The use of O-trifluoroacetyl protection and profound influence of the nature of glycosyl acceptor in benzyl-free arabinofuranosylation

Article abstract of DOI:10.1016/j.carres.2014.05.017

The influence of O-trifluoroacetyl (TFA) groups at different positions of thioglycoside glycosyl donors on stereoselectivity of α- arabinofuranosylation leading to corresponding disaccharides was studied. It was shown that TFA group in thioglycoside glycosyl donors, when combined with 2-O-(triisopropylsilyl) (TIPS) non-participating group, may be regarded as an electron-withdrawing protecting group that may enhance 1,2-cis-selectivity in arabinofuranosylation, the results strongly depending on the nature of glycosyl acceptor. The reactivities of the glycosyl donors were compared with those of a similar thioglycoside with O-pentafluoropropionyl groups and the known phenyl 3,5-O-(di-tert-butylsilylene)-1-thio-α-d-arabinofuranosides with 2-O-TIPS and 2-O-benzyl groups. The 'matching' in the donor-acceptor combination was found to be critical for achieving both high reactivity of glycosyl donor and β-stereoselectivity of arabinofuranosylation. The use of glycosyl donors with TFA and silyl protection may be useful in the realization of the benzyl-free approach to oligoarabinofuranosides with azido group in aglycon - convenient building blocks for the preparation of neoglycoconjugates.

Full text of DOI:10.1016/j.carres.2014.05.017

Accepted Manuscript
The use of O-trifluoroacetyl protection and profound influence of the nature of
glycosyl acceptor in benzyl-free arabinofuranosylation
Polina I. Abronina, Ksenia G. Fedina, Nikita M. Podvalnyy, Alexander I. Zinin,
Alexander O. Chizhov, Nikolay N. Kondakov, Vladimir I. Torgov, Leonid O.
Kononov
PII:
S0008-6215(14)00216-X
http://dx.doi.org/10.1016/j.carres.2014.05.017
CAR 6756
DOI:
Reference:
Carbohydrate Research
To appear in:
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Revised Date:
Accepted Date:
4 March 2014
30 April 2014
26 May 2014
Please cite this article as: Abronina, P.I., Fedina, K.G., Podvalnyy, N.M., Zinin, A.I., Chizhov, A.O., Kondakov,
N.N., Torgov, V.I., Kononov, L.O., The use of O-trifluoroacetyl protection and profound influence of the nature of
glycosyl acceptor in benzyl-free arabinofuranosylation, Carbohydrate Research (2014), doi: http://dx.doi.org/
10.1016/j.carres.2014.05.017
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The use of O-trifluoroacetyl protection and profound influence of the nature of glycosyl
acceptor in benzyl-free arabinofuranosylation
Polina I. Abroninaa, Ksenia G. Fedinaa,b, Nikita M. Podvalnyya, Alexander I. Zinina, Alexander O.
Chizhova, Nikolay N. Kondakova, Vladimir I. Torgova, Leonid O. Kononova*
aN. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky
prosp., 47, 119991 Moscow, Russian Federation.
bHigher Chemical College of the Russian Academy of Sciences, Miusskaya pl. 9, 125047
Moscow, Russian Federation.
Footnotes
================
* Corresponding author. Tel: +7-495-9432946; fax: +7-499-1355328. E-mail:
kononov@ioc.ac.ru, leonid.kononov@gmail.com.
================
Abstract
The influence of O-trifluoroacetyl (TFA) groups at different positions of thioglycoside
glycosyl donors on stereoselectivity of α-arabinofuranosylation leading to corresponding
disaccharides was studied. It was shown that TFA group in thioglycoside glycosyl donors, when
combined with 2-O-(triisopropylsilyl) (TIPS) non-participating group, may be regarded as an
electron-withdrawing protecting group that may enhance 1,2-cis-selectivity in
arabinofuranosylation, the results strongly depending on the nature of glycosyl acceptor. The
reactivities of the glycosyl donors were compared with those of a similar thioglycoside with O-
pentafluoropropionyl groups and the known phenyl 3,5-O-(di-tert-butylsilylene)-1-thio-α-D-
arabinofuranosides with 2-O-TIPS and 2-O-benzyl groups. The “matching” in the donor–
acceptor combination was found to be critical for achieving both high reactivity of glycosyl donor
and β-stereoselectivity of arabinofuranosylation. The use of glycosyl donors with TFA and silyl

protection may be useful in the realization of the benzyl-free approach to oligoarabinofuranosides
with azido group in aglycon – convenient building blocks for the preparation of
neoglycoconjugates.
Keywords: arabinofuranose; benzyl-free approach; 1,2-cis-stereoselectivity; O-trifluoroacetyl
group; electron-withdrawing protecting groups.
1. Introduction
There has been growing interest1–12 in the synthesis of D-arabinofuranose oligosaccharides
related to the mycobacterial cell wall components (arabinogalactan, lipoarabinomannan and
arabinomannan from Mycobacterium tuberculosis), over recent years due to the necessity of
creating means for diagnostics, prevention and treatment of human tuberculosis, which remains a
major worldwide health problem and takes millions of lives annually.13,14 Mycobacterial arabinan
→3)
→5)
-, (α1
→2)
- and (β1
chains are composed of arabinofuranose residues forming (α1
-
glycosidic linkages.11
The known direct and indirect methods for the synthesis of 1,2-cis-arabinofuranosides (β-
glycosides) rely on the use of O-benzyl protecting groups1–12,15–18 which are difficult to remove in
the presence of azido group in aglycon, which may be useful for the preparation of
neoglycoconjugates.19 Recently we used a novel per-O-silyl protected thioglycoside glycosyl
donor to create 1,2-cis-linkage and thus introduced20 a benzyl-free approach, which may be useful
in the preparation of oligoarabinofuranosides with azido group in aglycon. It is known that
benzyl protecting groups are difficult to remove in the presence of azide. The use of catalytic
hydrogenolysis for de-O-benzylation is not possible since the azido group is reduced faster than
any substantial cleavage of O-benzyl groups occurs.
In continuation of this work we decided to study the influence of O-trifluoroacetyl (TFA)
groups at different positions of thioglycoside glycosyl donors on stereoselectivity of
arabinofuranosylation. Glycosyl donors with O-pentafluoropropionyl (PFP)21–23 and O-benzyl
2

protecting groups were used for comparison. The choice of TFA groups was based on the
following considerations.
Strongly electron-withdrawing O-protecting groups are known to modulate
stereoselectivity of glycosylation.24–28 Mostly O-alkane(arene)sulfonyl groups were used for this
purpose.24,28 Methanesulfonyl and benzenesulfonyl groups at O-2 of glycosyl donors are known to
influence of stereoselectivity of β-mannosylation.26 Crich and co-workers also reported that
mannopyranosylation with donor bearing O-(trifluoromethyl)benzenesulfonyl group at the O-2
position was β-selective.27 At the same time, the use of the latter group at O-2 position of
arabinofuranosyl donor showed only moderate yield of the β-glycoside.29 Remote electron-
withdrawing groups at O-3, O-4 or O-6 of pyranosyl donors or at O-3 or O-5 of furanosyl donors
(as in the case of β-ribofuranosylation), which would decrease the reactivity of glycosyl donors,
also affect the outcome of glycosylation.24,25
In spite of numerous investigations of the influence of O-alkane(arene)sulfonyl groups on
stereoselectivity of glycosylation, the application of O-acyl electron-withdrawing protecting
groups for this purpose was scarce.21–23,30 Electron-withdrawing substituents in O-acyl groups
may considerably reduce basicity and nucleophilicity of their carbonyl moieties thus (1) making
them less prone to stabilize oxocarbenium ion by neighboring or remote participation and (2)
reducing their ability to act as hydrogen bond acceptors. The latter feature seems to be essential
for the stereochemical outcome of glycosylation since the formation of hydrogen-bonded mixed
supramers of glycosyl donor and glycosyl acceptor has recently been shown to be possible.31,32
O-Trifluoroacetyl (TFA) group has rarely been used as a protecting group for alcohols,
because it is generally considered to be too labile.33 Nevertheless, it is known that TFA and
homologous PFP esters can be used in stereoselective synthesis of oligosaccharides.21–23
However, there are few reports which describe remote participating effect of TFA-groups,
evaluated in comparison with less electron-withdrawing acyl groups.30 Here we report the results
of the use of TFA-protected glycosyl donors in arabinofuranosylation of O-2 of arabinofuranose,
3

which allowed the preparation of Araf-(β1→2)-Araf disaccharide with functionalized aglycon
with a azido group.
2. Results and discussion
Synthesis of a series of TFA-substituted arabinofuranosyl derivatives started from the
known thioglycoside 134 with 2-OH unprotected (Scheme 1). After introducing TIPS group
(1→2) and O-debenzoylation (2→3), diol 3 was obtained in 95% yield. Treatment of diol 3 with
trifluoroacetic anhydride in CH2Cl2 in the presence of catalytic amount of CF3CO2Na led to 3,5-
bis(trifluoroacetate) 4 in 98% yield. This procedure (see Experimental for details) in which the
excess of base (CF3CO2Na) is removed by filtration is more convenient than the standard reaction
conditions21 (trifluoroacetic anhydride in pyridine (Py)) since aqueous work-up is excluded. Our
efforts to adapt the latter procedure for the synthesis of TFA derivatives was unsuccessful. O-
Trifluoroacetylation with (CF3CO)2O in the presence of soluble bases (Py or Et3N) did not allow
isolation of TFA-substituted arabinofuranosyl donors 4, 7, 11, 13 in pure form apparently due to
hydrolysis of O-trifluoroacetyl groups during aqueous extractions. Chromatography on silica gel
was also unacceptable because of lability of O-trifluoroacetyl groups. High resolution
electrospray mass spectrum of 4 showed the expected ion at m/z 613.1436 (M+Na+). Besides, 19F
NMR spectrum of 4 showed two signals at δF −75.56 and −75.63 ppm of equal intensities
corresponding to the two CF3CO moieties.
Glycosyl donor 13 with 2-O-TFA group was synthesized by 2-O-trifluoroacetylation of
the known alcohol 1220 with 3,5-di-O-tert-butyl silylene (DTBS) protecting group under the same
conditions. 19F NMR spectrum of 13 showed one signal of CF3CO group at δF −74.57 ppm.
For the synthesis of monosubstituted derivatives 7 and 11 with TFA groups at remote
positions differentiation of O-3 and O-5 positions in diol 3 was required. 5-Hydroxy group of 3
was selectively benzoylated with subsequent 3-O-trifluoroacetylation of the remaining free
hydroxy group to give derivative 7 with TFA group at O-3. On the other hand, selective
4

tritylation of 3 with TrCl/Py (3→8), benzoylation (8→9), followed by detritylation by TFA–H2O–
CH2Cl2 (10:1:90) at 20 °C led to alcohol 10 in 53% yield over 3 steps. Its hydroxy group at C-5
was O-trifluoroacetylated as described above to give glycosyl donor 11 with TFA group at O-5 in
94% yield. 19F NMR spectra of 7 and 11 showed one signal of CF3CO group at δF −75.53 and δF
−75.59 ppm, respectively. Glycosyl donor 5 with PFP groups at O-3 and O-5 was obtained by the
treatment of diol 3 with (CF3CF2CO)2O/Py, essentially as described.21
Having the series of TFA-substituted arabinofuranosyl glycosyl donors 4, 7, 11 and 3,5-
bis-O-PFP-protected glycosyl donor 5 at hand, our attention was focused on synthesis of 2-O-
unprotected glycosyl acceptors. Aiming at the realization of benzyl-free approach, we intended to
use benzoyl and silyl groups for protection of non-reacting hydroxyl groups. Besides, we needed
to prepare (β1→2)-linked disaccharide of arabinofuranose because it is known that terminal
fragment of M. tuberculosis arabinans containing this disaccharide is essential for pathogenicity of
M. tuberculosis. Hence, (β1→2)-linked disaccharide of arabinofuranose may be useful for
biomedical purposes, in particular, for serodiagnosis of tuberculosis.11,35,36
Thus, previously synthesized bis-O-chloroacetate 1434 was converted into 4-(2-
chloroethoxy)phenyl (CEP) glycoside 15 in 74% yield by reaction with 4-(2-chloroethoxy)phenol
(CEP-OH)37 in the presence of catalytic amount of TfOH (Scheme 2). After removal of O-
chloroacetyl group by treatment with Py/H2O, alcohol 16 with benzoyl groups and CEP aglycon
was obtained. It should be noted that CEP group is a multipurpose aglycon with dual function
which can easily be removed by oxidation (like 4-methoxyphenyl group) as well as functionalized
after replacement of chlorine atom with azido group (like ω-chloroalkyl aglycons) to give 4-(2-
azidoethoxy)phenyl group, which may be used in click chemistry. On the other hand, the azide
may be directly converted into amine. These opportunities can further be used for the preparation
of a wide range of neoglycoconjugates.19
Acetolysis of the known methyl glycoside 2138 led to glycosyl acetate 17 obtained as an
anomeric mixture (Scheme 2). Reaction of 17 with CEP-OH in CH2Cl2 in the presence of a
5

catalytic amount of TfOH gave glycoside 18 with CEP aglycon as a single anomer in 86% yield.
After debenzoylation (MeONa, MeOH) (18→19) and silylation ((t-Bu)2Si(OTf)2, Py) glycosyl
acceptor 20 with free 2-OH and CEP aglycon was obtained. For investigation of influence of
aglycon in glycosyl acceptor on the outcome of glycosylation, 2-O-unprotected methyl glycoside
23 was synthesized by analogous silylation of the known methyl arabinofuranoside 22.39
It is well known that stereoselectivity of β-arabinofuranosylation is highly dependent upon
the reaction temperature.2,7,8 At low temperature the stereoselectivity of β-arabinofuranosylation
is usually the best, while at higher temperatures all possible stereoisomeric glycosides may be
produced in roughly equal amounts. In order to achieve a high β-stereoselectivity of
arabinofuranosylation, herein glycosylations were performed at lowest possible temperature.
Promoter (NIS, AgOTf) was added at low temperature (−78 °C) and then the temperature was
allowed to rise slowly until appearance of persistent iodine color. This temperature (T) was taken
as the temperature at which the activation of glycosyl donor occurs.
Glycosylation of 3,5-di-O-benzoyl protected CEP glycoside 16 with the arabinofuranosyl
donors 4, 7, 11, 13, 24,20 257,29 (1.5 equiv) was performed under standard conditions (NIS,
AgOTf, MS 4Å, CH2Cl2, −78 °C → T (for details see Experimental and Table 1) to afford
anomeric mixtures of corresponding (1→2)-linked disaccharides (Scheme 3 and Table 1). After
glycosylation, TFA groups were removed from the TFA-containing disaccharides obtained by
treatment with NEt3 in MeOH to give disaccharides 26–29. Anomeric ratios of disaccharides 26–
31 were determined from the 1H NMR spectroscopic data for the disaccharide fractions obtained
by gel-chromatography on Bio-Beads S×3 in toluene (Table 1). We found that TFA at O-2
position of thioglycoside 13 (entry 7, Table 1) resulted in 1,2-trans-stereoselectivity α:β = 3.3:1.
This result probably indicates some neighboring participation of the TFA group, a possibility of
which is usually considered unlikely.30 When TFA groups were in remote O-3 or O-5 positions of
glycosyl donors 7 and 11 with 2-O-TIPS non-participating group (entries 5 and 6, Table 1), equal
6

ratio of anomers was obtained (α:β ≈ 1:1). It is interesting to note that bis-TFA-protected
thioglycoside 4 gave in reaction with glycosyl acceptor 16 moderate β-stereoselectivity (α:β =
1:2, entry 1, Table 1) which, surprisingly, was identical to that obtained in glycosylation of
glycosyl acceptor 16 by the well-known 2-O-benzyl-protected glycosyl donor 257,29 with 3,5-O-
DTBS protection (α:β = 1:2, entry 10). In spite of moderate β-selectivity of glycosylation in the
case of TFA-substituted arabinofuranosyl donors 4, 7, 11, there is a direct dependence of the
results of arabinofuranosylation on the positions of TFA groups in glycosyl donors.
Most commonly, stereochemical outcome of glycosylation is supposed to be linked to
conformation of the saccharide residue.40,41 For instance, glycosyl donors containing a cyclic 3,5-
di-O-DTBS protecting group were successfully used to increase β-stereoselectivity in the
preparation of arabinofuranosides.7–9 The fused DTBS group makes the flexible furanose ring in a
thioglycoside donor more rigid and, presumably, locks the oxacarbenium ion generated during
glycosylation in a E3 conformation that favors an attack of a nucleophile from β-face, hence β-
selectivity. Thus, the use of per-silylated glycosyl donor 2420 with 3,5-di-O-DTBS protection
improved the yield of β-anomer (α:β = 1:4.5, entry 8, Table 1). However, the situation is
obviously more complex since the presence of 3,5-O-DTBS protection does not guarantee high
β-stereoselectivity (α:β = 1:2, entry 10).
Another possible explanation of the low anomeric selectivities in this series may be
“matched/mismatched effect” in the donor–acceptor combination.42,43 The importance of this
effect in arabinofuranosylation has been demonstrated by comparison of stereoselectivities
achieved with D- and L-configured glycosyl donors 25 and ent-25.7,29 Taking into account this
possibility, we conducted another series of arabinofuranosylation reactions using 3,5-O-DTBS-
protected glycosyl acceptors 20 and 23 with CEP and methyl aglycons, respectively (Scheme 4).
We found that β-selectivity of glycosylation of alcohol 20 with CEP aglycon (entries 2 and 3,
Table 1) with bis-TFA-protected thioglycoside 4 is higher (α:β = 1:5.6 – 1:6.3) than that in the
7

case of per-O-silylated glycosyl donor 24 (entry 9, Table 1, α:β = 1:3). Analysis of results
achieved in the reactions of glycosyl acceptor 23 bearing methyl aglycon (entries 3 and 4, Table 1)
with glycosyl donors 4 and 5 showed that there is no remarkable difference in stereoselectivity of
arabinofuranosylation in case of use of bis-TFA-protected thioglycoside 4 (entry 3, Table 1, α:β =
1:5.6) and bis-PFP-protected thioglycoside 5 (entry 4, Table 1, α:β = 1:5.5) as glycosyl donors. It
is striking that the stereoselectivities obtained in reactions of 4 and 5 with glycosyl acceptor 23
matched that obtained in the reaction of glycosyl donor 4 with glycosyl acceptor 20 (entry 2,
Table 1, α:β = 1:6.3). This means that the nature of aglycon in these reactions is not critical for
achieving high stereoselectivity while the protecting group pattern of glycosyl acceptor is very
important (see also a discussion below).
We may conclude that in the studied cases glycosyl donors with two electron-withdrawing
acyl groups (TFA or PFP) at O-3 and O-5 and non-participating group 2-O-TIPS group strongly
favor β-selective glycosylation. Although the influence of 2-O-TIPS protection on
stereoselectivity seems to be very important, no unambiguous conclusions concerning the effects
of 2-O-TIPS and O-TFA/PFP groups can be made at the moment. A study of influence of 2-O-
TIPS group on stereoselectivity might be an interesting direction of future research.
The temperature T at which the glycosylation with 2-O-TIPS-protected glycosyl donors
commences (characterized by appearance of iodine color) deserves a special discussion. Analysis
of the data of Table 1 reavealed that the reactions of O-benzoylated glycosyl acceptor 16 with
−
TFA-protected thioglycosides 4, 7 and 11 (entries 1, 5, 6, Table 1) started at 22 °C irrespective
of the number and position of O-TFA groups, while glycosylations of 3,5-O-DTBS-protected
glycosyl acceptors 20 and 23 with bis-TFA-protected thioglycoside 4 (entries 2, 3, Table 1)
started at −30 °C, apparently lower temperature favoring higher β-selectivities (up to α:β =
1:6.3) as one would expect basing on the known2,7,8 precedents. This lower temperature of
activation suggests higher reactivity of the same glycosyl donor 4, which is clearly modulated by
8

the nature of protecting groups in the molecule of glycosyl acceptor. This observation may look
trivial since lower reactivity was observed in reaction with aparently less nucleophilic glycosyl
acceptor 16 with electron-withdrawing O-benzoyl groups. However this seemingly “bad”
glycosyl acceptor 16 cleanly reacted with per-O-silylated glycosyl donor 24, which was activated
at even lower temperature (−39 °C, entry 8, Table 1), to give disaccharide 30 with lower but
comparable stereoselectivity (α:β = 1:4.5). The same glycosyl donor 24 was activated at
somewhat lower temperature (−42 °C, entry 9, Table 1) when reacted with “good” 3,5-O-DTBS-
protected glycosyl acceptor 20, but the stereoselectivity dropped even further (α:β = 1:3).
These data suggest that it is the “matching” in the donor–acceptor combination that is
critical for achieving both high reactivity of glycosyl donor (low temperature T of activation) and
β-stereoselectivity of arabinofuranosylation, and three types of donor–acceptor combination can
be revealed. (1) When molecules of both glycosyl donor and glycosyl acceptor contain O-acyl
groups (TFA, PFP, Bz) (entries 1, 5, 6, Table 1) the temperature T of activation is high and
steroselectivity is low. (2) When only molecules of glycosyl acceptor or glycosyl donor contain
O-acyl groups (entries 2, 3, 4, 8, Table 1) the temperature T of activation is lower and
steroselectivity is high. (3) When molecules of both glycosyl donor and glycosyl acceptor do not
contain any O-acyl groups (entries 9, 10, Table 1) the temperature T of activation is very low but
steroselectivity is low too. The origin of this “matching” may be related to formation of
differently arranged hetero-supramers31 comprising molecules of both glycosyl donor and glycosyl
acceptor. Indeed, acyl groups are the hydrogen-bond acceptor sites, and their presence and
position in the molecules of glycosyl donors/acceptors would influence the structure of hydrogen-
bonded supramers hence chemical properties.31
It is necessary to stress that all data shown in Table 1 correspond to disaccharide fractions
obtained by gel-chromatography as anomeric mixtures since separation of anomers was
impossible or very difficult at this stage (even with HPLC). Their anomeric composition was
9

1
determined by integration of the respective signals in the H NMR spectra. In two cases (see
below), in which the best (from the preparative point of view) glycosylation results were
achieved, the disaccharide anomers were separated by preparative HPLC after change in
protecting group pattern (the simultaneous presence of O-benzoyl and hydroxyl group(s) and the
absence of silyl groups was found to facilitate separation). This allowed a new realization of the
benzyl-free approach20 to oligoarabinofuranosides with azido group in aglycon.
Thus, glycosylation of alcohol 16 with per-O-silyl-protected glycosyl donor 24 provided
access to disaccharide 30 in 92% yield with good stereoselectivity (entry 8, Table 1, α:β = 1:4.5,
corresponds to 75% yield of β-isomer). Similarly, glycosylation of alcohol 20 with bis-TFA-
protected thioglycoside 4 gave disaccharide 32 in 84% yield and even better stereoselectivity
(entry 2, Table 1, α:β = 1:6.3, corresponds to 73% yield of β-isomer). Disaccharide 30 was
desilylated (TBAF) to give after HPLC purification partially protected disaccharide 36 in 59%
yield as the single β-anomer (Scheme 5). The structure of the β-isomer of disaccharide 36
followed from NMR data, which revealed the presence of α-arabinofuranose residue (δC 106.4
(C-1I); singlet at δH 5.89 (H-1I)) and β-arabinofuranose residue (δC 103.0 (C-1II); doublet at δH
5.26 (H-1II, J = 4.6 Hz)). Besides, the expected correlations in HMBC spectra: (C-2I/H-1II and C-
1II/H-2I) were clearly observed, which proved the presence of (β1→2)-linkage.
Chlorine in the 2-chloroethyl moiety of 36 was substituted with azide (NaN3, 18-crown-6,
DMF) to give disaccharide 37 with azido group in aglycon in 78% yield. The presence of azido
group in the aglycon followed from the position of the signal of terminal methylene group
CH2CH2N3 (δC 50.2) in the 13C NMR spectrum of 37. The positions of other characteristic signals
1
in H and 13C NMR spectra of glycoside 37, coupling constants and correlations in HSQC and
HMBC spectra corresponded well to those observed for the β-isomer of glycoside 36 (see
Experimental).
10

Triol 37 was debenzoylated (MeONa, MeOH) to give in 95% yield the target deprotected
disaccharide 38 with 4-(2-azidoethoxy)phenyl aglycon, the structure of which was fully confirmed
by 1D and 2D NMR spectra (see Experimental). In particular, HSQC spectrum showed the
presence of correlations, which corresponded to α-arabinofuranose residue (δC 106.8 (C-1I);
doublet at δH 5.57 (H-1I, J = 2.0 Hz)) and β-arabinofuranose residue (δC 102.8 (C-1II); doublet at
δH 5.03 (H-1II, J=4.3 Hz)). Additional confirmation of the structure of disaccharide 38 was
obtained from the presence of the following correlations in HMBC spectra: H-1II/C-2I and H-2I/C-
1II.
Disaccharide 32 was benzoylated (BzCl, Py) and then desilylated (TBAF) to give after
HPLC purification partially protected disaccharide 39 in 47% yield as the single β-anomer
(Scheme 5). The structure of disaccharide 39 followed from NMR data, which revealed the
presence of α-arabinofuranose residue (δC 104.7 (C-1I); doublet at δH 5.56 (H-1I, J = 2.1 Hz)) and
β-arabinofuranose residue (δC 102.0 (C-1II); doublet at δH 5.28 (H-1II, J = 4.6 Hz)). Chlorine in
the 2-chloroethyl moiety of 39 was substituted with azide (NaN3, 18-crown-6, DMF) to give
disaccharide 40 with azido group in aglycon. High resolution electrospray mass spectrum of 40
showed the expected ion at m/z 674.1953 [M + Na]+. Azide 40 was debenzoylated (MeONa,
MeOH) to give the target deprotected disaccharide 38 with 4-(2-azidoethoxy)phenyl aglycon in
90% yield (from 39 over two steps) identical to that obtained from 31 by a different route.
3. Conclusions
TFA and PFP groups in glycosyl donors are electron-withdrawing protecting groups which,
when used in combination with 2-O-TIPS protecting group, may enhance 1,2-cis-selectivity in
arabinofuranosylation. The reactivities of the corresponding glycosyl donors were compared with
that of the known glycosyl donor with 2-O-benzyl and 3,5-O-DTBS groups. The “matching” in
the donor–acceptor combination was found to be critical for achieving both high reactivity of
11

glycosyl donor (low temperature T of activation) and β-stereoselectivity of arabinofuranosylation.
The use of glycosyl donors with TFA and silyl protection may be useful in the realization of the
benzyl-free approach to oligoarabinofuranosides with azido group in aglycon – convenient
building blocks for the preparation of neoglycoconjugates.
4. Experimental
4.1 General methods
All reactions sensitive to air and/or moisture were carried out under argon atmosphere. The
reactions were performed with the use of commercial reagents (Aldrich, Fluka, Acros Organics)
Anhydrous solvents were purified and dried (where appropriate) according to standard
procedures. Sodium trifluoroacetate (NaOCOCF3) was additionally dried by heating at 80 °C for
1 h before use. Powdered molecular sieves 4Å (Fluka) were activated before the reactions by
heating at 220 °C in high vacuum (0.02 bar) for 6 h. Column chromatography was performed on
silica gel 60 (40–63 µm, Merck). Thin-layer chromatography was carried out on plates with silica
gel 60 on aluminum foil (Merck). Spots of compounds were visualized under UV light and by
heating the plates (at ca. 150 °C) after immersion in a 1:10 (v/v) mixture of 85% aqueous H3PO4
and 95% EtOH. 1H, 13C and 19F NMR spectra were recorded for solutions in Me2CO-d6, CDCl3,
or CD3OD on a Bruker AC-200 instrument (200.13, 50.32, and 188.27 MHz for 1H, 13C and 19F,
respectively ), a Bruker AM-300 instrument (300.13, 75.48, and 282.40 MHz for 1H , 13C and
19F, respectively) or on a Bruker AVANCE 600 spectrometer (600.13 and 150.9 MHz for 1H and
13C, respectively). The 1H NMR chemical shifts are referred to the residual signal of CHCl3 (δH
7.27, CHD2OD (δH 3.31), or CHD2COCD3 (δH 2.05), the 13C NMR shifts – to the central line of
CDCl3 signal (δC 77.0), CD3OD signal (δC 49.0) or (CD3)2CO signal (δC 29.9). Assignments of
the signals in the NMR spectra were performed using 2D-spectroscopy (COSY, HSQC, HMBC)
and DEPT-135 experiments. High resolution mass spectra (electrospray ionization, HRESIMS)
12

were recorded in positive mode on a Bruker micrOTOF II mass spectrometer for 2 × 10−5 M
solutions in MeCN or MeOH. Optical rotations were measured using a PU-07 automatic digital
polarimeter (Russia). Analytical HPLC separations were performed on an Ultrasorb Si (5 µm)
column (165×4.6 mm ID) at 1 mL/min flow rate. Preparative HPLC separations were performed
on a Sialsorb 600 (7.5 µm) column (250 × 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.
4.2. Phenyl 3,5-di-O-benzoyl-1-thio-2-O-triisopropylsilyl-α-D-arabinofuranoside (2)
To the solution of alcohol 134 (417 mg, 0.93 mmol) in DMF (12 mL) collidine (370 µL,
2.78 mmol) and i-Pr3SiОTf (400 µL, 1.48 mmol) were added. The reaction mixture was stirred
for 1 h at 90 °C. The reaction mixture was diluted with CHCl3 (50 mL), washed with H2O (50
mL), 1 M KHSO4 (50 mL), H2O (50 mL) and satd aq NaHCO3 (50 mL). The aqueous layer was
extracted with CHCl3 (10 mL). Combined organic extracts were filtered through a cotton wool
plug, concentrated under reduced pressure (bath temperature ~30 °C), dried in vacuo, and
purified by silica gel column chromatography (light petroleum–EtOAc, 6 : 1) to give silyl ether 2
as a white foam (550 mg, 98%, Rf = 0.73, light petroleum–EtOAc, 6 : 1). [α]D21 +105.8 (c 1.0,
CHCl3). HRESIMS: found m/z 629.2369 [M + Na]+. Calcd for C34H42O6SSiNa: 629.2364. 1H
NMR (300 MHz, CDCl3): δΗ 1.11 (br. s, 21 H, CH(CH3)2), 4.69–4.73 (m, 3 H, H-2, H-5a, H-
5b), 4.76 (dd, J = 5.5, 2.7 Hz, 1 H, H-4), 5.43 (br. s, 1 H, H-3), 5.63 (s, 1 H, H-1), 7.26–7.36 (m,
3 H, Ph), 7.39–7.67 (m, 8 H, Ph), 8.06–8.21 (m, 4 H, Ph). 13C NMR (75 MHz, CDCl3): δC 11.9,
12.2 (CH(CH3)2), 17.7, 17.80, 17.81 (CH(CH3)2), 64.3 (C-5), 80.8 (C-3), 81.8 (C-4), 82.0 (C-2),
94.8 (C-1), 127.4, 128.3, 128.5, 129.0, 129.3, 129.7, 129.9, 130.0, 131.8, 133.0, 133.4, 134.6
(Ph), 165.5, 166.1 (CO).
4.3. Phenyl 2-O-triisopropylsilyl-1-thio-α-D-arabinofuranoside (3)
13

To the solution of dibenzoate 2 (171 mg, 0.28 mmol) in MeOH (4 mL) 1 M MeONa in
MeOH (0.9 mL) was added and the mixture was stirred at ~20 °C for 48 h. The reaction was
neutralized with Dowex 50W×4 (H+) ion-exchange resin. The resin was filtered off and washed
with MeOH (15 mL). The filtrate was concentrated and the residue was dissolved in CH2Cl2 (30
mL) and washed with satd aq NaHCO3 (30 mL). The aqueous layer was extracted with CH2Cl2 (5
mL). Combained organic extracts were filtered through a cotton wool plug, concentrated under
reduced pressure (bath temperature ~30 °C), dried in vacuo, and purified by silica gel column
chromatography (light petroleum–EtOAc) to give diol 3 as a colorless oil (100 mg, 89%; Rf =
0.19, petroleum ether–EtOAc, 4:1). [α]D20 +107.3 (c 1.0, CHCl3). HRESIMS: found m/z
421.1841 [M + Na]+. Calcd for C20H34O4SSiNa: 421.1839. 1H NMR (300 MHz, CDCl3): δΗ 1.08
(br. s, 21 H, CH(CH3)2)) 3.82–3.87 (m, 2 H, H-5a, H-5b), 4.13 (d, J = 3.8 Hz, 1 H, H-3), 4.28–
4.33 (m, 1 H, H-4), 4.34 (s, 1 H, H-2), 5.46 (s, 1 H, H-1), 7.28-7.40 (m, 3 H, Ph), 7.52 (d, J =
6.1 Hz, 2 H, Ph). 13C NMR (75 MHz, CDCl3): δC 12.0 (CH(CH3)2), 17.8 (CH(CH3)2), 62.2 (C-
5), 79.2 (C-3), 83.6 (C-4), 85.9 (C-2), 93.4 (C-1), 127.7, 129.0, 132.2, 133.6 (Ph), 162.3 (CO).
4.4.
Phenyl
2-O-triisopropylsilyl-3,5-di-O-trifluoroacetyl-1-thio-α-D-
arabinofuranoside (4)
To the solution of diol 3 (20 mg, 0.052 mmol) in anhydrous CH2Cl2 (1 mL), (CF3CO)2O (1
mL) and then solid NaOCOCF3 (7 mg, 0.052 mmol) were added at 0 °C (ice-water bath). After 3
h at 20 °C the reaction mixture was concentrated under reduced pressure (bath temperature ~30
°C), the residue was dissolved in CCl4 (30 mL), filtered through a cotton wool plug, concentrated
under reduced pressure (bath temperature ~30 °C), dried in vacuo to give trifluoroacetate 4 as a
23
colorless oil (30 mg, 98%, Rf = 0.80, light petroleum–EtOAc, 4:1). [α]D +66.5 (c 1.0, CHCl3).
1
HRESIMS: found m/z 613.1436 [M + Na]+. Calcd. for C24H32F6NaO6SSi: 613.1485. H NMR
(300 MHz, CDCl3): δH 1.05 (s, 18 H, CH(CH3)2), 1.08 (s, 3 H, 3xCH(CH3)2), 4.56–4.68 (m, 4 H,
H-5a, H-5b, H-4, H-2), 5.13 (dd, J = 3.7, 1.8 Hz, 1 H, H-3), 5.48 (d, J = 1.7 Hz, 1 H, H-1),
14

7.30–7.40 (m, 3 H, Ph), 7.46–7.57 (m, 2 H, Ph). 13C NMR (75.5 MHz, CDCl3): δC 11.9
(CH(CH3)2), 17.7 (CH(CH3)2), 65.9 (C-5), 79.1 (C-4 or C-2), 81.3 (C-4 or C-2), 83.7 (C-3), 94.3
(C-1), 114.25 (q, JCF = 285.5 Hz, CF3), 114.39 (q, JCF = 285.4 Hz, CF3), 128.0, 129.2, 132.2,
133.3 (Ph), 156.88 (q, JCF = 43.8 Hz, CF3CO),157.04 (q, JCF = 43.2 Hz, CF3CO). 19F NMR
(282.40 MHz, CDCl3): δF −75.58, −75.64 (CF3CO).
4.5. Phenyl 3,5-di-O-pentafluoropropionyl-2-O-triisopropylsilyl-1-thio-α-D-
arabinofuranoside (5)
To the solution of diol 3 (170 mg, 0.43 mmol) in anhydrous CH2Cl2 (0.5 mL) Py(1 mL) and
(CF3CF2CO)2O (0.5 mL) were added at 0 °C (ice-water bath). After 1 h at 0 °C the reaction
mixture was diluted with CHCl3 (100 mL), washed with H2O (100 mL), 1 M KHSO4 (100 mL),
H2O (100 mL) and satd aq NaHCO3 (100 mL). Organic extract was filtered through a cotton
wool plug and concentrated under reduced pressure (bath temperature ~30 °C) and dried in
vacuo. The residue was purified by silica gel column chromatography (light petroleum–toluene,
1:1) to give pentafluoropropionyl derivative 5 as a colorless oil (195 mg, 66%; Rf = 0.78, light
petroleum–EtOAc, 4:1). [α]D23 +68.8 (c 1.0, CHCl3). HRESIMS: found m/z 713.1414 [M + Na]+.
Calcd for C26H32F10O6SSiNa: 713.1421. 1H NMR (300 MHz, CDCl3): δH 1.08 (br. s, 21 H,
CH(CH3)2), 4.55–4.62 (m, 2 H, H-2, H-4), 4.62–4.73 (m, 2 H, H-5a, H-5b), 5.16 (dd, J = 3.7,
1.6 Hz, 1 H, H-3), 5.50 (d, J = 1.5 Hz, 1 H, H-1), 7.30–7.39 (m, 3 H, Ph), 7.44–7.55 (m, 2 H,
Ph). 13C NMR (75 MHz, CDCl3): δC 11.9 (CH(CH3)2), 17.7 (CH(CH3)2), 66.0 (C-5), 79.3, 81.4,
83.8 (C-2, C-3, C-4), 94.3 (C-1), 102.0, 102.6, 105.6, 106.1, 109.1, 109.6, 115.2, 115.6,
116.1(CF2CF3); 127.2, 127.6, 128.0, 129.1, 132.1, 133.3 (Ph); 157.5, 157.6, 157.9, 158.3, 158.3
(CO). 19F NMR (282.40 MHz, CDCl3): δF −83.38, −83.67, −122.15, −122.29 (CF2CF3).
4.6. Phenyl 5-O-benzoyl-2-O-triisopropylsilyl-1-thio-α-D-arabinofuranoside (6)
15

To the solution of diol 3 (232 mg, 0.61 mmol) in anhydrous CH2Cl2 (5 mL) Py (50 µL, 1.2 mmol)
and BzCl (70 µL, 0.61 mmol) were added sequentially at 0 °C (ice-water bath). After 1 h at 0 °C
the reaction mixture was diluted with CHCl3 (100 mL), washed with H2O (100 mL), 1 M KHSO4
(100 mL), H2O (100 mL) and satd aq NaHCO3 (100 mL). Organic extract was filtered through a
cotton wool plug and concentrated under reduced pressure, dried in vacuo to give alcohol 6 as a
colorless oil (235 mg, 80%; Rf = 0.36, light petroleum–EtOAc, 4:1). [α]D19 +101.3 (c 1.0,
CHCl3). HRESIMS: found m/z 525.2071 [M + Na]+. Calcd for C27H38O5SSiNa: 525.2101. 1H
NMR (300 MHz, CDCl3); δH 1.06 (br. s, 21 H, CH(CH3)2), 2.81 (br. s, 1 H, OH), 4.09 (br. s, 1
H, H-3), 4.36 (t, J = 2.1 Hz, H-2), 4.43–4.61 (m, 3 H, H-4, H-5a, H-5b), 5.46 (d, J = 1.7 Hz, 1
H, H-1), 7.22–7.34 (m, 3 H, Ph), 7.37–7.45 (m, 3 H, Рh), 7.46–7.60 (m, 3 H, Ph), 8.04 (d, J =
7.2 Hz, 2 H, Ph). 13C NMR (75 MHz, CDCl3): δC 11.9 (CH(CH3)2), 17.8 (CH(CH3)2), 64.2 (C-
5), 79.9 (C-3), 82.8 (C-4), 83.7 (C-2), 93.3 (C-1), 127.5, 128.3, 128.9, 129.7, 132.0, 133.1,
133.8 (Ph).
4.7. Phenyl 5-O-benzoyl-3-O-trifluoroacetyl-2-O-triisopropylsilyl-1-thio-α-D-
arabinofuranoside (7)
To the solution of alcohol 6 (166 mg, 0.34 mmol) in anhydrous CH2Cl2 (1 mL), (CF3CO)2O (1
mL) and solid NaOCOCF3 (23 mg, 0.17 mmol) were added at 0 °C (ice-water bath). After 1 h at
0 °C the reaction mixture was concentrated under reduced pressure (bath temperature ~30 °C),
then dissolved in CCl4 (30 mL), filtered through a cotton wool plug, concentrated under reduced
pressure (bath temperature ~30 °C), and dried in vacuo to give trifluoroacatate 7 as a colorless oil
(185 mg, 94%, Rf = 0.66 (petroleum ether–EtOAc, 9:1). HRESIMS: found m/z 525.2103 [M-
CF3CO+H+Na] +. Calcd for C27H38O5SSiNa: 525.2107. [α]D19 +82.5 (c 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3): δΗ 1.14 (br. s, 21 H, CH(CH3)2), 4.56–4.74 (m, 4 H, H-2, H-4, H-5a, H-5b),
5.26–5.37 (m, 1 H, H-3), 5.53 (d, J = 2.2 Hz, 1 H, H-1), 7.24–7.38 (m, 3 H, Ph), 7.39–7.68 (m, 5
16

H, Ph), 8.08 (d, J = 7.3 Hz, 2 H, Ph). 13C NMR (75.5 MHz, CDCl3): δC 11.9 (CH(CH3)2), 17.7
(CH(CH3)2), 63.5 (C-5), 80.0, 81.6 (C-2, C-4), 84.1 (C-3), 94.1 (C-1), 114.29 (q, JCF = 285.7
Hz, CF3), 127.8, 128.4, 129.1, 129.7, 132.0, 133.2 (Ph), 156.76 (q, JCF = 43.2 Hz, CF3CO),
165.9 (CO). 19F NMR (50.32 MHz, CDCl3): δF −75.53 (CF3CO).
4.8. Phenyl 3-O-benzoyl-2-O-triisopropylsilyl-1-thio-α-D-arabinofuranoside (10)
To the solution of diol 3 (63 mg, 0.16 mmol) in anhydrous Py (0.75 mL) TrCl (66.0 mg,
0.24 mmol) was added at 0 °C (ice-water bath). The reaction mixture was stirred at room
temperature ~20 °C for 24 h. After this time diol 3 was consumed and TLC indicated the presence
of triryl ether 8. Then BzCl (170 µL, 1.47 mmol) was added to the solution at 0 °C (ice-water
bath). The reaction mixture was stirred at room temperature ~20 °C for 1 h and then diluted with
CH2Cl2 (40 mL), washed with water (40 mL), 1 M KHSO4 (40 mL), water (40 mL), satd aq
NaHCO3 (40 mL). The aqueous layer was extracted with CH2Cl2 (7 mL). The combined organic
extracts were filtered through a cotton wool plug, concentrated under reduced pressure (bath
temperature ~40 °C), and dried in vacuo. To the solution of the obtained benzoate 9 in CH2Cl2 (5
mL) 90% aq TFA (0.5 mL) was added. After 30 seconds the reaction mixture became yellow and
reaction mixture was poured into satd aq NaHCO3 (30 mL) with stirring. Organic phase was
filtered through a cotton wool plug, concentrated under reduced pressure (bath temperature ~40
°C), dried in vacuo and purified by silica gel column chromatography (light petroleum–EtOAc) to
give alcohol 10 as a colorless oil (42 mg, 53% over three steps from 3 via 8 and 9; Rf = 0.30, light
petroleum–EtOAc, 9:1). [α]D22 +101.1 (c 1.0, CHCl3). HRESIMS: found m/z 525.2101 [M +
Na]+. Calcd for C27H38O5SSiNa: 525.2101. 1H NMR (300 MHz, CDCl3): δΗ 1.14–1.19 (m, 21 H,
CH(CH3)2), 3.97 (d, J = 3.8 Hz, 2 H, H-5a, H-5b), 4.51 (ddd ~q, J = 3.8 Hz, 1 H, H-4), 4.69 (d,
J = 1.0 Hz, 1 H, H-2), 5.25–5.29 (m, 1 H, H-3), 5.58 (s, 1 H, H-1), 7.27–7.38 (m, 3 H, Ph),
7.48–7.65 (m, 5 H, Ph), 8.11–8.20 (m, 2 H, Ph). 13C NMR (75 MHz, CDCl3): δC 11.9
17

(CH(CH3)2), 17.8 (CH(CH3)2), 62.4 (C-5), 80.6 (C-3), 81.6 (C-2), 84.6 (C-4), 94.8 (C-1), 127.5,
128.5, 129.0, 129.2, 129.7, 129.9, 131.8, 133.5, 134.6 (Ph), 165.9 (CO).
4.9. Phenyl 3-O-benzoyl-5-O-trifluoroacetyl-2-O-triisopropylsilyl-1-thio-α-D-
arabinofuranoside (11)
To the solution of alcohol 10 (85 mg, 0.17 mmol) in anhydrous CH2Cl2 (0.5 mL) and anhydrous
(COCF3)2O (1 mL) and solid NaOCOCF3 (12 mg, 0.17 mmol) were added at 0 °C (ice-water
bath). After 1 h at 0 °C the reaction mixture was concentrated under reduced pressure (bath
temperature ~30 °C), coevaporated with CCl4 (30 mL), then dissolved in CCl4 (20 mL), filtered
through a Teflon filter (0.45 µm), concentrated under reduced pressure (bath temperature ~30
°C), and dried in vacuo to give trifluoroacetate 11 as a colorless oil (102 mg, 94%, Rf = 0.66
(petroleum ether–EtOAc, 9:1)). [α]D20 +99.2 (c 1.0, CHCl3). HRESIMS: found m/z 621.1921 [M
+ Na]+. Calcd for C29H37O6SF3SiNa: 621.1930. 1H NMR (300 MHz, CDCl3)1H NMR (300 MHz,
CDCl3): δH 1.05–1.12 (m, 21 H, CH(CH3)2), 4.64–4.77 (m, 4 H, H-2, H-4, H-5a, H-5b), 5.20
(dd, J = 2.8, 1.2 Hz, 1 H, H-3), 5.56 (s, 1 H, H-1), 7.29–7.39 (m, 3 H, Ph), 7.47–7.57 (m, 4 H,
Ph), 7.60–7.67 (m, 1 H, Ph), 8.11–8.17 (m, 2 H, Ph). 13C NMR (75.5 MHz, CDCl3): δC 11.9
(CH(CH3)2), 17.8 (CH(CH3)2), 66.9 (C-5), 80.6 (C-3); 81.1, 81.7 (C-2, C-4), 95.0 (C-1), 114.49
(q, JCF = 285.4 Hz, CF3), 127.6, 128.6, 129.0, 129.1, 130.0, 131.89, 131.92, 131.96, 133.6,
134.2, 157.22 (q, JCF = 42.8 Hz, CF3CO), 165.7 (CO). 19F NMR (75.5 MHz, CDCl3): δ −75.59
(CF3CO).
4.10. 4-(2-Chloroethoxy)phenyl 3,5-di-O-benzoyl-2-O-chloroacetyl-α-D-arabinofuranoside
(15)
Glycosyl chloroacetate 14 (1.6 g, 3.13 mmol) and CEP-OH37 (1.08 g, 6.26 mmol) were
dissolved under Ar in CH2Cl2 (19 mL) at 0 °C (ice-water bath). Neat TfOH (41 µL, 0.47 mmol)
was added and the reaction mixture was stirred at ~20 °C for 1 h. The mixture was diluted with
18

CH2Cl2 (45 mL), washed with H2O (45 mL), satd aq NaHCO3 (45 mL) and 5% aq NaOH (40
mL). Aqueous layer was extracted with CH2Cl2 (2×10 mL). Combined organic extracts were
filtered through a cotton wool plug, concentrated, dried in vacuo, and purified by silica gel
column chromatography (toluene–EtOAc, 8:1) to give 15 as a colorless oil (1.37 g, 74%; Rf =
0.43, toluene–EtOAc, 8:1). [α]D28 +44.7 (c 1.0, CHCl3). HRESIMS: found m/z 611.0843 [M +
Na]+. Calcd for C29H26O9Cl2Na: 611.0846. 1H NMR (300 MHz, CDCl3): δH 3.79 (t, J = 5.9 Hz, 2
H, OCH2CH2Cl), 4.03 (d, J = 1.9 Hz, 2 H, COCH2Cl), 4.20 (t, J = 5.9 Hz, 2 H, OCH2CH2Cl),
4.65–4.83 (m, 2 H, H-5a, H-5b), 4.70–4.73 (m, 1 H, H-4), 5.55 (d, J = 3.9 Hz, 1 H, H-3), 5.62
(s, 1 H, H-2), 5.74 (s, 1 H, H-1), 6.88 (d, J = 9.0 Hz, 2 H, OC6H4O), 7.05 (d, J = 9.0 Hz, 2 H,
OC6H4O), 7.39–7.54 (m, 4 H, Ph), 7.54–7.68 (m, 2 H, Ph), 8.02–8.16 (m, 4 H, Ph). 13C NMR
(75 MHz, CDCl3): δC 40.3 (COCH2Cl), 41.9 (CH2Cl), 63.2 (C-5), 68.7 (OCH2), 77.3 (C-3), 81.6
(C-4), 82.9 (C-2), 104.4 (C-1), 115.8, 118.3 (OC6H4O), 128.4, 128.5, 129.7, 129.9, 133.2, 133.7
(Ph), 150.4, 153.9 (OC6H4O), 165.7, 166.0, 166.2 (CO).
4.11. 4-(2-Chloroethoxy)phenyl 3,5-di-O-benzoyl-α-D-arabinofuranoside (16)
Chloroacetate 15 (1.3 g, 2.21 mmol) was dissolved in Py (16 mL) and water (8 mL). The
reaction mixture was stirred at 80 °C (bath temperature) for 1 h. The mixture was diluted with
CH2Cl2 (45 mL), washed with 1 M KHSO4 (45 mL), H2O (45 mL) and a mixture of satd aq
NaHCO3 (45 mL) with satd NaCl (15 mL). Aqueous layer was extracted with CH2Cl2 (2×10 mL).
Combined extracts were filtered through the cotton wool plug, concentrated, dried in vacuo, and
purified by silica gel column chromatography (light petroleum–EtOAc) to give alcohol 16 as a
white foam (766 mg, 68%; Rf = 0.32, light petroleum–EtOAc, 3:1). [α]D20 +45.4 (c 1.0, CHCl3).
HRESIMS: found m/z 535.1127. Calcd for C27H25O8ClNa: 535.1130. 1H NMR (300 MHz,
CDCl3): δH 3.27 (br. s, 1 H, OH), 3.79 (t, J = 5.9 Hz, 2 H, CH2Cl), 4.20 (t, J = 5.9 Hz, 2 H,
OCH2), 4.62 (br. s, 1 H, H-2), 4.60-4.73 (m, 2 H, H-5a, H-5b), 4.74–4.80 (m, 1 H, H-4), 5.16
19

(dd, J = 6.0, 2.6 Hz, 1 H, H-3), 5.71 (s, 1 H, H-1), 6.84–6.90 (m, 2 H, OC6H4O), 6.99–7.05 (m,
2 H, OC6H4O), 7.39–7.51 (m, 4 H, Ph), 7.53–7.66 (m, 2 H, Ph), 8.04–8.10 (m, 4 H, Ph). 13C
NMR (75 MHz, CDCl3): δC 41.9 (CH2Cl), 63.7 (C-5), 68.7 (OCH2), 79.7 (C-4), 81.6 (C-2), 82.0
(C-3), 106.7 (C-1), 115.9, 118.1 (OC6H4O), 128.5, 128.6, 129.7, 129.9, 133.2, 133.8 (Ph),
150.8, 153.6 (OC6H4O), 166.2, 167.3 (CO).
4.12. 1-O-Acetyl-2,3,5-tri-O-benzoyl-D-arabinofuranose (17)
To the stirring solution of tribenzoate 2138 (250 mg, 0.52 mmol) in CH2Cl2 (1 mL)
BF3·Et2O (240 µL, 1.90 mmol) was added at 0 °C (ice-water bath) followed after 5 min by Ac2O
(800 µL, 8.49 mmol). The reaction mixture was stirred at 0 °C for 1.5 h and then diluted with
CH2Cl2 (30 mL), washed with water (25 mL) and satd NaHCO3 (25 mL). Organic extract was
filtered through a cotton wool plug, diluted with toluene (2×20 mL) and concentrated (bath
temperature 40–50 °C), dried in vacuo, and purified by silica gel column chromatography (light
petroleum–EtOAc) to give glycosyl acetate 17 as a white foam (250 mg, 94%; Rf = 0.24, light
petroleum –EtOAc, 3:1, α:β = 3.9:1). HRESIMS: found m/z 543.1051 [M + K]+. Calcd for
C28H24O9K: 543.1052. 1H NMR (300 MHz, CDCl3): δH 1.95 (s, 3 H, CH3CO-β), 2.20 (s, 3 H,
CH3CO-α), 4.60 (ddd~dt, J = 4.3 Hz, 5.8 Hz, 1 H, H-4β), 4.68–4.83 (m, 5 H, H-5aβ, H-5aα, H-
5bα, H-5bβ, H-4α), 5.65 (d, J = 3.7 Hz, 1 H, H-3α), 5.67 (s, 1 H, H-2α), 5.82 (dd, J = 6.8, 4.7
Hz, 1 H, H-2β), 5.98–6.03 (m, 1 H, H-3β), 6.50 (s, 1 H, H-1α), 6.67 (d, J = 4.8 Hz, 1 H, H-1β),
7.28–7.68 (m, 9 H, Ph), 8.00–8.13 (m, 6 H, Ph). 13C NMR (75 MHz, CDCl3): δC 20.8 (CH3CO-
β), 21.0 (CH3CO3-α), 63.5 (C-5α), 64.7 (C-5β), 75.5 (C-3β), 76.0 (C-2β), 77.5 (C-2α), 79.9 (C-
4β), 81.2 (C-3α), 83.1 (C-4α), 93.7 (C-1β), 99.4 (C-1α), 128.3, 128.3, 128.4, 128.5, 128.6,
128.6, 128.7, 128.9, 129.5, 129.7, 129.8, 129.8, 129.9, 129.9, 133.1, 133.1, 133.6, 133.7, 133.7
(Ph), 165.1, 165.5, 166.1, 169.1 (CO).
4.13. 4-(2-Chloroethoxy)phenyl 2,3,5- tri-O-benzoyl-α-D-arabinofuranoside (18)
20

To a stirred solution of glycosyl acetate 17 (842 mg, 1.67 mmol) in anhydrous CH2Cl2 (10 mL)
CEP-OH37 (576 mg, 3.34 mmol) was added. The mixture was cooled to 0 °C (ice-water bath),
then TfOH (22 µL, 0.25 mmol) was added. The reaction mixture was stirred at 0 °C for 1 h, then
diluted with CH2Cl2 (50 mL), washed with water (50 mL), satd aq NaHCO3 (50 mL). Organic
phase was concentrated and dried in vacuo. The residue was purified by silica gel column
chromatography (light petroleum–EtOAc, 3:1) to give glycoside 18 as a white foam (846 mg,
86%). Rf = 0.17 (light petroleum– EtOAc, 85:15). [α]D19 +21.7 (c 1.0, CHCl3). HRESIMS: found
m/z 639.1392 [M+Na]+. Calcd. for C34H29ClNaO9: 639.1392. 1H NMR (300 MHz, CDCl3): δH
3.80 (t, 2 H, J = 5.9 Hz, CH2Cl), 4.20 (t, 2 H, J = 5.9 Hz, OCH2CH2Cl), 4.69–4.89 (m, 3 H, H-4,
H-5a, H-5b), 5.72 (d, 1 H, J = 3.3 Hz, H-3), 5.81 (s, 1 H, H-2), 5.89 (s, 1 H, H-1), 6.86–6.95 (m,
2 H, OC6H4O), 7.11 (m, 2 H, OC6H4O), 7.22–7.69 (m, 10 H, Ph), 7.99–8.19 (m, 5 H, Ph). 13C
NMR (75.5 MHz, CDCl3): δC 42.0 (CH2Cl), 63.7 (C-5), 68.8 (OCH2), 77.8 (C-3), 82.0, 82.3 (C-
2, C-4), 105.1 (C-1), 116.0, 118.5 (OC6H4O), 128.4, 128.6, 129.6, 129.9, 130.0, 133.2, 133.7
(Ph), 150.7, 153.9 (OC6H4O), 165.5, 165.9, 166.3 (CO).
4.14. 4-(2-Chloroethoxy)phenyl α-D-arabinofuranoside (19)
Tribenzoate 18 (200 mg, 0.34 mmol) was dissolved in CH2Cl2 (2 mL) and 0.1 M MeONa in
MeOH (2 mL) was added to the reaction mixture, which then was stirred at ~20 °C for 48 h. The
reaction mixture was neutralized with ion-exchange resin Dowex 50W×4 (H+). The resin was
filtered off, washed with MeOH (10 mL) and the filtrate was concentrated. The residue was
purified by silica gel column chromatography (toluene–acetone, 1:1) to give triol 19 as a white
foam (89 mg, 86%; Rf = 0.33, EtOAc). [α]D20 +57.2 (c 1.0, MeOH). HRESIMS: found m/z
327.0609 [M+Na]+. Calcd. for C13H17ClNaO6: 327.0606. 1H NMR (300 MHz, acetone-d6): δH
3.64–3.81 (m, 2 H, H-5a, H-5b), 3.88 (m, 2 H, CH2Cl), 4.07 (d, J = 3.3 Hz, 1 H, H-4), 4.07–4.14
(m, 1 H, H-3), 4.22 (s, 1 H, H-2), 4.23–4.27 (m, 2 H, OCH2), 5.44 (d, J = 1.7 Hz, 1 H, H-1),
6.86–6.93 (m, 2 H, OC6H4O), 6.96–7.04 (m, 2 H, OC6H4O). 13C NMR (75 MHz, acetone-d6): δC
21

43.6 (CH2Cl), 62.7 (C-5), 69.7 (OCH2), 78.5 (C-4), 83.3 (C-2), 86.7 (C-3), 108.7 (C-1), 116.5,
119.0 (OC6H4O), 152.6, 154.5 (OC6H4O).
4.15. 4-(2-Chloroethoxy)phenyl 3,5-O-(di-tert-butylsilylene)-α-D-arabinofuranoside (20)
Triol 19 (70 mg, 0.23 mmol) was dissolved in anhydrous Py (1 mL), the reaction mixture was
cooled to 0 °C (ice-water bath) and (t-Bu)2Si(OTf)2 (81 µL) was added. After 2 h at 0°C the
reaction mixture was quenched by MeOH (0.1 mL), coevaporated with toluene (30×2 mL) and
purified by silica gel column chromatography (light petroleum–AcOEt, 5:1) to give silyl ether 20
(80 mg, 78 %) as a white foam. [α]D18 +73.24 (c 1.0, CHCl3);HRESIMS found m/z 467.1641
[M+Na]+. Calcd. for C21H33ClNaO6Si: 467.1627. 1H NMR (300 MHz, CD3OD): δH 1.03 and 1.10
(2 s, 18 H, C(CH3)3), 3.79 (t, J = 5.6 Hz, 2 H, CH2Cl), 3.88–4.01 (m, 1 H, H-5a), 4.14–4.26 (m,
4H, CH2O, H-3, H-4 ), 4.28–4.40 (m, 1 H, H-5b), 4.40–4.51 (m, 1 H, H-2), 5.43 (s, 1 H, H-1),
6.87 (br. s, 2 H, OC6H4O), 6.91–7.05 (m, 2H, OC6H4O). 13C NMR (75.5 MHz, CD3OD): δC 20.1
and 22.7 (C(CH3)3), 27.1 and 27.4 (C(CH3)3), 41.9 (CH2Cl), 67.4 (C-5), 68.8 (CH2O), 74.2, 81.3,
81.7 (C-2, C-3, C-4), 106.5 (C-1); 115.9, 117.8 (OC6H4O); 151.5, 153.6 (OC6H4O).
4.16. Methyl 3,5-O-(di-tert-butylsilylene)-α-D-arabinofuranoside (23)
To the solution of triol 2239 (89 mg, 0.54 mmol) in anhydrous Py (0.9 mL) (t-Bu)2Si(OTf)2
(193 µL, 0.60 mmol) and DMAP (3.3 mg, 0.03 mmol) were added at 0 °C (ice-water bath). The
reaction mixture was stirred at 0 °C for 2 h and then was quenched with MeOH and coevaporated
with toluene, dried in vacuo, and purified by silica gel column chromatography (toluene–EtOAc,
22
20:1) to give alcohol 23 as a colorless oil (102 mg, 62%; Rf = 0.21, toluene–EtOAc, 20:1). [α]D
+51.4 (c 1.0, CHCl3). HRESIMS: found m/z 327.1601 [M + Na]+. Calcd for C14H28O5SiNa:
327.1598. 1H NMR (300 MHz, CDCl3): δH 1.00 and 1.07 (2 s, 18H, C(CH3)3), 3.42 (s, 3 H,
OCH3), 3.91–3.98 (m, 3 H, H-3, H-4, H-5a), 4.09–4.14 (m, 1 H, H-5b), 4.29-4.40 (m, 1 H, H-2),
22

4.81 (d, J = 3.3 Hz, 1 H, H-1). 13C NMR (75 MHz, CDCl3): δC 20.1 and 22.6 (C(CH3)3), 27.1
and 27.4 (C(CH3)3), 56.1 (OCH3), 67.5 (C-5), 73.8 (C-4), 81.54 (C-2), 81.6 (C-3), 109.0 (C-1).
4.17. Phenyl 3,5-O-(di-tert-butylsilylene)-2-O-trifluoroacetyl-1-thio-α-D-
arabinofuranoside (13)
To the solution of phenyl 3,5-O-(di-tert-butylsilylene)-1-thio-α-D-arabinofuranoside 3820
(56 mg, 0.15 mmol) in anhydrous CH2Cl2 (2 mL), (CF3CO)2O (1 mL) and NaOCOCF3 (10 mg,
0.07 mmol) were added to the stirring mixture at 0 °C (ice-water bath). After 1 h at 0 °C the
reaction mixture was concentrated under reduced pressure (bath temperature ~30 °C), then
dissolved in CCl4 (30 mL), filtered through a cotton wool plug, concentrated under reduced
pressure (bath temperature ~30 °C), dried in vacuo to give 13 as a colorless oil (68 mg, 97%; Rf
= 0.77, light petroleum–EtOAc, 10:1). HRESIMS: found m/z 501.3736 [M + Na]+. Calcd for
19
1
C21H29O5SF3Si: 501.1349. [α]D +49.8 (c 1.0, CHCl3). H NMR (300 MHz, CDCl3): δH 0.98–
1.03, 1.03–1.08 (2 m, 18H, C(CH3)3), 3.89–4.15 (m, 2 H, H-5), 4.15–4.34 (m, 1 H, H-3), 4.33–
4.50 (m, 1 H, H-4), 5.25–5.76 (m, 2 H, H-1, H-2), 7.23–7.45 (m, 2 H, Ph), 7.45–7.70 (m, 3 H,
Ph). 13C NMR (75 MHz, CDCl3): δC 20.0 and 22.6 (C(CH3)3), 26.9 and 27.3 (C(CH3)3), 67.0 (C-
5), 73.7 (C-4), 79.2 (C-3), 84.1 (C-2), 88.2 (C-1), 114.37 (q, JCF = 285.6 Hz, CF3), 126.6, 128.3,
129.1 (Ph), 156.56 (q, JCF = 43.1 Hz, CF3CO). 19F NMR (282.40 MHz, CDCl3): δF −74.57
(CF3CO).
4.18. General procedure for glycosylation of glycosyl acceptors. Preparation of compounds
26–35
A mixture of a thioglycosyde (4, 5, 7, 11, 13, 24,20 or 257,29) (0.042 mmol, 1.5 equiv.) and a
glycosyl acceptor 16, 20 or 23 (0.028 mmol, 1 equiv.) was dried in vacuo for 2 h, then anhydrous
CH2Cl2 (1 mL) was added under argon. Freshly activated (220 °C, 6 h, in vacuo) powdered 4 Å
molecular sieves (100 mg) were added under argon to the resulting solution and the reaction flask
23

was flushed with argon. The suspension was stirred under argon at ~22 °C for 1 h, then cooled to
−78 °C (acetone–dry ice bath). Solid NIS (0.042 mmol, 1.5 equiv.) was added followed by
AgOTf (0.003 mmol, 0.1 equiv, 1 mg). Then the temperature was allowed to rise slowly until
appearance of persistent characteristic iodine color. This temperature, designated as T in Table 1,
−10 °C during 30
was kept for 30 min, and then the reaction mixture was allowed to warm to
min. The reaction was quenched by the addition of satd aq NaHCO3 (50 µL). The reaction
mixture was diluted with CHCl3 (15 mL) and filtered through a Celite pad. The solids were
thoroughly washed with CHCl3 (50 mL) and the filtrate was successively washed with a mixture
of satd aq Na2S2O3 (50 mL) and satd. aq. NaHCO3 (50 mL). The aqueous layer was back-
extracted with CHCl3 (2 × 5 mL). Combined organic extracts were filtered through a cotton wool
plug, concentrated and dried in vacuo. In those cases when glycosyl donor contained TFA-groups
the residue was additionally dissolved in MeOH (1.0 mL) and CH2Cl2 (1.0 mL) and then NEt3 (40
µL) was added to the solution. The reaction mixture was stirred at ~20 °C for 40 min and then
diluted with CHCl3 (15 mL) and washed with satd aq NaHCO3 (10 mL). The aqueous layer was
back-extracted with CHCl3 (2 × 5 mL). Combined organic extracts were filtered through a cotton
wool plug, concentrated, dried in vacuo. The residue was applied onto a gel-chromatography
column (50 × 2.5 cm) with Bio-Beads S×3 (200–400 mesh, Bio-Rad) using toluene as the eluent
and a differential refractometer (Knauer) as the detector. The first eluted fraction contained
disaccharides 26–35, which was analyzed by NMR spectroscopy to give anomeric ratio values.
The yields and α/β ratios are given in Table 1.
4.18.1. Data for 4-(2-chloroethoxy)phenyl 3,5-di-O-benzoyl-2-O-[2-O-triisopropylsilyl-D-
arabinofuranosyl]-α-D-arabinofuranoside (26) (entry 1, Table 1)
α/β = 1:2. Rf = 0.53, light petroleum–EtOAc, 4:1. HRESIMS: found m/z 823.283 [M +
Na]+. Calcd for C41H53ClO12SiNa: 823.2887. 1H NMR (600 MHz, CDCl3): δH = 0.96–1.06 (m,
CH(CH3)2 (β and α), 3.66–3.72 (m, H-5IIα-a, H-5IIα-b), 3.72–3.76 (m, H-5IIβ-a, H-5IIβ-b, CH2Cl),
24

3.76–3.79 (m, H-4IIβ), 3.95 (br. s, H-3IIα), 4.13–4.16 (m, CH2O, H-4IIα), 4.18 (s, H-2IIα), 4.19 (d,
J = 4.5 Hz, H-2IIβ), 4.26 (t, J = 7.63 Hz, H-3IIβ), 4.47–4.55 (m, H-5Iα-a, H-5Iβ-b, H-5Iβ-a), 4.56
(br. s, H-2Iβ), 4.59 (s, H-2Iα), 4.61 (d, J = 5.3 Hz, H-4Iα), 4.63–4.68 (m, H-4Iβ, H-5Iα-b), 4.97
(d, J = 4.5 Hz, H-1IIβ), 5.30 (s, H-1IIα), 5.32 (d, J = 3.8 Hz, H-3Iα), 5.56 (dd, J = 4.5, 2.4 Hz, H-
3Iβ), 5.65 (s, H-1Iβ), 5.69 (s, H-1Iα), 6.81 (m, OC6H4O), 6.91 (d, J = 8.8 Hz, OC6H4O (β)), 6.97
(d, J = 9.1 Hz, OC6H4O (α)), 7.32–7.44, 7.46–7.52 (m, Ph), 7.55 (t, J = 7.0 Hz, Ph), 8.00 (t, J =
7.2 Hz, Ph), 8.03 (dd, J = 7.3, 4.4 Hz, Ph). 13C NMR (151 MHz, CDCl3) δC = 11.8, 12.2
(CH(CH3)2, (β and α)), 17.7, 17.75, 17.83, 17.9 (CH(CH3)2 (β and α)), 41.9 (CH2Cl), 62.7 (C-
5IIα), 62.8 (C-5IIβ), 63.8 (C-5Iα), 63.9 (C-5Iβ), 68.8 (CH2O), 74.5 (C-3IIβ), 78.2 (C-3Iα, C-2IIβ),
78.3 (C-3Iβ), 78.6 (C-3II α)), 80.4 (C-4Iβ)), 80.9 (C-4Iα)), 81.7 (C-2II α)), 82.2 (C-4II β)), 84.9
(C-2Iα)), 85.9 (C-2Iβ), 87.8 (C-4II α), 102.0 (C-1II β), 105.2 (C-1Iβ), 105.7 (C-1Iα), 108.4 (C-
1II α), 115.88, 115.90 (OC6H4O (β and α)), 117.8 (OC6H4O (β)), 118.1 (OC6H4O (α)), 128.3,
128.4, 128.5, 129.15, 129.18, 129.7, 129.77, 129.79, 129.9, 130.0, 133.06, 133.14, 133.6, 133.7
(Ph (β and α)), 150.7 (OC6H4O (α)), 150.9 (OC6H4O (β)), 153.6 (OC6H4O (β)), 153.7 (OC6H4O
(α)), 165.7, 166.2, 166.5 (CO).
4.18.2. Data for 4-(2-chloroethoxy)phenyl 3,5-di-O-benzoyl-2-O-[5-O-benzoyl-2-O-
triisopropylsilyl-D-arabinofuranosyl]-α-D-arabinofuranoside (27) (entry 5, Table 1)
α/β = 1.2:1. Rf = 0.25, light petroleum–EtOAc, 10:1. HRESIMS: found m/z 927.3077 [M +
Na]+, 922.3519 [M + NH4]+. Calcd for C48H57ClO13SiNa: 927.3149. Calcd for
C48H57ClO13SiNH4: 922.3595. Selected signals: 1H NMR (300 MHz, CDCl3): δH 1.05 (br. s, 20
H, CH(CH3)2), 1.27 (s, CH(CH3)2), 3.75–3.87 (m, CH2Cl), 3.96–4.06 (m), 4.09–4.25 (m), 4.11–
4.24 (m, CH2O), 4.26–4.34 (m), 4.38–4.73 (m, H-5Iα-a, H-5Iβ-a, H-5Iα-b, H-5Iβ-b, H-5IIα-a, H-
5IIβ-a, H-5IIα-b, H-5IIβ-b), 5.14 (d, J = 3.5 Hz, 1 H, H-1IIβ), 5.38 (s, 1 H, H-1IIα), 5.39–5.43 (m, 1
H, H-2Iα), 5.64 (dd, J = 4.6, 2.7 Hz, 1 H, H-3Iα), 5.73 (s, 1 H, H-1Iβ), 5.82 (s, 1 H, H-1Iα), 6.72–
25

6.91 (m, 4 H, Ph), 6.93–7.06 (m, 4 H, OC6H4O), 7.14–7.26 (m, 4 H, OC6H4O), 7.32–7.66 (m, 20
H, Ph). 13C NMR (75 MHz, CDCl3): δC 11.8, 12.1 (CH(CH3)2), 17.7 CH(CH3)2), 41.9 (CH2Cl),
62.8, 63.8, 64.1, 64.5 (C-5Iα, C-5Iβ, C-5IIα, C-5IIβ), 68.7 (CH2O), 70.3, 76.4, 78.3, 78.6, 80.1,
80.4, 80.5, 81.0, 82.8, 84.2, 85.5, 86.4 (C-2α, C-2β, C-3α, C-3β, C-4α, C-4β), 102.2 (C-1IIβ),
105.1 (C-1Iβ), 106.1 (C-1Iα), 108.0 (C-1IIα), 115.8, 117.8, 118.0 (OC6H4O), 128.3, 128.5, 129.7,
129.8, 130.1, 133.1, 133.4, 133.5, 133.5, 133.6 (Ph), 153.6 (OC6H4O), 165.7, 166.0, 166.1,
166.1, 166.2 (CO).
4.18.3. Data for 4-(2-chloroethoxy)phenyl 3,5-di-O-benzoyl-2-O-[3-O-benzoyl-2-O-
triisopropylsilyl-D-arabinofuranosyl]-α-D-arabinofuranoside (28) (entry 6, Table 1)
α/β = 1:1. Rf = 0.25, light petroleum–EtOAc, 10:1. HRESIMS: found m/z 927.3067 [M +
Na]+, 922.3510 [M + NH4]+. Calcd for C48H57ClO13SiNa: 927.3149. Calcd for
C48H57ClO13SiNH4: 922.3595. Selected signals: 1H NMR (300 MHz, CDCl3): δH 1.05 (br. s, 20
H, CH(CH3)2), 1.27 (s, CH(CH3)2), 3.23–4.02 (m, CH2Cl), 4.02–4.12 (m), 4.12–4.27 (m), 4.27–
4.41 (m, CH2O), 4.43–4.91 (m), 5.01 (s), 5.14–5.27 (m), 5.36–5.54 (m), 5.84–5.67 (m, 1H),
6.94–6.68 (m, OC6H4O), 7.10–6.94 (m, OC6H4O), 7.33–7.10 (m, Ph), 7.71–7.33 (m, Ph), 8.25–
7.92 (m, Ph), 8.42–8.29 (m, Ph). 13C NMR (75 MHz, CDCl3): δC 11.8 (CH(CH3)2), 17.7
(CH(CH3)2), 41.9 (CH2Cl) 62.8, 63.8, 64.1, 64.6 (C-5Iα, C-5Iβ, C-5IIα, C-5IIβ), 68.7 (CH2O),
70.3, 76.4, 78.3, 78.6, 80.1, 80.6, 80.5, 81.0, 82.9, 84.2, 85.5, 86.4 (C-2α, C-2β, C-3α, C-3β, C-
4α, C-4β), 102.2 (C-1IIβ), 105.1 (C-1Iβ), 106.2 (C-1Iα), 108.0 (C-1IIα), 115.9, 117.8, 118.0
(OC6H4O), 128.5, 128.4, 128.5, 129.2, 129.7, 129.8, 129.8, 129.9, 133.1, 133.4, 133.5 (Ph),
150.8, 150.9, 153.6 (OC6H4O), 165.7, 166.0, 166.1, 166.3 (CO).
4.18.4.
Data
for
4-(2-chloroethoxy)phenyl
3,5-di-O-benzoyl-2-O-[3,5-O-(di-tert-
butylsilylene)-D-arabinofuranosyl]-α-D-arabinofuranoside (29) (entry 7, Table 1)
26

α/β = 3.3:1. Rf = 0.26, light petroleum–EtOAc, 5:1. HRESIMS: found m/z 802.2964 [M + NH4]+,
807.2513 [M + Na]+. Calcd for C40H49ClO12SiNH4: 802.3020. Calcd for C40H49ClO12Na:
1
807.2574. Selected signals: H NMR (300 MHz, CDCl3): δH 0.94–1.13 (m, (CH3)3C), 3.64–3.75
(m, H-4IIα), 3.75–3.83 (m, CH2Cl), 3.85–4.14 (m, H-3IIα, H-5aII), 4.14–4.26 (m, CH2O, H-2IIα),
4.27–4.33 (m, 1 H, H-5II-a), 4.52–4.75 (m, H-2Iα, H-4Iα, H-5I-a, H-5I-b), 4.76–4.85 (m, H-5II-b),
5.25–5.32 (m, H-1IIα, H-1IIβ), 5.43 (d, J = 3.5 Hz, H-3Iα), 5.77 (s, H-1Iβ), 5.85 (s, H-1Iα), 6.82–
6.92 (m, OC6H4O), 6.97–7.07 (m, OC6H4O), 7.38–7.52 (m, Ph), 7.52–7.65 (m, Ph), 8.01–8.13
(m, Ph). 13C NMR (75 MHz, CDCl3): δC 20.1, 22.5 (C(CH3)3), 26.9, 27.4 (C(CH3)3), 41.9
(CH2Cl), 63.7, 67.3 (C-5), 68.7 (CH2O), 74.0 (C-4IIα), 78.3 (C-3Iα), 81.1 (C-3IIα), 81.5 (C-2IIα,
C-4Iα), 85.8 (C-2Iα), 100.6 (C-1IIβ), 105.0 (C-1Iβ), 106.0 (C-1Iα), 108.1 (C-1IIα), 115.9, 117.9
(OC6H4O), 128.3, 128.5, 129.8, 133.3, 133.5 (Ph), 150.8, 153.5 (OC6H4O), 165.9, 166.4 (CO).
4.18.5.
Data
for
4-(2-chloroethoxy)phenyl
3,5-di-O-benzoyl-2-O-[3,5-O-(di-tert-
butylsilylene)-2-O-triisopropylsilyl-D-arabinofuranosyl]-α-D-arabinofuranoside (30) (entry
8, Table 1)
α/β = 1:4.5. Rf = 0.27, light petroleum–EtOAc, 20:1. HRESIMS: found m/z 958.4340 [M +
NH4]+, 963.3906 [M + Na]+. Calcd for C49H69ClO12Si2NH4: 958.4354. Calcd for
C49H69ClO12Si2Na: 963.3908. Selected signals: 1H NMR (600 MHz, CDCl3): δH 0.98 (s, 9 H,
C(CH3)3), 1.03–1.19 (m, 30 H, C(CH3)3, CH(CH3)2), 3.60–3.68 (m, 1 H, H-4IIβ), 3.80 (t, J = 5.9
Hz, 2 H, CH2Cl), 3.87–3.92 (m, 1 H, H-5IIβ-a), 4.16 (dd, J = 9.2, 5.0 Hz, 1 H, H-5IIβ-b), 4.19–
4.23 (m, 3 H, CH2O, H-3IIβ), 4.24–4.30 (m, 2 H, H-2IIβ), 4.57–4.61 (m, 3 H, H-2Iβ, H-5Iβ-a, H-
5Iβ-b), 4.71 (q, J = 5.2 Hz, 1 H, H-3Iβ), 5.19 (d, J = 5.0 Hz, 1 H, H-1IIβ), 5.21 (d, J = 3.0 Hz, 1
H, H-1IIα), 5.67 (dd, J = 4.5, 2.5 Hz, 1 H, H-4Iβ), 5.79 (s, 1 H, H-1Iβ), 5.85 (s, 1 H, H-1Iα),
6.85–6.90 (m, 2 H, OC6H4O), 7.02–7.06 (m, 2 H, OC6H4O), 7.35–7.66 (m, 6 H, Ph), 8.01–8.14
(m, 4 H, Ph). 13C NMR (151 MHz, CDCl3): δC 17.7 and 17.8 (CH(CH3)2), 20.0 and 22.6
(C(CH3)3), 27.1, 27.3, 27.4 (C(CH3)3), 41.9 (CH2Cl), 64.4 (C-5I), 68.2 (C-5II), 68.8 (CH2O), 73.8
27

(C-4II), 77.9 (C-3II), 78.4 (C-2II), 78.8 (C-4I), 81.1 (C-2I), 87.2 (C-3I), 102.0 (C-1IIβ), 105.7 (C-
1Iβ), 106.0 (C-1IIα), 109.6 (C-1Iα), 115.9, 118.0 (OC6H4O), 128.3, 128.4, 129.5, 129.7, 129.8,
129.8 , 129.8, 133.0, 133.0, 133.3, 133.4 (Ph), 151.0, 153.6 (OC6H4O), 165.6, 166.1 (CO).
4.18.6.
Data
for
4-(2-chloroethoxy)phenyl
3,5-di-O-benzoyl-2-O-[3,5-O-(di-tert-
butylsilylene)-2-O-benzyl-D-arabinofuranosyl]-α-D-arabinofuranoside (31) (entry 10, Table
1)
α/β =1:2. Rf = 0.14, light petroleum–acetone, 10:1. HRESIMS: found m/z 897.3037 [M + Na]+.
1
Calcd for C47H55ClO12SiNa: 897.3044. Selected signals: H NMR (600 MHz, CDCl3): δH 1.00–
1.10 (m, C(CH3)3), 5.20 (d, J = 4.9 Hz, H-1IIβ), 5.34 (s, H-1Iβ), 5.76 (s, H-1IIα), 5.83 (s, H-1Iα),
13
6.95–7.06 (m, OC6H4O), 7.14–7.66 (m, Ph), 8.08 (d, J = 7.6 Hz, Ph). C NMR (151 MHz,
CDCl3): δC 27.1, 27.5 (C(CH3)3), 41.9 (CH2Cl), 64.1, 64.2, 67.4, 68.1 (C-5IIα, C-5IIβ, C-5Iα, C-
5Iβ), 68.8(CH2O), 72.1, 72.2, 73.9, 74.1, 78.0, 78.3, 78.7, 81.1, 81.2, 81.2, 81.3, 86.3, 86.8,
87.6, 100.9 (C-1IIβ), 105.4 (C-1IIα), 105.9 (C-1Iβ), 107.4 (C-1Iα), 115.9, 117.9 (OC6H4O), 127.8,
128.0, 128.4, 128.5, 128.5, 129.8, 133.0, 133.1, 133.5 (Ph), 150.9, 153.6 (OC6H4O), 165.7,
166.2, 166.5 (CO).
4.18.7.
Data
for 4-(2-chloroethoxy)phenyl
3,5-O-(di-tert-butylsilylene)-2-O-[2-O-
triisopropylsilyl-D-arabinofuranosyl]-α-D-arabinofuranoside (32) (entry 2, Table 1)
α/β =1:6.3. Rf = 0.14, light petroleum–EtOAc, 3:2. HRESIMS: found m/z 755.3332 [M + Na]+.
Calcd for C35H61ClO10Si2Na: 755.3384. Selected signals: 1H NMR (600 MHz, CDCl3): δH 0.92–
1.13 (m, 39 H, CH(CH3)2), C(CH3)3)), 3.66 (dd, J = 13.0, 3.0 Hz, 1 H, H-5Iβ-a), 3.87–3.92 (m, 4
H, CH2Cl, H-5Iβ-b, H-4IIβ), 3.92–3.99 (m, 1 H, H-5IIβ-a), 4.06–4.16 (m, 2 H, H-3Iβ, H-4Iβ), 4.19
(t, J = 5.9 Hz, 2 H, CH2O), 4.24 (dd, J = 8.1, 4.4 Hz, 1 H, H-2IIβ), 4.34 (dd, J = 9.2, 4.6 Hz, 1 H,
H-5IIβ-b), 4.50 (dd, J = 8.0, 3.9 Hz, 1 H, H-2Iβ), 4.56 (t, J = 7.8 Hz, 1 H, H-3IIβ), 5.04 (d, J = 4.5
Hz, 1 H, H-1IIβ), 5.32 (s, H-1Iα), 5.40 (s, H-1IIα), 5.50 (d, J = 3.9 Hz, 1 H, H-1Iβ), 6.82–6.87 (m,
2 H, OC6H4O), 6.95–6.99 (m, 2 H, OC6H4O). 13C NMR (151 MHz, CDCl3): δC 12.1 (CH(CH3)2),
17.8 (CH(CH3)2), 20.1 and 22.7 (C(CH3)3), 27.0 and 27.3 (C(CH3)3)), 41.9 (CH2Cl), 61.3 (C-
5Iβ), 67.2 (C-5IIβ), 68.8 (CH2O), 73.4 (C-3Iβ), 74.1 (C-3IIβ), 78.4, 78.5 (C-2IIβ, C-4), 84.6 (C-
28

4Iβ), 85.5 (C-2Iβ), 100.6 (C-1IIβ), 105.1 (C-1Iβ), 105.8 (C-1IIα), 108.2 (C-1Iα), 115.9, 117.3,
118.2 (OC6H4O), 151.5, 153.6 (OC6H4O).
4.18.8. Data for 4-(2-chloroetoxy)phenyl 3,5-O-(di-tert-butylsilylene)-2-O-[3,5-O-(di-tert-
butylsilylene)-D-arabinofuranosyl]-α-D-arabinofuranoside (33) (entry 9, Table 1)
α/β = 1:3. Rf =0.75, light petroleum–EtOAc 10:1. HRESIMS: found m/z 895.4433 [M + Na]+.
Calcd for C43H77ClO10Si3Na: 895.4405. Selected signals:1H NMR (600 MHz, CDCl3): δH 0.94–
1.20 (m, CH(CH3)2, C(CH3)3), 3.69–3.76 (m), 3.77–3.85 (m), 3.78–3.83 (m, CH2Cl), 3.85–4.02
(m), 4.05–4.18 (m), 4.19–4.22 (m, CH2O), 4.23–4.41 (m), 5.12 (d, J = 4.1 Hz, H-1IIβ), 5.15 (d, J
= 3.0 Hz, H-1IIα), 5.48 (d, J = 2.9 Hz, H-1Iα), 5.57 (d, J = 3.0 Hz, 1 H, H-1β), 6.81–6.90 (m,
OC6H4O), 6.91–7.02 (m, OC6H4O). 13C NMR (151 MHz, CDCl3): δC 12.0, 17.8 (CH(CH3)2),
22.6 and 22.7 (C(CH3)3), 27.0 and 27.3 (C(CH3)3), 41.9 (CH2Cl), 67.4, 67.5 (C-5α, C-5β), 68.8
(CH2O), 73.5, 73.7, 74.7, 76.4, 79.0, 79.2, 80.3, 88.1 (C-2α, C-2β, C-3α, C-3β, C-4α, C-4β),
101.2 (C-1IIβ), 105.9 (C-1IIα), 106.6 (C-1Iα), 109.4 (C-1Iβ), 115.7, 115.8, 117.7, 118.7
(OC6H4O), 151.5, 153.4 (OC6H4O).
4.18.9. Data for methyl 3,5-O-(di-tert-butylsilylene)-2-O-[2-O-triisopropylsilyl-D-
arabinofuranosyl]-α-D-arabinofuranoside (34) (entry 3, Table 1)
α/β =1:5.6. Rf = 0.27, light petroleum–EtOAc, 6:1. HRESIMS: found m/z 615.3356 [M +
Na]+. Calcd for C28H56O9Si2Na: 615.3356. Selected signals: 1H NMR (600 MHz, CDCl3): δH
0.10–1.03 (m, CH(CH3)2), 1.50–1.13 (m, C(CH3)3, C(CH3)3), 3.35 (s, 3 H, CH3), 3.63 (dd, J =
12.9, 2.9 Hz, 1 H, H-5Iβ-a), 3.75–3.79 (m, 1 H, H-5Iβ-b), 3.83–3.87 (m, 1 H, H-4Iβ), 3.88–3.95
(m, 2 H, H-4IIβ, H-5IIβ-a), 4.03 (t, J = 8.7 Hz, 1 H, H-3IIβ), 4.14–4.18 (m, 1 H, H-2IIβ), 4.21–4.26
(m, 1 H, H-2Iβ), 4.29–4.33 (m, 1 H, H-5IIβ-b), 4.52 (t, J = 7.7 Hz, 1 H, H-3Iβ), 4.79 (d, J = 3.0
Hz, H-1IIα), 4.83 (d, J = 3.9 Hz, 1 H, H-1IIβ), 4.96 (d, J = 4.5 Hz, 1 H, H-1Iβ), 5.26 (s, H-1Iα).
13C NMR (151 MHz, CDCl3): δC 12.2 (CH(CH3)2), 17.8 (CH(CH3)2), 22.6 (C(CH3)3), 27.3 and
27.3 (C(CH3)3)), 55.9 (CH3), 61.4 (C-5Iβ), 67.4 (C-5IIβ), 73.4, 73.6 (C-3Iβ, C-4IIβ), 78.5, 78.7
29