Unexpected reductions of glycosyl spacer-armed phthalimides

Article abstract of DOI:10.1016/j.carres.2004.03.028

An unusual reductive ring-opening reaction in the title compounds, of the phthalimide group with sodium hydride in anhydrous DMF is observed for the first time and the presumed mechanism is described in detail. An unexpected hydrogenation of the phthalimide group was also observed.

Full text of DOI:10.1016/j.carres.2004.03.028

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 1497–1501
Unexpected reductions of glycosyl spacer-armed phthalimides
Xiang-Bao Meng, Hui Li, Qing-Hua Lou, Meng-Shen Cai and Zhong-Jun Li*
Department of Chemical Biology, School of Pharmaceutical Sciences, National Research Laboratory of Natural and Biomimetic Drugs,
Peking University, Beijing 100083, China
Received 10 November 2003; accepted 10 March 2004
Abstract—An unusual reductive ring-opening reaction in the title compounds, of the phthalimide group with sodium hydride in
anhydrous DMF is observed for the first time and the presumed mechanism is described in detail. An unexpected hydrogenation of
the phthalimide group was also observed.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Keywords: Phthalimide; Benzylation; Hydrogenation; Reduction
1. Introduction
3 was treated with sodium hydride (1.2 equiv per OH
group) and benzyl bromide (1.5 equiv per OH group) in
anhydrous DMF, an unexpected reaction of the
phthalimide group occurred. Compound 4 was isolated
from the complex reaction mixture as the main product
in 29% yield. Components more polar than 4 (>5 spots
on TLC) were speculated to be products of incomplete
benzylate (Scheme 1).
The phthaloyl group is widely used as an amino pro-
tecting group in carbohydrate and peptide chemistry. It
is quite stable under various conditions and is usually
removed with hydrazine hydrate in refluxing alcohol.1
The phthalimide can be reduced by hydrogen-transfer
reactions (such as zinc or tin in acetic acid, or hydro-
chloric acid) in low yield2–5 and by NaBH4.6 Recently,
however, we found specific phthalimides that are labile
to reduction under classical conditions of benzylation
and hydrogenation.
The hydride ion can attack one of the carbonyl car-
bons (transition state B) of the proposed intermediate A
to give the delocalized amide anion (D), which is further
N-benzylated to give the aldehyde (E). Reduction and
benzylation of the aldehyde then occurred repeatedly
and rapidly to give the product 4 (Scheme 1). The O-
benzylated product of the delocalized amide anion (D)
was not obtained from the reaction mixture, probably
because of its disfavored thermodynamic stability.
Benzylation of 3 was incomplete under these condi-
tions, although fully benzylated 4 could be isolated from
the reaction mixture. The flexible aglycon may play a
role in the benzylation of the carbohydrate moiety.
When 1.0 equiv of NaH per hydroxyl group was used,
compound 4 was isolated from the mixture in lower
yield (16%); and when 1.5 equiv of NaH per hydroxyl
group was used, compound 4 was obtained in higher
yield (46%). Although the formation of 4 is related to
the amount of NaH used, the reaction was still incom-
plete, even when a large excess of NaH was used.
2. Results and discussion
2.1. Reduction by NaH in anhydrous DMF
We chose phthaloyl protection of a primary amino
group in the synthesis of an oligosaccharide intermedi-
ate. After reduction of the azide group of compound 17
by hydrogenation, the resulting amine was treated with
phthalic anhydride to give the phthalimide 2.8 The 30,40-
dihydroxyl function of 2 was then regioselectively pro-
tected with an isopropylidene group.9 When compound
* Corresponding author. Tel.: +86-10-6209-1504; fax: +86-10-6236-
7134; e-mail: zjli@bjmu.edu.cn
0008-6215/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.03.028

1498
X.-B. Meng et al. / Carbohydrate Research 339 (2004) 1497–1501
OH
HO
OH
OH
O
O
a
O
O
O
HO
O
N3
OH
OH
1
OAc
OAc
O
OAc
O
O
b
O
O
AcO
O
AcO
O
N
OAc
OAc
2
O
O
OH
OH
O
O
O
c
O
O
O
O
HO
O
N
OH
OH
3
O
O
OBn
OBn
O
O
O
O
O
RO
O
BnO
O
O
N
O
OBn
N
OBn
O
A
O
O
O
O
CHO
O
CHO
H
RO
RO
N
N
N
N
O
O
H
B
D
H
O
C
CHO
O
CH2O
O
CH2OBn
H
BnBr
BnBr
RO
RO
RO
N
N
N
Bn
Bn
Bn
E
F
4
OH
OBn
OBn
O
OBn
d
O
O
O
O
HO
O
O
N
BnO
OBn
OBn
Bn
5
Scheme 1. Reagents and conditions: (a) (1) Pd–C, H2, EtOAc–HOAc, 6 h; (2) phthalic anhydride, MeOH, rt, 24 h; (3) Ac2O, pyridine, rt, overnight;
(b) (1) NaOMe, MeOH, rt, 3 h; (2) 2,2-dimethoxypropane, TsOH, DMF, rt, 24 h; Et3N, MeOH–H2O, refluxing; (c) BnBr, NaH, DMF, 0 ꢁC to rt,
overnight; (d) CF3CO2H–H2O (9:1), CH2Cl2, 0 ꢁC, 30 min.
Compound 4 was obtained in slightly higher yield under
these conditions. Compound 4 was observed even when
the reaction was quenched with methanol after 2 h. This
evidence indicates that the rate of reduction was com-
parable with the rate of benzylation.
To our knowledge, this is the first report of a
phthalimide group that was reduced under the standard
benzylation procedure.
acid. Acetylation gave, surprisingly the product 9, fully
1
characterized by H NMR, 13C NMR, 2D NMR, and
TOF MS as a 2,3-dihydro-isoindol-1-one derivative.
This unexpected hydrogenation of the phthalide took
place in nearly quantitative yield (TLC) and suggests a
novel method for preparing 2,3-dihydro-isoindol-1-one
derivatives (Scheme 2).
2.2. Phthalimide is reduced to a 2,3-dihydro-isoindol-1-
one by hydrogenation
3. Experimental
3.1. General methods
In an alternative synthetic route, intermediate 3 was
benzylated in the presence of Ag2O powder10 in anhy-
drous DMF (28.8% yield). After removal of the iso-
propylidene group of 6 by 90% TFA, the resulting diol 7
was treated with Bu2SnO in refluxing toluene, and then
with methyl bromoacetate under catalysis by tetra-n-
butylammonium iodide (Bu4NI) to afford the 30-alkyl-
ated product (8).11 Deprotection of the benzyl ether by
hydrogenation over 10% Pd–C was performed in acetic
1H and 13C NMR spectra were recorded on either
Varian VXR-300, or Jeol 300 spectrometers at ambient
temperature. 2D NMR spectra were recorded on an
Inova 500 spectrometer. Mass spectra were determined
on a ZAB-HS spectrometer (FAB) or an LDI-TOF
spectrometer (MALDI-TOF). Optical rotations were
measured with an AA-10R automatic polarimeter. Sol-
vents were dried and distilled conventionally. Column

X.-B. Meng et al. / Carbohydrate Research 339 (2004) 1497–1501
1499
O
OBn
OBn
O
O
a
O
O
O
O
3
O
BnO
N
O
OBn
OBn
6
O
OH
OBn
O
OBn
b
O
O
O
O
O
HO
O
O
N
BnO
OBn
OBn
O
7
OH
O
OBn
OBn
O
c
H3CO
O
O
O
O
O
N
BnO
O
OBn
OBn
O
8
OAc
O
OAc
OAc
O
d
O
O
H3CO
O
O
O
O
N
AcO
O
OAc
OAc
9
Scheme 2. Reagents and conditions: (a) BnBr, Ag2O, DMF, rt, 24 h; (b) CF3CO2H–H2O, CH2Cl2, 0 ꢁC; (c) (1) Bu2SnO, toluene, reflux, 4 h; (2)
BrCH2CO2Me, Bu4NI, 80 ꢁC, 2.5 h; (3) NaOMe, MeOH, rt, 3 h; (d) (1) Pd–C, H2, AcOH, 36 h; (2) Ac2O, pyridine, rt, 24 h.
chromatography was carried out on Silica Gel H
(Haiyang Chemical Factory, Qingdao, Shandong,
China). TLC was performed on Silica Gel GF254
(Haiyang Chemical Factory, Qingdao, Shandong, Chi-
na) with detection by UV fluorescence quenching and by
spraying with 10% H2SO4. 8-Azido-3,6-dioxaoctyl 4-O-
1H NMR (CDCl3): d 7.85 (dd, 2H, J 3.0, J 5.7 Hz,
Phth), 7.72 (dd, 2H, Phth), 5.34 (d, 1H, J 3.0 Hz), 5.22–
5.08 (m, 2H), 4.98–4.85 (m, 2H), 4.55–4.47 (m, 3H),
4.16–4.05 (m, 4H), 3.92–3.54 (m, 14H), 2.15, 2.12, 2.06,
2.05, 2.04, 2.03, 1.97 (7s, 21H, 7·CH3); 13C NMR: d
170.3, 170.3, 170.1, 170.0, 169.7, 169.6, 169.0, 168.2
(CO), 133.9, 132.1, 123.2 (Phth), 101.0, 100.6 (C-1, C-
10), 76.2, 72.7, 72.5, 71.6, 70.9, 70.6, 70.2, 70.0, 69.0,
67.9, 66.5, 62.0, 60.7, 60.3, 37.1, 21.0, 20.8, 20.8, 20.6,
20.6, 20.5 (7·CH3CO); MALDI-TOF MS: Calcd for
C40H51NO22: m=z 897.3. Found: 898.2 [M+H]þ.
(b-
D
-galactopyranosyl)-b-D-glucopyranoside (1) was
prepared by literature methods.7
3.2. 8-Phthalimido-3,6-dioxaoctyl 4-O-(b-D-galactopy-
ranosyl)-b-D-glucopyranoside (2)
A solution of the azide 1 (21.7 g, 36 mmol) in EtOAc
(200 mL) and AcOH (100 mL) was treated with hydro-
gen (0.42 MPa) in the presence of 10% Pd–C (500 mg)
for 6 h. After removal of insoluble materials through a
pad of Celite, the filtrate was concentrated to give a
colorless syrup, which was used in the next step without
further purification.
To a solution of the foregoing amine acetate (22.3 g,
36.0 mmol) in dry MeOH (300 mL) were added Et3N
(9.5 mL, 75.0 mmol) and phthalic anhydride (6.0 g,
40.5 mmol). The mixture was stirred at room tempera-
ture for 24 h. After evaporation of MeOH under
reduced pressure, Ac2O (30 mL) and pyridine (30 mL)
were added to the residue. The mixture was stirred at
room temperature overnight, poured into ice–water
(200 mL) and stirred vigorously for 2 h. The aq mixture
was extracted with toluene (100 mL · 3). The combined
extracts were then washed with aq saturated NaHCO3
and brine, dried (Na2SO4), filtered, and concentrated.
Column chromatography (3:2 petroleum ether–ether)
of the residue afforded 2 (25.8 g, 79.9% for two steps)
3.3. 8-Phthalimido-3,6-dioxaoctyl 4-O-(3,4-di-O-isoprop-
-galactopyranosyl)-b-D-glucopyranoside (3)
ylidene-b-
D
To a solution of compound 2 (19.6 g, 21.8 mmol) in dry
MeOH (400 mL) was added NaOMe (0.11 g, 2.0 mmol).
After stirring at rt for 3 h, the mixture was neutralized
with Hþ cation-exchange resin, filtered, and concen-
trated to give a pale-yellow syrup (12.8 g, 97.7%).
A mixture of the deacetylated product (10.5 g,
17.4 mmol), 2,2-dimethoxypropane (20 mL), and p-tol-
uenesulfonic acid hydrate (350 mg, 1.8 mmol) in dry
DMF (80 mL) was stirred at rt for 24 h. The mixture was
neutralized with Et3N and evaporated to dryness in
vacuo. The residue was dissolved in MeOH–H2O (10:1,
150 mL, v/v) and refluxed for 4 h. TLC indicated that the
intermediate (Rf 0.67, 20:1 CHCl3–MeOH) was con-
verted into the desired product (Rf 0.18, 20:1 CHCl3–
MeOH). Column chromatography (100:4:1 CHCl3–
MeOH–Et3N) afforded 3 (9.40 g, 84.0%) as a yellow
foam, ½aŠ
+32.8 (c 0.62, CHCl3); 1H NMR
(CDCl3+D2O): d 7.84 (dd, 2H, J 3.3, J 5.4 Hz, Phth),
7.22 (dd, 2H, Phth), 4.73 (m, 1H), 4.48 (d, 1H, J 8.1 Hz,
D
as a slightly yellow syrup, ½aŠ )6.4 (c 1.25, CHCl3);
D

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X.-B. Meng et al. / Carbohydrate Research 339 (2004) 1497–1501
H-1 or H-10), 4.34 (d, 1H, J 7.8 Hz, H-1 or H-10), 4.14–
3.90 (m, 3H), 3.88–3.78 (m, 8H), 3.73–3.41 (m, 12H,
OCH2CH2OCH2CH2OCH2CH2N), 1.49, 1.30 (2s, 6H,
2CH3); 13C NMR: d 168.3 (2·C@O), 134.0, 132.1, 123.3
(Phth), 110.3 [(CH3)2C], 103.0, 102.9 (C-1, C-10), 79.8,
79.4, 74.9, 74.6, 74.1, 73.9, 73.3, 70.3, 70.1, 68.8, 67.9,
62.1, 61.6, 37.3, 28.0, 26.2 (2·CH3). FAB MS: Calcd for
C29H41NO15: m=z 643.2. Found: 682.3 [M+K]þ.
136.7, 132.6, 132.4, 130.5, 128.9, 128.5, 128.4, 128.3,
128.2, 128.2, 128.0, 127.7, 127.5, 127.5, 127.1, 127.0,
103.9, 102.5 (C-1, C-10), 82.7, 81.7, 80.1, 76.5, 75.1, 74.8,
74.7, 73.6, 73.5, 73.2, 73.0, 70.6, 70.5, 70.3, 69.0, 68.8,
68.7, 68.4, 53.5, 52.2, 48.3, 47.5. MALDI-TOF MS:
Calcd for C75H83NO15: m=z 1237.6. Found: 1238.3
[M+H]þ.
3.6. 8-Phthalimido-3,6-dioxaoctyl 2,3,6-tri-O-benzyl-4-O-
(2,6-di-O-benzyl-3,4-di-O-isopropylidene-b-
pyranosyl)-b- -glucopyranoside (6)
3.4. 8-[N-Benzyl,N-(2-benzyloxymethylbenzoyl)]-6-dioxa-
octyl 2,3,6-tri-O-benzyl-4-O-(2,6-di-O-benzyl-3,4-di-O-
D-galacto-
D
isopropylidene-b-
oside (4)
D
-galactopyranosyl)-b-D-glucopyran-
To a solution of compound 3 (5.80 g, 9.0 mmol) in dry
DMF (80 mL) were added freshly prepared Ag2O pow-
der (18.6 g, 90 mmol) and BnBr (10.8 mL, 90 mmol). The
suspension was treated by ultrasonic irradiation for
15 min before being stirred in dark for 24 h at rt. After
removal of the solid through a pad of Celite, the filtrate
was diluted with toluene (200 mL), washed with brine,
dried (CaCl2), and concentrated. Column chromato-
graphy (2:1 petroleum ether–EtOAc) of the residue
To an ice-cold solution of compound 3 (1.30 g,
2.0 mmol) in dry DMF (30 mL) was added NaH (60%,
0.48 g, 12.0 mmol) and benzyl bromide (1.80 mL,
15.0 mmol). The temperature of the mixture was allowed
to rise to rt and it was stirred overnight. An excess of
MeOH was added dropwise to quench the reaction. The
clear solution was diluted with water (50 mL) and ex-
tracted with toluene (30 mL · 3). The extracts were
combined and washed with brine (50 mL · 2), dried
(Na2SO4), and concentrated. Column chromatography
(5:1 petroleum ether–EtOAc) of the residue afforded 4
afforded 6 (2.52 g, 28.8%) as a pale-yellow syrup, ½aŠ
D
1
+25.8 (c 1.55, CHCl3); H NMR (CDCl3): d 7.78–7.64
(m, 4H, Phth), 7.51–7.19 (m, 25H, 5 Ph), 4.90–4.84 (m,
2H), 4.77–4.62 (m, 3H), 4.55–4.26 (m, 5H), 4.01–3.91
(m, 4H), 3.88–3.31 (m, 22H), 1.36, 1.32, (2s, 6H, 2CH3);
13C NMR (CDCl3): d 168.2 (2·C@O), 139.0, 138.7,
138.5, 138.34, 138.2, 133.9, 132.1, 123.2 (Phth), 128.5,
128.3, 128.3, 128.2, 128.1, 128.0, 128.0, 127.8, 127.7,
127.5, 127.4, 127.2 (CH of 5 Ph), 109.7 [(CH3)2C], 103.8,
101.8 (C-1, C-10), 82.8, 81.6, 80.6, 79.3, 77.2, 76.8, 76.5,
76.3, 75.4, 74.3, 75.4, 75.0 74.7, 73.6, 73.3, 73.2, 73.1,
71.9, 70.5, 70.3, 70.0, 68.9, 68.9, 68.2, 67.9, 37.2, 29.0,
27.9 (2·CH3). MALDI-TOF MS: Calcd for
C64H71NO15: m=z 1093.5. Found: 1132.2 [M+K]þ.
(750 mg, 29.0%) as a yellow syrup, ½aŠ +25.0 (c 0.96,
D
1
CHCl3); H NMR (CDCl3): d 7.98 (m, 1H), 7.51–7.10
(m, 38H), 4.91–4.61 (m, 8H), 4.54–4.27 (m, 8H), 4.08–
3.49 (m, 20H), 3.39–3.18 (m, 6H), 1.37, 1.32 (2s, 6H,
2CH3); 13C NMR (CDCl3): d 171.1 (CO), 138.9, 138.6,
138.3, 138.1, 138.0, 137.6, 136.6, 135.6, 132.8, 132.6,
130.7, 130.6, 128.5, 128.5, 128.4, 128.3, 128.2, 128.2,
128.1, 128.0, 127.8, 127.6, 127.5, 127.2, 109.7 [(CH3)2C],
103.8, 102.5 (C-1, C-10), 82.8, 82.7, 81.6, 80.5, 80.0, 79.3,
76.4, 76.2, 75.3, 75.2, 75.0, 74.8, 73.5, 73.4, 73.3, 73.1,
72.8, 71.9, 70.5, 70.2, 53.5, 48.2, 47.7, 43.7, 27.9, 26.4
[(CH3)2C]. MALDI-TOF MS: Calcd for C78H87NO15:
m=z 1277.6. Found: 1278.7 [M+H]þ, 1316.8 [M+Na]þ.
3.7. 8-Phthalimido-3,6-dioxaoctyl 2,3,6-tri-O-benzyl-4-O-
D
(2,6-di-O-benzyl-b-
oside (7)
-galactopyranosyl)-b-D-glucopyran-
3.5. 8-[N-Benzyl,N-(2-benzyloxymethylbenzoyl)]-6-dioxa-
octyl 2,3,6-tri-O-benzyl-4-O-(2,6-di-O-benzyl-b-
galactopyranosyl)-b- -glucopyranoside (5)
D
-
To an ice-cold solution of compound 6 (640 g,
D
0.59 mmol) in CH2Cl2 (15 mL) was added CF3CO2H–
H2O (5.0 mL, 9:1, v/v). The mixture was stirred for 0.5 h
and diluted with 35 mL of CH2Cl2. The organic layer
was washed with saturated NaHCO3 solution and brine,
dried (Na4SO4), and concentrated. Column chroma-
tography (7:3 petroleum ether–EtOAc) of the residue
To an ice-cold solution of compound 4 (380 mg,
0.3 mmol) in CH2Cl2 (15 mL) was added CF3CO2H–
H2O (5.0 mL, 9:1, v/v). The mixture was stirred for
45 min and diluted with 20 mL of CH2Cl2. The organic
layer was washed with saturated NaHCO3 solution and
brine, dried (Na4SO4), and concentrated. Column
chromatography (2:1 petroleum ether–EtOAc) of the
residue afforded 5 (320 mg, 87.0%) as a pale-yellow
afforded 7 (550 mg, 89.3%) as a pale-yellow syrup, ½aŠ
D
1
+105.0 (c 1.08, CHCl3); H NMR (CDCl3): d 7.80 (dd,
2H, J 3.0, J 9.0 Hz, Phth), 7.65 (dd, 2H, Phth), 7.52–7.20
(m, 25H, 5 Ph), 4.98–4.74 (m, 3H), 4.70–4.55 (m, 3H),
4.45–4.35 (m, 4H), 4.02–3.92 (m, 3H), 3.86–3.79 (m,
4H), 3.69–3.34 (m, 19H); 13C NMR (CDCl3): d 168.2
(C@O), 129.0, 138.6, 138.3, 138.1, 137.9, 133.8, 132.0,
128.4, 128.3, 128.2, 128.2, 128.0, 127.9, 127.8, 127.7,
127.6,127.6, 127.5, 127.5, 127.4, 127.2, 126.9, 123.1
1
syrup, ½aŠ +30.6 (c 0.85, CHCl3); H NMR (CDCl3): d
D
8.00 (m, 1H), 7.48–7.12 (m, 38H), 4.98–4.55 (m, 7H),
4.46–4.36 (m, 6H), 4.05–3.92 (m, 3H), 3.87 (s, 2H,
PhCH2), 3.83–3.19 (m, 24H); 13C NMR (CDCl3): d
171.2 (CO), 139.2, 138.7, 138.4, 138.2, 138.1, 137.5,

X.-B. Meng et al. / Carbohydrate Research 339 (2004) 1497–1501
1501
(Phth, 5·Ph), 103.7, 102.5 (C-1, C-10), 82.6, 81.5, 79.9,
76.4, 75.1, 74.9, 74.8, 74.6, 73.4, 73.1, 72.8, 70.4, 70.3,
69.9, 68.9, 68.7, 68.6, 68.2, 67.8, 37.1. MALDI-TOF
MS: Calcd for C61H67NO15: m=z 1053.4. Found: 1092.6
[M+K]þ.
A solution of the hydrogenation product (20 mg,
30 lmol) in pyridine (1 mL) and Ac2O (1 mL) was stirred
at rt for 24 h. An excess of MeOH was added to consume
the remaining Ac2O. The mixture was evaporated to
dryness and the residue was subjected to column chro-
matography (3:4 petroleum ether–EtOAc) to give 9
(25 mg, 93%) as a colorless thick syrup, ½aŠD +5.2 (c 0.80,
CHCl3); 1H NMR (CDCl3): d 7.86–7.44 (m, 4H), 5.39 (d,
1H, J 3.0 Hz, H-40), 5.18 (t, 1H, J 9.5 Hz, H-3), 5.01 (dd,
1H, J 7.5 Hz, J 9.5 Hz, H-20), 4.87 (dd, 1H, J 8.0, 9.5 Hz,
H-2), 4.55 (s, 2H, ArCH2N), 4.52 (d, 1H, J 8.0 Hz, H-1),
4.88 (dd, 1H, J 1.5, 11.5 Hz, H-6a), 4.55 (d, 1H, J 8.0 Hz,
H-10), 4.14–4.05 (m, 5H, H-30, H-6b, H-6a0, CH2), 3.89–
3.73 (m, 6H), 3.72 (s, 3H, OCH3), 3.69–3.56 (m, 10H),
2.142, 2.137, 2.10, 2.08, 2.04, 2.02 (6s, 18H, 6·Ac); 13C
NMR (CDCl3): d 170.4, 170.4, 170.3, 170.1, 169.7, 169.7,
168.5 (7·C@O), 141.8, 132.7, 131.2, 127.8, 123.6, 122.6,
101.1 (C-10), 100.6 (C-1), 78.2 (C-60), 76.3 (C-6), 72.9 (C-
3), 72.7, 71.6 (C-2), 70.6 (C-20), 70.6, 70.5, 70.3, 70.1,
70.0, 69.1, 66.0, 65.0 (C-40), 62.1 (C-6), 61.2, 51.8
(ArCH2N), 51.6 (OCH3), 42.3 (OCH2CH2N), 20.9, 20.8,
20.8, 20.7 (CH3CO). MALDI-TOF MS: Calcd for
C41H55NO22: m=z 913.3. Found: 914.3 [M+H]þ.
3.8. 8-Phthalimido-3,6-dioxaoctyl 2,3,6-tri-O-benzyl-4-O-
(2,6-di-O-benzyl-3-O-methoxycarbonylmethylene-b-
galactopyranosyl)-b- -glucopyranoside (8)
D-
D
To a solution of compound 7 (1.79 g, 1.7 mmol) in
absolute toluene (100 mL) was added Bu2SnO (0.60 g,
1.4 mmol). The suspension was heated to reflux over a
Dean–Stark apparatus for 4 h and 60 mL of the solvent
were distilled out. The temperature of the clear solution
was allowed to drop to 80 ꢁC, methyl bromoacetate
(1.5 mL, 10 mmol) and Bu4NI (0.63 g, 1.7 mmol) were
added, and the solution was stirred for 2.5 h. The mix-
ture was concentrated under reduced pressure and the
residue was re-dissolved in a solution of 0.05 M NaOMe
in dry MeOH (100 mL). After stirring at rt for 2.5 h, the
mixture was neutralized with Hþ cation-exchange resin,
filtered, and concentrated. Column chromatography
(3:1 petroleum ether–EtOAc) of the residue afforded 8
(1.42 g, 82.7%) as a yellow syrup, ½aŠ )72.0 (c 0.85,
D
Acknowledgements
CHCl3); IR (cmꢀ1): 3482 (–OH), 1744 (C@O); 1H NMR
(CDCl3): d 7.80 (dd, 2H, J 3.0, J 9.0 Hz, Phth), 7.65 (dd,
2H, Phth), 7.48–7.22 (m, 25H, 5 Ph), 5.00–4.90 (m, 2H),
4.77–4.69 (m, 4H), 4.57–4.36 (m, 7H), 4.16–3.92 (m,
4H), 3.78 (s, 3H, OCH3), 3.74–3.20 (m, 21H); 13C NMR
(CDCl3): d 172.0, 168.2 (3CO), 139.0, 138.7, 138.5,
138.3, 138.2, 133.9, 132.1, 128.3, 128.3, 128.2, 128.2,
128.0, 127.8, 127.7, 127.6, 127.6, 127.5, 127.4, 127.2,
123.2 (5·Ph, Phth), 103.8, 102.4 (C-1, C-10), 84.1, 82.7,
81.6, 79.4, 77.2, 75.4, 75.2, 75.0, 74.7, 73.5, 73.1, 72.7,
70.6, 70.6, 70.0, 69.0, 68.4, 68.2, 66.5, 52.1, 50.6 (OCH3),
37.2. MALDI-TOF MS: Calcd for C64H71NO17: m=z
1125.5. Found: 1148.6 [M +Na]þ, 1164.5 [M+K]þ.
We thank the National Science Foundation of the PR
China (NSFC) for financial support (No. 29872005).
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carbonylmethyl-b-
D
-galactopyranosyl)-b-D-glucopyran-
oside (9)
To a solution of compound 8 (2.25 g, 2.0 mmol) in
HOAc (20 mL) was added 10% Pd–C (200 mg). The
suspension was treated with H2 (0.42 MPa) for 36 h.
TLC indicated that the starting material had been con-
verted completely into the desired product. The solid
was filtered off and the filtrate was concentrated.