Synthesis of penta- and hexasaccharide fragments corresponding to the O-antigen of Escherichia coli O150

Article abstract of DOI:10.1016/j.tetasy.2010.06.022

The chemical synthesis of a pentasaccharide and a hexasaccharide corresponding to the O-antigen of Escherichia coli O150 has been achieved using sequential glycosylation and [3+3] block glycosylation strategies. Suitably protected monosaccharide synthons have been prepared from the commercially available reducing sugars and then stereoselectively coupled to give the pentasaccharide and a hexasaccharide in excellent yields. 4-Methoxyphenyl and 2-(4-methoxyphenoxy) ethyl groups have been used as the anomeric-protecting groups in the target pentasaccharide and a hexasaccharide, respectively.

Full text of DOI:10.1016/j.tetasy.2010.06.022

Tetrahedron: Asymmetry 21 (2010) 2142–2152
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of penta- and hexasaccharide fragments corresponding
to the O-antigen of Escherichia coli O150
*
Rajib Panchadhayee, Anup Kumar Misra
Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata 700 054, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The chemical synthesis of a pentasaccharide and a hexasaccharide corresponding to the O-antigen of
Escherichia coli O150 has been achieved using sequential glycosylation and [3+3] block glycosylation
strategies. Suitably protected monosaccharide synthons have been prepared from the commercially
available reducing sugars and then stereoselectively coupled to give the pentasaccharide and a hexasac-
charide in excellent yields. 4-Methoxyphenyl and 2-(4-methoxyphenoxy) ethyl groups have been used as
the anomeric-protecting groups in the target pentasaccharide and a hexasaccharide, respectively.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 2 June 2010
Accepted 17 June 2010
Available online 17 August 2010
1. Introduction
Being an integral part of the endotoxin, the O-antigen plays an
important role in the pathogenicity of E. coli. In the past, glycocon-
Escherichia coli (E. coli) is a Gram-negative, nonmotile, faculta-
tively anaerobic bacterium capable of both respiratory and fermen-
tative metabolisms.1 E. coli serves a useful function in the human
body by suppressing the growth of harmful bacteria and by synthe-
sizing considerable amounts of vitamins.2 It colonizes the lower
gut of animals and survives when released into the natural envi-
ronment, allowing widespread distribution to the new hosts. De-
spite the usefulness of E. coli, a number of virulent E. coli strains
are responsible for severe infection of the enteric/diarrheal, urinary
tract infection, pulmonary, and nervous systems.3 Based on their
nature of infections, the enteropathogenic strains of E. coli have
been classified into several classes,4 which include (a) enteropath-
ogenic E. coli (EPEC); (b) enteroinvasive E. coli (EIEC); (c) enterotox-
igenic E. coli (ETEC); (d) enteroaggregative E. coli (EAEC); (e)
diffusely adherent E. coli (DAEC); and (f) enterohemorrhagic
E. coli (EHEC). Because of their capability to produce a bacterio-
phage-mediated Shiga-like toxin, EHEC strains are also termed as
‘Shiga toxin-producing E. coli’ (STEC).5 A well-studied and fre-
quently found Shiga toxin-producing EHEC strain is E. coli
O157:H7, which has been found to be associated with several
lethal intestinal infections and outbreaks in developed countries.6
Besides E. coli O157:H7, several other E. coli serotypes associated
with diarrheal diseases have been included in the STEC category,
which include E. coli O4, O26, O55, O103, O111, O145, O150 etc.7
Recently, Perepelov et al. reported the structure of the oligosaccha-
ride repeating unit of the O-antigen of E. coli O150,8 which is a
member of STEC family and is associated with several outbreaks
of gastrointestinal diseases in Europe (Fig. 1).9
jugates derived from the O-antigenic oligosaccharides from the
bacterial cell wall have been used to develop antibacterial vaccine
candidates.10 Several biological experiments are necessary for a de-
tailed understanding of the relationship between the O-antigen
with the pathogenicity of a particular bacterial strain, which in
turn demands substantial quantities of the oligosaccharides in
hand. The oligosaccharides isolated from the natural source cannot
meet such a requirement. Therefore, the development of a concise
chemical synthetic strategy is essential to provide the large quan-
tity of a particular oligosaccharide. In this direction,11 we report
herein a convenient synthesis of a pentasaccharide as its 4-
methoxyphenyl glycoside 1 together with a hexasaccharide as its
2-(4-methoxyphenoxy) ethyl glycoside 2 corresponding to the O-
antigen of E. coli O150 using sequential and [3+3] block glycosyla-
tion strategies (Figs. 2 and 3). The 4-methoxyphenyl (PMP) group
can be easily removed under oxidative conditions to provide the
pentasaccharide hemiacetal and hexasaccharide derivative linked
to an ethylene glycol linker useful for the
conjugate derivatives.
a preparation of glyco-
2. Results and discussion
This report comprises the synthesis of a pentasaccharide 1 and a
hexasaccharide 2 using sequential glycosylation and block syn-
thetic strategies, respectively. A [3+3] block synthetic strategy
has been developed for the convenient synthesis of the target
hexasaccharide as its 2-(4-methoxyphenoxy) ethyl glycoside 2
(Fig. 3). The synthetic strategy comprises a number of noteworthy
features, which are (a) the stereoselective [3+3] block glycosyla-
tion; (b) the use of readily available suitably protected monosac-
charide intermediates; (c) the exploitation of the orthogonal
* Corresponding author. Tel.: +91 33 25693240; fax: +91 33 2355 3886.
E-mail address: akmisra69@gmail.com (A.K. Misra).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.06.022

R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
2143
β-D-Glcp
1
↓
2
→3)-β-D-GlcpNAc4(Slac)-(1→2)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-α-L-Rhap-(1→3)-β-D-GlcpNAc-(1→
A
OR
β-D-Glcp
1
↓
2
→3)-α-L-Rhap-(1→3)-β-D-GlcpNAc-(1→3)-β-D-GlcpNAc4(Slac)-(1→2)-α-L-Rhap-(1→2)-α-L-Rhap-(1→
B
Figure 1. Structure of the hexasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O150.
OH
O
O
OPMP
HO
A
OPMP
NHAc
A
O
O
HO
HO
O
O
B
HO
O
B
O
OH
HO
HO
OH
O
O
O
C
OH
HO
O
HO
C
HO
HO
D
O
O
O
NHAc
NHAc
D
O
NHAc
HO
O
E
OH
HO
HO
O
E
HO
O
OH
OH
OH
PMP: 4-Methoxyphenyl
HO
F
O
HO
O
2
HO
PMP: 4-Methoxyphenyl
1
SEt
O
Ph
OPMP
Ph
O
SEt
O
O
O
O
O
BnO
BnO
HO
OPMP
BnO
NPhth
AcO
BnO
OMBn
OH
BnO
OAc
3
4
17
5
SEt
Ph
O
O
Ph
O
O
O
O
O
O
O
O
AcO
SEt
NPhth
BnO
AcO
SEt
NPhth
HO
SEt
BnO
OAc
NPhth
6
5
6
OAc
18
O
AcO
AcO
OPMP
OAc
SEt
O
O
AcO
AcO
AcO
SEt
BnO
BnO
7
AcO
OH
19
7
Figure 2. Structure of the synthesized pentasaccharide 1 corresponding to the O-
antigen of Escherichia coli O150 as its 4-methoxyphenyl glycoside.
Figure 3. Structure of the synthesized hexasaccharide 2 corresponding to the O-
antigen of Escherichia coli O150 as its 2-(4-methoxyphenoxy) ethyl glycoside.
property of thioglycoside 18 in the glycosylation of glycosyl
trichloroacetimidate donor; (d) the use of PMP disaccharide 26 as
a source of disaccharide trichloroacetimidate donor 27 to couple
with the thioglycoside 18; and (e) the preparation of 2-(4-
methoxyphenoxy) ethyl glycoside, which offers the access to an
ethylene glycol-linked hexasaccharide derivative for its further
use.
thio-a-L
-rhamnopyranoside 8,16 compound 4 was prepared by the
selective 4-methoxybenzylation under phase transfer condition fol-
lowed by acetylation of the remaining hydroxyl group in 70% yield.
The stereoselective glycosylation of
D-glucosamine hydrochloride-
derived compound 3 with -rhamnopyranosyl thioglycoside deriva-
L
Initially, the synthesis of a hexasaccharide as its 4-methoxy-
phenyl glycoside corresponding to the structure A (Fig. 1) was
attempted. For this purpose, a series of suitably protected monosac-
charide intermediates 3,12 4, 5,13 6,14 and 715 have been prepared
following the literature (Fig. 2). Starting from ethyl 4-O-benzyl-1-
tive 4 in the presence of N-iodosuccinimide (NIS) and trimethylsilyl
trifluoromethanesulfonate (TMSOTf) combination17 furnished
disaccharide derivative 9 in 81% yield, which was deacetylated to
give disaccharide acceptor 10 almost quantitatively. The NMR spec-
troscopic analysis of compound 9 confirmed its formation [d 5.69 (d,

2144
R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
J = 8.4 Hz, H-1A), 5.49 (s, PhCH), 4.56 (br s, H-1B) in 1H NMR and d
101.8 (PhCH), 98.0 (C-1A), 97.7 (C-1B) in 13C NMR spectra). The
NIS–TMSOTf17-mediated stereoselective glycosylation of com-
pound 10 with the thioglycoside derivative 5 afforded trisaccharide
derivative 11 in 80% yield, whichon deacetylation gave trisaccharide
acceptor 12 in 98% yield. The appearance of characteristic signals [d
102.0 (PhCH), 99.1 (C-1C), 97.9 (C-1A), 97.7 (C-1B)] in the 13C NMR
spectra confirmed the formation of compound 11. Glycosylation of
compound 12 with compound 5 in the presence of NIS–TMSOTf fur-
nished tetrasaccharide derivative 13 in 81% yield, which was deacet-
ylated to give tetrasaccharide acceptor 14 in 90% yield. The
appearance of characteristic signals in the NMR spectra [d 5.84 (d,
J = 8.4 Hz, H-1A), 5.55 (s, 1H, PhCH), 4.92 (br s, H-1C), 4.82 (br s, H-
1D), 4.58 (br s, H-1B) in 1H NMR and d 101.8 (PhCH), 100.2 (C-1C),
98.9 (C-1D), 97.9 (C-1A), 97.4 (C-1B) in 13C NMR) confirmed the for-
mation of compound 13. The stereoselective glycosylation of com-
pound 14 with the thioglycoside derivative 6 in the presence of
NIS–TMSOTf furnished pentasaccharide derivative 15 in 71% yield,
which was characterized by the appearance of signals in the NMR
spectra [d 5.76 (d, J = 8.4 Hz, H-1A), 5.54 (s, PhCH), 5.42 (s, PhCH),
5.40 (d, J = 8.3 Hz, H-1E), 4.82–4.80 (m, 2H, H-1C, H-1D), 5.45 (br s,
H-1B) in 1H NMR and d 101.8 (PhCH), 101.5 (PhCH), 100.8 (2C, C-
1C, C-1D), 100.4 (C-1E), 98.0 (C-1A), 97.6 (C-1B) in 13C NMR]. The
DDQ-mediated oxidative removal18 of the 4-methoxybenzyl group
from compound 15 afforded pentasaccharide acceptor 16 in 70%
yield. However, after the successful preparation of pentasaccharide
derivative 16, further NIS–TMSOTf-mediated b-selective glycosyla-
tion of the compound 16 with the thioglycoside 7 did not furnish
any expected hexasaccharide except the formation of the hemiace-
tal derivative from compound 7. In order to overcome this difficulty,
compound 7 was replaced with its per-O-benzoylated derivative to
act as a glycosyl donor and a series of thioglycoside activators e.g.
NIS–TfOH, methyl triflate, DMTST, IDCP etc. were used in different
reaction solvents such as, CH2Cl2, CH3CN, toluene, and 1,2-(CH2Cl)2.
However, all glycosylation conditions failed to produce the glycosyl-
ation product. The use of a per-O-acetylated glucosyl trichloroace-
timidate derivative in place of thioglycoside derivative in the
presence TMSOTf as a glycosylation activator did not lead to the for-
mation of the desired glycosylation product. This finding may be ex-
plained by considering the severe steric crowding around the
hydroxyl group of the acceptor. At this point, complete removal of
the functional groups of the compound 16 by hydrogenolysis19 fol-
lowed by deacetylation furnished the pentasaccharide fragment 1
as its 4-methoxyphenyl glycoside in 62% yield (Structure A, Figs. 1
and 2, Scheme 1). The structure of compound 1 was confirmed from
its NMR spectroscopic data [d 5.20–5.11 (m, H-1A, H-1E), 5.07 (br s,
H-1D), 4.71 (br s, H-1C), 4.52 (br s, H-1B) in the 1H NMR and d 102.9
(C-1A), 101.7 (C-1E), 101.8 (C-1D), 101.4 (C-1C), 96.5 (C-1B) in the
13C NMR spectra]. It is worth mentioning that in the immunological
studies the smaller oligosaccharide fragments are used to discover
the immunodominant fragment of the repeating unit. Therefore,
the structure of the repeating unit has been slightly rearranged
(Structure B, Fig. 1) to minimize such steric crowding and a hexasac-
charide repeating unit has been successfully synthesized as its 2-(4-
methoxyphenoxy) ethyl glycoside 2 (Fig. 3).
SEt
SEt
a
O
O
BnO
BnO
HO
AcO
OH
OMBn
4
8
Ph
O
O
O
O
b
A
3 + 4
OPMP
NPhth
O
B
BnO
RO
OMBn
9:
10:
R = Ac
R = H
c
b
5
Ph
O
O
O
A
O
OPMP
NPhth
BnO
B
O
BnO
BnO
C
O
O
OMBn
11:
RO
R = Ac
R = H
c
12
b
5
Ph
O
O
O
A
O
OPMP
NPhth
BnO
O
B
O
BnO
O
C
OMBn
BnO
O
BnO
BnO
O
D
13:
14:
R = Ac
R = H
c
RO
b
6
Ph
O
O
O
A
O
OPMP
BnO
O
B
O
NPhth
BnO
O
C
OR
BnO
O
15: R = MBn
16: R = H
BnO
BnO
O
D
d
e
1
Ph
O
O
O
E
O
b
7
AcO
NPhth
PMP: 4-Methoxyphenyl
No glycosylation
Scheme 1. Reagents and conditions: (a) (i) 4-methoxybenzyl chloride, 5% aq NaOH,
TBAB, CH2Cl2, room temperature, 5 h; (ii) acetic anhydride, pyridine, room
temperature, 2 h, 70%; (b) N-iodosuccinimide (NIS), TMSOTf, CH2Cl2, MS 4 Å,
ꢀ40 °C, 45 min, 81% for 9; 80% for 11; 81% for 13 and 71% for 15; (c) 0.01 M CH3ONa,
CH3OH, 30 min, room temperature, 97% for 10, 98% for 12 and 90% for 14; (d) DDQ,
CH2Cl2–H2O (6:1), room temperature, 2 h, 70%; (e) (i) ethylenediamine, n-butanol,
90 °C, 5 h; (ii) acetic anhydride, pyridine, room temperature, 2 h; (iii) H2, 20%
Pd(OH)2–C, CH3OH, room temperature, 24 h; (iv) 0.1 M CH3ONa, CH3OH, room
temperature, 5 h, 62% in four steps.
The target hexasaccharide as its 2-(4-methoxyphenoxy) ethyl
glycoside 2 was synthesized from a series of suitably protected
monosaccharide synthons 5,13 6,14 7,15 17, 18,14 and 1920 (Fig. 3).
dene-a-L-rhamnopyranoside 21 in 90% yield. Compound 21 was
2-(4-Methoxyphenoxy) ethyl 2,3,4-tri-O-acetyl-
a
-
L
-rhamnopyr-
subjected to a sequence of reactions involving benzylation using
benzyl bromide and sodium hydroxide,23 removal of the acetal ring
using 80% aqueous acetic acid, and selective benzylation of the
equatorial hydroxy group via stanylidene acetal formation24 to
anoside 20 was prepared from -rhamnose in 87% yield in a two-
L
step sequence involving per-O-acetylation using acetic anhydride
21
and HClO4–SiO2 followed by a reaction of the acetate with 2-
(4-methoxyphenoxy) ethanol in the presence of boron trifluoride
diethyl etherate.22 Saponification of compound 20 followed by ace-
tal formation using 2,2-dimethoxypropane and p-toluenesulfonic
acid furnished 2-(4-methoxyphenoxy) ethyl 2,3-O-isopropyli-
give 2-(4-methoxyphenoxy) ethyl 3,4-di-O-benzyl-
pyranoside 17 in 79% yield (Scheme 2).
a-L-rhamno-
The stereoselective glycosylation of compound 17 with
L-rham-
nose-derived thioglycoside 5 in the presence of NIS–TMSOTf17 fur-

R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
2145
In another experiment, compound 7 was allowed to couple ste-
reoselectively with compound 19 in the presence of NIS–TMSOTf17
to furnish disaccharide derivative 26 in 78% yield. The presence of
signals in the NMR spectra confirmed its formation [d 5.46 (br s, H-
1E), 4.60 (d, J = 8.0 Hz, H-1F) in 1H NMR and d 103.1 (C-1F), 98.0 (C-
1E) in 13C NMR]. Oxidative removal of the anomeric PMP group
from compound 26 using ceric ammonium nitrate (CAN)25 resulted
in the disaccharide hemiacetal derivative, which upon treatment
with trichloroacetonitrile in the presence of DBU26 furnished disac-
charide trichloroacetimidate derivative 27 in 73% yield, which was
used immediately for the next step. The stereoselective glycosyla-
tion of disaccharide trichloroacetimidate derivative 27 with thio-
glycoside glycosyl acceptor 18 under the Schmidt’s glycosylation
condition26 furnished exclusively the trisaccharide thioglycoside
derivative 28 in 75% yield. The appearance of the signals in the
NMR spectra [d 5.45 (s, PhCH), 5.28 (d, J = 10.6 Hz, H-1D), 4.66 (br
s, H-1E), 4.21 (d, J = 7.8 Hz, H-1F) in 1H NMR and d 102.5 (PhCH),
102.1 (C-1F), 99.8 (C-1E), 82.1 (C-1D) in 13C NMR] confirmed the
stereoselective formation of compound 28 (Scheme 4). Finally,
the stereoselective [3+3] glycosylation of compound 25 with com-
pound 28 in the presence of NIS–TfOH17 furnished hexasaccharide
derivative 29 in 76% yield. Spectroscopic analysis of compound 29
confirmed its formation [d 102.4 (C-1F), 102.0 (PhCH), 101.4
(PhCH), 101.3 (C-1D), 101.1 (C-1E), 100.0 (C-1B), 99.3 (C-1A), 97.8
(C-1C) in the 13C NMR]. Conversion of N-phthalimido group to acet-
amido group27 followed by hydrogenolysis19 and saponification of
compound 29 furnished the target hexasaccharide 2 as its 2-(4-
methoxyphenoxy) ethyl glycoside in 66% yield. 1D and 2D NMR
spectroscopic analyses confirmed the structure of compound 2 [d
5.18 (d, J = 8.3 Hz, H-1C), 4.95 (d, J = 8.5 Hz, H-1D), 4.78 (br s, H-
1E), 4.62 (br s, H-1A), 4.56 (br s, H-1B), 4.48 (d, J = 7.6 Hz, H-1F) in
1H NMR and d 104.9 (C-1F), 101.3 (C-1E), 100.2 (C-1B), 99.9 (C-
1A), 99.0 (C-1D), 98.2 (C-1C) in 13C NMR spectra] (Scheme 5).
O
OPMP
O
a
L-Rhamnose
AcO
AcO
OAc
20
b
O
O
O
OPMP
OPMP
O
c, d
BnO
HO
BnO
O
OH
17
O
21
Scheme 2. Reagents and conditions: (a) (i) acetic anhydride, HClO4–SiO2, room
temperature, 10 min; (ii) 2-(4-methoxyphenoxy) ethanol, BF3ꢁOEt2, CH2Cl2, room
temperature, 18 h, 87%; (b) (i) 0.1 M CH3ONa, CH3OH, room temperature, 3 h; (ii)
2,2-dimethoxypropane, p-TsOH, DMF, room temperature, 10 h, 90%; (c) (i) benzyl
bromide, NaOH, THF, TBAB, room temperature, 1 h; (ii) 80% aq AcOH, 80 °C, 1.5 h;
(d) (i) dibutyltin oxide, CH3OH, 80 °C, 2 h; (ii) benzyl bromide, TBAB, DMF, 60 °C,
20 h, 79%.
nished 2-(4-methoxyphenoxy) ethyl (2-O-acetyl-3,4-di-O-benzyl-
a-L-rhamnopyranosyl)-(1?2)-3,4-di-O-benzyl-a-L-rhamnopyr-
anoside 22 in 88% yield, which on deacetylation using sodium
methoxide gave compound 23 almost quantitatively. The forma-
tion of disaccharide derivative 22 was confirmed from its NMR
spectra [d 4.89 (br s, H-1A), 4.70 (br s, H-1B) in 1H NMR and d
99.6 (C-1A), 99.3 (C-1B) in 13C NMR]. Iodonium ion-mediated ster-
eoselective glycosylation of compound 23 with the thioglycoside
donor 6 in the presence of NIS–TMSOTf17 furnished trisaccharide
derivative 24 in 84% yield, which on deacetylation afforded trisac-
charide acceptor 25 in 94% yield (Scheme 3). The presence of sig-
nals at d 5.43 (s, PhCH), 5.38 (d, J = 8.3 Hz, H-1C), 4.87 (br s,
H-1A), 4.66 (br s, H-1B) in the 1H NMR and d 101.9 (PhCH), 101.4
(C-1C), 100.8 (C-1A), 99.3 (C-1B) in the 13C NMR spectra confirmed
the formation of compound 24.
7 + 19
a
O
OPMP
OR
A
O
BnO
O
E
AcO
BnO
a
BnO
OAc
OAc
5 + 17
O
F
BnO
O
O
AcO
B
O
BnO
26:
27:
R = PMP
R = C(NH)CCl3
BnO
OR
b
22
: R = Ac
23
: R = H
b
c
18
6
a
Ph
O
O
O
OPMP
O
D
O
SEt
A
O
NPhth
BnO
O
E
AcO
BnO
BnO
OAc
OAc
O
F
BnO
O
O
B
O
AcO
BnO
28
BnO
O
O
Ph
O
Scheme 4. Reagents and conditions: (a) NIS, TMSOTf, CH2Cl2, MS 4 Å, ꢀ30 °C,
45 min, 78%; (b) (i) CAN, CH3CN–H2O (9:1, v/v), room temperature, 2 h; (ii) CCl3CN,
DBU, CH2Cl2, ꢀ10 °C, 1 h, 73%; (c) TMSOTf, CH2Cl2, ꢀ20 °C, 1 h, 75%.
O
C
RO
NPhth
24
25
: R = Ac
: R = H
b
3. Conclusion
Scheme 3. Reagents and conditions: (a) N-iodosuccinimide (NIS), TMSOTf, CH2Cl2,
MS 4 Å, ꢀ30 °C, 1 h, 88% for 22 and 84% for 24; (b) 0.01 M CH3ONa, CH3OH, 30 min,
room temperature, 95% for 23 and 94% for 25.
In conclusion, a convenient synthesis of a pentasaccharide as its
4-methoxyphenyl glycoside and a hexasaccharide as its 2-(4-

2146
R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
(C-1), 79.4 (C-4), 77.2 (PhCH2), 76.5 (PhCH2), 73.9 (C-2), 72.1 (C-3),
25 + 28
68.0 (C-5), 55.1 (OCH3), 25.1 (SCH2CH3), 20.9 (COCH3), 18.0 (CCH3),
14.9 (SCH2CH3); ESI-MS: m/z 483.2 [M+Na]+; Anal. Calcd for
a
C25H32O6S (460.19): C, 65.19; H, 7.00. Found: C, 65.0; H, 7.26.
O
OPMP
A
O
BnO
4.1.2. 4-Methoxyphenyl [2-O-acetyl-4-O-benzyl-2-O-(4-
methoxybenzyl)- -rhamnopyranosyl]-(1?3)-4,6-O-
benzylidene-2-deoxy-2-N-phthalimido-b- -glucopyranoside 9
BnO
a-L
O
D
B
O
To a solution of compound 3 (2.0 g, 3.97 mmol) and compound
4 (2.2 g, 4.78 mmol) in anhydrous CH2Cl2 (15 mL) was added MS
4 Å (3 g) and the reaction mixture was allowed to stir at room tem-
perature under argon for 30 min. The reaction mixture was cooled
to ꢀ40 °C and N-iodosuccinimide (NIS; 1.3 g, 5.77 mmol) followed
BnO
BnO
Ph
Ph
O
O
O
O
O
O
O
C
D
O
O
NPhth
NPhth
O
E
AcO
BnO
OAc
OAc
by TMSOTf (10 lL) was added to it. After stirring at same temper-
F
BnO
O
ature for 45 min, the reaction mixture was filtered through a Cel-
iteÒ bed and washed with CH2Cl2 (100 mL). The organic layer
was successively washed with 5% Na2S2O3, satd. NaHCO3, and
water, dried (Na2SO4), and concentrated under reduced pressure.
The crude product was purified over SiO2 using hexane–EtOAc
(6:1) as the eluant to give pure 9 (2.9 g, 81%). Colorless oil;
O
PMP: 4-methoxyphenyl
AcO
29
b
½
a 2D5
ꢂ
¼ þ22 (c 1.0, CHCl3); mmax (neat): 3020, 2361, 1718, 1508,
2
1385, 1216, 1099, 758 cmꢀ1 1H NMR (300 MHz, CDCl3): d 7.80–
;
7.07 (m, 14H, Ar-H), 6.78–6.62 (m, 8H, Ar-H), 5.69 (d, J = 8.4 Hz,
1H, H-1A), 5.49 (s, 1H, PhCH), 5.01 (dd, J = 9.4, 3.3 Hz, 1H, H-3B),
4.61 (t, J = 8.2 Hz each, 1H, H-3A), 4.50–4.35 (m, 6H, PhCH2, H-1B,
H-2A), 3.85–3.83 (m, 1H, H-5B), 3.84–3.62 (m, 4H, H-4A, H-5A, H-
Scheme 5. Reagents and conditions: (a) NIS, TMSOTf, CH2Cl2, MS 4 Å, ꢀ30 °C, 1 h,
76%; (b) (i) ethylenediamine, n-butanol, 90 °C, 5 h; (ii) acetic anhydride, pyridine,
room temperature, 2 h; (iii) H2, 20% Pd(OH)2–C, CH3OH, room temperature, 24 h;
(iv) 0.1 M CH3ONa, CH3OH, room temperature, 5 h, 66% in four steps.
6
abA), 3.72 (s, 3H, OCH3), 3.64 (s, 3H, OCH3), 3.46–3.45 (m, 1H, H-
methoxyphenoxy) ethyl glycoside corresponding to the O-antigen
of E. coli O150 has been achieved using sequential and [3+3] block
glycosylation strategies, respectively. All glycosylation reactions
were highly stereoselective and high yielding. A thioglycoside deriv-
ative has been successfully used as a glycosyl acceptor exploiting its
orthogonal behavior. The use of a [3+3] glycosylation made it possi-
ble to achieve the target hexasaccharide in a minimum number of
steps. 2-(4-Methoxyphenoxy) ethyl glycoside provides the option
to obtain the final hexasaccharide linked with an ethylene glycol
linkage, which is useful for its further transformation.
2B), 3.35 (t, J = 9.4 Hz each, H-4B), 1.74 (s, 3H, COCH3), 0.71 (d,
J = 6.2 Hz, 3H, CCH3); 13C NMR (75 MHz, CDCl3): d 169.5 (COCH3),
167.6, 167.5 (2CO, Phth), 159.1–113.5 (Ar-C), 101.8 (PhCH), 98.0
(C-1A), 97.7 (C-1B), 80.1 (C-4A), 78.9 (C-4B), 76.3 (C-2B), 74.1
(PhCH2), 73.2 (C-3B), 72.6 (C-3A), 72.1 (PhCH2), 68.6 (C-6A), 67.8
(C-5B), 66.6 (C-5A), 56.5 (C-2A), 55.3 (OCH3), 55.0 (OCH3), 20.8
(COCH3), 17.1 (CCH3); ESI-MS: m/z 924.3 [M+Na]+; Anal. Calcd for
C
51H51NO14 (901.33): C, 67.91; H, 5.70. Found: C, 67.70; H, 6.00.
4.1.3. 4-Methoxyphenyl [4-O-benzyl-2-O-(4-methoxybenzyl)-
-rhamnopyranosyl]-(1?3)-4,6-O-benzylidene-2-deoxy-2-N-
phthalimido-b- -glucopyranoside 10
a-
L
4. Experimental
D
A solution of compound 9 (2.8 g, 3.10 mmol) in 0.01 M CH3ONa
in CH3OH (30 mL) was allowed to stir at room temperature for
30 min. The reaction mixture was neutralized with Dowex 50 W
X8 (H+), filtered, and evaporated to dryness. The crude product
was passed through a short pad of SiO2 using hexane–EtOAc
(3:1) as the eluant to give pure compound 10 (2.6 g, 97%). Colorless
4.1. General methods
General methods are the same as reported earlier.11
4.1.1. Ethyl 3-O-acetyl-4-O-benzyl-2-O-(4-methoxybenzyl)-1-
thio-a-
L
-rhamnopyranoside 4
oil; ½a 2D5
ꢂ
¼ ꢀ11 (c 1.0, CHCl3);
mmax (neat): 3020, 2361, 1720, 1598,
To a solution of compound 8 (3.0 g, 10.05 mmol) in CH2Cl2
(20 mL) were added 4-methoxybenzyl chloride (1.5 mL, 11.06
mmol), 5% aq NaOH (10 mL), TBAB (200 mg) and the biphasic reac-
tion mixture was allowed to stir at room temperature for 5 h. The
reaction mixture was diluted with CH2Cl2 (100 mL) and washed
with water, dried (Na2SO4), and concentrated under reduced pres-
sure. A solution of the crude product in acetic anhydride–pyridine
(10 mL; 1:1 v/v) was kept at room temperature for 2 h and concen-
trated under reduced pressure. The crude product was purified over
SiO2 using hexane–EtOAc (5:1) as an eluant to give pure 4 (3.2 g,
1513, 1426, 1216, 1046, 928, 761 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 7.89–7.21 (m, 14H, Ar-H), 6.85–6.70 (m, 8H, Ar-H), 5.78 (d,
J = 8.4 Hz, 1H, H-1A), 5.53 (s, 1H, PhCH), 4.73–4.63 (m, 2H, H-3A,
H-1B), 4.53–4.38 (m, 5H, PhCH2, H-2A), 3.86–3.61 (m, 6H, H-4A,
H-5A, H-6abA, H-3B, H-5B), 3.76 (s, 3H, OCH3), 3.68 (s, 3H, OCH3),
3.36 (br s, 1H, H-2B), 3.02 (t, J = 9.4 Hz each, 1H, H-4B), 0.73 (d,
J = 6.2 Hz, 3H, CCH3); 13C NMR (75 MHz, CDCl3): d 167.6, 167.5
(2CO, Phth), 159.3–113.7 (Ar-C), 102.0 (PhCH), 98.0 (C-1A), 97.3
(C-1B), 81.9 (C-4A), 80.4 (C-4B), 79.0 (C-2B), 74.4 (PhCH2), 73.7 (C-
3B), 72.0 (PhCH2), 70.8 (C-3A), 68.6 (C-6A), 67.5 (C-5B), 66.7 (C-
5A), 56.6 (C-2A), 55.4 (OCH3), 55.0 (OCH3), 17.2 (CCH3); ESI-MS:
m/z 882.3 [M+Na]+; Anal. Calcd for C49H49NO13 (859.32): C,
68.44; H, 5.74. Found: C, 68.22; H, 5.92.
70%). Colorless oil; ½a D25
¼ ꢀ89 (c 1.0, CHCl3); mmax (neat): 3020,
ꢂ
1734, 1514, 1370, 1216, 1092, 761 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 7.30–7.22 (m, 7H, Ar-H), 6.85 (d, J = 8.6 Hz, 2H, Ar-H), 5.16 (d,
J = 1.5 Hz, 1H, H-1), 5.07 (dd, J = 9.4, 3.3 Hz, 1H, H-3), 4.69 (d,
J = 11.4 Hz, 1H, PhCH2), 4.62 (d, J = 11.4 Hz, 1H, PhCH2) 4.57 (d,
J = 11.8 Hz, 1H, PhCH2), 4.43 (d, J = 11.8 Hz, 1H, PhCH2), 4.09–4.05
(m, 1H, H-5), 3.91–3.89 (m, 1H, H-2), 3.80 (s, 3H, OCH3), 3.58 (t,
J = 9.4 Hz, 1H, H-4), 2.64–2.49 (m, 2H, SCH2CH3), 1.90 (s, 3H, COCH3),
1.31 (d, J = 6.2 Hz, 3H, CCH3), 1.27 (t, J = 7.4 Hz, 3H, SCH2CH3); 13C
NMR (75 MHz, CDCl3): d 169.7 (COCH3), 159.4–113.8 (Ar-C), 81.6
4.1.4. 4-Methoxyphenyl (2-O-acetyl-3,4-di-O-benzyl-
rhamnopyranosyl)-(1?3)-[4-O-benzyl-2-O-(4-methoxybenzyl)-
-rhamnopyranosyl]-(1?3)-4,6-O-benzylidene-2-deoxy-2-N-
phthalimido-b- -glucopyranoside 11
a-L-
a-L
D
To a solution of compound 10 (2.2 g, 2.56 mmol) and compound
5 (1.3 g, 3.02 mmol) in anhydrous CH2Cl2 (15 mL) was added MS

R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
2147
4 Å (3 g) and the reaction mixture was allowed to stir at room tem-
perature under argon for 30 min. The reaction mixture was cooled
4 Å (2 g) and the reaction mixture was allowed to stir at room tem-
perature under argon for 30 min. The reaction mixture was cooled
to ꢀ40 °C and NIS (0.8 g, 3.55 mmol) followed by TMSOTf (10
l
L)
to ꢀ40 °C and NIS (470 mg, 2.08 mmol) followed by TMSOTf (5
lL)
was added to it. After stirring at the same temperature for
45 min, the reaction mixture was filtered through a CeliteÒ bed
and washed with CH2Cl2 (100 mL). The organic layer was succes-
sively washed with 5% Na2S2O3, satd. NaHCO3, and water, dried
(Na2SO4), and concentrated under reduced pressure. The crude
product was purified over SiO2 using hexane–EtOAc (6:1) as the
was added to it. After stirring at the same temperature for 45 min,
the reaction mixture was filtered through a CeliteÒ bed and
washed with CH2Cl2 (100 mL). The organic layer was successively
washed with 5% Na2S2O3, satd. NaHCO3, and water, dried (Na2SO4),
and concentrated under reduced pressure. The crude product was
purified over SiO2 using hexane–EtOAc (6:1) as the eluant to give
eluant to give pure 11 (2.5 g, 80%). Colorless oil; ½a D25
ꢂ
¼ ꢀ9 (c 1.0,
pure 13 (1.8 g, 81%). Colorless oil; ½a D25
¼ ꢀ3 (c 1.0, CHCl3); mmax
ꢂ
CHCl3); mmax (neat): 3020, 2362, 1723, 1593, 1216, 1042, 762,
(neat): 3021, 2360, 1722, 1598, 1514, 1423, 1216, 1046,
670 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d 7.83–7.45 (m, 24H, Ar-
762 cmꢀ1 1H NMR (300 MHz, CDCl3): d 7.81–7.16 (m, 34H, Ar-
;
H), 7.30–7.21 (m, 8H, Ar-H), 6.60 (d, J = 8.4 Hz, 1H, H-1A), 5.54 (s,
1H, PhCH), 5.39 (br s, 1H, H-2C), 4.98 (br s, 1H, H-1C), 4.88 (d,
J = 11.0 Hz, 1H, PhCH2), 4.62–4.36 (m, 10H, H-1B, H-2A, PhCH2),
3.96–3.92 (m, 1H, H-5C), 3.84–3.65 (m, 8H, H-3A, H-3B, H-3C, H-
4A, H-5A, H-5B, H-6abA), 3.71 (s, 3H, OCH3), 3.65 (s, 3H, OCH3),
3.43–3.33 (m, 2H, H-4B, H-4C), 3.30 (br s, 1H, H-2B), 2.07 (s, 3H,
COCH3), 1.35 (d, J = 6.1 Hz, 3H, CCH3), 0.72 (d, J = 6.2 Hz, 3H,
CCH3); 13C NMR (75 MHz, CDCl3): d 169.6 (COCH3), 167.7, 167.6
(2CO, Phth), 158.9–113.3 (Ar-C), 102.0 (PhCH), 99.1 (C-1C), 97.9
(C-1A), 97.7 (C-1B), 80.6 (C-4A), 80.2 (C-4B), 80.0 (C-4C), 78.9 (C-
2C), 78.0 (C-2B), 76.7 (C-3C), 75.1 (PhCH2), 74.8 (PhCH2), 74.4 (C-
3B), 71.9 (PhCH2), 71.6 (PhCH2), 68.8 (C-3A), 68.6 (C-6A), 68.3 (C-
5A), 68.2 (C-5B), 66.7 (C-5C), 56.5 (C-2A), 55.3 (OCH3), 54.9
(OCH3), 20.8 (COCH3), 17.9 (CCH3), 17.1 (CCH3); ESI-MS: m/z
1250.4 [M+Na]+; Anal. Calcd for C71H73NO18 (1227.48): C, 69.42;
H, 5.99. Found: C, 69.18; H, 6.25.
H), 6.85–6.80 (m, 4H, Ar-H), 6.70 (d, J = 9.1 Hz, 2H, Ar-H), 6.62 (d,
J = 9.2 Hz, 2H, Ar-H), 5.84 (d, J = 8.4 Hz, 1H, H-1A), 5.55 (s, 1H,
PhCH), 5.44 (s, 1H, H-2D), 4.92 (br s, 1H, H-1C), 4.89 (d,
J = 11.0 Hz, 1H, PhCH2), 4.84 (d, J = 11.2 Hz, 1H, PhCH2), 4.82 (br s,
1H, H-1D), 4.71 (d, J = 11.1 Hz, 1H, PhCH2), 4.65–4.32 (m, 12H, H-
1B, H-2A, H-3A, PhCH2), 3.92–3.60 (m, 11H, H-2C, H-3B, H-3C, H-
3D, H-4A, H-5A, H-5B, H-5C, H-5D, H-6abA), 3.75 (s, 3H, OCH3), 3.64
(s, 3H, OCH3), 3.43–3.21 (m, 4H, H-2B, H-4B, H-4C, H-4D), 2.11 (s,
3H, COCH3), 1.25 (d, J = 6.0 Hz, 3H, CCH3), 1.13 (d, J = 6.2 Hz, 3H,
CCH3), 0.64 (d, J = 6.1 Hz, 3H, CCH3); 13C NMR (75 MHz, CDCl3): d
169.6 (COCH3), 167.8, 167.7 (2CO, Phth), 158.9–113.4 (Ar-C),
101.8 (PhCH), 100.2 (C-1C), 98.9 (C-1D), 97.9 (C-1A), 97.4 (C-1B),
80.2 (2C, C-4A, C-4B), 80.0 (2C, C-2B, C-4C), 79.6 (C-2D), 79.1 (C-
2C), 77.4 (2C, C-3C, C-4D), 75.1 (PhCH2), 74.9 (PhCH2), 74.8 (PhCH2),
74.6 (C-3D), 74.4 (C-3B), 71.9 (PhCH2), 71.6 (PhCH2), 71.5 (PhCH2),
68.8 (C-3A), 68.5 (C-6A), 68.3 (2C, C-5A, C-5B), 68.2 (C-5D), 66.6
(C-5C), 56.4 (C-2A), 55.3 (OCH3), 54.8 (OCH3), 20.9 (COCH3), 17.9
(CCH3), 17.8 (CCH3), 17.1 (CCH3); ESI-MS: m/z 1576.6 [M+Na]+;
Anal. Calcd for C91H95NO22 (1553.63): C, 70.30; H, 6.16. Found: C,
70.10; H, 6.40.
4.1.5. 4-Methoxyphenyl (3,4-di-O-benzyl-a-L-rhamnopyranosyl)-
(1?3)-[4-O-benzyl-2-O-(4-methoxybenzyl)-a-L-rhamnopyranosyl]-
(1?3)-4,6-O-benzylidene-2-deoxy-2-N-phthalimido-b-D-gluco-
pyranoside 12
4.1.7. 4-Methoxyphenyl (3,4-di-O-benzyl-
(1?2)-(3,4-di-O-benzyl- -rhamnopyranosyl)-(1?3)-[4-O-ben-
zyl-2-O-(4-methoxybenzyl)- -rhamnopyranosyl]-(1?3)-4,6-O-
benzylidene-2-deoxy-2-N-phthalimido-b- -glucopyranoside 14
a-L-rhamnopyranosyl)-
A solution of compound 11 (2.0 g, 1.63 mmol) in 0.01 M CH3O-
Na in CH3OH (25 mL) was allowed to stir at room temperature for
30 min. The reaction mixture was neutralized with Dowex 50 W
X8 (H+), filtered, and evaporated to dryness. The crude product
was passed through a short pad of SiO2 using hexane–EtOAc
(3:1) as the eluant to give pure compound 12 (1.9 g, 98%). Colorless
a-L
a-L
D
A solution of compound 13 (1.5 g, 0.96 mmol) in 0.01 M CH3O-
Na in CH3OH (20 mL) was allowed to stir at room temperature for
30 min. The reaction mixture was neutralized with Dowex 50 W
X8 (H+), filtered, and evaporated to dryness. The crude product
was passed through a short pad of SiO2 using hexane–EtOAc
(3:1) as the eluant to give pure compound 14 (1.3 g, 90%). Colorless
oil; ½a 2D5
ꢂ
¼ þ29 (c 1.0, CHCl3);
m
max (neat): 3020, 2359, 1719, 1512,
1425, 1216, 1403, 761 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d 7.83–
7.18 (m, 24H, Ar-H), 6.83–6.62 (m, 8H, Ar-H), 5.78 (d, J = 8.2 Hz,
1H, H-1A), 5.55 (s, 1H, PhCH), 5.01 (s, 1H, H-1C). 4.84 (d,
J = 11.1 Hz, 1H, PhCH2), 4.64–4.60 (m, 10H, H-1B, H-2A, PhCH2),
3.94–3.90 (m, 1H, H-5C), 3.85–3.65 (m, 9H, H-2C, H-3A, H-3B, H-
3C, H-4A, H-5A, H-5B, H-6abA), 3.70 (s, 3H, OCH3), 3.66 (s, 3H,
OCH3), 3.43–3.25 (m, 3H, H-2B, H-4B, H-4C), 1.29 (d, J = 6.2 Hz,
3H, CCH3), 0.72 (d, J = 6.1 Hz, 3H, CCH3); 13C NMR (75 MHz, CDCl3):
d 167.7, 167.6 (2CO, Phth), 158.9–113.5 (Ar-C), 101.8 (PhCH), 100.7
(C-1C), 97.9 (C-1A), 97.7 (C-1B), 80.6 (C-4A), 80.2 (C-4B), 80.0 (C-4C),
79.9 (C-2B), 78.8 (C-2C), 77.0(C-3C), 75.0 (PhCH2), 74.8 (PhCH2),
74.4 (C-3B), 71.8 (2C, 2PhCH2), 68.7 (C-3A), 68.5 (C-6A), 68.3 (C-
5A), 67.9 (C-5B), 66.6 (C-5C), 56.5 (C-2A), 55.3 (OCH3), 54.9
(OCH3), 17.8 (CCH3), 17.1 (CCH3); ESI-MS: m/z 1208.4 [M+Na]+;
Anal. Calcd for C69H71NO17 (1185.47): C, 69.86; H, 6.03. Found: C,
69.67; H, 6.30.
oil; ½a 2D5
ꢂ
¼ þ4 (c 1.0, CHCl3); mmax (neat): 3020, 2361, 1717, 1610,
1509, 1216, 1098, 1404, 761 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d
7.81–7.16 (m, 34H, Ar-H), 6.85–6.80 (m, 4H, Ar-H), 6.70 (d,
J = 9.1 Hz, 2H, Ar-H), 6.61 (d, J = 9.1 Hz, 2H, Ar-H), 5.79 (d,
J = 8.4 Hz, 1H, H-1A), 5.55 (s, 1H, PhCH), 4.98–4.94 (m, 4H, H-1C,
H-1D, PhCH2), 4.85 (2 d, J = 10.9 Hz each, 2H, PhCH2), 4.69 (br s,
2H, PhCH2), 4.61 (br s, 1H, H-1B), 4.58–4.30 (m, 10H, H-2A, H-
3A, PhCH2), 4.08–4.05 (m, 1H, H-2D), 3.87–3.61 (m, 11H, H-2C,
H-3B, H-3C, H-3D, H-4A, H-5A, H-5B, H-5C, H-5D, H-6abA), 3.72 (s,
3H, OCH3), 3.66 (s, 3H, OCH3), 3.43–3.23 (m, 4H, H-2B, H-4B, H-
4C, H-4D), 1.29 (d, J = 6.1 Hz, 3H, CCH3), 1.11 (d, J = 6.1 Hz, 3H,
CCH3), 0.63 (d, J = 6.1 Hz, 3H, CCH3); 13C NMR (75 MHz, CDCl3):
167.8, 167.7 (2CO, Phth), 158.9–113.4 (Ar-C), 101.9 (PhCH),
100.5 (2C, C-1C, C-1D), 98.0 (C-1A), 97.6 (C-1B), 80.3 (C-4A), 80.2
(2C, C-4C, C-4B), 80.0 (C-2B), 79.7 (C-2D), 79.4 (2C, C-2C, C-3C),
79.1 (2C, C-4D), 78.8 (PhCH2), 75.2 (PhCH2), 74.8 (PhCH2), 74.7
(C-3D), 74.4 (C-3B), 72.2 (PhCH2), 72.0 (PhCH2), 71.7 (PhCH2),
68.6 (2C, C-3A, C-5A), 68.4 (2C, C-5B, C-6A), 67.9 (C-5D), 66.7 (C-
5C), 56.5 (C-2A), 55.4 (OCH3), 54.9 (OCH3), 18.0 (CCH3), 17.8
(CCH3), 17.1 (CCH3); ESI-MS: m/z 1534.6 [M+Na]+; Anal. Calcd
for C89H93NO21 (1511.62): C, 70.67; H, 6.20. Found: C, 70.84; H,
6.42.
4.1.6. 4-Methoxyphenyl (2-O-acetyl-3,4-di-O-benzyl-
pyranosyl)-(1?2)-(3,4-di-O-benzyl- -rhamnopyranosyl)-(1?3)-
[4-O-benzyl-2-O-(4-methoxybenzyl)- -rhamnopyranosyl]-(1?3)-
4,6-O-benzylidene-2-deoxy-2-N-phthalimido-b-D-glucopyrano-
side 13
a-L-rhamno-
a
a
-L
-L
To a solution of compound 12 (1.7 g, 1.43 mmol) and compound
5 (750 mg, 1.74 mmol) in anhydrous CH2Cl2 (10 mL) was added MS

2148
R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
4.1.8. 4-Methoxyphenyl (3-O-acetyl-4,6-O-benzylidene-2-
deoxy-2-N-phthalimido-b- -glucopyranosyl-(1?2)-(3,4-di-O-
benzyl- -rhamnopyranosyl)-(1?2)-(3,4-di-O-benzyl-
rhamnopyranosyl)-(1?3)-[4-O-benzyl-2-O-(4-methoxybenzyl)-
-rhamnopyranosyl]-(1?3)-4,6-O-benzylidene-2-deoxy-2-N-
phthalimido-b- -glucopyranoside 15
To a solution of compound 14 (1.0 g, 0.66 mmol) and compound
6 (380 mg, 0.78 mmol) in anhydrous CH2Cl2 (5 mL) was added MS
4 Å (1 g) and the reaction mixture was allowed to stir at room tem-
perature under argon for 30 min. The reaction mixture was cooled
CCH3), 1.06 (d, J = 6.1 Hz, 3H, CCH3), 0.65 (d, J = 6.2 Hz, 3H, CCH3);
13C NMR (75 MHz, CDCl3): d 169.7 (COCH3), 167.8, 167.7 (4CO,
2Phth), 155.5–114.4 (Ar-C), 101.8 (PhCH), 101.5 (PhCH), 100.8 (C-
1C), 100.5 (C-1D), 100.4 (C-1E), 99.5 (C-1B), 98.0 (C-1A), 80.5 (C-
4A), 80.4 (C-4E), 80.3 (C-4B), 79.8 (C-4C), 79.1 (2C, C-2B, C-3C),
79.0 (C-2D), 78.9 (C-4D), 75.8 (C-3D), 75.4 (PhCH2), 74.8 (PhCH2),
74.7 (PhCH2), 74.2 (C-3B), 72.5 (PhCH2), 71.8 (PhCH2), 70.9 (C-3E),
69.3 (C-3A), 68.6 (2C, C-5A, C-5E), 68.4 (C-6A), 68.3 (C-6E), 67.9 (C-
5B), 66.5 (C-5D), 65.7 (C-5C), 56.2 (C-2A), 55.3 (OCH3), 55.2 (C-2E),
20.5 (COCH3), 17.8 (CCH3), 17.6 (CCH3), 17.1 (CCH3); MALDI-MS:
m/z 1835.6 [M+Na]+; Anal. Calcd for C104H104N2O27 (1812.68): C,
68.86; H, 5.78. Found: C, 68.64; H, 6.05.
D
a-
L
a-L-
a-L
D
to ꢀ40 °C and NIS (200 mg, 8.44 mmol) followed by TMSOTf (3
lL)
was added to it. After stirring at the same temperature for 45 min,
the reaction mixture was filtered through a CeliteÒ bed and
washed with CH2Cl2 (50 mL). The organic layer was successively
washed with 5% Na2S2O3, satd. NaHCO3, and water, dried (Na2SO4),
and concentrated under reduced pressure. The crude product was
purified over SiO2 using hexane–EtOAc (6:1) as the eluant to give
4.1.10. 2-(4-Methoxyphenoxy) ethyl 2,3,4-tri-O-acetyl-a-L-
rhamnopyranoside 20
To a well-stirred solution of L-rhamnose monohydrate (5.0 g,
27.45 mmol) in acetic anhydride (30 mL, 317.65 mmol) was added
HClO4-SiO2 (500 mg) and the reaction mixture was allowed to stir
at room temperature for 10 min. The reaction mixture was poured
into ice-water and extracted with CH2Cl2 (200 mL). The organic
layer was washed with satd. NaHCO3 and water, dried (Na2SO4),
and concentrated under reduced pressure to give 1,2,3,4-tetra-O-
pure 15 (910 mg, 71%). Colorless oil; ½a D25
ꢂ
¼ ꢀ5 (c 1.0, CHCl3); mmax
(neat): 3021, 2359, 1520, 1425, 1216, 1403, 928, 764 cmꢀ1
;
1H
NMR (300 MHz, CDCl3): d 7.76–7.07 (m, 43H, Ar-H), 7.06–6.77
(m, 4H, Ar-H), 6.80 (d, J = 9.1 Hz, 2H, Ar-H), 6.78 (d, J = 9.0 Hz, 2H,
Ar-H), 6.02 (t, J = 9.9 Hz, 1H, H-3E), 5.76 (d, J = 8.4 Hz, 1H, H-1A),
5.54 (s, 1H, PhCH), 5.42 (s, 1H, PhCH), 5.40 (d, J = 8.3 Hz, 1H, H-
1E), 4.82–4.80 (m, 2H, H-1C, H-1D), 4.74 (d, J = 11.1 Hz, PhCH2),
5.44–4.25 (m, 12H, H-1B, H-2A, H-2E, PhCH2), 4.25–4.01 (m, 2H,
PhCH2), 4.15–3.44 (m, 17H, H-2C, H-2D, H-3A, H-3B, H-3C, H-3D,
H-4A, H-4E, H-5A, H-5B, H-5C, H-5D, H-5E, H-6abA, H-6abE), 3.70 (s,
3H, OCH3), 3.64 (s, 3H, OCH3), 3.27–2.94 (m, 4H, H-2B, H-4B, H-
4C, H-4D), 1.93 (s, 3H, COCH3), 1.20 (d, J = 6.0 Hz, 3H, CCH3), 1.02
(d, J = 6.1 Hz, 3H, CCH3), 0.61 (d, J = 6.0 Hz, 3H, CCH3); 13C NMR
(75 MHz, CDCl3): d 169.5 (COCH3), 167.8, 167.7 (4CO, 2Phth),
158.9–113.4 (Ar-C), 101.8 (PhCH), 101.5 (PhCH), 100.8 (2C, C-1C,
C-1D), 100.4 (C-1E), 98.0 (C-1A), 97.6 (C-1B), 80.5 (2C, C-4A, C-4E),
80.2 (2C, C-4B, C-4C), 79.1 (2C, C-2B, C-2D), 78.9 (C-4D), 78.7 (C-
2C), 77.6 (C-3C), 77.4 (C-3B), 75.8 (C-3D), 74.9 (PhCH2), 74.7 (PhCH2),
74.4 (C-3E), 72.5 (PhCH2), 71.8 (PhCH2), 71.7 (PhCH2), 69.3 (C-3A),
68.5 (2C, C-5A, C-6A), 68.3 (2C, C-5E, C-6E), 68.2 (C-5B), 66.7 (C-
5D), 65.6 (C-5C), 56.5 (C-2A), 55.3 (OCH3), 55.2 (C-2E), 54.9
(OCH3), 20.5 (COCH3), 18.0 (CCH3), 17.5 (CCH3), 17.3 (CCH3); MAL-
DI-MS: m/z 1955.7 [M+Na]+; Anal. Calcd for C112H112N2O28
(1932.74): C, 69.55; H, 5.84. Found: C, 69.36; H, 6.10.
acetyl-
a
/b-
L-rhamnopyranose (9.0 g), which was used directly for
the next step. To a solution of 1,2,3,4-tetra-O-acetyl-
a
/b- -rhamno-
L
pyranose (8.0 g, 24.07 mmol) in anhydrous CH2Cl2 (80 mL) were
added 2-(4-methoxyphenoxy) ethanol (8.0 g, 47.57 mmol) and
BF3ꢁOEt2 (6.0 mL, 48.61 mmol) and the reaction mixture was al-
lowed to stir at room temperature for 18 h. The reaction mixture
was poured into ice-water and extracted with CH2Cl2 (150 mL).
The organic layer was washed with satd. NaHCO3 and water, dried
(Na2SO4), and concentrated under reduced pressure. The crude
product was purified over SiO2 using hexane–EtOAc (5:1) as the
eluant to give pure 20 (9.2 g, 87%). Colorless oil; ½a D25
¼ ꢀ53 (c
ꢂ
1.0, CHCl3); mmax (neat): 2937, 1747, 1508, 1371, 1228, 1088,
1050, 827, 757 cmꢀ1 1H NMR (500 MHz, CDCl3): d 6.86–6.82 (m,
;
4H, Ar-H), 5.31–5.27 (m, 2H, H-2, H-3), 5.06 (t, J = 9.8 H33z, 1H,
H-4), 4.83 (d, J = 1.5 Hz, 1H, H-1), 4.11–4.09 (m, 2H, OCH2a),
3.99–3.93 (m, 2H, OCH2b), 3.85–3.81 (m, 1H, H-5), 3.76 (s, 3H,
OCH3), 2.15 (s, 3H, COCH3), 2.04 (s, 3H, COCH3), 1.98 (s, 3H, COCH3),
1.21 (d, J = 6.3 Hz, 3H, CCH3); 13C NMR (125 MHz, CDCl3): d 170.5
(COCH3), 170.4 (COCH3), 170.3 (COCH3), 154.5–115.0 (Ar-C), 98.0
(C-1), 71.5 (C-4), 70.2 (C-3), 69.4 (C-2), 67.9 (C-5), 66.9 (OCH2),
66.8 (OCH2), 56.1 (OCH3), 21.3 (COCH3), 21.2 (COCH3), 21.1
(COCH3), 17.7 (CCH3); ESI-MS: m/z 463.1 [M+Na]+; Anal. Calcd for
4.1.9. 4-Methoxyphenyl (3-O-acetyl-4,6-O-benzylidene-2-
deoxy-2-N-phthalimido-b-
benzyl- -rhamnopyranosyl)-(1?2)-(3,4-di-O-benzyl-
rhamnopyranosyl)-(1?3)-(4-O-benzyl- -rhamnopyranosyl)-
D-glucopyranosyl-(1?2)-(3,4-di-O-
a-
L
a
-L
-
C21H28O10 (440.17): C, 57.27; H, 6.41. Found: C, 57.04; H, 6.60.
a-L
(1?3)-4,6-O-benzylidene-2-deoxy-2-N-phthalimido-b-
D
-
4.1.11. 2-(4-Methoxyphenoxy) ethyl 2,3-O-isopropylidene-a-L-
glucopyranoside 16
rhamnopyranoside 21
To a solution of compound 15 (900 mg, 0.46 mmol) in CH2Cl2
(10 mL) was added DDQ (200 mg, 0.88 mmol) in H2O (5 mL) and
the reaction mixture was allowed to stir at room temperature for
2 h. The reaction mixture was diluted with CH2Cl2 (50 mL) and
washed with satd. NaHCO3, and water, dried (Na2SO4), and concen-
trated. The crude product was purified over SiO2 using hexane–
EtOAc (4:1) as the eluant to give pure 16 (580 mg, 70%). Colorless
A solution of compound 20 (8.0 g, 18.16 mmol) in 0.1 M CH3O-
Na in CH3OH (100 mL) was allowed to stir at room temperature for
3 h. The reaction mixture was neutralized with Dowex 50 W X8
(H+) resin, filtered, and concentrated. To a solution of the deacety-
lated product (5.7 g, 18.13 mmol) in dry DMF (15 mL) were added
2,2-dimethoxypropane (6.0 mL, 48.8 mmol) and p-toluenesulfonic
acid (200 mg) and the reaction mixture was allowed to stir at room
temperature for 10 h. The reaction was quenched with Et3N
(1.0 mL) and the solvents were removed under reduced pressure.
The crude product was purified over SiO2 using hexane–EtOAc
(3:1) as the eluant to give pure 21 (5.8 g, 90%). Colorless oil;
oil; ½a 2D5
ꢂ
¼ ꢀ18 (c 1.0, CHCl3);
m
max (neat): 2928, 2361, 1718, 1630,
1386, 1225, 1098, 768 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d 7.80–
7.05 (m, 43H, Ar-H), 6.77 (d, J = 9.0 Hz, 2H, Ar-H), 6.69 (d,
J = 9.2 Hz, 2H, Ar-H), 6.01 (t, J = 9.9 Hz, 1H, H-3E), 5.72 (d,
J = 8.2 Hz, H-1A), 5.52 (s, 1H, PhCH), 5.43 (s, 1H, PhCH), 5.41 (d,
J = 8.2 Hz, 1H, H-1E), 4.83 (br s, 1H, H-1C), 4.80 (br s, 1H, H-1D),
4.74 (d, J = 10.8 Hz, 1H, PhCH2), 4.61–4.26 (m, 12H, H-1B, H-2A,
H-2E, H-3A, PhCH2), 4.09–4.02 (m, 2H, H-5C, PhCH2), 3.93–3.46
(m, 16H, H-2B, H-2C, H-2D, H-3B, H-3C, H-3D, H-4A, H-4E, H-5A, H-
5B, H-5D, H-5E, H-6abA, H-6abE), 3.69 (s, 3H, OCH3), 3.21–2.94 (m,
3H, H-4B, H-4C, H-4D), 1.94 (s, 3H, COCH3), 1.16 (d, J = 6.1 Hz, 3H,
½
a 2D5
ꢂ
¼ ꢀ27 (c 1.0, CHCl3); mmax (neat): 2936, 1639, 1509, 1456,
1383, 1230, 1096, 1053, 924, 858 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d 6.86–6.81 (m, 4H, Ar-H), 5.04 (br s, 1H, H-1), 4.19–4.17 (m, 1H,
OCH2a), 4.11–4.06 (m, 3H, H-2, H-3, OCH2a), 4.02–3.98 (m, 1H,
OCH2b), 3.83–3.79 (m, 1H, OCH2b), 3.76 (s, 3H, OCH3), 3.75–3.70
(m, 1H, H-4), 3.42–3.38 (m, 1H, H-5), 1.52 (s, 3H, CH3), 1.34 (s,
3H, CH3), 1.28 (d, J = 6.2 Hz, 3H, CCH3); 13C NMR (125 MHz, CDCl3):

R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
2149
d 154.4–115.0 (Ar-C), 109.8 [C(OCH3)2], 97.7 (C-1), 78.6 (C-4), 76.0
(C-3), 74.6 (C-2), 68.0 (OCH2), 66.5 (C-5), 66.3 (OCH2), 56.1 (OCH3),
28.3 (CH3), 26.4 (CH3), 17.9 (CCH3); ESI-MS: m/z 377.1 [M+Na]+;
Anal. Calcd for C18H26O7 (354.17): C, 61.00; H, 7.39. Found: C,
60.78; H, 7.60.
2OCH2a), 3.86 (dd, J = 9.4 Hz, 3.3 Hz, 1H, H-3A), 3.85–3.80 (m, 1H,
OCH2b), 3.76 (dd, J = 9.4 Hz, 3.0 Hz, 1H, H-3A), 3.74–3.69 (m, 1H,
H-5A), 3.68–3.61 (m, 2H, H-5B, OCH2b), 3.66 (s, 3H, OCH3), 3.31 (2
t, J = 9.5 Hz each, 2H, H-4A, H-4B), 2.04 (s, 3H, COCH3), 1.22 (d,
J = 6.2 Hz, 3H, CCH3), 1.21 (d, J = 6.2 Hz, 3H, CCH3); 13C NMR
(125 MHz, CDCl3): d 170.2 (COCH3), 154.4–115.0 (Ar-C), 99.6 (C-
1A), 99.3 (C-1B), 80.4 (C-4A), 80.3 (C-4B), 80.2 (C-3B), 78.0 (C-3A),
75.8 (PhCH2), 75.6 (PhCH2), 74.6 (C-2A), 72.4 (PhCH2), 72.1 (PhCH2),
69.2 (C-2B), 68.6 (C-5A), 68.4 (C-5B), 68.1 (OCH2), 66.2 (OCH2), 56.0
(OCH3), 21.4 (COCH3), 18.4 (2C, CCH3); ESI-MS: m/z 885.3 [M+Na]+;
Anal. Calcd for C51H58O12 (862.39): C, 70.98; H, 6.77. Found: C,
70.75; H, 7.00.
4.1.12. 2-(4-Methoxyphenoxy) ethyl 3,4-di-O-benzyl-a-L-
rhamnopyranoside 17
To a solution of compound 21 (5.0 g, 14.11 mmol) in THF
(15 mL) were added powdered solid NaOH (1.8 g, 45.0 mmol), tet-
rabutylammonium bromide (TBAB, 200 mg, 0.62 mmol), and ben-
zyl bromide (3.5 mL, 29.42 mmol) and the reaction mixture was
allowed to stir at room temperature for 1 h. The reaction mixture
was poured into satd. NH4Cl solution and extracted with CH2Cl2
(100 mL). The organic layer was washed with water, dried
(Na2SO4), and concentrated. A solution of the benzylated product
in 80% aq AcOH (100 mL) was allowed to stir at 80 °C for 1.5 h
and the solvents were removed under reduced pressure. To a solu-
tion of the crude product (5.0 g, 12.36 mmol) in anhydrous CH3OH
(100 mL) was added dibutyltin oxide (4.5 g, 18.07 mmol) and the
reaction mixture was allowed to stir at 80 °C for 2 h. The solvents
were removed under reduced pressure and the crude product was
dissolved in dry DMF (15 mL). To the reaction mixture were added
benzyl bromide (3.0 mL, 25.22 mmol) and TBAB (500 mg,
1.55 mmol) and the reaction mixture was allowed to stir at 60 °C
for 10 h. The reaction mixture was poured into satd. NH4Cl and ex-
tracted with EtOAc (mL). The organic layer was washed with water,
dried (Na2SO4), and evaporated to dryness. The crude product was
purified over SiO2 using hexane–EtOAc (4:1) as the eluant to give
4.1.14. 2-(4-Methoxyphenoxy) ethyl (3,4-di-O-benzyl-
a-L-rham-
nopyranosyl)-(1?2)-3,4-di-O-benzyl- -rhamnopyranoside 23
a-L
A solution of compound 22 (4.0 g, 4.63 mmol) in 0.01 M CH3O-
Na in CH3OH (20 mL) was allowed to stir at room temperature for
30 min. The reaction mixture was neutralized with Dowex 50 W
X8 (H+), filtered, and evaporated to dryness. The crude product
was passed through a short pad of SiO2 using hexane–EtOAc
(3:1) as the eluant to give pure compound 23 (3.6 g, 95%). Colorless
oil; ½a 2D5
ꢂ
¼ ꢀ26 (c 1.0, CHCl3);
m
max (neat): 3466, 3011, 2911, 1509,
1454, 1360, 1235, 1055, 981, 920, 828, 753 cmꢀ1
;
1H NMR
(500 MHz, CDCl3): d 7.34–7.26 (m, 20H, Ar-H), 6.81 (d, J = 9.2 Hz,
2H, Ar-H), 6.78 (d, J = 9.1 Hz, 2H, Ar-H), 5.05 (br s, 1H, H-1A),
4.87–4.84 (m, 2H, PhCH2), 4.80 (br s, 1H, H-1B), 4.69–4.57 (m,
6H, PhCH2), 4.10–4.09 (m, 1H, H-2B), 4.04–4.01 (m, 3H, H-2A,
2OCH2a), 3.92–3.88 (m, 1H, OCH2b), 3.87–3.82 (m, 2H, H-3A, H-
3B), 3.80–3.78 (m, 1H, H-5A), 3.76–3.70 (m, 2H, H-5B, OCH2b),
3.72 (s, 3H, OCH3), 3.45 (t, J = 9.3 Hz, 1H, H-4A), 3.37 (t, J = 9.3 Hz,
1H, H-4B), 1.28, 1.27 (2 d, J = 6.2 Hz each, 6H, 2CCH3); 13C NMR
(125 MHz, CDCl3): d 154.4–115.0 (Ar-C), 101.1 (C-1A), 99.5 (C-1B),
80.7 (C-4A), 80.4 (C-4B), 80.2 (C-3A), 80.0 (C-3B), 75.7 (PhCH2),
75.6 (PhCH2), 74.8 (C-2A), 72.7 (PhCH2), 72.5 (PhCH2), 69.1 (C-2B),
68.4 (C-5A), 68.3 (C-5B), 68.2 (OCH2), 66.3 (OCH2), 56.0 (OCH3),
18.5 (CCH3), 18.3 (CCH3); ESI-MS: m/z 843.3 [M+Na]+; Anal. Calcd
for C49H56O11 (820.38): C, 71.69; H, 6.88. Found: C, 71.46; H, 7.10.
pure 17 (5.5 g, 79%). Colorless oil; ½a D25
¼ ꢀ35 (c 1.0, CHCl3); mmax
ꢂ
(neat): 2931, 2876, 1508, 1454, 1364, 1232, 1109, 1075, 1042,
985, 827, 746 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.25–7.20 (m,
;
10H, Ar-H), 6.77–6.72 (m, 4H, Ar-H), 4.82 (d, J = 1.2 Hz, 1H, H-1),
4.78 (d, J = 10.9 Hz, 1H, PhCH2), 4.58 (br s, 2H, 2PhCH2), 4.54 (d,
J = 11.0 Hz, 1H, PhCH2), 3.99–3.96 (m, 3H, H-2, H-3, H-5), 3.87–
3.83 (m, 1H, OCH2a), 3.78–3.75 (m, 1H, OCH2a), 3.74–3.66 (m, 2H,
2OCH2b), 3.66 (s, 3H, OCH3), 3.37 (t, J = 9.4 Hz, 1H, H-4), 1.22 (d,
J = 6.2 Hz, 3H, CCH3); 13C NMR (125 MHz, CDCl3): d 154.4–115.0
(Ar-C), 99.6 (C-1), 80.4 (C-4), 80.3 (C-3), 75.7 (PhCH2), 72.4 (PhCH2),
68.8 (C-2), 68.1 (OCH2), 67.8 (C-5), 66.4 (OCH2), 56.1 (OCH3), 18.3
(CCH3); ESI-MS: m/z 517.2 [M+Na]+; Anal. Calcd for C29H34O7
(494.23): C, 70.43; H, 6.93. Found: C, 70.25; H, 7.18.
4.1.15. 2-(4-Methoxyphenoxy) ethyl (3-O-acetyl-4,6-O-benzyli-
dene-2-deoxy-2-N-phthalimido-b-
di-O-benzyl- -rhamnopyranosyl)-(1?2)-3,4-di-O-benzyl-
rhamnopyranoside 24
D-glucopyranosyl-(1?2)-(3,4-
a-L
a-L-
To a solution of compound 23 (3.0 g, 3.65 mmol) and compound
6 (2.1 g, 4.34 mmol) in anhydrous CH2Cl2 (20 mL) was added MS
4 Å (3 g) and the reaction mixture was allowed to stir at room tem-
perature under argon for 30 min. The reaction mixture was cooled
4.1.13. 2-(4-Methoxyphenoxy) ethyl (2-O-acetyl-3,4-di-O-
benzyl-a-L-rhamnopyranosyl)-(1?2)-3,4-di-O-benzyl-a-L-
rhamnopyranoside 22
To a solution of compound 17 (3.0 g, 6.06 mmol) and compound
5 (3.1 g, 7.2 mmol) in anhydrous CH2Cl2 (25 mL) was added MS 4 Å
(5 g) and the reaction mixture was allowed to stir at room temper-
ature under argon for 30 min. The reaction mixture was cooled to
ꢀ30 °C and N-iodosuccinimide (NIS; 1.9 g, 8.44 mmol) followed by
to ꢀ30 °C and NIS (1.2 g, 5.33 mmol) followed by TMSOTf (20
lL)
was added to it. After stirring at the same temperature for 1 h,
the reaction mixture was filtered through a CeliteÒ bed and
washed with CH2Cl2 (100 mL). The organic layer was successively
washed with 5% Na2S2O3, satd. NaHCO3, and water, dried (Na2SO4),
and concentrated under reduced pressure. The crude product was
purified over SiO2 using hexane–EtOAc (4:1) as the eluant to give
TMSOTf (20 lL) was added to it. After stirring at the same temper-
ature for 1 h, the reaction mixture was filtered through a CeliteÒ
bed and washed with CH2Cl2 (100 mL). The organic layer was suc-
cessively washed with 5% Na2S2O3, satd. NaHCO3, and water, dried
(Na2SO4), and concentrated under reduced pressure. The crude
product was purified over SiO2 using hexane–EtOAc (6:1) as the
pure 24 (3.8 g, 84%). Colorless oil; ½a D25
¼ ꢀ11 (c 1.0, CHCl3); mmax
ꢂ
(neat): 2932, 1776, 1746, 1718, 1508, 1388, 1229, 1104, 1081,
1050, 1029, 998, 827, 738, 722 cmꢀ1 1H NMR (500 MHz, CDCl3):
;
d 7.42–7.08 (m, 29H, Ar-H), 6.79–6.78 (m, 4H, Ar-H), 6.03 (t,
J = 9.3 Hz each, 1H, H-3C), 5.43 (s, 1H, PhCH), 5.38 (d, J = 8.3 Hz,
1H, H-1C), 4.87 (br s, 1H, H-1A), 4.73 (d, J = 10.8 Hz, 1H, PhCH2),
4.66 (br s, 1H, H-1B), 4.58 (br s, 2H, PhCH2), 4.50 (d, J = 10.8 Hz,
1H, PhCH2)3333, 4.38 (dd, J = 8.4 Hz each, 1H, H-2C), 4.29 (d,
J = 11.2 Hz, 1H, PhCH2), 4.08–4.03 (m, 2H, PhCH2), 3.99–3.94 (m,
3H, H-2A, H-2B, PhCH2), 3.85–3.83 (m, 3H, H-6abC, OCH2a), 3.73–
3.58 (m, 7H, H-3A, H-3B, H-5A, H-5B, OCH2a, 2OCH2b), 3.72 (s, 3H,
OCH3), 3.52 (t, J = 10.2 Hz each, 1H, H-4C), 3.49–3.47 (m, 1H, H-
5C), 3.11 (t, J = 9.3 Hz each, 1H, H-4A), 3.06 (t, J = 9.4 Hz each, 1H,
eluant to give pure 22 (4.6 g, 88%). Colorless oil; ½a D25
¼ ꢀ34 (c
ꢂ
1.0, CHCl3); mmax (neat): 2921, 1744, 1508, 1454, 1369, 1233,
1106, 1055, 983, 826, 739 cmꢀ1 1H NMR (500 MHz, CDCl3): d
;
7.25–7.17 (m, 20H, Ar-H), 6.74 (d, J = 9.2 Hz, 2H, Ar-H), 6.71 (d,
J = 9.2 Hz, 2H, Ar-H), 5.44–5.43 (m, 1H, H-2B), 4.89 (br s, 1H, H-
1A), 4.82 (d, J = 10.9 Hz, 1H, PhCH2), 4.80 (d, J = 11.0 Hz, 1H, PhCH2),
4.70 (br s, 1H, H-1B), 4.66 (d, J = 11.0 Hz, 1H, PhCH2), 4.57 (br s, 2H,
PhCH2), 4.55 (d, J = 11.0 Hz, 1H, PhCH2), 4.51 (d, J = 10.9 Hz, 1H,
PhCH2), 4.46 (d, J = 11.0 Hz, 1H, PhCH2), 3.97–3.93 (m, 3H, H-2A,

2150
R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
H-4B), 1.93 (s, 3H, COCH3), 1.20 (d, J = 6.2 Hz, 3H, CCH3), 1.15 (d,
J = 6.1 Hz, 3H, CCH3); 13C NMR (125 MHz, CDCl3): d 170.3 (COCH3),
167.7, 167.6 (2CO, Phth), 154.4–115.0 (Ar-C), 101.9 (PhCH), 101.4
(C-1C), 100.8 (C-1A), 99.3 (C-1B), 81.0 (C-4C), 80.9 (C-4B), 79.6 (3C,
C-3A, C-3B, C-4A), 78.1 (C-5B), 76.0 (C-2A), 75.6 (PhCH2), 75.3
(PhCH2), 73.0 (PhCH2), 72.1 (PhCH2), 69.7 (C-3C), 68.9 (C-2B), 68.8
(C-6C), 68.1 (2C, C-5A, OCH2), 66.2 (OCH2), 66.1 (C-5C), 56.0
(OCH3), 55.7 (C-2C), 21.1 (COCH3), 18.4 (CCH3), 18.1 (CCH3); ESI-
MS: m/z 1264.5 [M+Na]+; Anal. Calcd for C72H75NO18 (1241.49):
C, 69.61; H, 6.08. Found: C, 69.40; H, 6.32.
PhCH2), 4.66 (d, J = 11.4 Hz, 1H, PhCH2), 4.61 (d, J = 11.2 Hz, 1H,
PhCH2), 4.60 (d, J = 8.0 Hz, 1H, H-1F), 4.20 (dd, J = 12.2, 5.5 Hz, 1H,
H-6aF), 4.04 (dd, J = 12.2, 2.4 Hz, 1H, H-6bF), 4.01–3.99 (m, 2H, H-
2E, H-3E), 3.77–3.73 (m, 1H, H-5E), 3.75 (s, 3H, OCH3), 3.64–3.60
(m, 1H, H-5F), 3.42 (t, J = 9.4 Hz each, 1H, H-4E), 2.02 (br s, 6H,
2COCH3), 1.90 (s, 3H, COCH3), 1.85 (s, 3H, COCH3), 1.24 (d,
J = 6.2 Hz, 3H, CCH3); 13C NMR (125 MHz, CDCl3): d 170.7 (COCH3),
170.5 (COCH3), 169.6 (2C, 2COCH3), 155.2–114.9 (Ar-C), 103.1 (C-
1F), 98.0 (C-1E), 80.6 (C-3E), 79.8 (C-4E), 78.3 (C-5E), 75.8 (PhCH2),
73.3 (PhCH2), 72.7 (C-3F), 72.1 (C-5F), 71.5 (C-2F), 69.0 (2C, C-2E,
C-4F), 62.3 (C-6F), 55.9 (OCH3), 21.0 (COCH3), 20.9 (2C, 2COCH3),
20.8 (COCH3), 18.2 (CCH3); ESI-MS: m/z 803.3 [M+Na]+; Anal. Calcd
for C41H48O15 (780.29): C, 63.07; H, 6.20. Found: C, 63.26; H, 6.46.
4.1.16. 2-(4-Methoxyphenoxy) ethyl (4,6-O-benzylidene-2-
deoxy-2-N-phthalimido-b-
benzyl- -rhamnopyranosyl)-(1?2)-3,4-di-O-benzyl-
rhamnopyranoside 25
D-glucopyranosyl)-(1?2)-(3,4-di-O-
a-
L
a-L-
4.1.18. Ethyl (2,3,4,6-tetra-O-acetyl-b-
(3,4-di-O-benzyl- -rhamnopyranosyl)-(1?3)-(4,6-O-benzyli-
dene-2-deoxy-2-N-phthalimido-1-thio-b- -glucopyranoside 28
D-glucopyranosyl)-(1?2)-
a-L
A solution of compound 24 (3.0 g, 2.41 mmol) in 0.01 M CH3O-
Na in CH3OH (30 mL) was allowed to stir at room temperature for
30 min. The reaction mixture was neutralized with Dowex 50 W
X8 (H+), filtered, and evaporated to dryness. The crude product
was passed through a short pad of SiO2 using hexane–EtOAc
(3:1) as the eluant to give pure compound 25 (2.7 g, 94%). Colorless
D
To a solution of compound 26 (2.5 g, 3.20 mmol) in CH3CN–H2O
(20 mL; 4:1, v/v) was added ammonium cerium nitrate (CAN; 2.6 g,
4.74 mmol) and the reaction mixture was allowed to stir at room
temperature for 2 h. The reaction mixture was diluted with CH2Cl2
(80 mL) and the organic layer was washed with satd. NaHCO3 and
water, dried (Na2SO4), and evaporated to dryness to give disaccha-
ride hemiacetal. To a solution of the hemiacetal in anhydrous
CH2Cl2 (15 mL) was added trichloroacetonitrile (2.8 mL,
27.92 mmol) and the reaction mixture was cooled to ꢀ10 °C. To
the cooled reaction mixture was added DBU (0.1 mL, 0.65 mmol)
and it was allowed to stir at ꢀ10 °C for 1 h. The reaction mixture
was evaporated to dryness and the crude product was passed
oil; ½a 2D5
ꢂ
¼ ꢀ10 (c 1.0, CHCl3);
mmax (neat): 2926, 1715, 1508, 1390,
1232, 1100, 1050, 994, 827, 739 cmꢀ1; 1H NMR (500 MHz, CDCl3): d
7.47–7.08 (m, 29H, Ar-H), 6.78–6.77 (m, 4H, Ar-H), 5.46 (s, 1H,
PHCH), 5.19 (d, J = 8.4 Hz, 1H, H-1C), 4.88 (br s, 1H, H-1A), 4.77 (t,
J = 8.4 Hz each, 1H, H-3C), 4.73 (d, J = 10.8 Hz, 1H, PhCH2), 4.67
(br s, 1H, H-1B), 4.57 (2 d, J = 10.8 Hz each, 2H, PhCH2), 4.48 (d,
J = 10.8 Hz, 1H, PhCH2), 4.31 (dd, J = 8.4 Hz each, 1H, H-2C), 4.25
(d, J = 12.2 Hz, 1H, PhCH2), 4.08 (d, J = 10.8 Hz, 1H, PhCH2), 4.02
(d, J = 11.2 Hz, 1H, PhCH2), 3.99–3.95 (m, 3H, H-2A, H-2B, PhCH2),
3.85–3.82 (m, 3H, H-6abC, OCH2a), 3.73–3.57 (m, 6H, H-3A, H-3B,
H-5A, 2OCH2b, OCH2a), 3.72 (s, 3H, OCH3), 3.52–3.49 (m, 2H, H-4C,
H-5B), 3.33–3.29 (m, 1H, H-5C), 3.09 (2 t, J = 9.7 Hz each, 2H, H-
4A, H-4B), 1.20 (d, J = 6.2 Hz, 3H, CCH3), 1.18 (d, J = 6.2 Hz, 3H,
CCH3); 13C NMR (125 MHz, CDCl3): d 168.7, 168.6 (2CO, Phth),
154.4–115.0 (Ar-C), 102.2 (PhCH), 101.5 (C-1C), 101.2 (C-1A), 99.4
(C-1B), 82.4 (C-4C), 81.0 (C-4A), 80.9 (C-4B), 79.6 (C-3A), 79.5 (C-
3B), 78.1 (C-5B), 76.0 (C-2A), 75.6 (PhCH2), 75.4 (PhCH2), 72.9
(PhCH2), 72.0 (PhCH2), 68.9 (C-3C), 68.8 (C-6C), 68.5 (C-2B), 68.1
(2C, C-5A, OCH2), 66.2 (OCH2), 66.1 (C-5C), 57.0 (C-2C), 56.0
(OCH3), 18.4 (CCH3), 18.1 (CCH3); ESI-MS: m/z 1222.4 [M+Na]+;
Anal. Calcd for C70H73NO17 (1199.48): C, 70.04; H, 6.13. Found: C,
70.25; H, 6.38.
through a short pad of SiO2 to furnish (2,3,4,6-tetra-O-acetyl-b-
D-
glucopyranosyl)-(1?2)-3,4-di-O-benzyl- -rhamnopyranosyl tri-
a-L
chloroacetimidate (27; 1.9 g, 73%), which was used immediately
for the next step. A solution of compound 18 (0.7 g, 1.58 mmol)
and compound 27 (1.9 g, 2.32 mmol) in anhydrous CH2Cl2
(15 mL) was cooled to ꢀ20 °C. To the cooled reaction mixture
was added TMSOTf (20
l
L) and it was allowed to stir at ꢀ20 °C
for 1 h. The reaction mixture was diluted with CH2Cl2 (50 mL)
and the organic layer was washed with satd. NaHCO3 and water
in succession, dried (Na2SO4), and evaporated to dryness. The crude
product was purified over SiO2 using hexane–EtOAc (5:1) as the
eluant to give pure 28 (1.3 g, 75%). Colorless oil; ½a D25
¼ ꢀ15 (c
ꢂ
1.0, CHCl3); mmax (neat): 2931, 1757, 1716, 1429, 1382, 1225,
1096, 1041, 994, 751, 722 cmꢀ1 1H NMR (500 MHz, CDCl3): d
;
7.82–7.12 (m, 19H, Ar-H), 5.45 (s, 1H, PhCH), 5.28 (d, J = 10.6 Hz,
1H, H-1D), 4.91 (t, J = 9.5 Hz each, 1H, H-3F), 4.78 (t, J = 9.6 Hz each,
1H, H-4F), 4.75 (dd, J = 7.8 Hz each, 1H, H-2F), 4.66 (br s, 1H, H-1E),
4.62 (d, J = 10.9 Hz, 1H, PhCH2), 4.56 (t, J = 9.2 Hz each, 1H, H-3D),
4.45 (d, J = 11.5 Hz, 1H, PhCH2), 4.38 (d, J = 10.9 Hz, 1H, PhCH2),
4.35–4.32 (m, 2H, H-4D, PhCH2), 4.25 (t, J = 10.2 Hz each, 1H, H-
2D), 4.21 (d, J = 7.8 Hz, 1H, H-1F), 4.01 (dd, J = 12.2, 4.2 Hz, 1H, H-
4.1.17. 4-Methoxyphenyl (2,3,4,6-tetra-O-acetyl-b-D-glucopyra-
nosyl)-(1?2)-3,4-di-O-benzyl- -rhamnopyranoside 26
a-L
To a solution of compound 19 (2.0 g, 4.44 mmol) and compound
7 (2.1 g, 5.35 mmol) in anhydrous CH2Cl2 (15 mL) was added MS
4 Å (2 g) and the reaction mixture was allowed to stir at room tem-
perature under argon for 30 min. The reaction mixture was cooled
6aF), 3.73–3.64 (m, 4H, H-2E, H-5D, H-6abD), 3.63–3.51 (m, 2H,
H-3E, H-6bF), 3.47–3.45 (m, 1H, H-5E), 3.14–3.08 (m, 2H, H-4E,
H-5F), 2.63–2.52 (m, 2H, SCH2CH3), 2.02 (s, 3H, COCH3), 1.92 (s,
3H, COCH3), 1.88 (s, 3H, COCH3), 1.65 (s, 3H, COCH3), 1.11 (t,
J = 7.4 Hz each, 3H, SCH2CH3), 0.77 (d, J = 6.2 Hz, 3H, CCH3); 13C
NMR (125 MHz, CDCl3): d 171.0 (COCH3), 170.5 (COCH3), 169.5
(COCH3), 169.3 (COCH3), 167.7, 167.6 (2CO, Phth), 138.9–124.1
(Ar-C), 102.5 (PhCH), 102.1 (C-1F), 99.8 (C-1E), 82.1 (C-1D), 81.2
(C-3E), 80.5 (C-4E), 79.7 (C-5D), 78.0 (C-5E), 75.6 (C-3D), 75.5
(PhCH2), 72.8 (PhCH2), 72.7 (C-3F), 71.8 (C-5F), 71.3 (C-4D), 71.1
(C-2F), 69.0 (2C, C-4F, C-6D), 68.6 (C-2E), 62.1 (C-6F), 56.0 (C-2D),
24.6 (SCH2CH3), 21.1 (COCH3), 21.0 (COCH3), 20.9 (COCH3), 20.8
(COCH3), 17.7 (SCH2CH3), 15.3 (CCH3); ESI-MS: m/z 1120.3
[M+Na]+; Anal. Calcd for C57H63NO19S (1097.37): C, 62.34; H,
5.78. Found: C, 62.15; H, 6.00.
to ꢀ30 °C and NIS (1.4 g, 6.22 mmol) followed by TMSOTf (25
lL)
was added to it. After stirring at the same temperature for
45 min, the reaction mixture was filtered through a CeliteÒ bed
and washed with CH2Cl2 (100 mL). The organic layer was succes-
sively washed with 5% Na2S2O3, satd. NaHCO3, and water, dried
(Na2SO4), and concentrated under reduced pressure. The crude
product was purified over SiO2 using hexane–EtOAc (5:1) as the
eluant to give pure 26 (2.7 g, 78%). Colorless oil; ½a D25
¼ ꢀ31 (c
ꢂ
1.0, CHCl3); mmax (neat): 2937, 1754, 1508, 1366, 1223, 1089,
1039, 978, 829, 753 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.37–
;
7.25 (m, 10H, Ar-H), 6.92 (d, J = 9.1 Hz, 2H, Ar-H), 6.79 (d,
J = 9.1 Hz, 2H, Ar-H), 5.46 (br s, 1H, H-1E), 5.22 (t, J = 9.6 Hz, 1H,
H-3F), 5.09 (dd, J = 7.9 Hz each, 1H, H-2F), 5.01 (t, J = 9.6 Hz, 1H,
H-4F), 4.81 (d, J = 10.8 Hz, 1H, PhCH2), 4.74 (d, J = 11.4 Hz, 1H,

R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
2151
4.1.19. 2-(4-Methoxyphenoxy) ethyl (2,3,4,6-tetra-O-acetyl-b-
glucopyranosyl)-(1?2)-(3,4-di-O-benzyl- -rhamnopyranosyl)-
(1?3)-(4,6-O-benzylidene-2-deoxy-2-N-phthalimido-b- -gluco-
pyranosyl)-(1?3)-(4,6-O-benzylidene-2-deoxy-2-N-phthalimido-
b- -glucopyranosyl)-(1?2)-(3,4-di-O-benzyl- -rhamnopyrano-
syl)-(1?2)-3,4-di-O-benzyl- -rhamnopyranoside 29
To a solution of compound 25 (1.0 g, 0.83 mmol) and compound
28 (1.2 g, 1.09 mmol) in anhydrous CH2Cl2 (10 mL) was added MS
4 Å (2 g) and the reaction mixture was allowed to stir at room tem-
perature under argon for 30 min. The reaction mixture was cooled
D
-
pressure of hydrogen for 24 h. The reaction mixture was filtered
through a CeliteÒ bed, washed with CH3OH (50 mL), and concen-
trated. A solution of the crude product in 0.1 M CH3ONa in CH3OH
(10 mL) was allowed to stir at room temperature for 5 h. The reac-
tion mixture was neutralized with Dowex 50 W X8 (H+), filtered,
and evaporated to dryness to give compound 1, which was purified
through a Sephadex LH-20 column using CH3OH–H2O (2:1) as the
eluant to give pure compound 1 (130 mg, 62%). White powder;
a-L
D
D
a-L
a-L
½
a 2D5
ꢂ
¼ ꢀ8 (c 1.0, CH3OH); mmax (KBr): 3018, 2929, 1744, 1376,
1220, 1069, 764 cmꢀ1 1H NMR (500 MHz, CD3OD): d 6.85 (d,
;
to ꢀ30 °C and NIS (300 mg, 1.33 mmol) followed by TMSOTf (5
l
L)
J = 9.1 Hz, 2H, Ar-H), 6.76 (d, J = 9.1 Hz, 2H, Ar-H), 5.20–5.11 (m,
2H, H-1A, H-1E), 5.07 (br s, 1H, H-1D), 4.71 (br s, 1H, H-1C), 4.52
(br s, 1H, H-1B), 4.13–4.03 (m, 2H, H-2A, H-2E), 3.92–3.74 (m, 7H,
H-2B, H-2C, H-2D, H-3B, H-3C, H-3D, H-5B), 3.73–3.52 (m, 10H, H-
3A, H-3E, H-4A, H-5A, H-5C, H-5D, H-6abA, H-6abE), 3.68 (s, 3H,
OCH3), 3.50–3.35 (m, 5H, H-4B, H-4C, H-4D, H-4E, H-5E), 2.12 (s,
3H, COCH3), 2.10 (s, 3H, COCH3), 1.27–1.17 (m, 9H, 3CCH3); 13C
NMR (125 MHz, CDCl3): d 169.9, 169.8 (2COCH3), 154.4–115.0
(Ar-C), 102.9 (C-1A), 101.7 (C-1E), 101.8 (C-1D), 101.4 (C-1C), 96.5
(C-1B), 80.7 (C-3A), 80.0 (C-2B), 78.8 (2C, C-2C, C-2D), 78.0 (C-2E),
77.1 (C-5A), 77.0 (2C, C-3B, C-5E), 73.2 (C-4A), 73.0 (C-4C), 71.9 (C-
4B), 71.3 (C-4D), 71.0 (2C, C-3C, C-3D), 70.7 (C-4E), 69.9 (C-5D),
69.3 (C-5C), 68.9 (C-5B), 61.8 (C-6A), 61.5 (C-6E), 57.2 (C-2A), 56.4
(C-2E), 55.1 (OCH3), 23.9, 21.7 (2COCH3), 16.8 (3C, 3CH3); ESI-MS:
m/z 991.3 [M+Na]+; Anal. Calcd for C41H64N2O24 (968.38): C,
50.82; H, 6.66. Found: C, 50.60; H, 6.94.
was added to it. After stirring at the same temperature for 1 h, the
reaction mixture was filtered through a CeliteÒ bed and washed
with CH2Cl2 (50 mL). The organic layer was successively washed
with 5% Na2S2O3, satd. NaHCO3, and water, dried (Na2SO4), and
concentrated under reduced pressure. The crude product was puri-
fied over SiO2 using hexane–EtOAc (3:1) as the eluant to give pure
29 (1.4 g, 76%). Colorless oil; ½a D25
¼ ꢀ9 (c 1.0, CHCl3); mmax (neat):
ꢂ
2931, 1745, 1717, 1507, 1381, 1225, 1104, 1096, 1050, 994, 827,
722 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.30–7.12 (m, 48H, Ar-
;
H), 6.77–6.76 (m, 4H, Ar-H), 5.42 (s, 1H, PhCH), 5.41 (s, 1H, PhCH),
5.29 (d, J = 8.3 Hz, 1H, H-1C), 4.99 (d, J = 8.4 Hz, 1H, H-1D), 4.94 (t,
J = 9.5 Hz each, 1H, H-2F), 4.90 (t, J = 9.5 Hz each, 1H, H-3F), 4.80
(br s, 1H, H-1E), 4.79 (t, J = 9.3 Hz each, 1H, H-4F), 4.73 (t,
J = 8.4 Hz each, 1H, H-3C), 4.71 (d, J = 11.0 Hz, 1H, PhCH2), 4.63
(br s, 1H, H-1A), 4.62 (d, J = 11.8 Hz, 1H, PhCH2), 4.52 (br s, 2H,
PhCH2), 4.50 (br s, 1H, H-1B), 4.45 (d, J = 10.9 Hz, 1H, PhCH2),
4.40–4.37 (m, 2H, PhCH2), 4.09 (m, 6H, H-2C, H-2D, H-3D, PhCH2),
4.08–4.0 (m, 1H, H-6aF), 3.98–3.95 (m, 5H, H-1F, H-6abC, PhCH2),
3.84–3.76 (m, 4H, H-6abD, 2OCH2a), 3.71 (s, 3H, OCH3), 3.71–3.39
(m, 14H, H-2A, H-2B, H-2E, H-3A, H-3B, H-3E, H-4C, H-4D, H-5A, H-
5B, H-5D, H-6bF, 2OCH2b), 3.48–3.45 (m, 1H, H-5C), 3.30 (br s, 1H,
H-5E), 3.10 (2 t, J = 9.3 Hz each, 2H, H-4A, H-4B), 3.08–3.06 (m,
1H, H-5F), 2.88 (t, J = 9.5 Hz each, 1H, H-4E), 2.04 (s, 3H, COCH3),
1.98 (s, 3H, COCH3), 1.92 (s, 3H, COCH3), 1.64 (s, 3H, COCH3), 1.17
(d, J = 6.2 Hz, 3H, CCH3), 1.09 (d, J = 6.2 Hz, 3H, CCH3), 0.72 (d,
J = 6.2 Hz, 3H, CCH3); 13C NMR (125 MHz, CDCl3): d 171.0 (COCH3),
170.5 (COCH3), 169.5 (COCH3), 169.3 (COCH3), 167.7, 167.6 (4CO,
2Phth), 154.0–115.0 (Ar-C), 102.4 (C-1F), 102.0 (PhCH), 101.4
(PhCH), 101.3 (C-1D), 101.1 (C-1E), 100.0 (C-1B), 99.3 (C-1A), 97.8
(C-1C), 81.2 (C-4E), 80.9 (C-4A), 80.8 (C-4B), 80.4 (C-3A), 80.0 (C-
3B), 79.7 (C-5B), 79.5 (C-3E), 79.0 (C-5D), 78.1 (C-5E), 78.0 (C-4F),
75.8 (2C, C-3D, C-4C), 75.6 (PhCH2), 75.4 (PhCH2), 75.2 (PhCH2),
74.6 (C-2A), 73.0 (PhCH2), 72.6 (C-3F), 72.5 (PhCH2), 72.0 (PhCH2),
71.7 (C-3C), 71.2 (C-2B), 69.1 (C-6C), 68.9 (C-6D), 68.7 (C-5C), 68.5
(C-4D), 68.1 (3C, C-2F, C-5F, OCH2), 66.5 (C-2E), 66.3 (C-5A), 66.2
(OCH2), 62.0 (C-6F), 57.0 (C-2D), 56.1 (C-2C), 56.0 (OCH3), 21.1
(COCH3), 20.9 (COCH3), 20.7 (COCH3), 18.4 (COCH3), 18.4 (CCH3),
18.0 (CCH3), 17.6 (CCH3); MALDI-MS: m/z 2257.8 [M+Na]+; Anal.
Calcd for C125H130N2O36 (2234.84): C, 67.13; H, 5.86. Found: C,
66.92; H, 6.15.
4.1.21. 2-(4-Methoxyphenoxy) ethyl (b-
-rhamnopyranosyl)-(1?3)-(2-acetamido-2-deoxy-b-
pyranosyl)-(1?3)-(2-acetamido-2-deoxy-b- -glucopyranosyl)-
(1?2)-( -rhamnopyranosyl)-(1?2)- -rhamnopyranoside 2
D-glucopyranosyl)-(1?2)-
(a-L
D-gluco-
D
a
-
L
a-L
To a solution of compound 29 (1.0 g, 0.45 mmol) in n-butanol
(20 mL) was added ethylenendiamine (0.5 mL, 7.48 mmol) and
the reaction mixture was allowed to stir at 90 °C for 5 h. The sol-
vents were removed under reduced pressure and a solution of
the crude product in acetic anhydride–pyridine (3 mL, 1:1 v/v)
was kept at the room temperature for 2 h. The solvents were re-
moved under reduced pressure and the crude product was passed
through a short pad of SiO2. To a solution of the N-acetylated prod-
uct in CH3OH (10 mL) was added 20% Pd(OH)2-C (150 mg) and the
reaction mixture was allowed to stir at room temperature under a
positive pressure of hydrogen for 24 h. The reaction mixture was
filtered through a CeliteÒ bed, washed with CH3OH (50 mL), and
concentrated. A solution of the crude product in 0.1 M CH3ONa in
CH3OH (20 mL) was allowed to stir at room temperature for 5 h.
The reaction mixture was neutralized with Dowex 50 W X8 (H+),
filtered, and evaporated to dryness to give compound 1, which
was purified through a Sephadex LH-20 column using CH3OH–
H2O (2:1) as the eluant to give pure compound 2 (350 mg, 66%).
White powder; ½a D25
ꢂ
¼ ꢀ14 (c 1.0, H2O); mmax (KBr): 3448, 3066,
3033, 2926, 2370, 1368, 1057, 696 cmꢀ1
;
1H NMR (500 MHz,
D2O): d 6.76–6.74 (m, 4H, Ar-H), 5.18 (d, J = 8.3 Hz, 1H, H-1C),
4.95 (d, J = 8.5 Hz, 1H, H-1D), 4.78 (br s, 1H, H-1E), 4.62 (br s, 1H,
H-1A), 4.56 (br s, 1H, H-1B), 4.48 (d, J = 7.6 Hz, 1H, H-1F), 3.93–
3.91 (m, 2H, H-2B, H-2C), 3.87–3.71 (m, 6H, H-2A, H-2D, H-2E, H-
4.1.20. 4-Methoxyphenyl (2-acetamido-2-deoxy-b-
nosyl-(1?2)-( -rhamnopyranosyl)-(1?2)-( -rhamnopyrano-
syl)-(1?3)-( -rhamnopyranosyl)-(1?3)-2-acetamido-2-deoxy-
b- -glucopyranoside 1
To a solution of compound 16 (400 mg, 0.22 mmol) in n-butanol
(10 mL) was added ethylenendiamine (0.5 mL, 7.48 mmol) and the
reaction mixture was allowed to stir at 90 °C for 5 h. The solvents
were removed under reduced pressure and a solution of the crude
product in acetic anhydride–pyridine (2 mL, 1:1 v/v) was kept at
room temperature for 2 h. The solvents were removed under re-
duced pressure and the crude product was passed through a short
pad of SiO2. To a solution of the N-acetylated product in CH3OH
(10 mL) was added 20% Pd(OH)2-C (100 mg) and the reaction mix-
ture was allowed to stir at room temperature under a positive
D-glucopyra-
a
-L
-L
a-L
a
D
6aC, H-6abF), 3.66–3.53 (m, 7H, H-2F, H-3A, H-3B, H-3E, H-6bC,
2OCH2a), 3.58 (s, 3H, OCH3), 3.51–3.57 (m, 9H, H-2F, H-3C, H-3D,
H-3F, H-4C, H-4F, H-5A, H-6abD), 3.35–3.25 (m, 3H, H-4D, 2OCH2b),
3.23–3.06 (m, 3H, H-5B, H-5C, H-5D), 2.94 (br s, 1H, H-5E), 2.87 (t,
J = 9.4 Hz each, 1H, H-4E), 2.80 (t, J = 9.2 Hz each, 1H, H-4B), 2.43–
2.41 (m, 1H, H-4A), 2.15–2.13 (m, 1H, H-5F), 1.86 (br s, 6H,
2COCH3), 1.00 (d, J = 6.2 Hz, 3H, CCH3), 0.94 (d, J = 6.2 Hz, 3H,
CCH3), 0.81 (d, J = 6.2 Hz, 3H, CCH3); 13C NMR (125 MHz, D2O): d
170.5, 170.2 (2COCH3), 153.9–115.5 (Ar-C), 104.9 (C-1F), 101.3
(C-1E), 100.2 (C-1B), 99.9 (C-1A), 99.0 (C-1D), 98.2 (C-1C), 82.1 (C-
5E), 80.9 (2C, C-2A, C-2E), 78.8 (2C, C-4E, C-5B,), 76.6 (C-5F), 75.8

2152
R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 21 (2010) 2142–2152
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(C-2F), 75.5 (C-3F), 75.3 (C-3C), 73.2 (C-5C), 72.6 (C-5D), 72.4 (2C, C-
4A, C-4B), 70.3 (C-3A), 70.0 (C-3B), 69.8 (C-3E), 69.7 (C-4F), 69.5 (C-
3D), 69.3 (C-4C), 69.1 (C-4D), 69.0 (C-5A), 68.7 (C-2B), 68.3 (C-6D),
66.5 (C-6C), 61.0 (2C, C-6F, OCH2), 60.2 (OCH2), 56.4 (C-2D), 56.2
(OCH3), 55.7 (C-2C), 24.4 (COCH3), 24.3 (COCH3), 17.0 (CCH3), 16.8
(2C, CCH3); ESI-MS: m/z 1197.4 [M+Na]+; Anal. Calcd for
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C49H78N2O30 (1174.46): C, 50.08; H, 6.69. Found: C, 50.25; H, 6.96.
Acknowledgments
R.P. thanks CSIR, New Delhi for providing a Senior Research Fel-
lowship. This work was supported by the Ramanna Fellowship
(A.K.M.),the Department of Science and Technology, New Delhi
(SR/S1/RFPC-06/2006) and the Bose Institute, Kolkata.
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