Synthesis of novel photolabile glycosides from methyl 4,6-O-(o-nitro)benzylidene-α-d-glycopyranosides

Article abstract of DOI:10.1016/j.tet.2008.09.018

Novel photolabile sugar derivatives bearing a 4- or 6-O-(o-nitro)benzyl group have been prepared from the corresponding methyl 4,6-O-(o-nitro)benzylidene α-d-glycopyranosides. Regioselective cleavage with BF₃·Et₂O/Et₃SiH led to the methyl 6-O-(o-nitro)benzyl gluco- and manno-α-d-glycopyranosides 3 and 6. Inversion of configuration at 4-OH position of gluco and manno derivatives offered the otherwise inaccessible methyl 6-O-(o-nitro)benzyl galacto- and talo-α-d-glycopyranosides 4, 5, and 7. Careful reaction with PhBCl₂/Et₃SiH (3 equiv of reagents, 10 min at -78 °C) led to the desired methyl 4-O-(o-nitro)benzyl gluco- and manno-α-d-glycopyranosides 8 and 9 in very good yield. However, prolonged reaction with 6 equiv of PhBCl₂/Et₃SiH transformed the methyl 4,6-O-(o-nitro)benzylidene α-d-glucopyranoside 11 into the reduced d-glucitol derivative 15. Oxidative cleavage of 5,6-diol function of 15 gave the corresponding photolabile l-xylose 17. The photolabile glucosides 3 and 8 have been further transformed into the photolabile α-C-allyl d-glucopyranosides 20 and 22.

Full text of DOI:10.1016/j.tet.2008.09.018

Tetrahedron 64 (2008) 10687–10693
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of novel photolabile glycosides from methyl 4,6-O-
(o-nitro)benzylidene-
a- -glycopyranosides
D
,
,
*
Chen-Jiang Zhu a b, Hua Yi a, Guo-Rong Chen b, Juan Xie a
a PPSM, Institut d’Alembert, ENS Cachan, CNRS, UniverSud, 61 av President Wilson, F-94230 Cachan, France
b Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel photolabile sugar derivatives bearing a 4- or 6-O-(o-nitro)benzyl group have been prepared from
Received 3 August 2008
Accepted 3 September 2008
Available online 17 September 2008
the corresponding methyl 4,6-O-(o-nitro)benzylidene
with BF3$Et2O/Et3SiH led to the methyl 6-O-(o-nitro)benzyl gluco- and manno-
and 6. Inversion of configuration at 4-OH position of gluco and manno derivatives offered the otherwise
a
-
D
-glycopyranosides. Regioselective cleavage
a-D
-glycopyranosides 3
inaccessible methyl 6-O-(o-nitro)benzyl galacto- and talo-a-D-glycopyranosides 4, 5, and 7. Careful re-
Keywords:
action with PhBCl2/Et3SiH (3 equiv of reagents, 10 min at ꢀ78 ꢁC) led to the desired methyl 4-O-(o-ni-
Carbohydrates
Photolabile protecting groups
Regioselectivity
Epimerization
Ring opening
C-Glycosides
tro)benzyl gluco- and manno-a-D-glycopyranosides 8 and 9 in very good yield. However, prolonged
reaction with 6 equiv of PhBCl2/Et3SiH transformed the methyl 4,6-O-(o-nitro)benzylidene
a
-
D
-gluco-
-glucitol derivative 15. Oxidative cleavage of 5,6-diol function of 15 gave
-xylose 17. The photolabile glucosides 3 and 8 have been further trans-
-C-allyl -glucopyranosides 20 and 22.
Ó 2008 Elsevier Ltd. All rights reserved.
pyranoside 11 into the reduced
D
the corresponding photolabile
L
formed into the photolabile
a
D
1. Introduction
realized by photoirradiation at 350–365 nm where most common
functional groups do not absorb in this region of spectrum.5f,7 Very
recently, o-nitrobenzyl photolabile protecting groups with red-
shifted absorption have been reported.8 Concerning photolabile
sugars, o-nitrobenzylated glycosides have been prepared.5 Iwamura
and co-workers reported an efficient synthesis of 6-O-(o-nitro)-
Photolabile protecting groups have found wide applications in
synthetic chemistry and bioorganic chemistry.1 As protecting
groups, their deprotection requires only light irradiation, no re-
agent is needed. The use of photolabile protecting groups in oli-
gonucleotides and peptide chemistry has been well established.
They have been successfully used in the photolithographic syn-
thesis of DNA chips2 and peptide arrays3 for use in genomics and
proteomics. Various caged proteins and nucleic acids have also
been synthesized for in situ delivery of reactive compounds or for
analysis of biological functions with respect to time and location1c
Though the photolabile groups have been used as linker for the
solid-phase synthesis of oligo- and polysaccharides,4 only a few
photoremovable sugar derivatives have been reported.5 With the
emergence of glycomics research,6 photolabile protecting groups
could also be employed for the light-directed synthesis of defined
oligosaccharides, glycoconjugates or carbohydrate arrays for the
biological investigation. Synthesis of various photolabile sugar
building blocks is therefore necessary.
benzyl-D-gluco- and manno-pyranosides (compounds 1 and 2 in
Fig. 1) by regioselective opening of the corresponding benzylidene
derivatives and their photo-deprotection to the corresponding
glycosides.5f However, the galacto derivative was not available with
this methodology. Moreover, synthesis of 4-O-(o-nitro)benzyl gly-
cosides has never been reported. We report herein the synthesis of
4- or 6-O-(o-nitro)benzyl-
D-glycopyranosides orthogonally pro-
tected with benzyl or acetyl groups from the corresponding methyl
4,6-O-(o-nitro)benzylidene a-D-glycopyranosides (compounds 3–9
in Fig. 1).
2. Results and discussion
Synthesis of methyl 6-O-(o-nitro)benzyl-a-D-glycopyranosides
Amongst the photolabile groups, the o-nitrobenzyl group is the
most popular. Deprotection of o-nitrobenzyl group is usually
3–7 was attempted from (o-nitro)benzylidene derivatives as shown
in Schemes 1 and 2. Methyl 4,6-O-(o-nitro)benzylidene-a-D-glu-
copyranoside 109 was firstly protected as benzyl ether 11. Reductive
opening of o-nitrobenzylidene acetal with BF3$Et2O (6 equiv)/
Et3SiH (12 equiv)5f led to the 6-O-(o-nitro)benzyl-
D
-glucoside 3 in
* Corresponding author. Tel.: þ33 1 47405586; fax: þ33 1 47402454.
E-mail address: joanne.xie@ppsm.ens-cachan.fr (J. Xie).
52% yield (Scheme 1). The galacto derivative 4 was obtained by
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.09.018

10688
C.-J. Zhu et al. / Tetrahedron 64 (2008) 10687–10693
NO2
NO2
NO2
NO2
O
OH
OBn
O
O
BnBr, NaH, DMF
r.t. 78 %
O
O
O
OR
O
O
HO
RO
O
O
HO
2 R = Ac
6 R = Bn
HO
BnO
1 R = Ac
3 R = Bn
RO
OR
12
OMe
13
OMe
NO2
OMe
OMe
BF3 Et2O, Et3SiH
O2N
78 %
CH2Cl2, r.t
O
OH
RO
O2N
O
OH
NO2
O
OBn
4 R = Bn
5 R = Ac
O
1. Tf2O, pyr.
OR
OMe
7
CH2Cl2, -15 °C
BnO
NO2
OH
O
OBn
O
OBn
O
O
2. NaNO2, DMF, r.t.
57 %
OMe
HO
NO2
BnO
BnO
OH
OMe
6
7
OMe
O
OBn
O
HO
O
BnO
8
O
9
Scheme 2. Synthesis of manno and talo derivatives 6 and 7.
BnO
BnO
OMe
OMe
unprotected 6-OH; while NaBH3CN/HCl, NaBH3CN/TFA or
BH3$NMe3/AlCl3/THF12 produce a free 4-OH group. Treatment of
the benzylidene 11 with NaBH3CN/TMSCl or BH3$NMe3/AlCl3/THF
did not induce any transformation. However, reaction with LiAlH4/
AlCl3 led to the free diol 1414 in 72% yield (Scheme 3). Similar result
has been obtained with DIBAL-H. This result may be explained by
previous reduction of o-nitro group to amine by LiAlH4/AlCl3 or
DIBAL-H, which might participate in the removal of the benzyli-
dene acetal. To check this hypothesis, we then decided to reduce
the o-nitrobenzylidene function with stannous chloride.15 Once
again, only the free diol 14 can be isolated.
Figure 1. Structure of methyl 4- or 6-O-(o-nitro)benzyl-
a-D-glycopyranosides.
inverting the configuration at C-4 position of the gluco-compound
3, by activation of alcohol function with Tf2O followed by treatment
with NaNO2.10 Similarly, the acetyl protected glucoside 1 has been
transformed into the galactoside 5 in 97% yield. The 6-O-(o-nitro)-
benzyl-
methyl 4,6-O-(o-nitro)benzylidene-
Protection as benzyl ether followed by regioselective ring opening
provided the 6-O-(o-nitro)benzyl- -mannopyranoside 6. Inversion
D
-manno- and talo-pyranosides 6 and 7 were prepared from
a-D
-mannopyranoside 12.9
D
of the configuration at C-4 gave the talopyranoside 7 in 57% yield
(Scheme 2).
LiAlH4, AlCl3, CH2Cl2
OH
Reductive ring opening of benzylidene acetals can be realized
with different reagents including LiAlH4/AlCl3, NaBH3CN/HCl,
NaBH3CN/TMSCl, NaBH3CN/TFA, BH3$NMe3/AlCl3, DIBAL-H or
PhBCl2/Et3SiH to give the monobenzyl ether of the corresponding
diols.11 In general, LiAlH4/AlCl3, DIBAL-H, NaBH3CN/TMSCl,
BH3$NMe3/AlCl3/PhMe12 or PhBCl2/Et3SiH13 give products with
Et2O, reflux, 72 %
O
HO
11
BnO
or DIBALH, CH2Cl2, r.t.
or SnCl2, 2H2O, AcOEt, 60 °C
BnO
14
OMe
Scheme 3. Reactivity of 11 with LAH, DIBALH or SnCl2.
We then decided to study the reactivity of the 4,6-O-(o-nitro)-
benzylidene acetal 11 with PhBCl2/Et3SiH.13 Treatment of 11 with
PhBCl2 and Et3SiH (6 equiv each) at ꢀ78 to ꢀ40 ꢁC for 2 h opened
regioselectively the benzylidene ring. However, the anomeric proton
and carbon disappeared on 1H and 13C NMR spectra, with the ap-
pearance of a new CH2 group. This new compound has been identi-
fied as the D-glucitol 15, resulting from the reductive opening of both
benzylidene and pyranoside rings (Fig. 2). The structure of 15 has
been further confirmed by its acetylated product 16 (Scheme 4).
NO2
NO2
O
O
BnBr, NaH, DMF
r.t. 72 %
O
O
O
O
HO
BnO
OH
BnO
11
10
OMe
OMe
BF3 Et2O, Et3SiH
CH2Cl2, r.t
Oxidative cleavage of 15 with NaIO4 led to the corresponding L-xylose
52 %
derivative 17. After careful examination of the reaction conditions, we
found that the opening of the benzylidene ring is faster than that of
the pyranoside. The desired 4-O-(o-nitro)benzyl protected gluco-
pyranoside 8 can be obtained using 3 equiv of reagents for 10 min at
ꢀ78 ꢁC in excellent yield. The manno derivative 9 can be prepared
under similar conditions in good yield (Scheme 4).
NO2
NO2
OH
O
O
O
1. Tf2O, pyr.
CH2Cl2, -15 °C
O
HO
BnO
2. NaNO2, DMF, r.t.
53 %
BnO
BnO
BnO
OMe
OMe
4
3
H
Et3Si
NO2
NO2
NO2
PhBCl2
OH
OH
PhBCl2
O
O
1. Tf2O, pyr.
O
O
OH
O
CH2Cl2, -15 °C
Ref. 5f
O
H
SiEt3
BnO
O
O
10
HO
AcO
BnO
NO2
2. NaNO2, DMF, r.t.
97 %
OMe
BnO
AcO
OMe
BnO
OMe
AcO
1
AcO
5
15
OMe
11
Scheme 1. Synthesis of gluco and galacto derivatives 3, 4, and 5.
Figure 2. Proposed mechanism for the formation of 15.

C.-J. Zhu et al. / Tetrahedron 64 (2008) 10687–10693
10689
to 4-O-(o-nitro)benzyl-
the reduced
In the latter case, photolabile
oxidative cleavage of 5,6-diol function of 15. Furthermore, 4- or
6-O-(o-nitro)benzyl- -glucosides have been successfully used as
glycosyl donor for the stereoselective synthesis of -C-allyl glu-
cosides 20 and 22. These novel photolabile sugars might find
applications in the synthesis of diverse sugar derivatives and
glycoconjugates.
D
-gluco- and manno-pyranosides 8, 9 or to
NO2
O
D
-glucitol 15, depending on the reaction conditions.
-xylose 17 can be prepared by
PhBCl2(6 eq.),
Et3SiH ((6 eq.)
L
OBn
Ac2O, Py
86 %
15
11
OMe
16
CH2Cl2, -78 to -40 °C
2 h, 80 %
AcO
D
OAc OBn
a
NaIO4, THF/H2O, 88 %
NO2
O
OBn
OMe
O
17
3. Experimental section
3.1. General
OBn
NO2
NO2
Solvents were purified by standard procedures. 1H and 13C NMR
spectra were recorded on Bruker AC-300 or Jeol 400 spectrometers
in CDCl3 solutions. Optical rotations were measured using a Perkin–
Elmer 241 polarimeter at rt with a 10-cm 1-mL cell. Column
chromatography was performed on E. Merck Silica Gel 60 (230–400
mesh). Analytical thin-layer chromatography was performed on
E. Merck aluminum percolated plates of Silica Gel 60F254 with de-
tection by UV and by spraying with 6 N H2SO4 and heating about
2 min at 300 ꢁC. High resolution mass spectra (HRMS) were
recorded on a MA1212 instrument using standard conditions (ESI,
70 eV). The UV light was supplied by a 200 W Hg–Xe high pressure
lamp (Hamamatsu LC6). The light was 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 200 mW/cm2 at
the optimal distance (about 1.0 cm away from its end).
R1
HO
R1
PhBCl2(3 eq.),
Et3SiH (3 eq.)
O
O
O
O
O
BnO
BnO
CH2Cl2, -78 °C
10 min
R2
R2
OMe
OMe
8 R1 = H, R2 = OBn 96 %
9 R1 = OBn, R2 = H 89 %
11 R1 = H, R2 = OBn
13 R1 = OBn, R2 = H
Scheme 4. Action of PhBCl2/Et3SiH on 4,6-O-(o-nitro)benzylidene acetals 11 and 13.
Photo-deprotection of 6-O-(o-nitro)benzyl-
already been realized by Iwamura and co-workers.5f Photolysis of
4-O-(o-nitro)benzyl- -gluco- and manno-pyranosides 8 and 9
was studied in a CH3CN soln. Both compounds can be fully depro-
tected to the free diols 14 and 1816 after 1 h irradiation at 365 nm in
91% yield (Scheme 5). These photolabile sugar derivatives should be
useful as building blocks. As shown in Scheme 6, we have suc-
a-D-glycosides have
a-D
ceeded in the synthesis of the first photolabile a-C-allyl glucosides
3.2. Synthesis of methyl 2,3-di-O-benzyl-4,6-O-(o-
20 and 22 from the methyl glucosides 3 and 8 under usual condi-
tions14,17 after acetylation of the 4- or 6-OH group.
nitro)benzylidene-
a-D-glucopyranoside 11
To a soln of 4,6-O-(o-nitro)benzylidene-
a-D-glucopyranoside
NO2
(10) (2.48 g, 7.6 mmol) in DMF (10 mL) was added NaH (60%,
790 mg, 19.76 mmol) at 0 ꢁC. After stirring at 0 ꢁC for 45 min, BnBr
(2.17 mL, 19.76 mmol) was added to the reaction mixture. After
16 h, the reaction was quenched with MeOH (10 mL) and evapo-
rated. The residue was dissolved in CH2Cl2, extracted with CH2Cl2
(3ꢂ20 mL) and the combined organic layer was washed with H2O,
dried over MgSO4, and filtered. Evaporation of the solvent and
purification by column chromatography (1:3 EtOAc–cyclohexane)
afforded 11 as a yellow oil (2.76 g, 72%). TLC: Rf¼0.67 (EtOAc–cy-
R1
O
R1
O
HO
HO
BnO
HO
hv 365 nm
CH3CN, rt, 1h
91 %
O
BnO
R2
R2
OMe
OMe
8 R1 = H, R2 = OBn
9 R1 = OBn, R2 = H
14 R1 = H, R2 = OBn
18 R1 = OBn, R2 = H
Scheme 5. Photolysis of compounds 8 and 9.
ꢀ31.2 (c 0.98, CH2Cl2); 1H NMR (300 MHz,
In conclusion, photolabile 6-O-(o-nitro)benzyl-D-gluco-, gal-
clohexane, 1:2); [
CDCl3):
a
]
D
acto-, manno-, and talo-pyranosides 3–7 have been successfully
prepared from the corresponding gluco- and manno-4,6-O-
(o-nitro)benzylidene derivatives. The key steps are regioselective
ring opening of benzylidene acetals by BF3$Et2O/Et3SiH to 6-O-
(o-nitro)benzyl derivatives followed by inversion of the config-
uration at 4-OH position to 6-O-(o-nitro)benzyl-
talo- derivatives. Both acetyl and benzyl protected
talo- derivatives can be prepared in this way. Reductive opening
of 4,6-O-(o-nitro)benzylidene acetals by PhBCl2/Et3SiH led either
d
3.39 (s, 3H, OMe), 3.54 (dd, 1H, J¼3.7, 9.5 Hz, H-2), 3.63 (t,
1H, J¼9.2 Hz, H-4), 3.69–3.79 (m, 2H, H-6a, H-6b), 3.99 (t, 1H,
J¼9.2 Hz, H-3), 4.22 (m,1H, H-5), 4.57 (d,1H, J¼3.7 Hz, H-1), 4.66 (d,
1H, 2J¼12 Hz, CHPh), 4.74 (d, 1H, 2J¼11.4 Hz, CHPh), 4.84 (d, 2H,
2J¼12 Hz, 2ꢂCHPh), 6.17 (s, 1H, H-7), 7.27–7.42 (m, 10H, 2ꢂPh), 7.45
(t,1H, J¼8.1 Hz, o-NO2–PhH), 7.65 (t,1H, J¼8.1 Hz, o-NO2–PhH), 7.75
(d, 1H, J¼8.1 Hz, o-NO2–PhH), 8.07 (d, 1H, J¼8.1 Hz, o-NO2–PhH);
D
-galacto- and
-galacto- and
D
13C NMR (75 MHz, CDCl3):
d 55.3, 62.0, 69.2, 73.8, 75.1, 78.3, 79.1,
82.3, 97.1, 99.2, 124.2, 127.4, 127.5, 127.8, 128.0, 128.1, 128.2, 128.4,
O(o-NO2)Bn
O(o-NO2)Bn
O
TMSAllyl, TMSOTf
Ac2O, Pyr.
r. t. 79 %
O
AcO
BnO
AcO
BnO
3
CH3CN, r.t. 65 %
BnO
BnO
OMe
OAc
20
19
OAc
O
O
(o-NO2)BnO
TMSAllyl, TMSOTf
CH3CN, r.t. 58 %
(o-NO2)BnO
BnO
Ac2O, Pyr.
r. t. 88 %
BnO
8
BnO
BnO
OMe
21
22
Scheme 6. Synthesis of photolabile
a-C-glycosides 20 and 22.

10690
C.-J. Zhu et al. / Tetrahedron 64 (2008) 10687–10693
129.6, 131.2, 132.7, 138.0, 138.6, 148.3. HRESIMS: calcd for
C28H29NO8Na: 530.1791; found: m/z 530.1798.
CH2Ph), 5.01 (d, 1H, J¼2.6 Hz, H-1), 5.29 (m, 2H, H-2, H-3), 7.45 (t,
1H, J¼8.0 Hz, o-NO2–PhH), 7.65 (t, 1H, J¼8.0 Hz, o-NO2–PhH), 7.75
(d, 1H, J¼8.0 Hz, o-NO2–PhH), 8.07 (d, 1H, J¼8.0 Hz, o-NO2–PhH);
3.3. Synthesis of methyl 2,3-di-O-benzyl-6-O-(o-nitro)benzyl-
13C NMR (75 MHz, CDCl3):
d 20.7, 20.8, 55.3, 68.0, 68.2, 68.6, 70.1,
a
-D-glucopyranoside 3
70.2, 70.5, 97.3, 124.7, 128.1, 128.5, 133.6, 134.3, 147.6, 169.9, 170.3.
HRESIMS: calcd for C18H23NO10Na: 436.1220; found: m/z 436.1225.
To a soln of compound 11 (1.42 g, 2.8 mmol) in CH2Cl2 (20 mL)
was added triethylsilane (5.32 mL, 33.6 mmol) and boron tri-
fluoride etherate (2.02 mL, 16.8 mmol) at 0 ꢁC under argon atmo-
sphere. After the reaction mixture was stirred 16 h at rt, the
reaction mixture was diluted with CH2Cl2 (20 mL). The solution was
successively washed with aqueous NaHCO3, H2O, dried over an-
hydrous MgSO4, filtered, evaporated under reduced pressure, and
the residue was purified by column chromatography (1:1 EtOAc–
cyclohexane) to afford 3 as a yellow oil (850 mg, 52%). TLC: Rf¼0.51
3.6. Synthesis of methyl 2,3-di-O-benzyl-4,6-O-(o-
nitro)benzylidene-a-D-mannopyranoside 13
The methyl 4,6-O-(o-nitro)benzylidene-
a-D-mannopyranoside
(12) (190 mg, 0.58 mmol) was benzylated as for the compound 10
to afford 13 as a yellow oil after purification by column chroma-
tography (1:3 EtOAc–cyclohexane) (229 mg, 78%). TLC: Rf¼0.84
(EtOAc–cyclohexane, 2:3); [
(300 MHz, CDCl3):
a
]
ꢀ10.3 (c 0.52, CH2Cl2); 1H NMR
D
(EtOAc–cyclohexane, 1:2); [
(300 MHz, CDCl3):
a
]
D
þ5.8 (c 0.28, CH2Cl2); 1H NMR
d
3.31 (s, 3H, OMe), 3.73 (td, 1H, J¼9.9, 4.2 Hz, H-
d
2.29 (d, 1H, J¼2.2 Hz, 4-OH), 3.40 (s, 3H, OMe),
5), 3.83 (dd, 1H, J¼1.2, 3 Hz, H-2), 3.87–3.93 (m, 2H, H-6a, H-6b),
4.20 (dd, 1H, J¼3.6, 10.2 Hz, H-3), 4.28 (t, 1H, J¼9.9 Hz, H-4), 4.59 (d,
1H, 2J¼12 Hz, CHPh), 4.68 (d, 1H, J¼1.2 Hz, H-1), 4.72 (d, 1H,
2J¼9.3 Hz, CHPh), 4.76 (d, 1H, 2J¼9.3 Hz, CHPh), 4.83 (d, 1H,
2J¼12.3 Hz, CHPh), 6.25 (s, 1H, H-7), 7.28–7.36 (m, 10H, 2ꢂPh), 7.50
(t,1H, J¼7.4 Hz, o-NO2–PhH), 7.62 (t,1H, J¼7.4 Hz, o-NO2–PhH), 7.87
3.54 (dd,1H, J¼3.7, 9.5 Hz, H-2), 3.62 (m,1H, H-5), 3.74–3.83 (m, 4H,
H-3, H-4, H-6a, H-6b), 4.65 (d, 1H, J¼3.7 Hz, H-1), 4.67 (d, 1H,
2J¼12.5 Hz, CHPh), 4.73 (d, 1H, 2J¼11.4 Hz, CHPh), 4.78 (d, 1H,
2J¼12.1 Hz, CHPh), 4.94 (m, 2H, 2ꢂCHPh), 5.04 (d, 1H, 2J¼11.4 Hz,
CHPh), 7.27–7.42 (m, 10H, 2ꢂPh), 7.45 (t, 1H, J¼7.4 Hz, o-NO2–PhH),
7.65 (t, 1H, J¼7.4 Hz, o-NO2–PhH), 7.75 (d, 1H, J¼7.4 Hz, o-NO2–
PhH), 8.07 (d, 1H, J¼7.4 Hz, o-NO2–PhH); 13C NMR (75 MHz, CDCl3):
(m, 2H, 2ꢂo-NO2–PhH); 13C NMR (75 MHz, CDCl3):
d 54.8, 63.8,
69.0, 72.8, 73.6, 76.1, 76.2, 79.4, 97.3, 100.5, 124.2, 127.4–128.3,
129.5, 131.5, 132.5, 138.0, 138.6, 148.4. HRESIMS: calcd for
C28H29NO8Na: 530.1791; found: m/z 530.1794.
d
55.2, 70.01, 70.04, 70.07, 70.14, 73.0, 75.4, 79.6, 81.3, 98.1, 124.5,
127.8–128.0, 128.4, 128.5, 128.6, 133.5, 134.9, 137.9, 138.6. HRESIMS:
calcd for C28H31NO8Na: 532.1947; found: m/z 532.1963.
3.7. Synthesis of methyl 2,3-di-O-benzyl-6-O-(o-nitro)benzyl-
3.4. Synthesis of methyl 2,3-di-O-benzyl-6-O-(o-nitro)benzyl-
a-
D-mannopyranoside 6
a
-D-galactopyranoside 4
Compound 13 (600 mg, 1.18 mmol) was treated with Et3SiH and
BF3$Et2O as for the compound 11 to afford 6 as a yellow oil after
To a soln of Tf2O (27.4
mL, 0.16 mmol) and pyridine (25.4 mL) in
CH2Cl2 (1 mL) was added a soln of compound 3 (52 mg, 0.1 mmol)
in CH2Cl2 (1 mL) at ꢀ15 ꢁC under argon. After 2 h at ꢀ15 ꢁC, the
reaction mixture was diluted with CH2Cl2 (2 mL) and extracted
with CH2Cl2 (3ꢂ2 mL). The combined organic layer was washed
successively with 5% HCl, saturated NaHCO3, and H2O, then dried
over MgSO4, filtered, and evaporated. The residue was dissolved in
DMF (2 mL) and then NaNO2 (73 mg, 1.05 mmol) was added. After
20 h stirring at rt, the reaction mixture was diluted with CH2Cl2
(5 mL), extracted with CH2Cl2 (3ꢂ5 mL), the combined organic
layer was washed with H2O, dried over MgSO4, filtered, and evap-
orated. The residue was purified by column chromatography (1:4
EtOAc–cyclohexane) to afford 4 as a yellow oil (27.4 mg, 53%). TLC:
purification by column chromatography (1:4 EtOAc–cyclohexane)
(468 mg, 78%). TLC: Rf¼0.63 (EtOAc–cyclohexane, 2:3); [
a
]
ꢀ10.7
D
(c 0.30, CH2Cl2); 1H NMR (300 MHz, CDCl3):
d
3.37 (s, 3H, OMe),
3.69–3.79 (m, 2H, H-3, H-5), 3.81 (dd, 1H, J¼1.8, 3 Hz, H-2), 3.91 (m,
2H, H-6a, H-6b), 4.11 (t, 1H, J¼9.6 Hz, H-4), 4.46 (d, 1H, 2J¼11.8 Hz,
CHPh), 4.59 (d, 1H, 2J¼11.7 Hz, CHPh), 4.64 (d, 1H, 2J¼12.3 Hz,
CHPh), 4.70 (d, 1H, 2J¼12.3 Hz, CHPh), 4.82 (d, 1H, J¼1.8 Hz, H-1),
5.00 (2d, 2H, PhCH2), 7.26–7.37 (m, 10H, 2ꢂPh), 7.40 (t, 1H, J¼8.1 Hz,
o-NO2–PhH), 7.58 (t, 1H, J¼8.1 Hz, o-NO2–PhH), 7.86 (d, 1H,
J¼8.1 Hz, o-NO2–PhH), 8.06 (d, 1H, J¼8.1 Hz, o-NO2–PhH); 13C NMR
(75 MHz, CDCl3):
d 54.8, 66.8, 69.9, 71.56, 71.63, 72.5, 73.6, 79.6,
Rf¼0.47 (EtOAc–cyclohexane, 1:2); [
a
]
þ39.6 (c 0.60, CH2Cl2); 1H
99.0,124.4,127.6–127.8,128.3,128.5,128.6,133.6,135.3,137.9,138.0.
HRESIMS: calcd for C28H31NO8Na: 532.1947; found: m/z 532.1951.
D
NMR (300 MHz, CDCl3):
d
2.53 (s, 1H, 4-OH), 3.40 (s, 3H, OMe),
3.73–4.06 (m, 6H, H-2, H-3, H-4, H-5, H-6a, H-6b), 4.66 (d, 1H,
J¼3.3 Hz, H-1), 4.67 (d, 1H, 2J¼12 Hz, CHPh), 4.72 (d, 1H, 2J¼11.7 Hz,
CHPh), 4.82 (d, 2H, 2J¼12.3 Hz, 2ꢂCHPh), 4.95 (s, 2H, CH2Ph), 7.30–
7.43 (m, 10H, 2ꢂPh), 7.45 (t, 1H, J¼7.4 Hz, o-NO2–PhH), 7.65 (t, 1H,
J¼7.4 Hz, o-NO2–PhH), 7.75 (d, 1H, J¼7.4 Hz, o-NO2–PhH), 8.07 (d,
3.8. Synthesis of methyl 2,3-di-O-benzyl-6-O-(o-nitro)benzyl-
a-
D-talopyranoside 7
Compound 6 (75 mg, 0.15 mmol) was treated with Tf2O and
NaNO2 as for the compound 3 to afford 7 as a yellow oil after pu-
rification by column chromatography (1:2 EtOAc–cyclohexane)
1H, J¼7.4 Hz, o-NO2–PhH); 13C NMR (75 MHz, CDCl3):
d
55.3, 67.9,
68.2, 69.9, 70.3, 72.8, 73.5, 75.6, 77.1, 98.5, 124.6, 127.7–127.9, 128.3,
128.4, 128.6, 133.5, 134.8, 138.0, 138.2. HRESIMS: calcd for
C28H31NO8Na: 532.1947; found: m/z 532.1943.
(43 mg, 57.3%). TLC: Rf¼0.65 (EtOAc–cyclohexane, 2:3); [
a
]
þ37.8
D
(c 2.22, CH2Cl2); 1H NMR (300 MHz, CDCl3):
d
3.36 (s, 3H, OMe),
3.77 (m, 1H), 3.88 (m, 2H, H-6a, H-6b), 3.98–4.02 (m, 2H), 4.54 (d,
1H, 2J¼11.7 Hz, CHPh), 4.56 (d, 1H, 2J¼12.1 Hz, CHPh), 4.68 (d, 1H,
2J¼11.7 Hz, CHPh), 4.69 (d, 1H, 2J¼12.1 Hz, CHPh), 4.74 (d, 1H,
J¼1.8 Hz, H-1), 4.94 (d, 1H, 2J¼12.3 Hz, CHPh), 5.04 (d, 1H,
2J¼12.3 Hz, CHPh), 5.45 (t, 1H, J¼9.9 Hz), 7.30–7.39 (m, 10H, 2ꢂPh),
7.42 (t, 1H, J¼8.1 Hz, o-NO2–PhH), 7.55 (t,1H, J¼8.1 Hz, o-NO2–PhH),
7.86 (d, 1H, J¼8.1 Hz, o-NO2–PhH), 8.07 (d, 1H, J¼8.1 Hz, o-NO2–
3.5. Synthesis of methyl 2,3-di-O-acetyl-6-O-(o-nitro)benzyl-
a
-D-galactopyranoside 5
Compound 1 (53 mg, 0.13 mmol) was treated with Tf2O and
NaNO2 as for the compound 3 to afford 5 as a yellow oil after pu-
rification by column chromatography (1:3 EtOAc–cyclohexane)
(51.4 mg, 97%). TLC: Rf¼0.34 (EtOAc–cyclohexane, 1:2); [
a
]
D þ129.4
PhH); 13C NMR (75 MHz, CDCl3):
d 55.3, 68.8, 69.4, 69.8, 72.2, 72.9,
(c 0.26, CH2Cl2); 1H NMR (300 MHz, CDCl3):
d
2.09 (s, 3H, OAc), 2.11
74.4, 77.1, 81.3, 98.9, 124.4, 127.6–128.4, 133.8, 134.9, 137.1, 137.7,
146.5. HRESIMS: calcd for C28H31NO8Na: 532.1947; found: m/z
532.1962.
(s, 3H, OAc), 2.61 (s, 1H, 4-OH), 3.42 (s, 3H, OMe), 3.85 (m, 2H, H-6a,
H-6b), 4.08 (t, 1H, J¼4.7 Hz, H-5), 4.25 (m, 1H, H-4), 4.97 (s, 2H,

C.-J. Zhu et al. / Tetrahedron 64 (2008) 10687–10693
10691
3.9. Synthesis of methyl 2,3-di-O-benzyl-4-O-(o-nitro)benzyl-
-glucopyranoside 8
water (25 mL), brine (2ꢂ25 mL), dried over MgSO4, filtered, and
then concentrated in vacuum. The crude product was purified by
flash column chromatography (2:8 EtOAc–cyclohexane) to give 15
as a yellow oil (430 mg, 80%). TLC: Rf¼0.61 (EtOAc–cyclohexane,
a-D
Molecular sieves 4 Å (1.0 g) were placed in a 10-mL flask and
dried at 140 ꢁC for 4 h under vacuum (ca. 0.1 mmHg). After cooling
to rt, a soln of compound 11 (105 mg, 0.207 mmol) in CH2Cl2 (2 mL)
was added to the flask under argon atmosphere. After stirring for
1 h at rt, the mixture was cooled to ꢀ78 ꢁC, and then Et3SiH
(0.100 mL, 0.62 mmol) and a soln of dichlorophenylborane in
CH2Cl2 (1.2 mL, 0.62 mmol) were added successively. After 10 min
at ꢀ78 ꢁC, TLC indicated a complete conversion of the starting
material. Et3N (0.5 mL) and MeOH (0.5 mL) were added succes-
sively, and the mixture was diluted with CHCl3 (20 mL), washed
with aqueous saturated NaHCO3 (2ꢂ10 mL), water (10 mL), brine
(2ꢂ10 mL), dried over MgSO4, filtered, and then concentrated in
vacuo. The crude product was purified by flash column chroma-
tography (3:7 EtOAc–cyclohexane) to give 8 as a yellow solid
3:7); [
a]
þ32.4 (c 0.63, CHCl3); 1H NMR (400 MHz, CDCl3):
d 3.36
D
(s, 3H, OMe), 3.61 (dd, 1H, J¼5.5, 10.5 Hz, H-1a), 3.70–3.73 (m, 2H,
H-1b, H-3), 3.80–3.83 (m, 1H, H-2), 4.14 (dd, 1H, J¼2.3, 6.4 Hz, H-
4), 4.23 (t, 1H, J¼8.7 Hz, H-6a), 4.45 (dd, 1H, J¼7.3, 8.7 Hz, H-6b),
4.57 (d, 1H, 2J¼11.9 Hz, CHPh), 4.60 (d, 1H, 2J¼11.5 Hz, CHPh), 4.71
(d, 1H, 2J¼11.5 Hz, CHPh), 4.76 (d, 1H, 2J¼11.9 Hz, CHPh), 4.78–
4.81 (m, 1H, H-5), 5.08 (d, 1H, 2J¼15.2 Hz, CHPh), 5.21 (d, 1H,
2J¼15.2 Hz, CHPh), 7.27–7.43 (m, 10H, 2ꢂPh), 7.67 (m, 2H, 2ꢂo-
NO2–PhH), 7.73 (d, 1H, J¼7.8 Hz, o-NO2–PhH), 7.90 (d, 1H,
J¼7.8 Hz, o-NO2–PhH); 13C NMR (100 MHz, CDCl3):
d 59.3, 67.2,
71.7, 72.3, 73.0, 74.6, 77.9, 78.3, 79.6, 81.9, 124.5, 127.6, 127.8,
127.9, 128.1, 128.2, 128.5, 128.6, 128.7, 131.4, 133.6, 134.7, 135.5,
138.0, 138.2, 146.6. HRESIMS: calcd for C28H33NO8Na: 534.2104;
found: m/z 534.2098.
(101 mg, 96%). TLC: Rf¼0.18 (EtOAc–cyclohexane, 3:7); [
a
]
D þ22.3 (c
2.22, CHCl3); 1H NMR (400 MHz, CDCl3):
d
1.93 (s, 1H, OH), 3.38 (s,
3H, OMe), 3.51 (dd, 1H, J¼3.7, 8.7 Hz, H-2), 3.60 (t, 1H, J¼8.7 Hz, H-
4), 3.69–3.72 (m, 2H, H-5,6a), 3.76–3.79 (m, 1H, H-6b), 4.00 (t, 1H,
J¼8.7 Hz, H-3), 4.58 (d, 1H, J¼3.7 Hz, H-1), 4.64–4.66 (m, 2H,
CH2Ph), 4.76 (d, 1H, 2J¼11.0 Hz, CHPh), 4.94 (d, 1H, 2J¼11.0 Hz,
CHPh), 4.98 (d, 1H, 2J¼14.6 Hz, CHPh), 5.23 (d, 1H, 2J¼14.6 Hz,
CHPh), 7.19–7.34 (m, 10H, 2ꢂPh), 7.39 (t, 1H, J¼8.2 Hz, o-NO2–PhH),
7.56 (t, 1H, J¼7.6 Hz, o-NO2–PhH), 7.69 (d, 1H, J¼7.6 Hz, o-NO2–
PhH), 8.01 (d, 1H, J¼8.2 Hz, o-NO2–PhH); 13C NMR (100 MHz,
3.12. Synthesis of 5,6-di-O-acetyl-2,3-di-O-benzyl-1-O-
methyl-4-O-(o-nitro)benzyl-D-glucitol 16
To a soln of compound 15 (29 mg, 0.057 mmol) in pyridine
(2 mL) was added Ac2O (0.8 mL) at rt. After 16 h, the reaction
mixture was evaporated and residue was dissolved in CH2Cl2,
washed with H2O, dried over MgSO4, and filtered. Evaporation of
the solvent gave a crude product, which was purified by column
chromatography (2:8 EtOAc–cyclohexane) to afford 16 (25 mg, 86%)
as a yellow oil. TLC: Rf¼0.3 (EtOAc–cyclohexane, 2:8); 1H NMR
CDCl3):
d 55.4, 61.9, 70.7, 71.3, 73.5, 75.7, 77.9, 80.1, 81.9, 98.3, 124.7,
127.6, 127.8, 127.9, 128.0, 128.1, 128.2, 128.4, 128.6, 133.7, 135.2, 138.1,
138.5, 146.9. HRESIMS: calcd for C28H31NO8Na: 532.1947; found: m/z
532.1942.
(400 MHz, CDCl3):
d 1.97 (s, 3H, OAc), 2.02 (s, 3H, OAc), 3.28 (s, 3H,
OMe), 3.56 (dd,1H, J¼6.0,10.1 Hz, H-1a), 3.62 (dd,1H, J¼4.1,10.1 Hz,
1H, H-1b), 3.73 (dd, 1H, J¼4.6, 6.4 Hz, 1H, H-3), 3.81–3.83 (m, 1H, H-
2), 3.95 (dd, 1H, J¼6.4, 3.7 Hz, 1H, H-4), 4.18 (dd, 1H, J¼7.3, 11.9 Hz,
H-6a), 4.49 (dd, 1H, J¼2.7, 11.9 Hz, H-6b), 4.56 (d, 1H, 2J¼11.4 Hz,
CHPh), 4.57 (d,1H, 2J¼11.9 Hz, CHPh), 4.63 (d,1H, 2J¼11.4 Hz, CHPh),
4.71 (d, 1H, 2J¼11.9 Hz, CHPh), 5.06 (d, 1H, 2J¼15.6 Hz, CHPh), 5.11
(d,1H, 2J¼15.6 Hz, CHPh), 5.35–5.37 (m,1H, H-5), 7.20–7.31 (m, 10H,
2ꢂPh), 7.41 (t, 1H, J¼7.6 Hz, o-NO2–PhH), 7.59 (t, 1H, J¼7.6 Hz,
o-NO2–PhH), 7.78 (d, 1H, J¼7.6 Hz, o-NO2–PhH), 8.05 (d, 1H,
3.10. Synthesis of methyl 2,3-di-O-benzyl-4-O-(o-
nitro)benzyl-a-D-mannopyranoside 9
Compound 13 (109 mg, 0.215 mmol) was treated with Et3SiH
and PhBCl2 as for the compound 11 to afford 9 as a yellow oil after
purification by column chromatography (3:7 EtOAc–cyclohexane)
(97 mg, 89%). TLC: Rf¼0.17 (EtOAc–cyclohexane, 3:7); [
a
]
D þ32.4 (c
0.63, CHCl3); 1H NMR (400 MHz, CDCl3):
d
2.08 (s, 1H, OH), 3.32 (s,
J¼8.2 Hz, o-NO2–PhH); 13C NMR (100 MHz, CDCl3):
d 20.9, 21.2,
3H, OMe), 3.63–3.68 (m, 1H), 3.75–3.79 (m, 2H), 3.82 (dd, 1H, J¼2.3,
11.9 Hz), 3.88 (dd, 1H, J¼2.8, 9.2 Hz), 4.02 (t, 1H, J¼9.6 Hz, H-4), 4.45
(d, 1H, 2J¼11.9 Hz, CHPh), 4.55 (d, 1H, 2J¼11.9 Hz, CHPh), 4.67 (d, 1H,
2J¼12.4 Hz, CHPh), 4.72 (d, 1H, J¼1.8 Hz, H-1), 4.75 (d, 1H,
2J¼12.4 Hz, CHPh), 5.04 (d, 1H, 2J¼14.6 Hz, CHPh), 5.31 (d, 1H,
2J¼14.6 Hz, CHPh), 7.21–7.33 (m, 10H, 2ꢂPh), 7.39 (t, 1H, J¼8.2 Hz,
o-NO2–PhH), 7.56 (t, 1H, J¼7.8 Hz, o-NO2–PhH), 7.71 (d, 1H,
J¼7.8 Hz, o-NO2–PhH), 8.01 (d, 1H, J¼8.2 Hz, o-NO2–PhH); 13C NMR
59.2, 62.9, 71.3, 72.3, 72.5, 73.3, 74.8, 78.1, 79.2, 80.3, 124.7, 127.8,
127.9, 128.0, 128.1, 128.2, 128.5, 128.8, 133.8, 135.3, 138.1, 138.4,
146.9, 170.3, 170.9. HRESIMS: calcd for C32H37NO10Na: 618.2315;
found: m/z 618.2310.
3.13. Synthesis of 3,4-di-O-benzyl-2-O-(o-nitro)benzyl-L-
xylose 17
(100 MHz, CDCl3):
d
55.0, 62.5, 71.3, 71.8, 72.1, 73.0, 74.3, 75.3, 80.1,
To a soln of 15 (52 mg, 0.102 mmol) in THF (2 mL) and H2O
(1.0 mL) was added NaIO4 (45 mg, 0.208 mmol) at rt. After 2 h,
the reaction mixture was evaporated and residue was diluted
with EtOAc (10 mL), washed with water (2ꢂ5 mL), brine
(2ꢂ5 mL), dried over MgSO4, filtered, and then concentrated in
vacuum. The crude product was purified by flash column chro-
matography (2:8 EtOAc–cyclohexane) to afford 43 mg (88%) of
aldehyde 17 as a yellow oil. TLC: Rf¼0.73 (EtOAc–cyclohexane,
99.4, 124.6, 127.5, 127.6, 127.8, 127.9, 128.4, 128.5, 129.0, 133.6, 135.4,
138.2,147.1. HRESIMS: calcd for C28H31NO8Na: 532.1947; found: m/z
532.1942.
3.11. Synthesis of 2,3-di-O-benzyl-1-O-methyl-4-O-(o-
nitro)benzyl-D-glucitol 15
Molecular sieves 4 Å (2.0 g) were placed in a 10-mL flask and
dried at 140 ꢁC for 4 h under vacuum (ca. 0.1 mmHg). After
cooling to rt, a soln of compound 11 (532 mg, 1.05 mmol) in
CH2Cl2 (20 mL) was added to the flask under argon atmosphere.
After stirring for 1 h at rt, the mixture was cooled to ꢀ78 ꢁC, and
then Et3SiH (1.0 mL, 6.2 mmol) and a soln of dichlorophenylbor-
ane in CH2Cl2 (0.8 mL, 6.2 mmol) were added successively. After
being stirred for 2 h at ꢀ78 to ꢀ40 ꢁC, Et3N (2 mL) and MeOH
(2 mL) were added, and the mixture was diluted with CHCl3
(50 mL), washed with aqueous saturated NaHCO3 (2ꢂ25 mL),
3:7); [
a
]
þ21.8 (c 0.40, CHCl3); 1H NMR (400 MHz, CDCl3):
d 3.26
D
(s, 3H, OMe), 3.45 (dd, 1H, J¼4.6, 9.2 Hz, H-5a), 3.53 (dd, 1H,
J¼5.5, 9.2 Hz, H-5b), 3.80–3.83 (m, 1H, H-4), 3.98–4.04 (m, 2H, H-
2, H-3), 4.48 (d, 1H, 2J¼11.5 Hz, CHPh), 4.51 (d, 1H, 2J¼11.5 Hz,
CHPh), 4.64 (d, 1H, 2J¼11.4 Hz, CHPh), 4.71 (d, 1H, 2J¼11.4 Hz,
CHPh), 4.88 (d, 1H, 2J¼14.7 Hz, CHPh), 5.09 (d, 1H, 2J¼14.7 Hz,
CHPh), 7.24–7.32 (m, 10H, 2ꢂPh), 7.44 (t, 1H, J¼7.8 Hz, o-NO2–
PhH), 7.62 (t, 1H, J¼7.8 Hz, o-NO2–PhH), 7.78 (d, 1H, J¼7.8 Hz,
o-NO2–PhH), 8.05 (d, 1H, J¼8.3 Hz, o-NO2–PhH), 9.75 (s, 1H, H-1);
13C NMR (100 MHz, CDCl3):
d 59.2, 69.9, 71.4, 73.2, 74.3, 76.5,

10692
C.-J. Zhu et al. / Tetrahedron 64 (2008) 10687–10693
78.9, 82.8, 124.8, 127.9, 128.3, 128.4, 128.5, 128.6, 128.7, 129.1,
133.9, 134.4, 137.6, 137.8, 147.3, 199.7. HRESIMS: calcd for
C27H29NO7Na: 502.1842; found: m/z 502.1836.
J¼4.1, 11.9 Hz, H-6a), 4.29 (dd, 1H, J¼1.8, 11.9 Hz, H-6b), 4.60 (d, 1H,
J¼3.2 Hz, H-1), 4.64 (d, 1H, 2J¼11.0 Hz, CHPh), 4.65 (d, 1H,
2J¼11.9 Hz, CHPh), 4.78 (d, 1H, 2J¼11.9 Hz, CHPh), 4.95 (d, 1H,
2J¼11.0 Hz, CHPh), 4.96 (d, 1H, 2J¼14.7 Hz, CHPh), 5.24 (d, 1H,
2J¼14.7 Hz, CHPh), 7.17–7.34 (m, 10H, 2ꢂPh), 7.41 (t, 1H, J¼7.8 Hz, o-
NO2–PhH), 7.58 (t, 1H, J¼7.8 Hz, o-NO2–PhH), 7.72 (d, 1H, J¼7.8 Hz,
o-NO2–PhH), 8.04 (d, 1H, J¼8.2 Hz, o-NO2–PhH); 13C NMR
3.14. Photolysis of compounds 8 and 9
A soln of compound 8 (35 mg, 0.069 mmol) or 9 (42 mg,
0.082 mmol) in acetonitrile (1.0 mL) was irradiated by 365 nm UV-
light (200 mW/cm2) in quartz cell for 1 h. After evaporation of the
solvent under reduced pressure, the residue was purified by flash
column chromatography (1:1 EtOAc–cyclohexane) to afford the
corresponding free diols 14 or 18 in 91% yield.
(100 MHz, CDCl3): d 20.9, 55.5, 63.2, 68.5, 71.3, 73.5, 75.8, 78.1, 80.0,
81.8, 98.2, 124.7, 127.7, 127.9, 128.1, 128.2, 128.4, 128.6, 133.8, 135.1,
138.0, 138.4, 146.7, 170.8. HRESIMS: calcd for C30H33NO9Na:
574.2053; found: m/z 574.2048.
3.18. Synthesis of 3-(60-O-acetyl-20,30-di-O-benzyl-40-O-(o-
nitro)benzyl-a-D-glucopyranosyl)-1-propene 22
3.15. Synthesis of methyl 4-O-acetyl-2,3-di-O-benzyl-6-O-(o-
nitro)benzyl-a-D-glucopyranoside 19
Compound 21 (42 mg, 0.076 mmol) was C-allylated as for the
compound 19. Purification by flash column chromatography (3:7
EtOAc–cyclohexane) afforded 22 (25 mg, 58%) as a yellow oil. TLC:
To a soln of compound 3 (390 mg, 0.77 mmol) in pyridine (8 mL)
was added Ac2O (1 mL) at rt. After 16 h, the reaction mixture was
evaporated and residue was dissolved in CH2Cl2, washed with H2O,
extracted with CH2Cl2, dried over MgSO4, and filtered. Evaporation
of the solvent gave a crude product, which was purified by column
chromatography (1:5 EtOAc–cyclohexane) to afford 19 (388 mg,
Rf 0.62 (EtOAc–cyclohexane, 3:7); [
a
]
þ52.0 (c 0.33, CHCl3); 1H
D
NMR (400 MHz, CDCl3):
d
2.06 (s, 3H, OMe), 2.50 (m, 2H, H-3), 3.52
(t, 1H, J¼8.7 Hz), 3.72–3.76 (m, 2H), 3.80 (t, 1H, J¼8.7 Hz), 4.07–4.12
(m, 1H, H-10), 4.16 (dd, 1H, J¼5.0, 11.4 Hz, H-60a), 4.25 (dd, 1H, J¼1.8,
11.4 Hz, H-60b), 4.59–4.69 (m, 3H, 3ꢂCHPh), 4.87–4.94 (m, 2H,
2ꢂCHPh), 5.08–5.16 (m, 2H, H-1), 5.25 (d, 1H, 2J¼14.7 Hz, CHPh),
5.73–5.83 (m, 1H, H-2), 7.17–7.30 (m, 10H, 2ꢂPh), 7.41 (t, 1H,
J¼7.1 Hz, o-NO2–PhH), 7.59 (t,1H, J¼7.1 Hz, o-NO2–PhH), 7.72 (d,1H,
J¼7.1 Hz, o-NO2–PhH), 8.04 (d, 1H, J¼8.2 Hz, o-NO2–PhH); 13C NMR
92%) as a yellow oil. TLC: Rf¼0.53 (EtOAc–cyclohexane, 1:3); [
a]
D
þ50.0 (c 0.53, CH2Cl2); 1H NMR (300 MHz, CDCl3):
d 1.89 (s, 3H,
OAc), 3.42 (s, 3H, OMe), 3.58–3.63 (m, 3H, H-2, H-6a, H-6b), 3.84–
3.89 (m, 1H, H-5), 3.94 (t, 1H, J¼9.5 Hz, H-3), 4.63 (d, 1H, J¼3.8 Hz,
H-1), 4.65 (d, 1H, 2J¼11.4 Hz, CHPh), 4.66 (d, 1H, 2J¼11.4 Hz, CHPh),
4.79–4.96 (m, 4H, 2ꢂCH2Ph), 5.07 (dd, 1H, J¼9.6, 9.2 Hz, H-4), 7.27–
7.38 (m, 10H, 2ꢂPh), 7.41 (t, 1H, J¼8.1 Hz, o-NO2–PhH), 7.54 (t, 1H,
J¼8.1 Hz, o-NO2–PhH), 7.85 (d, 1H, J¼8.1 Hz, o-NO2–PhH), 8.05 (d,
(100 MHz, CDCl3): d 20.9, 29.9, 63.7, 69.8, 71.3, 73.7, 75.4, 77.4, 78.7,
80.1, 81.8, 117.1, 124.8, 127.8, 127.9, 128.0, 128.1, 128.5, 128.6, 138.1,
138.4, 146.7, 171.3. HRESIMS: calcd for C32H35NO8Na: 584.2260;
found: m/z 584.2255.
1H, J¼8.1 Hz, o-NO2–PhH); 13C NMR (75 MHz, CDCl3):
d 20.8, 55.3,
68.6, 69.8, 69.9, 70.2, 73.4, 75.3, 79.2, 79.6, 98.1, 124.4, 127.5, 127.8–
128.4, 128.6, 133.7, 134.8, 137.9, 138.5, 146.9, 169.6. HRESIMS: calcd
for C30H33NO9Na: 574.2053; found: m/z 574.2039.
Acknowledgements
3.16. Synthesis of 3-(40-O-acetyl-20,30-di-O-benzyl-60-O-(o-
nitro)benzyl-a-D-glucopyranosyl)-1-propene 20
C.-J.Z. thanks the French Ministry of Foreign Affairs for an Eiffel
Doctorate scholarship. Y.H. thanks the CNRS for a post-doc fel-
lowship. The research was supported by CNRS (Convention CNRS-
NSC) and Shanghai Science and Technology Community (No.
074107018).
To a soln of 19 (52 mg, 0.094 mmol) in CH3CN (2 mL), were
added allylTMS (0.08 mL, 0.5 mmol) and TMSOTF (0.1 mL,
0.5 mmol) at rt. After 72 h, the reaction mixture was diluted with
CH2Cl2 (5 mL), extracted with CH2Cl2 (2ꢂ5 mL), washed with
H2O, dried over MgSO4, filtered, and evaporated. The residue was
purified by column chromatography (1:3 EtOAc–cyclohexane) to
afford 20 as a yellow oil (34 mg, 65%). TLC: Rf¼0.59 (EtOAc–cy-
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CDCl3):
a
]
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D
d
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