Synthesis of hexasaccharide fragment of lipoarabonomannan from Mycobacteria: Advantages of the benzyl-free approach

Article abstract of DOI:10.1007/s11172-015-0992-5

Spacered branched hexaarabinofuranoside, which corresponds to the terminal fragment of mycobacterial lipoarabinomannan and arabinogalactan, was synthesized via three different routes. Synthetic scheme which involved only acyl and silyl protective groups (

Full text of DOI:10.1007/s11172-015-0992-5

Russian Chemical Bulletin, International Edition, Vol. 64, No. 5, pp. 1149—1162, May, 2015
1149
Synthesis of hexasaccharide fragment of lipoarabonomannan
from Mycobacteria: advantages of the benzylꢀfree approach*
N. M. Podvalnyy, P. I. Abronina, K. G. Fedina, N. N. Kondakov, A. I. Zinin,
A. O. Chizhov, V. I. Torgov, V. V. Kachala, L. O. Kononov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: polinaꢀabronina@yandex.ru, kononov@ioc.ac.ru
Spacered branched hexaarabinofuranoside, which corresponds to the terminal fragment of
mycobacterial lipoarabinomannan and arabinogalactan, was synthesized via three different
routes. Synthetic scheme which involved only acyl and silyl protective groups (benzylꢀfree
approach) allows one to reduce the number of deprotection steps, enhance the overall yield,
and keep the azido group until the end of the synthesis.
Key words: arabinofuranose, lipoarabinomannan, benzylꢀfree approach, 1,2ꢀcisꢀglycoꢀ
sylation.
Because of the urgent need for novel tools for diagnosis
of tuberculosis and investigation of biosynthetic pathways
in Mycobacterium, in recent years (since 19981) the numꢀ
ber of studies, which are targeted at the synthesis of comꢀ
pounds corresponding to mycobacterial polysaccharide
fragments, is being increased.2—17 The main efforts
of researchers in this field have been concentrated at
compounds corresponding to the terminal motifs of
the arabinan region of arabinogalactan (AG) and lipoaraꢀ
binomannan (LAM), which are principal polysaccharides
of the mycobacterial cell wall and, differently from other
polysaccharides, comprise Dꢀgalactose and Dꢀarabinose exꢀ
clusively as furanoses.18—21 The longest oligosaccharides
were synthesized in laboratories headed by Lowary (Canꢀ
ada),12 Ito (Japan),13 FraserꢀReid (USA),16 Hotha (Inꢀ
dia),17 using different synthetic strategies. A number of
other researchers synthesized smaller compounds which
corresponded to different parts of AG and LAM.1,2,4,7—9
Our group is developing a novel approach22,23 to seꢀ
lective protection of hydroxyl groups in arabinofuranose
useful for facile preparation of monosaccharide building
blocks on the basis of arabinofuranose. It was used for the
synthesis of a pentasaccharide corresponding to the terꢀ
minal part of the arabinogalactan region of AG and LAM
of Mycobacteria.24 In this communication we compare
different strategies of synthesis of spacered hexasacchaꢀ
ride 1 (Scheme 1) related to the terminal part of AG and
LAM including the benzylꢀfree approach24,25 which relies
on the presence of exclusively acyl and silyl groups in the
molecule of the protected oligosaccharide.** We planned
to obtain the target oligosaccharide both as 2ꢀaminoꢀ,
and 2ꢀazidoethyl glycosides (1a and 1b, respectively)
suitable for subsequent conversion into different neoglyꢀ
cocongugates that can be used as components of tubercuꢀ
losis diagnosticums.26
Hexasaccharides 1a,b can be obtained by bisꢀglycosyꢀ
lation of the corresponding tetrasaccharide diol and
subsequent removal of protective groups (see Scheme 1).
Preparation of compounds similar to hexasaccharide 1
using this approach have been described previously.2,7,9
Two principal approaches to the synthesis and deprotecꢀ
tion of oligosaccharide 1 can be envisaged. The first strategy
involves modification of the preꢀspacer aglycon at the early
stages of synthesis and bisꢀglycosylation of a tetrasacchaꢀ
ride, which has a precursor of the amino group in the preꢀ
spacer, thus decreasing the number of steps for modificaꢀ
tion of protective groups in the assembled hexasaccharide.
The second approach involves the preꢀspacer methodology
and keeps 2ꢀchloroethyl aglycon until the end of oligosacꢀ
charide assembly; it can be employed for the preparation of
a series of hexasaccharide derivatives with aglycons of difꢀ
ferent structure from the single precursor (here, a 2ꢀchloroꢀ
ethyl derivative), without accomplishing the assembly of the
hexasaccharide each time. Besides, it is known that the
functional group in the aglycon of the glycosyl acceptor
can influence the outcome of glycosylation.27—29
Starting from the tetrasaccharide 2,30 a number of
glycosyl acceptors 3—5 (Scheme 2) was prepared for apꢀ
* On the occasion of the 100th anniversary of the birth of Acadeꢀ
mician N. K. Kochetkov (1915—2005).
** Part of this material has been published as a preliminary comꢀ
munication.26
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1149—1162, May, 2015.
1066ꢀ5285/15/6405ꢀ1149 © 2015 Springer Science+Business Media, Inc.

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Podvalnyy et al.
Scheme 1
1: X = NH2 (a), N3 (b)
LG is leaving group.
R, R´ is different protective groups.
Scheme 2
plication of these two methodologies and comparison of
these synthetic approaches. Chloroacetyl groups in tetraꢀ
saccharide 2 were selectively removed by heating in aqueꢀ
ous pyridine to give diol 3, 2ꢀchloroethyl group of the latter
was converted into 2ꢀazidoethyl group by heating with
NaN3 in DMF in the presence of 18ꢀcrownꢀ6 to furnish
compound 4. Azide 4 was reduced (PPh3, H2O, THF) to
give amine, which was acylated with trifluoroacetic anꢀ
hydride in the presence of NEt3 without isolation from the
reaction mixture (under these conditions, Oꢀtrifluoroꢀ
acetylation took place along with Nꢀtrifluoroacetylation).
OꢀTrifluoroacetic groups were selectively removed during
the subsequent aqueous extraction to furnish 2ꢀ(trifluoroꢀ
acetamido)ethyl glycoside 5. The presence of the trifluoꢀ
roacetamido group in compound 5 was confirmed by the
presence of resonance of NHCOCF3 in the 1H NMR specꢀ
trum, which is observed as a broadened singlet at H 7.06,
along with the presence of the signal of CH2NHCOCF3
in the 13C NMR spectrum (C 39.6, whereas the signal
of CH2N3 in compound 4 is located at 50.7) and the
presence of a single peak in the 19F NMR spectrum
(F –76.6).
Reagents and conditions: a. Py, H2O, 65 C, 85%; b. NaN3,
18ꢀcrownꢀ6, DMF, 80 C, 97%; c. 1) Ph3P, H2O, THF;
2) (CF3CO)2O, NEt3, THF; 3) aqueuos treatment, 75%.
Target hexasaccharides 1a,b contain two ꢀlinked araꢀ
binofuranose residues (1,2ꢀcisꢀglycosidic linkage). One of
the most efficient approaches to formation of the chalꢀ
lenging 1,2ꢀcisꢀarabinofuranoside linkage involves the
presence of a bridgeꢀforming group in the glycosyl donor
(for example, 3,5ꢀOꢀdiꢀtertꢀbutylsilylene, DTBS31 or 3,5ꢀOꢀ
(1,1,3,3ꢀtetraisopropoxy)disiloxaneꢀ1,3ꢀdiyl, TIPDS8),
which is believed to lock the conformation of the glycosyl
cation.31 The group at O(2) of the glycosyl donor has to be
nonꢀparticipating (for example, a benzyl or a silyl group).
Ethyl and phenyl thioglycosides of arabinofuranose 6,
7 (Scheme 3) with a 3,5ꢀOꢀTIPDS group were successfulꢀ
ly used8 as glycosyl donors for preparation of fragments
of LAM. However, they were found to be unsuitable for
glycosylation of Oꢀbenzoylated glycosyl acceptor 3 (see
Scheme 3). The reaction gave the mixture of all four posꢀ

Benzylꢀfree approach to arabinans
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1151
Scheme 3
Reagents and conditions: i. NIS, AgOTf, CH2Cl2, MS 4 Å, –70 C  –50 C.
sible stereoisomers 8 (70—74%), and the content of the
target ꢀisomer in the mixture (~25%) was evaluated
using NMR spectroscopy after the isolation of pairs of
isomers (,  and , ) by preparative TLC on silica
gel. Presumably, the result of glycosylation depended on
the protective group pattern of the glycosyl acceptor. The
achieved stereoselectivity was insufficient for our purpose
and thus glycosyl donors with TIPDS protection were
abandoned.
On the contrary, 3,5ꢀOꢀDTBSꢀsubstituted glycosyl
donors 9 (see Refs31,32) and 10 (see Ref.24) with 2ꢀOꢀ
benzyl and 2ꢀOꢀtriisopropylsilyl (TIPS) protective groups,
respectively (see Scheme 3), were successfully used for the
preparation of protected hexasaccharides 11—14 starting
from tetrasaccharide glycosyl acceptors 3—5 with differꢀ
ent aglycons (Scheme 4).
A number of glycosylation reactions was accomplished
between tetrasaccharide glycosyl acceptors 3—5 with difꢀ
ferent aglycons and glycosyl donors 9 and 10 (see Scheme 4).
The reactions were performed in CH2Cl2 at –47 C (for
glycosyl donor 9) and –56 C (for glycosyl donor 10) for
1—1.5 h (see Table 1). Glycosylation reactions of comꢀ
pounds 3—5 with glycosyl donors 9, 10 proceeded simiꢀ
larly, the reaction was initiated soon after the promoters
were added. The yield of the hexasaccharide fraction isoꢀ
lated by gel chromatography exceeded 93% in all cases.
Table 1. Results of glycosylation of glycosyl acceptors 3—5 with glycosyl donors 9, 10 (see Scheme 4)
Experiꢀ
ment
Glycosyl
acceptor
X
Glycosyl
donor
Product
Т/C
Percentage
,ꢀisomer
(%)
Yield of
Yield of the
,ꢀisomerа hexasaccharide fractionb
(%)
42
(%)
1
2
3
4
3
4
5
3
Cl
N3
NHTFA
Cl
19
19
19
10
11
12
13
14
–46
–47
–47
–56
61c
56c
64c
59e
1197
~100
1193
1197
d
—
42
49f
а After preparative HPLC.
b The hexasaccharide fraction was obtained after chromatography on BioBeads S1 in toluene.
c According to analytical HPLC data (silica gel UltraSphere (5 m) column (120×4.6 mm), eluted with ethyl acetate—petroleum
ether, 12 : 88).
d Isomers were not isolated.
e Percentage of the target ꢀisomer of the hexasaccharide 24, which was isolated after the step of substitutition of chlorine atom with
azido group and desilylation followed by preparative HPLC, calculated with respect to the mass of all isomers.
f Yield of ꢀisomer of compound 24 (see Scheme 7) isolated from the mixture of isomers after substitutition of chlorine atom with
azido group and desilylation followed by preparative HPLC.

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Podvalnyy et al.
Scheme 4
X = Cl (3), N3 (4), NHTFA (5)
Compounds
X
R
Bn
TIPS
Bn
Compounds
X
N3
NHTFA
Cl
R
Bn
Bn
9
10
11
—
—
Cl
12
13
14
TIPS
Reagents and conditions: i. NIS, AgOTf, CH2Cl2, MS 4 Å (see Table 1).
The content of ,ꢀisomer for compounds 11—13 was
assessed by analytical HLPC on silica gel and ranged from
56% to 64% according to HPLC data (Table 1). Indiviꢀ
dual ,ꢀisomers of hexasaccharides 11 and 13 were isoꢀ
lated using preparative HPLC in 42% yield with respect to
the glycosyl acceptor and then used for preparation of
unprotected hexasaccharide 1a. As isomers of fully protectꢀ
ed hexasaccharide 14 could not be separated by chromꢀ
atography, the separation of hexasaccharide stereoisomers
was performed after removal of silyl and silylene groups,
as discussed below.
compound 13 with a 2ꢀ(trifluoroacetamido)ethyl aglycon
a resonance at F –75.5 was observed.
It can be concluded from the results of glycosylation
reactions (see Table 1) that the type of the functional
group in C2ꢀaglycon of the tetrasaccharide glycosyl acꢀ
ceptor does not have a considerable effect on the yield and
stereoselectivity of glycosylation; hence, any of glycosyl
acceptors 3—5 can be used in preparative synthesis.
After ,ꢀisomers of fully protected hexasaccharides 11
and 13, which contain Oꢀbenzyl groups, were synthesized,
we started their deprotection. For compound 11, multiple
steps (Scheme 5) of aglycon modification and change
or removal of protective groups were needed for the
preparation of deblocked oligosaccharide with a spacer
ready for conjugation. The chlorine atom in 2ꢀchloroꢀ
ethyl aglycon in hexasaccharide 11 was replaced with
azido group by heating with NaN3 in DMF in the
presence of 18ꢀcrownꢀ6 to give azide 12 (yield 99%). Subꢀ
stitution of the chlorine atom in aglycon with azido group
results in the change of the resonance of the terminal carꢀ
bon of the preꢀspacer (C 50.7 for CH2N3 in the spectrum
of 12 as compared with C 42.7 ppm for CH2Cl in the
spectrum of 11). Silylene protective groups of the comꢀ
pound 12 were removed by treatment with Bun4NF in
tetrahydrofurane (THF) in the presence of AcOH, which
The structure of derivatives 11—14 was confirmed
by massꢀspectrometry and NMR spectroscopy. The presꢀ
ence of the residues AraV and AraVI in these compounds
was apparent from the resonances of anomeric carbons
C(1)V and C(1)VI of the prevailing ꢀisomer (C ~100),
and also from the resonances of hydrogens of CH2 of 2ꢀOꢀ
benzyl protective groups (H 4.62—4.80) (for benzylated comꢀ
pounds 11—13) and intensive resonances at H 0.95—1.08 of
1
DTBSꢀgroup of the residues AraV and AraVI in H and
13C NMR spectra. The chemical shifts of CH2CH2R of the
aglycon in 13C NMR spectra of compounds 11—14 are
different: C 50.6 for azide 12, C 39.7 for trifluoroacetꢀ
amide 13. Chemical shift of CH2CH2Cl in spectra of deꢀ
rivatives 11 and 14 was 42.7. In 19F NMR spectrum of

Benzylꢀfree approach to arabinans
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1153
is added to keep Oꢀbenzoyl groups intact. Purification by
HPLC on silica gel afforded 15 in 78% yield.
in the spectrum of derivative 16). Then compound 18 was
Oꢀdeacylated by MeONa in МеОН, and derivative 19
(yield 56%) was subjected to hydrogenolysis (H2 over
Pd(OH)2/C) to give hexasaccharide 20 (yield 72%) with
free hydroxyl groups and 2ꢀ(trifluoroacetamido)ethyl
aglycon, which is suitable for long storage as a precursor of
the target amine 1а. In 13С NMR spectrum of comꢀ
pound 20, resonances of С(1)V and С(1)VI ꢀlinked
arabinofuranose residues were observed at C 103.5, 103.6,
and the chemical shifts of С(1) of the four ꢀlinked araꢀ
binofuranose residues were at C 108—111.
Scheme 5
Compound 20 was treated with ionꢀexchange resin
Amberlyst Aꢀ26 (OH–ꢀ form) in water to give amine 1a
(yield 53%). Treatment with NaOH in МеОН followed by
chromatography on Sephadex LHꢀ20 (МеОН) was found
to be more efficient, and gave the conjugationꢀready
2ꢀaminoethyl glycoside 1а in 90% yield. Deprotection and
aglycon modification were performed in 20% total yield
with respect to the protected hexasaccharide 11.
The sequence of deprotection steps for hexasacchaꢀ
ride 13 is considerably shorter as its aglycon was subjected
to preliminary modification during the preparation of the
tetrasaccharide precursor 5. Similarly to the previous case,
the silylene protective groups in compound 13 (Scheme 6)
Scheme 6
Reagents and conditions: a. NaN3, DMF, 70 C, 99%; b. Bun4NF,
AcOH, THF, 78%; c. BzCl, Py, 97%; d. PPh3, THF, H2O,
0 C  20 C; e. (CF3CO)2O, NEt3, THF, 74% over two steps;
f. NaOMe, MeOH, 56%; g. H2, Pd(OH)2/C, MeOH—H2O,
28 C, 72%, h. 1) NaOH, MeOH, 90%.
Deprotected hydroxy groups of the compound 15 were
blocked by benzoylation with BzCl in pyridine to afford
fully benzoylated 16 in 97% yield. Upon treatment with
PPh3 in the THF–H2O mixture the azido group in the
aglycon of compound 16 was reduced to the amino group.
The amino group of 17 without further isolation from the
reaction mixture and purification was acylated with trifluꢀ
oroacetic anhydride in the presence of triethylamine to
afford trifluoroacetamide 18 (74% yield over two steps).
Conversion of azido group of 16 to trifluoroacetamido
group of compound 18 was confirmed by the change of the
13С chemical shift of CH2 group of the preꢀspacer aglycon
(C 39.6 in the spectrum of 18 as compared with C 50.6
Reagents and conditions: a. Bun4NF, THF, 95%; b. H2, Pd(OH)2/C,
MeOH, 40%; c. NaOH, MeOH, 50%.

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Podvalnyy et al.
were removed by treatment with Bun4NF in THF in the
presence of АсОН to give 21 in 95% yield. Hexaol 22 was
obtained by hydrogenolysis of 21 (H2 over Pd(OH)2/C) in
40% yield. The 1H NMR analysis of 22 was severely hamꢀ
pered by considerable broadening of the signals. Saponifiꢀ
cation of compound 22 gave the conjugationꢀready deproꢀ
tected hexasaccharide 1а with the 2ꢀaminoethyl aglycon
in 50% yield, which corresponds to 19% total yield with
respect to hexasaccharide 13.
Totally protected hexasaccharide 14, which was obꢀ
tained by the benzylꢀfree approach24,25 from glycosyl acꢀ
ceptor 3 with 2ꢀchloroethyl aglycon and glycosyl donor 10
with TIPS protective group at О(2) (see Scheme 4),
bears only benzoyl and siliconꢀbased protective groups.
Only two steps are required for its deprotection. The abꢀ
sence of benzyl groups in 14 allowed us to avoid the hydroꢀ
genolysis and keep the azido group in the aglycon until the
final step of the synthesis (Scheme 7). The mixture of
isomeric hexasaccharide 2ꢀchloroethyl glycosides 14 was
heated with NaN3 in DMF in the presence of 18ꢀcrownꢀ6
in DMF (see Scheme 7). 2ꢀAzidoethyl glycosides 23 thus
obtained in quantitative yield, were desilylated with TBAF
in THF in the presence of АсОН at 40 С to give hexaol 24
in 86% yield as a mixture of stereoisomers. At this step we
managed to isolate the target ꢀisomer using prepatative
HPLC, its proportion in the mixture of isomers being 59%.
Thus, the yield of the ꢀisomer of hexasaccharide 24
was 49% with respect to the tetrasaccharide 3 over three
steps. Hexaol 24 was deacylated by MeONa in MeOH,
followed by NaOH in MeOH to give 2ꢀazidoethyl glycoꢀ
side 1b, which can be used both for the synthesis of the
amine 1а and straightforward preparation of conjugates
by cycloaddition reactions.33—41 Azide 1b was reduced by
1,4ꢀdithiotreitol to give the target amine 1а (88%).
Overall yields for each of three sequences of hexaꢀ
saccharide 1a can be calculated with respect to the tetraꢀ
saccharide precursor 3. The highest efficiency of the synꢀ
thesis was achieved when the benzylꢀfree approach was
used. The overall yield of amine 1a with respect to tetraꢀ
saccharide 3 was 8.4% when the hexasaccharide was asꢀ
sembled from glycosyl donor 9 and glycosyl acceptor 3, it
was 5.8% when glycosyl donor 9 and glycosyl acceptor 5
were used, and the yield was as high as 38% in case glycoꢀ
syl donor 10 and glycosyl acceptor 3 were used for assemꢀ
bling hexasaccharide. It should be noted that only appliꢀ
cation of benzylꢀfree approach allows the synthesis of
deprotected hexasaccharide 1b with an azido group in
the aglycon.
Scheme 7
Experimental
The reactions were performed using commercial reꢀ
agents (Aldrich, Fluka). Anhydrous solvents were purified and
dried according to standard procedures. Chromatography and
extraction were performed using solvents purified and distilled
according to standard procedures. Powdered molecular sieves 4 Å
(MS 4A) were activated in vacuo at 200 C for 4 h. Thin layer
chromatography was carried out on plates DCꢀAlufolien Kieselꢀ
gel 60 F254 (Merck) on aluminum foil or on glass using mixtures
of solvents described in the experiment (proportions are given in
volume fractions). Spots of carbohydrateꢀcontaining compounds
were visualized by heating on a hot plate (at ca. 150 C) followed by
immersion of the plate into the solution of 85% aqueous H3PO4
in 96% EtOH (1 : 10 v/v mixture) and additional heating. Spots
of compounds, which absorb UV light, were visualized by their
absorbance at 254 nm. Spots of compounds, which contain amino
groups, were visualized by heating after immersion in 0.2% solution
of ninhydrin in acetone. Column chromatography was performed
on silica gel 60 (40—63 m, Merck), and preparative HPLC
separation was performed on a Silasorb 600 (7.5 m, Chemapol)
column (25×250 mm). Gel permeation chromatography was perꢀ
formed on BioꢀBeads S×1 (400×40 mm) and BioꢀBeads S×3
(400×22 mm) gel columns in toluene or on a Sephadex LHꢀ20
column (900×10 mm) in methanol. Analytical HPLC separations
were performed on a silica gel Ultrasphere (5 m) column
(120×4.6 mm). Target ,ꢀisomer was isolated by preparative
HPLC on a Silasorb 600 (7.5 m, Chemapol) column (250×25 mm).
Reagents and conditions: a. NaN3, 18ꢀcrownꢀ6, 100%, mixture
of isomers; b. 1) TBAF•H2O, AcOH, THF, 40 C, 86%, mixture
of isomers, 2) HPLC on silica gel, 51% with respect to 23, 49%
with respect to tetrasaccharide 3, pure ꢀisomer; c. 1) MeONa.
MeOH, 2) NaOH, MeOH, 89%; d.1,4ꢀdithiothreitol, NaHCO3,
H2O, 88%.

Benzylꢀfree approach to arabinans
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1155
1H and 13C NMR spectra were recorded on a Bruker AM
500 instrument (500.13 and 125.37 MHz, respectively), and a
Bruker AM 300 instrument (300.13 and 75.47 MHz, respectiveꢀ
ly), and a Bruker AVANCE 600 instrument (600.13 and 150.9
MHz, respectively). 19F NMR spectra were recorded on a Brukꢀ
er AM 300 instrument (282.40 MHz). The 1H chemical shifts
ed 1a, were lyophilized to give the amine 1a (8.6 mg, 88%).
Rf 0.37 (EtOH—BuOH—Py—AcOH—H2O, 100 : 10 : 10 : 3 : 10).
 23 +44.6 (c 1.0, МеОН). MS, m/z: 854.3138 [M + Н]. Calꢀ
D
culated for C32H56NO25: 854.3136. 1H NMR (600.13 MHz,
CD3OD), : 3.49—3.54 (m, 1 H, OCH2CH2NH2); 3.61—3.69 (m, 6 H);
3.71—3.85 (m, 12 H); 3.89—3.95 (m, 5 H); 3.95—4.07 (m, 12 H);
4.12—4.16 (m, 3 H); 4.18—4.22 (m, 1 H); 4.90 (br.s, 1 H, H(1)II);
4.96 (s, 1 H, H(1)I); 5.03—5.05 (m, 2 H, H(1)V, H(1)VI); 5.09 (d, 1 H,
J = 2.1 Hz); 5.17 (d, 1 H, J = 2.2 Hz, H(1)III, H(1)IV). 13C NMR
(150.9 MHz, CD3OD), : 42.28 (OCH2CH2NH2); 62.56, 62.63
(C(5)III, C(5)IV); 64.56 (2 C, C(5)V, C(5)VI); 68.07 (OCH2CH2ꢀ
NH2); 68.09 (C(5)I); 75.92, 75.98 (C(2)V, C(2)VI); 76.43, 76.61
(C(3)III, C(3)IV); 78.93, 78.98 (2 C) (C(4)V, C(4)VI, C(2)II);
81.77, 83.15, 83.23, 83.59 (C(2)I, C(3)II, C(4)I, C(4)II); 84.07,
84.14 (C(4)III, C(4)IV); 84.51 (2 C, C(3)V, C(3)VI); 84.75, 89.37,
89.62 (C(2)III, C(2)IV, C(3)II); 102.58, 102.68 (C(1)V, C(1)VI),
107.21, 107.53 (C(1)III, C(1)IV); 109.68 (C(1)I), 109.83 (C(1)II).
2ꢀAzidoethyl 5ꢀOꢀ{3,5ꢀdiꢀOꢀ[2ꢀOꢀ(ꢀDꢀarabinofuranosyl)ꢀꢀ
Dꢀarabinofuranosyl]ꢀꢀDꢀarabinofuranosyl}ꢀꢀDꢀarabinofuranoꢀ
side (1b). Partially benzoylated compound 24 (81.0 mg,
0.0503 mmol) was dissolved in anhydrous МеОН (2.5 mL),
MeONa (116 L of 1 М solution in МеОН) was added, and the
solution was kept for 2 days at ~20 C. Water (6 L) was added,
and reaction mixture was stirred for 2 h. The reaction mixture
was concentrated to ~1.5 mL (both temperature ~20 C), the
residue was applied onto the Sephadex LHꢀ20 column (packed
in methanol) and the product was eluted with methanol. Fracꢀ
tions which contained compound 1b were concentrated, and the
residue (49.1 mg) was subjected to chromatography on a SepꢀPak
Сꢀ18 cartridge, and the product was eluted with water (10 mL)
and 1, 2, 4, 10, 20, 30, 40, 50, 60, 70% aqueous solutions of
methanol (5 mL each). Fractions, which contained the comꢀ
pound 1b, were concentrated to ~2 mL under water aspirator
pump vacuum, diluted with water up to ~10 mL, concentrated
again to ~2 mL, diluted with water up to ~5 mL, frozen and
lyophilized to give the compound 1b as white flakes (39.5 mg,
are referred to the residual signal of СHCl3 ( 7.27) for soluꢀ
H
tions in СDCl3, DMSOꢀd5 (H 2.50) for solutions in DMSOꢀd6,
CHD2OD (H 3.31) for solutions in CD3OD and HDO (H 4.80)
for solutions in D2O. The 13C NMR chemical shifts are referred
to the central signal of the solvent (C 77.0 for solutions in CDCl3,

C 39.50 for solutions in DMSOꢀd6 and  49.0 for solutions in
C
CD3OD) or the signal of external 1,4ꢀdioxane (C 67.4) for soluꢀ
tions in D2O. The 19F NMR chemical shifts are referred to the
external signal of CFCl3 (F 0). Assignments of the signals in the
1H and 13C NMR spectra were performed using the APT
(JMODXH) and 2Dꢀexperiments (COSY, TOCSY, HSQC,
HMBC, HSQC—TOCSY, ROESY). High resolution mass spectra
with electrospray ionization (ESI) were recorded on Bruker
micrоTOF II mass spectrometer for 2•10–5M solutions in MeCN
or MeOH. Optical rotations were measured using a PUꢀ07 autoꢀ
matic digital polarimeter (Russia) at 16—34 C.
2ꢀAminoethyl 5ꢀOꢀ{3,5ꢀdiꢀOꢀ[2ꢀOꢀ(ꢀDꢀarabinofuranosyl)ꢀ
ꢀDꢀarabinofuranosyl]ꢀꢀDꢀarabinofuranosyl}ꢀꢀDꢀarabinofurꢀ
anoside (1а). А. 2ꢀ(Trifluoroacetamido)ethyl derivative 20 (2.0 mg,
0.0021 mmol) was dissolved in МеОН (1 mL), and 0.1 М soluꢀ
tion of NaOH in МеОН (300 L, 0.03 mmol) was added. The
reaction mixture was stirred at ~20 C for 18 h. The reaction was
monitored by TLC (Rf 0.37 1а), EtOH—BuOH—Py—AcOH—
H2O, 100 : 10 : 10 : 3 : 10). The reaction mixture was applied onto
a Sephadex LHꢀ20 gel column and eluted with methanol. The
fraction, which contained the amine 1а, was concentrated and
dried in vacuo to give the compound 1а (1.7 mg, 90%).
B. 2ꢀ(Trifluoroacetamido)ethyl derivative 20 (2.0 mg,
0.0021 mmol) was dissolved in water (2.0 mL), then the ionꢀ
exchange resin Amberlyst Aꢀ26 (OH–ꢀform) was added (518 mg,
wet weight). The reaction mixture was stirred for 3 h (by shaking
the flask on the shaker with the frequency 40 rpm) at ~20 C, and
filtered through a glass filter. The ionꢀexchange resin was washed
with water (2×2 mL), the filtrate was lyophilized to give 2ꢀaminoꢀ
ethyl glycoside 1a (1.0 mg, 53%).
С. Benzoylated derivative 22 (37.1 mg, 0.0221 mmol) was
dissolved in anhydrous МеОН (3.5 mL), then MeONa (175 L
of 1 М solution in МеОН) was added, and stirred at ~20 C for
16 h. TLC showed that the reaction mixture contained trifluoroꢀ
acetamide 20 and amine 1а. Water (6 L) was added to the
reaction mixture, and the solution was stirred for 2 h. The reacꢀ
tion mixture was concentrated to ~0.3 mL, the residue was disꢀ
solved in МеОН (1 mL) and applied onto a Sephadex LHꢀ20
column in methanol and the product was eluted with methanol.
The fraction, which contained 1a, was concentrated, the residue
(11.5 mg) was dissolved in water (3 mL), extracted with benzene
(5×3 mL) to remove the residual methyl benzoate. Lyophilizaꢀ
tion of the aqueous layer gave totally deprotected compound 1а
as white flakes (9.5 mg, 50%).
89%). Rf 0.61 CHCl3—EtOH—BuOH—Py—AcOH—H2O,
30
66 : 100 : 10 : 10 : 10 : 3). 
+40.7 (c 1, H2O). MS, m/z:
D
902.2853 [M + Na]. Calculated for C32H53N3NaO25: 902.2860.
1H NMR (600 MHz, D2O), : 3.49—3.57 (m, 2 H, CH2CH2N3);
3.67—3.79 (m, 5 H); 3.79—3.83 (m, 4 H); 3.84—3.90 (m, 4 H);
3.90—3.98 (m, 4 H) (H(3)II, H(5)I, H(5)II, H(5)III, H(5)IV
,
H(5)V, H(5)VI, CH2CH2N3); 4.01—4.19 (m, 7 H); 4.19—4.23
(m, 2 H); 4.30 (s, 1 H); 4.32 (td, 1 H, J = 5.4 Hz, J = 3.0 Hz);
(H(2)I, H(2)II, H(2)III, H(2)IV, H(2)V, H(2)VI, H(3)I, H(3)II,
H(3)III, H(3)IV, H(3)V, H(3)VI, H(4)I, H(4)II, H(4)III, H(4)IV
,
H(4)V, H(4)VI, 5.08 (d, 1 H, H(1)I, J = 1.8 Hz); 5.12
(s, 1 H, H(1)II); 5.15 (s, 1 H, J = 1.7 Hz); 5.16 (d, 1 H, H(1)V,
H(1)VI, J = 1.7 Hz); 5.19 (d, 1 H, H(1)III, J = 1.7 Hz); 5.26 (d, 1 H,
H(1)VI, J = 1.8 Hz). 13C NMR (151 MHz, D2O), : 51.6
(CH2CH2N3); 61.85, 61.89 (C(5)III, C(5)IV), 64.20, 64.23 (C(5)V,
C(5)VI), 67.6, 67.7, 68.0 (C(5)I, C(5)II, CH2CH2N3), 75.4, 75.5
(C(2)V, C(2)VI), 76.0, 76.1 (C(3)III, C(3)IV); 77.5, 77.8, 80.4
(C(2)II, C(4)V, C(4)VI); 82.3, 83.0, 83.2, 83.3 (C(2)I, C(3)I, C(4)I,
C(4)II), 83.8 (C(3)II), 84.1, 84.2 (C(4)III, C(4)IV), 88.1, 88.3
(C(2)III, C(2)IV), 101.9, 102.0 (C1V, C(1)VI), 106.7, 106.9
(C(1)III, C(1)IV), 108.7 (C(1)II), 108.8 (C(1)I).
D. Azide 1b (10 mg, 0.0114 mmol) was dissolved in water
(1.0 mL), then 0.50 М aqueous solution of NaHCO3 was added
followed by 1,4ꢀdithiothreitol (8.8 mg, 0.0568 mmol). The reacꢀ
tion mixture was stirred for 6 h at 20 С, and then applied on
a column (880×16 mm) with Sephadex Gꢀ10 (packed in water) and
the product was eluted with water. The fractions, which containꢀ
2ꢀChloroethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ[2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
(3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl)ꢀꢀDꢀarabinofuranoꢀ
syl)]ꢀꢀDꢀarabinofuranoside (3). Solution of bisꢀchloroacetate 2
(1.960 g, 1.315 mmol) in the mixture of Py (40 mL) and Н2О

1156
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
Podvalnyy et al.
(20 mL) was stirred for 3.5 h at 65 С, then concentrated, coꢀ
concentrated with toluene (2×20 mL), the residue was dissolved
in CH2Cl2 (150 mL), washed with water (200 mL), the organic
phase was filtered through cotton wool plug, concentrated, and the
residue was dried in vacuo. Chromatography on silica gel (gradiꢀ
ent elution with toluene—AcOEt, 6 : 1  toluene—AcOEt, 4 : 1)
gave 3 as a white solid foam (1.498 g, 85%). Rf 0.44 (toluene—
(C(4)I, C(4)II); 81.2 (2 C, C(2)III, C(2)IV); 81.65, 81.74, 81.8,
82.0, 82.2, 82.3, 82.8 (C(2)I, C(2)II, C(3)I, C(3)III, C(3)IV
,
C(4)III, C(4)IV); 105.5, 105.8 (C(1)I, C(1)II); 107.8, 107.9
(C(1)III, C(1)IV); 128.3, 128.37, 128.40, 128.6, 128.9, 129.0,
129.1, 129.2, 129.6, 129.7, 129.8, 129.88, 129.90, 133.1, 133.3,
133.5, 133.5 (Ph); 165.3, 165.4, 165.8, 166.11, 166.16, 166.9
(2 C) (CO).
EtOAc, 3 : 1).  25 +171.3 (c 1.0, CHCl3). MS, m/z: 1359.3437
2ꢀTrifluoroacetamidoethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ[2ꢀOꢀbenzoꢀ
ylꢀ3,5ꢀdiꢀOꢀ(3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl)ꢀꢀDꢀaraꢀ
binofuranosyl]ꢀꢀDꢀarabinofuranoside (5). To a stirred and cooled
(ice—water bath) solution of azide 4 (211 mg, 0.156 mmol) in
THF (8 mL) PPh3 (82.3 mg, 0.314 mmol) was added. The reacꢀ
tion mixture was strirred for 3 h at 0 С, then H2O (400 L) was
added, and the mixture was kept for 20 h at ~20 C. The reaction
mixture was diluted with toluene (10 mL), concentrated, the
residue was coꢀconcentrated with toluene (2×10 mL) and dried
in vacuo. The resulting mixture (which contained free amine,
PPh3, and triphenylphosphine oxide) was dissolved in THF
(8 mL), and NEt3 (435 L, 3.11 mmol) and (CF3CO)2O (215 L,
1.54 mmol) were added to this solution upon stirring and cooling
(ice—water bath). The reaction mixture was stirred for 30 min at
0 С, then diluted with CH2Cl2 (100 mL), washed with saturated
aqueous solution of NaHCO3 (100 mL), filtered through a cotꢀ
ton wool plug, concentrated, and the residue was dried in vacuo.
The residue was applied on a column with BioBeads S×3 and
eluted with toluene. The fraction, which contained the target
product 5, was subjected to chromatography on silica gel (eluent
toluene—AcOEt, 4 : 1). The product 5 was obtained as a colorꢀ
D
[M + Na]. Calculated for C71H65ClNaO24SF. 1359.3447.
1H NMR (600.13 MHz, CDCl3), : 2.95 (d, 1 H, OH, J = 3.43 Hz);
3.18 (d, 1 H, OH, J = 3.29 Hz); 3.65—3.71 (m, 2 H, CH2Cl);
3.78—3.83 (m, 1 H, OCH(a)H(b)CH2Cl); 3.85—3.90 (m, 2 H,
H(5a)I, H(5a)II); 3.98 (ddd, 1 H, OCH(a)H(b)CH2Cl, J = 11.29 Hz,
J = 5.90 Hz, J = 5.73 Hz); 4.06 (dd 1 H, H(5a)II, J = 11.66 Hz,
J = 4.80 Hz); 4.17 (dd, 1 H, H(5b)I, J = 11.18 Hz, J = 4.19 Hz);
4.21 (br.s, 1 H, H(2)IV); 4.29 (br.s, 1 H, H(2)III); 4.32 (d, 1 H,
H(3)II, J = 5.63); 4.45—4.48 (m, 2 H, H(4)I, H(4)II); 4.49—4.69
(m, 6 H, H(5)aIII, H(5b)III, H(5a)IV, H(5b)IV, H(4)III, H(4)IV);
4.97 (dd, 1 H, H(3)IV, J = 6.45 Hz, J = 3.02 Hz); 5.03 (dd, 1 H,
H(3)III, J = 5.90 Hz, J = 2.61 Hz); 5.24 (s, 1 H, H(1)III); 5.26
(s, 1 H, H(1)I); 5.31 (s, 1 H, H(1)IV); 5.35 (s, 1 H, H(1)II); 5.40
(s, 1 H, H(2)II); 5.44 (s, 1 H, H(2)I); 5.61 (d, 1 H, H(3)I,
J = 4.80); 7.29—7.59 (m, 21 H, Ph); 7.88—7.98 (m, 8 H, Ph);
8.00—8.07 (m, 6 H, Ph). 13C NMR (151 MHz, CDCl3), : 42.8
(CH2Cl), 63.7 (C(5)III), 63.75 (C(5)IV), 65.3 (C(5)I), 65.9
(C(5)II), 67.4 (CH2O), 76.9 (C(3)I), 79.00, 79.1 (C(4)I, C(4)II),
81.13, 81.19 (C(2)III, C(2)IV), 81.6, 81.73 (2 C, C(3)I, C(3)III
,
C(3)IV), 81.79, 82.1, 82.4, 82.7 (C(2)II, C(2)I, C(3)II, C(4)I,
C(4)II), 105.5 (C(1)II), 105.6 (C(1)I), 107.8 (C(1)IV), 107.9
(C(1)III), 128.33, 128.36, 128.39, 128.4, 128.6, 128.8, 129.0,
129.13, 129.17, 129.5, 129.66, 129.68, 129.71, 129.76, 129.86,
129.88, 133.1, 133.3, 133.43, 133.47, 133.49, 133.56 (Ph); 165.28,
165.35, 165.8, 166.10, 166.15, 166.91, 166.93 (CO).
less solid film (165 mg, 75%). Rf 0.44 (toluene—EtOAc, 2 : 1).
22

+71.7 (c 1.0, CHCl3). MS, m/z: 1436.3776 [M + Na].
D
Calculated for C73H66F3NNaO25: 1436.3768. 1H NMR (300.13
MHz, CDCl3), : 3.09 (d, 1 H, OH, J = 3.6), 3.20 (d, 1 H, OH,
J = 3.5); 3.56—3.65 (m, 2 H, CH2CH2NHCOCF3); 3.66—3.76
2ꢀAzidoethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ[2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
(3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl)ꢀꢀDꢀarabinofuranosyl]ꢀ
ꢀDꢀarabinofuranoside (4). The mixture of 2ꢀchloroethyl glycoꢀ
side 3 (516.8 mg, 0.386 mmol), NaN3 (125 mg, 1.93 mmol) and
18ꢀcrownꢀ6 (46 mg, 0.174 mmol) in anhydrous DMF (4.3 mL)
was stirred at 70 С for 42 h. The reaction mixture was diluted
with toluene (~150 mL), washed with water (3×70 mL), the
combined aqueous phase (~200 mL) was extracted with toluene
(3×50 mL). The combined organic phase of the last three extracꢀ
tions was washed with water (2×50 mL). The combined organic
extracts (~300 mL) were filtered through cotton wool plug, concenꢀ
trated, and the residue was dried in vacuo. Glycoside 4 was obꢀ
tained as a solid colorless film (502 mg, 97%). Rf 0.44 (toluene—
(m, 1 H, CH2CH2NHCOCF3); 3.82—3.94 (m, 3 H,
CH2CH2NHCOCF3, H(5a)I, H(5b)I); 4.06 (dd, 1 H, H(5b)II,
J = 11.6 Hz, J = 4.5 Hz); 4.13 (dd, 1 H, H(5b)I, J = 11.3 Hz,
J = 4.4 Hz); 4.25—4.32 (m, 2 H, H(2)IV, H(3)III); 4.33—4.73
(m, 9 H, H(2)III, H(4)I, H(4)I, H(4)II, H(4)III, H(4)IV
,
H(5a,b)III, H(5a,b)IV); 4.98—5.07 (m, 2 H, H(3)III, H(3)IV);
5.21 (s, 1 H, H(1)III); 5.23 (s, 1 H, H(1)I); 5.32 (s, 1 H); 5.34
(s, 1 H, H(1)II, H(1)IV); 5.40 (s, 2 H, H(2)I, H(2)II); 5.65 (dd, 1 H,
H(3)I, J = 5.3 Hz, J = 1.8 Hz); 7.06 (br.s, 1 H, NH); 7.28—7.61
(m, 21 H, Ph); 7.88—8.08 (m, 14 H, Ph). 13C NMR (75.47 MHz,
CDCl3), : 39.6 (CH2CH2NHCOCF3), 63.73, 63.77 (C(5)I,
C(5)II), 65.51 (2 C, C(5)III, C(5)IV), 65.97 (CH2CH2NHꢀ
COCF3), 76.8 (C(3)II), 79.1 (2 C, C(4)III, C(4)IV), 81.2 (2 C),
EtOAc, 3 : 1).  22 +100.4 (c 1.0, CHCl3). MS, m/z: 1366.3870
81.3, 81.8 (2 C); 81.9, 82.1, 82.4, 82.7 (C(2)I, C(2)II, C(2)III
,
D
[M + Na]. Calculated for C71H65N3NaO24: 1366.3850. 1H NMR
(300.13 MHz, CDCl3), : 2.95—3.00 (br.s, 1 H, OH); 3.30—3.47
(br.s, 1 H, OH); 3.40—3.47 (m, 2 H, OCH2CH2N3); 3.64—3.73
(m, 1 H, OCH2CH2N3); 3.84—3.99 (m, 3 H, H(5a)II,
OCH2CH2N3); 4.06 (dd, 1 H, H(5b)I, J = 11.6 Hz, J = 4.7 Hz);
4.15—4.23 (m, 2 H, H(2)III, H(5b)I); 4.27—4.34 (m, 2 H, H(3)II,
C(2)IV, C(3)I, C(3)III, C(3)IV, C(4)I, C(4)II); 105.7, 106.1 (C(1)I,
C(1)II); 107.7, 108.0 (C(1)III, C(1)IV); 128.3, 128.4, 128.5, 128.6,
128.77, 128.81, 128.9, 129.1, 129.5, 129.66, 129.71, 129.76,
129.9, 133.1, 133.4, 133.5, 133.6, 133.7 (Ph), 165.4, 165.6, 165.7,
166.1, 166.2, 166.91, 166.97 (CO). 19F NMR (282 MHz, CDCl3),
: –76.6 (COCF3).
2ꢀChloroethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
[2ꢀOꢀ(2ꢀOꢀbenzylꢀ3,5ꢀOꢀdiꢀtertꢀbutylsilyleneꢀꢀDꢀarabinofurꢀ
anosyl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀarabinoꢀ
furanosyl}ꢀꢀDꢀarabinofuranoside (11). Glycosyl donor 9 (120 mg,
0.254 mmol) and glycosyl acceptor 3 (99 mg, 0.074 mmol) were
coꢀconcentrated with anhydrous toluene (3×2 mL), dried in vacuo,
dissolved in anhydrous CH2Cl2 (6 mL), and the solution was
cannulated via a doubleꢀtipped needle into a flask with freshly
H(2)IV); 4.43— 4.70 (m, 8 H, H(4)I, H(4)II, H(4)III, H(4)IV
,
H(5a,b)III, H(5a,b)IV); 4.94—4.99 (m, 1 H, H(3)IV); 5.00—5.06
(m, 1 H, H(3)III); 5.24 (s, 2 H, H(1)III, H(1)I); 5.31 (s, 1 H,
H(1)VI); 5.36 (s, 1 H, H(1)II); 5.41 (s, 1 H, H(2)II); 5.44 (s, 1 H,
H(2)I); 5.63 (d, 1 H, H(3)I, J = 4.9 Hz); 7.25—7.61 (m, 21 H,
Ph); 7.85—8.09 (m, 14 H, Ph). 13C NMR (75.47 MHz, CDCl3),
: 50.7 (OCH2CH2N3); 63.8 (2 C, C(5)I, C(5)II); 65.3, 65.9
(C(5)III, C(5)IV); 66.4 (OCH2CH2N3); 77.2 (C(3)II); 79.0, 79.2

Benzylꢀfree approach to arabinans
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1157
activated molecular sieves 4 Å (600 mg). The resulting mixture
was stirred for ~16 h at ~20 C under Ar, then cooled to –47 С
(acetone—dry ice bath), and NIS (57.1 mg, 0.254 mmol, dried
in vacuo for 40 min) followed by AgOTf (10.3 mg, 0.040 mmol)
were added under Ar. After the appearance of iodine color
the temperature of the reaction mixture was maintained at
were added under Ar. After appearance of iodine color the temꢀ
–
–
perature of the reaction mixture was maintained at 45— 46 С
for 1 h, then the temperature was allowed to increase gradually
within 1.5 h to –30 С, and NEt3 (40 L) was added. The reacꢀ
tion mixture was filtered through Celite (the filter was washed
thoroughly with CH2Cl2, 5×10 mL), washed with a solution preꢀ
pared from crystalline Na2S2O3•5H2O (~2.5 g) and saturated
aqueous NaHCO3 (100 mL). Aqueous phase was extracted with
CH2Cl2 (3×20 mL). Combined organic extracts (~100 mL) were
filtered through a cotton wool plug, concentrated, and the resiꢀ
due was dried in vacuo. Chromatography on BioBeads S×1 gel in
toluene gave a fraction of isomeric hexasaccharides 12 (43.2 mg,
100%). The content of the target ,ꢀisomer according to HPLC
analysis (eluent petroleum ether—EtOAc, 88 : 12) was 56%.
Individual isomers were not isolated.
–
–
45— 46 С for 1 h, then the temperature was increased graduꢀ
ally within 1 h to –30 С, and NEt3 (50 L) was added. The
reaction mixture was filtered through Celite (the filter was thorꢀ
oughly washed with CH2Cl2, 5×10 mL), and with a solution
prepared from crystalline Na2S2O3•5H2O (~2.5 g) and saturated
aqueous NaHCO3 (50 mL). Aqueous phase was extracted with
CH2Cl2 (3×20 mL). Combined extracts (~100 mL) were filtered
through a cotton wool plug, concentrated, and the residue was
dried in vacuo. Gelꢀchromatography on a BioBeads S×1 column
in toluene gave a fraction of isomeric hexasaccharides 11
(149.7 mg, 97%). The content of the target ꢀisomer according
to HPLC analysis (eluent petroleum ether—EtOAc, 88 : 12) was
61%. Preparative HPLC (eluent petroleum ether—EtOAc,
88 : 12) gave ꢀisomer 11 (64.8 mg, 42%). Rf 0.45 (toluene—
B. 2ꢀChloroethyl glycoside 11 (263 mg, 0.127 mmol) was
dissolved in anhydrous DMF, and NaN3 (25 mg, 0.382 mmol)
and 18ꢀcrownꢀ6 (15.2 mg, 0.057 mmol) were added. The mixꢀ
ture was stirred for 40 h at 70 С, coꢀconcentrated with toluene
(3×10 mL), the residue was dissolved in toluene—petroleum ether
(1 : 1) (70 mL) mixture, washed with water (3×70 mL), comꢀ
bined aqueous phase (~200 mL) was extracted with toluene—
petroleum ether mixture (3×50 mL) and the combined organic
phase from the last three extractions was washed with water
(2×50 mL). The combined organic phase (~200 mL) was filtered
through a cotton wool plug, concentrated, the residue was dried
in vacuo. Compound 12 was obtained as a solid colorless film
EtOAc, 10 : 1).  22 –6.8 (c 1.0, CHCl3). MS, m/z: 2803.7271
D
[M + Na]. Calculated for C111H125ClNaO32Si2: 2803.7273.
1H NMR (600.13 MHz, CDCl3), : 0.98 (s, 9 H, But2Si), 0.99
(s, 9 H, But2Si), 1.04 (s, 9 H, But2Si); 1.05 (s, 9 H, But2Si);
3.53—3.61 (m, 2 H, H(3)V, H(3)VI); 3.63—3.70 (m, 2 H,
OCH2CH2Cl); 3.75—3.97 (m, 9 H, OCH2CH2Cl, H(2)V, H(2)VI
,
H(4)V, H(4)VI, H(5)); 4.06—4.16 (m, 4 H, H(5)); 4.30 (d, 1 H,
H(2)III, J = 1.7 Hz); 4.32—4.38 (m, 3 H, H(2)IV, H(5)); 4.40—4.55
(m, 8 H, H(3)III, H(4)III, H(3)IV, H(4)IV, H(5)); 4.70 (d, 1 H,
CH2Ph, J = 12.1 Hz); 4.75 (d, 1 H, CH2Ph, J = 12.1 Hz); 4.77
(s, 2 H, CH2Ph); 5.05 (d, 1 H, H(1)VI, J = 5.1 Hz); 5.11 (d, 1 H,
H(1)V, J = 5.1 Hz); 5.22 (s, 1 H, H(1)I); 5.26 (s, 1 H, H(1)IV);
5.31 (s, 1 H, H(1)II); 5.40 (d, 1 H, H(2)II J = 1.4 Hz); 5.47—5.52
(m, 3 H, H(1)III, H(2)I, H(3)II); 5.55 (d, 1 H, H(3)I, J = 5.0 Hz);
7.16—7.24 (m, 2 H, Ph); 7.26—7.50 (m, 18 H, Ph); 7.53—7.56
(m, 1 H, Ph); 7.82—7.84 (m, 1 H, Ph); 7.90—7.97 (m, 4 H, Ph);
8.01—8.04 (m, 2 H, Ph); 8.04—8.07 (m, 2 H, Ph). 13C NMR
(150.9 MHz, CDCl3), : 20.0, 22.5 ((CH3)3CSi); 27.1, 27.5
((CH3)3CSi); 42.7 (OCH2CH2Cl); 64.2, 64.4 (C(5)V, C(5)VI),
23
(262.3 mg, 99%). []D –14.3 (c 1.19, CHCl3). Rf 0.48 (toluꢀ
ene—EtOAc, 10 : 1). MS, m/z: 2090.7676 [M + Na]. Calculated
for C111H125N3Na]O32Si2: 2090.7677. 1H NMR (500.13 MHz,
CDCl3), : 0.98 (d, 18 H, But, J = 1.8Hz); 1.04 (s, 9 H, But); 1.05
(s, 9 H, But); 3.36—3.46 (m, 2 H, OCH2CH2N3); 3.52—3.61
(m, 2 H, H(3)V, H(3)VI); 3.63—3.68 (m, 1 H, OCH2CH2N3);
3.79—3.95 (m, 6 H, H(2)V, H(2)VI, H(4)V, H(4)VI, OCH2CH2N3);
4.07—4.16 (m, 3 H, H(5)); 4.30 (br.s, 1 H, H(2)III); 4.32—4.38
(m, 3 H, H(2)IV, H(5)); 4.40—4.56 (m, 8 H, H(3)III, H(3)IV
,
H(4)III, H(4)IV, H(5)); 4.68—4.78 (m, 4 H, PhCH2); 5.04 (d, 1 H,
H(1)VI, J = 5.1 Hz); 5.11 (d, 1 H, H(1)V, J = 5.1 Hz); 5.20
(s, 1 H, H(1)I); 5.26 (s, 1 H, H(1)III); 5.32 (s, 1 H, H(1)II); 5.41
(s, 1 H, H(2)II); 5.47—5.51 (m, 3 H, H(1)II, H(2)I, H(3)III);
5.56 (d, 1 H, H(3)I, J = 4.6 Hz); 7.15—7.24 (m, 3 H, Ph); 7.24—7.51
(m, 25 H, Ph); 7.51—7.56 (m, 1 H, Ph); 7.83 (d, 2 H, Ph,
J= 7.3 Hz); 7.89—7.97 (m, 5 H, Ph); 7.99—8.04 (m, 3 H, Ph);
8.04—8.08 (m, 2 H, Ph). 13C NMR (126 MHz, CDCl3,), : 20.1,
22.5, 27.2, 27.5 (But), 50.7 (OCH2CH2N3), 64.2, 64.4 (C(5)V,
65.8, 67.4, 68.1, 68.2 (C(5)I, C(5)II, C(5)III
, ,
C(5)IV
OCH2CH2Cl), 71.8, 71.9 (CH2Ph), 73.8, 73.9 (C(3)V, C(3)VI),
77.1 (C(3)I), 78.1, 78.2 (C(2)V, C(2)VI, C(3)III, C(3)IV), 80.4,
80.7, 80.7, 80.8, 80.9, 81.8, 82.1, 82.1, 83.2 (C(2), C(3), C(4)),
86.2 (C(4)V, C(4)VI), 100.4 (C(1)V, C(1)VI), 105.6, 105.7, 106.2
(C(1)I, C(1)II, C(1)IV); 107.1 (C(1)IV); 127.6, 127.7, 127.9, 128.0,
128.2, 128.3, 128.30, 128.35, 128.40, 128.5, 129.07, 129.15,
129.18, 129.22, 129.4, 129.6, 129.76, 129.79, 129.82, 129.9,
132.8, 133.13, 133.16, 133.2, 133.4, 133.5, 137.8, 137.9 (Ph);
165.29, 165.34, 165.4, 165.5, 165.6, 165.9, 166.1 (CO).
C(5)VI), 65.8, 65.9, 66.4, 68.1, 68.2 (C(5)I, C(5)II, C(5)III, C(5)IV
,
OCH2CH2N3), 71.8, 71.9 (PhCH2), 73.9, 74.0 (C(3)VI, C(3)VI),
77.2 (C(3)I), 78.2, 78.3, 80.4, 80.7, 80.8, 80.9, 81.0, 82.0, 82.1,
82.2, 83.3, 86.2 (C(2), C(3), C(4)); 100.4 (C(1)V, C(1)VI), 105.7,
105.9, 106.2, 107.1 (C(1)I, C(1)II, C(1)III, C(1)IV), 127.6, 127.7,
127.95, 127.98, 128.28, 128.31, 128.33, 128.38, 128.41, 128.6,
129.13, 129.16, 129.21, 129.28, 129.4, 129.66, 129.69, 129.79,
129.87, 129.90, 132.9, 133.1, 133.2, 133.3, 133.4, 133.5, 137.86,
137.94 (Ph); 165.32, 165.39, 165.45, 165.55, 165.65, 166.0,
166.1 (CO).
2ꢀAzidoethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
[2ꢀOꢀ(2ꢀOꢀbenzylꢀ3,5ꢀOꢀdiꢀtertꢀbutylsilyleneꢀDꢀarabinofuranoꢀ
syl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀarabinofuranoꢀ
syl}ꢀꢀDꢀarabinofuranoside (12). А. Glycosyl donor 9 (32.9 mg,
0.0695 mmol) and glycosyl acceptor 4 (27.1 mg, 0.0202 mmol)
were coꢀconcentrated with anhydrous toluene (3×2 mL), dried
in vacuo, dissolved in anhydrous CH2Cl2 (1.6 mL), and the soluꢀ
tion was cannulated via a doubleꢀtipped needle into a flask with
freshly activated molecular sieves 4 Å (160 mg). The resulting mixꢀ
ture was stirred for ~16 h at ~20 C under Ar, then cooled to –47 С
(acetone—dry ice bath), and NIS (15.7 mg, 0.0695 mmol, dried
in vacuo for 40 min) followed by AgOTf (1.8 mg, 0.00695 mmol)
2ꢀ(Trifluoroacetamido)ethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoꢀ
yl(3,5ꢀdiꢀOꢀ[2ꢀOꢀ(2ꢀOꢀbenzylꢀ3,5ꢀOꢀdiꢀtertꢀbutylsilyleneꢀꢀDꢀ
arabinofuranosyl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀ
arabinofuranosyl}ꢀꢀDꢀarabinofuranoside (13). Glycosyl donor 9
(190 mg, 0.404 mmol) and glycosyl acceptor 5 (165.5 mg,
0.117 mmol) were coꢀconcentrated with anhydrous toluene

1158
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
Podvalnyy et al.
(3×5 mL), dried in vacuo, dissolved in anhydrous CH2Cl2 (11 mL),
and the solution was cannulated via a doubleꢀtipped needle into
a flask with freshly activated molecular sieves 4 Å (1.10 g). The
resulting mixture was stirred for ~1.5 h at ~25 C under Ar, then
cooled to –48 С (acetone—dry ice bath), and NIS (90.9 mg,
0.404 mmol, dried in vacuo for 40 min) followed by AgOTf
(10.4 mg, 0.0404 mmol) were added under Ar. After appearance
of iodine color the temperature of the reaction mixture was mainꢀ
(8 mL) under Ar, and freshly activated molecular sieves 4 Å
(760 mg) were added under Ar. The resulting mixture was stirred
for 1 h at ~20 C under Ar. The reaction mixture was cooled to
–25 С, NIS (140 mg, 0.622 mmol, dried in vacuo for 1 h) was
added, the reaction mixture was stirred for ~5 min, cooled to
–60 С, and AgOTf (17.3 mg, 0.067 mmol) was added. The
reaction mixture was allowed to warm up slowly for 0.5 hour.
After the appearance of iodine color (at –56 С) the temperaꢀ
ture of the reaction mixture was maintained constant (–56 С)
for 1 h, then the temperature it was allowed to increase to –35 С
within 1.5 h, and 10 mL of solution prepated from
Na2S2O3•5H2O (5 g) and saturated aqueous NaHCO3 (100 mL)
was added the reaction mixture was diluted with CH2Cl2 (~50
mL), filtered through Celite, the filter was washed with CH2Cl2
(5×10 mL) and with aqueous solution of NaHCO3—Na2S2O3
(5×10 mL), the filtrate was washed with the NaHCO3—Na2S2O3
solution, the aqueous phase was additionally extracted with
CH2Cl2 (3×15 mL). Combined extracts (~150 mL) were filtered
through a cotton wool plug, concentrated, and the residue was
dried in vacuo. Chromatography on BioBeads S×1 gel in toluene
gave a fraction of isomeric hexasaccharides 14 (359.7 mg,
97%). The isomers of compound 14 could not be separated by
chromatography. Rf 0.44 (toluene—EtOAc, 25 : 1). 1H NMR
(600 MHz, CDCl3), : 0.94—0.97 (m, 18 H, But, Pri); 0.99—1.08
(m, 60 H, But, Pri); 3.54—3.61 (m, 2 H); 3.54—3.61 (m, 2 H);
3.68 (td, 2 H, J = 5.8 Hz, J = 1.6 Hz); 3.76—3.87 (m, 5 H);
3.93—3.98 (m, 2 H); 4.03—4.19 (m, 9 H); 4.03—4.19 (m, 1 H);
4.34—4.38 (m, 3 H); 4.42—4.56 (m, 10 H); 5.03 (d, 1 H, J = 9.1 Hz);
5.04—5.06 (m, 1 H); 5.22 (s, 1 H); 5.24 (s, 1 H); 5.29 (s, 1 H);
5.33 (d, 1 H, J = 1.8 Hz); 5.46—5.48 (m, 2 H); 5.49—5.51 (m, 1 H);
5.52 (dd, 2 H, J = 4.7 Hz, J = 1.7 Hz); 7.87 (dd, 2 H, Ph, J = 8.2 Hz,
J = 1.1 Hz); 7.92—7.98 (m, 7 H, Ph); 8.00 (dd, 2 H, Ph, J = 8.2 Hz,
J = 1.1 Hz); 8.02—8.07 (m, 5 H, Ph). 13C NMR (151 MHz,
CDCl3) (the signals of the target ꢀisomer are given), : 12.0,
17.69, 17.71, 17.75, 17.79 (Pri); 20.0, 22.5 ((CH3)3CSi); 27.1,
27.4 ((CH3)3CSi); 42.7 (CH2CH2Cl); 64.3, 64.5 (C(5)III, C(5)IV),
66.1, 66.3 (C(5)I, C(5)II); 67.5 (CH2CH2CCl); 68.27, 68.31
(C(5)V, C(5)VI); 73.7, 73.8 (C(4)V, C(4)VI); 76.2 (2 C, C(2)V,
C(2)VI); 77.2 (C(3)II); 78.1, 78.3 (C(3)III, C(3)IV); 78.7, 78.9
(C(3)V, C(3)VI); 80.52, 80.53 (C(4)III, C(4)IV); 80.6, 81.80, 81.83,
81.9 (C(2)I, C(3)I, C(4)I, C(4)II); 83.3 (C(2)II); 86.2, 86.4
(C(2)III, C(2)IV); 101.3, 101.5 (C(1)V, C(1)VI); 105.7, 105.8, 106.0
(C(1)I, C(1)II, C(1)III); 107.4 (C(1)IV); 128.2, 128.25, 128.29,
128.37, 128.40, 128.5, 129.1, 129.2, 129.3, 129.5, 129.6, 129.7,
129.85, 129.89, 132.8, 133.1, 133.2, 133.4, 133.5 (Ph); 165.21,
165.38, 165.46, 165.55 (2 C), 165.89, 166.04 (CO).
–
–
tained at 46— 48 С for 1 h, then the temperatue was allowed
to increase gradually within 1 h to –30 С, and NEt3 (70 L) was
added. The reaction mixture was filtered through Celite (the
filter was thoroughly washed with CH2Cl2, 5×10 mL), washed
with a solution prepared from crystalline Na2S2O3•5H2O (~2 g)
and saturated aqueous NaHCO3 (100 mL). Aqueous phase was
extracted with CH2Cl2 (3×20 mL). Combined extracts (~100 mL)
were filtered through a cotton wool plug, concentrated, and the
residue was dried in vacuo. Chromatography on BioBeads S×1 gel
in toluene gave a fraction of isomeric hexasaccharides 13 (226.5 mg,
93%). The content of the target ꢀisomer according to HPLC
analysis (petroleum ether—EtOAc, 88 : 12 was used as an eluent)
was 64%. Preparative HPLC (eluent petroleum ether—EtOAc,
85 : 15) gave ꢀisomer 13 (103.2 mg, 42%). Rf 0.28 (toluene—
EtOAc, 10 : 1).  26 +23.6 (c 0.94, CHCl3). MS, m/z: 2155.8001
D
[M + NH4]. Calculated for C113H130F3N2O33Si2: 2155.8041.
1H NMR (600.13 MHz, CDCl3), : 0.99 (s, 18 H, But), 1.05 (s, 9 H,
But), 1.06 (s, 9 H, But), 3.54—3.63 (m, 4 H, OCH2CH2NHꢀ
COCF3, H(5)); 3.65—3.70 (m, 1 H, H(5)); 3.80—3.93 (m, 7 H,
H(2)V, H(2)VI, H(4)V, H(4)VI, H(5)); 4.07 (dd, 1 H, H(5),
J = 11.5 Hz, J = 5.2 Hz); 4.09—4.17 (m, 3 H, H(5)); 4.31 (s, 1 H,
H(2)IV); 4.33—4.39 (m, 3 H); 4.40—4.45 (m, 2 H); 4.46—4.57
(m, 7 H); 4.70 (d, 1 H, PhCH2, J = 12.0 Hz); 4.74—4.79 (d, 3 H,
PhCH2); 5.09 (d, 1 H, H(1)VI, J = 5.1 Hz); 5.11 (d, 1 H, H(1)V,
J = 5.1 Hz); 5.17 (s, 1 H, H(1)I); 5.28 (s, 1 H); 5.29 (s, 1 H,
H(1)II, H(1)IV); 5.40 (s, 1 H, H(2)II); 5.43 (br.s, 1 H, H(2)I);
5.49—5.54 (m, 3 H, H(1)III, H(3)III, H(3)IV); 5.59—5.62 (m, 1 H,
H(3)I); 7.20—7.25 (m, 2 H, Ph); 7.26—7.53 (m, 3 H, Ph); 7.57
(t, 1 H, Ph, J = 7.5 Hz); 7.83 (d, 2 H, Ph, J = 7.8 Hz); 7.91—7.97
(m, 6 H, Ph); 7.99 (d, 2 H, Ph, J = 7.7 Hz); 8.02 (d, 2 H, Ph,
J = 7.8 Hz); 8.06 (d, 2 H, Ph, J = 7.8 Hz). 13C NMR
(150.9 MHz, CDCl3); : 20.1, 22.6 ((CH3)3CSi), 27.2, 27.2,
27.5 ((CH3)3CSi), 39.7 (OCH2CH2NHCOCF3), 64.2, 64.4,
65.8, 66.0, 68.1, 68.2 (C(5)I, C(5)II, C(5)III, C(5)IV, C(5)V,
C(5)VI, OCH2CH2NHCOCF3), 71.86, 71.92 (CH2Ph), 73.9,
74.0 (C(3)VI, C(3)VI), 76.7 (C(3)I), 78.1, 78.2, 78.3 (C(3)III
,
C(3)IV, C(2)V, C(2)VI); 80.5, 80.68, 80.74, 80.8, 81.7, 82.0, 82.5,
83.3 (C(2)I, C(2)II, C(2)III, C(2)IV, C(3)I, C(3)II, C(3)IV, C(4)I,
C(4)II, C(4)III, C(4)IV), 86.2, 86.3 (C(4)VI, C(4)V), 100.4, 100.5
2ꢀAzidoethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
[2ꢀOꢀ(2ꢀOꢀbenzylꢀꢀDꢀarabinofuranosyl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀ
arabinofuranosyl]ꢀꢀDꢀarabinofuranosyl}ꢀꢀDꢀarabinofuranoside
(15). Starting hexasaccharide 12 (24.4 mg, 0.0118 mmol) was
dissolved in THF (3.0 mL), then АсОН (11 L, 0.19 mmol) and
Bu4NF (75 L of 1 М solution in THF, 0.075 mmol) were added.
The reaction mixture (pH 7—8) was stirred for 26 h at ~20 C,
concentrated, and the resudue was dissolved in CH2Cl2
(~50 mL), washed with water (~50 mL), the combined organic
phase was filtered through a cotton wool plug, concentrated and
dried in vacuo. Compound 15 was obtained by chromatoꢀ
graphy on silica gel (PrepSepSi cartridge, elution with toluꢀ
enetoluene—EtOAc, 1 : 2) as a colorless solid film (16.5 mg,
(C(1)V, C(1)VI), 105.9, 106.1, 106.2, 107.1 (Cꢀ(1)I, Cꢀ(1)II, Cꢀ(1)III
,
Cꢀ(1)IV), 127.7, 127.8, 128.00, 128.04, 128.31, 128.35, 128.38,
128.41, 128.5, 128.6, 128.9, 129.0, 129.1, 129.2, 129.4, 129.66,
129.71, 129.78, 129.79, 129.92, 132.94, 132.9, 133.2, 133.3,
133.4, 133.6, 133.7, 137.8, 137.9 (Ph), 165.44, 165.49, 165.54,
165.6, 165.8, 166.0, 166.1 (CO). 19F NMR (188 MHz, CDCl3),
: –75.5 (COCF3).
2ꢀChloroethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
[2ꢀOꢀ(2ꢀOꢀtriisopropylsilylꢀ3,5ꢀOꢀdiꢀtertꢀbutylsilyleneꢀꢀDꢀaraꢀ
binofuranosyl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀaraꢀ
binofuranosyl}ꢀꢀDꢀarabinofuranoside (14) (mixture of isomers).
Glycosyl donor 10 (335.3 mg, 0.622 mmol) and glycosyl accepꢀ
tor 3 (225.0 mg, 0.168 mmol) were coꢀconcentrated with anhydrous
toluene (3×5 mL), dried in vacuo, dissolved in anhydrous CH2Cl2
24
78%). Rf 0.33 (toluene—EtOAc, 2 : 1). []D +15.9 (c 0.416,
CH2Cl2). MS, m/z: 1810.5650 [M + Na]. Calculated for

Benzylꢀfree approach to arabinans
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1159
C95H93N3NaO32: 1810.5634. 1H NMR (600.13 MHz, CD3OD),
: 2.67—2.74 (m, 2 H, OH); 3.30—3.32 (m, 2 H, OH); 3.35—3.43
(m, 2 H, OCH2CH2N3); 3.61—3.69 (m, 4 H, H(5a)V, H(5a,b);
OCH2CH2N3); 3.71 (dd, 1 H, H(5b)V, J = 12.0 Hz, J = 3.5 Hz);
3.73—3.79 (m, 2 H, H(4)V, H(4)VI); 3.82 (dd, 1 H, H(5a)II,
J = 11.6 Hz, J = 1.9 Hz); 3.85—3.91 (m, 4 H, H(2)V, H(2)VI, H(5a)I,
OCH2CH2N3); 4.03—4.11 (m, 2 H, H(5b)I, H(5b)II); 4.21—4.27
(m, 2 H, H(3)V, H(3)VI); 4.33 (br.s, 1 H, H(2)III); 4.41—4.64
C(3)II, C(3)III, C(3)IV, C(3)V, C(3)IV, C(4)I, C(4)II, C(4)III
,
C(4)IV, C(4)V, C(4)IV); 100.22, 100.23 (C(1)V, C(1)VI), 105.65,
105.78, 105.87, 106.48 (C(1)I, C(1)II, C(1)III, C(1)IV); 127.78,
127.87, 128.05, 128.14, 128.20, 128.24, 128.36, 128.42, 128.50,
129.00, 129.03, 129.07, 129.13, 129.19, 129.32, 129.33, 129.56,
129.62, 129.66, 129.69, 129.76, 129.84, 132.61, 132.65, 132.80,
132.83, 133.06, 133.31, 133.35, 133.47, 137.27, 137.39 (Ph);
165.32, 165.39, 165.50, 165.56, 165.61, 165.62, 165.85, 165.87,
165.96, 166.07 (CO).
(m, 14 H, H(2)IV, H(3)III, H(3)IV, H(4)III, H(4)IV, H(5a,b)III
,
H(5a,b)IV); 4.99 (d, 1 H, H(1)VI, J = 4.4 Hz); 5.02 (d, 1 H,
H(1)V, J = 4.4 Hz); 5.15 (s, 1 H, H(1)III); 5.16 (s, 1 H, H(1)I);
5.32—5.34 (m, 2 H, H(1)II, H(3)III); 5.36—5.39 (m, 2 H, H(2)II,
H(3)IV); 5.41 (s, 1 H, H(2)I); 5.47 (s, 1 H, H(1)IV); 5.53 (d, 1 H,
H(3)I, J = 5.1 Hz); 7.08—7.30 (m, 18 H, Ph); 7.30—7.41 (m, 10 H,
Ph); 7.74 (d, 1 H, Ph, J = 7.3 Hz); 7.81—7.83 (m, 2 H, Ph);
7.85—7.90 (m, 4 H, Ph); 7.93—8.00 (m, 6 H, Ph). 13C NMR
(150.9 MHz, CD3OD), : 50.2 (OCH2CH2N3); 62.6, 62.7
(C(5)V, C(5)VI); 63.7 (C(5)III); 64.0 (C(5)IV); 65.1, 65.2 (C(5)I,
C(5)II); 66.0 (OCH2CH2N3); 72.0, 72.3 (PhCH2); 72.6 (C(3)V,
C(3)VI); 76.7 (C(3)I); 78.4, 78.5 (C(3)III, C(3)IV); 80.0 (C(4)III);
80.1 (C(4)IV); 80.4 (C(3)II); 81.58, 81.62 (C(2)I, C(4)I, C(4)II);
82.15, 82.19 (C(4)V, C(4)VI); 82.7 (C(2)II), 83.5 (C(2)VI); 83.7
(C(2)V); 84.0 (C(2)IV); 84.2 (C(2)III); 99.3 (C(1)VI); 99.5 (C(1)V);
105.3 (C(1)I, C(1)II, C(1)IV); 106.3 (C(1)III); 127.3, 127.6,
127.84, 127.89, 127.9, 128.0, 128.2, 128.3, 128.47, 128.51,
128.55, 128.57, 128.9, 129.0, 129.11, 129.18, 129.23, 129.25,
129.29, 129.4, 132.66, 132.69, 132.99, 133.02, 133.10, 133.16,
133.23, 137.2 (Ph), 165.16, 165.20, 165.5, 165.88, 165.89, 166.0,
166.2 (CO).
2ꢀ(Trifluoroacetamido)ethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoꢀ
ylꢀ3,5ꢀdiꢀOꢀ[2ꢀOꢀ(2ꢀOꢀbenzylꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinoꢀ
furanosyl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀarabinoꢀ
furanosyl}ꢀꢀDꢀarabinofuranoside (18). To the stirred and cooled
(ice—water bath) solution of azide 16 (34.0 mg, 0.0154 mmol) in
THF (1.0 mL), PPh3 (8 mg, 0.305 mmol) was added. The reacꢀ
tion mixture was stirred at 0 С for 1 h, then H2O (10 L) was
added and the mixture was kept for 16 h at ~20 С. The reaction
mixture was diluted with toluene (2 mL), concentrated, the residue
was coꢀconcentrated with toluene (2×2 mL) and dried in vacuo.
The resulting mixture (which contained amine 17, triphenylphosꢀ
phine and triphenylphosphine oxide) was dissolved in anhydrous
pyridine (2 mL), and (CF3CO)2O (100 L, 0.70 mmol) was added
to the solution while stirring and cooling (ice—water bath).
The reaction mixture was stirred for 16 h at ~20 C and
kept for 12 h at ~20 С, then cooled (ice—water bath) and NEt3
(50 L, 0.358 mmol) was added to the solution while stirring,
the reaction mixture was stirred for 3 h at ~20 C, and then
saturated aqueous solution of NaHCO3 (~2 mL) was added.
The reaction mixture was diluted with CHCl3 (~50 mL), washed
with water (~50 mL), 1 М aqueous solution of KHSO4
(~50 mL), saturated aqueous solution of NaHCO3 (~50 mL),
filtered through a cotton wool plug, concentrated, and dried
in vacuo. The residue was subjected to chromatography on Bioꢀ
Beads S×3 in toluene to give compound 18 (26.0 mg, 74%).
2ꢀAzidoethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
[2ꢀOꢀ(2ꢀOꢀbenzylꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl)ꢀ3,5ꢀ
diꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀarabinofuranosyl}ꢀꢀDꢀ
arabinofuranoside (16). Starting compound 15 (67.7 mg,
0.0368 mmol) was dissolved in anhydrous pyridine (2 mL), cooled
in the ice—water bath, BzCl (200 L, 1.72 mmol) was added and
the reaction mixture was stirred for 1 h, then МеОН was added
(2 mL) and the reaction mixture was strirred for another 30 min.
The reaction mixture was diluted with CH2Cl2 (~50 mL), washed
with 1 М aqueous solution of KHSO4 (~50 mL), water (~50 mL),
saturated aqueuos solution of NaHCO3, organic phase was concenꢀ
trated, and the residue was dried in vacuo. Compound 16 (81.3 mg,
97%) was obtained by chromatography on silica gel (gradient
toluenetoluene—AcOEt, 10 : 1), Rf 0.44 (toluene—EtOAc, 4 : 1).
Rf 0.33 (toluene—EtOAc, 4 : 1). MS, m/z: 2297.6620 [M + NH4].
22
Calculated for C125H114F3N2O37C: 2297.6635. 
–10.4
D
(c 1.72, CHCl3). 1H NMR (600.13 MHz, CDCl3), : 3.54—3.63
(m, 2 H, OCH2CH2NHCOCF3); 3.64—3.70 (m, 1 H, OCH2ꢀ
CH2NHCOCF3); 3.83—3.90 (m, 2 H, H(5), OCH2CH2NHꢀ
COCF3); 3.92 (dd, 1 H, H(5), J = 11.5 Hz, J = 3.1 Hz); 4.05—4.13
(m, 2 H, H(5)); 4.29—4.35 (m, 3 H); 4.40—4.45 (m, 2 H); 4.46—4.49
(m, 1 H); 4.50—4.68 (m, 12 H); 4.71—4.78 (m, 3 H); 5.04 (s, 1 H,
H(1)I); 5.17 (s, 1 H, H(1)IV); 5.28 (s, 1 H, H(1)II); 5.32 (d, 1 H,
J = 4.4 Hz); 5.34—5.37 (m, 2 H, H(1)V, H(1)VI, H(2)); 5.43—5.45
(m, 2 H, H(3)); 5.52—5.57 (m, 3 H, H(1)III, H(3)); 5.59 (dd, 1 H,
H(3)I, J = 5.5 Hz, J = 2.1 Hz); 5.66—5.69 (m, 1 H); 5.69—5.72
(m, 1 H, H(3)V, H(3)VI); 7.18—7.36 (m, 22 H, Ph); 7.38—7.53
(m, 15 H, Ph); 7.55—7.58 (m, 1 H, Ph); 7.60—7.65 (m, 2 H, Ph);
7.85—7.94 (m, 8 H, Ph); 7.97—8.07 (m, 10 H, Ph). 13C NMR
(150.9 MHz, CDCl3), : 39.64 (OCH2CH2NHCOCF3); 64.10,
25
[]D –11.9 (c 2.0, CHCl3). MS, m/z: 2226.6691 [M + Na].
Calculated for C123H109N3O36: 2226.6683. 1H NMR (600.13 MHz,
CDCl3), : 3.39—3.47 (m, 2 H, OCH2CH2N3), 3.65—3.70 (m, 1 H,
OCH2CH2N3), 3.90—3.96 (m, 2 H, H(5); OCH2CH2N3); 3.99
(dd, 1 H, H(5), J = 11.4 Hz, J = 2.9 Hz); 4.31—4.37 (m, 4 H);
4.46—4.52 (m, 3 H); 4.53—4.71 (m, 12 H); 4.75—4.80 (m, 3 H);
5.24 (s, 1 H, H(1)I); 5.31 (s, 1 H, H(1); H(1)IV); 5.36 (d, 1 H,
J = 4.4 Hz); 5.37 (d, 1 H, H(1)V, H(1)VI, J = 4.4 Hz); 5.43 (s, 1 H,
H(1)II); 5.48 (s, 1 H, H(2)); 5.52 (s, 1 H, H(2)); 5.54—5.61 (m, 4 H,
H(2), H(3)); 5.67—5.71 (m, 1 H); 5.71—5.75 (m, 1 H) (H(3)V,
H(3)VI); 7.20—7.53 (m, 40 H, Ph); 7.56 (t, 1 H, Ph, J = 7.4);
7.60—7.65 (m, 2 H, Ph); 7.87—7.95 (m, 10 H, Ph); 7.99—8.10
(m, 11 H, Ph). 13C NMR (150.9 MHz, CDCl3), : 50.60
(OCH2CH2N3); 64.07, 64.28, 65.80, 65.92, 65.99, 66.07, 66.37
(C(5)I, C(5)II, C(5)III, C(5)IV, C(5)V, C(5)IV, OCH2CH2N3);
72.29, 72.48 (PhCH2); 77.21, 77.40, 78.19, 78.32, 79.30, 79.43,
80.86, 80.92, 81.25, 81.43, 81.65, 81.90, 81.98, 82.11, 83.52,
84.95, 85.05 (C(2)I, C(2)II, C(2)III, C(2)IV, C(2)V, C(2)IV, C(3)I,
64.30, 65.80, 65.99 (3 C); 66.08 (C(5)I, C(5)II, C(5)III, C(5)IV
,
C(5)V, C(5)IV, OCH2CH2NHCOCF3); 72.36, 72.52 (PhCH2);
76.84, 77.39, 78.24, 78.34, 79.33, 79.48, 80.91, 80.98, 81.49,
81.68, 81.86, 83.50, 84.92, 85.14 (C(2)I, C(2)II, C(2)III, C(2)IV
,
C(2)V, C(2)IV, C(3)I, C(3)II, C(3)III, C(3)IV, C(3)V, C(3)IV, C(4)I,
C(4)II, C(4)III, C(4)IV, C(4)V, C(4)IV), 100.23, 100.28 (C(1)V,
C(1)VI); 105.57, 106.03, 106.14, 106.45 (C(1)I, C(1)II, C(1)III
,
C(1)IV); 127.82, 127.91, 128.09, 128.19, 128.24, 128.28, 128.41,
128.45, 128.51, 128.58, 129.60, 129.66, 129.71, 129.72, 129.79,
132.67, 132.70, 132.85, 132.89, 133.05, 133.12, 133.36, 133.41,
133.58, 133.69, 137.30, 137.40 (Ph); 165.36, 165.44, 165.52,

1160
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
Podvalnyy et al.
165.59, 165.61, 165.67, 165.75, 165.91, 165.93, 166.01, 166.13
(CO). 19F NMR (188 MHz, CDCl3), : –75.5 (COCF3).
2ꢀ(Trifluoroacetamido)ethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenꢀ
zoylꢀ3,5ꢀdiꢀOꢀ[2ꢀOꢀ(2ꢀOꢀbenzylꢀꢀDꢀarabinofuranosyl)ꢀ3,5ꢀdiꢀOꢀ
benzoylꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀarabinofuranosyl}ꢀꢀDꢀaraꢀ
binofuranoside (21). Fully protected hexasaccharide 13 (125 mg,
0.0584 mmol) was dissolved in THF (3.0 mL), and Bun4NF (700 L
of 1 М solution in THF, 0.70 mmol) and АсОН (141 L,
2.47 mmol) were added. The reaction mixture (pH 7—8) was
stirred at 16 h at ~20 C, then concentrated, the residue was
dissolved in CH2Cl2 (75 mL), washed with water (100 mL),
aqueous phase was extracted with CH2Cl2 (3×25 mL), comꢀ
bined organic phase was filtered through a cotton wool plug,
concentrated, and the residue was dried in vacuo. Chromatoꢀ
graphy on silica gel (eluent benzene—acetone, 3 : 1) gave tetraol 21
2ꢀ(Trifluoroacetamido)ethyl 5ꢀOꢀ{3,5ꢀdiꢀOꢀ[2ꢀOꢀ(2ꢀOꢀbenzylꢀ
ꢀDꢀarabinofuranosyl)ꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀarabinofuranoꢀ
syl}ꢀꢀDꢀarabinofuranoside (19). ОꢀBenzoylated compound 18
(23.6 mg, 0.0104 mmol) was dissolved in anhydrous МеОН (1 mL),
and CH2Cl2 (0.5 mL) was added followed by МеОNa (20 L of
1 М solution in МеОН) and EtOCOCF3 (50 L), the mixture
was stirred for 16 h at ~20 C, then АсОН (115 L of 1% solution
in MeOH, 20 mol) was added until pH became neutral, and the
mixture was concentrated. The residue was subjected to chroꢀ
matography on Sephadex LHꢀ20 in methanol to give 19 (6.6 mg,
56%). []D +27.0 (c 2.0, MeOH). 1H NMR (600.13 MHz,
25
D2O), : 3.46—3.49 (m, 2 H, OCH2CH2NHCOCF3); 3.59—3.70
(m, 7 H); 3.71—3.83 (m, 8 H); 3.84—3.91 (m, 3 H); 3.93 (dd,
1 H, J = 6.0 Hz, J = 3.4 Hz); 3.95—3.99 (m, 1 H); 4.00—4.10
(m, 10 H); 4.10—4.15 (m, 2 H); 4.18 s, 1 H); 4.23—4.26 (m, 1 H);
4.74 (d, 1 H, PhCH2, J = 4.1 Hz); 4.76 (d, 1 H, PhCH2, J = 4.2 Hz);
4.84 (d, 1 H, H(1), J = 0.9 Hz); 4.93 (d, 1 H, H(1), J = 1.5 Hz);
4.96 (d, 1 H, H(1), J = 2.1 Hz); 4.99 (d, 1 H, J = 4.4 Hz); 5.00
(d, 1 H, H(1)V, H(1)VI, J = 4.3 Hz); 5.03 (s, 1 H, H(1));
7.40—7.48 (m, 10 H, PhCH2). 13C NMR (150.9 MHz, D2O); :
40.8 (OCH2CH2NHCOCF3); 61.9, 62.0, 64.2, 64.3, 66.8, 67.9,
67.9 (C(5)I, C(5)II, C(5)III, C(5)IV, C(5)V, C(5)IV, OCH2CH2ꢀ
NHCOCF3); 74.4, 74.4, 74.5, 74.6, 75.8, 75.9, 77.9, 80.4, 82.0,
82.8, 82.8, 82.9, 83.5, 83.6, 84.0, 84.1, 84.7, 84.9, 87.9, 88.3
(PhCH2, C(2)I, C(2)II, C(2)III, C(2)IV, C(2)V, C(2)IV, C(3)I,
as a colorless solid film (103 mg, 95%). Rf 0.27 (benzene—aceꢀ
24
tone, 3 : 1). 
+10.9 (c 1.0, CHCl3). MS, m/z: 1875.5989
D
[M + NH4]. Calculated for C97H94F3NNaO33: 1875.5998.
1H NMR (500.13 MHz, D2O), : 3.54—3.59 (m, 2 H,
OCH2CH2NHCOCF3), 3.61—3.66 (m, 1 H, OCH2CH2NHꢀ
COCF3); 3.67—3.74 (m, 2 H); 3.77—3.87 (m, 5 H); 3.87—3.93
(m, 2 H); 4.02 (dd, 1 H, J = 11.4 Hz, J = 5.3 Hz); 4.12 (dd, 1 H,
J = 11.7 Hz, J = 3.8 Hz); 4.35—4.56 (m, 11 H); 4.58—4.65 (m, 3 H,
PhCH2); 4.69 (d, 1 H, PhCH2, J = 11.6 Hz); 5.06 (d, 1 H,
H(1)VI, J = 4.5 Hz); 5.08—5.11 (m, 2 H, H(1)V, H(1)); 5.19
(s, 1 H, H(1)); 5.29 (s, 1 H, H(1)); 5.36—5.39 (m, 3 H, H(2),
H(3)); 5.43 (dd, 1 H, H(3), J = 4.3 Hz, J = 1.8 Hz); 5.52 (s, 1 H,
H(1)IV); 5.55 (dd, 1 H, H(3)I, J = 5.6 Hz, J = 2.1 Hz); 7.16—7.31
(m, 16 H, Ph); 7.32—7.37 (m, 5 H, Ph); 7.38—7.58 (m, 10 H,
Ph). 13C NMR (126 MHz, D2O), : 39.6 (OCH2CH2NHꢀ
COCF3), 62.5, 62.6, 64.0, 64.1, 65.5, 65.9, 66.0 (C(5)I, C(5)II,
C(5)III, C(5)IV, C(5)V, C(5)IV, OCH2CH2NHCOCF3); 72.4,
72.6, 72.7 (PhCH2, C(3)V, C(3)VI); 78.8, 78.9, 80.3, 80.4, 81.5,
C(3)II, C(3)III, C(3)IV, C(3)V, C(3)IV, C(4)I, C(4)II, C(4)III
,
C(4)IV, C(4)V, C(4)IV); 100.5, 100.7 (C(1)V, C(1)VI); 106.2,
106.8, 108.7, 108.9 (C(1)I, C(1)II, C(1)III, C(1)IV); 129.9, 130.0,
130.1, 130.1, 130.2, 138.1 (Ph). 19F NMR (188 MHz, D2O),
: –75.4 (COCF3).
81.7, 82.1, 82.4, 82.9, 83.9, 84.0, 84.1, 84.4 (C(2)I, C(2)II, C(2)III
,
2ꢀ(Trifluoroacetamido)ethyl 5ꢀOꢀ{3,5ꢀdiꢀOꢀ[2ꢀOꢀ(ꢀDꢀaraꢀ
binofuranosyl)ꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀarabinofuranosyl}ꢀꢀ
Dꢀarabinofuranoside (20). Benzyl ether 19 (6.6 mg, 5.84 mole)
was dissolved in methanol (1 mL), 10% Pd(OH)2 on carbon
(20 mg) was added, and the flask was filled with Н2 (by evacuatꢀ
ing of the reaction vessel while stirring followed by filling with
Н2; the procedure was repeated 3 times). The reaction mixture
was stirred for 16 h under Н2, filtered through Celite, washed
with МеОН (5×5 mL), the filtrate was concentrated under vacꢀ
uum of the water aspirator pump. The residue was subjected to
chromatography on Sephadex LHꢀ20 in MeoH to give 20
(4.0 mg, 72%). Rf 0.84 (EtOH—BuOH—Py—AcOH—H2O,
C(2)IV, C(2)V, C(2)IV, C(3)I, C(3)II, C(3)III, C(3)IV, C(4)I,
C(4)II, C(4)III, C(4)IV, C(4)V, C(4)IV), 99.3, 99.5 (C(1)V, C(1)VI),
105.5, 105.9, 106.1, 106.6 (C(1)I, C(1)II, C(1)III, C(1)IV), 127.9,
128.00, 128.05, 128.1, 128.2, 128.39, 128.42, 128.46, 128.50,
128.53, 128.58, 128.8, 129.0, 129.5, 129.7, 129.8, 133.0, 133.4,
133.5, 133.6, 133.7 (Ph); 165.4, 165.6, 165.7, 166.1, 166.16,
166.19, 166.25 (CO).
2ꢀ(Trifluoroacetamido)ethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{3,5ꢀdiꢀ
Oꢀ[2ꢀOꢀ(2ꢀOꢀbenzylꢀꢀDꢀarabinofuranosyl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀ
Dꢀarabinofuranosyl]ꢀꢀDꢀarabinofuranosyl}ꢀꢀDꢀarabinofuranoꢀ
side (22). Benzyl ether 21 (103 mg, 0.554 mmole) was dissolved
in methanol (5.5 mL), 10% Pd(OH)2 on carbon (200 mg) was
added, and the flask was filled with H2 (by evacuating of the
reaction vessel followed by filling with H2; the procedure was
repeated 3 times). The reaction mixture was stirred under Н2 for
3 h at 30 С, then another portion of Pd(OH)2 on carbon was
added (185 mg), the reaction mixture was stirred at 30 С for
another 16 h, the third portion of Pd(OH)2 on carbon (205 mg)
was added and the mixture was stirred for 3 h. The reaction
mixture was diluted with MeOH (10 mL), filtered through Celite,
washed thoroughly with МеОН (5×5 mL), the filtrate was conꢀ
centrated, and the residue was dissolved in the benzene—aceꢀ
tone (2 : 3) mixture (10 mL) and filtered through coarse silica
gel (70—230 m, Merck), the filter was washed thoroughly
with the same mixture of solvents (~50 mL), the filtrate was
concentrated, and the residue was dried in vacuo. The residue
was subjected to chromatography on Sephadex LHꢀ20 in methaꢀ
22
100 : 10 : 10 : 3 : 10). []D +40.7 (c 0.5, МеОН). MS, m/z:
967.3236 [M + NH4]. Calculated for C34H58F3N2O26: 967.3224.
1H NMR (600.13 MHz, CD3OD), : 3.49—3.52 (m, 2 H); 3.55—3.69
(m, 7 H); 3.71—3.73 (m, 1 H); 3.73—3.75 (m, 1 H); 3.76—3.85
(m, 6 H); 3.89—3.94 (m, 2 H); 3.94—4.02 (m, 5 H); 4.02—4.06
(m, 3 H); 4.12—4.16 (m, 3 H); 4.17—4.22 (m, 1 H); 4.90 (d, 1 H,
H(1); J = 1.2 Hz); 4.96 (s, 1 H, H(1)); 5.03—5.05 (m, 2 H,
H(1)); 5.09 (d, 1 H, H(1), J = 2.1 Hz); 5.17 (d, 1 H, J = 2.3 Hz)
(H(1)V, H(1)VI). 13C NMR (150.9 MHz, CDCl3), : 41.95
(OCH2CH2NHCOCF3), 63.45, 63.53, 65.41, 65.45, 67.62,
68.81, 68.93 (C(5)I, C(5)II, C(5)III, C(5)IV, C(5)V, C(5)IV
,
OCH2CH2NHCOCF3), 76.80, 76.87, 77.34, 77.51, 79.79, 79.83,
79.84, 82.66, 82.95, 83.46, 84.08, 84.33, 84.76, 84.97, 85.03,
85.34, 85.39, 85.60, 90.29 (C(2)I, C(2)II, C(2)III, C(2)IV, C(2)V,
C(2)IV, C(3)I, C(3)II, C(3)III, C(3)IV, C(3)V, C(3)IV, C(4)I,
C(4)II, C(4)III, C(4)IV, C(4)V, C(4)IV); 103.49, 103.58 (C(1)V,
C(1)VI); 108.13, 108.45, 110.62 (C(1)I, C(1)II, C(1)III, C(1)IV).
19F NMR (188 MHz, CD3OD), : –75.4 (COCF3).
nol to give 22 as a colorless solid film (37.1 mg, 40%). Rf 0.53
24
(benzene—acetone, 1 : 1). 
+20.3 (c 1.0, МеОН). MS,
D
m/z: 1695.5044 [M + NH4]. Calculated for C83H86F3N2O33
:

Benzylꢀfree approach to arabinans
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1161
1695.5059. The signals in the 1Н NMR spectrum are broadened.
1H NMR (300.13 MHz, CDCl3,), : 0.77—1.93 (m, 13 H);
1.97—2.40 (m, 4 H); 3.06—4.70 (m, 30 H); 4.83—5.51 (m, 8 H);
5.51—5.68 (m, 2 H); 7.05—7.65 (m, 21 H, Ph); 7.75—8.13
(m, 14 H, Ph). 13C NMR (75.47 MHz, CDCl3), : 39.6
(OCH2CH2NHCOCF3); 54.84, 61.77, 61.95, 62.07, 63.72,
2ꢀAzidoethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
[2ꢀOꢀ(ꢀDꢀarabinofuranosyl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinoꢀ
furanosyl]ꢀꢀDꢀarabinofuranosyl}ꢀꢀDꢀarabinofuranoside (24).
Hexasaccharide 23 (359.8 mg, 0.162 mmol) was dissolved in
THF (5.0 mL), АсОН (322 L, 5.47 mmol) and Bun4NF (201 L
of 1 М solution in THF, 0.201 mmol) were added. The reaction
mixture (pH 7—8) was stirred for 5 days at ~20 C. TLC analysis
showed that the reaction was not complete. Additional amounts
of AcOH (322 L, 5.47 mmol) and Bun4NF (201 L of 1 М
solution in THF, 0.201 mmol) were added to the reaction mixꢀ
ture, and it was kept for 8 h at 40 С. The reaction mixture was
concentrated, the residue was dissolved in CH2Cl2 (~50 mL),
washed with water (~50 mL), combined organic phase was filꢀ
tered through a cotton wool plug, concentrated, and the residue
was dried in vacuo. Chromatography of the residue on silica gel
(eluent aceton—benzene, 35 : 90) gave hexaol 24 (a mixture of
isomers) as a solid colorless film (231 mg, 86%). The mixture of
isomers 24 (179.4 mg) to HPLC (250×25 mm) on Silasorb 600
(7.5 m, «Chemapol») column (250×25 mm), eluent PriOH—
CHCl3—petroleum ether, 1 : 3 : 6), and pure ,ꢀisomer 24 was
isolated (106.4 mg, 59% with respect to the starting mixture 23,
64.00, 65.81, 65.91 (C(5)I, C(5)II, C(5)III, C(5)IV, C(5)V, C(5)IV
,
OCH2CH2NHCOCF3); 74.19, 77.20, 78.37, 79.49, 79.73, 81.45,
81.63, 81.69, 82.30, 82.43, 82.53, 83.40, 85.12, 85.27, 85.83,
86.50 (C(2)I, C(2)II, C(2)III, C(2)IV, C(2)V, C(2)IV, C(3)I, C(3)II,
C(3)III, C(3)IV, C(3)V, C(3)IV, C(4)I, C(4)II, C(4)III, C(4)IV
,
C(4)V, C(4)IV); 101.04, 101.38 (C(1)V, C(1)VI); 105.65, 106.07,
106.59 (C(1)I, C(1)II, C(1)III, C(1)IV); 128.18, 128.29, 128.39,
128.44, 128.54, 128.60, 128.72, 128.75, 128.84, 128.99, 129.32,
129.43, 129.63, 129.70, 129.80, 133.21, 133.61 (Ph); 165.69
(3 C); 166.20, 166.31 (3 C, CO). 19F NMR(188 MHz, CDCl3),
: –77.7 (COCF3).
2ꢀAzidoethyl 2,3ꢀdiꢀOꢀbenzoylꢀ5ꢀOꢀ{2ꢀOꢀbenzoylꢀ3,5ꢀdiꢀOꢀ
[2ꢀOꢀ(2ꢀOꢀtriisopropylsilylꢀ3,5ꢀOꢀdiꢀtertꢀbutylsilyleneꢀꢀDꢀaraꢀ
binofuranosyl)ꢀ3,5ꢀdiꢀOꢀbenzoylꢀꢀDꢀarabinofuranosyl]ꢀꢀDꢀaraꢀ
binofuranosyl}ꢀꢀDꢀarabinofuranoside (23) (mixture of isomers).
The mixture of isomers of hexasaccharide 14 with a chloroethyl
aglycon (354.7 mg, 0.162 mmol) was dissolved in anhydrous
DMF (3 mL), NaN3 (50.0 mg, 0.770 mmol) and 18ꢀcrownꢀ6
(25.0 mg, 0.094 mmol) were added. The mixture was stirred for
60 h at 70 С, coꢀconcentrated with toluene (10 mL + 2×5 mL),
the residue was dissolved in toluene (~100 mL), washed with
water (3×80 mL), combined aqueous phase (~250 mL) was exꢀ
tracted with toluene (3×50 mL), and combined organic phase
from the last three extractions was washed with water (2×50 mL).
Combined organic phase (~250 mL) was filtered through a cotꢀ
ton wool plug, concentrated and the residue was dried in vacuo.
Glycoside 23 was obtained as a solid transparent film (359.8 mg,
100%). Rf 0.48 (toluene—EtOAc, 25 : 1). MS, m/z: 2222.9413
[M + Na]. Calculated for C115H153N3NaO32Si4: 2222.9406.
1H NMR (600.13 MHz, CDCl3), : 0.94—0.98 (m, 18 H, But, Pri);
0.98—1.10 (m, 60 H, But, Pri); 3.37—3.48 (m, 2 H); 3.55—3.61
(m, 2 H); 3.64—3.69 (m, 1 H); 3.82 (dd, 1 H, J = 11.7 Hz,
J = 2.4 Hz); 3.85 (dd, 2 H, J = 10.6 Hz, J = 9.4 Hz); 3.91—4.00
(m, 3 H); 4.04—4.19 (m, 9 H); 4.37 (dd, 3 H, J = 10.1 Hz,
J = 2.0 Hz); 4.42—4.56 (m, 10 H); 5.01 (s, 1 H); 5.03 (d, 1 H,
J = 4.5 Hz); 5.05 (d, 1 H, J = 4.9 Hz); 5.21 (s, 1 H); 5.25 (s, 1 H);
5.31 (s, 1 H); 5.34 (d, 1 H, J = 1.9 Hz); 5.47 (s, 1 H); 5.49
(d, 1 H, J = 1.4 Hz); 5.50 (dd, 1 H, J = 4.4 Hz, J = 2.1 Hz); 5.52
(dd, 1 H, J = 4.5 Hz, J = 2.3 Hz); 5.54 (dd, 1 H, J = 5.2 Hz,
J = 1.1 Hz); 7.28—7.51 (m, 23 H, Ph); 7.52—7.57 (m, 2 H, Ph);
7.88 (dd, 2 H, Ph, J = 8.3 Hz, J = 1.1 Hz); 7.91—7.98 (m, 7 H,
Ph); 7.99—8.04 (m, 5 H, Ph); 8.07 (dd, 2 H, Ph, J = 8.2 Hz,
J = 1.1 Hz). 13C NMR (151 MHz, CDCl3); : 12.0, 17.68,
17.70, 17.75, 17.8 (Pri); 20.0, 22.5, ((CH3)3CSi); 27.1, 27.3,
49% with respect to tetrasacharide 3) was isolated. Rf 0.45 (toluꢀ
22
ene—acetone, 2 : 5). 
+11.4 (c 1, MeOH). MS, m/z:
D
1630.4682 [M
+ Na]. Calculated for C81H81N3NaO32:
1630.4695. 1H NMR (600 MHz, CDCl3), : 1.20—1.22 (m, 2 H,
OH); 1.99 (br.c, 1 H, OH); 2.92 (d, 1 H, OH, J = 8.6 Hz);
3.13—3.26 (m, 3 H); 3.34 (br.s, 1 H); 3.38—3.47 (m, 3 H);
3.63—3.70 (m, 3 H); 3.73—3.82 (m, 5 H); 3.84 (dd, 1 H, J = 11.6 Hz,
J = 2.5 Hz); 3.90—3.96 (dd, 2 H); 3.99—4.06 (m, 3 H); 4.11 (dd,
2 H, J = 15.7 Hz, J = 11.6 Hz, J = 4.2 Hz); 4.20 (dt, 2 H,
J = 15.2 Hz, J = 7.7 Hz); 4.29 (dd, 1 H, J = 6.2 Hz, J = 1.3 Hz);
4.39 (d, 1 H, J = 1.7 Hz); 4.40—4.52 (m, 6 H); 4.52—4.60
(m, 4 H); 4.99 (d, 1 H, J = 4.9 Hz); 5.04 (d, 1 H, J = 4.9 Hz);
5.21 (s, 1 H); 5.24 (s, 1 H); 5.34—5.37 (m, 4 H); 5.42 (dd, 1 H,
J = 5.2 Hz, J = 2.9 Hz); 5.45 (d, 1 H, J = 1.1 Hz); 5.58 (d, 1 H,
J = 5.0 Hz); 7.24—7.30 (m, 5 H, Ph); 7.31—7.36 (m, 7 H, Ph);
7.37—7.52 (m, 10 H, Ph); 7.52—7.58 (m, 2 H, Ph); 7.84 (dd, 4 H,
Ph, J = 9.6 Hz, J = 8.2 Hz); 7.89—7.93 (m, 4 H, Ph); 7.98 (dd,
2 H, Ph, J = 8.2 Hz, J = 1.0 Hz); 8.00—8.04 (m, 4 H, Ph).
13C NMR (151 MHz, CDCl3); : 62.0, 62.1 (C(5)V, C(5)IV);
63.6, 63.9, 65.7 (2 C, C(5)I, C(5)II, C(5)III, C(5)IV); 66.5
(OCH2CH2N3); 74.40, 74.43, 77.1, 77.86, 77.91, 78.4, 78.6, 79.5,
79.8, 81.7, 82.0, 82.2, 82.5, 82.55, 82.63, 83.7, 85.2, 86.0 (C(2)I,
C(2)II, C(2)III, C(2)IV, C(2)V, C(2)IV, C(3)I, C(3)II, C(3)III
,
C(3)IV, C(3)V, C(3)IV, C(4)I, C(4)II, C(4)III, C(4)IV, C(4)V,
C(4)IV); 101.1, 101.4 (C(1)V, C(1)IV); 105.5, 105.8, 106.6, 106.8
(C(1)I, C(1)II, C(1)III, C(1)IV); 128.35, 128.37, 128.43, 128.5,
128.6, 129.7, 129.76, 129.79, 129.81, 129.9, 133.18, 133.21,
133.5, 133.58, 133.62, 133.7 (Ph).
27.4, 29.7 ((CH3)3CSi); 50.6 (CH2CH2N3); 64.3, 64.5 (C(5)III
,
This work was financially supported by the Russian
Foundation for Basic research (Projects No. 13ꢀ03ꢀ00666
and 14ꢀ03ꢀ31479) and by the Council on Grants at the
President of the Russian Federation (State Program for
Support of Leading Scientific Schools of the Russian Fedꢀ
eration and Young Scientists, Grant MKꢀ6405.2014.3).
C(5)IV); 65.9, 66.3 (C(5)I, C(5)II); 66.4 (CH2CH2N3);
68.26, 68.30 (C(5)V, C(5)VI); 73.7, 73.8 (C(4)V, C(4)VI); 76.2
(2 C, C(2)V, C(2)VI), 77.3 (C(3)II); 78.1, 78.3 (C(3)III, C(3)IV);
78.7, 78.9 (C(3)V, C(3)VI); 80.5, 80.6, 81.8, 81.9, 82.0,
83.3 (C(2)I, C(3)I, C(4)I, C(4)II, C(4)III, C(4)IV); 86.2 86.4
(C(2)III, C(2)IV); 101.3, 101.4 (C(1)V, C(1)VI); 105.81, 105.84,
106.0 (C(1)I, C(1)II, C(1)III); 107.4 (C(1)IV); 128.21, 128.24,
128.3, 128.4, 128.5, 128.6, 129.10, 129.14, 129.2, 129.3, 129.4,
129.6, 129.69, 129.71, 129.85, 129.88, 132.8, 133.1, 133.2,
133.36, 133.44 (Ph); 165.2, 165.4, 165.46, 165.53, 165.6, 165.9,
166.0 (CO).
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Received April 1, 2015;
in revised form April 13, 2015