Synthesis, glycosylation and photolysis of photolabile 2-(2-nitrophenyl) propyloxycarbonyl (NPPOC) protected glycopyranosides

Article abstract of DOI:10.1039/b908404e

The photolabile NPPOC group has been successfully introduced into the 6-position of various glycopyranosides in 91-97% yield. Glycosylation of NPPOC-protected phenyl β-D-thiogluco- and galactopyranosides with appropriate acceptors afforded the correspondi

Full text of DOI:10.1039/b908404e

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis, glycosylation and photolysis of photolabile 2-(2-nitrophenyl)-
propyloxycarbonyl (NPPOC) protected glycopyranosides†
Hua Yi, Ste´phane Maisonneuve and Juan Xie*
Received 28th April 2009, Accepted 29th June 2009
First published as an Advance Article on the web 22nd July 2009
DOI: 10.1039/b908404e
The photolabile NPPOC group has been successfully introduced into the 6-position of various
glycopyranosides in 91–97% yield. Glycosylation of NPPOC-protected phenyl b-D-thiogluco- and
galactopyranosides with appropriate acceptors afforded the corresponding disaccharides in good yield.
Excellent b-stereoselectivity (b/a ≥ 10/1) can be obtained when the glycosylation was realized in
CH3CN at -40 ◦C. Furthermore, the 6-O-NPPOC thioglucoside 6 can also be readily converted into the
corresponding glucopyranose or glucosyl fluoride. The photolysis of 6-O-NPPOC diacetone
D-galactose 4 has been studied by UV–vis absorption in CH3CN in the presence of water or DBU at
365 nm. At 100 mM concentration, photocleavage of 4 was accomplished after 5 min irradiation, with
t1/2 = 37 s (10% water), 75 s (1 equiv. DBU) or 87 s (0.05 M DBU). The formation of the nitroso
byproduct can be avoided in the presence of 0.05 M DBU. All the NPPOC-protected mono- or
disaccharides can be readily removed by photolysis at 365 nm in CH3CN the presence of water or DBU
in more than 87% yield.
as for the design and synthesis of caged glycoconjugates for various
Introduction
biological investigations.
Carbohydrates exist in all living systems and play key roles in
The 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) group has
biological recognition processes.1 Protection and deprotection of
been proved to be very efficient in the photolithographic synthesis
of DNA.11 This group can be photodeprotected at 365 nm by a
b-elimination reaction in the presence of water or an amine base
such as piperidine, DIPEA or DBU.11a,12 Through b-elimination
cleavage, formation of the reactive nitroso byproduct, usually
generated from the o-nitrobenzyl type of protecting group, can
be suppressed (Scheme 1).11a,12c The NPPOC group has also been
employed in peptide chemistry.4b,13 To the best of our knowledge,
this photolabile group has never been used in carbohydrate
chemistry. As part of a continuing program on the synthesis of
novel photolabile glycosides,14 we decided to investigate NPPOC-
protected glycosides. Herein we report our synthesis of NPPOC-
protected glycopyranosides and their use as glycosyl donors in the
glycosylation reaction.
hydroxyl groups are indispensable for the chemical synthesis of
carbohydrate. Recently, the use of photolabile protecting groups
has been considerably increased in synthetic as well as biological
chemistry because of their easy removal upon light irradiation2
and their orthogonality compared to classical protecting groups.
Photolabile protecting groups have been successfully used in the
photolithographic synthesis of DNA chips3 and peptide arrays4
for genomics and proteomics. Various caged amino acids, peptides,
nucleic acids as well as porphyrin have also been synthesized for
in situ delivery of reactive compounds or for analysis of biological
functions with respect to time and location.2c,5 Light-activation
of gene function in mammalian cells via ribozymes has also been
reported.6 The nitrobenzyl photolabile group has been used as a
linker for the solid-phase synthesis of oligo- and polysaccharides,7
however, only a few sugar derivatives protected with photoremov-
able groups have been reported.8 No glycosylation reaction has
ever been studied with photolabile sugars for oligosaccharides
synthesis. With the emergence of glycomics research9 and the
increasing use of sugars in biomedical application,10 there is a
real need to synthesize various photolabile carbohydrates, and
to study their reactivity and their photodeprotection efficiency
in the glycosylation reaction. These results will certainly be
very useful for the development of light-directed syntheses of
oligosaccharides, glycoconjugates or carbohydrate arrays, as well
Scheme 1 Principal photo cleavage products of NPPOC groups.12e
Results and discussion
We have firstly introduced the NPPOC group on the 6-position
of various glycopyranosides (Table 1). Treatment of methyl a-
D-glucopyranoside 1 and diacetone a-D-galactopyranose 3 with
1.5 equiv. of NPPOC chloride13 in pyridine led to the desired
compounds 2 and 4 in very good yield. We have also prepared
PPSM, Institut d’Alembert, ENS de Cachan, CNRS UMR 8531, 61 Avenue
du Pt Wilson, F-94235 Cachan, France. E-mail: joanne.xie@ens-cachan.fr;
Fax: (+33) 147402454; Tel: (+33) 147405586
† Electronic supplementary information (ESI) available: 1H and 13C spectra
of compounds 2,4,6,8, 10–20. See DOI: 10.1039/b908404e
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Table 1 Synthesis of NPPOC-protected glycopyranosides
Table 2 Photolysis of the NPPOC-protected galactopyranose 4
b
Entry
Conditiona
Concentration
Reaction time
t1/2
1
2
3
4
5
10% (v) H2O
1 equiv. DBU
0.05 M DBU
10% (v) H2O
1 equiv. DBU
100 mM
100 mM
100 mM
10 mM
10 mM
5 min
5 min
5 min
25 min
30 min
37 s
75 s
87 s
n.d.c
n.d.c
Substrate
Product
Yielda (%)
91
a Irradiation with a 200X Hg-Xe high pressure lamp at 365 nm in CH3CN.
b Calculated from the kinetics of photolysis following UV absorption.
c n.d. = not determined.
97
NPPOC-protected glycosides were obtained as a mixture of two
diastereomers which made their 1H NMR spectra more complex.
Photodeprotection of NPPOC-protected compounds can be
realized in aqueous MeOH or CH3CN,12 or in a CH3CN solution
of piperidine or DBU (0.05 M).11a We have studied the photolysis
of the NPPOC galactose 4 under different conditions and followed
the reaction by TLC and UV–vis absorption (Table 2 and Fig. 1
and 2). In the aqueous CH3CN at 100 mM concentration (entry
1, Table 2), the photolysis is completed after 5 min irradiation.
The half time was estimated to be 37 s (Fig. 2a) which is in
accordance with the value reported by A. Hasan et al. in a solution
of MeOH/H2O (1:1, t1/2 = 40 s).12a The cleavage rate is dependent
on the reaction concentration, with shorter reaction times in a
more diluted medium since at higher concentration (10 mM,
entry 4), 25 min irradiation was necessary to accomplish the
photodeprotection. The absorption spectra showed the presence
of nitroso byproduct at 290 and 317 nm (Fig. 1a and 2a).12c We have
also realized the reaction in the presence of DBU. With 1 equiv. of
DBU (entry 2), the reaction was finished after 5 min, with a half
time of 75 s (Fig. 2b) which is a little bit longer than in the presence
92
91
96
a Isolated yield after column chromatography.
phenyl b-D-thioglycosides 6, 8 and 10, which can be further used as
glycosyl donors in the glycosylation reaction. It is to be noted that
due to the presence of an asymmetric carbon in the NPPOC group,
Fig. 1 Normalized UV–vis spectra of 4 before and after photolysis at 365 nm in CH3CN/H2O 9:1 (v/v) (a) or in CH3CN containing 1 equiv. of DBU
(b) at 100 mM or 10 mM concentrations.
Fig. 2 UV–vis traces of photolysis of 4 at 100 mM concentration in CH3CN/H2O 9:1 (v/v) (a), in CH3CN containing 1 equiv. of DBU (b), or 0.05 M
DBU (c). Inset: titration curve of the absorbance at 288 or 284 nm as a function of irradiation time.
3848 | Org. Biomol. Chem., 2009, 7, 3847–3854
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Table 3 Deprotection of NPPOC-protected glycopyranosides
Table 5 Glycosylation of glycosyl donors 6 and 8 with alcohol 1
Entry
Substrate
Product
Method Aa
Method Ba
1
2
3
4
5
2
1
3
5
7
9
95%
95%
93%
97%
95%
91%
96%
95%
98%
95%
Entry
Donor
Solvent
T (◦C)
Yielda
a : bb
4
6
8
10
1
2
3
4
6
6
8
8
CH2Cl2
CH3CN
CH2Cl2
CH3CN
-78
-40
-78
-40
92
87
91
90
1:1.5
1:20
1:10
1:20
a Isolated yield after column chromatography.
a Isolated yield after column chromatography. b The ratio was determined
by 1H NMR.
of water. Nitroso byproduct was also present in this case (Fig. 1b).
Nevertheless, formation of nitroso byproduct can be suppressed
when the reaction was conducted in the presence of 0.05 M DBU
(Fig. 2c), condition optimized by M. Beier and J. D. Hoheisel.11a
The half time of the reaction was estimated to be 87 s. At 10 mM
concentration in the presence of 1 equiv. of DBU (entry 5), no
nitroso byproduct was observed at the end of the reaction (30 min)
(Fig. 1b).
We then realized the photodeprotection of the NPPOC-
protected glycosides (~0.05 M solution) in CH3CN in the presence
of DBU (1 equiv.) (Method A) or 10% water (Method B) for 1
to 2 h irradiation at 365 nm (Table 3). The result showed that
whatever the reaction conditions, the deprotected glycosides were
obtained in excellent yield after purification.
shift in the 13C NMR spectrum at 104.5 ppm (C-1¢). In a similar
way, glycosylation of the NPPOC-protected b-D-thiogalactoside
8 with 3 in CH2Cl2 led successfully to the disaccharide 12 in 97%
yield with a 1:2.3 a:b ratio (entry 4). In this case, the a/b anomers
can be separated by column chromatography. As for the gluco
derivative 11, the b-anomer 12 had the anomeric proton around
1
4.40 ppm with J1¢,2¢ = 7.8 Hz in the H NMR spectrum and the
anomeric carbon at 104.8 ppm (C-1¢) in the 13C NMR spectrum.
For the a-anomer, the anomeric proton appeared at 4.91 ppm with
J1¢,2¢ = 2.3 Hz in the 1H NMR spectrum and the anomeric carbon
at 97.7 ppm (C-1¢) in the 13C NMR spectrum. Better b-selectivity
was obtained in CH3CN (entries 5 and 6).
In the second step, we turned our attention to the glycosylation
reaction with NPPOC-protected b-D-thioglycosides 6 and 8
(Table 4). Glycosylation of 6 with 3 using NIS in the presence of
TfOH in CH2Cl2 at -78 ◦C afforded the desired disaccharide 11 as
a mixture of a/b (1:1.7) isomers in 89% yield (entry 1). In order to
increase the b-selectivity, the reaction was then realized in CH3CN
(entries 2 and 3).15 The best b-selectivity (a:b = 1:10) was obtained
at -40 ◦C. The b-anomeric configuration was confirmed on the
basis of its coupling constant (J1¢,2¢ = 7.8 Hz, H-1¢) for the anomeric
We have also used methyl a-D-glucopyranoside 1 as a glycosyl
acceptor for the glycosylation reaction (Table 5). Reaction of 6
with 1 in CH2Cl2 afforded the disaccharide 13 with similar yield
and stereoselectivity (a:b = 1:1.5) as obtained with the glycosyl
acceptor 3 (entry 1). Glycosylation in CH3CN improved the b-
selectivity (a:b = 1:20, entry 2). For the galactosyl donor 8,
the disaccharide 14 was obtained with a very good b-selectivity
whatever the reaction conditions (entry 3 and 4).
After the successful glycosylation reaction, we tried the pho-
tolysis of the NPPOC-protected disaccharides (~0.05 M solution)
(Table 6). Once again, the photodeprotection can be easily realized
in the presence of water or DBU, leading to the corresponding
1
proton at 4.46 ppm in the H NMR spectrum and the chemical
Table 4 Effects of solvents and temperature on the glycosylation of
glycosyl donors 6 and 8 with alcohol 3
Table 6 Deprotection of NPPOC-protected disaccharides
Entry
Donor
Solvent
T (◦C)
Yielda
a : bb
Substrate
Product
Method Aa,c
Method Bb,c
1
2
3
4
5
6
6
6
6
8
8
8
CH2Cl2
CH3CN
CH3CN
CH2Cl2
CH3CN
CH3CN
-78
-15
-40
-78
-15
-40
89%
90%
87%
97%
91%
89%
1:1.7
1:8
1:10
1:2.3
1:8
11
12
13
14
15
16
17
18
89%
87%
90%
88%
91%
92%
93%
90%
1:20
a Irradiation at 365 nm in the presence of 50 mL DBU in 2 mL of CH3CN.
b Irradiation at 365 nm in aqueous CH3CN (CH3CN/H2O: 9:1). c Isolated
yield after column chromatography.
a Isolated yield after column chromatography. b The ratio was determined
by 1H NMR.
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disaccharides 15, 16,16 1717 and 1818 in good yield. These com-
pounds can be further employed as glycosyl acceptors for the
synthesis of complex oligosaccharides.
at the optimal distance (about 1.0 cm away from its end). UV/vis
absorption spectra were recorded on a Uvikon-940 KONTRON
spectrophotometer. The kinetics of the photolysis of 4 was realized
in CH3CN at 100 mM concentration by irradiation at 365 nm. The
order 1 kinetics reactions are fitted with the model eqn (1). An is the
measured absorbance, Amax is the finished reaction absorbance. t0:
It’s well known that thioglycosides can be easily hydrol-
ysed or transformed into other glycosyl donors. Treatment of
NPPOC-protected glucopyranoside 6 with NBS in a mixture of
THF/H2O led to the corresponding glucopyranose 19 in 94% yield
(Scheme 2). This compound can be further transformed into other
glycosyl donors like trichloroacetimidate. By treatment with NIS
and DAST, compound 6 can also be converted into the glucosyl
fluoride 20 as a mixture of a/b anomers.
time zero, tn: time of irradiation. The half-time (t1 ) was calculated
2
according to eqn (2):
An = Amax.(1 - exp(-(tn+t0) t -1
)
(1)
(2)
t1 = t ln2
2
General procedure for the synthesis of NPPOC-protected
glycopyranosides
To a solution of glycopyranoside (1 mmol) in anhydrous pyridine
(10 mL) at 0 ◦C, was added dropwise a solution of 2-(2-
nitrophenyl) propyloxycarbonyl chloride (1.5 mmol in 2.5 mL
CH2Cl2). The mixture was stirred for 2 h at 0 ◦C and then gradually
raised to rt. After evaporation, the residue was diluted in EtOAc,
washed with HCl (0.5 N, 2 ¥ 5 mL), saturated NaHCO3 (3 ¥
10 mL) and brine (3 ¥ 10 mL). The organic layer was dried over
MgSO4 and concentrated under vacuum to give a crude product
which was purified by column chromatography to give the desired
NPPOC-protected product.
Scheme 2 Transformation of NPPOC-protected glucopyranoside 6.
Conclusions
In summary, we have synthesized for the first time the 6-O-NPPOC
protected glycopyranosides in very good yield. The NPPOC-
protected thioglycosides have been successfully used as glycosyl
donors for photolabile disaccharide synthesis with very good
b-selectivity in CH3CN. The 6-O-NPPOC thioglucoside 6 can
also be readily converted into the corresponding glucopyranose
or glucosyl fluoride, which could extend the application of
NPPOC-protected sugars. Finally, we have demonstrated that
NPPOC-protected carbohydrates can be easily photodeprotected
under neutral or basic conditions. At 100 mM concentration, the
NPPOC group was removed in less than five minutes. These
results showed that the NPPOC group should be useful as a
photolabile protecting group in carbohydrate chemistry, especially
in automated oligosaccharide synthesis as well as for caged sugar
derivatives.
General procedure for the glycosylation of NPPOC protected
thioglycosides
A mixture of NPPOC protected thioglycoside (1.0 mmol), glycosyl
˚
acceptor (1.5 mmol), NIS (2.0 mmol), and powdered 4 A molecular
sieves (1 g) in CH2Cl2 (20 mL) or CH3CN (20 mL) was stirred
for 20 min at -78 ◦C (or -40 ◦C) before the addition of TfOH
(0.015 mmol). The mixture was stirred at -78 ◦C (or -40 ◦C) for
2 h and then gradually raised to rt. After the completion of the
reaction, Na2SO3 (2 g), NaHCO3 (2 g), and a few drops of water
were added into the reaction mixture, and the mixture was stirred
for 5 min, then diluted with CH2Cl2 (25 mL), filtered through
Celite, washed with saturated NaHCO3 (3 ¥ 10 mL) and brine (3 ¥
10 mL), dried over MgSO4, and concentrated in vacuum to give a
crude product which was purified by chromatography.
Experimental section
General procedure for the photolysis of NPPOC-protected
saccharides
General techniques
A solution of NPPOC-protected saccharide (0.1 mmol) in CH3CN
(2.0 mL) in the presence of DBU (Method A) or H2O (10% v)
(Method B) in a 1 cm path-length quartz cell was irradiated
by 365 nm UV-light. The reaction was monitored by UV/vis
absorption spectra or TLC. After the completion of the reaction,
the reaction mixture was evaporated to dryness and the residue
purified by column chromatography to give the desired photode-
protected product.
1H and 13C NMR spectra were recorded on a 400 MHz spec-
trometer. Column chromatography was performed on Silica Gel
60 (230–400 mesh). Analytical thin-layer chromatography was
performed on aluminium percolated plates of Silica Gel 60F-
254 with detection by UV and by spraying with 6 N H2SO4 and
◦
heating for about 2 min at 300 C. IR spectra were recorded on
a Thermo Nicolet Nexus FT-IR spectrometer. ESI-HRMS mass
spectra were recorded on a Thermo LTQ-Orbitrap spectrometer at
the Service of Mass Spectrometry of University Pierre and Marie
Curie. The UV light was supplied by a 200 W Hg-Xe high pressure
lamp (Hamamatsu LC6). The light is passed successively through
a 365 nm interference filter, only light of a wavelength of 365 nm
was used. The output from the light guide is about 150 mW/cm2
Methyl 2,3,4-tri-O-benzyl-6-O-2-(2-nitrophenyl)propyloxycar-
bonyl-a-D-glucopyranoside 2. Methyl 2,3,4-tri-O-benzyl-a-D-
glucopyranoside 1 (0.47 g, 1.0 mmol) was treated with NPPOCCl
according to the general procedure. Purification by column
chromatography (EtOAc:cyclohexane, 1:9–1:4) gave 0.61 g (91%)
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of compound 2 as an oil. Rf = 0.57 (EtOAc:cyclohexane, 3:7). 1H
NMR (400 MHz, CDCl3): d 1.33 and 1.34 (2d, J = 6.8 Hz, 3H,
CH3), 3.32 (s, 3H, OMe), 3.41–3.52 (m, 2H, 2 ¥ CH), 3.65–3.72
(m, 1H, CH), 3.76 (td, J = 3.0, 9.8 Hz, 1H), 3.96 (t, J = 9.6 Hz,
1H), 4.23–4.26 (m, 2H, CH2), 4.50 (dd, J = 10.1 and 11.0 Hz,
1H), 4.55 (d, J = 3.7 Hz, 1H), 4.63 (d, J = 12.4 Hz, 1H), 4.77 (d,
J = 11.9 Hz, 1H), 4.79 (d, J = 10.6 Hz, 1H), 4.83 (dd, J = 5.0,
11.0 Hz, 1H), 4.97 (d, J = 10.6 Hz, 1H), 7.23–7.31 (m, 16H),
7.42–7.54 (m, 2H, 2 ¥ CH), 7.73 (d, J = 9.2 Hz, 1H). 13C NMR
(100 MHz, CDCl3):d 17.9, 33.3, 33.4, 55.4, 66.5, 68.6, 68.6, 71.6,
73.5, 75.2, 75.8, 77.3, 77.4, 79.9, 82.1, 98.1, 124.5, 127.6, 127.7,
127.9, 128.0, 128.1, 128.2, 128.4, 128.5, 128.56, 128.58, 132.8,
136.9, 138.0, 138.2, 138.8, 150.28, 150.32. ESI HRMS (m/z): calcd
for C38H41NNaO10: 694.2628, found: 694.2623.
71.7, 71.8, 73.0, 73.2, 73.3, 74.5, 75.6, 75.7, 75.8, 77.2, 84.1, 87.8,
124.3, 124.4, 127.3, 127.66, 127.70, 127.8, 128.1, 128.3, 128.4,
128.6, 128.9, 131.7, 131.8, 132.80, 132.84, 134.0, 136.9, 138.2,
138.3, 138.4, 150.3, 154.7, 154.9. ESI HRMS (m/z): calcd for
C43H43NNaO9S: 772.2556, found: 772.2551.
Phenyl 2,3-O-acetyl-4-O-benzyl-6-O-2-(2-nitrophenyl)propyl-
oxycarbonyl-1-thio-b-D-glucopyranoside 10. Phenyl 2,3-O-
acetyl-4-O-benzyl-1-thio-b-D-glucopyranoside
9
(90 mg,
0.20 mmol) was treated with NPPOCCl according to the general
procedure. Purification by column chromatography (EtOAc :
cyclohexane, 1:9–1:4) gave 126 mg (96%) of compound 10 as an
1
oil. Rf = 0.30 (EtOAc:cyclohexane, 1:4). H NMR (400 MHz,
CDCl3): d 1.39 (d, J = 6.8 Hz, 1.5H, 0.5 ¥ CH3), 1.40 (d,
J = 7.3 Hz, 1.5H, 0.5 ¥ CH3), 1.93 and 1.94 (2 s, 3H, Ac), 2.07 (s,
3H, Ac), 3.61–3.66 (m, 2H, H-4,5), 3.33–3.81 (m, 1H, CH-Ar),
4.21–4.24 (m, 1H, H-6), 4.28–4.36 (m, 2H), 4.42 (dd, J = 4.6,
11.4 Hz, 1H), 4.51–4.58 (m, 2H), 4.67 (d, J = 8.9 Hz, 1H, H-1),
4.87 and 4.88 (2t, J = 10.1 Hz, H-2), 5.22–5.27 (m, 1H, H-3),
7.21–7.41 (m, 9H, Ar), 7.45–7.50 (m, 3H, Ar), 7.55–7.60 (m,
1H, Ar), 7.76–7.80 (m, 1H, Ar). 13C NMR (400 MHz, CDCl3)
d 18.0, 18.1, 21.0, 33.46, 33.53, 66.3, 66.4, 70.6, 71.9, 75.0, 75.6,
76.2, 77.1, 77.5, 85.9, 124.6, 127.9, 128.2, 128.3, 128.36, 128.43,
128.5, 128.8, 129.1, 132.2, 133.0, 133.1, 137.0, 137.3, 137.4, 150.4,
154.9, 169.8, 170.2. ESI HRMS (m/z): calcd for C33H35NNaO11S:
676.1828, found: 676.1823.
1,2:3,4-Di-O-isopropylidene-6-O-2-(2-nitrophenyl)propyloxy-
carbonyl-a-D-galactopyranose 4. 1,2:3,4-Diisopropylidene-a-D-
galactopyranose 3 (0.52 g, 2 mmol) was treated with NPPOCCl
according to the general procedure. Purification by column
chromatography (EtOAc:cyclohexane, 1:9–1:4) gave 0.9 g (97%)
of compound 4 as an oil. Rf = 0.50 (EtOAc:cyclohexane, 3:7).
1H NMR (400 MHz, CDCl3): d 1.23–1.42 (m, 15H, 5 ¥ CH3),
3.61–3.62 (m, 1H), 3.95–3.97 (m, 1H), 4.15–4.23 (m, 6H), 4.51–
4.53 (m, 1H), 5.42–5.43 (m, 1H), 7.26–7.30 (m, 1H), 7.38–7.41 (m,
1H), 7.47–7.50 (m, 1H), 7.65–7.68 (m, 1H). 13C NMR (100 MHz,
CDCl3): d 17.6, 17.8, 24.4, 25.85, 25.92, 33.24, 33.29, 65.6, 66.5,
70.3, 70.5, 70.7, 71.4, 96.1, 108.7, 109.5, 124.2, 127.5, 128.3, 132.7,
136.8, 150.1, 154.8. ESI HRMS (m/z): calcd for C22H29NNaO10:
490.1689, found: 490.1681.
2,3,4-Tri-O-benzyl-6-O-2-(2-nitrophenyl)propyloxycarbonyl-
b-D-glucopyranosyl-(1→6)-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranose 11. Compound 6 (66 mg, 0.088 mmol) was
treated with alcohol 3 (35 mg, 0.13 mmol) in CH3CN accord-
ing to the general procedure. Purification by chromatography
(EtOAc:cyclohexane, 1:4–1:2) gave 69 mg (87%) of 11 (b/a = 10:1)
as an oil. Rf = 0.62 (EtOAc:cyclohexane, 3:7). 1H NMR (400 MHz,
CDCl3): d 1.31–1.49 (m, 15H, 5 ¥ CH3), 3.40–3.50 (m, 2H), 3.61–
3.78 (m, 3H), 4.06–4.14 (m, 2H), 4.23–4.38 (m, 5H), 4.46 (d,
J = 7.8 Hz, 1H), 4.50 (dd, J = 5.0, 11.0 Hz, 1H), 4.59 (dd, J = 2.8,
8.3 Hz, 1H), 4.72 (d, J = 11.0 Hz, 1H), 4.77 (d, J = 11.0 Hz, 1H),
4.83 (d, J = 10.6 Hz, 1H), 4.98 (d, J = 11.0 Hz, 1H), 5.06 (d,
J = 11.0 Hz, 1H), 5.57 (d, J = 2.3 Hz, 1H), 7.22–7.42 (m, 16H),
Phenyl 2,3,4-tri-O-benzyl-6-O-2-(2-nitrophenyl)propyloxycar-
bonyl-1-thio-b-D-glucopyranoside 6. Phenyl 2,3,4-tri-O-benzyl-
1-thio-b-D-glucopyranoside 5 (0.38 g, 0.71 mmol) was treated
with NPPOCCl according to the general procedure. Purification
by column chromatography (EtOAc : cyclohexane, 1:9–1:4)
gave 0.49 g (92%) of compound 6 as an oil. Rf = 0.27
1
(EtOAc:cyclohexane, 1:4). H NMR (400 MHz, CDCl3): d 1.38
(d, J = 6.9 Hz, 3H, CH3), 3.46–3.53 (m, 3H), 3.68–3.76 (m,
2H), 4.21–4.25 (m, 1H), 4.30(d, J = 6.4 Hz, 2H, CH2), 4.37 (d,
J = 11.4 Hz, 1H), 4.54 and 4.55 (2d, J = 11.0 Hz, 1H), 4.63 and
4.64 (2d, J = 9.6 Hz, 1H), 4.72 (d, J = 10.1 Hz, 1H), 4.82–4.92 (m,
4H), 7.22–7.39 (m, 19H), 7.45–7.54 (m, 4H), 7.74–7.78 (m, 1H).
13C NMR (400 MHz, CDCl3) d 18.0, 33.4, 66.8, 71.6, 75.2, 75.6,
76.0, 77.4, 80.9, 86.8, 87.7, 124.5, 127.7, 127.9, 128.07, 128.18,
128.36, 128.43, 128.48, 128.59, 128.63, 128.67, 129.1, 132.0, 132.2,
132.9, 133.7, 137.0, 137.7, 138.0, 138.4, 150.3, 155.0. ESI HRMS
(m/z): calcd for C43H43NNaO9S: 772.2556, found: 772.2551.
7.47–7.49 (m, 1H), 7.53–7.58 (m, 1H), 7.76 (d, J = 8.2 Hz, 1H). 13
C
NMR (100 MHz, CDCl3) d 18.0, 24.5, 25.0, 25.1, 26.0, 26.1, 33.3,
60.5, 62.4, 66.6, 66.7, 67.4, 70.2, 70.5, 70.8, 71.4, 71.5, 72.8, 74.4,
75.2, 75.8, 77.2, 81.4, 84.4, 96.4, 96.4, 104.5, 108.6, 108.7, 109.5,
124.5, 127.6, 127.7, 127.9, 128.0, 128.2, 128.3, 128.4, 128.5, 128.6,
128.8, 132.8, 136.9, 137.8, 138.6, 150.2, 150.2, 154.9. ESI HRMS
(m/z): calcd for C49H57NNaO15: 922.3626, found: 922.3620.
Phenyl 2,3,4-tri-O-benzyl-6-O-2-(2-nitrophenyl)propyloxycar-
2,3,4-Tri-O-benzyl-6-O-2-(2-nitrophenyl)propyloxycarbonyl-
b-D-galactopyranosyl-(1→6)-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranose 12. Compound 8 (108 mg, 0.14 mmol) was
treated with alcohol 3 (65 mg, 0.25 mmol) in CH3CN accord-
ing to the general procedure. Purification by chromatography
(EtOAc:cyclohexane, 1:4–1:2) gave 117 mg (91%) of 12 (b/a = 8:1)
as an oil. Reaction in CH2Cl2 followed by purification allowed us to
isolate a small quantity of a-anomer as the minor product. Data
bonyl-1-thio-b-D-galactopyranoside
8. Phenyl
2,3,4-tri-O-
benzyl-1-thio-b-D-galactopyranoside 7 (0.54 g, 1 mmol) was
treated with NPPOCCl according to the general procedure.
Purification by column chromatography (EtOAc : cyclohexane,
1:9–1:4) gave 0.68 g (91%) of compound 8 as an oil. Rf = 0.28
1
(EtOAc:cyclohexane, 1:4). H NMR (400 MHz, CDCl3): d 1.34
and 1.45 (2d, J = 6.9 Hz, 3H, CH3), 3.59–3.73 (m, 3H), 3.89–3.92
(m, 2H), 4.08–4.20 (m, 1H), 4.23–2.29 (m, 3H), 4.56–4.62 (m,
2H), 4.71–4.77 (m, 4H), 4.98 and 4.99 (2d, J = 11.4 Hz, 1H),
7.20–7.50 (m, 22H), 7.56–7.61 (m, 2H), 7.76–7.78 (m, 1H). 13C
NMR (100 MHz, CDCl3) d 17.8, 17.9, 33.3, 66.3, 66.6, 71.6,
1
for a-Anomer: Rf = 0.26 (EtOAc:cyclohexane, 1:4). H NMR
(400 MHz, CDCl3): d 1.28–1.42 (m, 15H, 5 ¥ CH3), 3.61–3.67 (m,
2H), 3.85–4.01 (m, 6H), 4.06–4.11 (m, 1H), 4.20–4.24 (m, 4H),
4.47–4.55 (m, 2H), 4.67 (s, 2H), 4.69 (d, J = 11.5 Hz, 1H), 4.79
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(d, J = 11.5 Hz, 1H), 4.87 and 4.89 (2d, J = 11.0 Hz, 1H), 4.91
and 4.92 (2d, J = 2.3 Hz, 1H), 5.42 and 5.43 (2d, J = 2.3 Hz,
1H), 7.19–7.34 (m, 16H), 7.37–7.41 (m, 1H), 7.46–7.52 (m, 1H),
7.68–7.72 (m, 1H). 13C NMR (100 MHz, CDCl3) d 18.0, 24.7, 25.0,
26.1, 26.2, 33.3, 33.4, 65.9, 66.4, 66.6, 66.7, 70.7, 70.8, 71.6, 72.9,
73.4, 74.5, 74.6, 74.8, 76.3, 77.4, 78.9, 96.4, 97.7, 108.6, 109.3,
124.5, 127.5, 127.6, 127.7, 127.8, 127.9, 128.4, 128.5, 132.9, 137.0,
138.4, 138.7, 138.9, 150.3, 154.8. Data for b-Anomer: Rf = 0.25
2H), 4.76–4.80 (m, 4H), 4.93–4.98 (m, 3H), 7.19–7.34 (m, 31H),
7.41–7.43 (m, 1H), 7.50–7.54 (m, 1H), 7.70–7.74 (m, 1H). 13C
NMR (100 MHz, CDCl3) d 17.8, 17.9, 33.2, 33.3, 55.3, 66.2, 66.6,
68.58, 68.64, 70.0, 71.77, 71.82, 71.9, 72.0, 73.2, 73.3, 73.4, 74.6,
75.0, 75.3, 75.8, 77.4, 78.1, 79.9, 82.19, 82.24, 98.0, 104.1, 104.2,
124.4, 127.5, 127.6, 127.7, 128.0, 128.1, 128.2, 128.3, 128.4, 128.51,
128.54, 132.8, 132.9, 136.9, 138.3, 138.4, 138.5, 138.7, 139.0,
150.4, 154.7, 154.7. ESI HRMS (m/z): calcd for C65H69NNaO15:
1126.4565, found: 1126.4559.
1
(EtOAc:cyclohexane, 1:4). H NMR (400 MHz, CDCl3): d 1.30
(s, 6H, 3 ¥ CH3), 1.36 (2d, J = 7.8 Hz, 3H, CH3), 1.44 (s, 3H,
CH3), 1.48 (s, 3H, CH3), 3.48–3.58 (m, 1H), 3.64–3.76 (m, 1H),
3.80–3.83 (m, 1H), 4.06–4.14 (m, 2H), 4.16–4.32 (m, 3H), 4.40
and 4.41 (2d, J = 7.8 Hz, 1H), 4.57 (td, J = 2.3, 7.8 Hz, 1H), 4.60
(t, J = 11.9 Hz, 1H), 4.74 and 4.75 (2d, J = 11.9 Hz, 1H), 4.83
(d, J = 11.9 Hz, 1H), 4.94 (dd, J = 6.0, 11.4 Hz, 1H), 5.05 (d,
J = 11.0 Hz, 1H), 5.56 (d, J = 1.0 Hz, 1H), 7.24–7.38 (m, 15H),
7.44–7.47 (m, 2H), 7.53–7.58 (m, 1H), 7.75 (d, J = 8.2 Hz, 1H).
13C NMR (100 MHz, CDCl3) d17.9, 24.6, 26.08, 26.11, 33.3, 66.3,
66.6, 67.5, 69.9, 70.6, 70.8, 71.5, 71.68, 71.74, 71.8, 71.9, 73.1, 73.2,
73.4, 74.5, 74.8, 77.4, 79.0, 81.8, 96.4, 104.7, 104.8, 108.7, 109.4,
109.4, 124.4, 127.5, 127.5, 127.6, 127.67, 127.72, 127.8, 128.2,
128.3, 128.4, 128.6, 128.7, 132.8, 136.86, 136.89, 138.3, 138.59,
138.61, 139.0, 150.3, 154.6, 154.7. ESI HRMS (m/z): calcd for
C49H57NNaO15 (M + Na+) 922.3626, found 922.3620.
2,3,4-Tri-O-benzyl-b-D-glucopyranosyl-(1→6)-1,2:3,4-di-O-
isopropylidene-a-D-galactopyranose 15. Photolysis of compound
11 (b/a = 8:1) (40 mg, 0.04 mmol) according to the gen-
eral procedure gave, after purification by chromatography
(EtOAc:cyclohexane, 1:4–3:7) 27 mg (89%) of 15 (b/a = 8:1) as
an oil. Data for b-anomer: Rf = 0.18 (EtOAc:cyclohexane, 1:4).
1H NMR (400 MHz, CDCl3): d 1.32, 1.34, 1.52, 1.54 (4 s, 12H, 4 ¥
CH3), 2.21 (s, 1H, OH), 3.36 (ddd, J = 2.7, 5.0, 9.6 Hz, 1H), 3.42
(dd, J = 8.2, 9.2 Hz, 1H), 3.50 (dd, J = 8.7, 9.6 Hz, 1H), 3.63–3.68
(m, 1H), 3.66 (t, J = 9.2 Hz, 1H), 3.77 (dd, J = 6.4, 10.1 Hz,
1H), 3.83–3.3.86 (m, 1H), 4.02–4.06 (m, 1H), 4.09 (dd, J = 5.0,
10.1 Hz, 1H), 4.28 (dd, J = 4.6, 7.8 Hz, 1H), 4.33 (dd, J = 2.8,
5.0 Hz, 1H), 4.50 (d, J = 7.8 Hz, 1H), 4.61 (d, J = 10.6 Hz, 2H),
4.71 (d, J = 11.0 Hz, 1H), 4.79 (d, J = 11.0 Hz, 1H), 4.84 (d,
J = 11.0 Hz, 1H), 4.95 (d, J = 11.0 Hz, 1H), 5.01 (d, J = 11.4 Hz,
1H), 5.57 (d, J = 5.0 Hz, 1H), 7.24–7.31 (m, 15H). 13C NMR
(100 MHz, CDCl3) d 24.6, 25.1, 26.1, 26.2, 62.3, 67.2, 69.5, 70.6,
70.9, 71.3, 74.6, 75.1, 75.2, 75.8, 77.4, 77.8, 81.9, 84.5, 96.5, 104.3,
108.8, 109.6, 127.7, 128.0, 128.1, 128.4, 128.5, 128.6, 138.1, 138.6,
138.7. ESI HRMS (m/z): calcd for C39H48NaO11: 715.3094, found:
715.3089.
Methyl 2,3,4-tri-O-benzyl-6-O-2-(2-nitrophenyl)propyloxycar-
bonyl-b-D-glucopyranosyl-(1→6)-2,3,4-tri-O-benzyl-a-D-
glucopyranoside 13. Compound 6 (154 mg, 0.2 mmol) was
treated with alcohol 1 (116 mg, 0.25 mmol) in CH3CN accord-
ing to the general procedure. Purification by chromatography
(EtOAc:cyclohexane, 1:4–1:2) gave 198 mg (87%) of the desired
product 13 (b/a = 20:1) as an oil. Rf = 0.13 (EtOAc:cyclohexane,
1:4). 1H NMR (400 MHz, CDCl3): d 1.32 and 1.33 (2d, J = 6.9 Hz,
3H, CH3), 3.31 (s, 3H, CH3), 3.42–3.52 (m, 6H), 3.59–3.72 (m, 3H),
3.77–3.79 (m, 1H), 3.98 (t, J = 9.6 Hz, 1H), 3.99–4.14 (m, 1H), 4.18
(dd, J = 4.6, 11.4 Hz, 1H), 4.25–4.27 (m, 2H), 4.31 and 4.32 (2d,
J = 7.8 Hz, 1H), 4.36 (d, J = 11.4 Hz, 1H), 4.47 (d, J = 11.0 Hz,
1H), 4.51 (d, J = 11.0 Hz, 1H), 4.59 (d, J = 3.2 Hz, 1H), 4.65 (d,
J = 12.8 Hz, 1H), 4.71 (d, J = 12.8 Hz, 1H), 4.76–4.84 (m, 4H),
4.92 (d, J = 11.0 Hz, 1H), 4.95 (d, J = 10.6 Hz, 2H), 7.15–7.34
(m, 31H), 7.42–7.45 (m, 1H), 7.49–7.55 (m, 1H), 7.71–7.75 (m,
1H). 13C NMR (100 MHz, CDCl3) d17.9, 33.4, 55.3, 66.7, 68.6,
69.8, 71.6, 71.7, 73.0, 73.5, 75.1, 75.2, 75.8, 79.9, 82.0, 82.1, 84.8,
98.2, 103.7, 124.5, 127.68, 127.74, 127.8, 127.97, 128.04, 128.1,
128.16, 128.19, 128.3, 128.49, 128.5, 128.6, 132.8, 136.9, 137.8,
138.2, 138.3, 138.4, 138.9, 150.3, 154.9. ESI HRMS (m/z): calcd
for C65H69NNaO15: 1126.4565, found: 1126.4559.
2,3,4-Tri-O-benzyl-b-D-galactopyranosyl-(1→6)-1,2:3,4-di-O-
isopropylidene-a-D-galactopyranose 16. Photolysis of compound
12 (b/a = 8:1) (32 mg, 0.035 mmol) according to the
general procedure gave, after purification by chromatography
(EtOAc:cyclohexane, 1:4–3:7) 21 mg (87%) of 16 (b/a = 8:1) as
an oil. Rf = 0.12 (EtOAc:cyclohexane, 1:4). vmax/cm-1 3411, 2923,
1641, 1453, 1381, 1254, 1210, 1167, 1069, 1028, 1006, 898, 734,
698.1H NMR (400 MHz, CDCl3): d 1.32 (s, 3H, CH3), 1.34 (s, 3H,
CH3), 1.45 (s, 3H, CH3), 1.51 (s, 3H, CH3), 2.21 (s, 1H, OH), 3.35–
3.39 (m, 1H), 3.42 (dd, J = 8.2, 9.2 Hz, 1H), 3.51 (t, J = 8.7 Hz,
1H), 3.64–3.68 (m, 1H), 3.66 (t, J = 9.2 Hz, 1H), 3.83–3.86 (m,
1H), 4.04 (td, J = 1.4, 6.4 Hz, 1H), 4.27 (dd, J = 1.8, 7.8 Hz, 1H),
4.33 (dd, J = 2.8, 5.0 Hz, 1H), 4.50 (d, J = 7.8 Hz, 1H), 4.59–4.62
(m, 2H), 4.71 (d, J = 11.0 Hz, 1H), 4.79 (d, J = 11.0 Hz, 1H),
4.84 (d, J = 11.0 Hz, 1H), 4.95 (d, J = 11.0 Hz, 1H), 5.01 (d,
J = 11.4 Hz, 1H), 5.56 (d, J = 5.0 Hz, 1H), 7.26–7.31 (m, 15H).
13C NMR (100 MHz, CDCl3) d 24.6, 25.2, 26.1, 26.2, 62.2, 67.4,
69.5, 70.7, 70.9, 71.4, 73.2, 73.6, 74.3, 74.8, 75.0, 79.4, 82.2, 96.6,
104.8, 108.8, 109.5, 127.6, 127.8, 128.1, 128.3, 128.6, 128.7, 128.8,
138.3, 138.6, 139.1.
Methyl 2,3,4-tri-O-benzyl-6-O-2-(2-nitrophenyl)propyloxycar-
bonyl-b-D-galactopyranosyl-(1→6)-2,3,4-tri-O-benzyl-a-D-gluco-
pyranoside 14. Compound 8 (168 mg, 0.22 mmol) was treated
with alcohol 1 (123 mg, 0.26 mmol) in CH3CN accord-
ing to the general procedure. Purification by chromatography
(EtOAc:cyclohexane, 1:4–1:2) gave 0.22 g (90%) of the desired
product 14 (b/a = 20:1) as an oil. Rf = 0.42 (EtOAc:cyclohexane,
3:7). 1H NMR (400 MHz, CDCl3): d 1.33 and 1.34 (2d, J = 6.9 Hz,
3H, CH3), 3.31 (s, 3H, CH3), 3.46–3.53 (m, 4H), 3.58–3.64 (m, 1H),
3.70–3.76 (m, 1H), 3.80–3.89 (m, 4H), 3.97 (t, J = 9.0 Hz, 1H),
4.10–4.16 (m, 2H), 4.19–4.31 (m, 3H), 4.50 (2d, J = 11.0 Hz,
1H), 4.55–4.60 (m, 2H), 4.63 (d, J = 11.4 Hz, 1H), 4.67–4.72 (m,
Methyl 2,3,4-tri-O-benzyl-b-D-glucopyranosyl-(1→6)-2,3,4-tri-
O-benzyl-a-D-glucopyranoside 17. Photolysis of compound 13
(38 mg, 0.04 mmol) according to the general procedure gave,
after purification by chromatography (EtOAc:cyclohexane, 1:4–
3:7) 28 mg (90%) of 17 as an oil. Rf = 0.17 (EtOAc:cyclohexane,
1:4). vmax/cm-1 3659, 2972, 2901, 1453, 1357, 1140, 1067, 1028, 737,
695. 1H NMR (400 MHz, CDCl3): d 1.98 (s, 1H, OH), 3.32 (s, 3H),
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3.22–3.34 (m, 1H), 3.45 (dd, J = 7.8, 9.2 Hz, 1H), 3.49–3.57 (m,
3H), 3.64 (t, J = 9.2 Hz, 2H), 3.68 (dd, J = 4.1, 10.5 Hz, 1H), 3.75–
3.84 (m, 2H), 3.97 (t, J = 9.6 Hz, 1H), 4.08 (dd, J = 1.4, 11.0 Hz,
1H), 4.36 (d, J = 7.8 Hz, 1H), 4.48 (d, J = 11.5 Hz, 1H), 4.60–4.64
(m, 3H), 4.66 (d, J = 12.4 Hz, 1H), 4.70 (d, J = 11.0 Hz, 1H), 4.73–
4.97 (m, 7H), 7.24–7.31 (m, 30H). 13C NMR (100 MHz, CDCl3)
d 55.4, 62.1, 68.8, 69.9, 73.5, 75.0, 75.1, 75.2, 75.9, 77.7, 77.9,
79.8, 82.1, 84.7, 98.3, 103.9, 127.1, 127.8, 127.9, 128.0, 128.08,
128.13, 128.2, 128.3, 128.5, 128.60, 128.64, 138.1, 138.2, 138.3,
138.4, 139.5, 138.9.
Na2SO3 (250 mg), NaHCO3 (250 mg), and a few drops of water
were added. The mixture was stirred for 5 min, then diluted with
CH2Cl2 (50 mL), filtered through Celite, washed with saturated
NaHCO3 (2 ¥ 10 mL) and brine (2 ¥ 10 mL), dried over MgSO4,
and concentrated in vacuum. Purification by chromatography
(EtOAc: cyclohexane, 1:9–1:4) gave 61 mg (90%) of 20 as a mixture
of a and b anomers about 1:1. Rf = 0.2 (EtOAc:cyclohexane, 1:9).
1H NMR (400 MHz, CDCl3): d 1.35 and 1.37 (2d, J = 6.8 Hz, 3H,
CH3), 3.49–3.75 (m, 3.7H), 3.94–4.01 (m, 1.3H), 4.20–4.41 (m,
4H), 4.49–4.58 (m, 1H), 4.68–4.72 (m, 1H), 4.77 (d, J = 11.0 Hz,
1H), 4.81–4.91 (m, 2H), 4.97 (d, J = 11.0 Hz, 1H), 5.26 (dd, J = 6.9,
52.7 Hz, 0.5H, H-1b), 5.26 (dd, J = 6.9, 52.7 Hz, 0.5H, H-1b), 5.49
and 5.51 (2dd, J = 2.3, 52.7 Hz, 0.5H, H-1a), 7.23–7.35 (m, 16H),
7.42–7.46 (m, 1H), 7.60–7.66 (m, 1H), 7.75 (m, 1H). 13C NMR
(100 MHz, CDCl3): d 18.0, 33.3, 65.8, 66.2, 71.2, 71.8, 72.9, 73.7,
74.5, 75.1, 75.3, 75.4, 75.9, 76.1, 76.2, 76.4, 79.2, 79.5, 81.2, 81.4,
83.4, 83.5, 104.2, 106.5, 108.5, 110.7, 124.5, 127.7, 127.9, 128.0,
128.1, 128.2, 128.25, 128.3, 128.4, 128.6, 128.63, 128.7, 132.8,
136.9, 137.6, 137.7, 138.2, 138.4, 150.3, 154.8. ESI HRMS (m/z):
calcd for C37H38FNNaO9: 682.2428, found: 682.2428.
Methyl 2,3,4-tri-O-benzyl-b-D-galactopyranosyl-(1→6)-2,3,4-
tri-O-benzyl-a-D-glucopyranoside 18. Photolysis of compound
14 (31 mg, 0.028 mmol) according to the general procedure gave,
after purification by chromatography (EtOAc:cyclohexane, 1:4–
3:7) 22 mg (88%) of 18 as an oil. Rf = 0.13 (EtOAc:cyclohexane,
1:4). vmax/cm-1 3519, 3064, 3031, 2923, 1496, 1453, 1357, 1212,
1086, 1060, 1028, 911, 736, 696, 679. 1H NMR (400 MHz, CDCl3):
d 3.31 (s, 3H, CH3), 3.45–3.52 (m, 4H), 3.64 (dd, J = 4.5, 11.0 Hz,
1H), 3.73–3.77 (m, 1H), 3.80–3.83 (m, 1H), 3.85 (dd, J = 7.8,
9.6 Hz, 1H), 3.98 (t, J = 9.2 Hz, 1H), 4.10 (dd, J = 1.8, 11.0 Hz,
1H), 4.30 (d, J = 7.8 Hz, 1H), 4.51 (d, J = 11.4 Hz, 1H), 4.58 (d,
J = 3.7 Hz, 1H), 4.61 (d, J = 11.9 Hz, 1H), 4.64 (d, J = 11.9 Hz,
1H), 4.71–4.79 (m, 8H), 4.91–4.97 (m, 3H), 7.19–7.34 (m, 30H).
13C NMR (100 MHz, CDCl3) d 55.3, 62.2, 68.9, 70.2, 73.2, 73.4,
73.5, 74.3, 74.8, 75.0, 75.3, 75.8, 78.2, 79.5, 80.0, 82.2, 82.5, 98.1,
104.4, 126.8, 127.67, 127.72, 127.76, 127.8, 128.0, 128.1, 128.3,
128.4, 128.5, 128.6, 128.7, 138.3, 138.4, 138.5, 138.6, 138.8, 139.0.
Notes and references
1 (a) A. Varki, Glycobiology, 1993, 3, 97–130; (b) R. A. Dwek, Chem.
Rev., 1996, 96, 683–720; (c) C.-H. Wong, Acc. Chem. Res., 1999, 32,
376–385.
2 (a) V. N. R. Pillai, Synthesis, 1980, 1–26; (b) C. G. Bochet, J. Chem.
Soc., Perkin Trans., 2002, 1, 125–142; (c) C. G. Bochet, Synlett, 2004,
2268–2274; (d) G. Mayer and A. Heckel, Angew. Chem., Int. Ed., 2006,
45, 4900–4921.
2,3,4-Tri-O-benzyl-6-O-2-(2-nitrophenyl)propyloxycarbonyl-a-
D-glucopyranose 19. To a solution of compound 6 (0.15 g,
0.20 mmol) in THF/H2O (10/1, 5 ml), was added NBS (0.80 g,
1.0 mmol) at 0 ◦C. The reaction mixture was stirred 2 h at rt.
After completion of the reaction, Na2SO3 (1 g), NaHCO3 (1 g),
and a few drops of water were added. The mixture was stirred
for 20 min, diluted with EtOAc (50 mL), washed with saturated
NaHCO3 (3 ¥ 10 mL) and brine (3 ¥ 10 mL), dried over MgSO4,
and concentrated in vacuum to give a crude product which was
purified by chromatography (EtOAc:cyclohexane, 1:4–1:2) to give
0.124 g (94%) of 19 as a mixture of a and b anomers about 3:2.
Rf = 0.09 (EtOAc:cyclohexane, 1:4).1H NMR (400 MHz, CDCl3):
d 1.33 and 1.34 (2d, J = 6.8 Hz, 3H, CH3), 3.29–3.31 (m, 0.6H),
3.37–3.60 (m, 2.2H), 3.63–3.86 (m, 2H), 3.99 (t, J = 9.2 Hz, 0.6H),
4.07–4.40 (m, 4.8H), 4.50–4.58 (m, 1H), 4.67–4.77 (m, 2H), 4.82–
4.86 (m, 2H), 4.93–4.98 (m, 1.2H), 5.18 (m, 0.6H), 7.23–7.31 (m,
16H), 7.42–7.54 (m, 2H, 2 ¥ CH), 7.73 (d, J = 9.2 Hz, 1H). 13C
NMR (100 MHz, CDCl3): d 17.9, 33.3, 66.6, 66.7, 68.9, 71.7, 71.8,
72.9, 73.0, 73.4, 74.8, 75.2, 75.8, 77.3, 77.4, 80.0, 81.7, 83.0, 83.10,
84.6, 91.2, 97.5, 124.4, 127.6, 127.8, 127.9, 128.0, 128.1, 128.3,
128.4, 128.5, 128.56, 128.59, 128.63, 132.8, 132.9, 137.5, 137.8,
137.9, 138.0, 138.4, 138.5, 138.6, 150.3, 154.9, 155.0. ESI HRMS
(m/z): calcd for C37H39NNaO10: 680.2472, found: 680.2466.
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