Direct and stereoselective synthesis of 1,3-cis-3- arylsulphonaminodeoxydisaccharides and oligosaccharides

Article abstract of DOI:10.1021/jo300791v

The 3-aminoglycosides are ubiquitous in biologically important classes of glycoconjugates and naturally occurring oligosaccharides. Despite the rapid growth in the development of synthetic method of 3-amino glycosides, the current state-of-the art suffers from limited substrate scope, low yields, long reaction times, and anomeric mixtures. This work presents a novel direct method for the synthesis of 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides via α-selective glycosylation and hydroamination of glycal in a one-pot manner. This efficient multicomponent reaction methodology provides ready access to 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides and allows derivatization by variation of each component.

Full text of DOI:10.1021/jo300791v

Article
pubs.acs.org/joc
Direct and Stereoselective Synthesis of 1,3-cis-3-
Arylsulphonaminodeoxydisaccharides and Oligosaccharides
Feiqing Ding, Ronny William, Shuting Cai, Jimei Ma, and Xue-Wei Liu*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
21 Nanyang Link, Singapore 637371
S
* Supporting Information
ABSTRACT: The 3-aminoglycosides are ubiquitous in biologically important classes of glycoconjugates and naturally occurring
oligosaccharides. Despite the rapid growth in the development of synthetic method of 3-amino glycosides, the current state-of-
the art suffers from limited substrate scope, low yields, long reaction times, and anomeric mixtures. This work presents a novel
direct method for the synthesis of 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides via α-selective
glycosylation and hydroamination of glycal in a one-pot manner. This efficient multicomponent reaction methodology provides
ready access to 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides and allows derivatization by variation of each
component.
indirect approach whereby the glycosyl donors possess a
protected heteroatom at C2 that directs facial selectivity of the
reaction, and the protecting group can be cleaved at later stage.7
Our interest in drug discovery motivated us to devise new
methodologies for the aminosugar syntheses.8 Recently, we
derived a strategy for ready access to 3-arylsulphonamino-2,3-
dideoxysugars via regio- and stereoselective tandem hydro-
amination/glycosylation of glycal.9 In conjunction with our
previous work, herein, we wish to report a direct and reliable
synthetic approach that provides 1,3-cis-3-arylsulphonamino-
2,3-deoxydisaccharides and oligosaccharides with not only
exclusive anomeric stereoselectivity, but also a wide range of
derivatization. We envisaged a straightforward synthesis of 1,3-
cis-3-arylsulphonamino-2,3-dideoxyglycosides by a three-com-
ponent reaction of the glycosyl donor, glycosyl acceptor, and
sulfonamide/carbamate in a one-pot manner. This method-
ology involves regio- and stereoselective tandem hydro-
amination/glycosylation on the protected glycal scaffold
(Figure 2).
INTRODUCTION
■
2,3-Di- and 2,3,6-trideoxyaminosaccharides are key compo-
nents of many biologically active natural products,1 and their
synthesis is particularly challenging.2 Significant attention has
been placed on them over the past years as they constitute
important elements in many pharmacological compounds.
Noteworthy, their roles in aminodeoxy di- and oligosaccharide
anthracycline antibiotics such as daunosaminyl daunosamine,
rubomycin, marcellomycin, and aclacinomycin has been one of
the main focus in recent years (Figure 1).3 The synthesis of 3-
amino-2,3-dideoxyglycosides with linkages to other sugar
residues via either 1,3-cis- or 1,3-trans-3-amino O-glycosidic
bonds have attracted growing interest due to their broad
spectrum of applications in chemistry, medicine, and
pharmaceutical fields.4
Stereocontrolled glycosylation in the assembly of glycosidic
bonds in deoxysugar derivatives is inherently difficult to achieve
because of the lack of stereodirecting substituents at C2.5
Therefore, many advances in the synthesis of 3-amino-
deoxyglycosides in the past decades have predominantly
focused on the stereoselective formation of glycosidic bond.6
However, the development of reliable methods for stereo-
selective construction of both α- and β-deoxyglycosides remains
a challenging area of research. Although the α-deoxyglycosides
are relatively more accessible than the β-anomers because of the
anomeric effect, glycosylation of 2-deoxyglycosides under acidic
conditions frequently provides a mixture of both anomers. In
addition, the routinely used methods for the synthesis of 1,3-cis-
3-aminodeoxydisaccharides and oligosaccharides employ an
RESULTS AND DISCUSSION
■
We first sought to examine the feasibility in constructing the N-
protected 1,3-cis-3-aminodeoxydisaccharides through a one-pot
three-component reaction. In our initial studies, treatment of
glycosyl donor 3,4,6-tri-O-acetyl-D-glucal (1a), glucose acceptor
(2a) and p-toluenesulfonamide (3a) with 1.1 equiv of BF3·OEt2
Received: August 6, 2011
Published: May 31, 2012
© 2012 American Chemical Society
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Figure 1. Anthracycline antibiotics containing 3-amino-2,3-dideoxy di- and trisaccharides.
Figure 2. Quick access to 1,3-cis-3-arylsulphonaminodeoxyglycosides via regio- and stereoselective tandem hydroamination/glycosylation of glycols.
a
Table 1. Optimization of Reaction Conditions for Selective Formation of 1,3-cis-3-Arylsulphonaminodeoxydisaccharides
b
entry
promoter (equiv)
solvent
yield (%)
1
2
3
4
5
6
7
8
9
BF3·OEt2 (1.1)
TMSOTf (2.2)
SnCl4 (2.2)
DCE
DCE
DCE
DCE
DCE
DCE
toluene
THF
19
trace
trace
c
TsOH (2.2)
−
Cu(OTf)2 (2.2)
BF3·OEt2 (2.2)
BF3·OEt2 (2.2)
BF3·OEt2 (2.2)
BF3·OEt2 (2.2)
−
68
61
d
n.r.
MeCN
26
a
Reaction conditions: donor 1a (1 equiv), acceptor 2a (1.1 equiv), and TsNH2 3a (1.1 equiv) were mixed together in 2 mL/0.1 mmol of solvent
b
c
d
under N2 atmosphere, and finally promoter was added, 25 °C, 15 min. Isolated yield. Complex mixture. No reaction.
in 1,2-dichloroethane (DCE) at room temperature for 15 min
provided the desired 1,3-cis-3-tosylaminodeoxydisaccharide 4a
in 19% yield (Table 1, entry 1). The structural and
stereochemical characterization of 4a was determined by
extensive NMR studies (1H NMR, 13C NMR, COSY,
HMQC, HMBC, NOESY, see the Supporting Information).
Although the glycosylation reaction resulted in poor yield, the
desired disaccharide 4a was isolated with exclusive α-selectivity.
Further optimization revealed that an increase in promoter
loading (2.2 equiv) led to an increase in the yield of 4a to 68%
(Table 1, entry 6). In addition, trace amount of the desired
disaccharide 4a was detected when the model glycosylation
reaction was conducted in the presence of stronger Lewis acids
such as TMSOTf (2.2 equiv) and SnCl4 (2.2 equiv). On the
other hand, the use of Lewis acid Cu(OTf)2 as the glycosylation
promoter did not result in the desired product (Table 1, entries
2, 3, and 5). Furthermore, a complex mixture of products was
obtained in the presence of 2.2 equiv of strong Bronsted acid
̈
TfOH (Table 1, entry 4). Solvent screening demonstrated that
DCE was the optimal solvent for the effective assembly of
glycosidic linkage via this one-pot strategy (Table 1, entries 6−
9). These results indicated that the optimal condition is
employing 2.2 equiv of BF3·OEt2 with anhydrous DCE as
solvent at room temperature for 15 min. It is noteworthy that
the present one-pot methodology is operationally simple, and
more importantly, the product in all cases was obtained as a
pure diastereomer.
With the optimized condition in hand, we investigated
versatility of the method by preparation of α-linked deoxyglyco-
sides composing of various N-protected 2,3-dideoxy- and 2,3,6-
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a
Table 2. Substrate Scope Studies for BF3·OEt2-Promoted Three-Component α-Selective Glycosylation
a
Reaction conditions: donor 1 (1 equiv), acceptor 2 (1.1 equiv), and 3 (1.1 equiv) were mixed together in 2 mL/0.1 mmol of DCE under N2
b
atmosphere, and finally BF3·OEt2 (2.2 equiv) was added, 25 °C, 15 min. All products were characterized by 1H NMR, 13C NMR, IR, and HRMS.
c
Isolated yield.
trideoxy-1,3-cis-3- aminodisaccharides and oligosaccharides 4a−
4s (Table 2). We found that a combination of 2D NMR
spectroscopy methods such as COSY, HMQC, HMBC,
NOESY (see the Supporting Information) is critical in
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determining the structural and stereochemical outcome of the
reaction. For example, the structure of product 4b as shown in
Figure 3 was analyzed from the result of such NMR studies. On
corresponding 3-benzyloxycarbonylamino-2,3-dideoxydisac-
charide 4t in moderate yields (Table 2, entry 8). Hydro-
genolysis of the benzyloxycarbonyl (Cbz) group in the resulting
product is expected to liberate the amino group.9b For example,
removal of the acetyl group by treating 3-benzyloxycarbonyla-
mino-2,3-dideoxydisaccharide 4jb with NaOMe in methanol,
followed by direct removal of the Cbz group through treatment
with Pd/C under H2 provided 3-amino-2,3-deoxydisaccharide 6
in 74% with exclusive stereo- and regioselection (Scheme 1).
We next examined the glycosylation of 2a with a variety of
glycosyl donors 1c−1e under BF3·OEt2-mediated conditions.
All the reactions afforded the expected arylsulphonaminodeox-
ydisaccharides 4h−4k in moderate to good yields with exclusive
α-selectivity (Table 2, entries 6−9). Similarly, N-protected 3-
amino-2,3-dideoxydisaccharides 4ma and 4mb were prepared
by the treatment of disaccharides donor 1e with nucleophiles
2g and 2h bearing primary hydroxyl moieties (Table 2, entry
11). With this expedient protocol, we synthesized L-menthol
glucoside 4n in 55% yield (Table 2, entry 11), which
exemplifies a common 3-arylsulphonamino-2,3-dideoxydisac-
charide motif appended to biologically important natural
products. To demonstrate that the current method can be
employed for oligosaccharide synthesis, a number of deoxy-
trisaccharides 4p−4s were prepared from disaccharide donors
hex-O-acetyl-D-maltal (1f), hex-O-acetyl-D-lactal (1g), and
acceptors (Table 2, entries 12−15). Further exploration
revealed that a more armed donor 1h in which the hydroxyl
group at C-4 and C-6 was protected by benzyl group failed to
provide the desired N-protected 1,3-cis-3-aminodisaccharide
(Scheme 2). To the best of our knowledge, the BF3·OEt2-
Figure 3. Selected data of 1H NMR and NOESY for 1,3-cis-3-
tosylaminodeoxydisaccharide 4b.
the basis of the COSY spectrum, we were able to assign each
individual peak to the corresponding protons of the product.
Appearance of small coupling constants JH1−H2 of 2.8 Hz for
anomeric proton H-1 signal at δ 4.91 in 1H NMR is diagnostic
for α-linked glycosides. NOESY experiments further confirmed
the stereochemical assignment at C1 and C3 position on the
basis of observed correlation for N−H/H-5 and H-2a/H-4. In
contrast, no correlation was observed in the signals for H-1/N−
H or H-1/H-3. These results indicated that the newly
introduced sulfonamido group and glycosyl acceptor are in cis
configuration and the α-glycosyl linkage was formed.
The glycosylation of glucosides 2b and 2c, which possess free
hydroxyl groups at C6 position, with 3,4,6-tri-O-acetyl-D-glucal
(1a) and p-toluenesulfonamide (3a) under the optimized
condition afforded the corresponding 1,3-cis-3-tosylamino-2,3-
deoxydisaccharides 4b and 4c in 69 and 86% yield, respectively
(Table 2, entries 1, 2). Pivaloyl protected glycals also gave the
desired product 4c in moderate yield under standard
conditions. The possibility of secondary alcohol as viable
nucleophilic glycosyl acceptor was also investigated. Accord-
ingly, glycosylation of glycosides 2d and 2e possessing hydroxyl
groups at C4 with glucal donor (1a) and p-toluenesulfonamide
provided disaccharides 4e and 4f as pure α-isomers in poor
yields (Table 2, entries 3, 4). When glucose thiol 2f was
employed as the glycosyl acceptor, the corresponding S-linked
deoxyglycoside 4g was obtained in slightly lower yield (Table 2,
entry 5). Importantly, the α-linked 3-arylsulphonamino-2,3-
deoxydisaccharides did not decompose under the reaction
conditions. In our protocol, we found that aromatic and
aliphatic sulfonamides such as TsNH2, NsNH2, and MsNH2
worked particularly well for this reaction and provided the
corresponding products in good yields and are anomerically
pure (Table 2, entry 10). In the same manner, the reaction with
benzyl carbamate (CbzNH2) proceeded smoothly to afford the
Scheme 2. Three-Component Reaction with More Armed
Donor 1h
promoted one-pot α-selective tandem hydroamination/glyco-
sylation is the first example of a direct and stereoselective
synthesis of N-protected 2,3-dideoxy- or 2,3,6-trideoxy-1,3-cis-
3-aminodisaccharides and oligosaccharides.
In our initial attempt to probe the reaction mechanism, we
found that when C-3 epimer of 3,4,6-tri-O-acetyl-D-glucal 1i
was reacted under the same reaction conditions, the
disaccharide formed was of the same configuration as that
obtained from the corresponding D-glucal in 64% yield
(Scheme 3). This observation implies that both acetyl
protected D-glucal and its epimer led to a common reactive
intermediate that eventually converged to the resulting
Scheme 1. Deprotection of 3-Benzyloxycarbonylamino-2,3-dideoxydisaccharide 4jb to Synthesize 3-Amino-2,3-
dideoxydisaccharide 6
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Scheme 3. Three-Component Reaction with More Armed Donor 1i
Scheme 4. Proposed Reaction Mechanism
disaccharide. The use of TMSN3, which lacks acidic hydrogen,
did not result in desired product formation. Additionally, when
secondary sulfonamide (TsNHCH3) was employed as one of
the nucleophiles, no desired disaccharide was obtained as well.
The diastereofacial selectivities observed in the absence of a
directing group at C2 position is novel and prompted us to look
into the mechanistic cause. Though a detailed mechanism of
exclusive stereoselectivity facilitated the purification to a great
extent. Additionally, the method works with a broad range of
disarmed sugars, and primary amines make derivatization
possible. Because of the aforementioned advantages, the
present methodology is believed to be able to find broad
applications in glycochemistry.
the present protocol still awaits further studies, a plausible
pathway is postulated (Scheme 4). One possibility is that the
EXPERIMENTAL SECTION
■
General Experimental Procedures. All solvents were distilled
under nitrogen from the following drying agents immediately before
use: tetrahydrofuran (THF) was distilled from sodium/benzophenone
ketyl; dichloromethane and 1,2-dichloroethane were distilled from
calcium hydride. BF3·OEt2 was distilled from calcium hydride before
use. The 3,4-di-O-acetyl-6-deoxy-L-glucal (1a), glycosyl acceptor 2e,
2g−2k, and N-containing nucleophiles 3a−3d were purchased from
commercial suppliers and used without further purification. Glycosyl
acceptor 1b−1i and glycosyl acceptor 2a−2d, 2f were prepared
according to literature reported procedure.12 The promoters were
purchased from commercial suppliers and used without further
purification. Analytical thin layer chromatography (TLC) was
performed using precoated silica gel plate. Visualization was achieved
by UV light (254 nm) and/or KMnO4 stain. Flash chromatography
was performed using silica gel and a gradient solvent system (EtOAc/
hexane as eluent). NMR spectra were recorded at room temperature
on Bruker ACF 300, Bruker DPX 400, Bruker AMX 500, and JEOL
ECA 400 NMR spectrometers. Chemical shifts (ppm) were recorded
with tetramethylsilane (TMS) as the internal reference standard.
Multiplicities are given as follows: s (singlet), bs (broad singlet), d
(doublet), t (triplet), dd (doublet of doublets), or m (multiplet). The
number of protons (n) for a given resonance is indicated by nH, and
coupling constants are reported in Hz. High resolution mass spectra
(HRMS) were recorded on Waters Q-Tof premier mass spectrometer.
General Procedure for Synthesis of 1,3-cis-3-Arylsulphona-
minodeoxydisaccharides and Oligosaccharides 4. To a solution
of glycosyl donor 1 (0.1 mmol, 1.0 equiv) and nitrogen nucleophiles 3
(1.1 equiv) in DCE (2 mL, dry) was added glycosyl acceptor 2 (1.1
equiv) under N2 atmosphere. BF3·OEt2 (2.2 equiv) was then added to
this mixture. The reaction mixture was stirred for 15 min at room
temperature, quenched with saturated NaHCO3 (3 mL) and
reaction proceeds through allyloxocarbenium ion intermediate
7. Preferential attack of N-nucleophile occurs from stereo-
electronically favored α face of the presumably almost planar
conformation of the allyloxocarbenium intermediate to
generate 8. Rapid proton transfer follows to generate the
corresponding oxocarbenium ion. Subsequently, nucleophilic
addition of carbohydrate oxygen or sulfur nucleophiles to the
oxonium ion proceeds readily to furnish the desired product
with high stereo- and regioselectivity. The observed α-anomeric
selectivity can reasonably be explained by considering addition
of O-nucleophile to the stereoelectronically preferred face of
the more stable conformer.10 The facial selectivity might be
further reinforced by possible effective coordination (hydrogen
bonding) between the nitrogen and the incoming O-
nucleophile (ROH) as shown in structure 9.9,11 In this way,
the carbohydrate alcohol or thiol is directed to attack
pseudoaxially from the same face of the oxocarbenium ion on
the C1 carbon to furnish the thermodynamically favored 1,3-cis
α-isomer.
CONCLUSION
■
In conclusion, we have described a highly efficient direct and
stereoselective one-pot procedure for assembly of N-protected
1,3-cis-3-aminodeoxydisaccharides and oligosaccharides via
BF3·OEt2-promoted hydroamination and α-selective glycosyla-
tion on glycal scaffold. This multicomponent reaction protocol
offers simplicity over the conventional indirect method and the
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subsequently extracted with CH2Cl2 (3 × 5 mL). The extract was
dried and concentrated. The residue was subjected to column
chromatography (silica gel, hexane/EtOAc) to obtain pure 1,3-cis-3-
arylsulphonaminodeoxydisaccharides or oligosaccharides 4.
NMR (CDCl3, 400 MHz) δ 7.79 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4
Hz, 2H), 6.34 (d, J = 3.6 Hz, 1H), 6.07 (d, J = 9.6 Hz, 1H), 5.54 (d, J
= 10.0 Hz, 1H), 5.13 (d, J = 9.6 Hz, 1H), 5.03 (dd, J = 10.4, 3.6 Hz,
1H), 4.86 (d, J = 3.2 Hz, 1H), 4.64 (dd, J = 10.4, 4.0 Hz, 1H), 4.08−
4.17 (m, 4H), 3.93−3.97 (m, 1H), 3.59 (dd, J = 12.4, 2.4 Hz, 1H),
3.57 (dd, J = 12.0, 2.0 Hz, 1H), 2.43 (s, 3H), 2.19 (s, 3H), 2.12 (s,
3H), 2.09 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H), 1.99 (s, 3H), 1.80 (dt, J
= 14.8, 4.0 Hz, 1H), 1.55 (dd, J = 14.4, 2.4 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ 170.7, 170.4, 170.1, 169.8, 169.6, 169.0, 143.2,
138.5, 129.7, 126.9, 97.6, 88.9, 71.0, 69.5, 69.4, 68.2, 66.9, 64.9, 64.5,
62.7, 47.9, 32.9, 21.5, 20.9, 20.85, 20.79, 20.7, 20.67, 20.5; IR (CHCl3)
3317, 2947, 1751, 1435, 1373, 1219, 1157, 1041, 933, 756, 671, 601,
547 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for C31H41NO17SNa
754.1951, found 754.1954.
1,3-cis-3-Tosylaminodeoxydisaccharide (4e). Compound 4e
(gummy liquid, 46 mg, 54% yield) was prepared according to the
general procedure from glycosyl donor 1a (27.2 mg, 0.1 mmol),
glycosyl acceptor 2d (51.2 mg, 0.11 mmol), and p-toluenesulfonamide
3a (18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +34.3 (c 1.0 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 7.73 (d, J = 8.8 Hz, 2H), 7.29−7.38 (m,
12H), 7.22−7.25 (m, 3H),7.02−7.04 (m, 2H), 5.89 (d, J = 11.2 Hz,
1H), 5.25 (d, J = 3.6 Hz, 1H), 4.96 (d, J = 11.2 Hz, 1H), 4.72 (d, J =
8.8 Hz, 1H), 4.69 (d, J = 9.2 Hz, 1H) 4.58−4.62 (m, 3H), 4.50 (dd, J =
8.4, 3.6 Hz, 1H), 4.26 (d, J = 11.2 Hz, 1H), 4.08 (dd, J = 12.0, 4,4 Hz,
1H), 3.98−4.02 (m, 1H), 3.77−3.89 (m, 4H), 3.56−3.69 (m, 3H),
3.50 (dd, J = 8.4, 3.6 Hz, 1H), 3.45 (s, 3H), 2.38 (s, 3H), 2.09 (s, 3H),
1.98 (s, 3H), 1.51 (dt, J = 14.8, 4.0 Hz, 1H), 1.20 (dd, J = 14.4, 2.4 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ 170.6, 170.3, 143.4, 138.3,
138.1, 137.7, 137.6, 129.8, 128.6, 128.5, 128.4, 128.2, 128.1, 127.9,
127.8, 127.7, 127.4, 126.9, 98.7, 97.7, 82.3, 80.1, 77.2, 75.5, 73.5, 73.2,
69.7, 69.1, 67.0, 64.8, 62.7, 55.6, 47.7, 32.8, 21.5, 21.0, 20.8; IR
(CHCl3) 3433, 2924, 1743, 1643, 1450, 1357, 1242, 1157, 1049, 910,
740, 548 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for
C45H53NO13SNa 870.3133, found 870.3135.
1,3-cis-3-Tosylaminodeoxydisaccharide (4f). Compound 4f
(gummy liquid, 43 mg, 47% yield) was prepared according to the
general procedure from glycosyl donor 1a (27.2 mg, 0.1 mmol),
glycosyl acceptor 2e (56 mg, 0.11 mmol), and p-toluenesulfonamide
3a (18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +98.6 (c 1.0 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 8.10 (d, J = 7.2 Hz, 2H), 8.00−8.08 (m,
4H), 7.86 (d, J = 8.4 Hz, 2H), 7.33−7.46 (m, 11H), 6.03 (d, J = 9.2
Hz, 1H), 5.81 (dd, J = 11.2, 3.2 Hz, 1H), 5.61 (dd, J = 11.2, 3.6 Hz,
1H), 5.33 (d, J = 3.6 Hz, 1H), 4.95 (d, J = 3.2 Hz, 1H), 4.56 (d, J = 3.2
Hz, 1H), 4.49−4.56 (m, 2H), 4.43 (t, J = 6.8 Hz, 1H), 4.16−4.21 (m,
2H), 3.95−3.98 (m, 1H), 3.68 (dd, J = 9.2, 3.6 Hz, 1H), 3.49 (s, 3H),
3.24 (dd, J = 8.4, 3.0 Hz, 1H), 2.43 (s, 3H), 1.98 (s, 3H), 1.90 (s, 3H),
1.80 (dt, J = 14.8, 3.6 Hz, 1H), 1.62 (dd, J = 14.8, 2.8 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 170.4, 170.2, 166.0, 165.8, 143.4, 138.4,
133.7, 133.6, 133.3, 130.0, 129.7, 129.6, 129.3, 129.2, 128.8, 128.7,
128.6, 128.5, 128.4, 127.0, 126.9, 98.0, 97.5, 73.9, 69.4, 68.8, 67.6, 66.5,
64.9, 62.3, 61.9, 55.8, 47.7, 32.7, 21.6, 20.9, 20.6; IR (CHCl3) 3333,
3063, 2955, 1728, 1450, 1265, 1111, 1057, 710 cm−1; HRMS (ESI) m/
z [M + H]+ calcd for C45H47NO16SNa 912.2505, found 912.2513.
1,3-cis-3-Tosylaminodeoxydisaccharide (4g). Compound 4g
(gummy liquid, 40 mg, 53% yield) was prepared according to the
general procedure from glycosyl donor 1a (27.2 mg, 0.1 mmol),
glycosyl acceptor 2f (40 mg, 0.11 mmol), and p-toluenesulfonamide 3a
(18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = −1.5 (c 0.5 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 7.79 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.0
Hz, 2H), 5.68 (d, J = 10.0 Hz, 1H), 5.21 (t, J = 9.2 Hz, 1H), 5.05 (t, J
= 10.0 Hz, 1H), 4.96 (t, J = 9.2 Hz, 1H), 4.86 (td, J = 10.8, 2.0 Hz,
1H), 4.68−4.73 (m, 2H), 4.27 (dd, J = 8.4, 4.8 Hz, 1H), 4.16 (dd, J =
12.4, 2.0 Hz, 1H), 4.05 (dd, J = 12.4, 4.8 Hz, 1H), 3.78 (dd, J = 12.4,
2.4 Hz, 1H), 3.68 (dq, J = 10.0, 2.0 Hz, 1H), 3.54 (dq, J = 8.8, 1.6 Hz,
1H), 3.05 (td, J = 12.0, 4.0 Hz, 1H), 2.42 (s, 3H), 2.39−2.41 (m, 1H),
2.06 (s, 3H), 2.05 (s, 6H), 2.03 (s, 3H), 2.01 (s, 3H), 2.00 (s,3H),
1.92−1.95 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 171.1, 170.5,
Characterization of 1,3-cis-3-Tosylaminodeoxydisaccharide
(4a). Compound 4a (gummy liquid, 57 mg, 68% yield) was prepared
according to the general procedure from glycosyl donor 1a (27.2 mg,
0.1 mmol), glycosyl acceptor 2a (51.2 mg, 0.11 mmol), and p-
toluenesulfonamide 3a (18.8 mg, 0.11 mmol) and purified by column
chromatography (hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +45.2 (c
1.0 CHCl3); 1H NMR (CDCl3, 400 MHz) δ 7.65 (d, J = 8.4 Hz, 2H),
7.23−7.39 (m, 17H), 6.08 (d, J = 9.2 Hz, 1H), 5.02 (d, J = 11.2 Hz,
1H), 4.95 (d, J = 10.8 Hz, 1H), 4.77−4.84 (m, 3H), 4.69−4.74
(m,2H), 4.62 (dd, J = 10.4, 3.6 Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H),
4.26 (dd, J = 13.6, 4.8 Hz, 1H), 4.15 (m, 2H), 4.05 (t, J = 9.2 Hz, 1H),
3.81−3.91 (m, 1H), 3.70−3.75 (m, 1H), 3.72 (m, J = 11.2, 4.4 Hz,
1H), 3.55−3.58 (m, 2H), 3.46 (s, 3H), 3.34 (t, J = 9.2 Hz, 1H), 2.39
(s, 3H), 2.07 (s, 3H), 2.02 (s, 3H), 1.80 (td, J = 10.4, 3.6 Hz, 1H), 1.52
(dd, J = 9.6, 2.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 170.7,
170.5, 143.3, 138.6, 138.1, 138.0, 137.9, 129.8, 128.5, 128.4, 128.3,
128.1, 128.01, 127.95, 127.92, 127.8, 127.7, 126.8, 97.9, 97.2, 81.8,
80.0, 78.6, 75.8, 75.3, 73.3, 69.3, 67.2, 66.8, 64.5, 62.6, 55.6, 47.9, 32.6,
21.5, 21.0, 20.8; IR (CHCl3) 3426, 3024, 2932, 1744, 1643, 1450,
1366, 1242, 1157, 1057, 756 cm−1; HRMS (ESI) m/z [M + Na]+ calcd
for C45H53NO13SNa 870.3142, found 870.3135.
1,3-cis-3-Tosylaminodeoxydisaccharide (4b). Compound 4b
(gummy liquid, 43 mg, 69% yield) was prepared according to the
general procedure from glycosyl donor 1a (27.2 mg, 0.1 mmol),
glycosyl acceptor 2b (26 mg, 0.11 mmol), and p-toluenesulfonamide
3a (18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +46.3 (c 1.0 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 7.68 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.4
Hz, 2H), 6.11 (d, J = 8.8 Hz, 1H), 4.91 (d, J = 2.8 Hz, 1H), 4.87 (d, J
= 3.6 Hz, 1H), 4.65 (dd, J = 10.4, 3.6 Hz, 1H), 4.21−4.33 (m, 3H),
3.90−3.93 (m, 1H), 3.79 (dd, J = 10.0, 6.4 Hz, 1H), 3.68−3.72 (m,
1H), 3.64 (s, 3H), 3.62−3.53 (m, 1H), 3.57 (s, 3H), 3.50−3.53 (m,
1H), 3.55 (s, 3H), 3.47 (s, 3H), 3.19 (dd, J = 9.6, 3.6 Hz, 1H), 2.97 (t,
J = 9.2 Hz, 1H), 2.42 (s, 3H), 2.08 (s, 3H), 2.02 (s, 3H), 1.82 (dt, J =
14.8, 3.6 Hz, 1H), 1.52 (dd, J = 14.8, 2.4 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ 170.7, 170.5, 143.3, 138.1, 129.8, 126.8, 97.3, 97.2, 83.3,
81.8, 80.4, 69.4, 67.0, 66.9, 64.5, 62.7, 60.9, 60.7, 59.0, 55.5, 48.0, 32.6,
21.5, 21.05, 20.8; IR (CHCl3) 3426, 2947, 2839, 1744, 1643, 1342,
1242, 1157, 1096, 1049, 903, 579 cm−1; HRMS (ESI) m/z [M + Na]+
calcd for C27H41NO13SNa 642.2198, found 642.2196.
1,3-cis-3-Tosylaminodeoxydisaccharide (4c). Compound 4c
(gummy liquid, 54 mg, 59% yield) was prepared according to the
general procedure from glycosyl donor 1b (40 mg, 0.1 mmol), glycosyl
acceptor 2a (51.2 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
mg, 0.11 mmol) and purified by column chromatography (hexane/
1
ethyl acetate = 2:1 to 1:1): [α]D = +55.2 (c 1.0 CHCl3); H NMR
20
(CDCl3, 400 MHz) δ 7.65 (d, J = 8.0 Hz, 2H), 7.28−7.37 (m, 15H),
7.22 (d, J = 8.0 Hz, 2H), 5.95 (d, J = 9.2 Hz, 1H), 5.02 (d, J = 10.8 Hz,
1H), 4.95 (d, J = 11.2 Hz, 1H), 4.77−4.84 (m, 3H), 4.69−4.72 (m,
2H), 4.54 (d, J = 11.2 Hz, 1H), 3.94−3.96 (m, 1H), 3.84 (t, J = 8.0 Hz,
1H), 3.73 (dd, J = 10.4, 6.8 Hz, 1H), 3.57 (d, J = 10.4 Hz, 1H), 3.51
(dd, J = 10.0, 3.6 Hz, 1H), 3.46 (s, 3H), 3.30 (t, J = 9.6 Hz, 1H), 2.38
(s, 3H), 1.71 (dt, J = 14.8, 3.6 Hz, 1H), 1.33 (dd, J = 14.4, 2.4 Hz,
1H), 1.25 (s, 9H), 1.17 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ
178.0, 177.6, 143.2, 138.6, 138.5, 138.0, 137.9, 129.8, 128.5, 128.4,
128.0, 127.9, 127.8, 127.7, 127.6, 127.2, 127.1, 126.7, 97.9, 97.3, 81.8,
80.0, 78.6, 75.8, 75.3, 73.3, 69.7, 67.1, 66.9, 64.7, 62.7, 55.7, 48.4, 38.9,
32.4, 27.2, 27.0, 21.5, 14.2; IR (CHCl3) 3419, 2972, 1732, 1629, 1454,
1346, 1284, 1165, 1091, 981, 752, 667 cm−1; HRMS (ESI) m/z [M +
H]+ calcd for C51H66NO13S 932.4255, found 932.4238.
1,3-cis-3-Tosylaminodeoxydisaccharide (4d). Compound 4d
(gummy liquid, 63 mg, 86% yield) was prepared according to the
general procedure from glycosyl donor 1a (27.2 mg, 0.1 mmol),
glycosyl acceptor 2c (39 mg, 0.11 mmol), and p-toluenesulfonamide
3a (18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +81.5 (c 1.0 CHCl3); 1H
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1
170.1, 169.7, 169.4, 169.2, 143.6, 138.5, 129.4, 127.2, 81.7, 81.3, 77.2,
76.0, 75.8, 73.8, 70.0, 68.3, 66.7, 62.6, 61.9, 44.5, 39.6, 21.5, 20.83,
20.76, 20.62, 20.59, 20.55; IR (CHCl3) 3271, 2955, 1744, 1435, 1373,
1335, 1157, 1041, 910, 817, 756, 671, 586 cm−1; HRMS (ESI) m/z [M
+ Na]+ calcd for C31H41NO16S2Na 770.1764, found 770.1764.
1,3-cis-3-Tosylaminodeoxydisaccharide (4ha). Compound
4ha (gummy liquid, 32 mg, 51% yield) was prepared according to
the general procedure from glycosyl donor 1c (27.2 mg, 0.1 mmol),
glycosyl acceptor 2a (51.2 mg, 0.11 mmol), and p-toluenesulfonamide
3a (18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +40.9 (c 1.0 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 7.76 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0
Hz, 2H), 6.23 (d, J = 8.4 Hz, 1H), 4.96 (d, J = 2.8 Hz, 1H), 4.89 (d, J
= 3.6 Hz, 1H), 4.76 (d, J = 2.4 Hz, 1H), 4.30 (t, J = 6.4 Hz, 1H),
4.04−4.07 (m, 2H), 3.72−3.80 (m, 2H), 3.65−3.64 (m, 1H), 3.63 (s,
3H), 3.59−3.56 (m, 1H), 3.57 (s, 3H), 3.54 (s, 3H), 3.53−3.50 (m,
1H), 3.49 (s, 3H), 3.22 (dd, J = 9.6, 3.6 Hz, 1H), 2.98 (t, J = 9.2 Hz,
1H), 2.42 (s, 3H), 2.07 (s, 3H), 2.03 (s, 3H), 1.99−2.03 (m, 1H), 1.52
(d, J = 14.8, 2.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 170.3,
169.5, 143.4, 138.0, 129.8, 127.0, 97.4, 97.0, 83.3, 81.9, 80.6, 77.2, 69.2,
67.8, 66.9, 63.4, 62.9, 60.9, 60.6, 59.0, 55.6, 47.6, 28.5, 21.5, 20.8; IR
(CHCl3) 3310, 2932, 2832, 1744, 1373, 1335, 1227, 1157, 1096, 1049
cm−1; HRMS (ESI) m/z [M + Na]+ calcd for C27H41NO13SNa
642.2195, found 642.2196.
ethyl acetate = 2:1 to 1:1): [α]D = −5.28 (c 1.0 CHCl3); H NMR
20
(CDCl3, 400 MHz) δ 7.68 (d, J = 8.0 Hz, 2H), 7.32−7.41 (m, 7H),
7.25−7.31 (m, 3H), 7.20−7.22 (m, 3H), 7.12−7.16 (m, 4H), 6.29 (d, J
= 9.6 Hz, 1H), 5.07 (d, J = 10.8 Hz, 1H), 4.72−4.81 (m, 5H), 4.49 (d,
J = 11.2 Hz, 1H), 4.27−4.31 (m, 2H), 4.04 (t, J = 8.8 Hz, 1H), 3.91−
3.98 (m, 1H), 3.80−3.87 (m, 2H), 3.66−3.73 (m, 2H), 3.50 (t, J = 9.6
Hz, 1H), 3.41 (s, 3H), 3.30 (dd, J = 10.0, 2.0 Hz, 1H), 2.34 (s, 3H),
2.08 (s, 3H), 1.59 (dd, J = 14.4, 3.2 Hz, 1H), 1.18 (dd, J = 14.4, 2.4
Hz, 1H), 1.16 (d, J = 6.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ
170.7, 142.9, 139.1, 138.9, 138.2, 138.1, 129.8, 128.3−128.4 (m, 5C),
128.1, 127.8, 127.7, 127.6, 126.7, 98.0, 96.1, 81.9, 80.6, 76.2, 75.6, 74.5,
73.4, 72.6, 68.8, 64.1, 62.0, 55.4, 48.1, 32.9, 21.4, 21.1, 17.4; IR
(CHCl3) 3302, 2932, 1736, 1450, 1342, 1234, 1157, 1064, 1026, 987,
910, 817, 748,702, 671 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for
C43H51NO11SNa 812.3082, found 812.3081.
1,3-cis-3-Benzyloxycarbonylaminodeoxydisaccharide (4jb).
Compound 4jb (gummy liquid, 49 mg, 64% yield) was prepared
according to the general procedure from glycosyl donor 1e (22 mg, 0.1
mmol), glycosyl acceptor 2a (51.2 mg, 0.11 mmol), and benzyl
carbamate 3d (17 mg, 0.11 mmol) and purified by column
chromatography (hexane/ethyl acetate = 2:1 to 1:1): [α]D
=
20
1
−12.2 (c 1.0 CHCl3); H NMR (CDCl3, 400 MHz) δ 7.25−7.34 (m,
20H), 6.32 (d, J = 9.6 Hz, 1H), 5.10 (d, J = 12.8 Hz, 1H), 4.87−4.98
(m, 3H), 4.80 (d, J = 9.6 Hz, 1H), 4.43−4.63 (m, 6H), 4.31−4.34 (m,
1H), 3.91−4.01 (m, 2H), 3.83 (dd, J = 2.0, 10.0 Hz, 1H),3.74−3.79
(m, 1H), 3.46−3.52 (m, 2H), 3.38−3.42 (m, 1H), 3.29 (s, 3H), 1.96
(dt, J = 10.8, 3.6 Hz, 1H),1.91 (s, 3H), 1.82 (dd, J = 14.4, 2.0 Hz, 1H),
1.15 (d, J = 2.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 170.2, 156.3,
138.7, 138.2, 138.1, 137.1, 128.5, 128.3−124 (m, 4C), 128.1, 128.0,
127.9, 127.89, 127.8, 127.7, 127.66, 98.0, 96.4, 82.1, 80.6, 75.8, 75.0,
73.2, 73.19, 69.5, 66.2, 65.1, 61.7, 55.2, 45.4, 33.4, 20.8, 17.4; IR
(CHCl3) 3402, 2931, 1728, 1512, 1430, 1366, 127, 1065, 910, 748
cm−1; HRMS (ESI) m/z [M + Na]+ calcd for C44H51NO11Na
792.3356, found 792.3360.
1,3-cis-3-Tosylaminodeoxydisaccharide (4hb). Compound
4hb (gummy liquid, 47 mg, 56% yield) was prepared according to
the general procedure from glycosyl donor 1a (27.2 mg, 0.1 mmol),
glycosyl acceptor 2b (26 mg, 0.11 mmol), and p-toluenesulfonamide
3a (18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +29.3 (c 1.0 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 7.72 (d, J = 8.4 Hz, 2H), 7.27−7.40 (m,
14H), 7.23−7.26 (m, 3H), 6.21 (d, J = 8.4 Hz, 2H), 5.02 (d, J = 10.8
Hz, 1H), 4.95 (d, J = 11.2 Hz, 1H), 4.89 (d, J = 2.8 Hz, 1H), 4.78−
4.83 (m, 2H), 4.70−4.76 (m, 2H), 4.56 (d, J = 11.2 Hz, 1H), 4.24 (t, J
= 6.0 Hz, 1H), 3.94−4.08 (m, 3H), 3.87 (td, J = 9.2, 3.6 Hz, 1H), 3.71
(dd, J = 10.4, 6.8 Hz, 1H), 3.56−3.64 (m, 3H), 3.48 (s, 3H), 3.32−
3.37 (m, 1H), 2.40 (s, 3H), 2.06 (s, 3H), 1.96−2.01 (m, 1H), 1.92 (s,
3H), 1.50 (d, J = 14.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 170.4,
169.5, 143.4, 138.6, 138.04, 138.02, 137.97, 129.8, 128.51, 128.48,
128.46, 128.11, 128.05, 127.95, 127.88, 127.71, 127.68, 127.0, 97.9,
97.0, 81.8, 80.0, 78.7, 75.8, 75.2, 73.2, 69.3, 67.7, 66.9, 66.3, 62.8, 55.7,
47.6, 28.4, 21.5, 20.8, 20.7; IR (CHCl3) 3317, 2916, 1744, 1405, 1427,
1366, 1227, 1157, 1087, 1049, 740, 702, 548 cm−1; HRMS (ESI) m/z
[M + Na]+ calcd for C45H53NO13SNa 870.3144, found 870.3135.
1,3-cis-3-Tosylaminodeoxydisaccharide (4i). Compound 4i
(gummy liquid, 69 mg, 81% yield) was prepared according to the
general procedure from glycosyl donor 1d (27.2 mg, 0.1 mmol),
glycosyl acceptor 2a (51.2 mg, 0.11 mmol), and p-toluenesulfonamide
3a (18.8 mg, 0.11 mmol) and purified by column chromatography
1,3-cis-3-Tosylaminodeoxydisaccharide (4k). Compound 4k
(gummy liquid, 46 mg, 58% yield) was prepared according to the
general procedure from glycosyl donor 1e (22 mg, 0.1 mmol), glycosyl
acceptor 2d (51.2 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
mg, 0.11 mmol) and purified by column chromatography (hexane/
1
ethyl acetate = 2:1 to 1:1): [α]D = −17.8 (c 1.0 CHCl3); H NMR
20
(CDCl3, 400 MHz) δ 7.69 (d, J = 7.6 Hz, 2H), 7.43 (d, J = 7.2 Hz,
2H), 7.24−7.33 (m, 15H), 5.84 (d, J = 8.8 Hz, 1H), 5.19 (d, J = 10.8
Hz, 1H), 4.73−4.78 (m, 4H), 4.60−4.63 (m, 4H), 4.35 (d, J = 12.0
Hz, 1H), 4.15 (d, J = 2.4 Hz, 2H), 3.84 (t, J = 8.0 Hz, 1H), 3.60−3.69
(m, 2H), 3.53 (dd, J = 10.8, 2.0 Hz, 1H), 3.43 (dd, J = 10.8, 2.4 Hz,
1H), 3.40 (s, 3H), 2.41 (s, 3H), 1.93 (s, 3H), 1.49 (dt, J = 14.4, 4.0 Hz,
1H), 1.28 (dd, J = 14.0, 2.8 Hz, 1H), 0.67 (d, J = 2.0 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 170.5, 143.4, 138.7, 138.5, 138.0, 137.3,
129.6, 128.5, 128.4, 128.2, 128.14, 128.10, 128.0, 127.9, 127.3, 127.2,
127.0, 98.0, 96.7, 80.8, 79.6, 75.6, 74.2, 73.6, 73.3, 72.6, 70.1, 68.3,
62.2, 55.5, 48.1, 33.4, 21.5, 20.9, 16.8; IR (CHCl3) 3318, 2932, 2862,
1736, 1450, 1342, 1242, 1165, 1096, 1049 cm−1; HRMS (ESI) m/z [M
+ Na]+ calcd for C43H51NO11SNa 812.3073, found 812.3081.
1
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +9.0 (c 1.0 CHCl3); H
NMR (CDCl3, 400 MHz) δ 7.69 (d, J = 8.4 Hz, 2H), 7.11−7.41 (m,
17H), 6.27 (d, J = 9.6 Hz, 1H), 5.07 (d, J = 10.8 Hz, 1H), 4.84 (d, J =
3.2 Hz, 1H), 4.72−4.81 (m, 4H), 4.58 (dd, J = 10.8, 4.0 Hz, 1H), 4.50
(d, J = 11.6 Hz, 1H), 4.35 (d, J = 1.6 Hz, 1H), 4.25 (dd, J = 12.0, 3.6
Hz, 1H), 4.17 (dd, J = 12.0, 2.0 Hz, 1H), 4.01−4.07 (m, 2H), 3.90−
3.94 (m, 1H), 3.83 (dd, J = 9.6, 3.2 Hz, 1H), 3.65−3.72 (m, 2H), 3.49
(t, J = 8.8 Hz, 1H), 3.40 (s, 3H), 3.83 (dd, J = 10.0, 3.6 Hz, 1H), 2.35
(s, 3H), 2.08 (s, 3H), 2.04 (s, 3H), 1.61 (td, J = 12.4, 4.0 Hz, 1H), 1.17
(dd, J = 14.4, 3.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 170.7,
170.4, 143.0, 139.0, 138.9, 138.2, 138.1, 129.8, 128.3−128.4 (m, 5C),
128.1, 127.8, 127.7, 127.6, 126.6, 98.0, 96.1, 81.9, 80.7, 75.9, 75.5, 74.5,
73.4, 68.6, 66.9, 64.4, 63.9, 62.7, 55.4, 48.1, 32.6, 21.4, 21.0, 20.8; IR
(CHCl3) 3479, 3032, 2916, 1744, 1450, 1358, 1258, 1196, 1072, 1026,
741, 694 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for
C45H53NO13SNa 870.3132, found 870.3135.
1,3-cis-3-Mesylaminodeoxydisaccharide (4la). Compound 4la
(gummy liquid, 60 mg, 69% yield) was prepared according to the
general procedure from glycosyl donor 1a (27.2 mg, 0.1 mmol),
glycosyl acceptor 2a (51.2 mg, 0.11 mmol), and p-nitrosulfonamide 3b
(23 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D = +44.0 (c 1.0 CHCl3);
20
1H NMR (CDCl3, 400 MHz) δ 8.28 (d, J = 8.8 Hz, 2H), 7.94 (d, J =
8.8 Hz, 2H), 7.26−7.39 (m, 15H), 6.38 (d, J = 9.2 Hz, 1H), 5.01 (d, J
= 11.2 Hz, 1H), 4.96 (d, J = 11.2 Hz, 1H), 4.86 (d, J = 2.8 Hz, 1H),
4.80−4.83 (m, 2H), 4.63−4.71 (m, 3H), 4.56 (d, J = 8.8 Hz, 1H), 4.25
(dd, J = 12.4, 4.4 Hz, 1H), 4.12−4.17 (m, 2H), 4.06 (t, J = 9.2 Hz,
1H), 3.97−4.00 (m, 1H), 3.83−3.87 (m, 1H), 3.75 (dd, J = 10.4, 6.4
Hz, 1H), 3.60 (dd, J = 10.0, 1.6 Hz, 1H), 3.53 (t, J = 9.6, 3.6 Hz, 1H),
3.44 (s, 3H), 3.34 (t, J = 9.6 Hz, 1H), 2.07 (s, 3H), 2.01 (s, 3H), 1.86
(dt, J = 10.8, 3.6 Hz, 1H), 1.51 (dd, J = 14.4, 2.0 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ 170.5, 170.3, 150.0, 147.1, 138.5, 138.1 137.9,
128.53, 128.51, 128.47, 128.2, 128.03, 127.96, 127.9, 127.8, 127.69,
1,3-cis-3-Tosylaminodeoxydisaccharide (4ja). Compound 4ja
(gummy liquid, 59 mg, 75% yield) was prepared according to the
general procedure from glycosyl donor 1e (22 mg, 0.1 mmol), glycosyl
acceptor 2a (51.2 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
mg, 0.11 mmol) and purified by column chromatography (hexane/
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124.4, 98.1, 97.1, 81.6, 80.2, 78.6, 77.2, 75.8, 75.2, 73.4, 69.4, 67.2,
66.7, 64.5, 62.5, 55.7, 48.5, 32.7, 20.9, 20.7; IR (CHCl3) 3309, 2932,
1744, 1527, 1350, 1234, 1056, 856, 740, 694, 617 cm−1; HRMS (ESI)
m/z [M + Na]+ calcd for C44H50N2O15SNa 901.2827, found 901.2835.
1,3-cis-3-Nosylaminodeoxydisaccharide (4lb). Compound 4lb
(gummy liquid, 47 mg, 61% yield) was prepared according to the
general procedure from glycosyl donor 1a (27.2 mg, 0.1 mmol),
glycosyl acceptor 2a (51.2 mg, 0.11 mmol), and methanesulfonamide
3c (11 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +47.3 (c 1.0 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 7.26−7.38 (m, 15H), 5.95 (d, J = 8.8 Hz,
1H), 4.92−5.01 (m, 2H), 4.68−4.82 (m, 4H), 4.55 (d, J = 11.2 Hz,
1H), 4.28 (d, J = 12.0, 4.4 Hz, 1H), 4.09−4.16 (m, 2H), 4.03 (t, J = 9.2
Hz, 1H), 3.85−3.97 (m, 1H), 3.69 (dd, J = 10.4, 7.2 Hz, 1H), 3.62
(dd, J = 10.4, 2.4 Hz, 1H), 3.54 (dd, J = 9.6, 3.6 Hz, 1H), 3.43 (s, 3),
3.31 (t, J = 9.2 Hz, 1H), 2.87 (s, 3H), 2.17 (s, 3H), 2.11 (dt, J = 12.0,
4.4 Hz, 1H), 2.09 (s, 3H), 2.04 (s, 3H), 2.00 (dd, J = 14.4, 2.4 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ 170.6, 170.0, 138.6, 138.1,
138.0, 128.5, 128.4, 128.3, 128.04, 128.0, 127.9, 127.88, 127.7, 127.6,
97.9, 97.0, 81.8, 80.1, 78.7, 75.8, 75.1, 69.3, 67.1, 67.05, 64.5, 62.6,
55.5, 48.5, 41.6, 33.8, 30.9, 21.0, 20.7; IR (CHCl3) 3332, 2924, 1744,
1450, 1365, 1334, 1234, 1149, 1056, 910, 748, 702 cm−1; HRMS (ESI)
m/z [M + Na]+ calcd for C39H49NO13SNa 794.2825, found 794.2822.
1,3-cis-3-Tosylaminodeoxydisaccharide (4ma). Compound
4ma (gummy liquid, 55 mg, 71% yield) was prepared according to
the general procedure from glycosyl donor 1f (56 mg, 0.1 mmol),
glycosyl acceptor 2g (12 mg, 0.11 mmol), and p-toluenesulfonamide
3a (18.8 mg, 0.11 mmol) and purified by column chromatography
Hz, 2H), 5.69 (d, J = 10.0 Hz, 1H), 5.42−5.46 (m, 1H), 5.24 (dd, J =
10.4, 2.4 Hz, 1H), 5.12 (t, J = 10.0 Hz, 1H), 4.93 (d, J = 1.6 Hz, 1H),
4.47 (dd, J = 12.0, 2.4 Hz, 1H), 4.19−4.33 (m, 3H), 4.09−4.17 (m,
4H), 3.95−3.98 (m, 1H), 3.75 (dd, J = 9.6, 4.0 Hz, 1H), 2.49 (t, J = 2.4
Hz, 1H), 2.43 (s, 3H), 2.20 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H), 2.04 (s,
3H), 2.00 (s, 3H), 1.61 (dt, J = 14.4, 3.6 Hz, 1H), 1.31 (dd, J = 14.8,
2.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 170.6, 170.4, 170.3,
170.0, 169.6, 143.6, 138.1, 129.9, 126.8, 95.7, 92.1, 78.2, 75.4, 70.0,
68.6, 68.4, 68.1, 66.1, 62.9, 61.7, 60.4, 54.9, 46.2, 31.5, 21.5, 20.9, 20.8,
20.7, 20.6, 14.2; IR (CHCl3) 3413, 1657, 1542, 1364, 1217, 1154,
1049, 687 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for
C32H41NO16SNa 750.2044, found 750.2042.
1,3-cis-3-Tosylaminodeoxydisaccharide (4n). Compound 4n
(gummy liquid, 45 mg, 55% yield) was prepared according to the
general procedure from glycosyl donor 1f (56 mg, 0.1 mmol), glycosyl
acceptor 2j (18 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
mg, 0.11 mmol) and purified by column chromatography (hexane/
1
ethyl acetate = 2:1 to 1:1): [α]D = +83.4 (c 1.0 CHCl3); H NMR
20
(CDCl3, 400 MHz) δ 7.66 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 7.6 Hz,
2H), 5.94 (d, J = 10.0 Hz, 1H), 5.42−5.48 (m, 2H), 5.27 (dd, J = 10.4,
3.6 Hz, 1H), 5.11 (t, J = 10.0 Hz, 1H), 4.76 (d, J = 2.8 Hz, 1H), 4.45
(dd, J = 11.6, 2.4 Hz, 1H), 4.31 (dd, J = 11.6, 4.8 Hz, 1H), 4.20−4.29
(m, 1H), 4.17 (d, J = 3.6 Hz, 1H), 4.09−4.13 (m, 1H), 3.87−3.93 (m,
2H), 3.69 (dd, J = 10.0, 4.0 Hz, 1H), 3.24 (td, J = 9.6, 4.0 Hz, 1H),
2.42 (s, 3H), 2.20 (s, 3H), 2.10 (s, 3H), 2.08 (s, 3H), 2.03 (s, 3H),
1.99 (s, 3H), 1.73−1.80 (m, 1H), 1.63−1.67 (m, 2H), 1.48 (dt, J =
14.4, 3.6 Hz, 1H), 1.38−1.41 (m, 1H), 1.10−1.28 (m, 4H), 0.85−0.98
(m, 8H), 0.63 (d, J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ
170.6, 170.5, 170.4, 170.0, 169.6, 143.5, 138.2, 129.7, 126.7, 99.1, 91.2,
82.3, 70.0, 68.5, 68.4, 68.1, 68.0, 65.3, 63.3, 61.7, 48.9, 46.1, 43.1, 34.0,
32.0, 31.7, 25.5, 22.8, 22.3, 21.6, 21.4, 21.0, 20.9, 20.7, 20.66, 20.6,
15.8; IR (CHCl3) 3302, 2924, 2870, 1751, 1435, 1373, 1334, 1226,
1165, 1041, 910, 756, 671, 555 cm−1; HRMS (ESI) m/z [M + Na]+
calcd for C39H57NO16SNa 850.3309, found 850.3296.
(hexane/ethyl acetate = 2:1 to 1:1): [α]D = +105.2 (c 1.0 CHCl3);
20
1H NMR (CDCl3, 400 MHz) δ 7.64 (d, J = 8.4 Hz, 2H), 7.35−7.42
(m, 3H), 7.27−7.29 (m, 4H), 5.85 (d, J = 10.0 Hz, 1H), 5.42−5.47
(m, 2H), 5.25 (dd, J = 3.6, 10.4 Hz, 1H), 5.11 (t, J = 9.6 Hz, 1H), 4.79
(d, J = 2.4 Hz, 1H), 4.71 (d, J = 12.0 Hz, 1H), 4.49 (dd, J = 2.8, 12.0
Hz, 1H), 4.43 (d, J = 11.6 Hz, 1H), 4.31 (dd, J = 12.0, 4.0 Hz, 1H),
4.19 (dd, J = 11.6, 4.0 Hz, 1H), 4.09−4.17 (m, 2H), 3.90−3.97 (m,
2H), 3.75 (dd, J = 9.6, 4.0 Hz, 1H), 2.43 (s, 3H), 2.18 (s, 3H), 2.10 (s,
6H), 2.03 (s, 3H), 1.99 (s, 3H), 1.55 (dt, J = 14.8, 3.6 Hz, 1H), 1.25
(dd, J = 14.8, 2.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 170.6,
170.4, 170.3, 169.9, 169.5, 143.5, 138.3, 136.6, 129.8, 128.7, 128.3,
127.8, 126.8, 96.2, 91.9, 70.1, 69.8, 68.7, 68.5, 68.4, 68.2, 65.8, 63.1,
61.7, 46.3, 31.6, 21.6, 20.9, 20.8, 20.7, 20.63, 20.61; IR (CHCl3) 3302,
3024, 2954, 1751, 1435, 1373, 1334, 1226, 1165, 1041, 910, 756, 671
cm−1; HRMS (ESI) m/z [M + Na]+ calcd for C36H45NO16SNa
802.2357, found 802.2359.
1,3-cis-3-Tosylaminodeoxydisaccharide (4o). Compound 4o
(gummy liquid, 40 mg, 48% yield) was prepared according to the
general procedure from glycosyl donor 1f (56 mg, 0.1 mmol), glycosyl
acceptor 2k (17 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
mg, 0.11 mmol) and purified by column chromatography (hexane/
1
ethyl acetate = 2:1 to 1:1): [α]D20 = +108.1 (c 1.0 CHCl3); H NMR
(CDCl3, 400 MHz) δ 7.71 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.1 Hz,
2H), 6.29 (d, J = 9.6 Hz, 1H), 5.44−5.51 (m, 2H), 5.29 (dd, J = 10.5,
3.9 Hz, 1H), 5.10−5.17 (m, 2H), 4.43−4.46 (m, 1H), 4.30−4.37 (m,
2H), 4.22 (dd, J = 12.6, 1.8 Hz, 1H), 4.11−4.15 (m, 1H), 3.88−3.97
(m, 2H), 3.71 (dd, J = 9.6, 3.6 Hz, 1H), 2.45 (s, 3H), 2.23 (s, 3H),
2.12 (s, 3H), 2.08 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H), 1.61−1.86 (m,
15H), 1.48 (dt, J = 14.4, 3.6 Hz, 1H), 0.96−1.05 (m, 1H); 13C NMR
(CDCl3, 100 MHz) δ 170.6, 170.5, 170.4, 170.0, 169.6, 143.4, 138.4,
129.7, 126.8, 91.2, 90.3, 75.9, 70.1, 68.4−68.5 (m, 4C), 68.0, 67.2,
65.4, 62.8, 61.7, 46.3, 42.5, 36.1, 32.3, 30.6, 21.6, 21.0, 20.8, 20.7, 20.6;
IR (CHCl3) 3294, 2916, 2854, 1751, 1435, 1372, 1226, 1165, 1041,
756, 678 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for
C39H53NO16SNa 846.2980, found 846.2983.
1,3-cis-3-Tosylaminodeoxydisaccharide (4mb). Compound
4mb (gummy liquid, 45 mg, 62% yield) was prepared according to
the general procedure from glycosyl donor 1f (56 mg, 0.1 mmol),
glycosyl acceptor 2h (7 mg, 0.11 mmol), and p-toluenesulfonamide 3a
(18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +79.1 (c 1.0 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 7.72 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.4
Hz, 2H), 5.85−5.91 (m, 2H), 5.44−5.49 (m, 2H), 5.25−5.31 (m, 3H),
5.14 (t, J = 9.6 Hz, 1H), 4.78 (d, J = 2.4 Hz, 1H), 4.51 (dd, J = 12.0,
2.8 Hz, 1H), 4.33 (dd, J = 12.0, 4.4 Hz, 1H), 4.18−4.25 (m, 2H),
4.12−4.15 (m, 2H), 3.92−3.99 (m, 3H), 3.76 (dd, J = 9.6, 4.0 Hz,
1H), 2.45 (s, 3H), 2.22 (s, 3H), 2.13 (s, 3H), 2.11 (s, 3H), 2.06 (s,
3H), 2.02 (s, 3H), 1.57 (dt, J = 14.8, 3.6 Hz, 1H), 1.23−1.29 (m, 1H);
13C NMR (CDCl3, 100 MHz) δ 170.6, 170.5, 170.3, 170.0, 169.6,
143.6, 138.2, 133.1, 129.9, 126.8, 117.9, 96.3, 91.6, 77.2, 70.0, 68.6,
68.5, 68.4, 68.2, 68.1, 65.5, 63.0, 61.6, 46.2, 31.6, 21.6, 21.0, 20.8, 20.7,
20.6; IR (CHCl3) 3309, 2916, 1751, 1435, 1373, 1334, 1226, 1165,
1041, 910, 817, 756, 678 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for
C32H43NO16SNa 752.2200, found 752.2197.
1,3-cis-3-Tosylaminodeoxytrisaccharide (4p). Compound 4p
(gummy liquid, 52 mg, 46% yield) was prepared according to the
general procedure from glycosyl donor 1f (56 mg, 0.1 mmol), glycosyl
acceptor 2a (51.2 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
mg, 0.11 mmol) and purified by column chromatography (hexane/
1
ethyl acetate = 2:1 to 1:1): [α]D = +61.6 (c 1.0 CHCl3); H NMR
20
(CDCl3, 400 MHz) δ 7.66 (d, J = 8.4 Hz, 2H), 7.28−7.39 (m, 15H),
7.23 (d, J = 8.0 Hz, 2H), 5.87 (d, J = 11.2 Hz, 1H), 5.43−5.49 (m,
2H), 5.29 (dd, J = 12.4, 3.6 Hz, 1H), 5.12 (t, J = 9.6 Hz, 1H), 5.04 (d,
J = 11.2 Hz, 1H), 4.98 (d, J = 11.2 Hz, 1H), 4.78−4.86 (m, 2H), 4.70−
4.74 (m, 3H), 4.57 (d, J = 11.2 Hz, 1H), 4.45 (dd, J = 12.4, 4.0 Hz,
1H), 4.19 (dd, J = 10.0, 2.4 Hz, 2H), 4.03−4.10 (m, 3H), 3.79−3.92
(m, 3H), 3.70−3.74 (m, 2H), 3.51−3.56 (m, 2H), 3.47 (s, 3H), 3.34
(t, J = 8.4 Hz, 1H), 2.39 (s, 3H), 2.17 (s, 3H), 2.10 (s, 3H), 2.03(s,
3H), 2.02 (s, 3H), 2.01 (s, 3H), 1.50−1.54 (m, 1H), 1.20−1.25 (m,
1H); 13C NMR (CDCl3, 100 MHz) δ 170.6, 170.4, 170.2, 170.0,
169.5, 143.5, 138.7, 138.3, 138.0, 129.9, 128.6, 128.5, 128.4, 128.3,
1,3-cis-3-Tosylaminodeoxydisaccharide (4mc). Compound
4mc (gummy liquid, 49 mg, 67% yield) was prepared according to
the general procedure from glycosyl donor 1f (56 mg, 0.1 mmol),
glycosyl acceptor 2i (7 mg, 0.11 mmol), and p-toluenesulfonamide 3a
(18.8 mg, 0.11 mmol) and purified by column chromatography
(hexane/ethyl acetate = 2:1 to 1:1): [α]D20 = +67.4 (c 1.0 CHCl3); 1H
NMR (CDCl3, 400 MHz) δ 7.71 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0
5252
dx.doi.org/10.1021/jo300791v | J. Org. Chem. 2012, 77, 5245−5254

The Journal of Organic Chemistry
Article
128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 126.7, 98.0, 97.2, 91.5, 81.8,
80.1, 78.6, 75.6, 75.3, 73.3, 70.2, 69.6, 68.5, 68.4, 68.0, 67.7, 67.2, 65.4,
62.8, 61.6, 55.8, 46.1, 31.6, 30.9, 21.5, 20.9, 20.8, 20.7, 20.6; IR
(CHCl3) 3417, 1751, 1643, 1365, 1226, 1041, 740, 555 cm−1; HRMS
(ESI) m/z [M + Na]+ calcd for C57H69NO21SNa 1158.3986, found
1158.3981.
1,3-cis-3-Tosylaminodeoxytrisaccharide (4q). Compound 4q
(gummy liquid, 50 mg, 44% yield) was prepared according to the
general procedure from glycosyl donor 1f (56 mg, 0.1 mmol), glycosyl
acceptor 2d (51.2 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
1226, 1157, 1072, 910, 817, 748, 702, 601 cm−1; HRMS (ESI) m/z [M
+ Na]+ calcd for C57H69NO21SNa 1158.3975, found 1158.3981.
Procedure for Deprotection of 3-Benzyloxycarbonylamino-
2,3-dideoxydisaccharide 4ib to Synthesize 3-Amino-2,3-
dideoxydisaccharide 6. To a solution of 3-benzyloxycarbonylami-
no-2,3-dideoxydisaccharide 4jb (71.0 mg, 0.1 mmol) in MeOH (2
mL) was added NaOMe (3.0 mg, 0.03 mmol, 0.3 equiv) under N2
atmosphere. The reaction mixture was stirred at room temperature for
5 h, filtered with silica gel, and washed with MeOH. The filtrate was
concentrated. The crude product 5 was dissolved in MeOH (2 mL),
and palladium on carbon (10%, 7 mg) was added. The mixture was
degassed and then stirred overnight under H2. The mixture was
filtered through a pad of Celite and washed with EtOAc. The solvent
was evaporated under reduced pressure, and the residue was subjected
to column chromatography (silica gel, CHCl3/MeOH = 1:1) to obtain
3-amino-2,3-dideoxydisaccharide 6 (two-step yield: 74%).
mg, 0.11 mmol) and purified by column chromatography (hexane/
1
ethyl acetate = 2:1 to 1:1): [α]D = +44.3 (c 1.0 CHCl3); H NMR
20
(CDCl3, 400 MHz) δ 7.76 (d, J = 6.8 Hz, 2H), 7.22−7.45 (m, 15H),
7.00 (d, J = 6.0 Hz, 2H), 6.21 (d, J = 10.0 Hz, 1H), 5.51 (t, J = 6.0 Hz,
1H), 5.45 (d, J = 4.8 Hz, 1H), 5.26−5.28 (m, 1H), 5.14 (d, J = 4.8 Hz,
1H), 5.12 (t, J = 9.2 Hz, 1H), 4.88 (d, J = 10.8 Hz, 1H), 4.79 (d, J =
12.0 Hz, 1H), 4.70 (d, J = 12.8 Hz, 1H), 4.57−4.65 (m, 4H), 4.02−
4.17 (m, 5H), 3.88−3.91 (m, 2H), 3.37−3.77 (m, 3H), 3.49−3.59 (m,
2H), 3.46 (s, 3H), 2.39 (s, 3H), 2.12 (s, 3H), 2.09 (s, 3H), 2.05 (s,
3H), 2.00 (s, 3H), 1.95−1.98 (m, 4H), 1.11 (d, J = 13.6 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 170.6, 170.3, 170.2, 170.0, 169.5, 143.4,
138.9, 137.7, 137.0, 129.9, 128.7, 128.6, 128.4, 128.3, 128.1, 128.2,
127.9, 127.8, 127.7, 127.6, 126.9, 97.8, 97.3, 91.2, 82.7, 79.9, 76.7, 76.5,
75.5, 73.6, 73.3, 70.2, 70.1, 69.0, 68.7, 68.5, 68.1, 68.0, 65.7, 63.0, 61.6,
55.6, 45.6, 31.6, 21.5, 20.8, 20.7, 20.6, 20.5; IR (CHCl3) 3433, 2945,
1746, 1447, 1241, 1040, 765 cm−1; HRMS (ESI) m/z [M + Na]+ calcd
for C57H69NO21SNa 1158.3975, found 1158.3972.
1,3-cis-3-Tosylaminodeoxytrisaccharide (4r). Compound 4r
(gummy liquid, 50 mg, 43% yield) was prepared according to the
general procedure from glycosyl donor 1f (56 mg, 0.1 mmol), glycosyl
acceptor 2e (56 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
mg, 0.11 mmol) and purified by column chromatography (hexane/
ethyl acetate = 2:1 to 1:1): [α]D20 = +104.2 (c 1.0 CHCl3); 1H NMR
(CDCl3, 400 MHz) δ 8.11 (d, J = 7.2 Hz, 2H), 7.99−8.01 (m, 4H),
7.89 (d, J = 8.4 Hz, 2H), 7.70−7.72 (m, 1H), 7.45−7.60 (m, 6H),
7.34−7.38 (m, 4H), 5.92−5.96 (m, 2H), 5.55 (dd, J = 10.8, 3.6
Hz,1H), 5.46 (d, J = 2.0 Hz, 1H), 5.37 (d, J = 3.6 Hz, 1H), 5.28−5.30
(m, 2H), 5.08−5.11 (m, 2H), 4.84 (d, J = 2.4 Hz, 1H), 4.40−4.48 (m,
3H), 4.23−4.25 (m, 1H), 4.08 (dd, J = 10.4, 6.0 Hz, 1H), 3.98−4.02
(m, 2H), 3.72 (dt, J = 14.4, 2.4 Hz, 1H), 3.62 (dd, J = 9.6, 4.0 Hz, 1H),
3.58 (dd, J = 12.0, 2.0 Hz, 1H), 3.49 (s, 3H), 3.44 (dd, J = 12.0, 4.4
Hz, 1H), 2.45 (s, 3H), 2.30 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H), 2.02 (s,
3H), 1.88 (s, 3H), 1.54 (dt, J = 14.8, 3.6 Hz, 1H), 1.40 (dd, J = 14.4,
2.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 170.6, 170.5, 170.0,
169.9, 169.5, 165.9, 165.8, 165.7, 143.7, 138.3, 134.5, 133.6, 133.3,
130.1, 129.9, 129.6, 129.3, 129.2, 129.1, 128.7, 128.5, 128.4, 128.3,
127.0, 97.4, 97.3, 91.4, 73.2, 70.2, 69.2, 68.7, 68.6, 68.5, 68.4, 67.8,
67.6, 65.8, 62.3, 62.0, 61.5, 55.8, 45.8, 31.5, 21.6, 21.1, 20.71, 20.68,
20.62, 20.59; IR (CHCl3) 3317, 2954, 1728, 1597, 1450, 1365, 1226,
1165, 1103, 1041, 910, 756, 709 cm−1; HRMS (ESI) m/z [M + Na]+
calcd for C57H63NO24SNa 1200.3357, found 1200.3358.
1,3-cis-3-Benzyloxycarbonylaminodeoxydisaccharide (5).
1
Data: H NMR (CDCl3, 400 MHz) δ 7.24−7.33 (m, 20H), 6.42 (d,
J = 8.0 Hz, 1H), 5.07 (q, J = 12.4 Hz, 2H), 5.01 (d, J = 12.4 Hz, 1H),
4.95 (d, J = 10.8 Hz, 1H), 4.79 (d, J = 10.8 Hz, 1H), 4.40−4.57 (m,
5H), 4.11−4.18 (m, 1H), 3.98 (t, J = 9.2 Hz, 1H), 3.82 (d, J = 10.0 Hz,
1H), 3.73−3.75 (m, 2H), 3.45−3.50 (m, 2H), 3.37−3.38 (m, 2H),
3.26 (s, 3H), 3.03−3.05 (m, 1H), 1.81−1.94 (m, 2H), 1.26 (d, J = 5.6
Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 158.4, 138.7, 138.2, 138.13,
137.08, 136.4, 128.6, 128.49, 128.45, 128.41, 128.23, 128.15, 128.10,
128.05, 127.93, 127.86, 127.8, 127.7, 97.8, 96.1, 82.0, 80.5, 75.8, 75.0,
73.6, 73.2, 69.4, 67.0, 64.9, 64.4, 55.2, 48.7, 33.4, 17.5; HRMS (ESI)
m/z [M + Na]+ calcd for C42H49NO10Na 750.3254, found 750.3259.
1,3-cis-3-Aminodeoxydisaccharide (6). Data: [α]D = 2.02 (c
20
1
1.0 MeOH); H NMR (CD3OD, 400 MHz) δ 4.59 (d, J = 3.6 Hz,
1H), 3.80 (dd, J = 2.4, 10.8 Hz, 1H), 3.70−3.76 (m, 1H), 3.45−3.52
(m, 1H), 3.31 (s, 3H), 3.19−3.30 (m, 4H), 3.02−3.07 (m, 1H), 1.80−
1.96 (m, 2H), 1.15 (d, J = 6.0 Hz, 3H); 13C NMR (CD3OD, 100
MHz) δ 100.0, 96.9, 73.7, 72.1, 71.4, 70.7, 69.7, 65.8, 63.0, 54.3, 33.1,
16.9; HRMS (ESI) m/z [M + H]+ calcd for C13H26NO8 324.1658,
found 324.1653.
ASSOCIATED CONTENT
■
S
* Supporting Information
NMR spectra of compounds 4a−4r, 5, and 6. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: xuewei@ntu.edu.sg.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
1,3-cis-3-Tosylaminodeoxytrisaccharide (4s). Compound 4s
(gummy liquid, 61 mg, 54% yield) was prepared according to the
general procedure from glycosyl donor 1g (56 mg, 0.1 mmol), glycosyl
acceptor 2a (51.2 mg, 0.11 mmol), and p-toluenesulfonamide 3a (18.8
We gratefully acknowledge Nanyang Technological University
(RG50/08) and the Ministry of Education, Singapore (MOE
2009-T2-1-030) for the financial support of this research.
mg, 0.11 mmol) and purified by column chromatography (hexane/
1
ethyl acetate = 2:1 to 1:1): [α]D = +2.38 (c 1.0 CHCl3); H NMR
20
REFERENCES
■
(CDCl3, 400 MHz) δ 7.71 (d, J = 8.0 Hz, 2H), 7.23−7.39 (m, 17H),
5.37 (d, J = 2.8 Hz, 1H), 5.22 (d, J = 6.0 Hz, 1H), 5.15 (dd, J = 10.4,
7.6 Hz, 1H), 4.97−5.01 (m, 2H), 4.78−4.86 (m, 3H), 4.69−4.73 (m,
2H), 4.65 (d, J = 3.6 Hz, 1H), 4.45 (d, J = 3.6 Hz, 1H), 4.43 (d, J = 8.0
Hz, 1H), 4.15−4.17 (m, 1H), 4.05−4.11 (m, 2H), 3.89−4.00 (m, 5H),
3.66−3.71 (m, 3H), 3.51−3.56 (m, 2H), 3.46 (t, J = 9.2 Hz, 1H), 3.35
(s, 3H), 2.28 (s, 3H), 2.11−2.18 (m, 4H), 2.04 (s, 3H), 2.03(s, 6H),
1.99 (s, 3H), 1.46 (dt, J = 13.6, 4.0 Hz, 1H); 13C NMR (CDCl3, 100
MHz) δ 170.33, 170.27, 170.1, 170.0, 169.4, 143.7, 138.8, 138.3, 138.2,
137.4, 129.8, 128.4−128.5 (m, 6C), 128.13, 128.10, 127.9, 127.8,
127.7, 127.6, 127.1, 101.7, 98.2, 97.9, 82.0, 80.0, 75.8, 75.0, 73.3, 72.5,
71.0, 70.5, 69.7, 68.6, 67.3, 66.7, 64.1, 60.9, 55.1, 47.4, 32.3, 21.3, 20.8,
20.7, 20.6, 20.5; IR (CHCl3) 3302, 2924, 1751, 1450, 1365, 1334,
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