Four-component one-pot synthesis of a branched manno-pentasaccharide: Tert-butyldiphenylsilyl ether as an in situ removable carbohydrate-protecting group

Article abstract of DOI:10.1016/j.tet.2011.03.109

A branched mannose-pentasaccharide was synthesized in a convergent one-pot sequence involving chemo- and regioselective glycosylations of suitable acceptors and in situ removal of tert-butyldiphenylsilyl group. The process demonstrated that a combination

Full text of DOI:10.1016/j.tet.2011.03.109

Tetrahedron 67 (2011) 4118e4122
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Four-component one-pot synthesis of a branched manno-pentasaccharide: tert-
butyldiphenylsilyl ether as an in situ removable carbohydrate-protecting group
*
Swarbhanu Sarkar, Samrat Dutta, Gora Das, Asish Kumar Sen
Chemistry Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A branched mannose-pentasaccharide was synthesized in a convergent one-pot sequence involving
chemo- and regioselective glycosylations of suitable acceptors and in situ removal of tert-butyldiphe-
nylsilyl group. The process demonstrated that a combination of TMSOTf and TfOH can be used as an
effective reagent for the fast and selective in situ de-protection of tert-butyldiphenylsilyl group, and also
serve as part of the promoter system for the subsequent glycosylation reaction.
Received 26 November 2010
Received in revised form 25 March 2011
Accepted 30 March 2011
Available online 8 April 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
manno-Pentasaccharide
Sequential one-pot glycosylation
In situ removal of tert-butyldiphenylsilyl
ether
1. Introduction
Lectins are proteins having high binding specificity towards
specific mono-, oligo- and poly-saccharides. Recent X-ray studies1
of methyl a-D-mannopyranoside bound lectin, isolated from Musa
paradisiaca, showed it contains, unlike other lectins of the same
class, two mannose specific primary binding sites (PI and PII).
Modelling studies also revealed that the two non-reducing ends
Fig. 1. Branched manno-pentasaccharide.
of a branched
Manp-(1/6)-[
a
a
-manno-pentasaccharide ({
a
-
D
-Manp-(1/3)-
a-D-
glycosylation step. Many one-pot syntheses of oligosaccharides rely
on differences in reactivity of the anomeric groups.3 Pre-activation4
or chemoselective activation5 of the donor in presence of an ac-
ceptor also enables rapid assembly of oligosaccharides; a well
established two directional glycosylation strategy. Regioselective
glycosylation6 depends on the reactivity of unprotected hydroxyl
groups present in a glycosyl acceptor thus glycosylation occurs at
the most reactive hydroxyl group. When the reactivity of hydroxyl
groups is similar, selective protection/de-protection steps become
important to avoid formation of undesired products. Thus, a major
limitation of these methods is that the glycosyl acceptors cannot
carry hydroxyl groups of similar reactivity, which can be avoided
through in situ removal of protecting groups.7 In this communi-
cation we described an efficient one-pot synthesis of the manno-
pentasaccharide involving sequential chemo- and regioselective
glycosylation of suitably protected acceptors, in situ removal of 6-
O-tert-butyldiphenylsilyl protecting group by TMSOTf/TfOH fol-
lowed by a regioselective glycosylation to form the protected target
compound without purification of intermediates.
-
D
-Manp-(1/6)- -Manp-(1/3)]-a-D
a
-
D
-Manp})
could effectively bind with the two primary sites PI and PII of the
lectin, providing a structural explanation for the lectin’s specificity
for branched
and to study the X-ray crystallographic structure of oligosacchar-
ideelectin complex, conformationally locked -benzyl glycoside of
a-mannans only. In order to confirm the hypothesis
a
the manno-pentasaccharide (Fig. 1) was synthesized using a rapid
and convenient synthetic strategy.
A number of one-pot glycosylation2 approaches have been ex-
plored during the past years to minimize the overall time of the
synthesis and to circumvent tedious chromatographic purification
of multiple synthetic intermediates. Synthesis of oligosaccharides is
often complex because of the presence of multiple hydroxyl groups
and the possibility to produce stereoisomers during the
* Corresponding author. Tel.: þ91 33 24995720; fax: þ91 33 24735197; e-mail
address: aksen@iicb.res.in (A. K. Sen).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.109

S. Sarkar et al. / Tetrahedron 67 (2011) 4118e4122
4119
2. Results and discussion
The alternative approach employed diol acceptor 5, prepared
starting from the 6-O silylated benzyl mannoside 10 via 2,3-
isopropylidene formation, acetylation of the remaining 4-OH
group followed by removal of isopropylidene group using aque-
ous acetic acid. Using those already established building blocks (4
and 5) together with readily accessible acetobromomannose 2
and the benzoylated 6-OH thioethyl mannoside 3, the assembly
of the protected target 1 was then carried out in a one-pot
sequence.
Retrosynthetic analysis indicated that the mannose pentamer
could be obtained by condensation of four moieties (Scheme 1).
Building blocks 2 and 3 were prepared by literature8,9 procedures and
synthetic strategy of the building blocks 4 and 5 starting from phenyl
thioglycoside10 (7) and benzyl mannopyranoside11 (10), respectively,
are described in Scheme 2. The structures of all new products were
well supported by spectroscopic and analytical data.
Chemoselective glycosylation of acetobromomannose
2
OH
(1.1 equiv) and thioethyl acceptor 3 (1.0 equiv) at ꢁ20 ꢀC in the
presence of AgOTf23 furnished disaccharide 13. The thioethyl donor
disaccharide 13 was then activated in situ by addition of NIS. Sub-
sequent addition of diol acceptor 5 (1.0 equiv) produced regiose-
lectively 3-O-glycosylated trisaccharide 14.
OBz
OAc
O
BzO
BzO
OAc
O
OAc AcO
OAc
OAc
SEt
3
OAc
AcO
OAc
OAc
O
O
O
AcO
AcO
OAc
AcO
AcO
AcO
O
OAc
O
OAc
OAc
AcO
AcO
O
O
OBz
O
Br
All linkages and structure were established by COSY, gHSQC,
HMBC and NOESY experiments. Strong correlation between HB-
1 and CA-3, and the absence of a cross peak linking HB-1 and CA-2 in
2
BzO
BzO
O
AcO
OH
O
O
OTBDPS
AcO
SPh
O
4
OH
HMBC (Fig. 2) indicated that regioselective
a-glycosylation had
O
AcO
HO
OR
taken place at the O-3 position.
1
OH
R = Bn
R = Me
OBn
5
OH
O
1a
BnO
HO
3.94, 68.63
OCH3
OAc
6
5.22,
OAc
O
65.97
62.2
Scheme 1. Retrosynthetic analysis for the pentasaccharide.
AcO
Ac O
4.85, 97.55
4.65, 69.77
H
5.31
69.3
[C]
5.39
68.9
O
66.63
OAc
OAc
OAc
5.87
66.7
OBz
O
OAc
O
AcO
AcO
OAc
OAc
O
OH
AcO
AcO
OAc
5.23, 98.47
BzO
BzO
OH
O
OAc
O
H
9
a
OCNHCCl3
O
HO
HO
AcO
HO
5.56
70.65
5.35
66.8
[B]
AcO
OTBDPS
5.76
72.02, 3.91
O
12
b
69.83
OH
SPh
SPh
63.46
SPh
7
4
8
O
AcO
5.1, 98.61
O
H
OTBDPS
OH
OTBDPS
OTBDPS
[A]
HA 4.57, HB 4.8,
J 11.4, 68.86
H
4.15,
80.37
O
OH
O
O
O
H
RO
AcO
HO
c
e
HO
HO
O
OCH2Ph
4.26, 69.82
OBn
R = OH
12 R = OAc
Scheme 2. Synthesis of building blocks
OBn
OBn
10
11
Fig. 2. Important correlations of 14 [HMBC (/), COSY (/)].
5
d
4
and 5. Reagents and conditions: (a)
Removal of the 6-O-tert-butyldiphenylsilyl group was achieved
rapidly (within 5 min) by adding TMSOTf24 (1.5 equiv) and TfOH
(2.0 equiv) at a slightly higher temperature (ꢁ5 ꢀC) leading to diol
trisaccharide acceptor 16. Then, disaccharide thiophenyl donor 4
(1.0 equiv) together with NIS (2.5 equiv) was added into the
reaction mixture. TfOH already present in the reaction mixture
activated thioglycosides 4 and glycosylation proceeded through the
primary 6-OH group producing the desired branched penta-
saccharide 1 in 30% overall yield after column chromatography.
Formation of compound 1 was characterized by 13C NMR, HRMS
and as well as by 1H NMR. Traces of impurity could be detected in
the 1H NMR. Finally, de-acetylation/benzoylation was conducted at
room temperature in ammonia-saturated methanol yielding 17 in
good yield (Scheme 3).
The plausible mechanism for the desilylation of 14 is depicted in
Fig. 3. In a separate experiment, compound 14 was first treated with
TMSOTf, then with TfOH followed by the addition of anhydrous
Et3N (with in 2e3 min) to quench the reaction. HR ESI-MS of this
reaction mixture indicated the presence of acceptor trisaccharide
16 along with O-6 trimethylsilylated trisaccharide 15 only. Acidic
condition is sufficient for the cleavage of tert-butyldiphenylsilyl
ether 14, however longer reaction time and high reaction temper-
ature may be required. TMSOTf generates an equilibrium25 be-
tween 14 and TMSylated cation (B), and thus it activates TBDPSOR
(14) and transforms it to acid-labile TMSOR 15 through heterolytic
fission and TfOH acid cleavage.
CH(OCH3)3, CSA, DMF, 10 min; 80% AcOH, 35 ꢀC, 45 min; AcCl/Py/ꢁ40 ꢀC, 30% based on
7; (b) TMSOTf, CH2Cl2, ꢁ20 ꢀC, 15 min, 85%; (c) 2,2-dimethoxypropane, p-TsOH, DMF,
12 h, 82%; (d) Ac2O, Pyridine, 6 h, 95%; (e) 80% AcOH, 80 ꢀC, 45 min, 75%.
Phenyl thioglycoside 7 first treated with triethylorthoacetate in
presence of camphorsulfonic acid (CSA) as catalyst produced
2,3:4,6-di-O-orthoester, in situ ring opening of which gave 2,4- and
2,6-acyl protected thioglycosides nearly in 1:1 ratio.12 Selective
acetylation of the primary hydroxyl13 in presence of secondary
hydroxyl groups was then carried out by treating the mixture with
acetyl chloride in pyridine at ꢁ40 ꢀC to produce triacetylated
phenyl thiomannopyranoside (8) in 30% overall yield after flash
chromatography. Coupling of trichloroacetimidate donor14 (9) with
acceptor 8 was achieved by chemoselective activation of the former
by TMSOTf15 in CH2Cl2 at ꢁ20 ꢀC to produce compound 4 in 85%
yield. Neither self-condensation product of the thioglycosides nor
b
-stereoisomer was detected in the reaction mixture.
Initial attempts were to assemble the pentasaccharide using triol
616 as an acceptor via regioselective 6-O-glycosylation with di-
saccharide donor 4, was not successful because of the formation of
both the 6-O and 3-O glycosylated products. This is probably due to
the increased reactivity of the 3-OH group induced by the presence
of free 2-OH group.17 Different reaction conditions, including vari-
ation in the solvents (Et2O, CH2Cl2, Toluene), and various promoter
22
systems (TfOH/NIS,18 AgOTf/NIS,19 MeOTf,20 DMTST,21 HgSO4
were tested to improve the regioselectivity but without success.
)

4120
S. Sarkar et al. / Tetrahedron 67 (2011) 4118e4122
OAc
OAc
4.1.1. Phenyl 2,4,6-tri-O-acetyl-1-thio-a-D-mannopyranoside (8). To
OAc
OAc
a solution of compound 7 (0.1 g, 0.37 mmol) in DMF (2 ml) trime-
thylorthoacetate (0.01 ml, 0.81 mmol) and p-TsOH (10 mg) were
added. The mixture was stirred for 10 min at room temperature. To
the reaction mixture 2 ml 80% AcOH was added and stirred for
45 min. The solution was co-evaporated with toluene till it becomes
completely acid free and dried over P2O5. The crude residue in 1 ml
O
AcO
AcO
O
AcO
AcO
O
OBz
O
a
b
OTBDPS
OH
O
O
3
OBz
O
BzO
BzO
BzO
BzO
AcO
O
SEt
13
OBn
pyridine was then cooled to ꢁ40 ꢀC and AcCl (0.18 mmol, 126
ml,
14
OH
0.5 equiv based on 7) was added. Stirring was continued for 6 h at
ꢁ40 ꢀC when TLC indicated 50% formation of a new product. MeOH
(0.1 ml) was added to destroy excess AcCl and diluted with CH2Cl2,
washed with water and evaporated to dryness. Flash chromatogra-
phy generated pure 8 (0.045 mg, 30% based on 7) as a colourless
OAc
OH
O
OAc
O
c
OH
HO
AcO
AcO
OH
OH
HO
OH
O
HO
O
HO
HO
O
OBz
O
O
O
BzO
BzO
O
OH
OR
e
d
24 þ114.79 (c 0.57, CHCl3); 1H NMR (CDCl3, 300 MHz):
d 2.05
OH
O
O
1
HO
HO
syrup. [
a
]
D
AcO
OH
O
(s, 3H, COCH3), 2.16 (s, 3H, COCH3), 4.06e4.14 (m, 2H), 4.29e4.35 (m,
1H), 4.50e4.52 (m,1H), 5.09e5.12 (m,1H), 5.32e5.33 (m,1H), 5.56 (s,
1H, H-1), 7.26e7.47 (m, 5H, aromatic protons); 13C NMR (CDCl3,
O
HO
O
OBn
15
R = TMS
17
OBn
16 R = H
75 MHz):
d 20.50, 20.64, 20.73, 62.43, 68.79, 68.99, 69.38, 73.49,
Scheme 3. Synthesis of pentasaccharide 17. Reagents and conditions: (1) One-pot
sequence. (a) 2, AgOTf, CH2Cl2, ꢁ20 ꢀC, 15 min; (b) 5, NIS, CH2Cl2, ꢁ20 ꢀC, 20 min;
(c) TMSOTf, ꢁ5 ꢀC to 0 ꢀC, 5 min, TfOH; (d) 4, NIS, ꢁ20 ꢀC, 15 min, 30% overall yield. (2)
De-protection of 1: (e) NH3/MeOH, 80%.
85.47, 127.83, 128.96, 131.79, 132.65, 170.31, 170.51, 170.60 ppm;
HRMS (ESI) calcd for C18H22O8SNa 421.0933 and found 421.0958.
4.1.2. Phenyl 2,3,4,6-tetra-O-acetyl-
a-D-mannopyranoside-(1/3)-
2,4,6-tri-O-acetyl-1-thio- -mannopyranoside (4). A solution of
a-D
Slow
tBuPh2Si
O
R
tBuPh2Si-O-R Me3SiOTf
OTf
thioglycoside acceptor 8 (0.1 g, 0.14 mmol), trichloroacetimidate
donor 9 (0.09 g, 0.15 mmol) and freshly activated molecular sieves
SiMe3
[B]
14
[
]
[A]
ꢀ
ꢀ
(4 A) in dry CH2Cl2 (1 ml) was stirred at ꢁ20 C under nitrogen for
15 min when TMSOTf (5 l) in CH2Cl2 was added into the reaction
m
TfOH/ fast
O
mixture. After 15 min TLC (Rf¼0.5; 7% MeOH in CH2Cl2) indicated
complete conversion of starting material. It was then quenched
with Et3N and stirring was continued for additional 5 min. The
R1O
O
TfOH
tBuPh2SiOTf
R1O
Me3SiOR
15
ROH
16
OR
[
]
1
[ ]
mixture was then diluted, filtered and concentrated. Silica gel col-
[
]
24
umn chromatography yielded 4 (0.15 mg, 85%) as syrup. [a]
D
þ44.00 (c 1.12, CHCl3); 1H NMR (CDCl3, 600 MHz):
d
2.00 (s, 3H,
Fig. 3. Plausible mechanism for the formation of 1.
COCH3), 2.05 (s, 3H, COCH3), 2.07 (s, 3H, COCH3), 2.15 (s, 3H, COCH3),
2.16 (s, 3H, COCH3), 2.18 (s, 3H, COCH3), 2.22 (s, 3H, COCH3),
4.09e4.11 (m, 2H), 4.16 (dd, J¼3.6, 9.6 Hz, 1H), 4.25 (dd, J¼1.5,
6.3 Hz, 1H), 4.27 (dd, J¼1.8, 2.4 Hz, 1H), 4.43e4.46 (m, 1H), 5.03 (s,
1H), 5.03 (d, J¼1.8 Hz, 1H), 5.04 (s, 1H), 5.21e5.27 (m, 2H), 5.35 (t,
J¼4.95 Hz, 1H), 5.49e5.5 (m, 1H), 5.52 (s, 1H), 7.30e7.47 (m, 4H,
3. Conclusion
In summary, wehave developed a simple, rapid and efficientone-
pot protocol for the synthesis of higher branched manno-oligosac-
charide. Regioselective 6-O-glycosylation in presence of free 2-OH
and 3-OH was not possible due to significant increase in reactivity of
the 3-OH, induced by free 2-OH group. This problem was elegantly
overcome by protecting the 6-OH group with tert-butyldiphenylsilyl
ether, regioselective 3-O-glycosilation, in situ removal of the tert-
butyldiphenylsilyl ether followed by 6-O-glycosylation sequentially.
Use of TMSOTf/TfOH allows almost instantaneous removal of the
tert-butyldiphenylsilyl ether group, which leads to a faster and ef-
fective one-pot synthesis.
aromatic protons); 13C NMR (CDCl3, 150 MHz):
d 20.62, 20.63, 20.71,
20.74, 20.85, 20.92, 62.5, 62.62, 65.91, 67.97, 68.11, 69.53, 69.63,
69.89, 72.25, 74.99, 85.71, 98.87, 128.20, 129.24, 131.96, 132.39,
169.59, 169.84, 169.90, 170.04, 170.32, 170.56, 170.74 ppm; HRMS
(ESI) calcd for C30H38O16SNa 751.1884 and found 751.1934.
4.1.3. Benzyl 2,3-O-isopropylidene-6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside (11). To a stirred solution of compound 10
(140 mg, 0.28 mol) in dry DMF (2 ml), 2,2-dimethoxypropane
(0.034 g, 0.04 ml, 0.33 mol) and p-TsOH (20 mg) were added. The
mixture was stirred at room temperature for 12 h. It was then
quenched with Et3N, concentrated to syrup, which on column
4. Experimental
4.1. General information
chromatography (Rf¼0.71; 10% EtOAc in Toluene) gave 11
24
D
All solvents used were distilled and/or dried before use. Evapo-
rations were conducted below 40 ꢀC under reduced pressure unless
stated otherwise. Analytical thin-layer chromatography was per-
formed on silica gel 60 F254 aluminium plates. The spots were vi-
sualized by charring with 10% (v/v) H2SO4 in EtOH or detected using
UV light. Column chromatography and flash column chromatogra-
phy were performed on 60e120 and 230e400 mesh silica gel, re-
spectively. Optical rotations were measured with a PerkineElmer
model 241-MC automatic polarimeter for solutions in a 1-dm cell.1H
and 13C NMR spectrawere recorded in Bruker DPX 300/600 MHz and
Bruker DPX 75/150 MHz spectrometer, respectively, using tetra-
(0.125 mg, 82%) as a yellow syrup. [
a
]
þ17.59 (c 1.22, CHCl3); 1H
NMR (CDCl3, 300 MHz):
d 1.07 [s, 9H, Ph2SiC(CH3)3], 1.34 [s, 3H,
C(CH3)2], 1.49 [s, 3H, C(CH3)2], 3.72e3.95 (m, 4H), 4.17 (m, 2H), 4.48
(d, J¼11.7 Hz, 1H, OCH2Ph), 4.69 (d, J¼11.7 Hz, 1H, OCH2Ph), 5.08 (s,
1H, H-1), 7.24e7.72 (m, 15H, aromatic protons); 13C NMR (CDCl3,
75 MHz): d 19.22, 26.15, 26.81, 27.9, 64.33, 68.79, 69.89, 70.3, 75.48,
78.46, 95.98, 109.46, 127.72, 127.75, 127.92, 128.23, 128.44, 129.78,
133.03, 133.19, 135.58, 135.67, 136.88 ppm; HRMS (ESI) calcd for
C32H40O6SiNa 571.2496 and found 571.2492.
4.1.4. Benzyl 2,3-O-isopropylidene-4-O-acetyl-6-O-tert-butyldiphe-
nylsilyl-a-D-mannopyranoside (12). Compound 11 (100 mg,
methylsilane (
d
¼0.00) as an internal standard at 25 ꢀC. ESI-MS
(positive) was conducted using LC-ESI-Q-TOF micro Mass
spectrometer.
0.18 mmol) was dissolved in pyridine (1 ml) and Ac2O (0.2 ml) was
added drop wise at 0 ꢀC. The resulting mixture was warmed

S. Sarkar et al. / Tetrahedron 67 (2011) 4118e4122
4121
gradually to room temperature and stirred. After 6 h TLC indicated
(Rf¼0.84; 5% EtOAc in Toluene) complete conversion of the starting
material. The reactionwas quenched with methanol(0.2 ml), diluted
with CH2Cl2 (10 ml) and washed with water and brine. The organic
129.91, 133.14, 133.64, 133.67, 137.03, 165.15, 165.62, 165.64, 169.51,
169.62, 169.72, 169.85, 169.96, 170.02, 170.46, 170.56, 170.83; HRMS
(ESI) calcd for C82H94O41Na 1757.5168 and found 1757.5136.
layer was separated and dried over Na2SO4 to get pure 12 (0.1 g, 95%)
4.1.7. Ethyl 2,3,4,6-tetra-O-acetyl-a-D-mannopyranoside-(1/6)-2,3,
24
24
as a thick glass. [
a
]
þ17.01 (c 0.68, CHCl3); 1H NMR (CDCl3,
4-tri-O-benzoyl-1-thio-a-D-mannopyranoside (13). Thick glass. [a]
D
D
300 MHz):
d
1.06 [s, 9H, Ph2SiC(CH3)3], 1.34 [s, 3H, C(CH3)3], 1.55 [s,
ꢁ1.32 (c 1.26, CHCl3); 1H NMR (CDCl3, 600 MHz):
1.4 (t, J¼7.2 Hz, 3H,
d
3H, C(CH3)3], 1.93 (s, 3H, COCH3), 3.64 (d, J¼11.1 Hz, 1H), 3.74e3.88
(m, 2H), 4.19e4.27 (m, 2H), 4.56 (d, J¼11.7 Hz, 1H, OeCH2ePh), 4.79
(d, J¼11.7 Hz,1H, OeCH2ePh), 5.04 (t, J¼8.7 Hz,1H), 5.16 (s,1H, H-1),
7.24e7.71 (m, 15H, aromatic protons); 13C NMR (CDCl3, 75 MHz):
SeCH2eCH3), 1.94 (s, 3H, COCH3), 2.0 (s, 3H, COCH3), 2.05 (s, 3H,
COCH3), 2.13 (s, 3H, COCH3), 2.72e2.82 (m, 2H, SeCH2eCH3), 3.65 (dd,
J¼10.8,1.8 Hz, 1H), 3.98e4.0 (m, 3H), 4.1e4.12 (m, 1H), 4.72e4.75 (m,
1H), 4.84 (d, J¼1.8 Hz, 1H), 5.25 (t, J¼10.2 Hz, 1H), 5.29e5.3 (m, 1H),
5.37 (dd, J¼3.6, 10.2 Hz, 1H), 5.56 (s, 1H), 5.79 (dd, J¼1.2, 3.0 Hz, 1H),
5.83 (dd, J¼3.3, 9.9 Hz, 1H), 5.9 (t, J¼10.2 Hz, 1H), 7.24e8.12 (m, 15H,
d
19.18, 20.81, 26.41, 26.53, 26.72, 27.56, 63.13, 68.69, 69.46, 69.79,
75.84, 76.20, 95.66, 109.84, 127.60, 127.67, 127.94, 128.28, 128.45,
129.64, 133.22, 133.27, 135.59, 135.69, 136.82, 169.63 ppm; HRMS
(ESI) calcd for C34H42O7SiNa 613.2597 and found 613.2597.
aromatic protons); 13C NMR (CDCl3, 150 MHz):
d 14.66, 20.58, 20.70,
20.74, 20.85, 25.27, 62.24, 65.89, 66.47, 67.23, 68.54, 68.94, 69.32,
69.72, 70.45, 72.11, 81.78, 97.31, 128.31, 128.53, 128.74, 128.88, 129.26,
129.71, 129.84, 129.91, 133.22, 133.56, 133.64, 165.36, 165.52, 165.54,
169.59, 169.73, 169.93, 170.55 ppm; HRMS (ESI) calcd for
C43H46O17SNa 889.2353 and found 889.2423.
4.1.5. Benzyl 4-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-mannopyr-
anoside (5). Compound 12 (100 mg, 0.18 mmol) dissolved in 80%
AcOH (2 ml) was heated at 80 ꢀC for 45 min when TLC (Rf¼0.82; 5%
MeOH in DCM) indicates formation of a new product. Column
chromatography produced pure 5 (0.07 g, 75%). [
a
]
24.0 þ62.76 (c 0.1,
4.1.8. Benzyl 3-O-(2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-acetyl-
a-
D
CHCl3); 1H NMR (CDCl3, 300 MHz):
d
1.06 [s, 9H, Ph2SiC(CH3)3], 1.97
D
-mannopyranosyl)- -mannopyranosyl)-4-O-acetyl-6-O-tert-bu-
a-D
24.0
(s, 3H, COCH3), 2.42 (br s, 1H, OH), 2.98 (br s, 1H, OH), 3.70e3.97 (m,
5H), 4.54 (d, J¼11.7 Hz, 1H, OeCH2ePh), 4.76 (d, J¼11.7 Hz, 1H,
OeCH2ePh), 4.98e5.08 (m, 2H), 7.26e7.69 (m, 15H, aromatic pro-
tyldiphenylsilyl-a-D-mannopyranoside (14). Yellow syrup. [a]
D
ꢁ4.37 (c 1.5, CHCl3); 1H NMR (CDCl3, 600 MHz):
d 1.08 [s, 9H,
Ph2SiC(CH3)3], 1.95 (s, 3H, COCH3), 1.97 (s, 3H, COCH3), 2.0 (s, 3H,
COCH3), 2.09 (s, 3H, COCH3), 2.12(s, 3H, COCH3), 3.63 (dd, J¼1.8, 10.8 Hz,
1H), 3.71 (dd, J¼5.55, 11.10 Hz, 1H), 3.85e3.97 (m, 5H), 4.12e4.15 (m,
2H), 4.26 (s,1H), 4.57 (d, J¼12.0 Hz, 1H, OeCH2Ph), 4.64e4.67 (m, 1H),
4.8 (d, J¼11.4 Hz, 1H, OeCH2Ph), 4.85 (s,1H), 5.1 (s, 1H), 5.22e5.30 (m,
3H), 5.36 (t, J¼9.9 Hz, 1H), 5.4 (dd, J¼3.3, 10.2 Hz, 1H), 5.56e5.57 (m,
1H), 5.76 (dd, J¼3.3, 9.9 Hz, 1H), 5.87 (t, J¼5.1 Hz, 1H), 7.26e8.09 (m,
tons); 13C NMR (CDCl3, 75 MHz):
d 19.23, 20.91, 26.77, 63.21, 68.85,
70.24, 70.54, 70.84, 71.17, 98.31, 127.67, 127.72, 127.92, 128.02,
128.46, 129.71, 133.27, 135.63, 135.69, 136.99, 171.72 ppm; HRMS
(ESI) calcd for C31H38O7SiNa 573.2284 and found 573.2277.
4.1.6. Benzyl 6-O-(2,4,6-tri-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-
mannopyranosyl)- -mannopyranosyl)-3-O-(2,3,4-tri-O-benzoyl-6-O-
(2,3,4,6-tetra-O-acetyl- -mannopyranosyl)- -mannopyranosyl)-4-
O-acetyl- -mannopyranoside (1). A solution of compound
(100 mg, 0.19 mmol) and 2 (84 mg, 0.2 mmol) in dry CH2Cl2 (1 ml)
a-D-
a-D
30H, aromatic protons); 13C NMR (CDCl3, 150 MHz):
d 19.19, 20.54,
a-D
a-D
20.68, 20.81, 26.77, 26.83, 62.20, 63.49, 65.98, 66.64, 66.66, 66.80,
68.62, 68.87, 68.90, 69.30, 69.78, 69.82, 69.90, 70.64, 71.97, 80.38, 97.53,
98.48, 98.61, 127.64, 127.68, 127.79, 127.96, 128.22, 128.38, 128.49,
128.67, 128.71, 128.80, 128.86, 128.92, 129.05, 129.10, 129.65, 129.67,
129.84, 129.89, 133.05, 133.26, 133.32, 133.58, 133.61, 135.65, 135.68,
137.14, 165.07, 165.57, 165.64, 169.52, 169.72, 169.84, 170.05,
170.54 ppm; HRMS (ESI) calcd for C72H78O24SiNa 1377.4550 and found
1377.4514.
a-D
3
ꢀ
ꢀ
was stirred at ꢁ20 C with powdered molecular sieves (4 A) under
nitrogen. After 30 min, AgOTf (10 mg) was added and stirring was
continued for further 15 min when TLC (compound 13, Rf¼0.33; 20%
EtOAc in Toluene) indicated complete consumption of starting ma-
terials, NIS (87 mg, 0.32 mmol) along with 5 (94 mg, 0.17 mmol) was
added in it. After 20 min TLC (Rf¼0.4; 3% MeOH in CH2Cl2) showed
formation of a new product (14). The reaction temperature was then
raised to ꢁ5 ꢀC. TMSOTf (0.06 g, 0.3 mmol) in CH2Cl2 (1 ml) was
added and stirring was continued for 5 min at the end of which TfOH
(0.06 g, 0.4 mmol) was added to it. TLC (Rf¼0.27; 3% MeOH in CH2Cl2)
indicated formation of a new product (16). Compound 4 (95 mg,
0.13 mmol) and NIS (55 mg, 0.2 mmol) dissolved in CH2Cl2 (1 ml)
were then added into the reaction mixture at ꢁ20 ꢀC and allowed to
react for 15 min. It was then quenched with Et3N and stirring was
continued for additional 10 min. The mixture was then diluted, fil-
tered and concentrated. The residue was subjected to silica gel col-
umn chromatography (Rf¼0.54; 3% MeOH in CH2Cl2) to yield 1 (30%)
4.1.9. Benzyl 3-O-(2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-acetyl-a-
D
-mannopyranosyl)-
thylsilyl- -mannopyranoside (15). Colourless syrup. [
0.2, CHCl3); 1H NMR (CDCl3, 600 MHz):
a-D-mannopyranosyl)-4-O-acetyl-6-O-trime-
a-D
a]
D
24 ꢁ5.37 (c
d
0.26 (s, 9H, Si(CH3)3), 1.9 (s,
3H, COCH3),1.98(s,3H,COCH3), 2.03(s,3H, COCH3), 2.13 (s,3H, COCH3),
2.22 (s, 3H, COCH3), 3.55e3.59 (m, 3H), 3.64 (dd, J¼1.8, 10.8 Hz, 1H),
3.86 (dd, J¼1.8,12.6 Hz,1H), 3.92 (ddd, J¼1.8, 5.1 and 4.95 Hz,1H), 3.96
(dd, J¼4.8,11.1Hz,1H), 4.09(d, J¼5.4Hz,1H), 4.1e4.11(m,1H), 4.26(dd,
J¼2.4, 3.0 Hz, 1H), 4.4e4.42 (m, 1H), 4.57 (d, J¼8.4 Hz, 1H), 4.67 (d,
J¼12.0 Hz, 1H), 4.85 (s, 1H), 4.87 (s, 1H), 5.28 (t, J¼10.2 Hz, 1H),
5.35e5.41 (m, 3H), 5.45 (dd, J¼10.2, 3.0 Hz, 1H), 5.57e5.58 (m, 1H),
5.92 (dd, J¼10.2, 3.0 Hz,1H), 6.07 (t, J¼10.2 Hz,1H), 7.24e8.14 (m, 20H,
as a syrup. [
a
]
24 þ124.01 (c 0.68, CHCl3); 1H NMR (CDCl3, 600 MHz):
D
d
1.96 (s, 3H, COCH3),1.97 (s, 3H, COCH3), 1.99 (3H, s, COCH3), 2.01 (3H,
aromatic protons); 13C NMR (CDCl3, 150 MHz):
d 0.52, 20.50, 20.69,
s, COCH3), 2.02 (3H, s, COCH3), 2.03 (3H, s, COCH3), 2.05 (s, 3H,
COCH3), 2.08 (s, 3H, COCH3), 2.11 (s, 3H, COCH3), 2.11 (s, 3H, COCH3),
2.13 (s, 3H, COCH3), 2.14 (s, 3H, COCH3), 3.6e3.63 (m, 3H), 3.92e4.31
(m, 14H), 4.58 (t, J¼10.62 Hz, 1H), 4.64e4.67 (m, 1H), 4.7 (d,
J¼11.64 Hz, 1H), 4.84 (s, 1H), 4.92 (s, 1H), 4.98 (s, 1H), 5.2e5.44 (m,
10H), 5.58 (m, 1H), 5.76e5.79 (m, 1H), 5.85e5.88 (m, 1H), 7.24e8.09
20.75, 20.84, 20.88, 61.38, 62.08, 65.76, 66.44, 66.72, 68.66, 68.82,
69.15, 69.30, 69.39, 69.48, 69.68, 70.57, 71.67, 71.86, 76.08, 98.13, 98.91,
99.62, 127.93, 127.95, 128.28, 128.50, 128.52, 128.83, 128.88, 129.03,
129.14, 129.74, 129.93, 133.11, 133.55, 133.59, 137.24, 165.22, 165.28,
165.57,169.37,169.74,169.78,170.49,171.61 ppm; HRMS (ESI) calcd for
C59H68O24SiNa 1211.3767 and found 1211.3767.
(m, 20H); 13C NMR (CDCl3, 150 MHz):
d 20.57, 20.69, 20.76, 20.82,
20.85, 20.91, 20.97, 62.20, 62.28, 62.51, 62.54, 65.90, 65.95, 65.98,
66.34, 66.61, 67.67, 68.38, 68.68, 68.84, 68.89, 69.30, 69.38, 69.58,
69.78, 69.86, 69.88, 70.31, 70.66, 70.94, 74.63, 80.03, 80.27, 97.27,
97.61, 98.78, 98.90, 98.99, 127.89, 127.95, 128.03, 128.27, 128.43,
128.46, 128.52, 128.65, 128.69, 128.75, 129.02, 129.08, 129.70, 129.86,
4.1.10. Benzyl
(1/6)-[ -mannopyranosyl-(1/6)-
-mannopyranoside (17). A solution of 1 (20 mg, 0.01 mmol) in
MeOH (2 ml) was added to a saturated solution of ammonia in MeOH
(2 ml). After days at room temperature the solution was
a
-
D
-mannopyranosyl-(1/3)-
a-D-mannopyranosyl-
a
-
D
a-D
-mannopyranosyl-(1/3)]-
a-D
6

4122
S. Sarkar et al. / Tetrahedron 67 (2011) 4118e4122
2. (a) Ritter, T. K.; Mong, K.-K. T.; Liu, H.; Nakatani, T.; Wong, G.-H. Angew. Chem., Int.
Ed. 2003, 42, 4657; (b) Mong, K.-K. T.; Wong, C.-H. Angew. Chem., Int. Ed. 2002, 41,
4087; (c) Wang, C.-C.; Lee, J.-C.; Luo, S.-Y.; Fan, H.-F.; Pai, C.-L.; Yang, W.-C.; Lu, L.-
D.; Hung, S.-C. Angew. Chem., Int. Ed. 2002, 41, 2360; (d) Lee, J.-C.; Wu, C.-Y.; Apon,
J. V.; Siuzdak, G.; Wong, C.-H. Angew. Chem., Int. Ed. 2006, 45, 2753; (e) Lahmann,
M.; Oscarson, S. Org. Lett. 2000, 2, 3881; (f) Mukhopadhyay, B.; Maurer, S. V.;
Rudolph, N.; Well, R. M. v.; Russell, D. A.; Field, R. A. J. Org. Chem. 2005, 70, 9059.
3. (a) Boeckel, C. A. A. V.; Beetz, T.; Aelst, S. F. V. Tetrahedron 1984, 40, 4097;
(b) Huang, L.; Wang, Z.; Huang, X. Chem. Commun. 2004, 1960.
concentrated, and the residue was purified by Biogel P-2 (F) column
(1.0 cm I.Dꢂ90 cm; water as eluent) to produce 17 (80%). [
a
]
24 þ37.24
D
(c 0.1, MeOH); 1H NMR (D2O, 600 MHz):
d 3.53e4.02 (m, 30H, ring
protons), 4.57(d, J¼11.6Hz,1H), 4.63 (d, J¼11.6 Hz,1H), 4.75 (s,1H), 4.77
(s, 1H), 4.84 (s, 1H), 4.94 (s, 1H), 5.03 (s, 1H), 7.3e7.37 (m, 5H, aromatic
protons); 13C NMR (D2O, Me2O, 150 MHz):
d 61.66, 61.73, 61.76, 66.64,
67.40, 67.52, 67.64, 70.42, 70.73, 70.79, 70.86, 70.89, 71.18, 71.39, 71.51,
72.05, 72.40, 73.47, 73.65, 74.06, 74.08, 79.52, 80.09, 100.45, 100.49,
103.03, 103.14, 103.48, 129.38, 129.43, 129.63, 129.66, 137.67 ppm;
HRMS (ESI) calcd for C37H58O26Na 941.3114 and found 941.3121.
4. (a) Huang, X.; Huang, L.; Wang, H.; Ye, X.-S. Angew. Chem., Int. Ed. 2004, 43, 5221;
(b) Zeng, Y.; Wang, Z.; Whitfield, D.; Huang, X. J. Org. Chem. 2008, 73, 7952.
5. (a)
ˇ
Zhu, T.; Boons, G.-J. Angew. Chem., Int. Ed. 1999, 38, 3495; (b) Geurtsen, R.;
ꢁ
Cote, F.; Hahn, M. G.; Boons, G.-J. J. Org. Chem. 1999, 64, 7828.
6. Tanaka, H.; Adachi, M.; Tsukamoto, H.; Ikeda, T.; Yamada, H.; Takahashi, T. Org.
Lett. 2002, 4, 4213.
Acknowledgements
7. (a) Bhattachryya, S.; Magnusson, B. G.; Wellmar, U.; Nilsson, U. J. J. Chem. Soc.,
Perkin Trans. 1 2001, 886; (b) Vohra, Y.; Vasan, M.; Venot, A.; Boons, G.-J. Org.
Lett. 2008, 10, 3247; (c) Zhu, T.; Boons, G.-J. Tetrahedron Lett. 1998, 39, 2187.
8. Kumar, R.; Maulik, P. R.; Misra, A. K. Glycoconjugate J. 2008, 25, 595.
9. Boons, G.-J.; Grice, P.; Leslie, R.; Ley, S. V.; Yeung, L. L. Tetrahedron Lett. 1993, 34,
8523.
10. Tennant-Eyles, R. J.; Davis, B. G.; Fairbanks, A. J. Tetrahedron: Asymmetry 2003,
14, 1201.
11. Cmoch, P.; Pakulski, Z. Tetrahedron: Asymmetry 2008, 19, 1494.
12. Smiljanic, N.; Halila, S.; Moreau, V.; Djedaïni-Pilard, F. Tetrahedron Lett. 2003,
44, 8999.
The authorsexpresstheirgratitudetoProf. S. Roy, Director, IICBfor
continuous encouragements, Prof. M. Vijayan, Honorary Professor,
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, for
suggesting the problem and CSIR, New Delhi, for providing fellow-
ships to S.S. and S.D. We are indebted to Dr. R. Mukherjee,
Mr. K. Sarkar and Mr. E. Padmanaban for recording NMR and ESI-MS.
13. Gemma, E.; Lahmann, M.; Oscarson, S. Carbohydr. Res. 2005, 340, 2558.
14. Wu, Z.; Kong, F. Carbohydr. Res. 2003, 338, 1727.
Supplementary data
15. Rising, T. W. D. F.; Claridge, T. D. W.; Davies, N.; Gamblin, D. P.; Moir, J. W. B.;
Spectroscopic characterization data, 1H, 13C NMR spectra for all
new compounds are included in the supplementary data. Supple-
mentary data associated with this article can be found in online
version at doi:10.1016/j.tet.2011.03.109. These data include MOL
files and InChiKey of the most important compounds described in
this article.
Fairbanks, A. J. Carbohydr. Res. 2006, 341, 1574.
16. (a) Eby, R.; Schuerch, C. Carbohydr. Res. 1982, 100, C41; (b) Ashry, E. S. H. E.;
Schuerch, C. Bull. Chem. Soc. Jpn. 1986, 59, 1581.
17. Oscarson, S.; Tedebark, U. Carbohydr. Res. 1995, 278, 271.
18. Magaud, D.; Dolmazon, R.; Anker, D.; Doutheau, A. Org. Lett. 2000, 2, 2275.
19. Gemma, E.; Lahmann, M.; Oscarson, S. Carbohydr. Res. 2006, 341, 1533.
20. (a) Lonn, H. Carbohydr. Res. 1985, 139, 105; (b) Lonn, H. J. Carbohydr. Chem. 1987,
6, 301.
21. Fugedi, P.; Garegg, P. J. Carbohydr. Res. 1986, 149, C9.
22. Ferrier, R. J.; Hay, R. W.; Vethaviyasar, N. Carbohydr. Res. 1973, 27, 55.
23. (a) Arnarp, J.; Haraldsson, M.; Lonngren, J. J. Chem. Soc., Perkin Trans. 1 1985,
535; (b) Spijiker, N. M.; Boeckel, C. A. A. Angew. Chem., Int. Ed. Engl. 1991, 30, 180.
24. Hunter, R.; Hinz, W.; Richards, P. Tetrahedron Lett. 1999, 40, 3643.
25. Bou, V.; Vilarrasa, J. Tetrahedron Lett. 1990, 31, 567.
References and notes
1. Singh, D. D.; Saikrishnan, K.; Kumar, P.; Surolia, A.; Sekar, K.; Vijayan, M. Gly-
cobiology 2005, 15, 1025.