Synthesis of branched arabinofuranose pentasaccharide fragment of mycobacterial arabinans as 2-azidoethyl glycoside

Article abstract of DOI:10.1016/j.carres.2012.05.021

Branched arabinofuranose pentasaccharide with 2-azidoethyl aglycon was prepared for the first time by [3+1+1] bis-(1,2-cis)-glycosylation of trisaccharide diol with silyl-protected thioglycoside glycosyl donor. The presence of 2-azidoethyl aglycon would e

Full text of DOI:10.1016/j.carres.2012.05.021

Carbohydrate Research 357 (2012) 62–67
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of branched arabinofuranose pentasaccharide fragment
of mycobacterial arabinans as 2-azidoethyl glycoside
Ksenia G. Fedina a,b, Polina I. Abronina a, Nikita M. Podvalnyy a, Nikolay N. Kondakov a,
Alexander O. Chizhov a, Vladimir I. Torgov a, Leonid O. Kononov a,
⇑
a N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky Prosp., 47, 119991 Moscow, Russian Federation
b The Higher Chemical College of the Russian Academy of Sciences, Miyuskaya pl. 9, 125047 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Branched arabinofuranose pentasaccharide with 2-azidoethyl aglycon was prepared for the first time by
[3+1+1] bis-(1,2-cis)-glycosylation of trisaccharide diol with silyl-protected thioglycoside glycosyl donor.
The presence of 2-azidoethyl aglycon would enable the preparation of neoglycoconjugates using the click
chemistry approaches.
Received 29 March 2012
Received in revised form 17 May 2012
Accepted 18 May 2012
Available online 28 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Arabinofuranose
1,2-cis-Glycosylation
Pentasaccharide
Aglycon
Azide
1. Introduction
ment7–9,12,13,16–21 prepared as reducing sugars,7,9 simple
alkyl8,9,17,18 or alkylidene16,19,21 glycosides or functionalized glyco-
Human tuberculosis (TB) remains a major worldwide health
problem and takes millions of lives annually.1,2 This disease has
received increasing attention due to emerging drug-resistant
strains of Mycobacterium tuberculosis, the microorganism that
causes TB.3 For this reason, an important area of research may in-
clude the synthesis of natural carbohydrates present on the cell
wall of M. tuberculosis, their fragments and neoglycoconjugates
thereof for identification of new drug targets for treatment of TB,
development of conjugate vaccines for prevention of TB as well
as for design of new agents for diagnosis of TB.
sides with carboxy12 or amino7,22 group at the terminal position of
the aglycon. However, the synthesis of the larger structures7,21 (up
to 31 residues20) requires a lot of effort and exceptionally high
qualification and expertise.
At the same time, it is known that in many cases behavior of
complex oligo- or polysaccharides can be successfully modeled by
neoglycoconjugates comprising only small (usually terminal) oligo-
saccharide fragments of the parent natural saccharide.23 Currently,
many neoglycoconjugates, including non-glycosidically-linked
oligosaccharides,24–26 glycosyl-clusters,24,27,28 glycodendrimers,27
glycopolymers,27 glycopeptides,24,26,29–31 b-cyclodextrin ana-
logs,24,27,32 are being prepared by click-chemistry24,27,29,33–38 which
enables an easy coupling of chemically diverse structures. Although
different reactions27,30,39 can be used for click-chemistry, the most
popular approach relies on the use of Cu(I)-catalyzed29,33,36,40,41 or
strain-promoted39,42–44 Huisgen 1,3-dipolar cycloaddition of azides
to terminal alkynes.
The cell wall of M. tuberculosis consists mainly of two polysac-
charides, the mycolyl-arabinogalactan-peptidoglycan complex
(mAGP) and lipoarabinomannan (LAM), both of which contain an
arabinan domain which is composed of
the furanose form which are linked in a combination of
-(1?5), and b-(1?2) glycosidic linkages.4–6 The arabinan chains
are capped at the nonreducing ends with the branched pentasac-
charide fragment [b- -Ara(1-2)- -Ara(1-5)]-[b- -Ara(1-2)-
Ara(1-3)]- -Ara.
D
-arabinose residues in
a-(1?3),
a
D
a-D
D
a-
D
-
The preparation of mycobacterial oligosaccharides with azido
group in aglycon is an important task since azido group can pro-
vide a possibility to use the power of click chemistry for synthesiz-
ing various neoglycoconjugates27 including, for example, new
covalent conjugates with recombinant proteins of M. tuberculosis22
in order to obtain in vitro glycosylated antigens for serodiagnosis
of TB. As the first step in this direction we set out to prepare termi-
a
-D
Various strategies7–16 have been developed for the synthesis of
oligosaccharides containing this terminal pentasaccharide frag-
⇑
Corresponding author. Tel.: +7 495 943 2946; fax: +7 499 1355328.
E-mail
addresses:
leonid.kononov@gmail.com,
kononov@ioc.ac.ru
nal pentasaccharide fragment as 2-azidoethyl45 glycoside
8
(L.O. Kono nov).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.05.021

K. G. Fedina et al. / Carbohydrate Research 357 (2012) 62–67
63
(Scheme 1), which can further be used for the preparation of wide
range of neoglycoconjugates.
virtually inert under the most conditions used during oligosaccha-
ride synthesis. In this context, it is worth mentioning that 2-chlo-
roethyl glycosides, unlike 2-azidoethyl glycosides, may survive
even the conditions of catalytic hydrogenolysis (L. O. Kononov et
al., unpublished results).
2. Results and discussion
The majority of the known approaches (for
exception7 see the discussion above) used for the assembly of
oligosaccharides containing the pentasaccharide fragment [b-
Ara(1-2)- -Ara(1-5)]-[b- -Ara(1-2)- -Ara(1-3)]- -Ara are
a possible
Although an azide-containing monosaccharide derivative of
arabinofuranose has been prepared and used in click chemistry-
based preparation of b-arabinofuranose glycosyl triazoles,46 there
are no examples of the synthesis of arabinofuranose oligosaccha-
rides with azido group in aglycon to the best of our knowledge.
Different strategies can be used for the introduction of function-
alized aglycon into an oligosaccharide as required for the prepara-
tion of neoglycoconjugates.23 One of the popular approaches
makes use of temporary protecting group at the anomeric position.
After the assembly of the required oligosaccharide the anomeric
protection is cleaved and the resulting hemiacetal is converted into
a suitable glycosyl donor and then to the glycoside with a function-
alized spacer aglycon. In this context it is necessary to note that
this strategy has been successfully used7 for the synthesis of hemi-
acetals of otherwise O-benzoylated oligosaccharides related to the
Mycobacterial arabinans (including a pentasaccharide similar to
compound 8). These derivatives could have been used as glycosyl
donors for the synthesis of spacered glycosides. In such a case, if
the preparation of 2-azidoethyl glycoside is required, glycosylation
of 2-azidoethyl alcohol or other simple alcohols like 2-chloro- or 2-
bromoethanol would be necessary. However, it is known47 that in
some cases glycosidations of complex oligosaccharides by simple
alcohols may lead to the mixtures of anomers, which are difficult
to separate due to their close chromatographic mobilities.
D-
a
-D
D
a-
D
a-D
not compatible with azido group in the aglycon since most of them
rely on the use of O-benzyl protecting groups either in glycosyl
acceptors13,17–19 or in glycosyl donors7,9,13,17–19,22,51 used for the
construction of 1,2-cis-linkage, which are difficult to remove in
the presence of azide. For example, the use of catalytic hydrogen-
olysis for de-O-benzylation is not possible since the azido group
is reduced faster than any substantial cleavage of O-benzyl groups
occurs. The related problem of removal of O-benzyl groups from
the derivatives with azido group in aglycon even with concomitant
reduction of the latter to amino function is recognized in neoglyco-
conjugate chemistry. In many cases the required de-O-benzylated
derivative with amino group in aglycon can be easily obtained by
a simple catalytic hydrogenolysis.49 However, in other cases more
sophisticated by-pass routes are required that rely on initial reduc-
tion of azido group in the aglycon to amino group (for example, by
Ph3P13 or controlled hydrogenation49) followed by its protection
(for example, as trifluoroacetamide13,49), exhaustive hydrogenoly-
sis of O-benzyl groups and final amine deprotection. Unfortunately,
all these approaches do not allow preservation of the azido group
in the aglycon and thus could not be used for the synthesis of
pentasaccharide 8. For this reason, we started developing a novel
benzyl-free strategy for the assembly of arabinoligosaccharides, de-
signed several useful O-benzoylated arabinofuranose building
blocks (including those with 2-chloroethyl aglycon)52,53 and suc-
cessfully used them as glycosyl acceptors in the synthesis of oligo-
saccharides22,54 with spacer aglycons.
For this reason, we used an alternative pre-spacer approach,23
which would avoid such problems in the synthesis of the title
pentasaccharide. This approach is based on the preparation of pro-
tected pentasaccharide as 2-chloroethyl glycoside48 starting from
2-chloroethyl glycoside of the monosaccharide at the reducing
end (corresponds to the residue AraI in trisaccharide 1) and further
introduction of azide into the aglycon at the stage of pentasaccha-
ride. The advantages of using 2-chloroethyl aglycon48 over the use
of 2-azidoethyl aglycon45 already on the monosaccharide building
block are multiple. Most importantly, although there is evidence
that the presence of azide in aglycon of glycosyl acceptor may neg-
atively influence the outcome of glycosylation in some cases,49,50
the corresponding influence of the chlorine is not documented to
the best of our knowledge. Moreover, the aliphatic chlorine is
Stereoselective introduction of two b-linked arabinofuranose
residues is the most crucial and challenging step during any
synthesis of the pentasaccharide in question and may rely on
different approaches developed for the introduction of 1,2-cis
linkages.8,9,12,55,56 In our previous work22 we used b-selective
arabinofuranose thioglycoside donor11 with 2-O-benzyl and 3,5-O-
di-tert-butylsilylene protecting groups. Since now we had to avoid
using O-benzyl protecting groups, all the variety of glycosyl donors
OR1
OR2
BzO
OH
O
III
V
V
O
O
OBz
O
O
R3O
BzO
O
OBz
HO
R1O
HO
I
O
O
RO
O
OBz
O
O
Cl
III
III
II
O
OBz
O
O
OR
O
O
O
O
OBz
OR1
I
OR
BzO
I
e
OBz
c
OR
Cl
O
N3
O
1 = COCH2Cl
1
R
a
II
II
2 R1 = H
O
O
HO
BzO
R3O
RO
HO
O
O
R1O
+
OR2
O
O
O
O
IV
IV
V
t-Bu
Si
SR1
O
OR2
OH
t-Bu
R1 = Ph, R2 = H
R
R
R
R
1 =TIPS; R2, R3 = (t-Bu)2Si
1 = R2 = R3 = H
7
8
3
4a
4b
5
6
R = Bz
R = H
f
d
1 = Tol, R2 = TIPS
1 = Ph, R2 = TIPS
b
Scheme 1. Synthesis of unprotected pentasaccharide 2-azidoethyl glycoside 8. Reagents and conditions: (a) Py, H2O, 70 °C (96%); (b) TIPSOTf, sym-collidine, DMF, 90 °C (94%);
(c) NIS, AgOTf, DCM, MS 4 Å, ꢀ40 °C?ꢀ13 °C (77% of 5, mixture of isomers, bb:other isomers = 6.14:1); (d) TBAF, THF, AcOH (77%, mixture of isomers); (e) (1) NaN3, 18-
crown-6, DMF, 70 °C; (2) HPLC on silica gel, i-PrOH–CHCl3–petroleum ether, 1:3:6 (55% of 7); (f) MeONa, MeOH (93%). TIPS = i-Pr3Si.

64
K. G. Fedina et al. / Carbohydrate Research 357 (2012) 62–67
Table 1
with non-participating 2-O-benzyl protecting group developed ear-
lier9,13,17,19,51 could not be used in our synthesis. Fortunately for us,
Ito and co-workers described8 a synthesis of arabinofuranose tolyl
thioglycoside 4a with 2-O-silyl and 3,5-O-di-tert-butylsilylene pro-
tecting groups, which can potentially be removed with fluoride-
based reagents57,58 in the presence of azido group. Although this gly-
13C NMR chemical shifts (151 MHz, CDCl3, dC)
2
4
5
6
7
8a
1I
105.9
107.7
108.1
—
—
—
—
—
92.8
—
—
106.1
106.0
107.3
101.7
101.4
82.9
86.5
86.4
76.3
76.3
80.3
78.2
78.2
79.0
78.8
81.8
81.0
80.6
73.9
73.9
66.7
64.5b
64.3b
68.3
68.3
67.5
42.5
105.7
106.46
106.47
101.6
101.0
83.4
85.8
85.3
78.0
77.9
82.2
78.3
78.6
74.1
74.1
81.5
79.8
79.8
82.6
82.6
65.9
63.7b
63.6b
62.0
62.0
67.5
42.4
105.8
106.3
106.5
101.5
101.0
83.2
85.7
85.1
77.82
77.75
81.7b
78.4
109.7
107.0
107.5
102.4
102.4
82.0
1II
1III
1IV
1V
cosyl
donor
demonstrated
moderate
stereoselectivity
—
(b:a
= 5.36:1)8 in glycosylation reactions with O-benzylated glyco-
2I
82.9
80.9
81.21
—
2II
89.4
sylacceptorsitsuseforthebenzyl-freesynthesisofazido-containing
oligosaccharides seemed to be justified.
2III
2IV
2V
—
—
89.3
75.9b
75.8b
84.5
For the synthesis of pentasaccharide 2-azidoethyl glycoside 8 we
used a similar glycosyl donor with thiophenyl aglycon 4b, prepared
in 94% yield by silylation (TIPSOTf, sym-collidine, DMF) of the
known51 alcohol 3. The required glycosyl acceptor, trisaccharide
diol 2 with O-benzoyl protecting groups, was prepared in 96% yield
by removal of two chloroacetyl groups (Py, H2O) from the known54
trisaccharide 1 with 2-chloroethyl48 aglycon (Scheme 1).
Glycosyl donor 4b and glycosyl acceptor 2 were coupled in a
[3+1+1] bis-(1,2-cis)-glycosylation reaction to give a mixture of
diastereomeric pentasaccharides 5 in 77% yield, the required bb-
—
82.1b
—
3I
81.19
81.7
81.9
—
3II
—
—
—
73.4
—
76.5c
76.2c
84.4
3III
3IV
3V
78.6
74.3
—
74.2
84.4
4I
82.0
79.8
79.1
—
81.8b
79.8
82.9
4II
—
—
—
84.0d
83.8d
78.8
4III
4IV
4V
79.8
82.5c
82.6c
65.9
—
82.2b
—
78.8
67.8
5I
66.1
63.9b
63.8b
—
—
67.5
42.5
isomer dominating (bb:(aa+ab+ba) = 6.14:1, NMR data); the sepa-
ration of isomers was not possible at this stage (see below). It is
known that bis-glycosylation is a more complex process due to for-
5II
—
—
—
67.4
—
63.8d
64.0d
62.1e
62.0e
66.2
62.5e
62.4e
64.4f
64.3f
67.6
5III
5IV
5V
mation of four anomers of glycoside formed (
ab, ba, aa, and bb)
OCH2
CH2X
than mono-glycosylation, which leads only to two anomers (
a
—
50.4
51.8
and b). Assuming that stereoselectivity of every glycosylation step
is the same (which is not entirely correct; see below), it is possible
to calculate that b-selectivity of a single glycosylation step was
a
In CD3OD.
Signals may be interchanged.
b–f
higher (b:
saccharide diol 2 (bb:(aa
thioglycoside 4b than that reported (b:
a
= 12.76:1) in the bis-glycosylation of O-benzoylated tri-
b+b ) = 6.14:1) performed with phenyl
= 5.36:1)8 for the mono-
+a
a
a
Fully protected pentasaccharide 5 was desilylated (TBAF, DMF)
glycosylations performed with similar thioglycoside 4a in reac-
tions with O-benzylated glycosyl acceptors as one would expect
to give hexaol 6 as the mixture of anomers in 77% yield. The NMR
data confirmed the structure of pentasaccharide 6. The presence of
lower proportion of bb-isomer (bb:(aa
+
a
b+b
a
) = 2.45:1) in the lat-
both
trum—three
a
-Araf and b-Araf linkages was apparent from HSQC spec-
ter case. It is worthy of note that the efficiency of the bis-glycosyl-
ation of O-benzoylated trisaccharide diol 2 with thioglycoside 4b
(66% yield of bb-isomer of 5) is comparable to that achieved in
the bis-glycosylation of the related O-benzylated trisaccharide
methyl glycoside using a novel 2,3-O-xylylene-protected arabino-
furanosyl donor59 (65% yield of bb-isomer of the pentasaccharide
methyl glycoside), which was shown to be highly b-selective
a
C-1 and singlet H-1 signals: dC 105.7 (C-1I) and dH
5.21 (1H, s, H-1I), 106.46 (C-1II) and 5.42 (1H, s, H-1II), 106.47 (C-
1III) and 5.22 (1H, s, H-1III), as well as two b C-1 and doublet H-1
signals with large coupling constants: dC 101.6 (C-1IV) and dH
5.18 (1H, d, J = 4.9 Hz, H-1IV), 101.0 (C-1V) and 5.06 (1H, d,
J = 4.8 Hz, H-1V) (see Section 4 and Tables 1–3). Chlorine in the
2-chloroethyl aglycon of 6 was substituted (NaN3, 18-crown-6,
DMF) to give O-benzoylated 2-azidoethyl glycoside 7 in 55% yield
as the single diastereoisomer after HPLC separation. The NMR data
confirmed the structure of pentasaccharide 7 in a way similar to
the one used for determining the structure of 5. The presence of
azido group in the aglycon followed from the position of the termi-
nal methylene group CH2CH2N3 (dC 50.4) in the 13C NMR spectrum
of 7. The positions of characteristic signals in 1H and 13C NMR spec-
tra of 2-azidoethyl glycoside 7, coupling constants and correlations
in HSQC and HMBC spectra corresponded well to those observed
for the major isomer of 2-chloroethyl glycoside 5 (see Section 4
(b:
charide acceptor. It is interesting that the latter value is very close
to our estimate of b-selectivity (b: = 12.76) of a single glycosyla-
a
= 12.6)59 in mono-glycosylation of a O-benzylated monosac-
a
tion step during the synthesis of 5 (see above). These results
suggest that the stereoselectivity of glycosylation with arabinofur-
anosyl glycosyl donors is fairly sensitive to the nature of protecting
groups on glycosyl acceptor (as was earlier reported by other
groups7–9,55,56,59) and that results of mono-glycosylation may not
be directly transferable to bis-glycosylation.
The structure of the major isomer of protected pentasaccharide
5 followed from NMR data (see Section 4 and Tables 1–3), which
and Tables 1–3):
a
C-1 and singlet H-1 signals [dC 105.8 (C-1I),
revealed three linked
a
-arabinofuranose residues [dC 106.1 (C-1I),
106.3 (C-1II), 106.5 (C-1III), dH 5.17 (1H, s, H-1I), 5.44 (1H, s, H-
1II), 5.23 (1H, s, H-1III)], two b C-1 and doublet H-1 signals with
the large coupling constants [dC 101.5 (C-1IV), 101.0 (C-1V), dH
5.03 (1H, d, J = 4.5 Hz, H-1V) 5.14 (1H, d, J = 4.6 Hz, H-1IV)]. HMBC
was used to show intersaccharide correlations between
CH2CH2Cl/H-1I, C-1II/H-3I, C-3I/H-1II, C-5I/H-1III, C-1III/H-5Ia, C-1III/
H-5Ib, C-1IV/H-2II, C-2II/H-1IV, C-1V/H-2III, C-2III/H-1V.
106.0 (C-1II), 107.3 (C-1III); three singlets at dH 5.16 (H-1I), 5.49
(H-1II), 5.25 (H-1III)] and two linked b-arabinofuranose residues
[(dC 101.7 (C-1IV), 101.4 (C-1V); a multiplet signal at dH 5.15 (H-
1IV), a doublet at dH 5.06 (H-1V, J1,2 = 4.5 Hz)]. The presence of agly-
con at AraI residue, 1,3-intersaccharidic linkage between AraII and
AraI, 1,5-linkage between AraIII and AraI, and two 1,2-linkages be-
tween AraIV and AraII, and AraV and AraIII residues, respectively, fol-
lowed from the observation of the following correlations in HMBC
spectra: CH2CH2Cl/H-1I, C-1II/H-3I, C-5I/H-1III, C-1III/H-5I, C-1IV/H-
2II, C-1V/H-2III. After glycosylation reaction the signals of C-2 of
AraII and AraIII residues moved to the lower field (dC ꢁ86.5 for 5
and dC ꢁ81 for 2) indicating that the corresponding oxygens in
pentasaccharide 5 are glycosylated.
Hexaol 7 was debenzoylated (MeONa, MeOH) to give in 93%
yield the target deprotected pentasaccharide with 2-azidoethyl
aglycon 8 as the single isomer. The structure of 8 was fully con-
firmed by 1D and 2D NMR spectra (see Section 4 and Tables 1–
3). The obtained values of chemical shifts of anomeric protons
(dH 4.94 (s), 5.03 (2H, d, J = 4.3 Hz), 5.04 (2H, d, J = 4.2 Hz), 5.08
(2H, d, J = 2.2 Hz), 5.17 (2H, d, J = 2.4 Hz)) and anomeric carbons

K. G. Fedina et al. / Carbohydrate Research 357 (2012) 62–67
65
Table 2
1H NMR chemical shifts (600 MHz, CDCl3, dH
)
2
4
5
6
7
8a
1I
5.21 s
—
5.16 br s
5.21 s
5.17 s
4.94 s
1II
1III
1IV
1V
2I
5.41 s
5.21 s
—
—
5.33 s
4.46 s
4.31 d
—
—
—
—
5.31 d
—
—
—
—
4.26 dd
—
—
—
5.49 s
5.25 br s
5.15 m
5.06 d
5.24 d
4.40 d
4.36 d
4.22–4.25 m
4.15–4.17 m
4.42 d
5.56 dd
5.51 dd
4.15–4.22 m
4.15–4.22 m
4.29–4.33 m
4.55–4.57 m
4.53–4.55 m
3.63–3.64 m
3.56–3.58 m
4.04–4.07 m
3.80–3.83 dd
4.45–4.51 m
4.45–4.51 m
4.45–4.51 m
4.45–4.51 m
4.15–4.22 m
3.89–3.91 m
4.08–4.12 m
3.86–3.88 m
3.89–3.93 m
3.73–3.78 m
3.60 t
5.42 s
5.22 s
5.18 d
5.06 d
5.28 s
4.49–4.54 m
4.40 s
4.01–4.14 m
4.01–4.14 m
4.28–4.30 m
5.49 dd
5.44 s
5.23 s
5.14 d
5.03 d
5.26 s
4.49–4.51 m
4.38 s
4.08–4.13 m
4.03–4.07 m
4.31 s
5.17 d
5.08 d
5.03 d
5.04 d
4.15–4.16 m
4.13 dd
2II
2III
2IV
2V
3I
4.14–4.15 m
3.98–4.00 m
3.96–3.99 m
4.04–4.07 m
4.03–4.04 m
4.02–4.03 m
3.77–3.79 m
3.77–3.79 m
4.16–4.19 m
—
4.36–4.39 m
5.09 d
5.03 d
—
—
4.32–4.35 m
4.58–4.61 m
4.56–4.59 m
—
3II
3III
3IV
3V
4I
5.48 br s
5.37 br s
4.25 t
4.22 t
5.38 d
4.25 t
4.19 t
—
3.96–4.05 m
—
—
—
4.32–4.35 m
4.56–4.62 m
4.56–4.62 m
3.73–3.86 m
3.73–3.86 m
4.01–4.14 m
3.73–3.86 m
4.56–4.62 m
4.49–4.54 m
4.56–4.62 m
4.49–4.54 m
3.73–3.86 m
3.66–3.71 m
3.73–3.86 m
3.66–3.71 m
3.89–3.94 m
3.73–3.86 m
3.60 t
4.31 s
4II
4III
4IV
4V
5Ia
5Ib
5II
4.56–4.59 m
4.57–4.61 m
3.80–3.83 m
3.78–3.82 m
4.06–4.09 m
3.80–3.84 m
4.54–4.61 m
4.47–4.53 m
4.54–4.61 m
4.47–4.53 m
3.75–3.82 m
3.65–3.70 m
3.75–3.82 m
3.65–3.70 m
3.84–3.88 m
3.60–3.64 m
3.27–3.37 m
3.27–3.37 m
3.97–4.00b
m
m
3.91–3.92b
—
3.96–4.01 m
3.96–4.01 m
3.90–3.92 m
3.74–3.76 m
3.79–3.81 m
3.63–3.64 m
3.79–3.81 m
3.63–3.64 m
—
3.96–4.05 m
—
—
—
—
—
—
—
—
4.37 q
3.96–4.05 m
—
—
—
—
4.06 dd
3.83 dd
4.63–4.68 m
4.54–4.61 m
4.63–4.68 m
4.54–4.61 m
—
—
—
—
a
5II
b
5III
a
5III
b
5IV
5IV
5V
3.77–3.79c
m
a
3.66d
3.72c
d
t
b
a
5V
3.64–3.65d
m
b
OCH2a
OCH2b
CH2aX
CH2bX
3.90–3.95 m
3.74–3.79 m
3.61 t
3.85–3.88 m
3.61–3.63 m
3.37–3.46 m
3.37–3.46 m
3.61 t
3.60 t
3.60 t
a
In CD3OD.
Signals may be interchanged.
b–d
3. Conclusions
Table 3
Coupling constants in 1H NMR spectra (600 MHz, CDCl3, J, Hz)
In summary, we suggested a benzyl-free approach for the con-
struction of the arabinofuranose branched oligosaccharides found
at the non-reducing end of mycobacterial arabinans using the
synthesis of pentasaccharide 2-azidoethyl glycoside 8 as a repre-
sentative example. The presence of 2-azidoethyl aglycon in penta-
saccharide fragment would allow the use of the click-chemistry
approaches and the preparation of neoglycoconjugates.
Monosaccharide residue
2
4
5
6
7
8a
b
b
b
b
b
b
b
b
b
b
b
b
b
b
b
b
I
I
I
II
II
II
III
III
III
IV
IV
IV
V
V
V
V
J4,5a
J4,5b
J5a,5b
J1,2
J3,4
J2,3
J1,2
J2,3
J3,4
J1,2
4.5
2.3
—
—
—
—
—
—
—
—
—
—
—
—
5.3
4.9
2.8
11.4
11.7
b
b
2.4
b
5.1
4.1
4.4
b
2.1
2.6
5.4
b
b
1.2
2.2
b
b
b
2.1
4. Experimental
b
5.9
—
—
—
—
—
—
—
5.9
5.9
4.3
4.2
4.9
7.7
7.7
4.8
7.5
b
4.6
7.4
7.4
4.5
7.2
4.3
b
b
b
J2,3
J3,4
J1,2
J2,3
4.1. General methods
b
4.5
4.2
All reactions sensitive to air and/or moisture were carried out
under argon atmosphere with anhydrous solvents. The reactions
were performed with the use of commercial reagents (Aldrich, Flu-
ka, Acros Organics) and distilled solvents purified and dried (where
appropriate) according to standard procedures. Powdered molecu-
lar sieves 4 Å (Fluka) were activated before the reactions by heat-
ing at 180 °C in high vacuum for 2 h. Column chromatography
b
b
6.4
b
b
b
b
J3,4
7.5
7.2
b
b
J4,5a
JCH2X,OCH2
JCH2X,OCH2
3.7
2.8
b
b
b
b
OCH2CH2X
OCH2CH2X
6.0
6.0
5.9
5.9
b
—
a
In CD3OD.
b
Coupling constant could not be determined.
was performed on Silica Gel 60 (40–63 lm, Merck). Thin-layer
(dC 102.4 (2C), 107.0, 107.5, 109.7) of pentasaccharide 8 in CD3OD
were in good agreement with the reported NMR data in D2O for the
anomeric signals of previously synthesized pentasaccharides
methyl glycoside13 (anomeric protons: dH 4.88 (s), 5.06 (2H, d,
J = 3.8 Hz), 5.10 (s), 5.16 (s); anomeric carbons: dC 101.02, 101.09,
105.88, 106.03, 108.86) and 1,2-O-isopropylidene acetal16 (ano-
meric protons: dH 4.90 (d, J = 4.20 Hz), 5.10 (d, J = 4.65 Hz), 5.15
(s), 5.28 (s), 6.00 (d, J = 4.8 Hz); anomeric carbons: dC 102.0,
102.1, 106.3, 106.5, 106.9).
chromatography was carried out on plates with Silica Gel 60 on
glass or on aluminum foil (Merck). Spots of compounds were visu-
alized under UV light and by heating the plates after immersion in
a 1:10 (v/v) mixture of 85% aqueous H3PO4 and 95% EtOH. NMR
spectra were recorded for solutions in CDCl3 or CD3OD on a Bruker
AC-200 instrument (200.13, and 50.32 MHz, respectively), a Bruker
AM-300 instrument (300.13, and 75.48 MHz, respectively) or on a
Bruker AVANCE 600 spectrometer (600.13 and 150.9 MHz, respec-
tively). The 1H NMR chemical shifts are referred to the residual sig-

66
K. G. Fedina et al. / Carbohydrate Research 357 (2012) 62–67
nal of CHCl3 (dH 7.27) or CHD2OD (dH 3.31) and the 13C NMR shifts
to the CDCl3 signal (dC 77.0) or CD3OD signal (dC 49.0). Assignments
of the signals in the NMR spectra were performed using 2D-spec-
troscopy (COSY, HSQC, HMBC) and DEPT-135 experiments, NMR
data for all compounds are listed in Tables 1–3. High resolution
mass spectra (electrospray ionization, HRESIMS) were measured
in a positive mode on a Bruker micrOTOF II mass spectrometer
for 2 ꢂ 10ꢀ5 M solutions in MeCN or MeOH. Optical rotations were
measured using a PU-07 automatic polarimeter (Russia). Analytical
4.4. 2-Chloroethyl 2-O-benzoyl-3,5-di-O-[3,5-di-O-benzoyl-2-O-
(3,5-di-O-tert-butylsilylene-2-O-triisopropylsilyl-b-
arabinofuranosyl)- -arabinofuranosyl]-
arabinofuranoside (5)
D-
a-
D
a-D-
Freshly activated molecular sieves 4 Å (1 g) were added under
Ar to the mixture of diol 2 (263.7 mg, 0.26 mmol) and thioglyco-
side 4b (526.5 mg, 0.98 mmol) in CH2Cl2 (12.7 mL) and the reaction
mixture was stirred at ꢁ20 °C for 16 h. The reaction mixture was
cooled to ꢀ58 °C and N-iodosuccinimide (220.3 mg, 0.98 mmol)
and AgOTf (27.4 mg, 0.11 mmol) were added. The reaction mixture
was stirred at ꢀ40 °C for 40 min, and then the temperature was al-
lowed to warm to ꢀ13 °C during 1 h and then the reaction was
HPLC separations were performed on an Ultrasorb Si (5
umn (165 ꢂ 4.6 mm ID) at 1 mL/min flow rate. Preparative HPLC
separations were performed on a Sialsorb 600 (7.5 m) column
lm) col-
l
(250 ꢂ 15 mm ID) with a 1:3:6 i-PrOH–CHCl3–petroleum ether
mixture as the eluent at 15 mL/min flow rate. A Knauer differential
refractometer was used as the detector.
quenched by the addition of satd NaHCO3 (50 lL). The reaction
mixture was diluted with CH2Cl2 (40 mL) and filtered through a
layer of Celite. The reaction mixture was washed with a mixture
of satd Na2S2O3 (75 mL) and satd NaHCO3 (75 mL). The aqueous
layer was extracted with CH2Cl2 (10 mL) two times. Combined or-
ganic extracts were filtered through cotton wool plug, concen-
trated, dried in vacuo, and purified by silica gel column
chromatography (toluene–EtOAc, 7:1) to give 5 as a colorless oil
4.2. 2-Chloroethyl 2-O-benzoyl-3,5-di-O-(3,5-di-O-benzoyl-a-D-
arabinofuranosyl)-a-D-arabinofuranoside (2)
2-Chloroethyl
2-O-benzoyl-3,5-di-O-(3,5-di-O-benzoyl-2-O-
chloroacetyl-
a-
D-arabinofuranosyl)- -arabinofuranoside
a-D
(1)54
(470.9 mg, 0.41 mmol) was dissolved in anhydrous Py (7.75 mL)
and water (4 mL) was added to the stirring mixture. The reaction
mixture was stirred at 70 °C (bath temperature) for 1 h and was
co-concentrated with toluene (40 mL, bath temperature ꢁ50 °C).
Then the reaction mixture was diluted with CHCl3 (100 mL),
washed with 1 M KHSO4 (70 mL), water (70 mL), and satd NaHCO3
(70 mL). Organic extract was filtered through cotton wool plug,
concentrated under reduced pressure (bath temperature ꢁ30 °C),
dried in vacuo, and purified by silica gel column chromatography
(petroleum ether–EtOAc, 3:2) to give 2 as a white solid foam
(368.4 mg, 77%; Rf = 0.20, petroleum ether–EtOAc, 7:1).
½ ꢃ
a 2D3
ꢀ12.1 (c 1.0, CHCl3). HRESIMS: found m/z 1870.8472 [M+NH4]+.
Calcd for C96H137O26ClSi4NH4: 1870.8502. According to analytical
HPLC with a 15:1 petroleum ether–ethyl acetate mixture as the
eluent the product contained 78% of bb-isomer (tR = 27.0 min)
and 22% of other isomers (aa, ab, ba; three peaks with tR = 14.1,
19.1, 25.3 min). According to NMR data the product contained
86% of bb-isomer and 14% of other isomers. NMR data are listed
in Tables 1–3 except for the following signals: 1H NMR
(600 MHz, CDCl3) dH 0.95 (br s, 18H, C(CH3)3), 0.96 (br s, 18H,
C(CH3)3), 1.03–1.07 (m, 42H, CH(CH3)2, CH(CH3)2), 7.29–7.36 (m,
9H, Ph) 7.41–7.57 (m, 7H, Ph) 7.89–8.05 (m, 9H, Ph). 13C NMR
(151 MHz, CDCl3) dC 12.1 (CH(CH3)2), 17.8 and 17.7 (CH(CH3)2),
20.0 and 22.6 (C(CH3)3), 27.1 and 27.4 (C(CH3)3), 128.26, 128.33,
128.35, 128.4, 129.2, 129.4, 129.7, 129.8, 129.9, 132.9, 133.1,
133.3 (Ph), 165.5, 165.9 (CO). HMBC correlations: C-1II/H-3I, C-5I/
H-1III, C-1III/H-5I, C-1IV/H-2II, C-1V/H-2III, CH2CH2Cl/H-1I.
(392.3 mg, 96%; Rf = 0.22, petroleum ether–EtOAc, 3:2).
½ ꢃ
a 2D2
+46.9 (c 1.0, CHCl3). HRESIMS: found m/z 1019.2491 [M+Na]+.
Calcd for C52H49O18ClNa: 1019.2500. NMR data are listed in Tables
1–3 except for the following signals: 1H NMR (600 MHz, CDCl3): dH
7.30–7.39 (m, 8H, Ph), 7.42 (t, 2H, J = 7.7 Hz, Ph), 7.46–7.53 (m, 4H,
Ph), 7.57 (t, 1H, J = 7.5 Hz, Ph), 7.92 (d, J = 7.8 Hz, 4H, Ph), 7.98–8.04
(m, 6H, Ph). 13C NMR (151 MHz, CDCl3): dC 128.36, 128.37, 128.40,
128.42, 128.49, 128.52, 128.8, 128.9, 129.0, 129.5, 129.62, 129.66,
129.76, 129.80, 133.1, 133.2, 133.4, 133.56, 133.62 (Ph), 165.5,
166.15, 166.18, 166.9, 167.0 (CO). HMBC correlations: C-1II/H-3I,
C-5I/H-1III, CH2CH2Cl/H-1I.
4.5. 2-Azidoethyl 3,5-di-O-[2-O-(b-
benzoyl- -arabinofuranosyl]-2-O-benzoyl-
arabinofuranoside (7)
D-arabinofuranosyl)-3,5-di-O-
a-
D
a-D-
4.3. Phenyl 3,5-di-O-tert-butylsilylene-2-O-triisopropylsilyl-1-
thio-a-D-arabinofuranoside (4b)
Protected pentasaccharide 5 as the mixture of isomers (377 mg,
0.20 mmol) was dissolved in anhydrous THF (7 mL) under Ar. AcOH
(0.4 mL, 7.0 mmol) and a 1.0 M solution of TBAF in THF (2.5 mL,
8.63 mmol) were added in that order to the cooled (ice-water bath)
reaction mixture. The reaction mixture was stirred at ꢁ20 °C for
16 h. The reaction was diluted with toluene (30 mL), concentrated
(bath temperature 40–50 °C), dried in vacuo, and purified by silica
gel column chromatography (petroleum ether–acetone, 4:5) to
give desilylated pentasaccharide 6 as a colorless oil (194.4 mg,
77% (mixture of isomers); Rf = 0.20, petroleum ether–acetone,
4:5). NMR data are listed in Tables 1–3 except for the following sig-
nals: 1H NMR (600 MHz, CDCl3) dH 7.29–7.38 (m, 8H, Ph), 7.43–
7.54 (m, 6H, Ph), 7.59 (t, J = 7.3 Hz, 1H, Ph), 7.85 (d, J = 7.6 Hz, 2H,
Ph), 7.90 (d, J = 7.7 Hz, 2H, Ph), 7.94 (d, J = 7.7 Hz, 2H, Ph), 8.00
(d, J = 7.7 Hz, 2H, Ph), 8.03 (d, J = 7.9 Hz, 2H, Ph). 13C NMR
(151 MHz, CDCl3) dC 128.3, 128.37, 128.44, 128.5, 128.7, 128.8,
129.0, 129.3, 129.5, 129.6, 129.70, 129.73, 129.8, 133.2, 133.5,
133.6, 133.7 (Ph), 165.7, 166.2, 166.3 (CO). HMBC correlations: C-
1II/H-3I, C-5I/H-1III, C-1IV/H-2II, C-1V/H-2III, CH2CH2Cl/H-1I.
Phenyl 3,5-di-O-tert-butylsilylene-1-thio-
side (3)51 (62.1 mg, 0.16 mmol) was dissolved in anhydrous DMF
(2 mL). sym-Collidine (65 L, 0.49 mmol) and i-Pr3SiOSO2CF3 (TIP-
SOTf) (70 L, 0.26 mmol) were added to the stirring mixture. The
a-D-arabinofurano-
l
l
reaction mixture was stirred at 90 °C (bath temperature) for 1 h
and then was diluted with CHCl3 (30 mL), washed with 1 M KHSO4
(20 mL), water (20 mL), and satd NaHCO3 (20 mL). Organic extract
was filtered through a cotton wool plug, concentrated under re-
duced pressure (bath temperature ꢁ30 °C), dried in vacuo, and
purified by silica gel column chromatography (petroleum ether–
toluene, 3:1) to give 4b as a colorless oil (80.9 mg, 94%; Rf = 0.27,
petroleum ether–toluene, 3:1).
½
a 2D2
+130.0 (c 1.0, CHCl3).
ꢃ
HRESIMS: found m/z 556.3319 [M+NH4]+. Calcd for C28H50O4S-
Si2NH4: 556.3307. NMR data are listed in Tables 1–3 except for
the following signals: 1H NMR (600 MHz, CDCl3) dH 1.03 (s, 9H,
C(CH3)3), 1.10 (s, 9H, C(CH3)3), 1.15–1.17 (m, 21H, CH(CH3)2,
CH(CH3)2), 7.27–7.35 (m, 3H, Ph), 7.51–7.54 (m, 2H, Ph). 13C NMR
(151 MHz, CDCl3) dC 12.2 (CH(CH3)2), 17.9 and 18.0 (CH(CH3)2),
20.1 and 22.7 (C(CH3)3), 27.1 and 27.3 (C(CH3)3), 127.2, 128.9,
131.2, 135.1 (Ph).
2-Chloroethyl glycoside 6 (194.6 mg, 0.15 mmol, mixture of iso-
mers) was dissolved in anhydrous DMF (1.5 mL) and NaN3 (30 mg,
0.46 mmol) and 18-crown-6 (18.3 mg, 0.07 mmol) were added to
the reaction mixture. The reaction mixture was stirred at 70 °C

K. G. Fedina et al. / Carbohydrate Research 357 (2012) 62–67
67
9. Lee, Y. J.; Lee, K.; Jung, E. H.; Jeon, H. B.; Kim, K. S. Org. Lett. 2005, 7, 3263–3266.
10. Fraser-Reid, B.; Lu, J.; Jayaprakash, K. N.; Lopez, J. C. Tetrahedron: Asymmetry
2006, 17, 2449–2463.
11. Liang, X.-Y.; Deng, L.-M.; Liu, X.; Yang, J.-S. Tetrahedron 2010, 66, 87–93.
12. Marotte, K.; Sanchez, S.; Bamhaoud, T.; Prandi, J. Eur. J. Org. Chem. 2003, 3587–
3598.
13. Yin, H.; D’Souza, F. W.; Lowary, T. L. J. Org. Chem. 2002, 67, 892–903.
14. Gadikota, R. R.; Callam, C. S.; Appelmelk, B. J.; Lowary, T. L. J. Carbohydr. Chem.
2003, 22, 459–480.
15. Tam, P.-H.; Lowary, T. L. In Carbohydr. Chem.; Rauter, A. P.; Lindhorst, T. K., Eds.;
the Royal Society of Chemistry, 2010; Vol. 36, pp 38–63, and references cited
therein.
16. Mereyala, H. B.; Hotha, S.; Gurjar, M. K. Chem. Commun. 1998, 685–686.
17. D’Souza, F. W.; Lowary, T. L. Org. Lett. 2000, 2, 1493–1495.
18. Sanchez, S.; Bamhaoud, T.; Prandi, J. Tetrahedron Lett. 2000, 41, 7447–7452.
19. Ishiwata, A.; Akao, H.; Ito, Y.; Sunagawa, M.; Kusunose, N.; Kashiwazaki, Y.
Bioorg. Med. Chem. 2006, 14, 3049–3061.
for 48 h. The reaction was diluted with toluene (15 mL) and con-
centrated (bath temperature 40–50 °C) (co-evaporation was re-
peated three times), dried in vacuo, dissolved in EtOAc (50 mL),
washed with water (40 mL), filtered through a cotton wool plug,
concentrated under reduced pressure (bath temperature ꢁ35 °C),
and purified by silica gel column chromatography (petroleum
ether–acetone, 4:5) to give 7 as a white solid foam (136.6 mg,
72% (mixture of isomers); Rf = 0.21, petroleum ether–acetone,
4:5), which was subjected to the preparative HPLC (i-PrOH–
CHCl3–petroleum ether, 1:3:6) to give the pure bb-isomer of penta-
saccharide 7 (104.6 mg, 55% after two steps, tR = 25.6 min (analyt-
ical HPLC in the same eluent)). ½a D22
ꢃ
+28.2 (c 1.0, CHCl3). HRESIMS:
found m/z 1290.3727 [M+Na]+. Calcd for C62H65O26N3Na:
1290.3749. NMR data are listed in Tables 1–3 except for the follow-
ing signals: 1H NMR (600 MHz, CDCl3) dH 7.25–7.35 (m, 8H, Ph),
7.39–7.50 (m, 6H, Ph), 7.56 (t, J = 7.3 Hz, 1H, Ph), 7.82 (d,
J = 7.7 Hz, 2H, Ph), 7.87 (d, J = 7.7 Hz, 2H, Ph), 7.90 (d, J = 7.7 Hz,
2H, Ph), 7.97 (d, J = 7.7 Hz, 2H, Ph), 8.01 (d, J = 7.7 Hz, 2H, Ph). 13C
NMR (151 MHz, CDCl3) dC 128.3, 128.37, 128.44, 128.5, 128.7,
128.8, 129.0, 129.3, 129.5, 129.6, 129.70, 129.73, 129.8, 133.2,
133.5, 133.6, 133.7 (Ph), 165.7, 166.2, 166.3 (CO). HMBC correla-
tions: C-1II/H-3I, C-3I/H-1II, C-5I/H-1III, C-1III/H-5Ia, C-1III/H-5Ib, C-
1IV/H-2II, C-2II/H-1IV, C-1V/H-2III, C-2III/H-1V.
20. Ito, Y. 16th European Carbohydrate Symposium Eurocarb 16, Sorrento, Italy,
July 3–7, 2011. E-Book of Abstracts, p 27, IL 01.
21. Ishiwata, A.; Ito, Y. J. Am. Chem. Soc. 2011, 133, 2275–2291.
22. Abronina, P. I.; Podvalnyy, N. M.; Melnikova, T. M.; Zinin, A. I.; Fedina, K. G.;
Kachala, V. V.; Torgov, V. I.; Kononov, L. O.; Panfertsev, E. A.; Baranova, E. V.;
Mochalov, V. V.; Dyatlova, V. I.; Biketov, S. F. Russ. Chem. Bull. 2010, 59, 2333–
2337.
23. Magnusson, G.; Chernyak, A. Y.; Kihlberg, J.; Kononov, L. O. In
Neoglycoconjugates: Preparation and Application; Lee, Y. C., Lee, R. T., Eds.;
Academic Press Inc.: San Diego, California, 1994; pp 53–143.
24. Dedola, S.; Nepogodiev, S. A.; Field, R. A. Org. Biomol. Chem. 2007, 5, 1006–1017.
25. Cheshev, P.; Marra, A.; Dondoni, A. Org. Biomol. Chem. 2006, 4, 3225–3227.
26. Hotha, S.; Kashyap, S. J. Org. Chem. 2006, 71, 364–367.
27. Dondoni, A. Chem. Asian J. 2007, 2, 700–708.
28. Marra, A.; Moni, L.; Pazzi, D.; Corallini, A.; Bridi, D.; Dondoni, A. Org. Biomol.
Chem. 2008, 6, 1396–1409.
4.6. 2-Azidoethyl 3,5-di-O-[2-O-(b-
D-arabinofuranosyl)-a-D-
arabinofuranosyl]- -arabinofuranoside (8)
a-D
29. Tornøe, C. W.; Christiensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–3064.
30. Dondoni, A. Angew. Chem., Int. Ed. 2008, 47, 8995–8997.
31. Macmillan, D.; Blanc, J. Org. Biomol. Chem. 2006, 4, 2847–2850.
32. Bodine, K. D.; Gin, D. Y.; Gin, M. S. J. Am. Chem. Soc. 2004, 126, 1638–1639.
33. Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952–3015.
34. Wilkinson, B. L.; Bornaghi, L. F.; Poulsen, S.-A.; Houston, T. A. Tetrahedron 2006,
62, 8115–8125.
35. Kolb, C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–2021.
36. Hong, V.; Presolski, S. I.; Ma, C.; Finn, M. G. Angew. Chem., Int. Ed. 2009, 48,
9879–9883.
37. Fazio, F.; Bryan, M. C.; Blixt, O.; Paulson, J. C.; Wong, C.-H. J. Am. Chem. Soc.
2002, 124, 14397–14402.
38. Zhang, X.; Yang, X.; Zhang, S. Synth. Commun. 2009, 39, 830–844.
39. Becer, C. R.; Hoogenboom, R.; Schubert, U. S. Angew. Chem., Int. Ed. 2009, 48, 2–
11.
Pentabenzoate 7 (35.0 mg, 0.03 mmol) was dissolved in MeOH
(4.0 mL) and 1 M MeONa in MeOH (219 L) was added to the reac-
l
tion mixture, which then was stirred at ꢁ20 °C for 48 h. The reac-
tion was neutralized with ion-exchange resin Dowex 50Wꢂ8 (H+).
The resin was filtered off, washed with MeOH (15 mL) and the fil-
trate was concentrated. Water (15 mL) was added to the residue
and the solution was washed with petroleum ether (15 mL). The
aqueous layer was freeze-dried in vacuo to give 8 as a white solid
foam (19.1 mg, 93% (bb-isomer); Rf = 0.75, EtOH–n-BuOH–Py–
AcOH–H2O, 100:10:10:10:3). ½a D20
ꢃ
+24.5 (c 1.0, MeOH). HRESIMS:
40. Bock, V. D.; Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem. 2006, 51–68.
41. Rostovstev, V.; Green, L. G.; Fokin, V. V.; Sharpless, B. K. Angew. Chem., Int. Ed.
2002, 41, 2596–2599.
42. Lutz, J.-F. Angew. Chem., Int. Ed. 2008, 47, 2182–2184.
43. Agard, N. J.; Prescher, J. A.; Bertozzi, C. R. J. Am. Chem. Soc. 2004, 126, 15046–
15047.
found m/z 770.2443 [M+Na]+. Calcd for C27H45O21N3Na:
770.2438. NMR data are listed in Tables 1–3. HMBC correlations:
C-1II/H-3I, C-3I/H-1II; C-5I/H-1III, C-1III/H-5I, C-1IV/H-2II, C-2II/H-
1IV, C-1V/H-2III, C-2III/H-1V, CH2CH2N3/H-1I, C-1I/CH2CH2N3.
44. Mbua, N. E.; Guo, J.; Wolfert, M. A.; Steet, R.; Boons, G.-J. ChemBioChem 2011,
12, 1912–1921.
45. Chernyak, A. Y.; Sharma, G. V. M.; Kononov, L. O.; Radha Krishna, P.; Levinsky,
A. B.; Kochetkov, N. K.; Rama Rao, A. V. Carbohydr. Res. 1992, 223, 303–309.
46. Wilkinson, B. L.; Long, H.; Sim, E.; Fairbanks, A. J. Bioorg. Med. Chem. Lett. 2008,
18, 6265–6267.
Acknowledgments
This work was supported by Russian Foundation for Basic Re-
search (projects No. 07-03-00830, 10-03-01019).
47. Wilstermann, M.; Kononov, L. O.; Nilsson, U.; Ray, A. K.; Magnusson, G. J. Am.
Chem. Soc. 1995, 117, 4742–4754.
48. Garegg, P. J.; Konradsson, P.; Kvarnström, I.; Norberg, T.; Svensson, S. C. T.;
Wigilius, B. Acta Chem. Scand. 1985, B39, 569–577.
Supplementary data
49. Kornilov, A. V.; Sherman, A. A.; Kononov, L. O.; Shashkov, A. S.; Nifant’ev, N. E.
Carbohydr. Res. 2000, 329, 717–730.
50. Yudina, O. N.; Sherman, A. A.; Nifantiev, N. E. Carbohydr. Res. 2001, 332, 363–
371.
51. Wang, Y.; Maguire-Boyle, S.; Dere, R. T.; Zhu, X. Carbohydr. Res. 2008, 343,
3100–3106.
Supplementary data (NMR spectra for new compounds) associ-
ated with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.carres.2012.05.021.
References
52. Podvalnyy, N. M.; Sedinkin, S. L.; Abronina, P. I.; Zinin, A. I.; Fedina, K. G.;
Torgov, V. I.; Kononov, L. O. Carbohydr. Res. 2011, 346, 7–15.
53. Abronina, P. I.; Podvalnyy, N. M.; Sedinkin, S. L.; Fedina, K. G.; Zinin, A. I.;
Chizhov, A. O.; Torgov, V. I.; Kononov, L. O. Synthesis 2012, 44, 1219–1225.
54. Abronina, P. I.; Sedinkin, S. L.; Podvalnyy, N. M.; Fedina, K. G.; Zinin, A. I.;
Torgov, V. I.; Kononov, L. O. Tetrahedron Lett. 2011, 52, 1794–1796.
55. Zhu, X.; Kawatkar, S.; Rao, Y.; Boons, G.-J. J. Am. Chem. Soc. 2006, 128, 11948–
11957.
1. Health Topics: Tuberculosis; World Health Organization: Geneva, 2012. http://
www.who.int/topics/tuberculosis/en (accessed March 15 2012).
2. Tuberculosis Fact Sheet No. 104; World Health Organization: Geneva, November
2010.
http://www.who.int/mediacentre/factsheets/fs104/en/index.html
(accessed March 15 2012).
3. Chiang, C.; Yew, W. W. Int. J. Tuberc. Lung Dis. 2009, 13, 304–311.
4. Brennan, P. J.; Nikaido, H. Annu. Rev. Biochem. 1995, 64, 29–63.
5. Brennan, P. J. Tuberculosis 2003, 83, 91–97.
56. Crich, D.; Pedersen, C. M.; Bowers, A. A.; Wink, D. J. J. Org. Chem. 2007, 72,
1553–1565.
57. Wuts, P. G. M.; Greene, T. W. Protective Groups in Organic Synthesis, 4th ed.; John
Wiley & Sons: Hoboken, New Jersey, 2007. pp 406–410.
58. Kocienski, P. J. Protecting Groups, 3rd ed.; Georg Thieme: Stuttgart, 2004. pp 28–
41, 110–114.
6. Kaur, D.; Guerin, M. E.; Skovierová, H.; Brennan, P. J.; Jackson, M. Adv. Appl.
Microbiol. 2009, 69, 23–78.
7. Joe, M.; Bai, Y.; Nacario, R. C.; Lowary, T. L. J. Am. Chem. Soc. 2007, 129, 9885–
9901.
59. Imamura, A.; Lowary, T. L. Org. Lett. 2010, 12, 3686–3689.
8. Ishiwata, A.; Akao, H.; Ito, Y. Org. Lett. 2006, 8, 5525–5528.