Synthesis of 4-cyanophenyl and 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-β-D-arabino- and -β-D-lyxopyranosides possessing antithrombotic activity

Article abstract of DOI:10.1016/S0008-6215(99)00320-1

Tri-O-acetyl-5-thio-D-ribopyranosyl bromide was converted into 3,4-di-O-benzoyl-1,5-anhydro-5-thio-D-erythro-pent-1-enitol (3,4-di-O-benzoyl-5-thio-D-ribal), the azidonitration of which afforded an unstable mixture of 2-azido-3,4-di-O-benzoyl-2-deoxy-1-O-

Full text of DOI:10.1016/S0008-6215(99)00320-1

www.elsevier.nl/locate/carres
Carbohydrate Research 325 (2000) 143–149
Note
Synthesis of 4-cyanophenyl and 4-nitrophenyl
2-azido-2-deoxy-1,5-dithio-b-
D
-arabino- and
-b-
D
-lyxopyranosides possessing antithrombotic activityꢀ
´
Eva Bozo´, Ja´nos Kuszmann *
Institute for Drug Research, PO Box 82, H-1325 Budapest, Hungary
Received 14 September 1999; accepted 25 November 1999
Abstract
Tri-O-acetyl-5-thio-
D
-ribopyranosyl bromide was converted into 3,4-di-O-benzoyl-1,5-anhydro-5-thio-D-erythro-
pent-1-enitol (3,4-di-O-benzoyl-5-thio-
3,4-di-O-benzoyl-2-deoxy-1-O-nitro-5-thio-
the corresponding 1-O-acetyl derivatives from which an a,b anomeric mixture of the 1-O-acetyl-2-azido-3,4-di-O-
benzoyl-2-deoxy-5-thio- -arabinopyranose isomers could be isolated in high yield. Glycosidation of this mixture with
D
-ribal), the azidonitration of which afforded an unstable mixture of 2-azido-
D
-pentopyranoside isomers. This was converted without separation into
D
4-cyano- or 4-nitrobenzenethiol, using trimethylsilyl triflate or boron trifluoride etherate, respectively, as promoters
gave the corresponding b anomers exclusively. Zemple´n debenzoylation afforded 4-cyanophenyl as well as 4-nitro-
phenyl 2-azido-2-deoxy-1,5-dithio-b-
deoxy-5-thio-
well as 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-b-
D-arabinopyranoside, respectively. When 1-O-acetyl-2-azido-3,4-di-O-benzoyl-2-
D
-lyxopyranose was used as glycosyl donor only the corresponding b anomers, i.e., 4-cyanophenyl as
D
-lyxopyranosides, could be isolated after Zemple´n debenzoyla-
tion in high yield. All four 1,5-dithioglycosides possess significant oral antithrombotic activity. © 2000 Elsevier
Science Ltd. All rights reserved.
Keywords: 2-Azido-2-deoxy-5-thio-
D-arabinose; 2-Azido-2-deoxy-5-thio-D-lyxose; Azidonitration reaction; Glycosidation reac-
tions; Thioglycosides; 1,5-Dithioglycosides; Oral antithrombotic activity
1. Introduction
topyranose moiety at C-3 (
D
-ribopyranoside)
or C-2 and C-3 ( -arabinopyranoside). A sim-
D
In our previous papers [1,2], we showed
that the oral antithrombotic activity of
ilar increase in this biological activity was
achieved by substituting the HO-2 group of 1
with an azido group (2) [4]. For our further
structure–activity studies, we decided to syn-
thesize such beciparcil analogs in which the
two aforementioned alterations are introduced
simultaneously, i.e., the sugar residue differs
4-cyanophenyl 1,5-dithio-b- -xylopyranoside
D
(beciparcil, 1) [3] could be significantly in-
creased by changing the chirality of the pen-
ꢀ Orally active antithrombotic thioglycosides, Part IX. For
Part VIII see [1].
* Corresponding author. Tel.: +36-1-3993441; fax: +36-
1-3993356.
from
D
-xylose in the chirality of C-2 and/or
C-3 and carries an azido group at C-2 (4 and
6) (Scheme 1).
E-mail address: h13757kus@ella.hu (J. Kuszmann)
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00320-1

´
E. Bozo´, J. Kuszmann / Carbohydrate Research 325 (2000) 143–149
144
2. Results and discussion
10 occurs mainly from the upper side, i.e.,
trans to the 3-O-benzoyl group. This is in
sharp contrast to the corresponding 3,4-di-O-
For the synthesis of 4 or 6, a properly
substituted 2-azido-2-deoxy-5-thio-pentopyr-
anose was needed as the donor molecule. Both
benzoyl-5-thio-
where the same reaction afforded a 1:1 mix-
ture of the corresponding cis ( -lyxo) 18 and
trans ( -xylo) isomers [4]. This difference is
D
-threo-pent-1-enitol isomer,
the corresponding 2-azido-2-deoxy-5-thio-
ribo and - -arabino derivatives can be theoret-
ically obtained from 3,4-di-O-benzoyl-1,5-
anhydro-5-thio- -erythro-pent-1-enitol (3,4-
di-O-benzoyl-5-thio- -ribal, 10) by applying
D
-
D
D
D
probably due to the steric arrangement of the
3-O-benzoyl substituent, which in 10 occupies
an axial position, whereas in the threo-pent-1-
enitol isomer it is equatorially oriented. It is
worthwhile mentioning that according to
NMR spectroscopy, the a anomer 12 occupies
D
D
the azidonitration reaction [4]. For this ap-
proach 10 was synthesized in a three-step pro-
cess starting from 2,3,4-tri-O-acetyl-5-thio-
4
D-ribopyranosyl bromide 7 [1] and converting
predominantly a C1 conformation, while the
1
it into a 95% yield of the 1-ene derivative 8 by
using zinc in ethyl acetate in the presence of
picoline [5,6]. Deacetylation and subsequent
benzoylation of 8 afforded crystalline 10 in
71% yield. The azidonitration reaction of 10
was carried out in acetonitrile with sodium
azide and ceric ammonium nitrate at −20 °C
and afforded a mixture of the corresponding
2-azido-1-O-nitro derivatives 11 showing, on
thin-layer chromatography (TLC), two dis-
tinct spots. This mixture could be purified by
column chromatography but the components
could not be separated because of their insta-
bility and their very similar Rf values. There-
fore, the mixture was immediately treated with
sodium acetate in acetic acid at 100 °C. The
1-O-acetates formed gave a single spot on
TLC, and could be isolated in a yield of 72%
after column chromatography. According to
NMR spectroscopy, this mixture contained
only two components in a 3:7 ratio, having
b anomer 13 is present in a C4 conformation.
For the synthesis of the corresponding 4-
cyanophenylthio glycoside, a 3:7 mixture of
the two 1-O-acetate anomers (12 and 13) was
used as donor, 4-cyanobenzenethiol as accep-
tor and trimethylsilyl triflate as promoter. The
reaction was carried out in 1,2-dichloroethane
at −10 °C, when only one isomer, the b
anomer 14, was formed. This is probably due
to the presence of the bulky axial substituent
4
at C-3 in the C1 conformation, which, be-
cause of the unfavoured 1,3-diaxial arrange-
ment, prohibits the formation of the
1
corresponding a anomer, while in the C4
conformation the axially oriented C-4 sub-
stituent and the weak anomeric effect [7], di-
minished further by the presence of the
exogenous sulfur atom [8], makes this anomer
energetically less favoured. Debenzoylation of
14 was carried out according to the Zemple´n
procedure, affording crystalline 15 in high
yield (80%). According to the NMR data, 15
is present in dimethyl sulfoxide solution in a
4C1l1C4 conformational equilibrium, which
is strongly shifted towards the latter con-
former (Scheme 2).
both the
D
-arabino configuration and differ-
ing only in the chirality of C-1, being the a
(12) and b anomers (13). This means that
during the azidonitration process addition of
the azido group to the double bond at C-2 of
Scheme 1.

´
E. Bozo´, J. Kuszmann / Carbohydrate Research 325 (2000) 143–149
145
Scheme 2.
When 4-nitrobenzenethiol was used in the
glycosylation reaction as acceptor, and boron
trifluoride etherate as promoter, the corre-
sponding b-thioglycoside 16 was isolated as a
crystalline compound in a yield of 62.5%.
Debenzoylation according to the Zemple´n
procedure afforded 17 as a syrup.
and 4-nitrobenzenethiol were carried out un-
der the same conditions mentioned above
(Scheme 3). In these reactions the b anomers
19 and 21 were formed in satisfactory yield
and no a anomers could be detected. That is
contrary to the results obtained with the same
donor in the reaction with methanol, where
the corresponding methyl a- and b-pyran-
osides were formed in a 5:2 ratio. This might
be due to the fact that the phenylthio group is
much bulkier than the methoxy group, there-
For the synthesis of the corresponding lyxo
isomers, 1-O-acetyl-2-azido-3,4-di-O-benzoyl-
2-deoxy-5-thio-a-
D
-lyxopyranose (18) [4] was
used as donor and the reactions with 4-cyano-

´
146
E. Bozo´, J. Kuszmann / Carbohydrate Research 325 (2000) 143–149
Scheme 3.
fore its equatorial arrangement prevailing in
the b anomers is energetically favoured, and
the anomeric effect that operates in the case of
the O-glycosides is less pronounced [8] in the
case of S-glycosides. Zemple´n debenzoylation
of crude 19 and 21 afforded the crystalline
thioglycosides 20 and 22 in high yield. The b
anomeric configuration of these compounds
was evident from their NMR spectra; accord-
ing to the large J3,4 8.7 Hz and J4,5ax 9.7 Hz
activity further. A change in the configuration
of C-3 (arabino“lyxo) (15“20 and 17“22)
was accompanied by a further minor increase
in the activity.
3. Experimental
General methods.—Organic solutions were
dried over MgSO4 and concentrated under
diminished pressure at or below 40 °C. TLC:
E. Merck precoated Silica Gel 60 F254 plates,
with hexane–EtOAc mixtures (A, 4:1; B, 3:1;
C, 1:1), EtOAc (D), and toluene–MeOH mix-
tures (E, 4:1); detection by spraying the plates
with a 0.02 M soln of I2 and a 0.30 M soln of
KI in 10% aq H2SO4 soln, followed by heating
at ca. 200 °C. For column chromatography
Kieselgel 60 was used. Melting points are un-
corrected. Optical rotations were determined
on 1.0% solns in CHCl3 at 20 °C unless stated
otherwise. NMR spectra were recorded with a
4
couplings, both are present in the C1 confor-
mation and an NOE could be observed on
H-3 (5%) and H-5a (2%) by irradiating H-1.
On the other hand, no long-range coupling
between H-5e and H-1 could be detected,
excluding the equatorial arrangement of the
latter.
Biological results.—The oral antithrom-
botic activity of 15, 17, 20 and 22 was deter-
mined on rats, using Pescador’s model [9] and
beciparcil 1 as the reference compound. For
comparison, the data of the
D
-arabinose
derivatives 3 and 5 are also given. All com-
pounds were administered orally 3 h before
ligation. From the data listed in Table 1, it
can be seen that the activity of the 2-azido-
derivatives 15 and 17 was much higher com-
pared with beciparcil (1), and practically
equalled that of the 2-hydroxy analogs (3 and
5). Consequently, the exchange of the 2-OH
group by the azido group did not increase the
Table 1
Oral antithrombotic activity of beciparcil (1), 4-cyanophenyl
and 4-nitrophenyl 1,5-dithio-b-
2-deoxy-1,5-dithio-b- -arabino- (15 and 17) as well as b-
lyxopyranosides (20 and 22) in rats using Pescador’s model [9]
D-arabino- (3 and 5), 2-azido-
D
D-
Compound
1
3
5
15
17
20
22
ED50 (mg/kg)
25
3.5
3.5
3
5
2
2

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flE. Bozo´, J. Kuszmann / Carbohydrate Research 325 (2000) 143–149
147
Bruker AC 250 spectrometer at 250 MHz (1H)
and 62.9 MHz (13C) for solns in CDCl3 (inter-
nal Me4Si) unless stated otherwise. Multiplic-
ities of the 13C NMR spectra were obtained
from DEPT experiments. The assignment of
the protons was based on homonuclear decou-
pling. Connectivities between identified pro-
tons and protonated carbons were observed
by means of HETCOR experiments. The ratio
of a:b anomeric mixtures was determined by
1H NMR.
H, J5ax,5eq 12.2 Hz, H-5ax), 3.03 (m, 1 H, J1,5eq
0.7 Hz, H-5eq); 13C NMR: l 165.4, 165.1
(CꢀO), 133.0–128.1 (aromatic), 126.4 (C-1),
117.5 (C-2), 69.4, 65.1 (C-3, C-4), 24.5 (C-5).
Anal. Calcd for C19H16O4S: C, 67.04; H, 4.74;
S, 9.42. Found: C, 67.15; H, 4.88; S, 9.39.
1-O-Acetyl-2-azido-2-deoxy-3,4-di-O-ben-
zoyl-5-thio-h- (12) and i- -arabinopyranose
D
(13).—Under argon, NaN3 (1.0 g, 15.4 mmol)
was added to a stirred solution of 10 (3.5 g,
10.28 mmol) in MeCN (60 mL). The slurry
was cooled to −20 °C, Ce(NH4)2(NO3)6 (16.9
g, 30.8 mmol) was added and stirring was
continued at −20 °C for 3 h. Then, the mix-
ture diluted with ice-cold CH2Cl2 (250 mL)
and washed with ice-water (50 mL), 6% aq
NaHCO3 and water. The residue obtained
upon concentration of the organic solution
was submitted to column chromatography
(solvent A) to yield a mixture of the 1-O-ni-
tro-isomers 11 (4.2 g, 92%) as an unstable
syrup. Rf 0.50 and 0.55 (solvent A). To a
stirred solution of crude 11 (4.2 g, 9.4 mmol)
in AcOH (25 mL), NaOAc (1.5 g, 18 mmol)
was added and stirring was continued at
100 °C for 1 h. After cooling to rt, the mixture
was diluted with CH2Cl2, washed with water,
6% aq NaHCO3, and water to yield 12 and 13
(3.0 g, 72%) as a 3:7 mixture; Rf 0.4 (solvent
3,4-Di-O-acetyl-1,5-anhydro-5-thio- -ery-
D
thro-pent-1-enitol (8).—To a stirred solution
of a 1:3 mixture of bromides 7a and 7b [1] (7.1
g, 20 mmol) in dry EtOAc (100 mL), 4-picol-
ine (2.1 mL, 21 mmol) and Zn powder (10 g)
were added and the mixture was refluxed for
20 min. The reaction was cooled to room
temperature (rt) and Zn was filtered off. The
filtrate was washed with M HCl, aq NaHCO3,
dried, concentrated and the residue was
purified by column chromatography (solvent
B) to yield 8 (4.1 g, 95%); [h]D +393°; Rf 0.6
1
(solvent B); H NMR: l 6.36 (d, 1 H, J1,2 10.0
Hz, H-1), 5.75 (dd, 1 H, J2,3 4.4 Hz, H-2), 5.28
(dd, 1 H, J3,4 4.6 Hz, H-3), 5.16 (m, 1 H, H-4),
3.00–3.10 (m, 2 H, H-5a, H-5b), 2.08 (s, 3 H,
13
OAc), 2.04 (s, 3 H, OAc); C NMR: l 169.9,
169.8 (CꢀO), 125.8 (C-1), 117.2 (C-2), 66.7,
66.4 (C-3, C-4), 26.3 (C-5), 21.0, 20.9 (OAc).
Anal. Calcd for C9H12O4S: C, 49.99; H, 5.59;
S, 14.83. Found: C, 50.10; H, 5.81; S, 14.77.
1
A); H NMR: 12 l 5.87 (d, 1 H, J1,2 5.8, H-1),
5.74 (ddd, 1 H, J3,4 2.3, J4,5ax 8.2, J4,5eq 2.9 Hz,
H-4), 5.38 (dd, 1 H, J2,3 6.7 Hz, H-3), 4.42
(dd, 1 H, H-2), 3.37 (dd, 1 H, J5ax,5eq 13.8 Hz,
H-5ax), 2.95 (dd, 1 H, H-5eq), 2.03 (s, 3 H,
OAc); 13 l 6.21 (dd, 1 H, J1,2 2.0 Hz, J1,5eq 1.2
Hz, H-1), 5.92 (m, 1 H, H-4), 5.63 (dd, 1 H,
J2,3 10.8, J3,4 2.8, Hz, H-3), 4.42 (dd, 1 H,
H-2), 3.45 (dd, 1 H, J4,5ax 1.5, J5ax,5eq 14.5 Hz,
H-5ax), 2.98 (ddd, 1 H, J4,5eq 4.3 Hz, H-5eq),
2.22 (s, 3 H, OAc); 13C NMR: 12 l 168.6,
165.3, 165.0 (CꢀO), 133.5–128.4 (aromatic),
72.0, 70.8, 67.7, 62.4 (C-1,2,3,4), 31.1 (C-5),
20.6 (OAc); 13 l 168.9, 165.3, 165.1 (CꢀO),
133.5–128.4 (aromatic), 73.0, 70.3, 68.7, 61.2
(C-1,2,3,4), 27.9 (C-5), 20.9 (OAc); Anal.
Calcd for C21H19N3O6S: C, 57.14; H, 4.34; N,
9.52; S, 7.26. Found: C, 57.18; H, 4.48; N,
9.60; S, 7.22.
3,4-Di-O-benzoyl-1,5-anhydro-5-thio- -ery-
D
thro-pent-1-enitol (10).—To a stirred solution
of 8 (4.3 g, 20 mmol) in MeOH (50 mL) M
NaOMe (0.1 mL) in MeOH was added and
the mixture was left at rt 1 h. The reaction
was neutralised with solid CO2 and concen-
trated. The residue (9) was dissolved in a
mixture of pyridine (15 mL) and CH2Cl2 (60
mL) and a soln of benzoyl chloride (7.0 mL,
60.3 mmol) in CH2Cl2 (35 mL) was added
dropwise during 10 min at rt. The reaction
was stirred at rt for 1 h, then poured into
water and processed in the usual way to yield
10 (4.8 g, 71%) after recrystallization from
EtOH; mp 93–95 °C; [h]D +451°; Rf 0.7 (sol-
vent B); 1H NMR: l 6.40 (dd, 1 H, J1,2 9.8 Hz,
H-1), 5.96 (dd, 1 H, J2,3 5.6 Hz, H-2), 5.85 (m,
1 H, J3,5eq 1.5 Hz, H-3), 5.59 (ddd, 1 H, J3,4
3.2, J4,5ax 11.2, J4,5eq 3.2 Hz, H-4), 3.45 (dd, 1
4-Cyanophenyl 2-azido-2-deoxy-3,4-di-O-
benzoyl - 1,5 - dithio - i -
D
- arabinopyranoside
(14).—Under argon, 4-cyanobenzenethiol (0.9

´
E. Bozo´, J. Kuszmann / Carbohydrate Research 325 (2000) 143–149
148
NaHCO3. The organic layer was separated,
washed with 6% aq NaHCO3, water and con-
centrated. The residue was submitted to
column chromatography (solvent A then B) to
yield 16 (1.1 g, 62.5%); mp 155–160 °C
(ether); [h]D 1 −293° (c 0.5, CHCl3); Rf 0.35
(solvent A); H NMR: l 8.15–7.40 (m, 14 H,
aromatic), 5.79 (ddd, 1 H, J3,4 2.7, J4,5ax 1.5,
J4,5eq 6.6 Hz, H-4), 5.55 (dd, 1 H, J2,3 8.5 Hz,
H-3), 4.74 (d, 1 H, J1,2 3.5 Hz, H-1), 4.68 (dd,
1 H, H-2), 3.28 (dd, 1 H, J5ax,5eq 14.1 Hz,
H-5ax), 3.06 (dd, 1 H, H-5eq); 13C NMR: l
165.2, 165.0 (CꢀO), 146.7-124.1 (aromatic),
71.1, 68.3 (C-3,4), 63.4 (C-2), 52.5 (C-1), 28.3
(C-5). Anal. Calcd for C25H20N4O6S2: C,
55.96; H, 3.76; N, 10.44; S, 11.95. Found: C,
55.93; H, 3.78; N, 10.51; S, 11.90.
g, 6.6 mmol) was added to a stirred solution
of 12 and 13 (1.45 g, 3.28 mmol) in dry
1,2-dichloroethane (30 mL). The mixture was
cooled to −10 °C, then Me3SiOTf (0.6 mL,
3.2 mmol) was added and the temperature was
slowly raised to ambient temperature. After
stirring at rt for 1 h, the reaction was
quenched with Et3N, concentrated, and the
residue was submitted to column chromatog-
raphy (solvent A) to yield 14 (1.35 g, 79%);
[h]D −315° (c 0.5, CHCl3); Rf 0.35 (solvent
1
A); H NMR: l 7.98–7.30 (m, 14 H, aro-
matic), 5.78 (ddd, 1 H, J3,4 2.8, J4,5ax 2.0, J4,5eq
6.6 Hz, H-4), 5.53 (dd, 1 H, J2,3 8.0 Hz, H-3),
4.69 (d, 1 H, J1,2 3.4 Hz, H-1), 4.66 (dd, 1 H,
H-2), 3.28 (dd, 1 H, J5ax,5eq 13.3 Hz, H-5ax),
3.05 (dd, 1 H, H-5eq); 13C NMR: l 165.2,
165.0 (CꢀO), 140.3–128.5 (aromatic), 118.2
(CN), 111.0 (C-4%), 71.0, 68.3 (C-3,4), 63.4
(C-2), 52.7 (C-1), 28.8 (C-5). Anal. Calcd for
C26H20N4O4S2: C, 60.45; H, 3.90; N, 10.85; S,
12.41. Found: C, 60.52; H, 3.88; N, 10.81; S,
12.37.
4-Nitrophenyl 2-azido-2-deoxy-1,5-dithio-
i- -arabinopyranoside (17).—To a stirred so-
D
lution of 16 (1.0 g, 1.86 mmol) in MeOH (30
mL) and 1,2-dichloroethane (10 mL), M
NaOMe (0.1 mL) in MeOH was added and
the mixture was kept at rt for 1 h. After
neutralization with solid CO2, the mixture was
concentrated and the residue was submitted to
column chromatography (solvent A, then D)
to yield 17 (0.54 g, 88.5%); [h]D −307° (c 0.5,
MeOH); Rf 0.3 (solvent C); 1H NMR (Me2SO-
d6): l 8.20–7.62 (m, 4 H, aromatic), 5.56 (d, 1
H, J3,OH 5.9 Hz, 3-OH), 5.15 (d, 1 H, J4,OH 4.9
Hz, 4-OH), 5.12 (d, 1 H, J1,2 3.4 Hz, H-1),
4.32 (dd, 1 H, J2,3 8.3 Hz, H-2), 4.01 (m, 1 H,
H-4), 3.78 (ddd, 1 H, J3,4 2.7 Hz, H-3), 2.80
(m, 2 H, H-5ax,5eq). Anal. Calcd for
C11H12N4O4S2: C, 40.24; H, 3.68; N, 17.06; S,
19.53. Found: C, 40.30; H, 3.75; N, 17.11; S,
19.59.
4-Cyanophenyl 2-azido-2-deoxy-1,5-dithio-
i- -arabinopyranoside (15).—To a stirred so-
D
lution of 14 (1.25 g, 2.4 mmol) in MeOH (30
mL) and 1,2-dichloroethane (10 mL), M
NaOMe (0.1 mL) in MeOH was added and
the mixture was kept at rt for 1 h. After
neutralization with solid CO2, the mixture was
concentrated and the residue was submitted to
column chromatography (solvent C, then D)
to yield 15 (0.6 g, 80%); mp 78–83 °C (water);
[h]D −322° (c 0.5, MeOH); Rf 0.3 (solvent C);
1H NMR (Me2SO-d6): l 7.80–7.55 (m, 4 H,
aromatic), 5.52 (d, 1 H, J3,OH 5.9 Hz, 3-OH),
5.14 (d, 1 H, J4,OH 4.6 Hz, 4-OH), 5.08 (d, 1
H, J1,2 3.4 Hz, H-1), 4.30 (dd, 1 H, J2,3 8.3 Hz,
H-2), 4.00 (m, 1 H, H-4), 3.76 (ddd, 1 H, J3,4
2.4 Hz, H-3), 2.78 (m, 2 H, H-5ax,5eq). Anal.
Calcd for C12H12N4O2S2: C, 46.74; H, 3.92; N,
18.17; S, 20.79. Found: C, 46.82; H, 3.85; N,
18.20; S, 20.85.
4-Cyanophenyl 2-azido-2-deoxy-1,5-dithio-
i- -lyxopyranoside (20).—Under argon, 4-
D
cyanobenzenethiol (0.6 g, 4.44 mmol) was
added to a stirred solution of 18 [4] (0.95 g,
2.15 mmol) in dry 1,2-dichloroethane (30 mL).
The mixture was cooled to −10 °C, then
Me3SiOTf (0.45 mL, 2.5 mmol) was added
and the temperature was slowly raised to am-
bient temperature. After stirring at rt for 1 h,
the reaction was quenched with Et3N, concen-
trated, and the residue was submitted to
column chromatography (solvent A) to yield
19 (0.54 g, 49%); Rf 0.4 (solvent A). To a
stirred solution of crude 19 (0.54 g) in MeOH
4-Nitrophenyl
2-azido-2-deoxy-3,4-di-O-
- arabinopyranoside
benzoyl - 1,5 - dithio - i -
D
(16).—To a stirred solution of 12 and 13 (1.45
g, 3.28 mmol) in dry 1,2-dichloroethane (30
mL) 4-nitrobenzenethiol (0.56 g, 3.6 mmol)
was added. After addition of BF3·Et2O (0.4
mL, 3.23 mmol), the mixture was stirred at rt
for 24 h, then poured into ice-cold 6% aq

´
E. Bozo´, J. Kuszmann / Carbohydrate Research 325 (2000) 143–149
149
76%); mp 174–176 °C (ether); [h]D1 −17° (c
0.5, MeOH); Rf 0.3 (solvent E); H NMR
(Me2SO-d6): l 8.20–7.65 (m, 4 H, aromatic),
5.74 (d, 1 H, J3,OH 3.9 Hz, 3-OH), 5.29 (d, 1
H, J4,OH 4.4 Hz, 4-OH), 5.06 (d, 1 H, J1,2 2.2
Hz, H-1), 4.35 (dd, 1 H, J2,3 2.6 Hz, H-2), 3.75
(m, 1 H, H-4), 3.64 (ddd, 1 H, J3,4 8.7 Hz,
H-3), 2.65 (m, 2 H, H-5ax,5eq). Anal. Calcd
for C11H12N4O4S2: C, 40.24; H, 3.68; N, 17.06;
S, 19.53. Found: C, 40.28; H, 3.72; N, 17.09;
S, 19.60.
(30 mL), M NaOMe (0.1 mL) in MeOH was
added and the mixture was kept at rt for 1 h.
After neutralization with solid CO2, the mix-
ture was concentrated and the residue was
submitted to column chromatography (solvent
E) to yield 20 (0.24 g, 75%); mp 154–157 °C
(ether); [h]D −80.5° (c 0.5, pyridine); Rf 0.3
1
(solvent E); H NMR (Me2SO-d6): l 7.80–
7.60 (m, 4 H, aromatic), 5.71 (d, 1 H, J3,OH 4.2
Hz, 3-OH), 5.26 (d, 1 H, J4,OH 4.5 Hz, 4-OH),
5.01 (d, 1 H, J1,2 2.3 Hz, H-1), 4.32 (dd, 1 H,
J2,3 3.0 Hz, H-2), 3.72 (m, 1 H, H-4), 3.62
(ddd, 1 H, J3,4 8.7 Hz, H-3), 2.64 (dd, 1 H,
J4,5ax 9.7, J5ax,5eq 13.2 Hz, H-5ax), 2.58 (dd, 1
H, J4,5eq 4.7 Hz, H-5eq). Anal. Calcd for
C12H12N4O2S2: C, 46.74; H, 3.92; N, 18.17; S,
20.79. Found: C, 46.80; H, 3.88; N, 18.21; S,
20.83.
Acknowledgements
The authors are very much indebted to Dr
Gabriella Szabo´ for the biological results and
to Sa´ndor Boros for recording the NMR spec-
tra.
4-Nitrophenyl 2-azido-2-deoxy-1,5-dithio-
i- -lyxopyranoside (22).—To a stirred solu-
D
tion of 18 [4] (0.65 g, 1.47 mmol) in dry
1,2-dichloroethane (10 mL) 4-nitroben-
zenethiol (0.25 g, 1.6 mmol) was added. After
addition of BF3·Et2O (0.2 mL, 1.6 mmol), the
mixture was stirred at rt for 24 h, then poured
into ice-cold 6% aq NaHCO3. The organic
layer was separated, washed with 6% aq
NaHCO3, water and concentrated. The
residue was submitted to column chromatog-
raphy (solvent A) to yield 21 (0.43 g, 54%); Rf
0.4 (solvent A). To a stirred solution of crude
21 (0.43 g) in MeOH (20 mL) and 1,2-
dichloroethane (10 mL), M NaOMe (0.1 mL)
in MeOH was added and the mixture was
kept at rt for 1 h. After neutralization with
solid CO2, the mixture was concentrated and
the residue was submitted to column chro-
matography (solvent E) to yield 22 (0.2 g,
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