Convergent synthesis of the pentasaccharide repeating unit of the O-antigen of Shigella boydii type 14

Article abstract of DOI:10.1016/j.tetasy.2011.08.004

An efficient synthesis of the pentasaccharide repeating unit of the O-antigen of Shigella boydii type 14 is reported. A one-pot, two step iterative glycosylation and [3+2] block synthetic strategy have been adopted for the construction of the pentasacchar

Full text of DOI:10.1016/j.tetasy.2011.08.004

Tetrahedron: Asymmetry 22 (2011) 1390–1394
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Convergent synthesis of the pentasaccharide repeating unit of the O-antigen
of Shigella boydii type 14
⇑
Rajib Panchadhayee, Anup Kumar Misra
Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata 700054, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 June 2011
Accepted 5 August 2011
Available online 2 September 2011
An efficient synthesis of the pentasaccharide repeating unit of the O-antigen of Shigella boydii type 14 is
reported. A one-pot, two step iterative glycosylation and [3+2] block synthetic strategy have been
adopted for the construction of the pentasaccharide derivative 11, which was then transformed into tar-
get compound 1 after a series of functional group transformations. The primary hydroxyl group has been
selectively oxidized to a carboxylic acid functionality without affecting the secondary hydroxyl groups.
HClO4–SiO2 has been used as a solid acid substitute in all glycosylation and functional group transforma-
tions. The yields were excellent in all glycosylation steps.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
O-antigen of a particular strain. Since the natural source cannot
fulfil such requirements, the chemical synthesis of the oligosaccha-
Shigella strains are well-known human pathogens that cause en-
teric diseases, such as diarrhoea and bacillary dysentery all over the
world, particularly in the developing countries.1 Shigella strains are
normally identified based on their O-antigens. Shigella strains are
classified into four species; Shigella dysenteriae, Shigella boydii, Shi-
gella flexneri, and Shigella sonnei.2 The O-antigen (O-polysaccharide)
is a constituent of the lipopolysaccharide (LPS) on the cell surface of
Gram-negative bacteria, which is mainly responsible for its patho-
genicity and its interactions with the host immune responses.3 The
O-antigen is one of the most variable constituents of the cell wall
due to the variation of the sugar moieties present in it and their
arrangements and linkages. Most of the O-antigens found in the cell
wall of Shigella are acidic in nature due to the presence of uronic
acid, or non-carbohydrate acidic components such as lactic acid,
pyruvic acid, and so on.2a L’vov et al. reported4 the structure of
the pentasaccharide repeating unit of the O-antigen of S. boydii type
14, which contains a glucuronic acid moiety (Fig. 1).
Despite the development of several therapeutics to combat Shi-
gella infections in the past, the emergence of drug resistant strains
poses a challenge in the development of newer alternative anti-
shigellosis agents.5 Being highly antigenic in nature, O-antigens
have the potential to be used in the development of glycoconjugate
based anti-shigellosis agents.6 Several reports have appeared for
the development of glycoconjugate based antimicrobial agents
using cell wall oligosaccharides.7 It is essential to have a large
quantity of the oligosaccharide for a detailed understanding of
the biological potential of the glycoconjugates derived from the
ride can provide the required quantity of the oligosaccharides in
addition to several analogues. With this objective in mind, we
herein report an efficient synthesis of the pentasaccharide repeat-
ing unit of the O-antigen of S. boydii type 14 as its sodium salt and
4-methoxyphenyl glycoside (Fig. 2).
2. Results and discussion
The synthesis of the target pentasaccharide 1 as its sodium salt
and 4-methoxyphenyl glycoside was achieved following a [3+2]
block synthetic strategy. A disaccharide thioglycoside derivative
10 was stereo- and regioselectively coupled with a trisaccharide
diol acceptor 9 to give the pentasaccharide derivative 11, which
was subjected to a number of functional group transformations
to furnish target pentasaccharide 1.
In order to synthesize pentasaccharide 1, the trisaccharide diol
acceptor 9 and the disaccharide thioglycoside 10 were synthe-
sized from suitably functionalized monosaccharide intermediates
2,8 3,9 4,10 511 and 612 (Fig. 2), derived from commercially avail-
able reducing sugars using a number of protection and deprotec-
tion steps. In the first step of the one-pot iterative glycosylations,
the stereoselective condensation of ethyl 2,3-di-O-benzyl-4,6-O-
benzylidene-1-thio-b-D-galactopyranoside 2 with ethyl 2,3-di-O-
→4)-β-D-Galp-(1→4)-β-D-GlcpNAc-(1→6)-α-D-Galp-
(1→4)-β-D-GlcpA-(1→6)-β-D-Galp-(1→
⇑
Corresponding author. Tel.: +91 33 25693240; fax: +91 33 2355 3886.
E-mail address: akmisra69@gmail.com (A.K. Misra).
Figure 1. Structure of the pentasaccharide repeating unit of the O-antigen of
Shigella boydii type 14.
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.08.004

R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 22 (2011) 1390–1394
1391
OBn
OBn
BnO
O
OH
O
HO
NH
HO
AcO
OH
E
D
BnO
SEt
O
O
AcO
E
HO
O
O
HO
CCl3
Ph
NPhth
D
O
HO
6
5
AcHN
HO
O
OBz
O
O
C
O
HO
ONa
O
O
O
HO
AcO
B
SEt
C
HO
BnO
SEt
O
OAc
BnO
B
O
HO
3
2
HO
HO
OH
BnO
O
O
Mp: 4-methoxyphenyl
A
OMp
HO
A
OMp
BnO
1
HO
BnO
4
Figure 2. Structure of the synthesized pentasaccharide as a sodium salt and 4-methoxyphenyl glycoside 1.
acetyl-6-O-benzoyl-1-thio-b-
D
-glucopyranoside 3 in the presence
4.59 (d, J = 7.8 Hz, H-1B) in the 1H NMR and at d 103.3 (C-1A),
100.6 (C-1B), 99.9 (C-1C) in the 13C NMR spectra]. In the proton
coupled 13C NMR spectrum, JC1-H1 values of the anomeric carbons
[156.0 Hz, 157.0 Hz and 170.0 Hz] further confirmed15 the pres-
of a combination13 of N-iodosuccinimide (NIS) and HClO4–SiO2
as the thioglycoside activator exploiting the principle of ‘armed-
disarmed’ glycosylation14 led to the formation of ethyl (2,3-di-
O-benzyl-4,6-O-benzylidene-
O-acetyl-6-O-benzoyl-1-thio-b-
a
-
D
-galactopyranosyl)-(1?4)-2,3-di-
-glucopyranoside 7. In the second
ence of two b-linked and one a-linked glycosidic bonds in com-
D
pound 8. Removal of the benzylidene acetal in compound 8
using HClO4–SiO2 at room temperature16 afforded trisaccharide
diol derivative 9 in 86% yield in a very short reaction time
(Scheme 1).
step, compound 7 formed in situ was allowed to react with com-
pound 4 in the presence of the same activator (present in the
reaction mixture) to give trisaccharide derivative 8 in 78% yield
together with a minor amount (ꢀ8%) of the other isomeric trisac-
charide derivative originating from the first step of glycosylation.
Due to the presence of 2-O-acetyl group in thioglycoside 3, it be-
came deactivated or disarmed and acted as a glycosyl acceptor in
the first step. In the first glycosylation step, the 1,2-cis-glycosyl
linked product was obtained as the major product due to the
presence of a non-participating 2-O-benzyl group in compound
2. However, a minor amount of 1,2-trans-glycosyl linked disac-
charide derivative was also formed, which was separated by chro-
matography after the second glycosylation step. In the second
glycosylation step, the formation of 1,2-trans-glycoside was ob-
served due to the presence of a neighbouring group participating
2-O-acetyl group in compound 7 formed in situ. The spectroscopic
analysis of compound 8 unambiguously confirmed its formation
[signals at d 5.15 (d, J = 3.4 Hz, H-1C), 4.79 (d, J = 7.7 Hz, H-1A),
In another experiment, the
idate derivative 5 was allowed to couple stereoselectively with the
-glucosamine derived thioglycoside acceptor 6 under Schmidt’s
reaction conditions17 using HClO4–SiO2 as the activator18 to fur-
nish ethyl (2-O-acetyl-3,4,6-tri-O-benzyl-b- -galactopyranosyl)-
(1?4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-N-phthalimido-1-thio-b-
-glucopyranoside 10 in 86% yield. In this case, the glycosyl trichlo-
D-galactose derived trichloroacetim-
D
D
D
roacetimidate derivative was successfully activated in the presence
of the thioglycoside derivative. The exclusive formation of com-
pound 10 was supported by its spectroscopic analysis [signals at
d 5.40 (d, J = 10.6 Hz, H-1D), 4.41 (d, J = 7.8 Hz, H-1E) in the 1H
NMR and at d 101.1 (C-1E), 81.2 (C-1D) in the 13C NMR spectra]
(Scheme 2).
The trisaccharide diol derivative 9 and the disaccharide thiogly-
coside derivative 10 were allowed to react regio- and stereoselec-
R2O
OR1
Ph
O
O
O
C
BnO
OBz
BnO
a
a
O
O
7
disaccharide derivative
O
AcO
B
O
C
BnO
SEt
OAc
BnO
OBz
OH
BnO
BnO
BnO
2
O
O
HO
AcO
B
O
SEt
A
OMp
A
OMp
BnO
OAc
BnO
1
R ; R2 = PhCH
3
BnO
8:
b
9: R1 = R2 = H
4
one pot, two step glycosylation
Scheme 1. Reagents and conditions: (a) N-iodosuccinimide (NIS), HClO4–SiO2, CH2Cl2, ꢁ15 °C, 30 min, then addition of 2, NIS, ꢁ15 °C, 30 min, 78%; (b) HClO4–SiO2, CH3CN,
room temperature, 20 min, 86%.

1392
R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 22 (2011) 1390–1394
5 + 6
3. Conclusion
In conclusion, an efficient synthetic strategy has been devel-
a
oped for the synthesis of the pentasaccharide repeating unit of
the O-antigen of S. boydii type 14 as its sodium salt and 4-
methoxyphenyl glycoside. A one pot, two step iterative glycosyla-
tions and block synthetic strategy have been adopted to achieve
the target compound in aminimum number of steps. HClO4–SiO2
has been used as a moisture tolerant, low cost, environmentally
benign solid acid catalyst in all glycosylation steps. Several elegant
concepts such as ‘armed-disarmed’ glycosylation, the use of
orthogonal anomeric protecting groups, selective activation of
one glycosyl donor in the presence of other, late stage selective oxi-
dation of a primary hydroxyl group, and so on, have been success-
fully incorporated in the synthetic strategy. Most of the reactions
were clean and the intermediates were obtained as solids in high
yield.
OBn
BnO
OBn
O
O
E
BnO
O
AcO
D
SEt
AcO
NPhth
10
Scheme 2. Reagents and conditions: (a) HClO4–SiO2, CH2Cl2, ꢁ5 °C, 30 min, 86%.
tively in the presence of a combination13 of NIS and HClO4–SiO2 to
give 4-methoxyphenyl (2-O-acetyl-3,4,6-tri-O-benzyl-b-
pyranosyl)-(1?4)-(3-O-acetyl-6-O-benzyl-2-deoxy-2-N-phthalim-
ido-b- -glucopyranosyl)-(1?6)-(2,3-di-O-benzyl- -galactopyr-
anosyl)-(1?4)-(2,3-di-O-acetyl-6-O-benzoyl-b- -glucopyranosyl)-
(1?6)-2,3,4-tri-O-benzyl-b- -galactopyranoside 11 in 77% yield.
D-galacto-
D
a-D
4. Experimental
4.1. General
D
D
The formation of the pentasaccharide derivative 11 was unambigu-
ously confirmed from its spectroscopic analysis [d 5.32 (d, J = 8.5 Hz,
H-1D), 4.80 (d, J = 3.9 Hz, H-1C), 4.78 (d, J = 7.6 Hz, H-1E), 4.42 (d,
J = 9.3 Hz, H-1A), 4.35 (d, J = 7.6 Hz, H-1B) in the 1H NMR and at d
103.4 (C-1E), 101.1 (C-1B), 100.7 (C-1A), 99.4 (C-1C), 98.5 (C-1D) in
the 13C NMR spectra]. It is worth mentioning that HClO4–SiO2 has
been used as an environmentally benign, moisture tolerant solid
acid substitute in most of the glycosylation reactions and functional
grouptransformations. Compound11wassubjectedtoareactionse-
quence involving; (a) the transformation of N-phthalimido group to
the acetamido group via hydrazinolysis19 followed by the N- and O-
acetylation and O-deacetylation; (b) TEMPO mediated selective oxi-
dation of a primary hydroxyl group to a carboxylic acid under phase
transfer reaction conditions;20 and (c) hydrogenolysis over Pearl-
man’s catalyst21 to furnish target pentasaccharide 1 as its sodium
salt and 4-methoxyphenyl glycoside in 62^ overall yield. The spec-
troscopic analysis of compound 1 unambiguously confirmed its for-
mation [signals at d 5.21 (d, J = 3.0 Hz, H-1C), 4.74 (d, J = 7.8 Hz, H-
1D), 4.48 (2 d, J = 8.4 Hz each, H-1A, H-1E), 4.31 (d, J = 8.0 Hz, H-1B)
in the 1H NMR and at d 103.1 (C-1A), 102.9 (C-1B), 102.7 (C-1E),
101.1 (C-1D), 100.9 (C-1C) in the 13C NMR spectra]. The application
All reactions were monitored by thin layer chromatography
over silica gel coated TLC plates. The spots on TLC were visualized
by warming ceric sulphate [2% Ce(SO4)2 in 2 N H2SO4] sprayed
plates on a hot plate. Silica gel 230–400 mesh was used for column
chromatography. 1H and 13C NMR, 2D COSY, HMQC spectra were
recorded on Bruker Avance DRX 500 MHz spectrometer using
CDCl3 and D2O as solvents and TMS as an internal reference unless
stated otherwise. Chemical shift values are expressed in d ppm.
ESI-MS spectra were recorded on a Micromass triple quadrupole
mass spectrometer. Elementary analysis was carried out on Carlo
Erba-1108 analyzer. Optical rotations were measured at 25 °C on
a Jasco-P2000 polarimeter. Commercially available grades of or-
ganic solvents of adequate purity were used in all reactions.
HClO4–SiO2 was prepared following the method previously
reported.22
4.1.1. 4-Methoxyphenyl (2,3-di-O-benzyl-4,6-O-benzylidene-
a-
D-galactopyranosyl)-(1?4)-(2,3-di-O-acetyl-6-O-benzoyl-b-D-
glucopyranosyl)-(1?6)-2,3,4-tri-O-benzyl-b-D-
galactopyranoside 8
of a late stage selective oxidation protocol to prepare the
D-glucu-
To a solution of compound 2 (1.5 g, 3.04 mmol) and compound
3 (1.2 g, 2.90 mmol) in anhydrous CH2Cl2 (10 mL) were added MS
ronic acid moiety is worth mentioning in this strategy (Scheme 3).
OBn
BnO
OBn
O
O
E
BnO
O
AcO
D
O
AcO
PhthN
HO
a
b,c,d,e
1
9
10
+
O
C
BnO
OBz
BnO
O
O
AcO
B
O
OAc
BnO
O
11
A
OMp
BnO
BnO
Scheme 3. Reagents and conditions: (a) NIS, HClO4–SiO2, CH2Cl2, ꢁ15 °C, 45 min, 77%; (b) (i) hydrazine hydrate, EtOH, 80 °C, 6 h; (ii) acetic anhydride, HClO4–SiO2, room
temperature, 30 min; (c) 0.1 M CH3ONa, CH3OH, room temperature, 2 h; (d) (i) NaBr, TBAB, TEMPO, NaHCO3, NaOCl, CH2Cl2, H2O, 0–5 °C, 3 h; (ii) tert-butanol, 2-methyl-but-
2-ene, NaClO2, NaH2PO4, room temperature, 3 h; (e) H2, 20% Pd(OH)2-C, CH3OH, room temperature, 24 h, over all 62%.

R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 22 (2011) 1390–1394
1393
4 Å (2.0 g) and the reaction mixture was allowed to stir at room
temperature for 1 h under argon. The reaction mixture was cooled
to ꢁ15 °C and N-iodosuccinimide (NIS; 700.0 mg, 3.11 mmol) fol-
lowed by HClO4–SiO2 (20.0 mg) were added to it and the reaction
mixture was allowed to stir at the same temperature for 30 min.
After complete consumption of the starting materials (TLC: hex-
73.3 (PhCH2), 72.2 (C-2B), 72.0 (C-5B), 69.1 (2C, C-6A, C-6C), 64.0 (C-
5C), 63.2 (C-6B), 55.9 (OCH3), 21.3, 21.0 (2COCH3); ESI-MS: 1271.4
[M+Na]+; Anal. Calcd for C71H76O20 (1248.49): C, 68.26; H, 6.13.
Found: C, 68.08; H, 5.90.
4.1.3. Ethyl (2-O-acetyl-3,4,6-tri-O-benzyl-b-
galactopyranosyl)-(1?4)-3-O-acetyl-6-O-benzyl-2-deoxy-
2-N-phthalimido-1-thio-b- -glucopyranoside 10
D-
ane–EtOAc 3:1), compound
4 (1.2 g, 2.15 mmol) and NIS
(550.0 mg, 2.44 mmol) were added to the reaction mixture and it
was allowed to stir at the same temperature for another 30 min.
The reaction mixture was filtered through a CeliteÒ bed and
washed with CH2Cl2 (100 mL). The organic layer was washed with
5% aq Na2S2O3, saturated aq NaHCO3 and water, dried (Na2SO4) and
concentrated to dryness. The crude product was purified over SiO2
using hexane–EtOAc (4:1) as eluent to give pure compound 8
D
A solution of compound 5 (1.6 g, 2.51 mmol) and compound 6
(1.0 g, 2.06 mmol) in anhydrous CH2Cl2 (10 mL) was cooled to
ꢁ5 °C. To the cooled reaction mixture was added HClO4–SiO2
(50.0 mg) and the reaction mixture was allowed to stir for
30 min at the same temperature. The reaction mixture was filtered
through a CeliteÒ bed and concentrated to dryness. The crude
product was purified over SiO2 using hexane–EtOAc (4:1) as eluent
to give pure compound 10 (1.7 g, 86%). White solid; mp 70–72 °C;
(2.3 g, 78%). White solid; mp 95–98 °C; ½a D25
¼ þ17:5 (c 1.2, CHCl3);
ꢂ
IR (KBr): 3031, 2867, 1754, 1720, 1507, 1454, 1240, 1099, 1065,
749, 697 cmꢁ1
;
1H NMR (500 MHz, CDCl3): d 8.01–7.22 (m, 35H,
½
a 2D5
ꢂ
¼ þ22:4 (c 1.2, CHCl3); IR (KBr): 3475, 3063, 3030, 2927, 2869,
1749, 1716, 1454, 1386, 1371, 1229, 1073, 1027, 737, 720,
698 cmꢁ1 1H NMR (500 MHz, CDCl3): d 7.70–7.22 (m, 24H, Ar-
Ar-H), 6.97 (d, J = 9.1 Hz, 2H, Ar-H), 6.87 (d, J = 9.1 Hz, 2H, Ar-H),
5.35 (s, 1H, PhCH), 5.30 (t, J = 9.2 Hz each, 1H, H-3B), 5.15 (d,
J = 3.4 Hz, 1H, H-1C), 4.99 (d, J = 10.9 Hz, 1H, PhCH2), 4.92 (dd,
J = 8.0 Hz each, 1H, H-2B), 4.89 (d, J = 11.5 Hz, 1H, PhCH2), 4.84 (d,
J = 10.9 Hz, 1H, PhCH2), 4.79 (d, J = 7.7 Hz, 1H, H-1A), 4.76–4.61
(m, 8H, H-6aB, PhCH2), 4.59 (d, J = 7.8 Hz, 1H, H-1B), 4.32 (dd,
J = 12.0, 4.9 Hz, 1H, H-6bB), 4.11 (d, J = 2.9 Hz, 1H, H-4C), 4.05–
4.00 (m, 3H, H-2C, H-4A, H-4B), 3.92–3.87 (m, 2H, H-3C, H-6aC),
3.84–3.78 (m, 1H, H-6aA), 3.75 (s, 3H, OCH3), 3.74–3.72 (m, 2H,
H-2A, H-6bC), 3.70–3.67 (m, 1H, H-6bA), 3.62–3.54 (m, 3H, H-5A,
H-5B, H-5C), 3.51 (dd, J = 9.8, 2.8 Hz, 1H, H-3A), 1.88 (s, 6H,
2COCH3); 13C NMR (125 MHz, CDCl3): d 170.2, 170.0 (2COCH3),
166.4 (PhCO), 155.6–115.1 (Ar-C), 103.3 (C-1A), 101.1 (PhCH),
100.6 (C-1B), 99.9 (C-1C), 82.1 (C-3A), 79.5 (C-4A), 76.4 (C-3C),
75.7 (PhCH2), 75.4 (C-4B), 75.2 (C-2C), 74.9 (PhCH2), 74.8 (C-3B),
74.7 (2C, C-4C, PhCH2), 74.5 (C-2A), 74.2 (C-5A), 73.6 (PhCH2), 73.3
(C-5B), 72.6 (C-2B), 72.5 (PhCH2), 69.5 (C-6C), 69.1 (C-6A), 64.2 (C-
5C), 63.4 (C-6B), 55.9 (OCH3), 21.4, 21.1 (2COCH3); ESI-MS: 1359.5
[M+Na]+; Anal. Calcd for C78H80O20 (1336.52): C, 70.05; H, 6.03.
Found: C, 69.82; H, 6.28.
;
H), 5.68 (t, J = 9.1 Hz each, 1H, H-3D), 5.40 (d, J = 10.6 Hz, 1H, H-
1D), 5.18 (dd, J = 7.9 Hz each, 1H, H-2E), 4.87 (d, J = 11.6 Hz, 1H,
PhCH2), 4.70 (d, J = 11.9 Hz, 1H, PhCH2), 4.60 (d, J = 12.2 Hz, 1H,
PhCH2), 4.50 (d, J = 11.8 Hz, 2H, PhCH2), 4.42 (d, J = 12.2 Hz, 1H,
PhCH2), 4.41 (d, J = 7.8 Hz, 1H, H-1E), 4.37 (d, J = 11.7 Hz, 1H,
PhCH2), 4.34 (d, J = 11.7 Hz, 1H, PhCH2), 4.24 (t, J = 10.4 Hz, 1H,
H-2D), 3.97 (t, J = 9.6 Hz each, 1H, H-4D), 3.89 (d, J = 2.3 Hz, 1H,
H-4E), 3.80–3.72 (m, 2H, H-6abD), 3.69–3.63 (m, 1H, H-5D), 3.56
(t, J = 8.5 Hz each, 1H, H-6aE), 3.47 (dd, J = 8.8, 4.9 Hz, 1H, H-6bE),
3.37–3.32 (m, 2H, H-3E, H-5E), 2.67–2.60 (m, 2H, SCH2CH3), 1.93,
1.73 (2 s, 6H, 2COCH3), 1.20 (t, J = 7.4 Hz each, 3H, SCH2CH3); 13C
NMR (125 MHz, CDCl3): d 170.2, 169.3 (2COCH3), 167.9, 167.8
(Phth), 138.9–123.8 (Ar-C), 101.1 (C-1E), 81.2 (C-1D), 80.8 (C-3E),
79.4 (C-5D), 75.5 (C-4D), 74.7 (PhCH2), 73.9 (PhCH2), 73.8 (PhCH2),
73.6 (C-5E), 72.7 (C-4E), 72.6 (C-2E), 72.2 (C-3D), 72.1 (PhCH2),
68.4 (C-6E), 68.3 (C-6D), 54.5 (C-2D), 24.4 (SCH2CH3), 21.4, 20.9
(2COCH3), 15.4 (SCH2CH3); ESI-MS: 982.3 [M+Na]+; Anal. Calcd
for C54H57NO13S (959.35): C, 67.55; H, 5.98. Found: C, 67.33, H,
6.22.
4.1.2. 4-Methoxyphenyl (2,3-di-O-benzyl-
a-D-
galactopyranosyl)-(1?4)-(2,3-di-O-acetyl-6-O-benzoyl-b-
D-
4.1.4. 4-Methoxyphenyl (2-O-acetyl-3,4,6-tri-O-benzyl-b-
D-
glucopyranosyl)-(1?6)-2,3,4-tri-O-benzyl-b-D-
galactopyranosyl)-(1?4)-(3-O-acetyl-6-O-benzyl-2-deoxy-2-N-
galactopyranoside 9
phthalimido-b-
D
-glucopyranosyl)-(1?6)-(2,3-di-O-benzyl-
a-
D-
To a solution of compound 8 (2.0 g, 1.49 mmol) in CH3CN
(15 mL) was added HClO4–SiO2 (50.0 mg) and the reaction mixture
was allowed to stir for 20 min at room temperature. The reaction
mixture was filtered through a CeliteÒ bed and concentrated to
dryness. The crude product was purified over SiO2 using hexane–
EtOAc (2:1) as eluent to give pure compound 9 (1.6 g, 86%). White
galactopyranosyl)-(1?4)-(2,3-di-O-acetyl-6-O-benzoyl-b-
glucopyranosyl)-(1?6)-2,3,4-tri-O-benzyl-b-D-
galactopyranoside 11
D
-
To a solution of compound 9 (1.2 g, 0.96 mmol) and compound
10 (970.0 mg, 1.01 mmol) in anhydrous CH2Cl2 (8 mL) were added
MS 4 Å (1.0 g) and the reaction mixture was allowed to stir at room
temperature for 1 h under argon. The reaction mixture was cooled
to ꢁ15 °C and NIS (270.0 g, 1.2 mmol) followed by HClO4–SiO2
(10.0 mg) were added and the reaction mixture was allowed to stir
at same temperature for 45 min. The reaction mixture was filtered
through a CeliteÒ bed and washed with CH2Cl2 (100 mL). The or-
ganic layer was washed with 5% aq Na2S2O3, saturated aq NaHCO3
and water, dried (Na2SO4) and concentrated to dryness. The crude
product was purified over SiO2 using hexane–EtOAc (4:1) as eluent
to give pure compound 11 (1.6 g, 77%). White solid; mp 98–100 °C;
solid; mp 78–80 °C; ½a D25
¼ ꢁ2:6 (c 1.2, CHCl3); IR (KBr): 3491,
ꢂ
3031, 2938, 2874, 1754, 1722, 1507, 1454, 1368, 1277, 1241,
1220, 1062, 749, 698 cmꢁ1 1H NMR (500 MHz, CDCl3): d 8.00–
;
7.21 (m, 30H, Ar-H), 6.99 (d, J = 9.0 Hz, 2H, Ar-H), 6.86 (d,
J = 9.0 Hz, 2H, Ar-H), 5.24 (t, J = 9.4 Hz each, 1H, H-3B), 5.00 (d,
J = 10.8 Hz, 1H, PhCH2), 4.98 (t, J = 9.5 Hz each, 1H, H-2B), 4.92 (d,
J = 11.4 Hz, 1H, PhCH2), 4.84 (d, J = 11.4 Hz, 1H, PhCH2), 4.81 (br s,
1H, H-1C), 4.78 (d, J = 11.8 Hz, 1H, PhCH2), 4.71–4.67 (m, 2H,
PhCH2), 4.65 (d, J = 8.0 Hz, 1H, H-1A), 4.63–4.56 (m, 7H, H-1B, H-
6abC, PhCH2), 4.03 (t, J = 8.0 Hz each, 1H, H-2A), 3.94 (br s, 1H, H-
½
a 2D5
ꢂ
¼ ꢁ0:3 (c 1.2, CHCl3); IR (KBr): 3466, 2923, 1753, 1718, 1507,
4C), 3.87 (t, J = 9.2 Hz each, 1H, H-4B), 3.85–3.81 (m, 2H, H-2C, H-
6aB), 3.80–3.70 (m, 5H, H-3C, H-4A, H-6bB, H-6abA), 3.76 (s, 3H,
OCH3), 3.64–3.77 (m, 2H, H-5A, H-5C), 3.65–3.51 (m, 2H, H-3A, H-
5B), 1.90, 1.89 (2 s, 6H, 2COCH3); 13C NMR (125 MHz, CDCl3): d
170.4, 170.3 (2COCH3), 166.8 (PhCO), 155.6–115.1 (Ar-C), 103.3
(C-1A), 100.8 (C-1B), 100.6 (C-1C), 82.1 (C-3A), 79.5 (C-4A), 77.4
(C-3C), 77.1 (C-4B), 76.4 (C-2C), 75.7 (PhCH2), 75.0 (C-4C), 74.8
(PhCH2), 74.2 (2C, C-3B, PhCH2), 74.0 (C-2A), 73.6 (2C, C-5A, PhCH2),
1454, 1386, 1233, 1064, 698 cmꢁ1 1H NMR (500 MHz, CDCl3): d
;
7.94–7.21 (m, 54H, Ar-H), 6.96 (d, J = 9.0 Hz, 2H, Ar-H), 6.81 (d,
J = 9.0 Hz, 2 Hz, Ar-H), 5.62 (t, J = 8.9 Hz each, 1H, H-3D), 5.32 (d,
J = 8.5 Hz, 1H, H-1D), 5.19 (t, J = 9.4 Hz each, 1H, H-3B), 5.17 (dd,
J = 8.0 Hz each, 1H, H-2E), 5.01 (d, J = 10.9 Hz, 1H, PhCH2), 4.90 (d,
J = 11.0 Hz, 1H, PhCH2), 4.88 (dd, J = 9.5 Hz each, 1H, H-2B), 4.85–
4.82 (2 d, J = 11.2 Hz each, 2H, PhCH2), 4.80 (d, J = 3.9 Hz, 1H, H-
1C), 4.78 (d, J = 7.6 Hz, 1H, H-1E), 4.74–4.71 (2 d, J = 11.2 Hz each,

1394
R. Panchadhayee, A. K. Misra / Tetrahedron: Asymmetry 22 (2011) 1390–1394
2H, PhCH2), 4.64–4.44 (m, 9H, PhCH2), 4.42 (d, J = 9.3 Hz, 1H, H-1A),
4.40–4.34 (m, 5H, H-6abB, PhCH2), 4.35 (d, J = 7.6 Hz, 1H, H-1B), 4.16
(dd, J = 8.6 Hz each, 1H, H-2D), 4.03 (dd, J = 9.0 Hz each, 1H, H-2A),
3.95–3.86 (m, 4H, H-4C, H-4D, H-5D, H-6aC), 3.85–3.77 (m, 4H, H-2C,
H-4B, H-4E, H-6aA), 3.76–3.62 (m, 5H, H-3C, H-4A, H-5A, H-6bA, H-
H-2D, H-3B, H-3D, H-3E, H-4C, H-5A, H-5D), 3.90–3.81 (m, 4H, H-
2A, H-2C, H-6abA), 3.80–3.50 (m, 10H, H-2B, H-2E, H-3C, H-4A, H-
4B, H-5C, H-6abC, H-6abD), 3.67 (s, 3H, OCH3), 3.48–3.38 (m, 4H, H-
3A, H-4D, H-4E, H-5E), 3.32–3.22 (m, 1H, H-5B), 2.21 (s, 3H,
NHCOCH3); 13C NMR (125 MHz, D2O): d 173.1 (COONa), 170.2
(NHCOCH3), 154.3–114.7 (Ar-C), 103.1 (C-1A), 102.9 (C-1B), 102.7
(C-1E), 101.1 (C-1D), 100.9 (C-1C), 78.6 (C-4D), 78.0 (C-4E), 76.0
(C-4B), 74.8 (C-5B), 74.7 (C-5E), 74.6 (C-5D), 74.4 (C-3B), 72.9 (C-
3D), 72.6 (C-2B), 72.2 (C-3A), 71.6 (C-2E), 71.0 (C-3E), 70.4 (2C, C-
2A, C-5A), 70.2 (C-4C), 69.1 (C-5C), 68.9 (C-3C), 68.7 (C-2C), 68.6
(C-4A), 68.5 (C-6A), 64.2 (C-6E), 60.0 (C-6C, C-6D), 55.5 (OCH3),
54.4 (C-2D), 20.6 (NHCOCH3); ESI-MS: 1012.3 [M+1]+; Anal. Calcd
for C39H58NNaO28 (1011.30): C, 46.29; H, 5.78. Found: C, 46.05;
H, 6.00.
6bC), 3.72 (s, 3H, OCH3), 3.61–3.58 (m, 3H, H-5B, H-6aD, H-6aE),
3.57–3.51 (m, 3H, H-3A, H-5C, H-6bD), 3.45–3.41 (m, 1H, H-6bE),
3.35–3.30 (m, 2H, H-3E, H-5E), 1.89, 1.86, 1.76, 1.70 (4 s, 12H,
4COCH3); 13C NMR (125 MHz, CDCl3): d 170.2, 170.1, 169.9, 169.3
(4COCH3), 167.8 (Phth), 165.8 (PhCO), 155.6–115.0 (Ar-C), 103.4
(C-1E), 101.1 (C-1B), 100.7 (C-1A), 99.4 (C-1C), 98.5 (C-1D), 82.2
(C-3A), 80.7 (C-3E), 79.6 (C-5A), 77.6 (C-2C), 76.4 (C-4B), 75.9 (C-
3C), 75.7 (PhCH2), 75.0 (2C, C-4A, C-4C), 74.9 (PhCH2), 74.7 (PhCH2),
74.4 (C-4D), 74.2 (C-2A), 74.0 (2C, 2 PhCH2), 73.8 (2C, C-3B, PhCH2),
73.7 (C-5C), 73.6 (C-5E), 73.5 (PhCH2), 72.7 (PhCH2), 72.5 (C-3D),
72.3 (C-2B), 72.0 (2C, C-5B, PhCH2), 71.9 (C-2E), 69.9 (C-4E), 69.3
(C-6D), 68.3 (2C, C-6A, C-6E), 68.0 (C-6C), 67.1 (C-5D), 63.7 (C-6B),
55.9 (OCH3), 55.4 (C-2D), 21.4, 21.2, 21.0, 20.9 (4COCH3); MALDI-
MS: 2168.8 [M+Na]+; Anal. Calcd for C123H127NO33 (2145.82): C,
68.80, H, 5.96. Found: C, 68.57, H, 5.74%.
Acknowledgments
R.P. thanks CSIR, New Delhi for providing a Senior Research Fel-
lowship. This work was supported by Bose Institute, Kolkata.
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pound 1 (350.0 mg, 62%) as a white powder; ½a D25
¼ þ30:6 (c 1.2,
ꢂ
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1221, 1082, 969, 754 cmꢁ1 1H NMR (500 MHz, D2O): d 7.00–6.77
;
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