Synthesis of DTPA-conjugated (1,4)-linked 2-aminoglycosides varying in the anomeric configuration and their MRI contrast effect

Article abstract of DOI:10.1039/b507824e

We describe the efficient synthesis of DTPA-conjugated oligosaccharides composed of α- and/ or β-linked tri to monoglucosamines. Gd(III) complex with DTPA-conjugated chitotriitol 1 has been reported to be an effective MRI contrast agent. In order to eluci

Full text of DOI:10.1039/b507824e

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A R T I C L E
Synthesis of DTPA-conjugated (1,4)-linked 2-aminoglycosides
varying in the anomeric configuration and their MRI contrast effect†
Hiroshi Tanaka,a Yoshio Ando,a Masatoshi Wadab and Takashi Takahashi*a
a Department of Applied Chemistry, Graduate School of Science and Engineering,
Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 152-8552, Japan
b Nihon Medi-Physics, 3-1, Kitasode, Sodegaura-Shi, Chiba, 299-0266, Japan
Received 3rd June 2005, Accepted 29th June 2005
First published as an Advance Article on the web 1st August 2005
We describe the efficient synthesis of DTPA-conjugated oligosaccharides composed of a- and/or b-linked tri to
monoglucosamines. Gd(III) complex with DTPA-conjugated chitotriitol 1 has been reported to be an effective MRI
contrast agent. In order to elucidate the structure–property relationships, we planned to synthesize the
DTPA-conjugated 2-amino-tri-, di-, and monosaccharides varying in configuration at the anomeric positions and the
C2 position on the reducing end. Our strategy for the synthesis of the DTPA-conjugated oligosaccharides involves
O-perbenzyl protected 2-amino-tri-, di-, and monosaccharides as key intermediates. The 2-aminoglycosides were
prepared by non-selective glycosidation of 2-azido-2-deoxyglycosyl donors, followed by separation of two anomeric
isomers. Although the synthesis involves separation of the stereoisomers, it circumvents not only the careful tuning of
reaction conditions, but also the time-consuming preparation of glycosyl donors attached to different protecting
groups. The protected 2-aminoglycosides were converted to the fully deprotected DTPA-conjugated tri- to
monosaccharides by the same operation. MRI phantom study using the Gd(III) complexes of DTPA-conjugated
oligosaccharides indicates that the number of the monosaccharide units was critical for enhancing the relative signal
intensity of water protons per Gd, and various stereoisomers would be candidate scaffolds for MRI contrast agents.
Introduction
Chitin is composed of poly-b(1,4) N-acetylglucosamine, and is
a skeletal material in crustaceans. Hydrolysis of the acetamide
groups in chitin under basic conditions provides chitosan, which
possesses amino groups. Recently, chitosan has served as an
effective biocompatible scaffold1–3 amenable to conjugation with
various functional devices via acylation of the C2 amino groups.3
Acidic hydrolysis of the glycosidic bonds on chitosan, followed
by reduction of the resulting hemiacetal to diol enables one
to prepare oligo-b(1,4) N-acetylglucosamines as structurally-
defined and water-soluble scaffolds. Additionally, the reduction
is effective for improvement of their hydrophilicity. However,
these degradation processes can unfortunately involve anomer-
ization to the thermodynamically more stable a-glycosidic bond,
and epimerization of the C2 amino group at the reducing end,
thereby providing several stereoisomers, of which the purifi-
cation and structure determination are difficult. Additionally,
in most cases, there is limited information on their structure–
property relationships because the stereoisomers of the chitosan
derivatives are not available from natural sources.
Fig. 1 Structure of CH3-DTPA–Gd (1).
of effective MRI contrast agents. Additionally, in order to
elucidate their structure–property relationships and confirm the
purity of the final product, the total chemical synthesis of the 2-
aminooligosaccharides varying in configuration at the anomeric
position and the C2 position on the reducing end is required.
Herein, we report an efficient synthesis of DTPA-conjugated
oligosaccharides and their application as MRI contrast agents.
Magnetic resonance imaging (MRI) is a powerful and non-
invasive diagnostic technique based on the differences between
relaxation rate of water protons, and provides important graph-
ical images of the inside of the human body.4 MRI contrast
agents such as gadolinium–diethylenetriamine-N,N,Nꢀ,Nꢀꢀ,Nꢀꢀ-
pentaacetic acid complexes (Gd–DTPA) assist improvement of
the tissue discrimination in the MRI images. Recently, CH3-
DTPA–Gd (1) composed of a chitotriitol attached with three
Gd–DTPA units on the amino groups, has been reported as an
effective MRI contrast agent (Fig. 1).5,6 The proton relaxivity
per Gd of 1 is R1 = 8.3 (mMs)−1 at 37 ◦C in water at 1.5
T, which is twice as great as that of Gd–DTPA (R1 = 3.1
(mMs)−1). This result suggested us that linking multiple Gd–
DTPA units with the various hydrophilic scaffolds such as the
chitosan hydrolysates would be an effective way for the synthesis
Results and discussion
We planned the synthesis of fourteen DTPA-conjugated
oligosaccharides: eight trisaccharides 2, four disaccharides 3
and two monosaccharides 4, each varying in configuration at
the anomeric positions and the C2 position at the reducing
end (Scheme 1). Our strategy for the synthesis of the DTPA-
conjugated oligosaccharides 2, 3, and 4 involves the perbenzyl
protected amino glycosides 5, 6, and 7 as key intermediates.
Acylation of the amines 5, 6, and 7 with the tert-butyl protected
DTPA mono acid 8,7 followed by deprotection of all protecting
groups provides the DTPA-conjugated oligosaccharides 2, 3 and
4. The intermediates 5, 6, and 7 would be prepared by non-
stereoselective glycosylation of alditols 13 and 14 with the 2-
azido glycosyl imidates 11 and 12,8 followed by chemoselective
reduction of the azido groups. Although this methodology
involves separation of the stereoisomers, it circumvents not
only the careful tuning reaction conditions, but also time-
consuming preparation of the glycosyl donors attached to
† Electronic supplementary information (ESI) available: NMR spectra.
See http://dx.doi.org/10.1039/b507824e
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 1 1
©

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Scheme 1 Strategy for the synthesis of the DTPA-conjugated amino glycosides 2, 3, and 4.
different protecting groups.9 Furthermore, transformation of
the resultant protected glycosides 9, 10, 13, and 14 to the
corresponding amino glycosides 5, 6, and 7 can be achieved
by the same operation.
Preparation of the protected alditols 13 and 14 is shown
in Scheme 2. The 2-azido glucoside 17 was prepared from
glucosamine (15) by the established procedure.10 Deacetylation
of 17, and formation of 4,6-benzyliden acetal provided acetal
19. Selective removal of the silyl ether of 19, followed by
reduction of the anomeric position afforded triol. Protection
of the resulting hydroxyl groups with benzyl ethers provided 21
in 91% yield from 17. Regioselective reductive opening of the
benzyliden acetal 21 provided acceptor 13 in 75% yield. The
Manno derivative 14 was prepared from mannosamine (16)10 by
the same procedure.
The synthesis of amines 5, 6, and 7 was conducted as shown in
Scheme 3. Glycosylation of 13 with imidate 12 using TMSOTf
in several solvents (CH2Cl2, Et2O, CH3CN, and toluene) at
−25 ◦C revealed that toluene was able to provide a mixture
of disaccharides 23 in 68% yield (b : a = 47 : 53). Glycosylation
of 14 with 12 under the same reaction conditions provided
disaccharides 24 in 61% yield (b : a = 61 : 39), respectively.
Deprotection of Lev group of 23 and 24, followed by separation
of the b- and a-isomers afforded the corresponding disaccharides
25b and 25a, and 26b and 26a in 43 and 48%, and 33 and 25%
yields based on 23 and 24, respectively. Glycosylation of the
a-linked disaccharide 25a and 26a with donor 11 in toluene
provided trisaccharides 9e and 9g in 80% yield (b : a = 50 :
50), and 9f and 9h in 90% (b : a = 42 : 58). Separation of
the mixtures by column chromatography on silica gel provided
trisaccharides 9e, 9g, 9f, and 9h in 31, 43, 34, and 47% yields,
based on disaccharides 25a and 26a, respectively. Glycosylation
of the b-linked disaccharide 25b with donor 11 under the same
reaction condition, unfortunately provided the b-isomer 9a as
the major product (81% yield, b : a= 79 : 21). After optimization
of the reaction conditions, we found that diethylether was
effective for the synthesis of a mixture of both isomers to provide
trisaccharides 9a and 9c in 83% yield (b : a = 52 : 48) from 25b,
and 9b and 9d in 70% (b : a = 59 : 41) from 26b. Separation of
the b- and a-isomers by chromatography on silica gel provided
Scheme 2 Reagents and conditions: (a) NaOMe, MeOH; (b) PhCH-
(OMe)2, p-TsOH, MeCN, 96% for 19; (c) HF–Py., Py.; (d) NaBH4, THF,
EtOH; (e) BnBr, NaH, TBAI, DMF, 91% for 21, 88% for 22; (f) TFA,
Et3SiH, CH2Cl2, 75% for 13, 89% for 14.
3 3 1 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8

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Scheme 3 Reagents and conditions: (a) TMSOTf, toluene, MS 4 A, −25 ◦C, 68% (b : a = 47 : 53) for 25, 61% (b : a = 61 : 39) for 26; (b)
˚
H2NNH2–H2O, AcOH, Py, rt, 43% for 25b, 48% for 25a from 23, 33% for 26b, 25% for 26a from 24; (c) TMSOTf, Et2O, MS 4 A −25 ◦C, 34% for
˚
9a, 40% for 9b, 46% for 9c, 28% for 9d; (d) TMSOTf, toluene, MS 4 A, −25 ◦C, 31% for 9e, 34% for 9f, 43% for 9g, and 47% for 9h; (e) BnBr, NaH,
˚
TBAI, DMF, 93% for 10a, 71% for 10b; 95% for 10c, 83% for 10d.
trisaccharides 9a, 9c, 9b, and 9d in 34, 46, 40, and 28% yields,
respectively. The disaccharides 10a–d bearing azido groups were
prepared by benzylation of alcohols 25a, 25b, 26a, and 26b in
excellent yields.
Next, we investigated the transformation of the protected
oligosaccharides 9, 10, 13, and 14 to DTPA-conjugates 2, 3,
and 4 (Scheme 4, and Table 1). Treatment of the azido 9a with
trimethylphosphine11 resulted in reduction to the corresponding
amine 5a. Tributyl- and triphenylphosphines were not effective
for the reduction. Acylation of the crude 5a with tBuDTPA-
OH 8 using HATU smoothly proceeded to provide the corre-
sponding DTPA conjugate 27a in 58% yield in 2 steps. Finally,
deprotection of the tert-butyl ester with TFA in the presence of
Et3SiH,12 followed by hydrogenolysis in the presence of Pd(OH)2
under H2 afforded the fully deprotected product 2a. It should
be noted that the order of the removal of the protecting groups
was critical for the success of the deprotection. Purification of
the crude 2a was achieved by reverse-phase HPLC to afford
the fully deprotected DTPA-conjugated oligosaccharide 2a in
23% yields. Transformation of azidos 9b–h, 10a–d, 13, and
14 to the DTPA-conjugated oligosaccharides 2b–h, 3a–d, 4a–
b was achieved by the same procedure to provide the desired
compounds 2b–h, 3a–d, and 4a–b in moderate yields (Table 1 and
Fig. 2).
Table 1 Yields of protected DTPA-conjugates 27, 28, and 29, and DTPA-conjugates 2, 3, and 4
Entry
Azido
Protected DTPA-conjugate
Yield of 27, 28, 29 (%)
DTPA-conjugate
Yield of 2, 3, 4 (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
9a
27a
27b
27c
27d
27e
27f
27g
27h
28a
28b
28c
28d
29a
29b
58%
71%
47%
46%
69%
81%
59%
78%
78%
80%
73%
77%
73%
74%
2a
2b
2c
2d
2e
2f
2g
2h
3a
3b
3c
3d
4a
4b
23%
36%
40%
33%
24%
30%
21%
36%
15%
28%
34%
20%
38%
43%
9b
9c
9d
9e
9f
9g
9h
10a
10b
10c
10d
13
14
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 1 3

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Table 2 Signal intensities of Gd containing DTPA-conjugated
oligosaccharide solution using SE sequence
Compound
Signal intensity (×106)
Standard division (×106)
3a
7.92
7.53
6.82
6.00
0.52
0.52
0.52
0.52
3c
4a
Gd–DTPA
3b
7.97
7.84
6.69
5.88
0.52
0.51
0.53
0.54
3d
4b
Gd–DTPA
2a
8.79
8.78
8.17
8.34
6.06
0.53
0.53
0.53
0.51
0.51
2c
2e
2g
Gd–DTPA
2b
8.82
8.50
8.37
8.78
6.01
0.54
0.53
0.52
0.53
0.51
2d
2f
2h
Gd–DTPA
and various stereoisomers could be candidate scaffolds for MRI
contrast agents. We plan to further study new biocompatible
and functional materials using the aminoglycoside scaffolds for
biomedical applications.
Experimental section
General
Scheme 4 Reagents and conditions: (a) PMe3, toluene, 0.1 M NaOH
aq.; (b) HATU, DIEA DMAP, CH2Cl2; (c) TFA, Et3SiH, CH2Cl2;
(d) Pd(OH)2, H2, EtOAc, MeOH, H2O.
NMR spectra were recorded on a JEOL Model ECP-400
(400 MHz for 1H, 100 MHz for 13C) instrument in the
indicated solvent. Chemical shifts are reported in units parts
per million (ppm) relative to the signal (0 ppm) for internal
MRI examination
1
tetramethylsilane for solutions in CDCl3. H NMR spectrum
MRI phantom studies using the Gd(III) complexes with the
DTPA-conjugated oligosaccharides 2a–h, 3a–d and 4a–b were
investigated. DTPA was used as a reference ligand for the MRI
study. 0.46 mM aqueous solutions of GdCl3 containing two
equivalents of DTPA units on each oligosaccharides 2a–h, 3a–d
and 4a–b were prepared. Free gadolinium ions were not detected
in these solutions. MRI images of each Gd complex solution
with DTPA-conjugated oligosaccharides were obtained using
spin echo (SE) sequence, where repetition time/echo time =
60 ms/10.3 ms, acquisition matrix = 256 × 256, number of
excitations = 16, field of view = 40 mm × 40 mm, slice
thickness = 5 mm, receiver band width = 50 kHz (Fig. 3 and
Table 2). Table 3 summarizes the relative signal intensity per
Gd in the regions of interest (ROI) based on Gd-DTPA. The
relative signal intensities of the trisaccharides 2a–h solution
were larger than those of di- and mono-saccharides 3a–d and
4a–b solution. However, there were no significant differences
between the stereoisomers 2a–h. These results clearly indicate
that the number of monosaccharide units is critical for the
signal enhancement ability per Gd. However, the shape of the
saccharide scaffolds did not largely influence this ability.
data are reported as follows: CDCl3 (7.26 ppm) or D2O (HOD
(4.8654 ppm at 285 K, 4.7015 ppm at 303 K, 4.6201 ppm at
311 K, 4.3560 ppm at 339 K as internal standard using 3-
(trimethylsilyl)-1-propanesulfonicacid sodium salt as external
standard)). 13C NMR spectrum data are reported as follows:
CDCl3 (77.0 ppm) or acetone-d6 (30.3 ppm) as internal standard
for D2O. Multiplicities are reported by using the following
abbreviations: s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet; br, broad; J, coupling constants in Hertz. IR
spectra were recorded on a Perkin-Elmer Spectrum One FT-IR
spectrophotometer. Only the strongest and/or structurally im-
portant peaks are reported as the IR data given in cm−1. Optical
rotations were measured on a JASCO model P-1020 polarimeter.
All reactions were monitored by thin-layer chromatography
carried out on 0.2 mm E. Merck silica gel plates (60F-254) with
UV light, visualized by 10% ethanolic phosphomolybdic acid,
p-anisaldehyde solution or 0.5% ninhydrin n-butanol solution.
Kanto silica gel was used for column chromatography. Fuji
silysia chemical NH–silica gel was used for column chromatog-
raphy. Gel permeation chromatography (GPC) for qualitative
analysis were performed on Japan Analytical Industry Model
LC908 (recycling preparative HPLC), on a Japan Analytical
Industry Model RI-5 refractive index detector and on a Japan
Analytical Industry Model 310 ultra violet detector with a
polystyrene gel column (JAIGEL-1H, 20mm × 600 mm), using
chloroform as solvent (3.5 mL min−1). High performance liquid
chromatography (HPLC) was performed on a Waters apparatus
using a Senshu Pak Silica 3301-N Column with a Waters 2996
photodiode array detector at 254 nm. ESI-TOF Mass spectra
were measured with P. E. Biosystems TK-3500 Biospectrom-
etry Workstation. High performance liquid chromatography
Conclusion
In summary we have demonstrated the efficient synthesis of
triaminoglycosides 2a–h attached with DTPA as MRI contrast
agents. All possible anomeric isomers were prepared by non-
stereoselective glycosidation of 2-azido glycosyl donors, fol-
lowed by separation of the b- and a-isomers. MRI phantom
studies to elucidate the signal enhancing ability of their Gd com-
plexes, revealed that the number of the monosaccharide units
was critical for enhancing the relative signal intensity per Gd,
3 3 1 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8

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Fig. 2 Structure of the DTPA-conjugated oligosaccharides 2, 3, and 4.
Fig. 3 MRI phantom images and signal intensities of Gd containing DTPA-conjugated oligosaccharide solution using SE sequence.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 1 5

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Table 3 Relative signal intensity per Gd based on Gd–DTPA
Entry
DTPA derivative
Relative signal intensity per Gd based on Gd–DTPA
Mean SD
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
2a
2b
2c
2d
2e
2f
2g
2h
3a
3b
3c
3d
4a
4b
DTPA
1.45
1.47
1.45
1.41
1.35
1.39
1.38
1.46
1.32
1.36
1.26
1.33
1.14
1.14
1
1.42 0.04a,d
—
—
—
—
—
—
—
1.32 0.04b,e
—
—
—
1.14c
—
1
a Trisaccharides 2a–h. b Disaccharides 3a–d. c Monosaccharides 4a–b. d p < 0.01 vs. b. e p < 0.005 vs c.
(HPLC) for qualitative and quantitative analysis were performed
NMR (400 MHz, CDCl3) d 7.35–7.49 (m, 5H, aromatic), 5.52
(s, 1H), 4.96 (d, 1H, anomeric, J = 1.4 Hz), 4.27 (dd, 1H, J =
4.8 Hz, J = 10.6 Hz), 3.91 (dd, 1H, J = 1.4 Hz, J = 3.9 Hz), 3.84
(dd, 1H, J = 3.9 Hz, J = 9.7 Hz), 3.83 (dd, 1H, J = 10.1 Hz,
J = 10.6 Hz), 3.70 (dd, 1H, J = 9.7 Hz, J = 9.2 Hz), 3.32 (ddd,
1H, J = 9.2 Hz, J = 4.8 Hz, J = 10.1 Hz), 0.94 (d, 9H), 0.16,
0.17 (2s, 6H); 13C NMR (100 MHz, CDCl3) d 136.97, 129.25,
128.30, 126.23, 102.11, 96.14 (anomeric), 78.40, 69.61, 68.32,
67.05, 66.33, 25.55, 17.90, −4.16, −5.46; IR (KBr) 3380, 3067,
2930, 2859, 2110 (cm−1).
R
on a Gilson 506C system using a Develosilꢀ ODS-UG-5
column. Dry THF, dry hexane, and dry diethylether, were
distilled from sodium were contained with a catalytic amount of
benzophenone. Dry benzene, dry toluene, were distilled from a
lump of sodium. Dry dichloromethane was distilled from P2O5.
Dry DMF, dry triethylamine and dry pyridine were distilled
from CaH2. Dry methanol and dry ethanol were distilled from
magnesium contained with a catalytic amount of iodine.
tert-Butyldimethylsilyl 2-azido-4,6-O-benzylidene-2-deoxy-b-
2-Azido-1,3,5-tri-O-benzyl-4,6-O-benzylidene-2-deoxy-D-
glucitol (21). To a stirred solution of tert-butyldimethylsilyl
2-azido-4,6-O-benzylidene-2-deoxy-b-D-glucopyranoside (19)
(1.39 g, 3.41 mmol) in dry pyridine (10 mL) was added hydrogen
fluoride–pyridine (1.00 mL) at 0 ◦C. After being stirred at
room temperature for 5 h, the reaction mixture was poured
into ice-cooled saturated aq. NaHCO3. The aqueous layer was
extracted with two portions of ethyl acetate. The combined
extract was washed with saturated aq. NaHCO3 and brine,
dried over MgSO4, filtered and evaporated in vacuo. The residue
was used for the next reaction without further purification.
To a stirred solution of NaBH4 (155 mg, 4.09 mmol) in dry
THF (15 mL) was added a solution of the residue in dry EtOH
(15 mL) at 0 ◦C. After being stirred at room temperature for
3 h, the reaction mixture was poured into saturated aq. NH4Cl.
The aqueous layer was extracted with two portions of ethyl
acetate. The combined extract was washed with aq. NH4Cl
and brine, dried over MgSO4, filtered and evaporated in vacuo.
The residue was used for the next reaction without further
purification. To a stirred 55% sodium hydride solution (367 mg,
15.3 mmol), which had been washed twice with dry hexane, was
added a solution of the residue in dry N,N-dimethylformamide
(5 mL) at 0 ◦C. The reaction mixture was stirred at 0 ◦C for
30 min. Then benzyl bromide (1.46 mL, 12.3 mmol) and a
catalytic amount of n-Bu4NI were added to the reaction mixture
at 0 ◦C. The reaction mixture was allowed to warm to room
temperature. After being stirred at the same temperature for
3 h, the reaction mixture was poured into saturated aq. NH4Cl.
The aqueous layer was extracted with two portions of ethyl
acetate. The combined extract was washed with 1 M HCl,
saturated aq. NaHCO3 and brine, dried over MgSO4. After
removal of the solvent in vacuo, the residue was purified by
column chromatography on silica gel with hexane–ethyl acetate
80 : 20 to give 2-azido-1,3,5-tri-O-benzyl-4,6-O-benzylidene-
2-deoxy-D-glucitol (21) (1.88 g, 3.32 mmol, 3 steps 94%) as a
D-glucopyranoside (19). To
a stirred solution of tert-
butyldimethylsilyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-b-D-
glucopyranoside (17) (20.0 g, 44.9 mmol) in MeOH (150 mL)
was added sodium (50 mg) at room temperature. After being
stirred at the same temperature for 3 h, the reaction mixture was
concentrated in vacuo and azeotroped with toluene. The residue
was used for the next reaction without further purification.
To a stirred solution of the residue in dry CH3CN (250 mL)
was added benzaldehyde dimethyl acetal (10.1 mL, 67.4 mmol)
and a catalytic amount of p-toluenesulfonic acid (200 mg) at
room temperature. After being stirred at the same temperature
for 2 h, the reaction mixture was neutralized with K2CO3
(18.7 g, 135 mmol) at the same temperature. After 30 min,
the reaction mixture was filtered through a pad of celite and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel with hexane–ethyl acetate 80 :
20 to give tert-butyldimethylsilyl-2-azido-4,6-O-benzylidene-2-
deoxy-b-D-glucopyranoside (19) (17.6 g, 43.2 mmol, 2 steps
96%) as a colorless oil. [a]2D7 −35.5 (c 1.00, CHCl3); H NMR
1
(400 MHz, CDCl3) d 7.36–7.49 (m, 5H, aromatic), 5.52 (s, 1H,
a), 4.63 (d, 1H, anomeric, J = 7.2 Hz), 4.28 (dd, 1H, J = 4.8 Hz,
J = 10.6 Hz), 3.77 (dd, 1H, J = 10.1 Hz, J = 10.1 Hz), 3.61 (dd,
1H, J = 9.2 Hz, J = 9.2 Hz), 3.55 (dd, 1H, J = 9.2 Hz, J = 9.2
Hz), 3.39 (ddd, 1H, J = 9.2 Hz, J = 9.7 Hz), 3.32 (dd, 1H, J =
7.7 Hz, J = 9.2 Hz), 0.94 (s, 9H), 0.16, 0.17 (2s, 6H); 13C NMR
(100 MHz, CDCl3) d 136.82, 129.35, 128.35, 126.26, 101.98,
97.52 (anomeric), 80.70, 71.72, 68.94, 68.51, 66.27, 25.23, 17.89,
−4.38, −5.21; IR (KBr) 3403, 3038, 2930, 2860, 2109 (cm−1).
tert-Butyldmethylsilyl 2-azido-4,6-O-benzylidene-2-deoxy-a-
D-mannopyranoside (20). According to the procedure for the
synthesis of 19, tetraacetate (18) (4.10 g, 9.20 mmol) was treated
with NaOMe, which was prepared from sodium (10.0 mg) in
MeOH (46 mL) to provide a tetraol. The tetraol was treated
with benzaldehyde dimethyl acetal (2.07 mL, 13.8 mmol) in
the presence of p-toluenesulfonic acid (40.0 mg) in CH3CN
(50 mL), followed by neutralization of the reaction mixture with
K2CO3 (3.81 g, 27.6 mmol, 3.00 eq.) to provide acetal 20 (3.75 g,
9.20 mmol, quant in 2 steps.); [a]2D5 −101.4 (c 1.25, CHCl3); 1H
1
colorless oil. [a]2D6 −9.6 (c 1.14, CHCl3); H NMR (400 MHz,
CDCl3) d 7.26–7.39 (m, 20H, aromatic), 5.23 (s, 1H), 4.79 (d,
1H, J = 11.6 Hz), 4.59 (d, 1H, J = 12.1 Hz), 4.57 (d, 1H, J =
11.1 Hz), 4.48 (d, 1H, J = 11.6 Hz), 4.47 (d, 1H, J = 12.1 Hz),
3 3 1 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8

View Article Online
4.40 (d, 1H, J = 11.6 Hz), 4.38 (dd, 1H, J = 4.8 Hz, J = 10.6
Hz), 3.98–4.03 (m, 2H), 3.87 (ddd, 1H, J = 5.3 Hz, J = 4.8 Hz,
J = 9.7 Hz), 3.71–3.75 (m, 2H), 3.61–3.65 (m, 1H), 3.56 (dd,
1H, J = 9.7 Hz, J = 10.6 Hz); 13C NMR (100 MHz, CDCl3) d
138.06, 137.74, 137.57, 137.38, 128.88, 128.49, 128.43, 128.35,
128.14, 128.00, 127.94, 127.80, 127.67, 127.63, 126.03, 101.10,
79.48, 76.47, 74.06, 73.28, 71.50, 69.43, 69.36, 68.35, 62.42; IR
(KBr) 3089, 3065, 3033, 2865, 2097 (cm−1).
3.4 Hz, J = 10.1 Hz), 3.82 (dd, 1H, J = 7.7 Hz, J = 8.2 Hz, J =
8.7 Hz), 3.77–3.81 (m, 2H, H-1), 3.72 (dd, 1H, J = 4.8 Hz, J =
10.1 Hz), 3.66–3.71 (m, 1H, H-2), 3.59 (ddd, 1H, J = 8.2 Hz,
J = 3.4 Hz, J = 4.8 Hz), 2.58 (d, 1H, J = 8.7 Hz); 13C NMR
(100 MHz, CDCl3) d 138.17, 138.10, 137.67, 137.62, 128.40,
128.38, 127.93, 127.86, 127.79, 127.70, 127.64, 127.63, 77.96,
75.91, 74.00, 73.51, 73.35, 71.63, 70.40, 69.94, 69.61, 62.05; IR
(KBr) 3536, 3089, 3065, 3032, 2866, 2099 (cm−1).
2-Azido-1,3,5-tri-O-benzyl-4,6-O-benzylidene-2-deoxy-D-
mannitol (22). According to the procedure for the synthesis
of 21, silyl glycoside 20 (3.75 g, 9.20 mmol) was treated with
hydrogen fluoride–pyridine (4.0 mL) in dry (18) pyridine
(40 mL) to provide an acetal. The acetal was treated with
NaBH4 (416 mg, 11.0 mmol) in THF (50 mL) and EtOH
(50 mL) to provide a triol. The triol was reacted with benzyl
bromide (3.94 mL, 33.1 mmol) in the presence of sodium
hydride (994 mg, 41.4 mmol) in DMF (45 mL) to afforded
tribenzyl ether 22 (4.60 g, 8.14 mmol, 3 steps 88%). [a]2d5 −27.7
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-O-
benzyl-2-deoxy-D-glucopyranosyl)-D-glucitol (25). A mixture
of
2-azido-3,6-di-O-benzyl-2-deoxy-4-O-levulinoyl-D-gluco-
pyranosyl trichloroacetimidate (12) (70.0 mg, 111 mmol), 2-
azido-1,3,5,6-tetra-O-benzyl-2-deoxy-D-glucitol (13) (52.5 mg,
˚
4 A in dry
92.5 mmol) and pulverized activated MS
toluene (1.5 mL) was stirred at −25 ◦C for 30 min under
argon to remove a trace amount of water. Trimethylsilyl
trifluoromethanesulfonate (1.67 lL, 9.25 lmol) was added to
the reaction mixture at the same temperature. After being stirred
for 1 h, the reaction mixture was neutralized with triethylamine
and filtered through a pad of celite. The filtrate was concentrated
in vacuo and the residue was purified by column chromatography
on silica gel with hexane–ethyl acetate 65 : 35, and further
purified by gel permeation chromatography (GPC) to give
2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-O-
benzyl-2-deoxy-4-O-levulinoyl-D-glucopyranosyl)-D-glucitol (23)
(a : b = 53 : 47, 65.0 mg, 0.0629 mmol, 68%). The a : b ratio
was determined by HPLC analysis (Senshu Pak Silica-3301-N,
Eluent: hexane–2-propanol = 99 : 1, 3 mL min−1; Retention
time: a-isomer 18.9 min, b-isomer 22.7 min). To a stirred solution
of 2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-levulinoyl-D-glucopyranosyl)-D-glucitol
(23) (2.55 g, 2.47 mmol) in dry pyridine (12 mL) was
added AcOH (18 mL) and hydrazine monohydrate (601 lL,
12.4 mmol) at 0 ◦C. After being stirred at room temperature
for 1 h, the reaction mixture was poured into ice-cooled water.
The aqueous layer was extracted with two portions of ethyl
acetate. The combined extract was washed with 1 M HCl,
saturated aq. NaHCO3 and brine, dried over MgSO4. After
removal of the solvent in vacuo, the residue was purified
by chromatography on silica gel with toluene–ethyl acetate
90 : 10 to give 2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-
azido-3,6-di-O-benzyl-2-deoxy-a-D-glucopyranosyl)-D-glucitol
(25a) (1.11 g, 1.19 mmol, 48%) and 2-azido-1,3,5,6-tetra-O-
benzyl-2-deoxy-4-O-(2-azido-3,6-di-O-benzyl-2-deoxy-b-D-
glucopyranosyl)-D-glucitol (25b) (995 mg, 1.06 mmol, 43%) as
a colorless oil.
1
(c 1.25, CHCl3); H NMR (400 MHz, CDCl3) d 7.21–7.48 (m,
20H, aromatic), 5.52 (s, 1H), 4.82 (d, 1H, J = 11.6 Hz), 4.53
(d, 1H, J = 11.6 Hz), 4.52 (m, 2H), 4.35 (d, 1H, J = 11.6 Hz),
4.47 (dd, 1H, J = 4.8 Hz, J = 10.6 Hz), 4.41 (d, 1H, J = 11.6
Hz), 3.95–4.02 (m, 3H), 3.90 (ddd, 1H, J = 4.8 Hz, J = 9.7
Hz), 3.83 (dd, 1H, J = 1.9 Hz, J = 10.6 Hz), 3.68 (dd, 1H,
J = 9.7 Hz, J = 10.6 Hz), 3.67 (dd, 1H, J = 10.6 Hz, J = 5.3
Hz); 13C NMR (100 MHz, CDCl3) d 137.90, 137.74, 137.72,
137.48, 128.88, 128.51, 128.41, 128.37, 128.15, 127.98, 127.71,
127.69, 127.64, 126.18, 101.33, 79.94, 75.50, 74.03, 73.33,
71.32, 69.80, 69.49, 68.40, 60.61; IR (KBr) 3064, 6033, 2866,
2097 (cm−1).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-D-glucitol
(13).
To a stirred solution of 2-azido-1,3,5-tri-O-benzyl-4,6-O-
benzylidene-2-deoxy-D-glucitol (21) (4.00 g, 7.07 mmol) in dry
CH2Cl2 (47 mL) was added triethylsilane (6.78 mL, 42.4 mmol)
and TFA (3.27 mL, 42.4 mmol) at 0 ◦C. After being stirred
at room temperature for 4 h, the reaction mixture was poured
into ice-cooled saturated aq. NaHCO3. The aqueous layer was
extracted with two portions of ethyl acetate. The combined
extract was washed with saturated aq. NaHCO3 and brine,
dried over MgSO4. After removal of the solvent in vacuo, the
residue was purified by column chromatography on silica gel
with hexane–ethyl acetate 75 : 25 to give 2-azido-1,3,5,6-tetra-
O-benzyl-2-deoxy-D-glucitol (13) (3.00 g, 5.28 mmol, 75%) as a
1
colorless oil. [a]2D4 −28.1 (c 1.10, CHCl3); H NMR (400 MHz,
CDCl3) d 7.22–7.34 (m, 20H, aromatic), 4.72 (d, 1H, J = 12.1
Hz), 4.66 (d, 1H, J = 11.1 Hz), 4.55 (m, 2H), 4.52 (m, 2H),
4.40 (d, 1H, J = 12.1 Hz), 4.38 (d, 1H, J = 11.1 Hz), 3.90 (dd,
1H, J = 6.8 Hz, J = 1.4 Hz), 3.85 (dd, 1H, J = 2.9 Hz, J =
9.7 Hz), 3.84 (dd, 1H, J = 3.4 Hz, J = 10.6 Hz), 3.75 (ddd, 1H,
J = 1.4 Hz, J = 7.7 Hz, J = 8.2 Hz), 3.69 (dd, 1H, J = 4.8 Hz,
J = 10.6 Hz), 3.66 (ddd, 1H, J = 2.9 Hz, J = 3.9 Hz, J = 6.8
Hz), 3.63 (dd, 1H, J = 3.9 Hz, J = 9.7 Hz), 3.59 (ddd, 1H, J =
7.7 Hz, J = 3.4 Hz, J = 3.9 Hz), 2.56 (d, 1H, J = 8.2 Hz);
13C NMR (100 MHz, CDCl3) d 138.12, 138.05, 137.68, 137.63,
128.41, 128.38, 127.99, 127.89, 127.86, 127.70, 127.65, 77.79,
76.86, 74.38, 73.50, 73.37, 71.63, 70.46, 69.65, 63.14; IR (KBr)
3473, 3089, 3065, 3032, 2867, 2098 (cm−1); HRMS (ESI) calcd.
[M + Na]+ 590.2625, found 590.2625.
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-a-D-glucopyranosyl)-D-glucitol (25a). [a]D29
+60.2 (c 1.35, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.21–7.42
(m, 30H, aromatic), 5.34 (d, 1H, anomeric, J = 3.4 Hz), 4.91 (d,
1H, J = 11.1 Hz), 4.87 (m, 2H), 4.58 (m, 2H), 4.52 (d, 1H, J =
11.1 Hz), 4.52 (d, 2H, J = 11.1 Hz), 4.41 (d, 1H, J = 11.1 Hz),
4.40 (m, 2H), 4.30 (br-dd, 1H, J = 8.2 Hz), 4.28 (d, 1H, J =
11.1 Hz), 4.11 (br-ddd, 1H, J = 9.2 Hz, J = 3.4 Hz, J = 4.3 Hz),
3.91 (br-dd, 1H, J = 8.2 Hz), 3.73–3.81 (m, 4H), 3.67 (dd, 1H,
J = 4.8 Hz, J = 8.7 Hz), 3.62 (dd, 1H, J = 7.7 Hz, J = 7.2 Hz),
3.55–3.53 (m, 1H), 3.52 (dd, 1H, J = 4.8 Hz, J = 7.2 Hz), 3.41
(dd, 1H, J = 3.4 Hz, J = 10.1 Hz), 3.30 (dd, 1H, J = 4.3 Hz,
J = 10.1 Hz), 3.21 (dd, 1H, J = 3.4 Hz, J = 9.7 Hz), 2.57 (s,
1H); 13C NMR (100 MHz, CDCl3) d 138.15, 138.05, 137.99,
137.89, 137.47, 128.51, 128.42, 128.35, 128.03, 127.88, 127.79,
127.70, 127.66, 127.54, 127.31, 97.99 (anomeric), 79.63, 79.36,
74.85, 74.38, 73.48, 73.41, 73.22, 72.59, 72.02, 69.73, 69.48,
69.30, 69.01, 62.81, 61.13; IR (KBr) 3486, 3089, 3022, 2919,
2868, 2108 (cm−1); HRMS (ESI) calcd. [M + Na]+ 957.4157,
found 957.4157.
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-D-mannitol (14).
According to the procedure for the synthesis of 13, acetal 22
(4.14 g, 7.32 mmol), with triethylsilane (7.01 mL, 43.9 mmol)
and TFA (3.38 mL, 43.9 mmol) in dry CH2Cl2 (40 mL) to provide
the secondary alcohol 14 (3.70 g, 6.52 mmol, 89%). [a]2D4 −22.1
1
(c 1.10, CHCl3); H NMR (400 MHz, CDCl3) d 7.12–7.35 (m,
20H, aromatic), 4.73 (d, 1H, J = 11.6 Hz), 4.57 (m, 2H), 4.55
(d, 1H, J = 11.6 Hz), 4.51 (d, 1H, J = 11.6 Hz), 4.48 (d, 1H,
J = 11.1 Hz), 4.39 (d, 1H, J = 11.6 Hz), 4.30 (d, 1H, J = 11.1
Hz), 3.91 (dd, 1H, J = 1.9 Hz, J = 7.7 Hz), 3.88 (dd, 1H, J =
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-b-D-glucopyranosyl)-D-glucitol (25b). [a]D26
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 1 7

View Article Online
−21.9 (c 1.10, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.23–7.40
(m, 30H, aromatic), 4.88 (d, 1H, J = 11.1 Hz), 4.78 (d, 1H,
J = 11.1 Hz), 4.70 (d,1H, J = 11.6 Hz), 4.60 (d, 2H, J = 11.6
Hz), 4.58 (d, 1H, anomeric, J = 8.2 Hz), 4.52 (d, 1H, J = 11.6
Hz), 4.30 (d, 1H, J = 11.6 Hz), 4.44 (m, 2H), 4.43 (d, 1H, J =
12.1 Hz), 4.41 (d, 1H, J = 11.6 Hz), 4.35 (d, 1H, J = 12.1 Hz),
4.21 (dd, 1H, J = 3.9 Hz, J = 4.8 Hz), 3.91 (ddd, 1H, J =
6.3 Hz, J = 3.4 Hz, J = 2.9 Hz), 3.84–3.89 (m, 3H), 3.78–3.81
(m, 1H), 3.64 (dd, 1H, J = 6.3 Hz, J = 10.1 Hz), 3.60 (dd, 1H,
J = 4.8 Hz), 3.57 (ddd, 1H, J = 9.7 Hz, J = 9.7 Hz, J = 1.9
Hz), 3.53 (dd, 1H, J = 4.8 Hz, J = 10.1 Hz), 3.48 (dd, 1H,
J = 3.4 Hz, J = 10.1 Hz), 3.32 (dd, 1H, J = 8.2 Hz, J = 10.1
Hz), 3.20 (ddd, 1H, J = 9.7 Hz, J = 4.8 Hz, J = 4.8 Hz), 3.17
(dd, 1H, J = 10.1 Hz, J = 9.7 Hz), 2.70 (d, 1H, J = 1.9 Hz);
13C NMR (100 MHz, CDCl3) d 138.41, 138.17, 138.11, 138.02,
137.86, 137.53, 128.55, 128.47, 128.41, 128.35, 128.19, 128.04,
127.96, 127.91, 127.85, 127.73, 127.66, 127.63, 127.58, 127.55,
127.47, 127.40, 100.67 (anomeric), 82.63, 78.11, 77.62, 75.00,
74.66, 73.63, 73.42, 73.29, 73.16, 72.49, 71.49, 70.40, 69.81,
67.61, 66.02, 62.21; IR (KBr) 3473, 3089, 3065, 3032, 2868,
2110 (cm−1); HRMS (ESI) calcd. [M + Na]+ 957.4157, found
957.4157.
J = 10.1 Hz), 3.67 (dd, 1H, J = 6.8 Hz, J = 10.1 Hz), 3.65 (dd,
1H, J = 4.8 Hz, J = 10.1 Hz), 3.63 (dd, 1H, J = 9.2 Hz, J =
9.7 Hz), 3.43 (dd, 1H, J = 8.2 Hz, J = 9.7 Hz), 3.25 (dd, 1H,
J = 4.3 Hz, J = 4.8 Hz, J = 9.7 Hz), 3.16 (dd, 1H, J = 9.7 Hz,
J = 9.2 Hz); 13C NMR (100 MHz, CDCl3) d 138.23, 138.19,
138.16, 138.02, 137.97, 137.56, 128.50, 128.44, 128.36, 128.31,
128.25, 128.02, 127.89, 127.79, 127.78, 127.73, 127.60, 127.54,
127.49, 127.44, 127.42, 100.84 (anomeric), 82.75, 77.81, 75.00,
74.22, 73.71, 73.24, 73.19, 73.15, 73.00, 70.98, 70.66, 70.27,
66.80, 65.74, 61.46; IR (KBr) 3474, 3089, 3065, 3032, 2868,
2110 (cm−1).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-
tri-O-benzyl-2-deoxy-b-D-glucopyranosyl)-D-glucitol (10a). To
a stirred 55% sodium hydride (4.87 mg, 0.203 mmol, 1.20 eq.),
washed twice with dry hexane, was added a solution of the
2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-O-
benzyl-2-deoxy-b-D-glucopyranosyl)-D-glucitol (25b) (158 mg,
0.169 mmol) in dry N,N-dimethylformamide (0.800 mL) at
0 ◦C. The reaction mixture was stirred at the same temperature
for 30 min. Then, benzyl bromide (21.1 lL, 0.177 mmol) and a
catalytic amount of n-Bu4NI were added to the reaction mixture
at the same temperature. After being stirred at room temperature
for 3 h, the reaction mixture was poured into saturated aq.
NH4Cl. The aqueous layer was extracted with two portions of
ethyl acetate. The combined extract was washed with 1 M HCl,
saturated aq. NaHCO3 and brine, and dried over MgSO4. After
removal of the solvent in vacuo, the residue was used for the next
reaction without further purification. The residue was purified
by chromatography on silica gel with hexane–ethyl acetate 70 :
30 to give 2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-
3,4,6-tri-O-benzyl-2-deoxy-b-D-glucopyranosyl)-D-glucitol
(10b) (173 mg, 0.168 mmol, 93%) as a colorless oil. [a]2D3 −15.7
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-O-
benzyl-2-deoxy-D-glucopyranosyl)-D-mannitol (26). According
to the procedure for the synthesis of 13, alcohol 14 (62.2 mg,
0.110 mmol) was treated with imidate 12 (82.9 mg, 0.132 mmol)
in the presence of trimethylsilyl trifluoromethanesulfonate
(1.99 lL, 11.0 lmol) in toluene (1.5 mL) to provide levulinoyl
disaccharide (a : b = 39 : 61, 69.0 mg, 0.0668 mmol, 61%, HPLC
retention time: a-isomer 17.6 min, b-isomer 19.6 min). The
levulinoyl disaccharide was treated with AcOH (21.6 mL) and
hydrazine monohydrate (737 lL, 15.2 mmol) in dry pyridine
(14.4 mL) to provide an a-glycoside (26a) (701 mg, 0.750 mmol,
25%) and b-glycoside (26b) (942 mg, 1.01 mmol, 33%).
1
(c 1.10, CHCl3); H NMR (400 MHz, CDCl3) d 7.16–7.35 (m,
35H, aromtic), 4.86 (d, 1H, J = 11.1 Hz), 4.79 (d, 1H, J = 11.1
Hz), 4.77 (d, 1H, J = 11.1 Hz), 4.74 (d, 1H, J = 11.6 Hz), 4.61
(d, 1H, J = 11.6 Hz), 4.59 (d, 1H, J = 12.1 Hz), 4.56 (d, 1H,
anomeric, J = 7.7 Hz), 4.54 (d, 1H, J = 11.1 Hz), 4.51 (m, 2H),
4.45 (d, 1H, J = 12.1 Hz), 4.44 (d, 1H, J = 12.1 Hz), 4.39 (d,
2H, J = 12.1 Hz), 4.35 (d, 1H, J = 12.1 Hz), 4.22 (dd, 1H, J =
3.4 Hz, J = 5.3 Hz), 3.98 (ddd, 1H, J = 5.8 Hz, J = 3.4 Hz,
J = 6.8 Hz), 3.94 (dd, 1H, J = 6.8 Hz, J = 3.4 Hz), 3.86–3.90
(m, 2H), 3.74 (dd, 1H, J = 4.8 Hz, J = 11.6 Hz), 3.68 (dd, 1H,
J = 5.8 Hz, J = 10.6 Hz), 3.58 (dd, 1H, J = 2.9 Hz, J = 11.1
Hz), 3.57 (dd, 1H, J = 8.2 Hz, J = 4.3 Hz), 3.51 (dd, 1H, J =
1.4 Hz, J = 11.1 Hz), 3.48 (dd, 1H, J = 3.4 Hz, J = 10.6 Hz),
3.38 (dd, J = 7.7 Hz, J = 10.1 Hz), 3.32 (dd, 1H, J = 10.1 Hz,
J = 8.2 Hz), 3.22 (ddd, 1H, J = 4.3 Hz, J = 2.9 Hz, J = 1.4
Hz); 13C NMR (100 MHz, CDCl3) d 138.47, 138.23, 138.07,
138.01, 137.93, 137.90, 128.42, 128.40, 128.36, 128.34, 128.31,
128.21, 127.94, 127.87, 127.85, 127.83, 127.67, 127.58, 127.50,
127.45, 127.39, 100.70 (anomeric), 83.23, 78.19, 77.71, 73.19,
71.46, 69.79, 68.50, 67.63, 66.67, 62.31; IR (KBr) 3089, 3064,
3031, 2867, 2110 (cm−1).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-a-D-glucopyranosyl)-D-mannitol (26a). [a]D23
+59.4 (c 1.11, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.21–7.42
(m, 30H, aromatic), 5.33 (d, 1H, anomeric, J = 3.9 Hz), 4.88
(d, 1H, J = 11.1 Hz), 4.85 (d, 1H, J = 11.1 Hz), 4.74 (d, 1H,
J = 10.6 Hz), 4.70 (d, 1H, J = 10.6 Hz), 4.52 (d, 1H, J = 11.6
Hz), 4.51 (m, 2H), 4.47 (m, 2H), 4.45 (d, 1H, J = 10.6 Hz),
4.40 (d, 1H, J = 12.1 Hz), 4.28 (d, 1H, J = 12.1 Hz), 4.13 (dd,
1H, J = 1.9 Hz, J = 6.8 Hz), 4.05 (ddd, 1H, J = 8.7 Hz, J =
3.4 Hz, J = 4.3 Hz), 3.94–3.88 (m, 2H), 3.81–3.84 (m, 2H), 3.79
(dd, 1H, J = 9.7 Hz, J = 9.7 Hz), 3.71–3.75 (m, 2H), 3.66–3.70
(m, 2H), 3.38 (dd, 1H, J = 3.4 Hz, J = 10.1 Hz), 3.28 (dd, 1H,
J = 4.3 Hz, J = 10.1 Hz), 3.20 (dd, 1H, J = 3.9 Hz, J = 9.7
Hz); 13C NMR (100 MHz, CDCl3) d 138.16, 138.10, 137.99,
137.72, 137.61, 128.53, 128.44, 128.40, 128.36, 128.31, 128.27,
128.05, 127.90, 127.79, 127.73, 127.69, 127.61, 127.53, 127.50,
98.15 (anomeric), 80.19, 79.27, 77.90, 76.51, 74.84, 74.30, 73.48,
73.39, 72.41, 71.95, 69.83, 69.39, 69.24, 69.16, 62.87, 62.39; IR
(KBr) 3481, 3089, 3065, 3032, 2917, 2868, 2107 (cm−1).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-
tri-O-benzyl-2-deoxy-a-D-glucopyranosyl)-D-glucitol (10c).
According to the procedure for the synthesis of 10a, alcohol 25a
(149 mg, 0.159 mmol) was treated with sodium hydride (4.59 mg,
0.191 mmol) and benzyl bromide (19.9 lL, 0.167 mmol) in, dry
N,N-dimethylformamide (0.800 mL) to provide disaccahride
10c (155 mg, 0.151 mmol, 95%); [a]2D4 +66.0 (c 1.00, CHCl3);
1H NMR (400 MHz, CDCl3) d 7.09–7.36 (m, 35H, aromatic),
5.39 (d, 1H, anomeric, J = 3.9 Hz), 4.91 (d, 1H, J = 11.1 Hz),
4.89 (d, 1H, J = 11.1 Hz), 4.86 (d, 1H, J = 11.1 Hz), 4.71 (d,
1H, J = 11.1 Hz), 4.59 (m, 2H), 4.52 (d, 1H, J = 12.1 Hz), 4.50
(d, 1H, J = 12.1), 4.48 (d, 2H, J = 11.1 Hz), 4.43 (d, 1H, J =
11.1 Hz), 4.41 (s, 2H), 4.33 (d, 1H, J = 8.2 Hz), 4.25 (br-d,
1H, J = 12.1 Hz), 4.11 (br-d, 1H, J = 9.7 Hz), 3.91 (dd, 1H,
J = 8.7 Hz, J = 1.4 Hz), 3.89 (dd, 1H, J = 10.1 Hz, J = 9.7
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-b-D-glucopyranosyl)-D-mannitol (26b). [a]D23
−40.5 (c 1.28, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.18–7.41
(m, 30H, aromatic), 4.87 (d, 1H, J = 11.0 Hz), 4.82 (d, 1H, J =
11.0 Hz), 4.57 (d, 1H, J = 12.1 Hz), 4.56 (d, 2H, J = 12.1 Hz,
J = 11.6 Hz), 4.52 (d, 1H, J = 11.6 Hz), 4.51 (d, 1H, J = 11.6
Hz), 4.49 (d, 1H, J = 10.1 Hz), 4.47 (d, 1H, anomeric, J = 8.2
Hz), 4.46 (d, 1H, J = 10.1 Hz), 4.45 (d, 1H, J = 11.6 Hz), 4.42
(d, 1H, J = 12.1 Hz), 4.29 (d, 1H, J = 12.1 Hz), 4.23 (dd, 1H,
J = 1.9 Hz, J = 7.7 Hz), 4.02 (ddd, 1H, J = 2.4 Hz, J = 6.8 Hz,
J = 7.2 Hz), 3.89 (dd, 1H, J = 2.4 Hz, J = 10.6 Hz), 3.87 (dd,
1H, J = 2.4 Hz, J = 10.1 Hz), 3.86 (dd, 1H, J = 7.2 Hz, J =
1.9 Hz), 3.82 (dd, 1H, J = 3.4 Hz, J = 10.6 Hz), 3.78 (ddd, 1H,
J = 7.7 Hz, J = 2.4 Hz, J = 3.4 Hz), 3.75 (dd, 1H, J = 4.3 Hz,
3 3 1 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8

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Hz), 3.75–3.80 (m, 2H), 3.72 (dd, 1H, J = 9.7 Hz, J = 9.7 Hz),
3.64–3.69 (m 1H), 3.63 (br-dd, 1H, J = 1.4 Hz, J = 7.7 Hz),
3.57 (ddd, 1H, J = 1.4 Hz, J = 4.8 Hz, J = 8.7 Hz), 3.53 (dd,
1H, J = 4.8 Hz, J = 7.7 Hz), 3.39 (dd, 1H, J = 1.9 Hz, J = 10.6
Hz), 3.26 (dd, 1H, J = 3.9 Hz, J = 10.1 Hz), 3.20 (dd, 1H, J =
1.4 Hz, J = 10.6 Hz); 13C NMR (100 MHz, CDCl3) d 138.16,
138.07, 138.05, 137.92, 137.81, 137.50, 128.42, 128.41, 128.32,
128.26, 127.96, 127.91, 127.85, 127.78, 127.74, 127.68, 127.66,
127.60, 127.51, 127.24, 98.00 (anomeric), 79.91, 79.81, 78.21,
75.17, 74.84, 74.39, 73.40, 73.22, 72.11, 70.64, 64.33, 68.95,
67.67, 63.48, 61.08; IR (KBr) 3089, 3065, 3032, 2916, 2867,
2107 (cm−1).
2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-
di-O-benzyl-2-deoxy-b-D-glucopyranosyl)-D-glucitol (25b)
(632 mg, 0.512 mmol) and pulverized activated MS 4 A
˚
in dry Et2O (12 mL) was stirred at −25 ◦C for 1 h under
argon to remove a trace amount of water. Trimethylsilyl
trifluoromethanesulfonate (9.25 lL, 51.2 lmol) was added
to the reaction mixture at the same temperature. After being
stirred for 1.5 h, the reaction mixture was neutralized with
triethylamine and filtered through a pad of celite. The filtrate
was concentrated in vacuo. Then, the residue was purified by
column chromatography on silica gel with hexane–ethyl acetate
70 : 30, and gel permeation chromatography (GPC) to give
2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-
D-glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol (9a) and
(9c) (b : a = 52 : 48, 590 mg, 0.424 mmol, 83%). The b : a
ratio was determined by 1H NMR analysis. The b/a-isomers
were separated by column chromatography on silica gel with
toluene–ethyl acetate 94 : 6 to give 2-azido-1,3,5,6-tetra-O-
benzyl-2-deoxy-4-O-(2-azido-3,6-di-O-benzyl-2-deoxy-4-O-
(2-azido-3,4,6-tri-O-benzyl-2-deoxy-b-D-glucopyranosyl)-b-D-
glucopyranosyl)-D-glucitol (9a) (242 mg, 0.174 mmol, 34%) and
2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-O-
benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-D-
glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol (9c) (326 mg,
0.236 mmol, 46%) as a colorless oil.
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-
tri-O-benzyl-2-deoxy-a-D-glucopyranosyl)-D-mannitol
(10d).
According to the procedure for the synthesis of 10a, alcohol 26a
(134 mg, 0.143 mmol) was treated with sodium hydride (4.13 mg,
0.172mmol) and benzyl bromide (17.8 lL, 0.150 mmol) in dry
N,N-dimethylformamide (0.800 mL) to provide disaccahride
10c (122 mg, 0.119 mmol, 83%); [a]2D3 +60.4 (c 0.87, CHCl3); 1H
NMR (400 MHz, CDCl3) d 7.09–7.37 (m, 35H, aromatic), 5.38
(d, 1H, anomeric, J = 3.4 Hz), 4.87 (d, 1H, J = 11.1 Hz), 4.83
(d, 1H, J = 11.1 Hz), 4.75 (d, 1H, J = 11.1 Hz), 4.71 (d, 2H, J =
10.6 Hz), 4.53 (d, 1H, J = 12.1 Hz), 4.51 (m, 2H), 4.49 (d, 2H,
J = 12.1 Hz), 4.48 (d, 1H, J = 8.7 Hz), 4.43 (d, 1H, J = 12.1
Hz), 4.43 (d, 1H, J = 10.6 Hz), 4.24 (d, 1H, J = 12.1 Hz), 4.14
(dd, 1H, J = 1.9 Hz, J = 6.3 Hz), 4.07 (br-d, 1H, J = 9.2 Hz),
3.91–3.93 (m, 2H), 3.90 (dd, 1H, J = 10.1 Hz, J = 8.7 Hz), 3.82
(dd, 1H, J = 5.3 Hz, J = 9.2 Hz), 3.73 (ddd, 1H, J = 6.3 Hz,
J = 5.3 Hz, J = 4.8 Hz), 3.70 (dd, 1H, J = 8.7 Hz, J = 9.2 Hz),
3.68 (br-d, 2H), 3.67 (dd, 1H, J = 4.8 Hz, J = 9.2 Hz), 3.37 (dd,
1H, J = 1.9 Hz, J = 10.6 Hz), 3.24 (dd, 1H, J = 3.4 Hz, J =
10.1 Hz), 3.17 (dd, 1H, J = 1.4 Hz, J = 10.6 Hz); 13C NMR
(100 MHz, CDCl3) d 138.21, 138.16, 138.14, 138.07, 138.00,
137.81, 137.66, 128.44, 128.40, 128.30, 128.28, 128.27, 127.96,
127.92, 127.79, 127.72, 127.67, 127.62, 127.56, 127.50, 127.46,
98.14 (anomeric), 80.37, 79.81, 78.22, 77.94, 76.54, 75.15, 74.81,
74.35, 73.41, 72.01, 70.65, 69.25, 69.17, 67.73, 63.54, 62.47; IR
(KBr) 3066, 3031, 2867, 2105 (cm−1).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-
di-O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-
b-D-glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol (9a). [a]D24
−26.5 (c 1.20, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.15–7.38
(m, 45H, aromatic), 5.01 (d, 1H, anomeric, J = 11.6 Hz), 4.84
(d, 1H, J = 10.4 Hz), 4.79 (d, 1H, J = 10.4 Hz), 4.77 (d, 1H,
J = 11.1 Hz), 4.71 (d, 1H, J = 11.6 Hz), 4.70 (d, 1H, J = 11.6
Hz), 4.61 (d, 1H, J = 11.6 Hz), 4.60 (d, 1H, J = 12.1 Hz), 4.54
(d, 1H, J = 11.1 Hz), 4.52 (d, 1H, J = 11.6 Hz), 4.50 (d, 1H,
J = 10.6 Hz), 4.48 (d, 1H, anomeric, J = 10.1 Hz), 4.47 (m,
2H), 4.40 (d, 1H, J = 12.1 Hz), 4.36 (d, 2H, J = 10.6 Hz), 4.35
(m, 2H), 4.33 (d, 1H, anomeric, J = 8.2 Hz), 4.16 (dd, 1H, J =
3.4 Hz, J = 4.8 Hz), 3.99 (dd, 1H, J = 9.7 Hz, J = 7.7 Hz), 3.97
(ddd, 1H, J = 5.8 Hz, J = 3.4 Hz, J = 6.8 Hz), 3.93 (dd, 1H,
J = 6.8 Hz, J = 3.4 Hz), 3.88 (dd, 1H, J = 3.4 Hz, J = 11.6 Hz),
3.85 (ddd, 1H, J = 4.8 Hz, J = 3.4 Hz, J = 3.4 Hz), 3.80 (dd,
1H, J = 3.4 Hz, J = 11.6 Hz), 3.75 (dd, 1H, J = 3.4 Hz, J =
11.1 Hz), 3.65 (dd, 1H, J = 5.8 Hz, J = 10.1 Hz), 3.63 (dd, 1H,
J = 9.7 Hz, J = 7.7 Hz), 3.62 (dd, 1H, J = 1.4 Hz, J = 9.7 Hz),
3.51 (dd, 1H, J = 1.9 Hz, J = 9.7 Hz), 3.51 (dd, 1H, J = 1.4 Hz,
J = 11.1 Hz), 3.45 (dd, 1H, J = 3.4 Hz, J = 10.1 Hz), 3.34
(dd, 1H, J = 8.2 Hz, J = 9.7 Hz), 3.30 (dd, 1H, J = 10.1 Hz,
J = 7.7 Hz), 3.27 (dd, 1H, J = 9.7 Hz, J = 9.7 Hz), 3.26 (dd,
1H, J = 7.7 Hz, J = 9.7 Hz), 3.21 (ddd, 1H, J = 7.7 Hz, J =
1.4 Hz, J = 1.9 Hz), 3.14 (ddd, 1H, J = 7.7 Hz, J = 3.4 Hz, J =
1.4 Hz); 13C NMR (100 MHz, CDCl3) d 138.47, 138.44, 138.25,
138.18, 138.03, 137.93, 137.86, 137.79, 128.46, 128.38, 128.31,
128.25, 128.21, 128.10, 127.98, 127.95, 127.83, 127.70, 127.62,
127.52, 127.44, 100.91 (anomeric), 100.60 (anomeric), 83.16,
81.19, 78.10, 77.79, 77.64, 75.97, 75.50, 75.16, 74.88, 74.82,
74.63, 73.32, 73.25, 71.41, 69.74, 68.49, 67.76, 67.47, 66.92,
66.15, 62.33; IR (KBr) 3090, 3065, 3032, 2869, 2110 (cm−1);
HRMS (ESI) calcd. [M + Na]+ 1414.6159, found 1414.6155.
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-
tri-O-benzyl-2-deoxy-b-D-glucopyranosyl)-D-mannitol
(10b).
According to the procedure for the synthesis of 10a, alcohol
26b (153 mg, 0.164 mmol) was treated with sodium (4.73 mg,
0.197 mmol) and benzyl bromide (20.5 lL, 0.172 mmol)in dry
N,N-dimethylformamide (0.800 mL) to provide disaccharide
10b (119 mg, 0.116 mmol, 71%); [a]2D4 −27.6 (c 1.12, CHCl3);
1H NMR (400 MHz, CDCl3) d 7.16–7.35 (m, 35H, aromatic),
4.85 (d, 1H, J = 10.6 Hz), 4.79 (d, 1H, J = 10.6 Hz), 4.76 (d,
1H, J = 10.6 Hz), 4.58 (d, 1H, J = 11.6 Hz), 4.57 (d, 1H, J =
12.1 Hz), 4.55 (d, 1H, J = 10.6 Hz), 4.53 (d, 1H, J = 11.6 Hz),
4.53 (m, 2H), 4.50 (m, 2H), 4.47 (d, 1H, anomeric, J = 7.7 Hz),
4.44 (d, 2H, J = 11.6 Hz), 4.30 (d, 1H, J = 11.6 Hz), 4.27 (dd,
1H, J = 1.4 Hz, J = 7.2 Hz), 4.13 (ddd, 1H, J = 2.4 Hz, J =
3.4 Hz, J = 7.7 Hz), 3.89 (dd, 1H, J = 7.7 Hz, J = 1.4 Hz),
3.88–3.90 (m, 1H), 3.85 (br-d, 1H, J = 8.7 Hz), 3.38 (br-d, 1H),
3.80 (br-dd, 1H, J = 9.2 Hz), 3.68 (m, 1H), 3.71 (br-d, 2H), 3.63
(dd, 1H, J = 9.2 Hz, J = 9.2 Hz), 3.38 (dd, 1H, J = 7.7 Hz,
J = 9.7 Hz), 3.31 (dd, 1H, J = 9.7 Hz, J = 9.2 Hz), 3.28 (br-dd,
1H); 13C NMR (100 MHz, CDCl3) d 138.28, 138.25, 138.08,
138.02, 128.41, 128.38, 128.34, 128.28, 128.26, 128.24, 127.93,
127.79, 127.74, 127.72, 127.65, 127.56, 127.45, 127.40, 100.95
(anomeric), 83.31, 77.91, 77.72, 77.39, 76.80, 75.39, 74.92,
74.87, 74.25, 73.39, 73.21, 73.16, 71.03, 70.19, 68.44, 66.98,
66.50, 61.26; IR (KBr) 3089, 3064, 3031, 2867, 2110 (cm−1).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-
D-glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol
(9c). [a]2D4
+14.5 (c 1.20, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.10–7.36
(m, 45H, aromatic), 5.64 (d, 1H, anomeric, J = 3.9 Hz), 5.01
(d, 1H, J = 10.1 Hz), 4.87 (d, 1H, J = 10.6 Hz), 4.83 (d, 1H,
J = 10.6 Hz), 4.81 (d, 1H, J = 10.1 Hz), 4.73 (d, 1H, J = 10.6
Hz), 4.72 (d, 1H, J = 11.6 Hz), 4.64 (d, 1H, anomeric, J =
7.7 Hz), 4.61 (d, 1H, J = 11.6 Hz), 4.60 (d, 1H, J = 11.6 Hz),
4.53 (d, 1H, J = 14.0 Hz), 4.51 (d, 1H, J = 14.0 Hz), 4.49 (d,
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-
di-O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-
D-glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol (9a) and
(9c). A mixture of 2-azido-3,4,6-tri-O-benzyl-2-deoxy-b-D-
glucopyranosyl trichloroacetimidate (11) (632 mg, 1.02 mmol),
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 1 9

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1H, J = 12.1 Hz), 4.45 (d, 1H, J = 10.6 Hz), 4.42 (d, 2H, J =
11.6 Hz), 4.39 (m, 2H), 4.33 (d, 1H, J = 12.1 Hz), 4.25–4.26
(m, 1H), 4.24 (d, 1H, J = 12.1 Hz), 3.92 (br-s, 2H), 3.88 (dd,
1H, J = 9.7 Hz, J = 9.7 Hz), 3.86–3.90 (m, 2H), 3.83 (dd, 1H,
J = 10.1 Hz, J = 8.7 Hz), 3.79 (dd, 1H, J = 5.3 Hz, J = 11.6
Hz), 3.69 (dd, 1H, J = 8.7 Hz, J = 9.7 Hz), 3.63 (ddd, 1H, J =
9.7 Hz, J = 2.4 Hz, J = 4.3 Hz), 3.64–3.67 (m, 1H), 3.63 (dd,
1H, J = 4.3 Hz, J = 11.1 Hz), 3.52 (dd, 1H, J = 2.4 Hz, J =
10.6 Hz), 3.51 (dd, 1H, J = 2.4 Hz, J = 11.1 Hz), 3.43 (dd, 1H,
J = 6.3 Hz, J = 9.7 Hz), 3.43 (dd, 1H, J = 2.4 Hz, J = 10.1
Hz), 3.39 (dd, 1H, J = 7.7 Hz, J = 10.1 Hz), 3.29 (br-d, 1H,
J = 10.6 Hz), 3.24 (ddd, 1H, J = 9.7 Hz, J = 4.3 Hz, J = 2.4
Hz); 13C NMR (100 MHz, CDCl3) d 138.43, 138.17, 138.05,
137.97, 137.93, 137.83, 137.76, 137.68, 128.46, 128.44, 128.35,
128.20, 127.97, 127.96, 127.92, 127.85, 127.80, 127.77, 127.74,
127.71, 127.57, 127.44, 127.41, 127.38, 100.65 (anomeric), 97.52
(anomeric), 83.65, 80.00, 78.17, 77.99, 77.76, 75.30, 74.97,
74.63, 74.59, 74.35, 73.49, 73.43, 73.38, 73.20, 72.58, 71.55,
71.39, 69.76, 68.89, 67.70, 67.66, 67.15, 63.20, 62.20; IR (KBr)
3089, 3065, 3031, 2867, 2110 (cm−1); HRMS (ESI) calcd. [M +
Na]+ 1414.6159, found 1414.6159.
4.57 (d, 1H, J = 12.1 Hz), 4.53 (d, 1H, J = 11.1 Hz), 4.52 (d,
1H, J = 12.1 Hz), 4.51 (d, 1H, J = 6.8 Hz), 4.49 (d, 1H, J = 9.7
Hz), 4.48 (d, 1H, J = 12.1 Hz), 4.46 (d, 1H, J = 9.7 Hz), 4.43
(d, 1H, J = 11.6 Hz), 4.42 (d, 2H, J = 12.1 Hz), 4.29 (d, 1H,
J = 11.6 Hz), 4.28 (br-dd, 1H, J = 1.0 Hz, J = 5.3 Hz), 4.18
(d, 1H, J = 12.1 Hz), 4.04 (ddd, 1H, J = 2.4 Hz, J = 4.3 Hz,
J = 6.3 Hz), 3.93 (dd, 1H, J = 8.7 Hz, J = 6.3 Hz), 3.92 (br-d,
1H, J = 6.3 Hz, J = 1.0 Hz), 3.90 (dd, 1H, J = 3.4 Hz, J =
11.1 Hz), 3.84 (dd, 1H, J = 10.6 Hz, J = 11.1 Hz), 3.79–3.85
(m, 3H), 3.75 (dd, 1H, J = 3.4 Hz, J = 11.1 Hz), 3.70 (dd, 1H,
J = 11.1 Hz, J = 11.1 Hz), 3.69 (dd, 1H, J = 4.3 Hz, J = 11.1
Hz), 3.64–3.67 (m, 2H), 3.48 (dd, 1H, J = 1.9 Hz, J = 10.6
Hz), 3.35–3.43 (m, 2H), 3.30 (dd, 1H, J = 3.9 Hz, J = 10.6
Hz), 3.30 (br-d, 1H, J = 6.3 Hz, J = 3.4 Hz, J = 4.3 Hz), 3.23
(br-d, 1H, J = 10.6 Hz); 13C NMR (100 MHz, CDCl3) d 138.31,
138.17, 137.92, 137.86, 137.84, 137.75, 137.67, 128.48, 128.44,
128.41, 128.33, 128.31, 128.29, 128.23, 128.18, 128.07, 127.96,
127.92, 127.84, 127.80, 127.76, 127.73, 127.66, 127.59, 127.47,
127.44, 127.41, 127.37, 127.35, 127.29, 100.91 (anomeric), 97.41
(anomeric), 83.76, 79.97, 77.95, 77.76, 77.24, 77.20, 75.29,
74.87, 74.56, 74.42, 74.26, 73.53, 73.41, 73.26, 73.20, 72.32,
71.26, 70.98, 70.04, 68.93, 67.60, 66.84, 66.71, 63.22, 61.15; IR
(KBr) 3090, 3065, 3032, 2867, 2110 (cm−1).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
glucopyranosyl)-a-D-glucopyranosyl)-D-mannitol (9b) and (9d).
According to the method for the synthesis of 9a and 9c,
disaccharide 26b (942 mg, 1.01 mmol) was treated with
donor 11 (1.25 g, 2.02 mmol) in the presence of trimethylsilyl
trifluoromethanesulfonate (18.3 lL, 0.101 mmol) in Et2O
(30 mL) to provide the mixture of 9b and 9d (b : a = 59 : 41,
983 mg, 0.706 mmol, 70%). Further purification of the mixture
afforded b-isomer 9d (570 mg, 0.409 mmol, 40%) and a-isomer
(9d) (390 mg, 0.280 mmol, 28%).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
glucopyranosyl)-a-D-glucopyranosyl)-D-glucitol (9e) and (9g).
According to the method for the synthesis of 9a and 9c,
disaccharide 25a (575 mg, 0.615 mmol) was treated with
donor 11 (763 mg, 1.23 mmol) in the presence of trimethylsilyl
trifluoromethanesulfonate (11.1 lL, 61.5 lmol) in toluene
(30 mL) to provide the mixture of 9e and 9g (b : a = 50 : 50,
685 mg, 0.492 mmol, 80%). Further purification of the mixture
afforded b-isomer 9e (265 mg, 0.190 mmol, 31%) and a-isomer
9g (368 mg, 0.264 mmol, 43%).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-b-
D-glucopyranosyl)-b-D-glucopyranosyl)-D-mannitol (9b). [a]D26
−32.1 (c 1.10, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.16–7.40
(m, 45H, aromatic), 5.03 (d, 1H, J = 11.1 Hz), 4.83 (d, 1H, J =
10.6 Hz), 4.78 (d, 1H, J = 10.6 Hz), 4.77 (d, 1H, J = 11.1Hz),
4.69 (d, 1H, J = 11.1 Hz), 4.61 (d, 1H, J = 12.1 Hz), 4.59 (d,
1H, J = 11.6 Hz), 4.56 (d, 1H, J = 10.6 Hz), 4.54 (d, 2H, J =
11.1 Hz), 4.50 (m, 2H), 4.48 (d, 1H, J = 10.6 Hz), 4.40 (d, 1H,
J = 12.1 Hz), 4.39 (d, 1H, anomeric, J = 8.7 Hz), 4.38 (d, 1H,
anomeric, J = 8.2 Hz), 4.35 (m, 2H), 4.29 (d, 1H, J = 11.6 Hz),
4.22 (br-d, 1H, J = 7.7 Hz), 4.11 (ddd, 1H, J = 2.4 Hz, J =
6.8 Hz, J = 8.7 Hz), 4.05 (dd, 1H, J = 9.2 Hz, J = 9.7 Hz),
3.83–3.89 (m, 4H), 3.83 (dd, 1H, J = 2.4 Hz, J = 10.1 Hz),
3.77–3.79 (m, 2H)3.69 (dd, 1H, J = 6.8 Hz, J = 10.1 Hz), 3.63
(dd, 1H, J = 9.7 Hz, J = 8.7 Hz), 3.63 (dd, 1H, J = 2.9 Hz,
J = 10.6 Hz), 3.50 (dd, 1H, J = 3.9 Hz, J = 10.6 Hz), 3.34
(dd, 1H, J = 8.2 Hz, J = 10.1 Hz), 3.33 (dd, 1H, J = 8.7 Hz,
J = 9.7 Hz), 3.26 (dd, 1H, J = 10.1 Hz, J = 9.7 Hz), 3.23 (dd,
1H, J = 9.7 Hz, J = 9.2 Hz), 3.19 (br-dd, 1H, J = 8.7 Hz, J =
2.9 Hz, J = 3.9 Hz); 13C NMR (100 MHz, CDCl3) d 138.51,
138.25, 138.21, 138.18, 138.01, 137.99, 137.96, 137.86, 128.44,
128.38, 128.37, 128.31, 128.28, 128.24, 128.11, 128.01, 128.04,
127.96, 127.86, 127.80, 127.73, 127.67, 127.63, 127.54, 127.50,
127.44, 127.41, 127.37, 100.81 (anomeric), 100.76 (anomeric),
83.11, 81.24, 77.79, 77.63, 77.20, 77.08, 76.62, 75.72, 75.49,
75.12, 74.82, 74.78, 74.68, 74.22, 73.38, 73.22, 73.15, 70.85,
70.15, 68.48, 67.79, 66.92, 66.58, 65.88, 60.95; IR (KBr) 3089,
3065, 3032, 2868, 2110 (cm−1).
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-b-
D-glucopyranosyl)-a-D-glucopyranosyl)-D-glucitol
(9e). [a]2D4
+25.7 (c 1.10, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.16–7.39
(m, 45H, aromatic), 5.32 (d, 1H, anomeric, J = 3.4 Hz), 5.09
(d, 1H, J = 11.1Hz), 4.90 (d, 1H, J = 11.1 Hz), 4.82 (d, 1H, J =
10.6 Hz), 4.77 (d, 2H, J = 10.6 Hz), 4.67 (d, 1H, J = 11.1 Hz),
4.66 (m, 2H), 4.54 (d, 1H, J = 11.1 Hz), 4.54 (d, 2H, J = 10.6
Hz), 4.49 (d, 1H, J = 10.6 Hz), 4.47 (d, 1H, J = 11.1 Hz), 4.41
(m, 2H), 4.35 (d, 1H, J = 12.1 Hz), 4.31 (dd, 1H, J = 1.4 Hz,
J = 5.8 Hz), 4.30 (d, 1H, J = 12.1 Hz), 4.15 (d, 1H, J = 12.1
Hz), 4.15 (br-dd, 1H, J = 10.1 Hz, J = 2.9 Hz), 4.12 (d, 1H,
anomeric, J = 8.2 Hz), 4.01 (dd, 1H, J = 8.7 Hz, J = 10.1 Hz),
3.89 (dd, 1H, J = 8.7 Hz, J = 1.4 Hz), 3.80 (dd, 1H, J = 8.7 Hz,
J = 10.1 Hz), 3.80 (dd, 1H, J = 5.3 Hz, J = 8.7 Hz), 3.74
(br-dd, 1H, J = 5.8 Hz, J = 5.6 Hz), 3.68 (dd, 1H, J = 5.3 Hz,
J = 8.7 Hz), 3.64 (br-dd, 1H, J = 1.4 Hz, J = 7.7 Hz), 3.62 (dd,
1H, J = 3.4 Hz, J = 11.1 Hz), 3.57 (br-dd, 1H, J = 1.4 Hz, J =
8.7 Hz), 3.55 (dd, 1H, J = 9.2 Hz, J = 9.2 Hz), 3.52 (dd, 1H,
J = 7.7 Hz), 3.52 (dd, 1H, J = 2.9 Hz, J = 9.7 Hz), 3.43 (dd,
1H, J = 4.8 Hz, J = 11.1 Hz), 3.32 (dd, 1H, J = 8.2 Hz, J =
9.7 Hz), 3.16 (br-d, 1H, J = 9.7 Hz), 3.13 (dd, J = 3.4 Hz, J =
8.7 Hz), 3.13 (ddd, 1H, J = 9.2 Hz, J = 3.4 Hz, J = 4.8 Hz),
3.12 (dd, 1H, J = 9.7 Hz, J = 9.2 Hz); 13C NMR (100 MHz,
CDCl3) d 138.55, 138.32, 138.13, 138.04, 137.92, 137.88, 137.66,
137.47, 128.49, 128.45, 128.42, 128.35, 128.30, 128.27, 128.21,
128.14, 128.09, 127.99, 127.88, 127.86, 127.79, 127.71, 127.69,
127.66, 127.60, 127.57, 127.49, 127.36, 127.31, 127.27, 100.64
(anomeric), 97.82 (anomeric), 82.99, 79.88, 77.92, 77.70, 77.56,
77.20, 77.11, 76.17, 75.42, 75.13, 74.78, 74.68, 74.39, 73.48,
73.27, 73.22, 72.31, 70.30, 69.32, 68.94, 68.60, 67.40, 66.71,
62.78, 61.08; IR (KBr) 3089, 3065, 3032, 2919, 2868, 2109
(cm−1); HRMS (ESI) calcd. [M + Na]+ 1414.6159, found
1414.6161.
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-
D-glucopyranosyl)-b-D-glucopyranosyl)-D-mannitol (9d). [a]D25
+7.8 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.09–7.37
(m, 45H, aromatic), 5.66 (d, 1H, anomeric, J = 3.9 Hz), 4.99 (d,
1H, J = 10.1 Hz), 4.87 (d, 1H, J = 10.6 Hz), 4.82 (d, 2H, J =
10.1 Hz), 4.72 (d, 1H, J = 11.6 Hz), 4.58 (d, 2H, J = 11.1 Hz),
3 3 2 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8

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2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-
D-glucopyranosyl)-a-D-glucopyranosyl)-D-glucitol
(anomeric), 97.97 (anomeric), 83.00, 80.52, 78.12, 77.92, 77.57,
76.19, 75.41, 75.16, 74.78, 74.69, 74.35, 73.44, 73.38, 73.27,
73.23, 72.20, 70.30, 69.33, 69.05, 68.61, 67.39, 66.70, 62.80,
62.34; IR (KBr) 3089, 3065, 3032, 2913, 2868, 2110 (cm−1).
(9g). [a]2D8
+90.6 (c 1.16, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.12–7.41
(m, 45H, aromatic), 5,69 (d, 1H, anomeric, J = 3.4 Hz), 5.39 (d,
1H, anomeric, J = 3.4 Hz), 4.96 (d, 1H, J = 10.1 Hz), 4.93 (d,
1H, J = 11.6 Hz), 4.91 (d, 1H, J = 10.6 Hz), 4.89 (d, 1H, J =
10.1 Hz), 4.87 (d, 1H, J = 10.6 Hz), 4.76 (d, 1H, J = 11.1 Hz),
4.60 (d, 1H, J = 12.1 Hz), 4.55 (d, 1H, J = 12.1 Hz), 4.54 (d,
1H, J = 12.1 Hz), 4.51 (d, 1H, J = 11.6 Hz), 4.50 (d, 1H, J =
12.1 Hz), 4.45 (d, 1H, J = 12.1 Hz), 4.45 (d, 1H, J = 11.1 Hz),
4.41 (m, 2H), 4.37 (d, 1H, J = 12.6 Hz), 4.30 (br-dd, 1H, J =
2.9 Hz, J = 5.8 Hz), 4.28 (d, 1H, J = 12.6 Hz), 4.15 (br-dd, 1H,
J = 8.7 Hz, J = 2.4 Hz), 4.15 (d, 1H, J = 12.1 Hz), 4.05 (dd,
1H, J = 9.2 Hz, J = 8.7 Hz), 4.03 (dd, 1H, J = 9.2 Hz, J = 9.2
Hz), 3.93 (dd, 1H, J = 10.6 Hz, J = 9.7 Hz), 3.92 (dd, 1H, J =
9.7 Hz, J = 2.9 Hz), 3.83 (dd, 1H, J = 5.3 Hz, J = 8.7 Hz), 3.73
(dd, 1H, J = 9.7 Hz, J = 8.7 Hz), 3.73 (br-ddd, 1H, J = 5.8 Hz,
J = 5.3 Hz, J = 5.3 Hz), 3.70 (dd, 1H, J = 5.3 Hz, J = 8.7 Hz),
3.64 (br-d, 1H, J = 8.2 Hz), 3.61 (br-ddd, 1H, J = 8.7 Hz, J =
2.4 Hz, J = 4.8 Hz), 3.57 (br-dd, 1H, J = 1.4 Hz, J = 4.8 Hz,
J = 9.7 Hz), 3.52 (dd, 1H, J = 4.8 Hz, J = 8.7 Hz), 3.48 (dd,
1H, J = 2.4 Hz, J = 11.1 Hz), 3.38 (dd, 1H, J = 2.4 Hz, J =
11.6 Hz), 3.30 (dd, 1H, J = 3.4 Hz, J = 9.2 Hz), 3.24 (br-dd,
1H, J = 4.8 Hz, J = 11.1 Hz), 3.23 (br-dd, 1H, J = 11.6 Hz),
3.21 (dd, 1H, J = 3.4 Hz, J = 10.6 Hz); 13C NMR (100 MHz,
CDCl3) d 138.26, 138.16, 138.10, 137.99, 137.93, 137.89, 137.63,
137.54, 137.45, 128.42, 128.37, 128.30, 128.26, 128.16, 127.96,
127.89, 127.85, 127.81, 127.68, 127.64, 127.54, 127.31, 127.20,
127.13, 97.79 (anomeric), 96.07 (anomeric), 80.98, 79.65, 79.59,
77.86, 75.17, 74.76, 74.42, 74.23, 73.43, 73.22, 72.50, 72.12,
71.17, 70.19, 69.35, 68.98, 68.36, 67.62, 64.00, 62.96, 61.13; IR
(KBr) 3089, 3065, 3032, 2922, 2867, 2107 (cm−1); HRMS (ESI)
calcd. [M + Na]+ 1414.6159, found 1414.6159.
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-a-D-
glucopyranosyl)-a-D-glucopyranosyl)-D-mannitol
(9h). [a]2D5
+102.0 (c 1.13, CHCl3); 1H NMR (400 MHz, CDCl3) d
7.12–7.42 (m, 45H, aromatic), 5.69 (d, 1H, anomeric, J = 3.9
Hz), 5.38 (d, 1H, anomeric, J = 3.4 Hz), 4.97 (d, 1H, J = 10.1
Hz), 4.90 (d, 1H, J = 10.6 Hz), 4.90 (d, 1H, J = 10.1 Hz),
4.86 (d, 1H, J = 10.6 Hz), 4.76 (d, 2H, J = 11.1 Hz), 4.72 (d,
1H, J = 11.1 Hz), 4.55 (d, 1H, J = 11.6 Hz), 4.55 (d, 1H, J =
11.6 Hz), 4.51 (d, 1H, J = 11.6 Hz), 4.49 (d, 1H, J = 11.6 Hz),
4.48 (d, 1H, J = 11.1 Hz), 4.48 (d, 1H, J = 11.6 Hz), 4.45 (d,
1H, J = 12.6 Hz), 4.42 (d, 1H, J = 11.6 Hz), 4.35 (d, 1H, J =
12.1 Hz), 4.27 (d, 1H, J = 12.1 Hz), 4.15 (d, 1H, J = 12.6 Hz),
4.12–4.14 (m, 2H), 4.03–4.07 (m, 2H), 3.91 (dd, 1H, J = 9.7 Hz,
J = 8.7 Hz), 3.90–3.96 (m, 2H), 3.87 (dd, 1H, J = 3.4 Hz, J =
8.2 Hz), 3.74 (dd, 1H, J = 8.7 Hz, J = 10.1 Hz), 3.67–3.70 (m,
4H), 3.60 (br-d, 1H, J = 10.1 Hz), 3.48 (dd, 1H, J = 1.9 Hz,
J = 10.6 Hz), 3.36 (dd, 1H, J = 1.9 Hz, J = 11.1 Hz), 3.28
(dd, 1H, J = 3.4 Hz, J = 9.7 Hz), 3.24 (dd, 1H, J = 1.0 Hz,
J = 10.6 Hz), 3.21 (dd, 1H, J = 3.9 Hz, J = 9.7 Hz), 3.20
(br-d, 1H, J = 11.1 Hz); 13C NMR (100 MHz, CDCl3) d 138.23,
138.18, 138.14, 138.10, 138.05, 137.92, 137.69, 137.60, 128.44,
128.39, 128.35, 128.30, 128.28, 128.18, 127.96, 127.90, 127.83,
127.79, 127.70, 127.67, 127.65, 127.48, 127.34, 127.12, 97.92
(anomeric), 97.80 (anomeric), 80.80, 80.22, 79.68, 77.93, 77.87,
75.17, 74.77, 74.35, 74.20, 73.41, 73.39, 73.19, 72.59, 72.02,
71.21, 70.13, 69.29, 69.18, 68.41, 67.65, 63.97, 62.99, 62.48; IR
(KBr) 3090, 3065, 3032, 2921, 2867, 2106 (cm−1).
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ-tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ-acetylamino)-4-O-
(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-b-D-
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-
glucopyranosyl)-a-D-glucopyranosyl)-D-mannitol (9f) and (9h).
According to the method for the synthesis of 9a and 9c,
disaccharide 26a (701 mg, 0.750 mmol) was treated with
donor 11 (930 mg, 1.50 mmol) in the presence of trimethylsilyl
trifluoromethanesulfonate (13.6 lL, 75.0 lmol) in toluene
(30 mL) to provide the mixture of 9e and 9g (b : a = 42 : 58,
933 mg, 0.670 mmol, 90%). Further purification of the mixture
afforded b-isomer 9e (357 mg, 0.256 mmol, 34%) and a-isomer
9g (485 mg, 0.348 mmol, 47%).
glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol (27a). To
a
solution of 2-azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-
(2-azido-3,6-di-O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-
benzyl-2-deoxy-b-D-glucopyranosyl)-b-D-glucopyranosyl)-D-
glucitol (9a) (97.1 mg, 69.7 mmol) in toluene (1.30 mL)
was added 0.1 M NaOH aq. (23.0 lL) and 1 M trimethyl
phosphine in toluene solution (0.230 mL, 0.230 mmol) at
room temperature. After being stirred at 110 ◦C for 1 h, the
reaction mixture was concentrated in vacuo. The residue was
purified by chromatography on NH–silica gel with CHCl3
to remove the NaOH. The residue was used without further
purification. To a solution of the residue and diethylenetriamine-
N,N,Nꢀ,Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetic
acid (8) (646 mg, 1.05 mmol) in CH2Cl2 (0.730 mL) was
added DIEA (0.182 mL, 1.05 mmol), DMAP (128 mg,
1.05 mmol) and HATU (399 mg, 1.05 mmol, 15.0 eq.) at room
temperature. After being stirred at the same temperature for
15 h, the reaction mixture was concentrated in vacuo. The
residue was chromatographed on NH-silica gel with CHCl3
and gel permeation chromatography (GPC) to give 1,3,5,6-
tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-b-D-
glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol (27a) (126 mg,
2-Azido-1,3,5,6-tetra-O-benzyl-2-deoxy-4-O-(2-azido-3,6-di-
O-benzyl-2-deoxy-4-O-(2-azido-3,4,6-tri-O-benzyl-2-deoxy-b-
D-glucopyranosyl)-a-D-glucopyranosyl)-D-mannitol (9f). [a]D21
+42.3 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.17–7.40
(m, 45H, aromatic), 5.32 (d, 1H, anomeric, J = 3.9 Hz), 5.09 (d,
1H, J = 11.1 Hz), 4.81 (d, 1H, J = 10.6 Hz), 4.77 (d, 2H, J =
10.6 Hz), 4.74 (d, 1H, J = 9.7 Hz), 4.71 (d, 1H, J = 9.7 Hz),
4.68 (d, 1H, J = 11.1 Hz), 4.54 (d, 1H, J = 11.6 Hz), 4.54 (d,
2H, J = 11.1 Hz), 4.52 (m, 2H), 4.51 (d, 1H, J = 10.1 Hz), 4.47
(d,1H, J = 10.1 Hz), 4.45 (d, 1H, J = 11.6 Hz), 4.35 (d, 1H, J =
12.1 Hz), 4.30 (d, 1H, J = 12.1 Hz), 4.15 (d, 1H, J = 12.1 Hz),
4.10 (d, 1H, anomeric, J = 8.2 Hz), 4.09–4.13 (m, 2H), 4.00
(dd, 1H, J = 10.1 Hz, J = 8.7 Hz), 3.89–3.93 (m, 2H), 3.85 (dd,
1H, J = 5.3 Hz, J = 9.7 Hz), 3.81 (dd, 1H, J = 8.7 Hz, J = 10.1
Hz), 3.73 (ddd, 1H, J = 5.3 Hz, J = 3.9 Hz), 3.66–3.70 (m, 3H),
3.63 (br-d, 1H, J = 10.6 Hz), 3.56 (dd, 1H, J = 9.2 Hz, J = 9.7
Hz), 3.52 (br-d, 1H, J = 12.6 Hz), 3.43 (dd, 1H, J = 4.3 Hz,
J = 10.6 Hz), 3.31 (dd, 1H, J = 8.2 Hz, J = 8.7 Hz), 3.13 (dd,
1H, J = 3.9 Hz, J = 8.7 Hz), 3.11 (dd, 1H, J = 8.7 Hz, J = 9.2
Hz), 3.09–3.13 (m, 2H); 13C NMR (100 MHz, CDCl3) d 138.56,
138.33, 138.18, 138.05, 138.04, 137.87, 137.62, 137.60, 128.51,
128.45, 128.38, 128.36, 128.31, 128.28, 128.22, 128.13, 128.09,
127.98, 127.89, 127.88, 127.80, 127.76, 127.73, 127.70, 127.66,
127.62, 127.57, 127.52, 127.44, 127.35, 127.31, 127.28, 100.65
1
40.5 lmol, 2 steps 58%); [a]2D6 +5.3 (c 1.00, CHCl3); H NMR
(400 MHz, CDCl3) d 8.15 (d, 1H, J = 8.2 Hz), 7.88 (d, 1H, J =
8.7 Hz), 7.58 (d, 1H, J = 9.7 Hz), 7.09–7.28 (m, 45H, aromatic),
5.06 (d, 1H, J = 11.6 Hz), 4.94 (d, 1H, anomeric, J = 7.7 Hz),
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 2 1

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4.87 (d, 1H, anomeric, J = 8.2 Hz), 4.80 (d, 1H, J = 11.6 Hz),
4.79 (d, 1H, J = 11.6 Hz), 4.67 (d, 1H, J = 10.1 Hz), 4.64 (d,
1H, J = 11.6 Hz), 4.58 (d, 1H, J = 12.1 Hz), 4.56 (d, 1H, J =
11.6 Hz), 4.53 (d, 2H, J = 11.6 Hz), 4.51 (d, 1H, J = 10.1 Hz),
4.50–4.55 (m, 1H), 4.50 (m, 2H), 4.44 (m, 2H), 4.32 (d, 1H,
J = 11.6 Hz), 4.28 (m, 2H), 4.26 (d, 1H, J = 11.6 Hz), 4.21
(dd, 1H, J = 1.9 Hz, J = 5.8 Hz), 4.00–4.05 (m, 4H), 3.91 (dd,
1H, J = 8.7 Hz, J = 9.7 Hz), 3.83 (dd, 1H, J = 7.7 Hz, J =
8.7 Hz), 3.71 (dd, 1H, J = 3.4 Hz, J = 10.6 Hz), 3.60–3.65 (m,
3H), 3.56 (br-d, 1H, J = 10.6 Hz), 3.46 (dd, 1H, J = 3.9 Hz,
J = 10.1 Hz), 3.44–3.45 (m, 3H), 3.29–3.33 (m, 2H), 3.30 (br-d,
1H, J = 10.1 Hz), 3.04–3.37 (m, 30H), 2.48–2.73 (m, 24H),
1.36–1.43 (m, 108H, t-Bu); 13C NMR (100 MHz, CDCl3) d
171.62, 171.23, 171.17, 171.11, 170.58, 170.53, 170.48, 170.43,
170.21, 139.58, 138.95, 138.86, 138.60, 138.52, 138.41, 138.35,
138.24, 128.22, 128.19, 128.15, 128.09, 128.02, 127.88, 127.62,
127.60, 127.47, 127.44, 127.34, 127.17, 127.08, 127.02, 126.67,
100.88 (anomeric), 99.30 (anomeric), 81.44, 81.28, 80.92, 80.71,
80.66, 80.50, 80.44, 80.20, 79.27, 78.44, 77.20, 76.87, 75.26,
74.95, 74.74, 74.22, 74.19, 73.50, 73.12, 72.77, 72.64, 72.32,
71.87, 70.16, 70.13, 68.78, 59.31, 59.06, 58.80, 56.89, 56.47,
56.24, 56.17, 55.89, 53.25, 52.77, 52.63, 52.50, 52.39, 52.28,
51.96, 47.33, 28.09; IR (KBr) 3338, 3090, 3065, 3032, 3979,
3933, 3870, 1733, 1674 (cm−1); MS(ESI-TOF) [M + H]+ calcd.
3114.80, found 3115.38, [M + 2H]2+ calcd. 1557.90, found
1558.12, [M + 3H]3+ calcd. 1038.93, found 1039.06.
(KBr) 3361, 3064, 3032, 2978, 2933, 2870, 1733, 1674 (cm−1);
MS(ESI-TOF) [M + 2H]2+ calcd. 1557.90, found, 1558.03, [M
+ 3H]3+ calcd. 1038.93, found 1039.00.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-a-D-
glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol (27c). Accor-
ding to the method for the synthesis of 27a, triazido 9c (96.4 mg,
69.2 mmol) was treated with 1 M trimethyl phosphine in toluene
solution (0.228 mL, 0.228 mmol) in toluene (1.30 mL) and
0.1 M NaOH aq. (22.8 lL) to provide a triamine. The triamine
was reacted with t-BuDTPAOH (8) (642 mg, 1.04 mmol) by
DMAP (127 mg, 1.04 mmol) and HATU (395 mg, 1.04 mmol)
in CH2Cl2 (0.732 mL) and DIEA (0.181 mL, 1.04 mmol) to
provide triamide 27c (100 mg, 32.1 lmol, 2 steps 47%); [a]D25
+18.2 (c 1.30, CHCl3); 1H NMR (400 MHz, CDCl3) d 8.00 (d,
1H, J = 8.7 Hz), 7.63 (d, 1H, J = 9.7 Hz), 7.58 (d, 1H, J =
9.7 Hz), 7.11–7.29 (m, 45H, aromatic), 5.51 (d, 1H, anomeric,
J = 3.4 Hz), 4.99 (d, 1H, anomeric, J = 6.3 Hz), 4.80 (d, 1H,
J = 11.6 Hz), 4.74 (d, 1H, J = 11.6 Hz), 4.68 (d, 1H, J = 11.1
Hz), 4.65 (d, 1H, J = 11.6 Hz), 4.60 (d, 2H, J = 11.6 Hz), 4.57
(d, 1H, J = 11.6 Hz), 4,54 (d, 1H, J = 11.6 Hz), 4.51–4.58 (m,
1H), 4.50 (d, 2H, J = 11.6 Hz), 4.47 (d, 1H, J = 11.1 Hz),
4.45 (d, 1H, J = 12.1 Hz), 4.45 (m, 2H), 4.41 (d, 1H, J = 12.1
Hz), 4.37 (ddd, 1H, J = 3.4 Hz, J = 8.7 Hz, J = 9.7 Hz), 4.34
(d, 1H, J = 12.1 Hz), 4.30, (d, 1H, J = 12.1 Hz), 4.29 (d, 1H,
J = 12.1 Hz), 4.25 (dd, 1H, J = 2.4 Hz, J = 5.3 Hz), 4.14 (m,
1H), 4.05 (br-d, 1H, J = 5.6 Hz,), 4.02 (m, 1H), 4.01 (m, 1H),
3.91 (m, 1H), 3.65–3.83 (m, 5H), 3.58 (dd, 1H, J = 6.3 Hz, J =
10.6 Hz), 3.48–3.53 (m, 3H), 3.32–3.41 (m, 2H), 3.05–3.37 (m,
30H), 2.52–2.77 (m, 24H)1.33–1.43 (m, 108H, t-Bu); 13C NMR
(100 MHz, CDCl3) d 171.48, 171.13, 170.94, 170.81, 170.61,
170.49, 170.46, 170.24, 138.94, 138.86, 138.60, 138.57, 138.44,
138.43, 138.27, 138.12, 137.74, 128.31, 128.18, 128.13, 128.05,
127.81, 127.60, 127.54, 127.48, 127.45, 127.40, 127.25, 127.21,
126.98, 100.68 (anomeric), 96.42 (anomeric), 81.27, 80.94,
80.83, 80.75, 80.69, 80.56, 80.52, 80.47, 79.04, 78.51, 74.36,
74.21, 73.53, 73.48, 73.29, 73.09, 72.64, 72.40, 71.92, 71.69,
70.22, 69.40, 68.28, 59.19, 58.84, 58.54, 56.43, 56.31, 55.90,
53.30, 52.84, 52.63, 52.49, 52.37, 52.24, 51.86, 47.39, 28.41,
28.10, 27.99; IR (KBr) 3351, 3065, 3032, 2979, 2933, 2869,
1733, 1682 (cm−1); MS(ESI-TOF) [M + H]+ calcd. 3114.80,
found 3115.33, [M + 2H]2+ calcd. 1557.90, found 1558.12, [M +
3H]3+ calcd. 1038.93, found 1039.06.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-a-D-
glucopyranosyl)-b-D-glucopyranosyl)-D-mannitol (27d). Accor-
ding to the method for the synthesis of 27a, triazido 9d (111 mg,
79.6 mmol) was treated with 1 M trimethyl phosphine in
toluene (0.263 mL, 0.263 mmol), in toluene (1.30 mL) and
0.1 M NaOH aq. (22.8 lL) to provide a triamine. The triamine
was reacted with t-BuDTPAOH 8 (735 mg, 1.19 mmol) by
DMAP (145 mg, 1.19 mmol) and HATU (452 mg, 1.19 mmol)
in CH2Cl2 (0.732 mL) and DIEA (0.207 mL, 1.19 mmol) to
provide triamide 27d (114 mg, 36.6 lmol, 2 steps 46%); [a]D24
+17.8 (c 0.96, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.90 (d,
1H, J = 8.7 Hz), 7.63 (d, 1H, J = 8.7 Hz), 7.62 (d, 1H, J =
9.7 Hz), 7.14–7.33 (m, 45H, aromatic), 5.54 (d, 1H, anomeric,
J = 3.4 Hz), 4.98 (d, 1H, anomeric, J = 7.2 Hz), 4.91 (d, 1H,
J = 12.1 Hz), 4.76 (d, 1H, J = 11.1 Hz), 4.68 (d, 1H, J = 11.1
Hz), 4.65 (d, 1H, J = 13.0 Hz), 4.61 (d, 1H, J = 11.1 Hz),
4.59 (d, 1H, J = 11.1 Hz), 4.52 (d, 1H, J = 12.1 Hz), 4.50 (m,
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-b-D-
glucopyranosyl)-b-D-glucopyranosyl)-D-mannitol
(27b).
According to the method for the synthesis of 27a, triazido
9b (129 mg, 92.7 mmol) was treated with 1 M trimethyl
phosphine in toluene solution (0.306 mL, 0.306 mmol) in
toluene (1.30 mL) and 0.1 M NaOH aq. (28.6 lL) to provide
a triamine. The triamine was reacted with t-BuDTPAOH
(8) (859 mg, 1.39 mmol) by DMAP (170 mg, 1.39 mmol),
HATU (528 mg, 1.39 mmol) in CH2Cl2 (0.904 mL) and DIEA
(0.242 mL, 1.39 mmol, 15.0 eq.) to provide triamide 27b
(205 mg, 65.8 lmol, 2 steps 71%); [a]2D5 +2.6 (c 1.22, CHCl3); 1H
NMR (400 MHz, CDCl3) d 8.18 (d, 1H, J = 8.7 Hz), 7.79 (d,
1H, J = 9.2 Hz), 7.60 (d, 1H, J = 8.7 Hz), 7.09–7.30 (m, 45H,
aromatic), 5.12 (d, 1H, J = 11.6 Hz), 4.95 (d, 1H, J = 12.1 Hz),
4.92 (d, 1H, anomeric, J = 8.2 Hz), 4.81 (d, 1H, anomeric, J =
7.2 Hz), 4.78 (d, 1H, J = 11.1H,), 4.66 (d, 1H, J = 10.6 Hz),
4.64 (d, 1H, J = 11.1 Hz), 4.54 (d, 3H, J = 11.6 Hz), 4.51 (d,
1H, J = 10.6 Hz), 4.50 (d, 1H, J = 10.6 Hz), 4.47 (d, 2H, J =
10.6 Hz), 4.45–4.51 (m, 1H), 4.40 (d, 1H, J = 11.6 Hz), 4.39 (d,
1H, J = 12.1 Hz), 4.36 (dd, 1H, J = 2.9 Hz, J = 8.7 Hz), 4.31
(d, 1H, J = 11.6 Hz), 4.24 (1H, J = 11.6 Hz), 4.22 (m, 2H),
4.02 (dd, 1H, J = 9.2 Hz, J = 8.7 Hz), 3.89–3.98 (m, 2H), 3.82
(br-dd, 1H, J = 8.7 Hz, J = 2.9 Hz), 3.81 (dd, 1H, J = 2.9 Hz,
J = 10.1 Hz), 3.79 (dd, 1H, J = 6.8 Hz, J = 2.9 Hz), 3.75–3.80
(m, 2H), 3.71 (m, 1H), 3.64 (dd, 1H, J = 9.7 Hz, J = 8.7 Hz),
3.58–3.66 (m, 3H), 3.53–3.56 (m, 2H), 3.44 (dd, 1H, J = 3.9 Hz,
J = 10.6 Hz), 3.28–3.39 (m, 2H), 3.01–3.39 (m, 30H), 2.47–2.73
(m, 24H), 1.37–1.43 (m, 108H, t-Bu); 13C NMR (100 MHz,
CDCl3) d 171.65, 171.44, 171.10, 170.62, 170.58, 170.52, 170.49,
170.46, 170.34, 139.69, 139.38, 138.73, 138.70, 138.61, 138.56,
138.38, 138.31, 138.26, 128.24, 128.17, 128.09, 127.99, 127.89,
127.66, 127.56, 127.54, 127.46, 127.38, 127.29, 127.20, 127.15,
126.93, 126.89, 126.64, 100.72 (anomeric), 99.74 (anomeric),
81.77, 81.29, 81.01, 80.84, 80.74, 80.70, 80.54, 79.94, 78.80,
78.35, 75.56, 75.38, 74.72, 74.25, 74.15, 73.32, 73.08, 72.98,
72.93, 72.62, 71.66, 69.33, 68.84, 68.54, 68.48, 59.35, 59.16,
58.30, 56.55, 56.34, 56.18, 55.96, 55.91, 55.79, 55.51, 53.15,
52.92, 52.67, 52.54, 52.44, 52.34, 52.02, 49.22, 28.43, 28.11; IR
3 3 2 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8

View Article Online
2H), 4.49 (d, 3H, J = 11.1 Hz), 4.45–4.50 (m, 1H), 4.43 (d,
1H, J = 11.1 Hz), 4.42 (d, 1H, J = 12.1 Hz), 4.40 (d, 1H, J =
11.1 Hz), 4.38 (d, 1H, J = 12.1 Hz), 4.35–4.42 (m, 2H), 4.30
(d, 1H, J = 12.1 Hz), 4.29 (d, 1H, J = 12.6 Hz), 3.87–4.07
(m, 4H), 3.77–3.87 (m, 5H), 3.79 (dd, 1H, J = 9.7 Hz, J =
8.2 Hz), 3.71 (dd, 1H, J = 8.7 Hz, J = 9.7 Hz), 3.60–3.66 (m,
2H), 3.61 (dd, 1H, J = 6.3 Hz, J = 9.7 Hz), 3.53 (dd, 1H, J =
1.9 Hz, J = 8.7 Hz), 3.37–3.51 (m, 2H), 3.07–3.39 (m, 30H),
2.57–2.74 (m, 24H), 1.34–1.44 (m, 108H, t-Bu); 13C NMR
(100 MHz, CDCl3) d 171.30, 171.03, 170.90, 170.84, 170.64,
170.61, 170.58, 170.51, 170.48, 170.45, 170.36, 139.30, 138.67,
138.57, 138.56, 138.54, 138.44, 138.30, 138.15, 137.75, 128.28,
128.17, 128.12, 128.05, 127.98, 127.87, 127.77, 127.57, 127.53,
127.50, 127.44, 127.34, 127.30, 127.23, 127.05, 126.95, 100.43
(anomeric), 96.18 (anomeric), 81.58, 80.97, 80.85, 80.70, 80.67,
80.56, 80.52, 80.46, 79.55, 78.93, 77.98, 74.56, 74.52, 74.31,
73.50, 73.35, 73.25, 72.88, 72.69, 71.60, 69.39, 69.13, 68.63,
68.30, 59.22, 58.60, 58.35, 56.43, 56.34, 56.13, 55.95, 55.89,
53.11, 52.90, 52.73, 52.65, 52.61, 52.46, 52.41, 52.31, 51.88,
49.50, 28.09, 27.98; IR (KBr) 3663, 2978, 1733, 1683 (cm−1);
MS(ESI-TOF) [M + H]+ calcd. 3114.80, found 3115.20, [M +
2H]2+ calcd. 1557.90, found 1558.03, [M + 3H]3+ calcd. 1038.93,
found 1038.99.
1675 (cm−1); MS(ESI-TOF) [M + H]+ calcd. 3114.80, found
3115.38, [M + 2H]2+ calcd. 1557.90, found 1558.11, [M + 3H]3+
calcd. 1038.93, found 1039.06.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-b-D-
glucopyranosyl)-a-D-glucopyranosyl)-D-mannitol (27f). Accord-
ing to the method for the synthesis of 27a, triazido 9f (115 mg,
82.9 mmol) was treated with 1 M trimethyl phosphine in
toluene (0.273 mL, 0.273 mmol) in toluene (1.30 mL) and
0.1 M NaOH aq. (27.3 lL), to provide a triamine. The triamine
was reacted with t-BuDTPAOH 8 (766 mg, 1.24 mmol) by
DMAP (151 mg, 1.24 mmol) and HATU (471 mg, 1.24 mmol)
in CH2Cl2 (0.732 mL) and DIEA (0.216 mL, 1.24 mmol) to
provide triamide 27f (208 mg, 66.8 lmol, 2 steps 81%); [a]D25
+23.2 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) d 8.11 (d,
1H, J = 8.7 Hz), 7.59 (d, 1H, J = 8.7 Hz), 7.54 (d, 1H, J = 9.7
Hz), 7.07–7.35 (m, 45H, aromatic), 5.34 (d, 1H, anomeric, J =
3.4 Hz), 5.05 (d, 1H, J = 11.6 Hz), 4.84 (d, 1H, anomeric, J =
7.7 Hz), 4.76 (d, 1H, J = 11.6 Hz), 4.70 (d, 1H, J = 11.1 Hz),
4.63 (d, 1H, J = 10.6 Hz), 4.62 (d, 1H, J = 11.6 Hz), 4.61 (m,
2H), 4.59 (d, 1H, J = 11.6 Hz), 4.55 (d, 1H, J = 10.6 Hz), 4.54
(d, 1H, J = 11.6 Hz), 4.52 (d, 1H, J = 10.6 Hz), 4.51–4.58 (m,
1H), 4.47 (d, 1H, J = 10.6 Hz), 4.45 (d, 1H, J = 11.1 Hz), 4.43
(d, 1H, J = 11.6 Hz), 4.32 (d, 1H, J = 11.6 Hz), 4.23 (m, 2H),
4.18 (dd, 1H, J = 9.6 Hz, J = 9.2 Hz), 4.15–4.21 (m, 2H), 4.08
(br-d, 1H, J = 9.2 Hz), 3.97 (m, 1H), 3.89 (dd, 1H, J = 3.4 Hz,
J = 9.7 Hz), 3.88 (dd, 1H, J = 8.2 Hz, J = 6.3 Hz), 3.82 (br-dd,
1H, J = 7.7 Hz, J = 8.7 Hz), 3.80–3.87 (m, 2H), 3.78 (dd, 1H,
J = 10.1 Hz, J = 9.6 Hz), 3.74 (dd, 1H, J = 2.9 Hz, J = 8.2
Hz), 3.71 (dd, 1H, J = 3.9 Hz, J = 10.6 Hz), 3.65 (br-d, 1H,
J = 8.2 Hz), 3.65 (br-d, 1H, J = 8.2 Hz), 3.59 (dd, 1H, J =
4.8 Hz, J = 10.6 Hz), 3.50 (br-d, 1H, J = 9.2 Hz), 3.39–3.41
(m, 1H), 3.18–3.22 (m, 1H), 3.00–3.04 (m, 30H), 2.43–2.89
(m, 24H), 1.38–1.44 (m, 108H, t-Bu); 13C NMR (100 MHz,
CDCl3) d 171.49, 170.94, 170.72, 170.60, 170.57, 170.49, 170.42,
170.37, 139.64, 138.57, 138.41, 138.38, 138.27, 138.08, 128.36,
128.27, 128.19, 128.15, 128.12, 128.05, 127.86, 127.82, 127.71,
127.60, 127.47, 127.43, 127.38, 127.21, 127.10, 127.07, 126.60,
126.49, 99.84 (anomeric), 98.25 (anomeric), 81.24, 80.89, 80.69,
80.63, 50.59, 50.52, 50.40, 78.89, 78.59, 78.08, 77.63, 75.10,
74.97, 74.74, 74.32, 74.09, 73.90, 73.03, 72.93, 72.84, 72.72,
72.17, 71.58, 69.63, 68.69, 68.41, 68.31, 59.38, 58.66, 58.22,
56.60, 56.26, 56.21, 56.14, 55.92, 55.87, 55.75, 55.65, 53.05,
52.84, 52.59, 52.54, 52.52, 52.35, 52.30, 52.12, 52.09, 51.76,
70.75, 28.09; IR (KBr) 3335, 3064, 3032, 2978, 2932, 1733, 1682
(cm−1); MS(ESI-TOF) [M + H]+ calcd. 3114.80, found 3115.19,
[M + 2H]2+ calcd. 1557.90, found 1558.03, [M + 3H]3+ calcd.
1038.93, found 1038.99.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-b-D-
glucopyranosyl)-a-D-glucopyranosyl)-D-glucitol (27e). Accord-
ing to the method for the synthesis of 27a, triazido 9e (94.1 mg,
67.6 mmol) was treated with 1 M trimethyl phosphine in
toluene (0.263 mL, 0.263 mmol), in toluene (1.30 mL) and
0.1 M NaOH aq. (22.3 lL) to provide a triamine. The triamine
was reacted with t-BuDTPAOH 8 (624 mg, 1.01 mmol) by
DMAP (123 mg, 1.01 mmol) and HATU (384 mg, 1.01 mmol)
in CH2Cl2 (0.732 mL) and DIEA (0.176 mL, 1.01 mmol) to
provide triamide 27e (145 mg, 46.6 lmol, 2 steps 69%); [a]D24
+23.9 (c 1.30, CHCl3); 1H NMR (400 MHz, CDCl3) d 8.04 (d,
1H, J = 8.0 Hz), 7.78 (d, 1H, J = 9.2 Hz), 7.69 (d, 1H, J =
9.7 Hz), 7.08–7.36 (m, 45H, aromatic), 5.34 (d, 1H, anomeric,
J = 3.9 Hz), 5.13 (d, 1H, J = 12.1 Hz), 4.81 (d, 1H, anomeric,
J = 7.7 Hz), 4.75 (d, 1H, J = 11.1 Hz), 4.74 (d, 1H, J = 11.6
Hz), 4.62 (d, 1H, J = 11.1Hz), 4.55 (m, 2H), 4.60 (m, 2H), 4.54
(d, 1H, J = 12.1 Hz), 4.52 (d, 1H, J = 12.1 Hz), 4.48 (d, 1H,
J = 12.1 Hz), 4.47 (d, 1H, J = 12.1 Hz), 4.46 (br-dd, 1H, J =
3.9 Hz, J = 9.2 Hz), 4.37 (d, 1H, J = 11.6 Hz), 4.24–4.31 (m,
1H), 4.27 (d, 1H, J = 12.1 Hz), 4.20–4.24 (m, 1H), 4.20 (d, 1H,
J = 12.1 Hz), 4.19 (d, 1H, J = 12.1 Hz), 4.17 (d, 1H, J = 12.1
Hz), 4.15–4.20 (m, 1H), 4.09 (m, 1H), 3.95 (m, 1H), 3.88 (m,
2H), 3.83 (br-dd, 1H, J = 1.9 Hz, J = 6.8 Hz), 3.77 (dd, 1H,
J = 6.8 Hz, J = 9.7 Hz), 3.73–3.75 (m, 1H), 3.73 (dd, 1H, J =
8.7 Hz, J = 9.7 Hz), 3.68 (dd, 1H, J = 4.3 Hz, J = 9.7 Hz),
3.61 (dd, 1H, J = 9.2 Hz, J = 8.7 Hz), 3.57 (br-d, 1H, J = 9.7
Hz), 3.51 (br-d, 1H, J = 9.2 Hz), 3.40 (dd, 1H, J = 3.9 Hz, J =
9.2 Hz), 3.27 (dd, 1H, J = 5.8 Hz, J = 9.2 Hz), 3.17–3.27 (m,
2H), 2.95–3.38 (m, 30H), 2.41–2.83 (m, 24H), 1.37–1.44 (m,
108H, t-Bu); 13C NMR (100 MHz, CDCl3) d 171.45, 171.33,
171.13, 171.09, 170.97, 170.55, 170.47, 170.42, 170.29, 139.77,
138.70, 138.59, 138.56, 138.46, 138.30, 137.98, 137.91, 128.32,
128.20, 128.15, 128.11, 128.02, 127.81, 127.70, 127.58, 127.43,
127.36, 127.31, 127.23, 127.14, 127.01, 126.66, 126.47, 99.43
(anomeric), 96.34 (anomeric), 81.69, 81.18, 80.82, 80.72, 80.68,
80.49, 80.46, 78.83, 78.22, 78.08, 75.78, 74.79, 74.59, 74.09,
74.06, 73.93, 73.71, 73.02, 72.76, 72.67, 72.38, 72.27, 71.19,
70.93, 70.62, 69.00, 68.70, 68.28, 59.39, 59.15, 58.66, 56.61,
56.55, 56.40, 55.99, 55.90, 55.85, 55.82, 55.75, 55.62, 53.16,
52.88, 52.65, 52.53, 52.29, 52.08, 51.77, 51.70, 48.25, 28.41,
28.09; IR (KBr) 3343, 3090, 3065, 3031, 2979, 2934, 2871, 1733,
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-a-D-
glucopyranosyl)-a-D-glucopyranosyl)-D-glucitol (27g). Accord-
ing to the method for the synthesis of 27g, triazido 9g (101 mg,
72.4 mmol) was treated with 1 M trimethyl phosphine in
toluene (0.239 mL, 0.239 mmol) in toluene (1.30 mL) and
0.1 M NaOH aq. (21.9 lL) to provide a triamine. The triamine
was reacted with t-BuDTPAOH 8 (673 mg, 1.09 mmol) by
DMAP (133 mg, 1.09 mmol) and HATU (414 mg, 1.09 mmol)
in CH2Cl2 (0.732 mL) and DIEA (0.190 mL, 1.09 mmol) to
provide triamide 27g (133 mg, 42.7 lmol, 2 steps 59%); [a]D24
+38.4 (c 1.30, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.95 (d,
1H, J = 10.1 Hz), 7.74 (d, 1H, J = 9.7 Hz), 7.14–7.35 (m, 45H,
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 2 3

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aromatic), 7.06 (d, 1H, J = 9.7 Hz), 5.34 (d, 1H, anomeric, J =
2.9 Hz), 5.30 (d, 1H, anomeric, J = 2.9 Hz), 4.75 (d, 1H, J =
9.2 Hz), 4.72 (d, 1H, J = 11.6 Hz), 4.62 (m, 2H), 4.60 (d, 1H,
J = 9.2 Hz), 4.58–4.62 (m, 1H), 4.57 (d, 1H, J = 11.6 Hz), 4.51
(m, 2H), 4.48 (d, 1H, J = 11.6 Hz), 4.45 (d, 1H, J = 13.0 Hz),
4.43 (m, 2H), 4.37 (d, 1H, J = 11.6 Hz), 4.33 (ddd, 1H, J =
2.9 Hz, J = 8.2 Hz, J = 9.7 Hz), 4.29 (d, 2H, J = 11.6 Hz),
4.22–4.31 (m, 1H), 4.19 (d, 1H, J = 11.6 Hz), 4.18–4.21 (m,
1H), 4.10–4.12 (m, 2H), 4.00 (m, 1H), 3.93 (dd, 1H, J = 2.9 Hz,
J = 9.7 Hz), 3.84–3.92 (m, 3H), 3.82 (dd, 1H, J = 2.9 Hz, J =
9.7 Hz), 3.76 (dd, 1H, J = 9.2 Hz, J = 8.7 Hz), 3.71 (dd, 1H, J =
8.2 Hz, J = 9.2 Hz), 3.72 (dd, 1H, J = 3.4 Hz, J = 9.7 Hz), 3.49
(dd, 1H, J = 2.4 Hz, J = 9.7 Hz), 3.49 (dd, 1H, J = 2.4 Hz, J =
10.1 Hz), 3.46 (dd, 1H, J = 6.3 Hz, J = 9.7 Hz), 3.33 (br-d, 1H,
J = 10.1 Hz), 3.18–3.30 (m, 2H), 2.80–3.41 (m, 30H), 2.44–2.73
(m, 24H), 1.35–1.45 (m, 108H, t-Bu); 13C NMR (100 MHz,
CDCl3) d 171.28, 170.95, 170.84, 170.71, 170.58, 170.52, 170.48,
170.44, 170.32, 138.61, 138.57, 138.52, 138.44, 138.19, 137.92,
137.79, 128.38, 128.25, 128.18, 128.14, 127.84, 127.79, 127.69,
127.63, 127.57, 127.47, 127.42, 127.37, 127.29, 127.26, 127.21,
127.07, 97.63 (anomeric), 96.07 (anomeric), 80.86, 80.69, 80.67,
80.61, 80.57, 80.51, 80.47, 80.36, 80.06, 77.97, 75.64, 74.45,
74.07, 73.80, 73.15, 73.03, 72.96, 72.77, 72.43, 71.69, 71.44,
71.05, 70.61, 70.52, 68.81, 68.57, 68.35, 59.19, 58.79, 57.55,
56.66, 56.00, 55.91, 55.86, 55.70, 68.35, 59.19, 58.79, 57.55,
56.66, 56.00, 55.91, 55.86, 55.70, 55.56, 53.12, 52.99, 52.66,
52.57, 52.48, 52.45, 52.21, 51.56, 50.79, 48.25, 28.09; IR (KBr)
3327, 3090, 3065, 3032, 2979, 2934, 2872, 1733, 1682 (cm−1);
MS(ESI-TOF) [M + H]+ calcd. 3114.80, found 3115.37, [M +
2H]2+ calcd. 1557.90, found 1558.11, [M + 3H]3+ calcd. 1038.93,
found 1039.06.
72.86, 72.78, 72.42, 72.20, 71.78, 71.28, 71.06, 69.75, 68.56,
68.37, 68.28, 58.70, 58.35, 57.60, 56.31, 55.91, 55.85, 55.66,
55.59, 52.99, 52.88, 52.57, 52.53, 52.45, 52.41, 52.30, 52.21,
51.97, 51.11, 50.72, 28.07; IR (KBr) 3339, 3065, 3032, 3979,
2931, 2870, 1733, 1682 (cm−1); MS(ESI-TOF) [M + H]+ calcd.
3114.80, found 3115.24, [M + 2H]2+ calcd. 1557.90, found
1558.01, [M + 3H]3+ calcd. 1038.93, found 1039.00.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ-tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ-acetylamino))-b-
D-glucopyranosyl)-D-glucitol (28a). According to the method
for the synthesis of 27a, diazido 10a (118 mg, 0.115 mmol) was
treated with 1 M trimethyl phosphine in toluene (0.253 mL,
0.253 mmol) in toluene (1.30 mL) and 0.1 M NaOH aq.
(25.3 lL) to provide a diamine. The diamine was reacted with
t-BuDTPAOH 8 (710 mg, 1.15 mmol) by DMAP (140 mg,
1.15 mmol) and HATU (473 mg, 1.15 mmol) in CH2Cl2
(0.732 mL) and DIEA (0.200 mL, 1.15 mmol) to provide
diamide 28a (187 mg, 86.1 lmol, 2 steps 75%); [a]22 +4.0 (c
D
1.00, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.97 (d, 1H, J =
8.7 Hz), 7.61 (d, 1H, J = 9.7 Hz), 7.12–7.30 (m, 35H, aromatic),
4.95 (d, 1H, anomeric, J = 7.7 Hz), 4.89 (d, 1H, J = 11.6 Hz),
4.76 (d, 1H, J = 11.1 Hz), 4.71 (d, 1H, J = 11.1 Hz), 4.67 (d,
1H, J = 11.1 Hz), 4.60 (d, 1H, J = 12.1 Hz), 4.55 (d, 1H, J =
11.6 Hz), 4.54 (d, 1H, J = 12.1 Hz), 4.50 (d, 1H, J = 11.1
Hz), 4.49–4.53 (m, 1H), 4.46 (d, 1H, J = 11.6 Hz), 4.46 (m,
2H), 4.38 (d, 1H, J = 11.6 Hz), 4.35 (d, 1H, J = 12.1 Hz),
4.30 (d, 1H, J = 12.1 Hz), 4.24 (dd, 1H, J = 1.9 Hz, J = 5.8
Hz), 4.01 (m, 2H), 3.94 (dd, 1H, J = 8.7 Hz, J = 9.7 Hz), 3.87
(ddd, 1H, J = 7.7 Hz, J = 8.7 Hz, J = 8.7 Hz), 3.73 (dd, 1H,
J = 3.4 Hz, J = 10.6 Hz), 3.60 (dd, 1H, J = 9.7 Hz, J = 8.2
Hz), 3.57–3.62 (m, 3H), 3.44–3.50 (m, 2H), 3.33–3.36 (m, 1H),
3.11–3.38 (m, 20H), 2.49–2.73 (m, 16H), 1.37–1.43 (m, 72H,
t-Bu); 13C NMR (100 MHz, CDCl3) d 171.42, 171.10, 170.70,
170.65, 170.58, 170.52, 170.49, 170.27, 139.16, 138.84, 138.64,
138.57, 138.50, 138.34, 138.24, 128.22, 128.15, 128.05, 127.79,
127.71, 127.57, 127.49, 127.32, 127.24, 127.18, 127.09, 100.99
(anomeric), 82.19, 81.07, 80.82, 80.71, 80.60, 80.51, 79.39,
78.61, 78.19, 74.67, 74.42, 73.90, 73.06, 72.72, 72.40, 72.02,
69.99, 69.80, 69.28, 59.23, 58.72, 56.44, 56.34, 55.95, 55.80,
53.25, 52.93, 52.70, 52.60, 52.55, 52.38, 25.21, 47.70, 28.12; IR
(KBr) 3355, 3065, 3031, 2979, 2933, 2869, 1733, 1675 (cm−1);
MS(ESI-TOF) [M + H]+ calcd. 2173.25, found 2173.67, [M +
2H]2+ calcd. 1087.13, found 1087.30, [M + 3H]3+ calcd. 725.09,
found 725.21.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-O-
(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-a-D-
glucopyranosyl)-a-D-glucopyranosyl)-D-mannitol (27h). Accord-
ing to the method for the synthesis of 27g, triazido 9h (115 mg,
82.9 mmol) was treated with 1 M trimethyl phosphine in
toluene (0.239 mL, 0.239 mmol) in toluene (1.30 mL) and
0.1 M NaOH aq. (27.4 lL) to provide a triamine. The triamine
was reacted with t-BuDTPAOH 8 (766 mg, 1.24 mmol) by
DMAP (151 mg, 1.24 mmol) and HATU (471 mg, 1.24 mmol)
in CH2Cl2 (0.732 mL) and DIEA (0.216 mL, 1.24 mmol) to
provide triamide 27h (205 mg, 65.8 lmol, 2 steps 79%); [a]D24
1
+34.6 (c 1.00, CHCl3); H NMR (400 MHz, CDCl3) d 7.72
(d, 1H, J = 9.7 Hz), 7.67 (d, 1H, J = 8.7 Hz), 7.11–7.33 (m,
45H, aromatic), 7.11–7.13 (m, 1H), 5.36 (d, 1H, anomeric, J =
3.4 Hz), 5.33 (d, 1H, anomeric, J = 2.9 Hz), 4.70 (d, 2H, J =
11.1 Hz, J = 11.1 Hz), 4.68 (d, 2H, J = 11.6 Hz, J = 12.1 Hz),
4.61 (d, 1H, J = 12.1 Hz), 4.58 (d, 1H, J = 11.6 Hz), 4.57 (d,
1H, J = 12.1 Hz), 4.57–4.62 (m, 1H), 4.56 (m, 2H), 4.54 (d,
1H, J = 11.1 Hz), 4.48 (d, 2H, J = 11.1 Hz), 4.48 (d, 1H, J =
12.1 Hz), 4.45 (d, 2H, J = 12.1 Hz), 4.45 (d, 1H, J = 12.1 Hz),
4.36 (d, 1H, J = 12.1 Hz), 4.32–4.38 (m, 1H), 4.29 (d, 1H, J =
12.1 Hz), 4.20–4.21 (m, 2H), 4.12–4.13 (m, 1H), 3.99–4.01 (m,
1H), 3.92–3.95 (m, 2H), 3.90 (dd, 1H, J = 11.6 Hz, J = 9.2
Hz), 3.82–3.89 (m, 3H), 3.76 (dd, 1H, J = 8.7 Hz, J = 9.2 Hz),
3.73 (m, 1H), 3.70 (dd, 1H, J = 9.7 Hz, J = 8.7 Hz), 3.69 (m,
1H), 3.62 (dd, 1H, J = 4.3 Hz, J = 9.7 Hz), 3.49–3.55 (m, 2H),
3.37–3.39 (m, 1H), 2.81–3.39 (m, 30H), 2.46–2.74 (m, 24H),
1.37–1.44 (m, 108H, t-Bu); 13C NMR (100 MHz, CDCl3) d
171.05, 170.77, 170.67, 170.52, 170.49, 170.45, 170.39, 138.47,
138.41, 138.35, 138.23, 138.15, 138.00, 137.92, 137.69, 128.38,
128.33, 128.22, 128.15, 128.12, 128.09, 127.75, 127.70, 127.63,
127.48, 127.41, 127.35, 127.29, 127.24, 127.18, 127.01, 98.09
(anomeric), 97.47 (anomeric), 80.93, 80.69, 80.63, 80.59, 80.55,
80.43, 80.34, 80.10, 78.76, 78.62, 74.72, 74.34, 73.69, 73.15,
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino))-b-D-
glucopyranosyl)-D-mannitol (28b). According to the method
for the synthesis of 27a, diazido 10b (95.0 mg, 92.7 lmol) was
treated with 1 M trimethyl phosphine in toluene (0.204 mL,
0.204 mmol) in toluene (1.30 mL) and 0.1 M NaOH aq.
(20.4 lL) to provide a diamine. The diamine was reacted with
t-BuDTPAOH 8 (573 mg, 0.927 mmol) by DMAP (113 mg,
0.927 mmol) and HATU (352 mg, 0.927 mmol) in CH2Cl2
(0.800 mL) and DIEA (0.161 mL, 0.927 mmol) to provide
diamide 28b (161 mg, 74.1 lmol, 2 steps 80%); [a]2D5 −0.3 (c
1
1.14, CHCl3); H NMR (400 MHz, CDCl3) d 7.95 (d, 1H J =
8.2), 7.66 (d, 1H, J = 9.2 Hz), 7.13–7.33 (m, 35H, aromatic),
4.96 (d, 1H, anomeric, J = 7.7 Hz), 4.86 (d, 1H, J = 11.1 Hz),
4.78 (d, 1H, J = 11.6 Hz), 4.72 (d, 1H, J = 10.6 Hz), 4.66 (d,
1H, J = 11.6 Hz), 4.56 (d, 1H, J = 11.1 Hz), 4.50 (d, 1H, J =
10.6 Hz), 4.49–4.58 (m, 1H), 4.47 (d, 1H, J = 12.1 Hz), 4.44
(d, 1H, J = 11.6 Hz), 4.42 (m, 2H), 4.38–4.45 (m, 1H), 4.37
(d, 1H, J = 12.1 Hz), 4.35 (d, 1H, J = 11.6 Hz), 4.33 (d, 1H,
J = 12.1 Hz), 3.82–3.89 (m, 4H), 3.70 (dd, 1H, J = 6.5 Hz,
3 3 2 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8

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J = 9.2 Hz), 3.59–3.68 (m, 5H), 3.59 (dd, 1H, J = 6.3 Hz, J =
9.2 Hz), 3.44–3.45 (m, 1H), 3.11–3.39 (m, 20H), 2.54–2.80 (m,
16H), 1.37–1.45 (m, 72H, t-Bu); 13C NMR (100 MHz, CDCl3)
d 171.33, 171.08, 170.69, 170.63, 170.56, 170.53, 170.47, 170.39,
139.18, 138.68, 138.61, 138.57, 138.39, 138.31, 138.21, 128.19,
128.02, 127.76, 127.70, 127.62, 127.55, 127.43, 127.40, 127.33,
127.27, 4127.22, 127.11, 127.03, 100.59 (anomeric), 82.28,
81.14, 80.72, 80.59, 80.52, 79.00, 78.23, 77.56, 74.91, 74.44,
74.15, 73.98, 73.27, 72.84, 72.76, 71.61, 69.16, 69.01, 68.60,
59.21, 58.29, 56.43, 56.39, 55.95, 55.89, 55.75, 53.13, 52.88,
52.70, 52.67, 52.57, 52.46, 52.39, 52.20, 48.94, 28.10, 28.05; IR
(KBr) 3366, 3065, 3031, 2978, 2932, 2867, 1732, 1674 (cm−1);
MS(ESI-TOF) [M + H]+ calcd. 2173.25, found 2173.70, [M +
2H]2+ calcd. 1087.13, found 1087.30, [M + 3H]3+ calcd. 725.09,
found 725.21.
(d, 1H, J = 11.6 Hz), 4.66 (d, 1H, J = 11.1 Hz), 4.64 (d, 1H,
J = 11.6 Hz), 4.56 (m, 2H), 4.55 (d, 1H, J = 11.6 Hz), 4.53
(d, 1H, J = 12.1 Hz), 4.52 (d, 1H, J = 11.6 Hz), 4.49 (d, 2H,
J = 11.6 Hz), 4.45 (d, 1H, J = 11.1 Hz), 4.41 (d, 1H, J = 12.1
Hz), 4.39–4.45 (m, 1H), 4.31 (d, 1H, J = 12.1 Hz), 4.25–4.30
(m, 1H), 4.20 (dd, 1H, J = 2.4 Hz, J = 9.2 Hz), 4.12 (br-d, 1H,
J = 8.2 Hz), 3.99 (dd, 1H, J = 6.3 Hz, J = 2.4 Hz), 3.95 (dd,
1H, J = 2.4 Hz, J = 10.1 Hz), 3.83–3.89 (m, 2H), 3.80 (dd,
1H, J = 10.1 Hz, J = 8.2 Hz), 3.75 (dd, 1H, J = 9.7 Hz, J =
10.1 Hz), 3.64–3.72 (m, 2H), 3.45 (dd, 1H, J = 2.9 Hz, J =
8.2 Hz), 3.36–3.39 (m, 1H), 2.85–3.44 (m, 20H), 2.47–2.75 (m,
16H), 1.28–1.44 (m, 72H, t-Bu); 13C NMR (100 MHz, CDCl3)
d 170.95, 170.81, 170.61, 170.58, 170.51, 170.44, 138.77, 138.58,
138.54, 138.48, 138.24, 138.13, 128.41, 128.29, 128.16, 128.09,
127.83, 127.74, 127.69, 127.55, 127.43, 127.34, 127.24, 127.10,
126.88, 97.96 (anomeric), 80.99, 80.81, 80.73, 80.71, 80.68,
80.59, 80.49, 79.01, 78.97, 77.70, 74.58, 74.42, 74.29, 73.35,
73.31, 72.99, 72.87, 72.34, 71.14, 70.00, 68.43, 58.76, 58.63,
56.44, 56.00, 55.95, 55.71, 53.10, 53.02, 52.69, 52.57, 52.51,
52.44, 52.21, 52.05, 50.85, 28.13; IR (KBr) 3338, 3090, 3065,
3031, 2979, 2934, 2870, 1733, 1679 (cm−1); MS(ESI-TOF) [M +
H]+ calcd. 2173.25, found 2173.70, [M + 2H]2+ calcd. 1087.13,
found 1086.79, [M + 3H]3+ calcd. 725.09, found 725.21.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-D-
glucitol (29a). According to the method for the synthesis
of 27a, azido 13 (27.3 mg, 48.1 mmol) was treated with 1 M
trimethyl phosphine in toluene (52.9 mL, 52.9 mmol) in toluene
(1.30 mL) and 0.1 M NaOH aq. (5.29 lL) to provide an
amine. The amine was reacted with t-BuDTPAOH 8 (29.7 mg,
48.1 lmol) by DMAP (5.88 mg, 48.1 mmol) and HATU
(18.3 mg, 48.1 lmol) in CH2Cl2 (0.481 mL) and DIEA
(0.185 mL, 1.06 lmol) to provide amide 29a (40.1 mg, 35.1
lmol, 2 steps 73%); [a]2D4 −7.0 (c 1.09, CHCl3); 1H NMR
(400 MHz, CDCl3) d 7.94 (d, 1H, J = 8.7 Hz), 7.25–7.32 (m,
20H, aromatic), 4.68 (d, 1H, J = 11.6 Hz), 4.60 (d, 1H, J = 11.0
Hz), 4.54 (d, 1H, J = 11.0 Hz), 4.53 (m, 2H), 4.50 (d, 1H, J =
12.1 Hz), 4.46 (d, 1H, J = 12.1 Hz), 4.42 (dddd, 1H, J = 5.3 Hz,
J = 6.8 Hz, J = 5.8 Hz, J = 8.7 Hz), 4.36 (d, 1H, J = 11.6
Hz), 4.08 (dd, 1H, J = 5.8 Hz, J = 2.9 Hz), 3.86 (dd, 1H, J =
2.9 Hz, J = 10.1 Hz), 3.72 (br-s, 1H), 3.66 (dd, 1H, J = 5.8 Hz,
J = 10.1 Hz), 3.60–3.64 (m, 1H), 3.60 (dd, 1H, J = 5.3 Hz, J =
9.2 Hz), 3.52 (dd, 1H, J = 6.8 Hz, J = 9.2 Hz), 3.15–3.40 (m,
10H), 2.67–2.76 (m, 8H), 1.40–1.44 (m, 36H, t-Bu); 13C NMR
(100 MHz, CDCl3) d 171.31, 170.68, 170.55, 138.55, 138.39,
138.01, 128.31, 128.27, 128.25, 128.22, 127.89, 127.83, 127.63,
127.60, 127.53, 127.43, 127.38, 81.14, 80.81, 80.72, 78.44, 75.56,
73.93, 73.32, 72.91, 71.94, 71.53, 70.47, 68.98, 58.84, 56.89,
55.97, 55.88, 53.22, 52.79, 52.61, 52.24, 50.30, 28.14, 28.08; IR
(KBr) 3357, 3065, 3032, 2979, 2932, 2867, 1733, 1674 (cm−1);
MS(ESI-TOF) [M + H]+ calcd. 1141.66, found 1141.83.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino))-a-D-
glucopyranosyl)-D-glucitol (28c). According to the method for
the synthesis of 27a, diazido 10c (109 mg, 0.106 mmol) was
treated with 1 M trimethyl phosphine in toluene (0.233 mL,
0.233 mmol) in toluene (1.30 mL) and 0.1 M NaOH aq.
(23.3 lL) to provide a diamine. The diamine was reacted with
t-BuDTPAOH 8 (655 mg, 1.06 mmol) by DMAP (130 mg,
1.06 mmol) and HATU (403 mg, 1.06 mmol) in CH2Cl2
(0.800 mL) and DIEA (0.185 mL, 1.06 mmol) to provide
diamide 28c (171 mg, 78.7 lmol, 2 steps 73%); [a]2D5 +39.1 (c
1.10, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.87 (d, 1H,
J = 9.7 Hz), 7.76 (d, 1H, J = 10.1 Hz), 7.06–7.32 (m, 35H,
aromatic), 5.34 (d, 1H, anomeric, J = 3.4 Hz), 4.83 (d, 1H, J =
11.6 Hz), 4.75 (d, 1H, J = 11.6 Hz), 4.64 (d, 2H, J = 10.6 Hz),
4.61 (d, 1H, J = 11.1 Hz), 4.60 (d, 1H, J = 11.6 Hz), 4.52 (d,
1H, J = 12.1 Hz), 4.52 (m, 2H), 4.45 (ddd, 1H, J = 3.4 Hz, J =
10.1Hz, J = 9.7 Hz), 4.43 (d, 1H, J = 10.6 Hz), 4.40 (d, 1H,
J = 11.6 Hz), 4.33 (d, 1H, J = 12.1 Hz), 4.32–4.39 (m, 1H),
4.26 (d, 1H, J = 12.1 Hz), 4.25 (d, 1H, J = 12.1 Hz), 4.22–4.25
(m, 1H), 4.16 (br-d, 1H), 4.01 (br-d, 1H), 3.90–3.94 (m, 2H),
3.82 (dd, 1H, J = 9.2 Hz, J = 9.2 Hz), 3.80–3.83 (m, 1H), 3.76
(dd, 1H, J = 10.1 Hz, J = 9.2 Hz), 3.43 (m, 1H), 3.26–3.33
(m, 3H), 2.92–3.40 (m, 20H), 2.50–2.74 (m, 16H), 1.38–1.44
(m, 72H, t-Bu); 13C NMR (100 MHz, CDCl3) d 171.20, 171.08,
171.01, 170.64, 170.59, 170.52, 170.48, 170.39, 138.82, 138.77,
138.67, 138.51, 138.14, 137.99, 137.88, 128.42, 128.29, 128.18,
128.15, 128.11, 128.04, 127.88, 127.79, 127.73, 127.66, 127.47,
127.37, 127.21, 127.11, 126.75, 96.23 (anomeric), 80.86, 80.70,
80.68, 80.52, 78.48, 77.85, 75.98, 74.30, 74.16, 73.56, 73.37,
73.20, 72.89, 72.54, 71.79, 70.74, 70.51, 68.90, 68.23, 59.13,
58.98, 56.68, 56.17, 56.13, 56.06, 55.96, 55.91, 55.66, 53.23,
53.05, 52.75, 52.58, 52.03, 48.29, 28.12; IR (KBr) 3348, 3065,
3032, 2978, 2932, 2869, 1733, 1679 (cm−1); MS(ESI-TOF) [M +
H]+ calcd. 2173.25, found 2173.68, [M + 2H]2+ calcd. 1087.13,
found 1087.30, [M + 3H]3+ calcd. 725.09, found 725.21.
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-D-
mannitol (29b). According to the method for the synthesis
of 27a, azido 14 (31.2 mg, 55.0 mmol) was treated with 1 M
trimethyl phosphine in toluene (60.5 mL, 60.5 mmol) in toluene
(1.30 mL) and 0.1 M NaOH aq. (6.05 lL) to provide an
amine. The amine was reacted with t-BuDTPAOH 8 (34.0 mg,
55.0 lmol) by DMAP 6.72 mg, 55.0 lmol) and HATU (20.9 mg,
55.0 lmol) in CH2Cl2 (0.550 mL) and DIEA (0.185 mL,
1.06 lmol) to provide amide 29b (46.4 mg, 40.7 lmol, 2 steps
74%); [a]2D1 −12.7 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) d
8.19 (d, 1H, J = 8.7 Hz), 7.17–7.34 (m, 20 H, aromatic), 4.80 (d,
1H, J = 11.6 Hz), 4.56 (d, 1H, J = 11.6 Hz), 4.56 (m, 2H), 4.50
(d, 1H, J = 11.6 Hz), 4.47 (d, 1H, J = 11.6 Hz), 4.45–4.55 (m,
1H), 4,42 (d, 1H, J = 11.6 Hz), 4.41 (d, 1H, J = 11.6 Hz), 3.97–
4.01 (m, 1H), 3.98 (dd, 1H, J = 1.4 Hz, J = 9.7 Hz), 3.80–3.84
(m, 1H), 3.79 (dd, 1H, J = 3.9 Hz, J = 9.7 Hz), 3.73–3.77 (m,
2H), 3.57 (dd, 1H, J = 5.3 Hz, J = 9.7 Hz), 3.20–3.40 (m, 10H),
1,3,5,6-Tetra-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,
Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino)-4-
O-(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetylamino))-a-D-
glucopyranosyl)-D-mannitol (28d). According to the method
for the synthesis of 27a, diazido 10d (101 mg, 98.5 mmol) was
treated with 1 M trimethyl phosphine in toluene (0.216 mL,
0.216 mmol) in toluene (1.30 mL) and 0.1 M NaOH aq.
(21.6 lL) to provide a diamine. The diamine was reacted with
t-BuDTPAOH 8 (609 mg, 0.985 mmol) by DMAP (120 mg,
0.985 mmol) and HATU (374 mg, 0.985 mmol) in CH2Cl2
(0.800 mL) and DIEA (0.185 mL, 1.06 mmol, 10.0 eq.) to
provide diamide 28c (164 mg, 75.5 lmol, 2 steps 77%); [a]D25
1
+30.0 (c 1.00, CHCl3); H NMR (400 MHz, CDCl3) d 7.66
(d, 2H, J = 9.7 Hz), 7.07–7.33 (m, 35H, aromatic), 5.38 (d,
1H, anomeric, J = 3.9 Hz), 4.77 (d, 1H, J = 11.6 Hz), 4.71
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 2 5

View Article Online
2.72–2.77 (m, 8H), 1.39–1.44 (m, 36H, t-Bu); 13C NMR
(100 MHz, CDCl3) d 172.49, 170.60, 170.51, 170.40, 138.72,
138.55, 138.32, 137.98, 128.30, 128.22, 128.15, 127.66, 127.63,
127.55, 127.51, 127.36, 127.25, 81.24, 80.78, 77.89, 75.68, 73.26,
72.98, 72.75, 71.56, 70.58, 69.64, 69.03, 58.74, 56.82, 55.98,
55.81, 53.12, 52.88, 52.55, 52.11, 49.01, 28.11, 28.03; IR (KBr)
3350, 3032, 2978, 2932, 2868, 1733, 1653 (cm−1); MS(ESI-TOF)
[M + H]+ calcd. 1141.66, found 1141.85.
method for the synthesis of 2a, tert-butyl ester 27c (70.3 mg,
22.6 lmol) was treated with triethylsilane (0.18 mL) and TFA
(0.45 mL) in dry CH2Cl2 (0.90 mL) to provide a carboxylic
acid. The residue was hydrolyzed with a palladium catalyst
under H2, followed by purification by reversed phase HPLC
(HPLC retention time: 14.9 min) to provide DTPA-conjugated
trisaccharide 2c (14.6 mg, 8.96 lmol, 2 steps 40%); [a]2D4 +9.4
(c 0.73, H2O); 1H NMR (400 MHz, D2O, 303K) d 5.39 (d, 1H,
anomeric, J = 3.4 Hz), 4.65 (d, 1H, anomeric, J = 7.7 Hz),
4.31 (dd, 1H, J = 6.8 Hz, J = 11.1 Hz), 3.62–4.11 (m, 47H),
3.31–3.55 (m, 14 H), 3.20–3.29 (m,12H); IR (solid) 3325, 1636
1394, 1231 (cm−1); MS(ESI-TOF) [M–2H]2− calcd. 813.30,
found 813.56, [M–3H]3− calcd. 541.86, found 542.05.
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -tetraacetic acid-
Nꢀꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetraacetic acid-Nꢀꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetria-
mine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-acetylamino)-b-D-glucopy-
ranosyl)-b-D-glucopyranosyl)-D-glucitol (2a). To
a
stirred
solution of 1,3,5,6-tetra-O-benzyl-2-deoxy-2-(diethylenetri-
amine-N,N,Nꢀ,Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ-
acetylamino)-4-O-(3,6-di-O-benzyl-2-deoxy-2-(diethylenetriamine-
N,N,Nꢀ,Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetyl-
amino)-4-O-(3,4,6-tri-O-benzyl-2-deoxy-2-(diethylenetriamine-
N,N,Nꢀ,Nꢀꢀ -tetrakis-(tert-butyloxycarbonylmethyl)-Nꢀꢀ -acetyl-
amino)-b-D-glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol
(27a) (83.0 mg, 34.0 lmol, 1.00 eq.) in dry CH2Cl2 (0.90 mL)
was added triethylsilane (0.18 mL) and TFA (0.45 mL) at
room temperature. After being stirred at the same temperature
for 15 h, the reaction mixture was concentrated in vacuo and
azeotroped with toluene. The residue was used for the next
reaction without further purification. To a solution of the
residue in MeOH (3.60 mL), ethyl acetate (0.60 mL) and water
(1.20 mL) was added Pd(OH)2 (80 mg). The reaction mixture
was hydolyzed for 12 h under H2 gas atmosphere. The reaction
mixture was filtered through a pad of celite and the filtrate was
concentrated in vacuo. The residue was purified by reversed
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetraacetic acid-Nꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetria-
mine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀ-acetylamino)-a-D-glucopy-
ranosyl)-b-D-glucopyranosyl)-D-mannitol (2d). According to
the method for the synthesis of 2a, tert-butyl ester 27d (97.0 mg,
31.2 lmol) was treated with triethylsilane (0.18 mL) and TFA
(0.45 mL) in dry CH2Cl2 (0.90 mL) to provide a carboxylic
acid. The residue was hydrolyzed with a palladium catalyst
under H2, followed by purification by reversed phase HPLC
(HPLC retention time: 16.0 min) to provide DTPA-conjugated
trisaccharide 2d (16.7 mg, 10.2 lmol, 2 steps 36%); [a]2D4 +17.9
(c 0.84, H2O); 1H NMR (400 MHz, D2O, 303 K) d 5.39 (d, 1H,
anomeric, J = 3.9 Hz), 4.67 (d, 1H, anomeric, J = 7.7 Hz), 4.22
(m, 1H), 3.44–4.12 (m, 61H), 3.21–3.28 (m, 12H); IR (solid)
3341, 3017, 1720, 1619 (cm−1); MS(ESI-TOF) [M–2H]2− calcd.
813.30, found 813.56, [M–3H]3− calcd. 541.86, found 542.05.
R
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetraacetic acid-Nꢀꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetria-
mine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-acetylamino)-b-D-glucopy-
ranosyl)-a-D-glucopyranosyl)-D-glucitol (2e). According to the
method for the synthesis of 2a, tert-butyl ester 27e (99.3 mg,
31.9 lmol) was treated with triethylsilane (0.18 mL) and TFA
(0.45 mL) in dry CH2Cl2 (0.90 mL) to provide a carboxylic
acid. The residue was hydrolyzed with a palladium catalyst
under H2, followed by purification by reversed phase HPLC
(HPLC retention time: 13.9 min) to provide DTPA-conjugated
trisaccharide 2e (12.7 mg, 7.79 lmol, 2 steps 24%); [a]2D4 +8.9 (c
phase HPLC (Develosilꢀ ODS-UG-5 column, Eluent: 0.1%
TFA in H2O–0.1% TFA in aq. 10% CH3CN, Gradient: 0.00 min.
[0.1% TFA in H2O] : [0.1% TFA in aq. 10% CH3CN] = 100 : 0,
30.0 min [0.1% TFA in H2O] : [0.1% TFA in aq. 10% CH3CN] =
75 : 25, 10 mL min−1; Retention time: 14.9 min) to give
2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetraacetic acid-Nꢀꢀ -acetylamino)-4-O-(2-deoxy-2-(diethyl-
enetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-acetylamino)-b-D-
glucopyranosyl)-b-D-glucopyranosyl)-D-glucitol (2a) (10.7 mg,
1
6.57 lmol, 2 steps 23%); [a]2D0 −4.2 (c 0.63, H2O); H NMR
(400 MHz, D2O, 303K) d 4.65 (d, 2H, anomeric x2, J = 8.3 Hz),
4.32 (br-s, 1H), 3.25–4.05 (m, 73H); IR (solid) 3332, 3019, 1723,
1632 (cm−1); MS(ESI-TOF) [M–2H]2− calcd. 813.30, found
813.56, [M–3H]3− calcd. 541.86, found 542.05.
1
0.64, H2O); H NMR (400 MHz, D2O, 303 K) d 5.11 (d, 1H,
anomeric, J = 2.9 Hz), 4.67 (d, 1H, anomeric, J = 9.2 Hz), 3.79
(dd, 1H, J = 9.2 Hz, J = 9.7 Hz), 3.60 (dd, 1H, J = 9.7 Hz,
J = 8.2 Hz), 3.58–4.25 (m, 48H), 3.20–3.55 (m, 28H); IR (solid)
3248, 2950, 1724, 1672, 1631 (cm−1); MS(ESI-TOF) [M–2H]2−
calcd. 813.30, found 813.56, [M–3H]3− calcd. 541.86, found
542.04.
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetraacetic acid-Nꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetria-
mine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀ-acetylamino)-b-D-glucopy-
ranosyl)-b-D-glucopyranosyl)-D-mannitol (2b). According to
the method for the synthesis of 2a, tert-butyl ester 27b (89.7 mg,
28.8 lmol) was treated with triethylsilane (0.18 mL) and TFA
(0.45 mL) in dry CH2Cl2 (0.90 mL) to provide a carboxylic
acid. The residue was hydrolyzed with a palladium catalyst
under H2, followed by purification by reversed phase HPLC
(HPLC retention time: 16.1 min) to provide DTPA-conjugated
trisaccharide 2b (16.7 mg, 10.2 lmol, 2 steps 36%); [a]2D6 −6.6
(c 0.84, H2O);1H NMR (400 MHz, D2O, 303K) d 4.66 (d, 1H,
anomeric, J = 7.7 Hz), 4.64 (d, 1H, anomeric, J = 8.7 Hz), 4.18
(m, 1H), 3.23–4.04 (m, 73H); IR (solid) 3316, 3014, 2966, 1723,
1673, 1630 (cm−1); MS(ESI-TOF) [M–2H]2− calcd. 813.30,
found 813.56, [M–3H]3− calcd. 541.86, found 542.05.
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetraacetic acid-Nꢀꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetria-
mine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-acetylamino)-b-D-glucopy-
ranosyl)-a-D-glucopyranosyl)-D-mannitol (2f). According to
the method for the synthesis of 2a, tert-butyl ester 27f (91.8 mg,
29.5 lmol) was treated with triethylsilane (0.18 mL) and TFA
(0.45 mL) in dry CH2Cl2 (0.90 mL) to provide a carboxylic
acid. The residue was hydrolyzed with a palladium catalyst
under H2, followed by purification by reversed phase HPLC
(HPLC retention time: 15.9 min) to provide DTPA-conjugated
trisaccharide 2e (14.3 mg, 8.78 lmol, 2 steps 30%); [a]2D5 +6.3
1
(c 0.72, H2O); H NMR (400 MHz, D2O, 303 K) d 4.87 (d,
1H, anomeric, J = 3.9 Hz), 4.67 (d, 1H, anomeric, J = 8.2
Hz), 4.08 (dd, 1H, J = 3.9 Hz, J = 11.1 Hz), 3.78 (dd, 1H,
J = 8.2 Hz, J = 10.6 Hz), 3.57–4.13 (m, 46H), 3.39–3.50 (m,
14H), 3.23–3.30 (m, 12H); IR (solid) 3263, 2881, 1671, 1624
(cm−1); MS(ESI-TOF) [M–2H]2− calcd. 813.30, found 813.56,
[M–3H]3− calcd. 541.86, found 542.05.
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetraacetic acid-Nꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetria-
mine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀ-acetylamino)-a-D-glucopy-
ranosyl)-b-D-glucopyranosyl)-D-glucitol (2c). According to the
3 3 2 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8

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2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetraacetic acid-Nꢀꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetria-
mine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-acetylamino)-a-D-glucopy-
ranosyl)-a-D-glucopyranosyl)-D-glucitol (2g). According to the
method for the synthesis of 2a, tert-butyl ester 27g (91.7 mg,
29.4 lmol) was treated with triethylsilane (0.18 mL) and TFA
(0.45 mL) in dry CH2Cl2 (0.90 mL) to provide a carboxylic
acid. The residue was hydrolyzed with a palladium catalyst
under H2, followed by purification by reversed phase HPLC
(HPLC retention time: 14.7 min) to provide DTPA-conjugated
trisaccharide 2g (10.1 mg, 6.20 lmol, 2 steps 21%); [a]2D4 +25.7
(c 0.51, H2O); 1H NMR (400 MHz, D2O, 303 K) d 5.42 (d, 1H,
anomeric, J = 3.4 Hz), 5.11 (d, 1H, anomeric, J = 3.4 Hz), 4.21
(m, 1H), 3.45–4.14 (m, 61H), 3.20–3.27 (m, 12H); IR (solid)
3288, 3007, 1728, 1673, 1636 (cm−1); MS(ESI-TOF) [M–2H]2−
calcd. 813.30, found 813.56, [M–3H]3− calcd. 541.86, found
542.05.
NMR (400 MHz, D2O, 303 K) d 4.67 (d, 1H, anomeric, J =
7.7 Hz), 4.21 (m, 1H), 3.69–4.05 (m, 19H), 3.60 (br-dd, 1H),
3.41–3.54 (m, 11H), 3.24–3.29 (m, 8H); 13C NMR (100 MHz,
D2O, acetone-d6) d 173.77, 173.39, 171.98, 171.47, 171.33,
171.13, 169.49, 168.04, 101.47 (anomeric), 78.42, 76.37, 74.15,
72.10, 70.48, 68.86, 62.91, 61.25, 61.19, 57.46, 57.32, 57.11,
56.89, 56.70, 55.10, 54.99, 54.93, 53.27, 53.11, 52.84, 51.04,
50.74; IR (solid) 3301, 1614, 1170, 1012 (cm−1); MS(ESI-TOF)
[M–H]− calcd. 1091.42, found 1091.73, [M–2H]2− calcd. 545.20,
found 545.37.
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetraacetic acid-Nꢀ-acetylamino)-a-D-glucopyranosyl)-D-glucitol
(3c). According to the method for the synthesis of 2a,
tert-butyl ester 28c (116 mg, 53.4 lmol) was treated with
triethylsilane (0.18 mL) and TFA (0.45 mL) in dry CH2Cl2
(0.90 mL) to provide a carboxylic acid. The residue was
hydrolyzed with a palladium catalyst under H2, followed
by purification by reversed phase HPLC (HPLC retention
time: 20.5 min) to provide DTPA-conjugated trisaccharide 3c
(19.7 mg, 18.0 lmol, 2 steps 34%); [a]2D0 +25.8 (c 0.99, H2O);
1H NMR (400 MHz, D2O, 303 K) d 5.11 (d, 1H, anomeric,
J = 3.4 Hz), 3.20–4.28 (m, 50H); 13C NMR (100 MHz, D2O,
acetone-d6) d 174.04, 173.68, 171.60, 171.21, 170.91, 168.30,
167.98, 99.28 (anomeric), 79.92, 73.45, 73.24, 71.58, 70.58,
70.53, 62.88, 61.77, 61.08, 57.10, 55.19, 54.91, 53.75, 53.63,
53.40, 53.29, 52.99, 51.26, 50.94, 50.84, 50.49; IR (solid) 3292,
2940, 1721, 1623 (cm−1); MS(ESI-TOF) [M–H]− calcd. 1091.41,
found 1091.70, [M–2H]2− calcd. 545.20, found 545.37.
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetraacetic acid-Nꢀꢀ-acetylamino)-4-O-(2-deoxy-2-(diethylenetria-
mine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-acetylamino)-a-D-glucopy-
ranosyl)-a-D-glucopyranosyl)-D-mannitol (2h). According to
the method for the synthesis of 2a, tert-butyl ester 27h (94.5 mg,
30.3 lmol) was treated with triethylsilane (0.18 mL) and TFA
(0.45 mL) in dry CH2Cl2 (0.90 mL) to provide a carboxylic
acid. The residue was hydrolyzed with a palladium catalyst
under H2, followed by purification by reversed phase HPLC
(HPLC retention time: 16.0 min) to provide DTPA-conjugated
trisaccharide 2h (17.6 mg, 10.8 lmol, 2 steps 36%); [a]2D6 +24.7
1
(c 0.88, H2O); H NMR (400 MHz, D2O, 303 K) d 5.42 (d,
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-
tetraacetic acid-Nꢀꢀ-acetylamino)-a-D-glucopyranosyl)-D-mannitol
(3d). According to the method for the synthesis of 2a,
tert-butyl ester 28d (101 mg, 46.5 lmol) was treated with
triethylsilane (0.18 mL) and TFA (0.45 mL) in dry CH2Cl2
(0.90 mL) to provide a carboxylic acid. The residue was
hydrolyzed with a palladium catalyst under H2, followed
by purification by reversed phase HPLC (HPLC retention
time: 11.5 min) to provide DTPA-conjugated trisaccharide 3d
(10.4 mg, 9.52 lmol, 2 steps 20%); [a]2D1 +13.0 (c 0.52, H2O);
1H NMR (400 MHz, D2O, 303 K) d 4.89 (d, 1H, anomeric,
J = 3.4 Hz), 3.42–4.21 (m, 42H), 3.21–3.29 (m, 8H); 13C NMR
(100 MHz, D2O, acetone-d6) d 174.01, 173.57, 171.32, 171.19,
171.08, 171.01, 168.07, 167.78, 100.52 (anomeric), 78.86, 74.63,
73.36, 71.59, 70.62, 70.12, 63.17, 61.34, 61.19, 57.53, 57.25,
56.99, 56.88, 55.11, 54.95, 54.56, 53.28, 53.30, 53.26, 53.14,
52.95, 52.84, 52.55, 51.15, 51.01, 50.92, 50.55; IR (solid) 3281,
2936, 1630, 1394, 1213 (cm−1); MS(ESI-TOF) [M–H]− calcd.
1091.42, found 1091.72, [M–2H]2− calcd. 545.20, found 545.37.
1H, anomeric, J = 3.4 Hz), 4.86 (d, 1H, anomeric, J = 3.4
Hz), 3.58–4.24 (m, 49H), 3.42–3.52 (m, 13H), 3.20–3.27 (m,
12H); IR (solid) 3268, 3966, 1677, 1630 (cm−1); MS(ESI-TOF)
[M–2H]2− calcd. 813.30, found 813.56, [M–3H]3− calcd. 541.86,
found 542.05.
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetraacetic acid-Nꢀꢀ-acetylamino)-b-D-glucopyranosyl)-D-glucitol
(3a). According to the method for the synthesis of 2a,
tert-butyl ester 28a (101 mg, 46.5 lmol) was treated with
triethylsilane (0.18 mL) and TFA (0.45 mL) in dry CH2Cl2
(0.90 mL) to provide a carboxylic acid. The residue was
hydrolyzed with a palladium catalyst under H2, followed
by purification by reversed phase HPLC (HPLC retention
time: 11.4 min) to provide DTPA-conjugated trisaccharide 3a
1
(7.6 mg, 6.95 lmol, 2 steps 15%); [a]1D9 −3.4 (c 0.38, H2O); H
NMR (400 MHz, D2O, 303 K) d 4.66 (d, 1H, anomeric, J = 8.2
Hz), 4.32 (ddd, 1H), 3.61 (dd, 1H, J = 10.6 Hz, J = 8.7 Hz),
3.42–4.20 (m, 40H), 3.23–3.41 (m, 8H); 13C NMR (100 MHz,
D2O, acetone-d6) d 173.81, 173.45, 173.35, 171.36, 171.34,
169.65, 168.43, 101.52 (anomeric), 79.54, 76.55, 74.19, 71.84,
70.50, 68.95, 62.75, 61.73, 61.39, 57.55, 57.36, 57.19, 56.74,
55.18, 55.05, 53.95, 53.11, 53.01, 52.78, 52.74, 51.80, 51.18,
50.99, 50.96, 50.75; IR (solid) 3275, 1623, 1391, 1202, 1071
(cm−1); MS(ESI-TOF) [M–H]− calcd. 1091.41, found 1091.73,
[M–2H]2− calcd. 545.20, found 545.37.
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-
Nꢀꢀ-acetylamino)-D-glucitol (4a). According to the method for
the synthesis of 2a, tert-butyl ester 29a (95.0 mg, 83.2 lmol)
was treated with triethylsilane (0.18 mL) and TFA (0.45 mL) in
dry CH2Cl2 (0.90 mL) to provide a carboxylic acid. The residue
was hydrolyzed with a palladium catalyst under H2, followed
by purification by reversed phase HPLC (HPLC retention
time: 14.8 min) to provide DTPA-conjugated trisaccharide 4a
(17.6 mg, 31.6 lmol, 2 steps 38%); [a]2D5 −5.0 (c 0.85, H2O); 1H
NMR (400 MHz, D2O, 303 K) d 4.14 (br-dd, 1H, J = 4.3 Hz,
J = 5.8 Hz), 4.04 (s, 2H), 3.97 (s, 4H), 3.95–3.97 (m, 1H), 3.91
(s, 2H), 3.80 (dd, 1H, J = 2.4 Hz, J = 11.6 Hz), 3.73 (dd, 1H,
J = 4.3 Hz, J = 11.6 Hz), 3.71–3.74 (m, 1H), 3.68 (s, 2H), 3.62
(dd, 1H, J = 5.8 Hz, J = 11.6 Hz), 3.62 (dd, 1H, J = 4.3 Hz, J =
11.6 Hz), 3.57 (dd, 1H, J = 1.4 Hz, J = 8.2 Hz), 3.22–3.49 (m,
8H); 13C NMR (100 MHz, D2O, acetone-d6) d 173.88, 171.64,
171.17, 168.30, 71.83, 71.71, 68.95, 63.57, 61.56, 57.33, 57.20,
57.04, 54.94, 53.19, 53.15, 51.13, 50.69; IR (solid) 3338, 1627,
2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-Nꢀꢀ-
acetylamino)-4-O-(2-deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ -
tetra-acdticacid-Nꢀꢀ-acetylamino)-b-D-glucopyranosyl)-D-mannitol
(3b). According to the method for the synthesis of 2a,
tert-butyl ester 28b (101 mg, 46.5 lmol) was treated with
triethylsilane (0.18 mL) and TFA (0.45 mL) in dry CH2Cl2
(0.90 mL) to provide a carboxylic acid. The residue was
hydrolyzed with a palladium catalyst under H2, followed
by purification by reversed phase HPLC (HPLC retention
time: 17.7 min) to provide DTPA-conjugated trisaccharide 3b
(14.3 mg, 13.1 lmol, 2 steps 28%); [a]2D4 −2.9 (c 0.72, H2O); 1H
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 3 1 1 – 3 3 2 8
3 3 2 7

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1394, 1205, 1085 (cm−1); MS(ESI-TOF) [M–H]− calcd. 555.21,
found 555.39.
and Y. Shigemasa, Trends Glycosci. Glycotechnol., 2002, 14, 205–222;
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2-Deoxy-2-(diethylenetriamine-N,N,Nꢀ,Nꢀꢀ-tetraacetic acid-
Nꢀꢀ-acetylamino)-D-mannitol (4b). According to the method for
the synthesis of 2a, tert-butyl ester 29b (97.7 mg, 85.6 lmol) was
treated with triethylsilane (0.18 mL) and TFA (0.45 mL) in dry
CH2Cl2 (0.90 mL) to provide a carboxylic acid. The residue
was hydrolyzed with a palladium catalyst under H2, followed
by purification by reversed phase HPLC (HPLC retention
time: 15.3 min) to provide DTPA-conjugated trisaccharide 4b
(20.6 mg, 37.0 lmol, 2 steps 43%); [a]2D6 −0.9 (c 1.00, H2O); 1H
NMR (400 MHz, D2O, 303 K) d 4.13 (ddd, 1H, J = 3.4 Hz, J =
6.3 Hz, J = 9.2 Hz), 4.04 (s, 2H), 3.97 (s, 4H), 3.90 (s, 2H), 3.88–
3.90 (m, 1H), 3.85 (dd, 1H, J = 3.4 Hz, J = 12.1 Hz), 3.80 (dd,
1H, J = 1.9 Hz, J = 11.6 Hz), 3.74 (dd, 1H, J = 6.3 Hz, J = 12.1
Hz), 3.71 (ddd, 1H, J = 8.2 Hz, J = 1.9 Hz, J = 5.8 Hz), 3.69 (s,
2H), 3.63 (dd, 1H, J = 5.8 Hz, J = 11.6 Hz), 3.41 (m, 5H), 3.22–
3.26 (m, 4H); 13C NMR (100 MHz, D2O, acetone-d6) d 173.68,
171.66, 171.21, 168.41, 71.45, 70.20, 68.76, 63.87, 61.65, 57.31,
57.10, 54.98, 53.34, 53.20, 53.05, 51.24, 50.80; IR (solid) 3276,
2955, 1629, 1399, 1202 (cm−1); MS(ESI-TOF) [M–H]− calcd.
555.21, found 555.40.
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