Ring opening of acylated β-d-arabinofuranose 1,2,5-orthobenzoates with nucleophiles allows access to novel selectively-protected arabinofuranose building blocks

Article abstract of DOI:10.1016/j.carres.2010.11.002

β-d-Arabinofuranose 1,2,5-orthobenzoates with 3-O-acetyl, 3-O-benzoyl, and 3-O-chloroacetyl groups were prepared in an efficient manner starting from readily available crystalline methyl 2,3,5-tri-O-benzoyl-α-d- arabinofuranoside, and ring-opening reactio

Full text of DOI:10.1016/j.carres.2010.11.002

Carbohydrate Research 346 (2011) 7–15
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Ring opening of acylated b-D-arabinofuranose 1,2,5-orthobenzoates with
nucleophiles allows access to novel selectively-protected arabinofuranose
building blocks
Nikita M. Podvalnyy, Sergey L. Sedinkin, Polina I. Abronina, Alexander I. Zinin, Ksenia G. Fedina,
⇑
Vladimir I. Torgov, Leonid O. Kononov
N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky prosp., 47, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 July 2010
Received in revised form 25 October 2010
Accepted 1 November 2010
Available online 5 November 2010
b-
were prepared in an efficient manner starting from readily available crystalline methyl 2,3,5-tri-O-ben-
zoyl- -arabinofuranoside, and ring-opening reactions of these compounds with O- and S-nucleophiles
were studied. Optimized conditions leading to the formation of the respective monosaccharide adducts
(up to 96% isolated yields) and to
-(1?5)-linked disaccharide thioglycosides with 50-OH unprotected
D-Arabinofuranose 1,2,5-orthobenzoates with 3-O-acetyl, 3-O-benzoyl, and 3-O-chloroacetyl groups
a
-D
a
(up to 30% isolated yields) were found. Basing on these results, a novel approach for effective differenti-
ation of 3,5-diol system and 2-hydroxy group in arabinofuranose thioglycosides was proposed. The selec-
tively protected derivatives prepared are valuable building blocks for the assembly of linear and branched
oligoarabinofuranosides.
Keywords:
Arabinofuranose
1,2,5-Orthobenzoate
Ring opening
Thioglycosides
Building blocks
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
group R at O-3 in thioglycoside C can be selectively removed in
the presence of 2-O-benzoate (such conditions are generally met if
A growing interest in the construction of
D-arabino-oligosaccha-
R = acetyl (Ac)4a or chloroacetyl (CA)4b). In addition, building block
rides related to mycobacterial cell wall components, arabinogalac-
tan, lipoarabinomannan, and arabinomannan from Mycobacterium
tuberculosis, has been developed over recent years (for leading refer-
ences see1,2) due to the necessity of creating means for diagnostics,
prevention, and treatment of human tuberculosis,3 a major world-
wide health problem taking millions of lives annually. During work
on the synthesis of oligosaccharide fragments of mycobacterial ara-
C could be used as a glycosyl donor/glycosyl acceptor for the assem-
bly of linear chains with a-(1?5) linkages.
Although various strategies have been developed for the prepa-
ration of selectively protected arabinofuranose monosaccharide
building blocks,1,2 the most versatile approach seems to be based
on the use of b-
intermediates.2 Fascinated by the apparent elegancy of this ap-
proach, which used unprotected and 3-O-alkyl b- -arabinofura-
nose 1,2,5-orthoesters,2 we attempted a synthesis of the known
b-
-arabinofuranose 1,2,5-orthobenzoate (1a)2,5 (Schemes 1 and
D-arabinofuranose 1,2,5-orthoesters as the key
binans we needed a series of 2-O-benzoyl-
D-arabinofuranose deriv-
D
atives with different protective groups at O-3 and O-5 (Scheme 1):
(1) building block A as the O-glycoside with the functionalized
aglycon serving as the glycosyl acceptor for the construction of
the (1?5)-linkage at the reducing end of the oligosaccharide chain,
(2) building block B as the 3,5-branching glycosyl acceptor with the
functionalized aglycon, (3) building block D as the 3,5-branching
unit capable of acting as a glycosyl donor, and (4) a related building
block F as the glycosyl acceptor for the construction of (1?2)-link-
age capable of functioning as a glycosyl donor (after protection of
2-OH). 2-Hydroxy block F could be prepared from 3,5-dihydroxy
building block E by simple exchange of protective groups, which
in turn can be prepared from block C provided that the protective
D
2) and subsequent ring-opening reactions of its 3-O-acyl-deriva-
tives with appropriate O- and S-nucleophiles (Schemes 3 and 4, Ta-
ble 1), which should lead to building blocks A, B, and C directly. We
were surprised to find the situation much more complex than we
expected initially based on literature data.2,5 In this report we
present the results of our studies aimed at solving problems faced
during the synthesis of the required building blocks.
2. Results and discussion
The first synthesis of the
scribedmorethan 40 yearsago byKochetkov et al.andreliedonspon-
taneous cyclization of methyl 1,2-orthobenzoate ( -enantiomer of 5)
L-enantiomer of orthoester 1a was de-
⇑
Corresponding author. Tel.: +7 499 1377570; fax: +7 499 1355328.
E-mail addresses: kononov@ioc.ac.ru, leonid.kononov@gmail.com (L.O. Kono-
nov).
L
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.11.002

8
N. M. Podvalnyy et al. / Carbohydrate Research 346 (2011) 7–15
HO
OBz
O
O
HO
X
OCA
A1
OBz
O
O
HO
OBz
X
O
OH
B
O
HO
Ref. 2
X
OBz
OBz
O
O
A2
Ph
CAO
OBz
O
O
O
X
OR
O
O
A
SR1
(R = Bz,CA)
OCA
D
OR
1a
1b
1c
1d
1e
(R = H)
R2O
HO
O
HO
(R = Bn) [Ref. 2]
(R = Ac)
OBz
SR1
OBz
OH
O
O
(R = Bz)
SR1
SR1
(R = CA)
R2O
OR
C
(R = Ac,Bz,CA)
OH
F
E
Scheme 1. Various arabinofuranose building blocks (A–F) accessible from 3-hydroxy- and 3-O-acyl-b-
D-arabinofuranose 1,2,5-orthobenzoates (1a,c–e); X = Cl or protected
functional group, R1 = Et or Ph, R2 = protective group(s), CA = ClCH2CO.
OMe
Ph
BzO
BzO
BzO
O
OBz
OBz
X
O
Ref. 8
a
b
c
O
O
O
D-(—)-arabinose
OMe
OBz
2
OBz
OBz
j or k
3a X = Cl
4
3b X = Br
OMe
O
Ph
Ph
Ph
HO
O
O
O
O
O
O
O
O
O
d, e or f
g,h or i
O
OH
OH
OR
5
1a
1c R = Ac
1d R = Bz
1e R = CA
Scheme 2. Synthesis of 3-O-acyl-b-D-arabinofuranose 1,2,5-orthobenzoates (1c–e). Reagents and conditions: (a) MeOCHCl2, SnCl4, CH2Cl2 (for 3a); (b) MeOH, n-Bu4NBr, Et3N,
molecular sieves 3 Å, CH2Cl2 (89% over two steps via 3a); (c) (1) NaOMe, MeOH; (2) silica gel column chromatography (79% of 5 and 8% of 1a); (d) CSA, CH2Cl2, MS 4 Å in the
reaction mixture, ꢀ20 °C (59–85%); (e) MgBr2, THF, 55 °C (78%); (f) TsOHꢁH2O, (CH2)2Cl2, molecular sieves 4 Å in the trap of a Soxhlet adapter, reflux, 90%; (g) Ac2O, Py (97% of
1c); (h) BzCl, Py (94% of 1d); (i) (ClCH2CO)2O, symm-collidine, CH2Cl2, (94% of 81e); (j) (1) HBr, CH2Cl2, 0 °C; (2) conditions as in (b); (3) conditions as in (c); (4) conditions as in
(f) (70% over four steps via 3b); (k) (1) HBr, AcOH, ꢀ20 °C; (2) conditions as in (b); (3) conditions as in (c); (4) conditions as in (f) (62% over four steps via 3b).
upon chromatography on deactivated Al2O3 or during prolonged dry-
Ph
ing of L-5 invacuo overP2O5 (Scheme2).5a However, the success of the
O
HO
original approach relied on use of several variables that need to be
carefully controlled: solvent preparation procedures, Al2O3 deactiva-
tion protocol, the absense of traces of a base (originally 2,6-lutidine)
used for the preparation of bicyclic orthoester L-5, etc. Not surpris-
ingly, over the years ‘slight modifications’2 of the initial procedure5a
were made. Although substantial changes in preparation of the
intermediate chloride (L-3a)6 and O-benzoylated methyl 1,2-ortho-
benzoate (L-4)7 were introduced and adequately described, the de-
tails of the two last steps and especially of the cyclization step
leading to the tricyclic orthoester 1a were not disclosed.2 The
importance of chromatographic purification of dihydroxy orthoester
5 on ‘triethylamine-deactivated silica’ prior to ring-closingreaction as
O
a, b or c
O
OBz
O
O
O
OR
Cl
OR
1a R = H
1d R = Bz
1e R = CA
6a R = H
6b R = Bz
6c R = CA
Scheme 3. Ring opening of 3-hydroxy- and 3-O-acyl-b-
D
-arabinofuranose 1,2,5-
orthobenzoates (1a,d,e) with 2-chloroethanol. Reagents and conditions: (a)
Cl(CH2)2OH (neat), SnCl4, 0 °C?ꢀ20 °C (76% of 6a, only ); (b) Cl(CH2)2OH (neat),
SnCl4, 0 °C?ꢀ20 °C (96% of 6b, only ); (c) Cl(CH2)2OH (neat), SnCl4, ꢀ20 °C (78% of
6c, only ).
a
a
a

N. M. Podvalnyy et al. / Carbohydrate Research 346 (2011) 7–15
9
Table 1
Conditions and products of reactions of 3-O-acyl-b-D-arabinofuranose 1,2,5-orthobenzoates 1c–e with thiols R1SH (see Scheme 4)a
Entry Orthoester
R
R1 Amount of 1,
mmol
Amount of SnCl4
(equiv)
Amount of R1SH
(equiv)
Reaction
Monosaccharide
(yield, %)c
Disaccharide
(yield, %)c
temperatureb (°C)
1
2
3
4
5
6
7
8
1c
1c
1c
1c
1d
1d
1e
1e
1e
1e
1e
1e
1b
1b
Ac Et
Ac Et
Ac Ph 0.72
Ac Ph 0.18
Bz Et
Bz Ph 0.15
CA Et
CA Et
CA Ph 0.16
CA Ph 0.64
CA Ph 1.60
CA Ph 0.16
1.80
0.13
0.14
0.3
0.2
0.3
0.27
0.3
0.1
0.1
0.35
0.26
0.25
0.3
1.2d
5.0e
1.2d
5.0e
5.0e
5.0e
2.4d
5.0d
4.5h
4.5e
4.5e
18.3e
1.2d
3.0d
ꢂ15
ꢂ25
ꢂ15
ꢂ25
ꢂ25
ꢂ25
ꢂ25
ꢂ25
ꢂ28
ꢂ28
ꢂ28?ꢂ4
ꢂ28
ꢂ15
ꢂ18
7a (70)
7a (62)
7b (66)
7b (60)
8a (85)f
8b (72)f
9a (76)
9a (94)
9b (62)
9b (68)
9b (62)
9b (67)
10 (77)j
14 (62)j
11a (27)
11a (12)
11b (30)
11b (27)
12a (12)g
12b (11)g
13a (16)
ndi
0.15
1.61
0.64
9
13b (25)
13b (17)
13b (23)
ndi
10
11
12
13
14
Bn Et
Bn Et
12.4
0.10
0.1
2.1
ndi
ndi
a
b
c
d
e
f
Published2 results of reactions of of 3-O-benzyl-b-
Bath temperature.
Isolated yields after silica gel chromatography.
D-arabinofuranose 1,2,5-orthobenzoate (1b) with EtSH are also presented for comparison.
The reaction was performed in the presence of molecular sieves 3 Å.
The reaction was performed in the presence of molecular sieves 4 Å.
Portions of compounds 8a (11%) and 8b (10%) were obtained as mixtures with the corresponding disaccharides 12a and 12b, the combined yields were calculated from 1
H
NMR spectra.
g
Compounds 12a and 12b were obtained as mixtures with the corresponding monosaccharides 8a and 8b, the yields were calculated from 1H NMR spectra.
The reaction was performed in the absence of molecular sieves.
The yield was not determined.
h
i
j
See Ref. 2.
HO
OBz
O
O
Ph
O
HO
HO
a
O
OR
OBz
SR1
SR1
O
OBz
OBz
O
O
O
OH
+
+
SR1
SR1
OR
1b—e
OR
OR
OR
14 R = Bn, R1 = Et
7a,b—9a,b,10
11a,b—13a,b
1
1
1b
7a
7b
11a
11b
R = Bn
R = Ac, R = Et
R = Ac, R = Et
1
1
1c R = Ac
1d R = Bz
R = Ac, R = Ph
R = Ac, R = Ph
8a R = Bz, R1 = Et
8b R = Bz, R1 = Ph
12a R = Bz, R1 = Et
12b R = Bz, R1 = Ph
1e
R = CA
9a R = CA, R1 = Et
13a R = CA, R1 = Et
1
1
9b
10
13b
R = CA, R = Ph
R = CA, R = Ph
1
R = Bn, R = Et
Scheme 4. Ring opening of 3-O-substituted b-D
-arabinofuranose 1,2,5-orthobenzoates (1b–e) with thiols R1SH. Reagents and conditions: (a) R1SH, CH2Cl2 (see Table 1 for the
details); R1 = Et or Ph.
well as the use of ‘large quantities of 4 Å molecular sieves (MS) to
trap the released methanol’ in the cyclization step was only
emphasized.2
the acid concentration is lower than the threshold—no reaction of
cyclization of 5 takes place at all. Molecular sieves added to the
reaction mixture to trap the released methanol are basic and do
bind sulfonic acid (TsOH5 or camphorsulphonic acid (CSA)2), thus
reducing the overall acidity of the medium. The necessity to attain
the fragile optimum acidity in the reaction mixture makes this
reaction difficult to reproduce and especially to scale-up. In our
hands, the yields of 1a obtained by this procedure2 varied from
59% to 85% depending on the scale (cf. the published2 yield of 86%).
In an attempt to solve the reproducibility problem (which is
very annoying on a large scale) we have developed new conditions
for the cyclization of 5, which relied on the use of MgBr2 in THF, the
yield of tricyclic orthoester 1a consistently being ꢀ78%.9 However,
it is important to stress that the highest yields of 1a (ꢀ90% after
crystallization of the product) were repeatedly achieved by follow-
ing another procedure suggested many years ago by Bochkov
et al.,5b in which the cyclization was effected by heating at reflux
in a solution of 5 in 1,2-dichloroethane containing TsOHꢁH2O. The
Because the chemistry of arabinose orthoesters is not trivial, we
had to optimize these steps independently and now report for the
first time the overall procedure for the reliable preparation of the
tricyclic orthoester 1a starting from the readily available8 crystal-
line methyl arabinofuranoside 2. The details of the procedures that
we used are described in the experimental part and in the Supple-
mentary data section. We wish to comment mainly on the trans-
formation of the bicyclic orthoester 5 to the tricyclic orthoester
1a. In our opinion, the most recently published procedure2 for
the transformation of 5 to 1a is far from being optimal. The prob-
lem is obvious and well-known2—both the starting compound 5
and the cyclization product 1a are acid-sensitive compounds while
the cyclization reaction itself is catalyzed by an acid. For these rea-
sons, if the acid concentration exceeds the threshold level required
for cyclization of 5, the primary product 1a polymerizes,5c while if

10
N. M. Podvalnyy et al. / Carbohydrate Research 346 (2011) 7–15
key feature of the latter procedure is that the released methanol is
trapped by molecular sieves, which are placed in a Soxhlet-type
adapter, that is, physically separated from the reactants rather than
added to the reaction mixture as in the procedure developed by
Prandi and co-workers.2 Such experimental design completely
solves the problem of controlling acidity of the reaction medium
thus ensuring high and reproducible yields of the target orthoester
1a. For this reason we recommend this advanced procedure5b for
the preparation of large quantities of the target orthoester 1a.
We also wish to emphasize that arabinofuranosyl chloride 3a6
in the reaction leading to bicyclic orthobenzoate 42,7 can be re-
placed with the corresponding bromide 3b8a (Scheme 2). Earlier,
obtained as the single a-isomer (isolated in 96% yield) only when
2-chloroethanol was used as the reaction solvent (Scheme 3).
Similarly, 3-O-chloroacetyl derivative 1e reacted with 2-chloroeth-
anol to give the corresponding a-arabinofuranoside 6c which was
isolated in 78% yield (Scheme 3). These reactions furnished build-
ing blocks A1 and A2 (Scheme 1). Compound 6a (building block B
in Scheme 1) was prepared directly from 3-O-unsubstituded
orthoester 1a in 76% yield (Scheme 3) (cf. Ref. 2).
Reaction of 3-O-acyl-orthoesters 1c–1e with thiols (EtSH or
PhSH) catalyzed by SnCl4 proceeded differently than was earlier re-
ported2 for the similar reactions of 3-O-benzyl-b-
D-arabinose 1,2,5-
orthobenzoate 1b (and other 3-O-alkyl derivatives) with EtSH. The
use of conditions recommended in Ref. 2, that is, a nearly equiva-
lent amount (1.2 equiv) of EtSH or PhSH, in reactions with of 3-
L-enantiomer of glycosyl bromide L-3b, prepared from methyl
arabinofuranoside L-2, was successfully used for the preparation
of orthoester L-4, isolated in 77% yield.5a However, later other
researchers2,7 abandoned the use of arabinofuranosyl bromide 3b
in favor of arabinofuranosyl chloride 3a because of ‘superior stabil-
ity’ of the latter.7 In our view, this attitude was based mainly on
low stability of bromide 3b in polar AcOH and technical problems
faced during work-up of the acidic reaction mixture since glycosyl
bromide 3b was originally prepared from methyl arabinofurano-
side 2 by treatment with HBr in AcOH.5a,8a Nevertheless, it was
tempting to use glycosyl bromide 3b for the preparation of ortho-
ester 4 because HBr is much cheaper than MeOCHCl2 required for
the synthesis of glycosyl chloride 3a from methyl glycoside 2. We
surmised that the use of HBr (generated from AcBr and MeOH)10 in
less polar CH2Cl2 (similar procedure has been described for gener-
ation of other labile glycosyl bromides under mild conditions)10c,d
would simplify isolation of glycosyl bromide 3b (no need to neu-
tralize excess AcOH) without compromising overall yield of 4.
Indeed, treatment of methyl glycoside 2 with HBr in CH2Cl2
smoothly gave glycosyl bromide 3b, which was immediately trans-
formed into 1,2-orthobenzoate 4. The latter was saponified to give
after chromatographic purification 5, which was transformed into
tricyclic orthoester 1a in 70% overall yield (with respect to 2) using
the advanced procedure5b described above. This yield is compara-
ble with that obtained by step-wise preparation of 1a via glycosyl
chloride 3a (74%) (Scheme 2). It is worthy of note that in our hands
the use of glycosyl bromide 3b generated by HBr in AcOH gave
somewhat lower overall yield of 1a (62%).
O-acetyl-b-D-arabinose 1,2,5-orthobenzoate 1c gave the expected
(cf. Ref. 2) monosaccharide thioglycosides 7a,b in 66–70% yields
(entries 1,3 in Table 1), which are comparable to those reported2
for reactions of 3-O-benzyl-b-D-arabinose 1,2,5-orthobenzoate 1b
(cf. entry 13 in Table 1). Unexpectedly, the remaining part of the
product was the disaccharide thioglycosides 11a,b isolated in
27–30% yields (entries 1,3 in Table 1), the latter apparently arising
from reaction of 5-OH group of the primary adducts 7a,b with
orthoester 1c (see Scheme 4 and Table 1). This reaction is the first
step in the known Lewis acid-catalyzed polymerization of arabi-
nose 1,2,5-orthoesters in the presence of alcohols.5c
The use of excess EtSH or PhSH (5 equiv) in reaction with ortho-
ester 1c did not change the ratio between monosaccharide adducts
7a,b and disaccharide thioglycosides 11a,b considerably (entries 2
and 4 in Table 1). This result is completely unexpected because
the corresponding dithioacetal 14 of the open form (entry 14 in Ta-
ble 1) has earlier been reported2 to be formed in a similar reaction
of 3-O-benzyl-b-D-arabinose 1,2,5-orthobenzoate (1b) with moder-
ate excess of EtSH (3 equiv). Moreover, we have never managed to
isolate dithioacetals similar to 14 from the reactions of 3-O-acyl-
ated orthoesters 1c–e with thiols. Similarly, the ratio between the
monosaccharide and the disaccharide products (8a,b and 12a,b,
respectively) did not change considerably when 3-O-benzoyl-b-D-
arabinose 1,2,5-orthobenzoate (1d) was involved into reaction with
excess EtSH or PhSH (5 equiv) (entries 5 and 6 in Table 1). Reaction
of 3-O-chloroacetyl-b-D-arabinose 1,2,5-orthobenzoate (1e) with
Acylation of the single free hydroxyl group b-
D
-arabinofuranose
PhSH also gave mixtures of both monosaccharide and disaccharide
products 9b and 13b, respectively. The use of excess PhSH (up to
18 equiv) did not change the yield significantly; the highest yield
of 3-O-chloroacetyl-arabinofuranoside phenyl thioglycoside 9b
being 68% (entries 9–12 in Table 1).
1,2,5-orthobenzoate (1a) with Ac2O, BzCl, and chloroacetic anhy-
dride cleanly afforded the respective 3-O-acyl-derivatives 1c–1e
in high yields (Scheme 2). It is instructive to note that while acet-
ylation and benzoylation were routinely performed in pyridine as
the solvent (also acting as a base) without any complications, the
use of pyridine as the medium for O-chloroacetylation, although
reported,4b should be generally discouraged. The reaction mixtures
are usually dark colored apparently due to side reactions initiated
by quaternization of pyridine nitrogen with chloroacetyl deriva-
tives (including the target esters). More importantly, not only does
this side reaction influence the appearance of the reaction mixture,
but also substantially decreases the yield of the target ester (data
not shown). The use of more sterically hindered base, such as
sym-collidine, in CH2Cl2 as the solvent resulted in clear reaction
mixture, from which the chloroacetate 1e was isolated in 94%
yield.
By contrast, the outcome of the reaction of 3-O-chloroacetyl-b-
D-arabinose 1,2,5-orthobenzoate (1e) with EtSH greatly depended
on the amount of the thiol taken. The use of a moderate excess
of EtSH (2.4 equiv) gave 76% of the monosaccharide adduct 9a to-
gether with 16% of the disaccharide thioglycoside 13a (entry 7 in
Table 1) similarly to other examples in Table 1. The use of excess
EtSH (5 equiv) in reaction with orthoester 1e resulted in clean for-
mation of monosaccharide ethyl thioglycoside 9a with 3-O-chloro-
acetyl group in 94% yield as the only isolable product (entry 8 in
Table 1).
Summarizing all the results, we may conclude that, generally,
two major products were formed in all cases—the expected (cf.
Ref. 2) monosaccharide adducts 7–9 and previously unknown
disaccharide thioglycosides 11–13 (in ꢀ2:1–7:1 ratio). The high
combined yield of monosaccharide and disaccharide thioglycosides
(85–97%) clearly indicates that further oligomerization of the
orthoester (cf. Ref. 5c) is largely suppressed under the conditions
used. It is important to note that the use of PhSH usually gave high-
er proportions of disaccharide product than the use of EtSH (see Ta-
ble 1). This result could be attributed to the lower nucleophilicity of
PhSH in comparison to that of EtSH, a feature that makes competing
Having prepared tricyclic orthoesters 1c–e with acyl groups at
O-3, we studied their reactions with nucleophiles (Schemes 3
and 4, Table 1). The known 3-O-benzyl-1,2,5-orthobenzoate (1b)
was reported to react with fivefold excess of alcohols in the pres-
ence of Lewis acids (both BF3ꢁEt2O and SnCl4 were equally effective
in these reactions) in CH2Cl2 to give the corresponding alkyl glyco-
sides exclusively with
a
-configuration.2 However, in the case of
reaction of 3-O-benzoyl-derivative 1d with 2-chloroethanol the
corresponding 2-chloroethyl arabinofuranoside 6b could be

N. M. Podvalnyy et al. / Carbohydrate Research 346 (2011) 7–15
11
reaction with 5-OH group of the monosaccharide adduct initially
formed more favorable when PhSH is used. It is interesting that
the presence or type of molecular sieves does not considerably
influence the yields or the products ratio (see Table 1).
procedures. Column chromatography was performed on Silica Gel
60 (40–63 m, Merck). Thin-layer chromatography was carried
l
out on plates with Silica Gel 60 on glass or on aluminum foil
(Merck). Spots of compounds were visualized under UV light and
by heating the plates after immersion in a 1:10 (v/v) mixture of
85% aqueous H3PO4 and 95% EtOH. The 1H, and 13C NMR spectra
were recorded for solutions in CDCl3 or DMSO-d6 on a Bruker AC-
200 instrument (200.13 and 50.32 MHz, respectively), a Bruker
AM-300 instrument (300.13 and 75.48 MHz, respectively), or on
a Bruker AVANCE 600 spectrometer (600.13 and 150.9 MHz,
respectively). The 1H NMR chemical shifts are referred to the resid-
ual signal of CHCl3 (dH 7.27) or DMSO-d5 (dH 2.50), the 13C NMR
shifts—to the CDCl3 signal (dC 77.0) or DMSO-d6 (dC 39.5). Assign-
ments of the signals in the NMR spectra were performed using
2D-spectroscopy (COSY, HSQC, NOESY) and APT (DEPT-135 or
JMODXH) experiments. The copies of NMR spectra of previously
unknown compounds, for which combustion analysis has not been
obtained, can be found in the Supplementary data section. High
resolution mass spectra (electrospray ionization, HRESIMS) were
Because 3-O-chloroacetyl group in compounds 9a,b can be
selectively removed in the presence of 2-O-benzoyl group,4b an
easy and efficient access to compound 9a found in this work opens
up a novel way to 3,5-dihydroxy-arabinofuranose thioglycosides
with protective group at O-2 (building block E in Scheme 1). Sim-
ilarly, 3-O-acetyl-derivatives 7a,b can be transformed to the same
3,5-diols E with 2-O-benzoyl protection by acid-catalyzed methan-
olysis4a by HCl in MeOH. Such arabinose thioglycosides with 3,5-
hydroxy groups selectively unprotected (similar to building block
E) have previously been accessible mainly by making use of selec-
tive temporary protection of 3,5-diol function in arabinofuranose
2,3,5-triols (giving building block F in Scheme 1) with organosil-
icon protective groups (e.g., TIPDS1c and DTBS1b) by fairly expen-
sive reagents or introduction of 1,2-O-isopropylidene group into
5-silylated arabinose11 and subsequent elaboration1g of 1,2-diol.
The importance of our finding is not limited to oligosaccharide
synthesis only since the known syntheses of a variety of nucleoside
analogs12 (e.g., potential antivirals13) often rely on effective differ-
entiation of 3,5-diol system4c,d and 2-hydroxy group in furanose
derivatives.
recorded on
a Bruker micrOTOF II mass spectrometer for
2 ꢃ 10ꢂ5 M solutions in MeCN or MeOH. Optical rotations were
measured using a PU-07 automatic polarimeter (Russia).
4.2. b-
D
-Arabinofuranose 1,2,5-orthobenzoate (1a)
These previously unknown features of ring opening of 3-O-acyl-
b-
D
-arabinofuranose 1,2,5-orthobenzoates made possible facile
Methyl 2,3,5-tri-O-benzoyl-a-D
-arabinofuranoside (2)8 (20.0 g,
preparative syntheses of monosaccharide and disaccharide adducts
with thiols. Although other routes to selectively protected arabin-
ofuranose thioglycosides could be devised1,2,11 no other simple
42.0 mmol) was dissolved in anhydrous CH2Cl2 (120 mL) and
cooled to 0 °C, then acetyl bromide (17.25 mL, 0.233 mmol) was
added. A solution of MeOH (7.65 mL, 0.189 mmol) in CH2Cl2
(20 mL) was added dropwise, and the reaction mixture was stirred
at 0 °C for 2 h. The reaction mixture was diluted with CH2Cl2
(500 mL), washed with ice-cold water (ice was always present in
the separation funnel!) twice (500 and 700 mL) and ice-cold satd
NaHCO3 (700 mL; with ice), filtered through cotton wool plug, con-
centrated under reduced pressure (bath temperature ꢀ30 °C), and
routes to
a
-(1?5)-linked disaccharide thioglycosides with 50-OH
unprotected are feasible. It is important to note that our approach
does allow preparation of disaccharide thioglycosides 11–13
(Scheme 4 and Table 1). These compounds contain unprotected
50-OH group, which can easily be protected with an orthogonal
protective group. This feature makes disaccharide thioglycosides
11–13 useful building blocks (serving as both glycosyl donors
dried in vacuo to give 2,3,5-tri-O-benzoyl-a-D-arabinofuranosyl
and acceptors) for the assembly of linear chains with
a
-(1?5)-
bromide 3b (Rf = 0.69, C6H6–EtOAc 9:1) as a white foam, which
was immediately used in the next step without additional
purification.
linkages. Especially valuable are the compounds 11a,b with 3-O-
acetyl groups, which can be prepared in 27–30% yields (entries
1,3,4 in Table 1). The moderate yield is compensated by the small
number of steps required for their preparation as compared with
the synthesis of similarly protected disaccharide derivatives by
step-wise approach based on conventional glycosylation proce-
dures and protection/deprotection reactions. This one-step ap-
proach discovered by us can substantially ease the synthesis of
The crude glycosyl bromide 3b was dissolved in anhydrous 2,6-
lutidine (20 mL, 171 mmol), and anhydrous MeOH (100 mL,
2.47 mol) was added. The mixture was kept at ꢀ20 °C for 1 h, then
MeOH was evaporated (bath temperature 35–40 °C), the residue
was dissolved in CH2Cl2 (200 mL), washed with water (200 mL),
1 M KHSO4 (160 mL) and satd NaHCO3 (200 mL). The black organic
layer was filtered through cotton wool plug and concentrated to
dryness. The residue was extracted with 2:1 (v/v) light petro-
leum–AcOEt mixture (400 mL + 3 ꢃ 50 mL), the combined extracts
were filtered through a silica gel layer (4 cm) on a glass filter, the
solids were washed with large volume (600 mL) of light petro-
leum–AcOEt mixture (6:4, v/v). The filtrate (1 L) was concentrated
to dryness, the residue was dried in vacuo to give dibenzoate 4
(18.80 g, Rf = 0.69, C6H6–EtOAc 9:1) as a lightly yellow sirup, which
was used without additional purification in the next step.
To a solution of dibenzoate 4 (18.80 g, 39.46 mmol) in anhy-
drous MeOH (100 mL), 1 M solution of MeONa in MeOH (4.2 mL,
4.2 mmol) was added. The mixture was kept at room temperature
long a-(1?5)-linked arabino-oligosaccharides.
3. Conclusions
In conclusion, we have studied ring opening of 3-O-acyl-b-D-
arabinofuranose 1,2,5-orthobenzoates with O- and S-nucleophiles
and developed conditions leading to the formation of the respec-
tive monosaccharide adducts and to
a-(1?5)-linked disaccharide
derivatives with 50-OH unprotected. These compounds themselves
and the related compounds, which can be prepared from them in a
few steps, are novel building blocks for the assembly of linear and
branched oligoarabinofuranosides.
þ
for 16 h, then neutralized with Dowex 50ꢃ8 (HNEt3 form), fil-
tered, solids were washed with MeOH (100 mL). The solution
was concentrated under reduced pressure; the residue was sepa-
rated by chromatography on silica gel column (10% acetone in ben-
zene + 0.2% NEt3?40% acetone in benzene + 0.2% NEt3) to give a
4. Experimental
4.1. General methods
mixture (9.35 g) of b-
D-arabinofuranose 1,2-(methyl)orthobenzo-
The reactions were performed with the use of commercial re-
agents (Aldrich, Fluka, Acros Organics) and distilled solvents puri-
fied and dried (where appropriate) according to standard
ate (5, Rf = 0.30, C6H6–acetone, 7:3) and b-
1,2,5-orthobenzoate (1a, Rf = 0.50, C6H6–acetone, 7:3) as a colorless
sirup.
D
-arabinofuranose

12
N. M. Podvalnyy et al. / Carbohydrate Research 346 (2011) 7–15
This mixture was coevaporated with toluene (3 ꢃ 20 mL), dried
light petroleum–AcOEt, 5:1) as white crystals. Mp 146–147 °C
in vacuo, dissolved in anhydrous 1,2-dichloroethane (110 mL) and
refluxed with molecular sieves 4 Å (ꢀ15 g), placed in Soxhlet-type
adapter,5b for 30 min. Then a solution of anhydrous TsOH in 1,2-
dichloroethane [prepared from TsOHꢁH2O (6.3 mg, 0.033 mmol)
and anhydrous 1,2-dichloroethane (12 mL) using 4 Å (15 g) as de-
scribed in Method C, part S4.4.3 in the Supplementary data section]
was added. The resulting mixture was refluxed with the same por-
tion of molecular sieves 4 Å (ꢀ15 g), placed in Soxhlet-type adap-
ter,5b for an additional 20 min, then quenched with Py (0.1 mL,
1.2 mmol), cooled, and concentrated to dryness. The residue was
crystallized from benzene–petroleum ether to give 1a (6.90 g,
70%, Rf = 0.56, C6H6–acetone, 6:4) as white crystals. Mp 147–
(lit.5a for L-1d 146–148 °C); ½a 2D0
ꢄ
ꢂ68.6 (c 1.0, CH2Cl2) (lit.5a for L-
1d [
a]
+75(c 1, CHCl3). Anal. Calcd for C14H14O6: C, 67.05; H,
D
4.74. Found: C, 67.56; H, 4.65. HRESIMS: found m/z 363.0847
[M+Na]. Calcd for C19H16NaO6: 363.0845. 1H NMR (200.13 MHz,
CDCl3): dH 4.22 (d, 2H, J4,5 = 2.2 Hz, H-5a, H-5b), 4.67–4.71 (m,
1H, H-4), 4.98 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 1.5 Hz, H-2), 5.59 (s, 1H,
H-3), 6.21 (d, 1H, J1,2 = 3.8 Hz, H-1), 7.35–7.54 (m, 5H, Ph), 7.57–
7.74 (m, 3H, PhCO), 8.03–8.14 (m, 2H, PhCO). 13C NMR
(75.48 MHz, CDCl3): dC 68.6 (C-5), 78.6 (C-4), 81.4, 81.6 (C-2, C-
3), 103.8 (C-1), 121.4 (PhC), 125.9, 128.0, 128.5, 129.1, 129.6,
129.8, 133.6, 135.7 (Ph), 165.5 (PhCO).
150 °C (lit.5a for L-1a 148–149 °C); ½a 1D6
ꢄ
ꢂ36.0 (c 1.0, DMF), ½a D25
ꢄ
4.5. 3-O-Chloroacetyl-b-D-arabinofuranose 1,2,5-orthobenzoate
(1e)
ꢂ28.2 (c 1.0, CHCl3), lit.2 ꢂ28 (c 0.9, CHCl3). Anal. Calcd for
C
12H12O5: C, 61.01; H, 5.12. Found: C, 61.07; H, 5.27. 1H NMR
(300.13 MHz, DMSO-d6): dH 3.89 (dd, 1H, J5a,5b = 12.8 Hz,
J5a,4 = 1.5 Hz, H-5a), 4.03 (dd, 1H, J5b,4 = 2.9 Hz, H-5b), 4.24 (d, 1H,
J3,OH = 3.9 Hz, 3-OH), 4.34–4.38 (m, 1H, H-4), 4.62 (dd, 1H,
J3,OH = 3.9 Hz, J3,4 = 1.3 Hz, H-3), 5.53 (d, 1H, J1,2 = 4.0 Hz, H-2),
6.14 (d, 1H, J1,2 = 4.0 Hz, H-1), 7.33–7.42 (m, 3 H, Ph), 7.49–7.58
(m, 2 H, Ph). 13C NMR (75.48 MHz, DMSO-d6): dC 68.5 (C-5), 76.0,
83.16, 83.24 (C-2, C-3, C-4), 103.5 (C-1), 120.0 (PhC), 125.8,
127.8, 129.2, 136.6 (Ph). 1H NMR (300.13 MHz, CDCl3): dH 2.10
(d, 1H, J3,OH = 7.2 Hz, 3-OH), 4.06 (dd, 1H, J5a,5b = 13.0 Hz,
J4,5a = 3.0 Hz, H-5a), 4.14 (dd, 1H, J5a,5b = 13.0 Hz, J4,5b = 1.1 Hz, H-
5b), 4.39–4.43 (m, 1H, H-4), 4.50 (d, 1H, J3,OH = 7.2 Hz, H-3), 4.71
(dd, 1H, J1,2 = 3.8 Hz, J2,3 = 1.5 Hz, H-2), 6.13 (d, 1H, J1,2 = 3.8 Hz,
H-1), 7.37–7.42 (m, 3H, Ph), 7.61–7.68 (m, 2H, Ph). 13C NMR
(75.48 MHz, CDCl3): dC 68.3 (C-5), 77.2, 83.7, 83.8 (C-2, C-3, C-4),
103.7 (C-1), 121.1 (PhC), 125.9, 128.1, 129.5, 135.9 (Ph).
To the solution of b-D-arabinofuranose 1,2,5-orthobenzoate 1a
(1.43 g, 6.05 mmol) in anhydrous CH2Cl2 (8.0 mL) symm-collidine
(3.24 mL, 24.32 mmol) was added. The mixture was cooled (ice-
water bath), and the solution of monochloroacetic anhydride
(1.85 g, 10.81 mmol) in CH2Cl2 (5 mL) was added dropwise and
the mixture was stirred at this temperature. After 30 min TLC
showed the reaction was complete. The mixture was diluted with
CH2Cl2 (150 mL), washed with satd aq NaHCO3 (100 mL), 1 M
KHSO4 (100 mL), satd aq NaHCO3 (100 mL), filtered through a layer
of ꢀ1:1 (v/v) silica gel–powdered Na2SO4 mixture, evaporated,
dried in vacuo to give 1e (1.770 g, 94%; Rf = 0.59, benzene–AcOEt,
4:1) as white crystals. Mp 128–129 °C (from EtOAc–light petro-
leum). ½a 1D6
ꢂ36.1 (c 1.0, CH2Cl2). HRESIMS: found m/z 313.0473
ꢄ
[M+H]. Calcd for C14H14ClO6: 313.0473. 1H NMR (200.13 MHz,
CDCl3): dH 4.12 (s, 2H, ClCH2), 4.14 (d, 2H, J4,5 = 2.1 Hz, H-5a, H-
5b), 4.53–4.57 (m, 1H, H-4), 4.84 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 1.7 Hz,
H-2), 5.38 (s, 1H, H-3), 6.12 (d, 1H, J1,2 = 3.8 Hz, H-1), 7.34–7.43
(m, 3H, Ph), 7.60–7.67 (m, 2H, Ph). 13C NMR (75.48 MHz, CDCl3):
dC 40.4 (ClCH2), 68.3 (C-5), 79.5 (C-4), 81.0, 81.1 (C-2, C-3), 103.6
(C-1), 121.4 (PhC), 125.8, 128.0, 129.6, 135.3 (Ph), 166.4 (CO).
4.3. 3-O-Acetyl-b-
D
-arabinofuranose 1,2,5-orthobenzoate (1c)
-arabinofuranose 1,2,5-orthobenzoate 1a
To the solution of b-
D
(1.00 g, 4.23 mmol) in anhydrous Py (5 mL, 62 mmol) acetic anhy-
dride (0.8 mL, 8.47 mmol) was added followed by DMAP (5 mg,
0.041 mmol). After 3 h the mixture was cooled (ice-water bath),
and MeOH (1 mL, 25 mmol) was added. The mixture was stirred
for 5 min, diluted with benzene, washed with satd NaHCO3, filtered
through a layer of ꢀ1:1 (v/v) Celite-powdered Na2SO4 mixture,
concentrated, and dried in vacuo. The residue was crystallized
from benzene–light petroleum to give 1c (1.144 g, 97%; Rf = 0.34,
light petroleum–AcOEt, 3:1; Rf = 0.48, benzene–AcOEt, 9:1) as
4.6. 2-Chloroethyl 2-O-benzoyl-a-D-arabinofuranoside (6a)
Tin tetrachloride (124.5
0.106 mmol) was added to the cold (ice-water bath) solution of
-arabinofuranose 1,2,5-orthobenzoate 1a (500 mg, 2.12 mmol)
lL of 10% (v/v) soln in CH2Cl2,
D
in 2-chloroethanol (7.5 mL, 110 mmol). The reaction mixture was
allowed to warm to room temperature (ꢀ20 °C). After 1.5 h of stir-
ring at that temperature TLC showed the complete conversion and
satd aqueous NaHCO3 solution (2 mL) was added. The mixture was
diluted with CH2Cl2 (100 mL), organic layer was washed with satd
NaHCO3 (75 mL), filtered through a cotton wool plug, concentrated,
the residue was coevaporated with toluene (2 ꢃ 20 mL), dried in
vacuo, and purified by silica gel column chromatography (tolu-
ene–ethyl acetate) to give 6a (504 mg, 76%; Rf = 0.39, toluene–ace-
white crystals. Mp 129–131 °C (lit.5a for L-1c 128–130 °C); ½a 1D7
ꢄ
ꢂ46.7 (c 1.0, CH2Cl2) (lit.5a for L-1c [
a]D +62 (c 1, CHCl3). Anal. Calcd
for C14H14O6: C, 60.43; H, 5.07. Found: C, 60.64; H, 4.94. 1H NMR
(200.13 MHz, CDCl3): dH 2.13 (s, 3H, Ac), 4.14 (d, 2H, J4,5 = 2.1 Hz,
H-5a, H-5b), 4.48–4.57 (m, 1H, H-4), 4.82 (dd, 1H, J1,2 = 3.7 Hz,
J2,3 = 1.5 Hz, H-2), 5.31 (br s, 1H, H-3), 6.12 (d, 1H, J1,2 = 3.7 Hz, H-
1), 7.34–7.43 (m, 3H, Ph), 7.60–7.70 (m, 2H, Ph). 13C NMR
(75.48 MHz, CDCl3): dC 20.8 (CH3CO), 68.4 (C-5), 78.2 (C-4), 81.3,
81.4 (C-2, C-3), 103.7 (C-1), 121.3 (PhC), 125.8, 128.0, 129.5,
135.6 (Ph), 169.9 (CH3CO).
tone, 3:2) as a colorless sirup. ½a D22
ꢄ
+58.8 (c 1.0, CH2Cl2). HRESIMS:
found m/z 339.0602 [M+Na]. Calcd for C14H17ClNaO6: 339.0606. 1H
NMR (300.13 MHz, CDCl3): dH 2.20 (br s, 1H, OH), 3.46 (br s, 1H,
OH), 3.70 (t, J = 5.5 Hz, 2 H, OCH2CH2Cl), 3.74–3.86 (m, 2H, H-5a,
OCH2aCH2Cl), 3.87–4.09 (m, 2H, H-5b, OCH2bCH2Cl), 4.15–4.29
(m, 2H, H-3, H-4), 5.15 (s, 1H, H-1), 5.31 (s, 1H, H-2), 7.44 (t, 2H,
J = 7.6 Hz, Ph), 7.53–7.64 (m, 1 H, Ph), 8.01 (d, 2H, J 8.1 Hz, Ph).
13C NMR (75.48 MHz, CDCl3): dC 42.8 (CH2Cl), 61.9 (OCH2CH2Cl),
67.5 (C-5), 76.4 (C-3), 84.5, 85.7 (C-2, C-4), 105.4, 128.5, 128.9,
129.7, 133.6 (Ph), 166.5 (CO).
4.4. 3-O-Benzoyl-b-D-arabinofuranose 1,2,5-orthobenzoate (1d)
To the solution of b-
(500 mg, 2.12 mmol) in anhydrous pyridine (5 mL, 62 mmol) ben-
zoyl chloride (230 L, 2.54 mmol) was added. After 15 min the
D-arabinofuranose 1,2,5-orthobenzoate 1a
l
reaction was quenched by addition of satd aq NaHCO3 (2 mL), di-
luted with chloroform (75 mL), washed with H2O (75 mL), 1 M
KHSO4 (75 mL), H2O (75 mL), satd aq NaHCO3 (50 mL), filtered
through a layer of ꢀ1:1 (v/v) Celite–powdered Na2SO4 mixture,
concentrated, and dried in vacuo. The residue was crystallized
from benzene–light petroleum to give 1d (678 mg, 94%; Rf = 0.53,
4.7. 2-Chloroethyl 2,3-di-O-benzoyl-a-D-arabinofuranoside (6b)
Tin tetrachloride (103
0.088 mmol) was added to the solution of 3-O-benzoyl-b-
l
L
of 10% (v/v) soln in CH2Cl2,
-arabino-
D

N. M. Podvalnyy et al. / Carbohydrate Research 346 (2011) 7–15
13
furanose 1,2,5-orthobenzoate 1d (600 mg, 176 mmol) in 2-chloro-
ethanol (6 mL, 89 mmol) and the reaction mixture was stirred at
room temperature (ꢀ20 °C). After 30 min TLC showed the complete
conversion and satd aq NaHCO3 solution (1 mL) was added, the mix-
ture was diluted with CHCl3 (75 mL), organic layer was washed with
satd aq NaHCO3 (75 mL) and H2O (75 mL), filtered through a layer of
ꢀ1:1 (v/v) Celite–powdered Na2SO4 mixture, concentrated, and
dried in vacuo. The residue was purified by silica gel column chro-
matography (gradient benzene?20% acetone in benzene) to give
6b (710 mg, 96%; Rf = 0.30, light petroleum–AcOEt, 2:1) as a color-
in 15–30 min intervals) to a stirring reaction mixture at the same
temperature. The reaction was monitored by TLC after addition
of each portion of SnCl4. When TLC showed that the reaction was
complete cold satd aq NaHCO3 (1–10 mL) was added, and the mix-
ture was allowed to warm up to room temperature, diluted with
CHCl3 or CH2Cl2, filtered through Celite if molecular sieves were
used, solids were washed with CHCl3 or CH2Cl2, the filtrate was
washed with satd NaHCO3 and water. The combined organic ex-
tract was filtered through a cotton wool plug, concentrated, and
dried in vacuo. The products were isolated by silica gel column
chromatography (typical eluants: petroleum ether–AcOEt, ben-
zene–acetone, benzene–AcOEt). The yields are given in Table 1.
less sirup.
½
a 2D2
ꢄ
ꢂ21.6 (c 1.0, CH2Cl2). HRESIMS: found m/z
443.0893 [M+Na]. Calcd for C21H21ClNaO7: 443.0874. 1H NMR
(200.13 MHz, CDCl3): dH 2.47 (br s, 1H, OH), 3.67–3.76 (m, 2H,
CH2Cl), 3.78–3.92 (m, OCH2a), 3.95–4.10 (m, 3H, OCH2b, H-5a, H-
5b), 4.36–4.45 (m, 1H, H-4), 5.31 (s, 1H, H-1), 5.47 (dd, 1H,
J2,3 = 1.6 Hz, J3,4 = 4.7 Hz, H-3), 5.56 (d, 1H, J2,3 = 1.6 Hz, H-2), 7.35–
7.67 (m, 6H, Ph), 8.01–8.15 (m, 4H, Ph). 13C NMR (75.48 MHz,
CDCl3): dC 42.7 (CH2Cl), 62.2 (C-5), 67.4 (OCH2CH2Cl), 77.4 (C-3),
81.6 (C-2), 83.9 (C-4), 105.5 (C-1), 128.4, 128.5, 128.9, 129.0,
129.8, 129.9, 133.5, 133.6, (Ph), 165.3, 166.1 (CO).
4.9.2. Data for ethyl 3-O-acetyl-2-O-benzoyl-1-thio-a-D-
arabinofuranoside (7a)
½
a 3D0
+107.7 (c 1.0, CHCl3). HRESIMS found m/z 363.0873
ꢄ
[M+Na]. Calcd for C16H20O6SNa: 363.0873. Rf = 0.49, benzene–
AcOEt, 8:2. 1H NMR (300.13 MHz, CDCl3): dH 1.32 (t, 1H,
J = 7.4 Hz, SCH2CH3), 2.14 (s, 1H, AcO), 2.30 (br s, 1H, 5-OH),
2.60–2.83 (m, 2H, SCH2CH3), 3.83–4.00 (m, 2H, H-5a, H-5b),
4.29–4.35 (m, H-4), 5.26 (dd, 1H, J3,4 = 5.6 Hz, J2,3 = 1.7 Hz, H-3),
5.37–5.40 (m, 1H, H-2), 5.50 (br s, 1H, H-1), 7.41–7.48 (m, 2H,
Ph), 7.55–7.62 (m, 1H, Ph), 8.01–8.06 (m, 2H, Ph). 13C NMR
(75.48 MHz, CDCl3): dC 14.7 (SCH2CH3), 20.8 (AcO), 25.2 (SCH2CH3),
61.7 (C-5), 77.4 (C-3), 82.4, 82.7 (C-2, C-4), 87.7 (C-1), 128.5, 128.9,
129.8, 133.5 (Ph), 165.3, 170.5 (CO).
4.8. 2-Chloroethyl 2-O-benzoyl-3-O-chloroacetyl-a-D-
arabinofuranoside (6c)
Tin tetrachloride (20
lL of 10% (v/v) soln in CH2Cl2,
0.088 mmol) was added to the solution of 3-O-chloroacetyl-b-
D
-
arabinofuranose 1,2,5-orthobenzoate 1e (136 mg, 0.44 mmol) in
2-chloroethanol (1.5 mL) and the reaction mixture was stirred at
room temperature (ꢀ20 °C). After 30 min TLC showed the com-
plete conversion and satd aq NaHCO3 solution (1 mL) was added,
the mixture was diluted with CHCl3 (50 mL), organic layer
(50 mL) was washed with satd aq NaHCO3 (50 mL) and H2O
(50 mL), filtered through a layer of ꢀ1:1 (v/v) Celite–powdered
Na2SO4 mixture, concentrated, and dried in vacuo. The residue
was purified by silica gel column chromatography (light petro-
leum–AcOEt, 2:1) to give 6c (133 mg, 78%; Rf = 0.16, light petro-
4.9.3. Data for phenyl 3-O-acetyl-2-O-benzoyl-1-thio-a-D-
arabinofuranoside (7b)
½
a 3D2
+125.7 (c 1.0, CHCl3). HRESIMS found m/z 411.0873
ꢄ
[M+Na]. Calcd for C20H20O6SNa: 411.0873. Rf = 0.54, benzene–
AcOEt, 8:2. 1H NMR (600.13 MHz, CDCl3): dH 2.17 (s, 3H), 2.26
(br s, 1H, 5-OH) 3.91 (dd, 1H, J5a,5b = 12.3, J4,5a = 3.9 Hz), 3.98 (dd,
J5a,5b = 12.3, J4,5b = 3.4 Hz, H-5b), 4.43–4.46 (m, 1H, H-4), 5.31–
5.32 (m, 1H, H-3), 5.57 (t, 1H, J = 1.9 Hz, H-2), 5.71–5.72 (m, 1H,
H-1), 7.28–7.35 (m, 4 H, Ph), 7.43–7.47 (m, 2H, Ph), 7.54–7.60
(m, 3H, Ph). 13C NMR (150.9 MHz, CDCl3): dC 20.8 (CH3CO), 61.7
(C-5), 77.2 (C-3), 82.3 (C-2), 83.0 (C-4), 91.1 (C-1), 127.8, 128.3,
128.4, 128.5, 128.9, 129.0, 129.7, 129.8, 132.1, 133.5, 133.6 (Ph),
165.2, 170.4 (CO).
leum–AcOEt, 2:1) as a colorless sirup. ½a D22
ꢄ
+25.7 (c 1.0, CHCl3).
HRESIMS found m/z 415.0297 [M+Na]. Calcd for C16H18Cl2O7Na:
415.0327. 1H NMR (300.13 MHz, CDCl3): dH 2.16 (br dd, 1H,
J = 7.3 Hz, J = 5.0 Hz, 5-OH), 3.69 (t, 2H, J = 5.7 Hz,ClCH2CH2O),
3.77–3.86 (m, 1H, OCH2a), 3.89–4.02 (m, 3H, OCH2b, H-5a, H-5b),
4.16 (s, 2H, ClCH2CO), 4.26–4.31 (m, 1H, H-4), 5.26 (s, 1H, H-1),
5.30 (dd, 1H, J2,3 = 1.3 Hz, J3,4 4.9 Hz, H-3), 5.40 (d, 1H,
J2,3 = 1.3 Hz, H-2), 7.45 (t, 2H, J = 7.7 Hz, Ph), 7.56–7.63 (m, 1H,
Ph), 8.02 (d, 2H, J = 7.3 Hz, Ph). 13C NMR (75.47 MHz, CDCl3): dC
40.6 (ClCH2CO), 42.7 (ClCH2CH2O), 61.8 (C-5), 67.4 (ClCH2CH2O),
78.5 (C-3), 81.5 (C-2), 83.3 (C-4), 105.4 (C-1), 128.5, 128.8, 129.8,
133.7 (Ph), 165.2, 167.0 (C@O).
4.9.4. Data for ethyl 2,3-di-O-benzoyl-1-thio-a-D-
arabinofuranoside (8a)
½
a 3D2
+47.3 (c 1.0, CHCl3). HRESIMS found m/z 441.0774 [M+K].
ꢄ
Calcd for C21H22O6SK: 441.0769. Rf = 0.63, benzene–AcOEt, 8:2.
1H NMR (300.13 MHz, CDCl3): dH 1.36 (t, 3H, J = 7.4 Hz, SCH2CH3),
2.44 (br s, 1H, 5-OH), 2.64–2.88 (m, 2H, SCH2CH3), 4.00–4.05 (m,
2H, H-5), 4.45–4.51 (m, 1H, H-4), 5.49–5.53 (m, 1H, H-3), 5.57–
5.59 (m, 1H, H-2), 5.59 (br s, 1H, H-1), 7.41–7.51 (m, 4H, Ph),
7.55–7.64 (m, 2H, Ph), 8.03–8.13 (m, 4H, Ph). 13C NMR
(75.48 MHz, CDCl3): dC 14.8 (SCH2CH3), 25.3 (SCH2CH3), 61.9 (C-
5), 77.9 (C-3), 82.6 (C-2), 83.1 (C-4), 88.0 (C-1), 128.5, 128.9,
129.8, 129.9, 133.5 (Ph), 165.3, 165.9 (CO).
4.9. Ring opening of 3-O-acyl b-D-arabinofuranose 1,2,5-
orthobenzoates (1c–e) with thiols
4.9.1. General procedure, see Table 1 for the details; for the large
scale procedure see Section 4.9.14
3-O-Acyl-b-D-arabinofuranose 1,2,5-orthobenzoate 1c, 1d, or 1e
4.9.5. Data for phenyl 2,3-di-O-benzoyl-1-thio-a-D-
(1 equiv, 0.13–1.8 mmol) was coevaporated with toluene (3 ꢃ 3–
10 mL), dried in vacuo and dissolved in anhydrous CH2Cl2
(6.5 mL per 1 mmol of 1). The resulting solution was stirred with
powdered molecular sieves 3 Å or 4 Å (650 mg per 1 mmol) for
1 h at ꢀ20 °C (in one case no molecular sieves were used, see entry
9 in Table 1). The mixture was cooled to the temperature specified
in Table 1 (ranging from ꢂ28 to ꢂ15 °C) and EtSH or PhSH (1.2–
18.3 equiv; the amount is specified in Table 1) was added. Tin tet-
rachloride (as a 10% (v/v) solution in CH2Cl2; the amount is speci-
fied in Table 1) was added portion-wise (3–6 ꢃ 0.05 equiv of SnCl4
arabinofuranoside (8b)
½
a 3D2
+80.8 (c 1.0, CHCl3). HRESIMS found m/z 473.1024 [M+Na].
ꢄ
Calcd for C25H22O6SNa: 473.0129. Rf = 0.70, benzene–AcOEt, 8:2.
1H NMR (300.13 MHz, CDCl3): dH 2.24 (t, 1H, J = 6.3 Hz, 5-OH),
4.02–4.08 (m, 2H, H-5), 4.58–4.64 (m, 1H, H-4), 5.56–5.59 (m, H-
3), 5.76 (t, 1H, J = 1.5 Hz, H-2), 5.81 (br s, 1H, H-1), 7.29–7.38 (m,
3H, Ph), 7.42–7.53 (m, 4H, Ph), 7.56–7.66 (m, 4H, Ph), 8.04–8.09
(m, 2H, Ph), 8.12–8.17 (m, 2H, Ph). 13C NMR (75.48 MHz, CDCl3):
dC 61.9 (C-5), 77.7 (C-3), 82.2, 83.7 (C-2, C-4), 91.4 (C-1), 127.8,

14
N. M. Podvalnyy et al. / Carbohydrate Research 346 (2011) 7–15
128.5, 128.9, 128.9, 129.0, 129.8, 130.0, 132.1, 133.6 (Ph), 165.2,
165.9 (CO).
4.9.10. Data for ethyl 5-O-(2,3-di-O-benzoyl-
a
-
D
-
arabinofuranosyl)-2,3-di-O-benzoyl-1-thio-
a
-
D
-
arabinofuranoside (12a)
4.9.6. Data for ethyl 2-O-benzoyl-3-O-chloroacetyl-1-thio-
arabinofuranoside (9a)
a
-
D
-
Compound 12a was obtained as a mixture with the correspond-
ing monosaccharide 8a (1:1.5). HRESIMS found m/z 765.1976
[M+Na]+. Calcd for C40H38O12SNa: 765.1976. Rf = 0.64, benzene–
AcOEt, 8:2. 1H NMR (300.13 MHz, CDCl3): dH 1.32 (t, 3H,
J = 7.5 Hz, SCH2CH3), 2.63–2.85 (m, 2H, SCH2CH3), 3.92–4.07 (m,
3H, H-5a, H-50a, H-50b), 4.24 (dd, 1H, J5a,5b = 11.2 Hz, J4,5b = 4.4 Hz,
H-5b), 4.45–4.54 (m, 1H, H-40), 4.57–4.65 (m, 1H, H-4), 5.42 (s,
½
a 3D3
+104.3 (c 1.0, CHCl3). HRESIMS found m/z 397.0481
ꢄ
[M+Na]+. Calcd for C16H19ClO6SNa: 397.0483. Rf = 0.36, benzene–
AcOEt, 10:1. 1H NMR (600.13 MHz, CDCl3): dH 1.34 (t, 1H,
J = 7.4 Hz, SCH2CH3), 2.19–2.34 (m ꢀ br s centered at 2.09, 1H, 5-
OH), 2.66–2.80 (m, 2H, SCH2CH3), 3.90–4.01 (m, 2H, H-5a, H-5b),
4.16 (d, 2H, J = 1 Hz, ClCH2CO), 4.36–4.39 (m, 1H, H-4), 5.35–5.37
(m, 1H, H-3), 5.40 (t, 1H, J2,3 = 1.8 Hz, H-2), 5.53 (br s, 1H, H-1),
7.44–7.48 (m, 2H, Ph), 7.58–7.61 (m, 1H, Ph), 8.03–8.05 (m, 2 H,
Ph). 13C NMR (75.48 MHz, CDCl3): dC 14.6 (SCH2CH3), 25.1
(SCH2CH3), 40.6 (ClCH2CO), 61.4 (C-5), 78.7 (C-3), 82.1, 82.5 (C-2,
C-4), 87.7 (C-1), 128.5, 128.8, 129.8, 133.6 (Ph), 165.3, 166.9 (CO).
1H, H-10), 5.45 (dd, 1H, J3 ,4 = 4.8 Hz, J3 ,2 = 1.3 Hz, H-30), 5.56 (t,
0
0
0
0
0
0
1H, J2,3 = 1.6 Hz, H-2), 5.59 (br s, 1H, H-1), 5.66 (d, 1H, J2 ,3 = 1.3 Hz,
H-20), 5.69 (br d, 1H, J3,4 = 4.7 Hz, H-3), 7.23–7.67 (m, 12H, Ph),
7.89–8.13 (m, 8H, Ph). 13C NMR (selected signals, 75.48 MHz,
CDCl3): dC 14.8 (SCH2CH3), 25.2 (SCH2CH3), 62.3 (C-50), 65.9 (C-5),
77.5 (C-30), 77.8 (C-3), 81.5, 81.7 (C-20, C-4), 82.6 (C-2), 83.7 (C-
40), 88.1 (C-1), 105.8 (C-10).
4.9.7. Data for phenyl 2-O-benzoyl-3-O-chloroacetyl-1-thio-a-D-
arabinofuranoside (9b)
4.9.11. Data for phenyl 5-O-(2,3-di-O-benzoyl-a-D-
arabinofuranosyl)-2,3-di-O-benzoyl-1-thio-a-D-
arabinofuranoside (12b)
Compound 12b was obtained as a mixture with the correspond-
ing monosaccharide 8b (1.7:1). HRESIMS found m/z 813.1992
[M+Na]+. Calcd for C44H38O12SNa: 813.1976. Rf = 0.66, benzene–
AcOEt, 8:2. 1H NMR (300.13 MHz, CDCl3): dH 2.29 (br s, 1H, OH),
3.90–4.07 (m, 3H, H-5a, H-50a, H-50b), 4.25 (dd, 1H, J5a,5b = 11.5 Hz,
J4,5b = 4.0 Hz, H-5b), 4.46–4.52 (m, H-40), 4.67–4.76 (m, H-4), 5.41
½
a 1D7
ꢄ
+112.4 (c 1.0, CHCl3). HRESIMS found m/z 445.0489
[M+Na]+. Calcd for C20H19ClO6SNa: 445.0483. Rf = 0.40, benzene–
AcOEt, 8:2. 1H NMR (300.13 MHz, CDCl3): dH 2.00–2.08 (m, 1H, 5-
OH), 3.88–4.06 (m, 2H, H-5a, H-5b), 4.19 (s, 2H, ClCH2CO), 4.46–
4.51 (m, 1H, H-4), 5.41 (dd, 1H, J3,4 = 5.3 Hz, J2,3 = 1.8 Hz, H-3),
5.57 (t, 1H, J2,3 = 1.8 Hz, H-2), 5.74 (br s, 1H, H-1), 7.29–7.38 (m,
3H, Ph), 7.42–7.49 (m, 2H, Ph), 7.53–7.64 (m, 3H, Ph), 8.01–8.06
(m, 2H, Ph). 13C NMR (75.48 MHz, CDCl3): dC 40.5 (ClCH2CO), 61.5
(C-5), 78.7 (C-3), 82.0, 82.7 (C-2, C-4), 91.0 (C-1), 127.9, 128.6,
128.8, 129.1, 129.9, 132.3, 133.2, 133.7 (Ph), 165.2, 166.8 (CO).
(s, 1H, H-10), 5.45 (dd, 1H, J3 ,4 = 4.9 Hz, J2 ,3 = 1.5 Hz, H-30), 5.65
(d, 1H, J2,3 = 1.5 Hz, H-2), 5.71–5.77 (m, 2H, H-20, H-3), 5.81 (br s,
1H, H-1), 7.14–7.68 (m, 17H, Ph), 7.86–8.18 (m, 8H, Ph). 13C NMR
(selected signals, 75.48 MHz, CDCl3): dC 62.3 (C-50), 66.0 (C-5),
77.2 (C-3), 77.7 (C-30), 81.7 (C-2), 82.1, 82.1 (C-20, C-4), 83.7 (C-
40), 91.2 (C-1), 105.8 (C-10).
0
0
0
0
4.9.8. Data for ethyl 5-O-(3-O-acetyl-2-O-benzoyl-a-D-
arabinofuranosyl)-3-O-acetyl-2-O-benzoyl-1-thio-a-D-
arabinofuranoside (11a)
½
a 3D4 +85.6 (c 1.0, CHCl3). HRESIMS found m/z 657.1404 [M+K]+.
ꢄ
Calcd for C30H34O12SK: 657.1403. Rf = 0.36, benzene–AcOEt, 8:2. 1H
NMR (300.13 MHz, CDCl3): dH 1.24 (t, 3H, J = 7.4 Hz, SCH2CH3), 1.82
(s, 3H, Ac), 2.05 (s, 3H, Ac), 2.53–2.75 (m, 2H, SCH2CH3), 3.72–3.89
(m, 3H, H-5a, H-50a, H-50b), 3.99 (dd, 1H, J5a,5b = 11.2 Hz,
J4,5b = 3.8 Hz, H-5b), 4.14–4.19 (m, H-40), 4.33–4.38 (m, 1H, H-4),
5.02–5.05 (m, 1H, H-30), 5.23 (s, 1H, H-10), 5.30 (t, 1H,
J2,3 = 1.9 Hz, J1,2 = 1.9 Hz H-2), 5.37–5.41 (m, 2H, H-20, H-3), 5.45
(br s, 1H, H-1), 7.32–7.43 (m, 4H, Ph), 7.46–7.54 (m, 2H, Ph),
7.91–7.96 (m, 2H, Ph), 8.00–8.04 (m, 2H, Ph). 13C NMR
(75.48 MHz, CDCl3): dC 14.7 (SCH2CH3), 20.5, 20.8 (Ac), 25.1
(SCH2CH3), 62.3 (C-50), 64.8 (C-5), 76.6 (C-30), 77.5 (C-3), 80.6 (C-
4), 81.5 (C-20), 82.9(C-2), 84.0 (C-40), 87.7 (C-1), 105.2 (C-10),
128.5, 128.5, 129.7, 129.8, 133.5, 133.5 (Ph), 165.0, 165.4, 170.0,
170.6 (CO).
4.9.12. Data for ethyl 5-O-(3-O-chloroacetyl-2-O-benzoyl-
arabinofuranosyl)-3-O-chloroacetyl-2-O-benzoyl-1-thio-
arabinofuranoside (13a)
a
-
D
-
a-
D
-
½
a 2D3 +76.3 (c 1.0, CHCl3). HRESIMS found m/z 709.0885 [M+Na]+.
ꢄ
Calcd for C30H32Cl2O12SNa: 709.0884. Rf = 0.51, benzene–AcOEt,
8:2. 1H NMR (300.13 MHz, CDCl3) dH 1.33 (t, 3H, J = 7.4 Hz,
SCH2CH3), 2.63–2.83 (m, 2H, SCH2CH3), 3.79–4.01 (m, 5H, H-5a,
H-50a, H-50b, ClCH2), 4.07 (1H, dd, J5a,5b = 11.5, J4,5b = 3.5 Hz, H-
5b), 4.17 (s, 2H, ClCH2), 4.22–4.28 (m, 1H, H-40), 4.44–4.50 (m,
1H, H-4), 5.23 (br d, 1H, J3 ,4 = 4.2 Hz, H-30), 5.33 (s, 1H, H-10),
5.39 (t, 1H, J2.3 = 2.0 Hz, H-2), 5.44 (d, 1H, J2,3 = 1.3 Hz, H-20),
5.52–5.59 (m, 2H, H-1, H-3), 7.40–7.55 (m, 4H, Ph), 7.55–7.66 (m,
2H, Ph), 7.99–8.05 (m, 2H, Ph), 8.07–8.13 (m, 2H, Ph). 13C NMR
(75.48 MHz, CDCl3): dC 14.7 (SCH2CH3), 25.2 (SCH2CH3), 40.4, 40.5
(CH2Cl), 62.0 (C-50), 64.6 (C-5), 78.0 (C-3), 78.7 (C-30), 80.1 (C-4),
81.2 (C-20), 82.6 (C-2), 83.8 (C-40), 87.4 (C-1), 105.3 (C-10), 128.5,
128.7, 128.9, 129.8, 129.8, 133.6, 133.8 (Ph), 165.0, 165.5, 166.8,
167.0 (CO).
0
0
4.9.9. Data for phenyl 5-O-(3-O-acetyl-2-O-benzoyl-a-D-
arabinofuranosyl)-3-O-acetyl-2-O-benzoyl-1-thio-a-D-
arabinofuranoside (11b)
½
a 3D3 +85.1 (c 1.0, CHCl3). HRESIMS found m/z 689.1667 [M+Na]+.
Calcd for C34H34O12SNa: 689.1663. Rf = 0.34, benzene–AcOEt, 8:2.
ꢄ
4.9.13. Data for phenyl 5-O-(2-O-benzoyl-3-O-chloroacetyl-a-D-
arabinofuranosyl)-2-O-benzoyl-3-O-chloroacetyl-1-thio-a-D-
arabinofuranoside (13b)
Compound 13b was obtained as a mixture with isomeric phenyl
5-O-(2-O-benzoyl-3-O-chloroacetyl-b-D-arabinofuranosyl)-2-O-
1H NMR (300.13 MHz, CDCl3): dH 1.91 (s, 3H, Ac), 2.17 (s, 3H, Ac),
3.83–3.90 (m, 2 H, H-5a, H-50a,), 3.94 (dd, 1H, J5 a,5 b = 11.9 Hz,
0
0
J4 ,5 b = 3.7 Hz, H-50b), 4.09 (dd, 1H, J5a,5b = 11.2 Hz, J4,5b = 3.7 Hz,
0
0
H-5b), 4.22–4.27 (m, 1H, H-40), 4.52–4.57 (m, 1H, H-4), 5.11–5.13
(m, 1H, H-30), 5.31 (s, 1H, H-10), 5.45 (d, 1H, J2 ,3 = 1.3 Hz, H-20),
5.50–5.53 (m, 1H, H-3), 5.55 (t, 1H, J2,3 = 2.0 Hz, H-2), 5.77–5.79
(m, 1H, H-1), 7.27–7.36 (m, 3H, Ph), 7.41–7.63 (m, 8H, Ph), 7.99–
8.13 (m, 4H, Ph). 13C NMR (75.48 MHz, CDCl3): dC 20.5, 20.8 (Ac),
62.3 (C-50), 64.9 (C-5), 76.5 (C-3), 77.4 (C-30), 81.1 (C-4), 81.5 (C-
20), 82.4 (C-2), 84.0 (C-40), 90.7 (C-1), 105.3 (C-10), 127.6, 128.5,
128.6, 129.0, 129.8, 129.9, 131.8, 133.5, 133.7 (Ph), 165.1, 165.4,
170.1, 170.7 (CO).
benzoyl-3-O-chloroacetyl-1-thio-
a
-
D
-arabinofuranoside (5:1). ½a D23
ꢄ
0
0
+83.2 (c 1.0, CHCl3). HRESIMS found m/z 709.0851 [M+Na]+. Calcd
for C34H32Cl2O12SNa: 709.0889. Rf = 0.21, benzene–AcOEt, 8:2. 1H
NMR (300.13 MHz, CDCl3): dH 3.80–4.00 (m, 5H, H-5a, H-50a, H-
50b, ClCH2CO), 4.04–4.27 (m, 4H, H-40, H-5b, ClCH2CO), 4.53–4.60
(m, 1H, H-4), 5.23 (br d, 1H, J3 ,4 = 4.8 Hz, H-30), 5.32 (s, 1H, H-10),
0
0
5.42 (d, 1H, J2 ,3 = 1.2 Hz, H-20), 5.56 (t, 1H, J2,3 = 2.2 Hz), 5.57–
5.60 (m, 1H, H-3), 5.79 (d, J1,2 = 2.2 Hz, 1H, H-1), 7.27–7.38 (m,
0
0

N. M. Podvalnyy et al. / Carbohydrate Research 346 (2011) 7–15
15
4H, Ph), 7.40–7.66 (m, 7H, Ph), 7.99–8.13 (m, 4H, Ph). 13C NMR
(75.48 MHz, CDCl3): dC 40.4, 40.5 (2 ꢃ ClCH2CO), 62.0 (C-50), 64.7
(C-5), 77.8 (C-3), 78.7 (C-30), 80.7 (C-4), 81.2 (C-20), 82.1 (C-2),
83.8 (C-40), 90.4 (C-1), 105.4 (C-10), 127.8, 128.5, 128.7, 129.1,
129.8, 129.8, 131.9, 133.6, 133.8 (Ph), 165.0, 165.4, 166.7, 167.0
(CO).
has not been obtained. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
j.carres.2010.11.002.
References
Selected signals for 5-O-(2-O-benzoyl-3-O-chloroacetyl-b-D-
arabinofuranosyl)-2-O-benzoyl-3-O-chloroacetyl-1-thio-a-D-arab-
1. (a) Joe, M.; Bai, Y.; Nacario, R. C.; Lowary, T. L. J. Am. Chem. Soc. 2007, 129, 9885–
9901; (b) Zhu, X.; Kawatkar, S.; Rao, Y.; Boons, G.-J. J. Am. Chem. Soc. 2006, 128,
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inofuranoside: 13C NMR (75.48 MHz, CDCl3): dc 65.3 (C-5), 67.3
(C-50), 76.4, 79.1, 80.9, 90.7 (C-1), 101.7 (C-10).
4.9.14. Ethyl 2-O-benzoyl-3-O-chloroacetyl-1-thio-a-D-
arabinofuranoside (9a) (large scale procedure)
3-O-Chloroacetyl-b-D-arabinofuranose 1,2,5-orthobenzoate 5
(4.17 g, 13.34 mmol, 1 equiv) was stirred with molecular sieves
3 Å (4.0 g) in anhydrous CH2Cl2 (80 mL) for 40 min. The mixture
was cooled to ꢂ25 °C and EtSH (4.93 mL, 66.7 mmol, 5 equiv)
2. Sanchez, S.; Bamhaoud, T.; Prandi, J. Eur. J. Org. Chem. 2002, 3864–3873.
3. http://www.who.int/topics/tuberculosis.
was added. Tin tetrachloride was added portionwise (150
10% v/v solution in CH2Cl2 (0.1 equiv), then 4 portions of 75
l
l
L of
L of
4. (a) Byramova, N. E.; Ovchinnikov, M. V.; Backinowsky, L. V.; Kochetkov, N. K.
Carbohydr. Res. 1983, 124, C8–C11; (b) Wuts, P. G. M.; Greene, T. W. In Protective
Groups in Organic Synthesis, 4th ed.; John Wiley & Sons: Hoboken, New Jersey,
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the same solution) with TLC control after each addition. The reac-
tion was quenched by addition of satd aq NaHCO3 (50 mL), the
mixture allowed to reach ꢀ20 °C, filtered through Celite, the solids
were washed with CH2Cl2. The organic layer was diluted with
CH2Cl2 (200 mL), washed with satd NaHCO3 (200 mL), filtered
through cotton wool plug, concentrated, and dried in vacuo. The
product was purified by column chromatography on silica gel
using a benzene–ethyl acetate eluant to give 9a (3.89 g, 69%).
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Acknowledgments
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Authors are grateful to Professor Y. V. Voznyi for stimulating
discussions, to V. I. Bragin for registration of NMR spectra on a
Bruker AVANCE 600 spectrometer, to Dr. A. O. Chizhov and Dr. N.
G. Kolotyrkina for the registration of mass spectra, and to Mr. N.
N. Kondakov for invaluable help with HLPC purification. This work
was financially supported by the Russian Foundation for Basic
Research (project No. 07-03-00830).
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Supplementary data
Supplementary data section contains all experimental proce-
dures, spectral and characterization data for all compounds pre-
pared (see Schemes 2–4) as well as the copies of NMR spectra of
previously unknown compounds, for which combustion analysis