyranosyl-(11)-2,3,6-
tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside 51: For 1β1α
anomer, Rf 0.2 (Hexanes/EtOAc, 2/1); [휶]ퟐ퐃ퟎ +81 (c = 2.10, CHCl3); 1H
NMR (500 MHz, CDCl3): δ = 8.72 (d, J = 5.0 Hz, 1H), 8.02 (d, J = 9.5 Hz,
2H), 7.87 (d, J = 9.5 Hz, 1H), 7.72 (t, J = 9.5 Hz, 1H), 7.48 (t, J = 9.0 Hz,
1H), 7.45 – 6.95 (m, 31H), 6.92 (d, J = 8.5 Hz, 2H), 5.76 (dd, J = 10.0, 12.5
Hz, 1H, H-2), 5.36 (t, J = 12.5 Hz, 1H, H-4), 5.02 (d, J = 14.0 Hz, 1H), 4.98
(d, J = 3.5 Hz, 1H, H-1), 4.70 (d, J = 10.0 Hz, 1H, H-1), 4.68– 4.57 (m,
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10.1002/chem.201700785
Chemistry - A European Journal
FULL PAPER
4H), 4.51 (d, J = 15.0 Hz, 1H), 4.44 (d, J = 14.0 Hz, 1H), 4.38 – 4.28 (m,
5H), 4.24 (d, J = 15.5 Hz, 1H), 4.12 (d, J = 15.5 Hz, 1H), 4.07 (t, J = 13.0
Hz, 1H, H-3), 4.03 (d, J = 3.0 Hz, H-4), 3.67 (dd, J = 3.0, 12.5 Hz, 1H, H-
3), 3.63 – 3.61 (m, 2H), 3.53 (dd, J = 1.5, 15.5 Hz, 1H), 3.50 3.44 (m, H-
2 and H-6a), 3.37 (dd, J = 5.0, 14.0 Hz, 1H, H-6b); 13C NMR (125 MHz,
CDCl3): δ = 165.0, 163.6, 149.8, 147.7, 138.5, 138.3, 138.0, 137.9, 137.8,
137.6, 136.7, 132.8, 130.4, 129.8, 128.4, 128.3, 128.3, 128.27, 128.2,
128.1, 128.0, 127.95, 127.9, 127.8, 127.74, 127.7, 127.6, 127.55, 127.4,
1H, H-4), 5.13 (t, J = 9.5 Hz, 1H, H-4), 4.95 (d, J = 10.5 Hz, 1H), 4.85 (d,
J = 8.5 Hz, 1H, H-1), 4.83 (d, J = 7.5 Hz, 1H, H-1), 4.81 – 4.59 (m, 3H),
4.48 (s, 2H), 4.28 (dd, J = 4.5, 12.0 Hz, 1H, H-6a), 4.15 (dd, J = 2.5, 12.5
Hz, 1H, H-6b), 3.89 – 3.83 (m, 3H, including H-2, H-3 and H-5), 3.72 –
3.67 (m, 1H, H-5), 3.64 (m, 2H, H-6), 3.54 (t, J = 8.0 Hz, 1H, H-2), 2.08
(s, 3H, OCH3), 2.04 (s, 3H, OCH3), 2.03 (s, 3H, OCH3); 13C NMR (125 MHz,
CDCl3): δ = 170.7, 170.5, 169.4, 164.1, 154.4, 149.8, 147.4, 138.1, 138.0,
137.7, 136.9, 128.6, 128.4, 128.3, 128.1, 127.8, 127.78, 127.4, 127.0,
125.6, 99.7 (C-1, JCH = 162.0 Hz), 97.5 (C-1, JCH = 161.3 Hz), 95.6 (CCl3),
81.3 (C-2), 81.0 (C-3), 75.2, 74.8, 74.5, 73.7, 73.3 (C-5), 72.4 (C-4), 72.1
(C-5), 72.0 (C-3), 69.7 (C-6), 68.4 (C-4), 62.0 (C-6), 56.0 (C-2), 22.7
127.2, 127.1, 126.6, 125.4, 102.1 (C-1, JCH = 156.5 Hz), 98.8 (C-1, JCH
=
172.7 Hz), 79.8 (C-3), 78.8 (C-2), 78.6 (C-3), 75.0, 74.7, 73.9, 73.4, 73.3,
72.5, 72.2 (C-4), 71.8, 71.7 (C-2), 71.2 (C-4), 69.6 (C-5), 68.3 (C-6);
HRMS‒ESI (m/z): [M + Na]+ calcd for C67H65NNaO13+, 1114.4348; found,
1114.4329.
(CH3CO), 20.7 (CH3CO), 20.6 (CH3CO); HRMS‒ESI (m/z): [M + Na]+ calcd
+
for C48H51Cl3N2NaO16
, 1039.2196; found, 1039.2213. For 1β1α
anomer of 57: Rf = 0.30 (hexanes/EtOAc 1/1); 1H NMR (500 MHz, CDCl3):
δ = 8.77 (d, J = 4.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.83 (dd, J = 1.5, 7.5
Hz, 1H), 7.50 (d, J = 1.0, 6.0 Hz, 1H, 7.35 – 7.20 (m, 10H), 7.11 – 7.06 (m,
5H), 6.70 (d, J = 7.0 Hz, NH), 5.75 (t, J = 10.0 Hz, H-3), 5.50 (d, J = 9.0
Hz, H-1), 5.46 (d, J = 3.0 Hz, H-1), 5.19 (t, J = 10.0 Hz, 1H, H-4), 4.99 (t,
J = 10.0 Hz, H-4), 4.87 – 4.82 (m, 2H), 4.74 (d, J = 12.0 Hz, 1H), 4.71 (d,
J =12.0 75.5 Hz, 1H), 4.65 (d, J = 11.0 Hz, 1H), 4.59 – 4.54 (m, 2H), 4.49
(dt, J = 2.5, 8.0 Hz, 1H, H-5), 4.38 (d, J = 13.0 Hz, 1H), 4.31 (dd, J = 4.5,
7.5 Hz, 1H, H-6a), 4.18 – 4.14 (m, 2H), 3.86 (broad d, J = 7.0 Hz, 1H, H-
5), 3.65 (dd, J = 4.0, 10.0 Hz, 1H, H-2), 3.59 – 3.54 (m, H-6), 3.43 (dd, J
= 9.0, 17.5 Hz, 1H, H-2), 2.05 (s, 3H, CH3), 2.02 (s, 3H, CH3), 1.82 (s, 3H,
CH3); 13C NMR (125 MHz, CDCl3): δ = 170.6, (C=O), 169.8 (C=O), 169.7
(C=O), 164.0 (C=O), 153.8 (OC=O), 149.9, 147.2, 138.1, 137.6, 137.0,
128.5, 128.3, 128.1, 128.99, 127.97, 127.95, 127.8, 127.4, 127.1, 125.6,
96.9 (C-1, JCH = 157.1 Hz), 95.8 (CCl3), 92.5 (C-1, JCH = 166.8 Hz), 78.6
(C-2), 78.5 (C-3), 75.5, 74.04, 73.95, 72.7 (C-5), 72.3, 71.7 (C-4), 70.4
(C-3), 69.9 (C-6), 69.6 (C-5), 68.8 (C-4), 62.2 (C-6), 52.0 (C-2), 20.7
(CH3CO), 20.6 (CH3CO), 20.5 (CH3CO).
2,3-Di-O-benzyl-4,6-O-benzylidene-β-D-mannopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside 53: Rf 0.2
(Hexanes/EtOAc, 2/1); [휶]퐃ퟐퟎ +8.4 (c = 0.35, CHCl3); 1H NMR (500 MHz,
CDCl3): δ = 8.77 (d, J = 5.5 Hz, 1H), 7.91 (d, J = 10.0 Hz, 1H), 7.78 (td, J
= 2.5, 10.0 Hz, 1H), 7.53 – 7.00 (m, 31H), 5.60 (s, 1H, benzylidene-H),
5.52 (t, J = 12.0 Hz, 1H, H-4), 5.06 (d, J = 15.0 Hz, 1H), 5.00 (d, J = 4.5
Hz, 1H, H-1), 4.95 (d, J = 15.0 Hz, 1H), 4.86 (d, J = 15.0 Hz, 1H), 4.82 (d,
J = 14.5 Hz, 1H), 4.67 – 4.60 (m, 3H), 4.55 (d, J = 16.0 Hz, 1H), 4.60 (s,
1H, H-1), 4.47 (d, J = 14.5 Hz, 1H), 4.42 – 4.40 (m, 3H including H-3 and
H-6  2), 3.94 (d, J = 3.5 Hz, 1H, H-2), 3.83 (t, J = 13.0 Hz, 1H, H-4), 3.73
(dd, J = 4.0, 12.0 Hz, 1H, H-2), 3.56 – 3.46 (m, 3H including H-3 and H-6
 2), 3.28 (td, J = 6.0, 12.5 Hz, 1H, H-5); 13C NMR (125 MHz, CDCl3): δ =
163.7 (C=O), 149.9, 147.7, 138.4, 138.3, 138.25, 138.1, 137.6, 137.5,
136.7, 128.8, 128.7, 128.5, 128.3, 128.2, 128.15, 128.1, 128.08, 128.0,
127.98, 127.9, 127.89, 127.54, 127.5, 127.4, 127.38, 126.8, 126.0, 125.4,
103.0 (C-1, JCH = 154.1 Hz), 101.8, 99.2 (C-1, JCH = 165.1 Hz), 80.4 (C-
2), 78.6, 78.3, 77.5 (C-3), 76.0 (C-2), 75.1, 74.8, 73.8, 73.5, 72.3, 71.3 (C-
4), 69.6, 68.5 (C-4), 68.1 (C-6), 67.7 (C-5); HRMS‒ESI (m/z): [M + Na]+
calcd for C60H59NNaO12+, 1008.3929; found, 1008.3924.
2,6-Di-O-acetyl-4-O-benzyl-3-O-(2-naphthylmethyl)-β-D-
glucopyranosyl-(11)-2,3,6-tri-O-benzyl-4-O-picoloyl-β-D-
glucopyranoside 58: Rf 0.18 (Hexanes/EtOAc, 1/1); [휶]ퟐ퐃ퟎ 4.3 (c = 0.65,
CHCl3); 1H NMR (500 MHz, CDCl3): δ = 8.74 – 8.71 (m, 1H), 7.96 (d, J =
8.0 Hz, 1H), 7.84 – 7.73 (m, 5H), 7.50 – 7.02 (m, 24H), 5.33 (t, J = 10.0
Hz, 1H, H-4), 5.16 (t, J = 8.5 Hz, 1H, H-2), 4.94 (m, 3H), 4.85 (d, J = 10.0
Hz, 1H, H-1), 4.83 (d, J = 7.5 Hz, 1H, H-1), 4.78 (d, J = 11.5 Hz, 1H), 4.62
(t, J = 11.0 Hz, 2H), 4.56 (d, J = 11.0 Hz, 1H), 4.45 (dd, J = 12.0, 14.5 Hz,
2H), 4.38 (dd, J = 1.5, 12.0 Hz, 1H, H-6a), 4.25 (dd, J = 4.5, 12.0 Hz, 1H,
H-6b), 3.84 (t, J = 9.0 Hz, 1H, H-3), 3.83 – 3.79 (m, 1H, H-5), 3.78 (d, J =
9.0 Hz, 1H, H-3), 3.73 (t, J = 9.5 Hz, 1H, H-4), 3.65 – 3.56 (m, 3H), 3.53 (t,
J = 8 Hz, 1H, H-2), 2.02 (s, 3H, OCH3), 1.95 (s, 3H, OCH3); 13C NMR (125
MHz, CDCl3): δ = 170.7, 169.7, 164.0, 149.8, 147.5, 138.3, 138.1, 137.7,
137.5, 136.8, 135.4, 133.2, 133.0, 128.5, 128.4, 128.2, 128.16, 128.1,
128.0, 127.9, 127.8, 127.6, 127.58, 127.5, 127.47, 127.3, 126.9, 126.5,
126.1, 126.0, 125.8, 125.5, 99.4 (C-1, JCH = 162.6), 97.0 (C-1, JCH = 163.4),
82.8 (C-3), 81.4 (C-2), 81.1 (C-3), 77.2 (C-4), 75.0, 74.96, 74.9, 74.6, 73.4,
73.2 (C-5’), 73.0 (C-5), 72.8 (C-2), 71.9 (C-4), 69.3, 62.8 (C-6), 20.9, 20.8;
HRMS‒ESI (m/z): [M + Na]+ calcd for C57H59NNaO14+, 1054.3984; found,
1054.4000.
2,3-Di-O-benzyl-4,6-O-benzylidene-β-D-mannopyranosyl-(11)-2-
azido-3,6-tri-O-benzyl-4-O-picoloyl-α-D-glucopyranoside 54: Rf 0.3
(Hexanes/EtOAc, 2/1); 1H NMR (500 MHz, CDCl3): δ = 8.72 – 8.69 (m, 1H),
7.89 (d, J = 8.0 Hz, 1H), 7.72 (td, J = 2.0, 8.0 Hz, 1H), 7.49 – 7.00 (m, 30
H), 5.53 (s, 1H, benzylidene-H), 5.49 (t, J = 9.5 Hz, 1H, H-4), 5.13 (d, J =
3.5 Hz, 1H, H-1), 4.66 (d, J = 12.0 Hz, 1H), 4.65 (s, 1H, H-1), 4.62 (d, J =
12.0 Hz, 1H), 4.56 – 4.51 (m, 2H), 4.42 – 4.38 (m, 2H including H-5), 4.35
(d, J = 11.5 Hz, 1H), 4.13 – 4.09 (m, 3H, including H-3, H-6a, and H-6b),
3.98 (d, J = 3.0 Hz, 1H, H-2), 3.76 (t, J = 10.5 Hz, 1H, H-4), 3.61 (dd, J =
3.5, 10.5 Hz, 1H, H-2), 3.54 (dd, J = 3.0, 10.0 Hz, 1H, H-3), 3.50 – 3.42
(m, 2H, H-6a and H-6b), 3.27 (td, J = 5.0, 10.0 Hz, 1H, H-5); 13C NMR
(125 MHz, CDCl3): δ = 163.8 (C=O), 149.9, 147.5, 138.5, 138.2, 137.5,
137.46, 137.2, 136.8, 128.9, 128.6, 128.4, 128.3, 128.26, 128.2, 128.15,
128.1, 127.9, 127.74, 127.7, 127.6, 127.57, 127.5, 127.47, 127.0, 126.0,
125.4, 102.5 (C-1), 101.4, 98.9 (C-1), 78.3, 77.9, 77.7 (C-3), 76.4 (C-2),
75.1, 74.9, 73.5, 72.4, 71.8 (C-4), 70.0, 68.4 (C-4), 68.0 (C-6), 67.8 (C-5),
+
63.4 (C-2); HRMS‒ESI (m/z): [M + Na]+ calcd for C53H52N4NaO11
,
943.3525; found, 943.3516.
3,4,5-Tri-O-acetyl-2-N-(2,2,2-trichloroethoxycarbonyl)-β-D-
glucopyranosyl-(11)-2,3,6-tri-O-benzyl-4-O-picoloyl-β-D-
glucopyranoside 57: Rf 0.1 (Hexanes/EtOAc, 1/1); [휶]ퟐ퐃ퟎ ‒3.08 (c = 0.65,
CHCl3); 1H NMR (500 MHz, CDCl3): δ = 8.74 (d, J = 4.0 Hz, 1H), 7.99 (d,
J = 8.0 Hz, 1H), 7.80 (td, J = 2.0, 9.5 Hz, 1H), 7.50 – 7.03 (m, 16H), 5.32
(d, J = 9.0 Hz, 1H, NH), 5.25 (t, J = 9.5 Hz, 1H, H-3), 5.16 (t, J = 9.5 Hz,
6-O-Acetyl-2,3-O-benzoyl-4-O-benzyl-β-D-glucopyranosyl-(11)-
2,3,6-tri-O-benzyl-4-O-picoloyl-β-D-glucopyranoside 59: Rf 0.4
(Hexanes/EtOAc, 1/1); [휶]퐃ퟐퟎ +5.4 (c = 0.37, CHCl3); H NMR (500 MHz,
1
CDCl3): δ = 8.71 (d, J = 4.0 Hz, 1H), 8.00 – 7.90 (m, 5H), 7.75 (td, J = 2.0,
8.0 Hz, 1H), 7.55 – 6.99 (m, 27H), 5.78 (t, J = 9.0 Hz, 1H, H-3), 5.46 (dd,
J = 8.0, 9.5 Hz, 1H, H-2), 5.17 (t, J = 15.0 Hz, 1H, H-4), 5.14 (d, J = 8.0
This article is protected by copyright. All rights reserved.

10.1002/chem.201700785
Chemistry - A European Journal
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We thank the Ministry of Science and Technology (previously
National Science Council) of Taiwan for finanical support (Grant
no.: MOST 105-2113-M-009-008)
Keywords: 1,1-glycosylation • 1,1-disaccharide • trimethylsilyl
glycoside acceptor • picoloyl protecting group • stereocontrol
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