Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio-L- and -D-arabinopyranosides possessing antithrombotic activity

Article abstract of DOI:10.1016/S0008-6215(98)00221-3

5-S-Benzoyl-2,3-O-isopropylidene-5-thio-L-arabinose, prepared from L-arabinose diethyl dithioacetal gave, on treatment with sodium methoxide in methanol, 4-O-benzoyl-2,3-O-isopropylidene-5-thio-L-arabinopyranose 12 which was converted into its 1-O-acetate 14. Hydrolysis of 12 in acetic acid-water afforded, after acetylation, 1,2,3-tri-O-acetyl-4-O-benzoyl-5-thio-L-arabinopyranose 17 which was transformed into 2,3-di-O-acetyl-4-O-benzoyl-5-thio-L-arabinopyranosyl bromide 20. Zemplen deacylation of 17 gave 5-thio-L-arabinopyranose which was converted via 1,2,3,4-tetra-O-acetyl-5-thio-β-L-arabinopyranose 5 into 2,3,4-tri-O-acetyl-5-thio-β-L-arabinopyranosyl bromide 6 and into O-(2,3,4-tri-O-acetyl-5-thio-L-arabinopyranosyl) trichloro-acetimidate 7. Glycosidation of 4-nitrophenol with 12 under the Mitsunobu conditions afforded 4-nitrophenyl 4-O-benzoyl-2,3-O-isopropylidene-5-thio-α- and β-L-arabinopyranoside in a ~1:2 ratio. Condensation of the glycosyl donors 6, 7, 17, and 20 with 4-cyano- and 4-nitrobenzenethiol yielded, after deacylation, 4-cyano- and 4-nitrophenyl 1,5-dithio-α- and β-L-arabinopyranosides 28α, 28β, 29α and 29β in different ratios and yields, depending on the reaction conditions applied. In a similar manner the corresponding D-isomers 30α, 30β, 31α and 31β were also prepared. All of these glycosides, except 28α, showed a stronger oral antithrombotic effect in rats as compared to beciparcil, used as reference. Copyright (C) 1998 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(98)00221-3

Carbohydrate Research 311 (1998) 191±202
Synthesis of 4-cyanophenyl and 4-nitrophenyl
1,5-dithio-l- and -d-arabinopyranosides
possessing antithrombotic activity1,2
Eva Bozo, Sandor Boros, Janos Kuszmann *
Institute for Drug Research, PO Box 82, H-1325 Budapest, Hungary
Received 27 May 1998; accepted 1 August 1998
Abstract
5-S-Benzoyl-2,3-O-isopropylidene-5-thio-l-arabinose, prepared from l-arabinose diethyl
dithioacetal gave, on treatment with sodium methoxide in methanol, 4-O-benzoyl-2,3-O-iso-
propylidene-5-thio-l-arabinopyranose 12 which was converted into its 1-O-acetate 14. Hydrolysis
of 12 in acetic acid±water a€orded, after acetylation, 1,2,3-tri-O-acetyl-4-O-benzoyl-5-thio-l-ara-
binopyranose 17 which was transformed into 2,3-di-O-acetyl-4-O-benzoyl-5-thio-l-arabinopyr-
anosyl bromide 20. Zemplen deacylation of 17 gave 5-thio-l-arabinopyranose which was
converted via 1,2,3,4-tetra-O-acetyl-5-thio-ꢀ-l-arabinopyranose 5 into 2,3,4-tri-O-acetyl-5-thio-ꢀ-
l-arabinopyranosyl bromide 6 and into O-(2,3,4-tri-O-acetyl-5-thio-l-arabinopyranosyl) tri-
chloro-acetimidate 7. Glycosidation of 4-nitrophenol with 12 under the Mitsunobu conditions
a€orded 4-nitrophenyl 4-O-benzoyl-2,3-O-isopropylidene-5-thio-ꢁ- and ꢀ-l-arabinopyranoside in
a ꢀ1:2 ratio. Condensation of the glycosyl donors 6, 7, 17, and 20 with 4-cyano- and 4-nitro-
benzenethiol yielded, after deacylation, 4-cyano- and 4-nitrophenyl 1,5-dithio-ꢁ- and ꢀ-l-arabi-
nopyranosides 28ꢀ, 28ꢁ, 29ꢀ and 29ꢁ in di€erent ratios and yields, depending on the reaction
conditions applied. In a similar manner the corresponding d-isomers 30ꢀ, 30ꢁ, 31ꢀ and 31ꢁ were
also prepared. All of these glycosides, except 28ꢀ, showed a stronger oral antithrombotic e€ect in
rats as compared to beciparcil, used as reference. # 1998 Elsevier Science Ltd. All rights reserved
Keywords: 5-Thio-l and d-arabinose derivatives; S!O-benzoyl migration; Glycosidation reactions; Thiogly-
cosides; Oral antithrombotic activity
1. Introduction
activity of 4-cyanophenyl 1,5-dithio-ꢀ-d-xylopyr-
anoside (beciparcil, 1) [6] could be signi®cantly
increased by replacing the individual hydroxyl
groups of the pentose unit with azido groups or by
using the hexose congener (5-thio-d-glucopyr-
anose). It was presumed [6] that these thioglyco-
sides express their antithrombotic activity by acting
in vivo as initiators in the biosynthesis of the nat-
ural antithrombotic glycosaminoglycans (GAGs),
increasing their concentration. Nevertheless the
In the previous parts of this series of papers
[2±5], we have shown that the oral antithrombotic
* Corresponding author. Fax: +36-1-399-3441; e-mail:
h13757kus@ella.hu
1
Orally active antithrombotic thioglycosides, Part VI.
For Part V, see [1].
2
Presented partly at the XVIIIth International Carbo-
hydrate Symposium, Milan, 21±26 July 1996. Abstr. BP092.
0008-6215/98/$Ðsee front matter # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00221-3

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E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
192
4
same e€ect could arise from blocking the galacto-
syltransferase I enzyme, that binds the primarily
formed free GAGs to proteins, yielding the endo-
genous proteoglycans (PGs), being void of any
antithrombotic activity. Accordingly, it was pre-
sumed that 1,5-dithio-d-galactopyranosides (2)
might possess some antithrombotic activity by
acting as enzyme inhibitors. As the synthesis of 5-
thio-d-galactose would be too demanding, that of
its pentose congener (5-thio-l-arabinose), as well
as that of its thiopyranosides (3) was decided
(Scheme 1).
(ꢁ:ꢀ=15:85). The cyclic C1 (ꢀ-l) conformation of
the separated 12ꢁ was evident from its NMR
3
spectrum as for H-1, besides a J1,2 coupling of
4
2.7 Hz a J1,5eq coupling of ꢀ1 Hz could be detec-
ted too. Because of the presence of the ring sulfur
atom, the trans fused dioxolane ring at C-2,3,
which has already been detected in xylopyranosides
[14] is well tolerated. The 4-O-benzoyl group of 12
could be removed by carrying out the deacylation
at re¯ux temperature yielding crystalline 13,
which proved to be a 1:9 mixture of the ꢁ,ꢀ-
anomers. In pyridine solution, a mutarotation
(+252ꢁ (5 min)!+230ꢁ (24 h)) could be detected.
Acetylation of 12 in pyridine with acetic anhydride
gave 14 as an anomeric mixture (ꢁ:ꢀ ꢀ 2:3) from
which a 1:1 mixture could be separated on crystal-
lization from methanol. When the isopropylidene
group of 12 was split o€ in boiling methanol with
concd hydrochloric acid, the 4-O-benzoyl group
remained intact and an anomeric mixture of the
corresponding methyl pyranosides was obtained
which was isolated after acetylation as its diacetate
15 (ꢁ:ꢀ ꢀ 1:6). The ester groups of this mixture
could be removed under normal Zemplen condi-
tions a€ording the crystalline methyl ꢀ-pyranoside
16ꢁ. When aqueous acetic acid was used for the
hydrolysis of the isopropylidene group of 12, the 4-
O-benzoate 18 was obtained in solid state contain-
ing the ꢁ:ꢀ-anomers in a ratio of 1:9. Acetylation
of this mixture gave the anomeric mixture of the
mixed ester 17. Debenzoylation of 18 according to
Zemplen's method gave crystalline 19ꢁ which yiel-
ded the tetra-acetate 5 on acetylation. For com-
paring the di€erent glycosidation methods, both
tetra-esters 5 and 17 were converted by treatment
with hydrogen bromide in acetic acid into the cor-
responding pyranosyl bromides 6 and 20, respec-
tively, which were used as glycosyl donors. For the
same purpose, the anomeric acetyl group of 5 was
selectively removed with hydrazine acetate, and the
formed anomeric mixture of the 1-OH derivative
21 was converted into its trichloroacetimidate 7.
The bene®t of using the 4-O-benzoates 17 and 20 in
2. Results and discussion
Synthesis of the donor molecules.ÐFor the
synthesis of the planned 3 type thioglycosides,
proper 5-thio-l-arabinopyranose donors 6 or 7
were needed. Bromide 6 was synthesized recently
[7] from the corresponding 5-O-tosyl dibenzyl
dithioacetal 4, which is however a rather unstable
intermediate, and decomposes easily yielding ben-
zyl 5-S-benzyl-1,5-dithio-arabinofuranoside [8,9].
Imidate 7 has not been described so far, but its
d-isomer was synthesized [10] using 1,2,3-tri-O-
acetyl-5-O-trityl-d-arabinofuranose 8 as an inter-
mediate which can be obtained from d-arabinose
in a multi-step process only. In order to avoid these
drawbacks, the readily available [3] and stable 5-O-
tosylate of 2,3-O-isopropylidene-l-arabinose die-
thyl dithioacetal 9 was used as starting material
and converted in excellent yield into the 5-S-
benzoate 10. The ethylthio groups of 10 were split
o€ with mercuric oxide in the presence of boron
tri¯uoride etherate [11] and the obtained aldehyde
11 was submitted to the Zemplen deacylation pro-
cedure at room temperature using 0.1 equiv of
sodium methoxide [12,13]. Under these conditions,
instead of deacylation only migration of the ben-
zoyl group from S-5 to O-4 took place and the
formed free thiol group closed immediately to a
pyranose ring a€ording 12 as an anomeric mixture
Scheme 1.

Â
E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
193
the glycosidation reactions was that the formed
anomeric mixtures could be separated, while
unseparable mixtures were formed when the
corresponding 4-O-acetate 6 was used as donor
(Schemes 2 and 3).
formed in a ratio of 1:4, and according to NMR
1
data 17ꢀ adopts preferably the C4(l) conforma-
4
tion, while 17ꢁ prefers the C1(l) conformation
(Scheme 4). That means that, although in 17ꢀ the
energy gained by the anomeric e€ect of the exo-
cyclic sulfur atom [17] compensates the steric strain
caused by the 1,3-diaxial arrangement of the two
It is worthwhile mentioning that the two anomers
of the 4-O-benzoyl triacetates (17ꢀ and 17ꢁ) are
Scheme 2.
Scheme 3.

Â
E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
194
Scheme 4.
acetoxy groups, this conformation is energetically
less favored than that in 17ꢁ for which no such
1,3-diaxial arrangement exist.
modest yield, deprotection of these glycosides was
not attempted.
In all further experiments the 2,3-O-acetate
derivatives were used as donors, di€ering in the
substitution at C-1 and O-4, and the results are
listed in Table 1. The reaction of the acetobromo
derivative 6 with the corresponding 4-cyano and 4-
nitrobenzenethiol was carried out in acetone in the
Glycosidation reactions.ÐAs the free anomeric
hydroxy group of O-isopropylidene protected car-
bohydrate derivatives can be glycosylated under
Mitsunobu conditions [18,19], in a model experi-
ment, the 2,3-O-isopropylidene derivative 12 was
treated with 4-nitrophenol in the presence of tri-
phenylphosphine and diethyl azodicarboxylate.
The resulting anomeric mixture of the nitrophenyl
glycosides could be separated by column chroma-
tography a€ording 22ꢀ and 22ꢁ in 35 and 18.6%
yield, respectively. However, when 4-nitro- or 4-
cyanobenzenethiol was used as aglycon, no thio-
glycosides could be isolated.
In our further experiments the O-isopropylidene
protected 1-acetate 14 was used as donor, tri-
methylsilyl tri¯ate as activator and 4-cyanobenze-
nethiol as acceptor. Under these conditions, an
ꢁ,ꢀ-anomeric mixture (7:3) of the corresponding
thioglycosides (23) was formed in 24% yield, from
which the anomers 23ꢀ and 23ꢁ could be sepa-
rated by column chromatography. Because of this
ꢁ
presence of potassium carbonate at 60 C. The
corresponding thioglycosides 24 and 25 were
formed in both cases as 1:1 anomeric mixtures (64
and 61%) which could not be separated by crys-
tallization or column chromatography. When the
imidate 7 was used as donor and 4-cyanobenze-
nethiol as acceptor in 1,2-dichloroethane in the
presence of boron tri¯uoride etherate as promoter,
the reaction became much faster and was com-
pletedꢁ within 15 min even at low temperature
( 15 C). Under these conditions, the anomerisa-
tion is a slower process and 24 was obtained in a
much higher ꢁ:ꢀ ratio (1:4) and from this mixture
24ꢁ could be separated by crystallization.
When the 1,2,3-tri-O-acetate-4-O-benzoate 17 was
used as donor, 4-cyanobenzenethiol as acceptor
Table 1
In¯uence of the reaction conditions on the glycosidation reactions with l-arabinopyranosyl donors
Run Donor Acceptora
Promoter
Solvent
Time
Temp. (ꢁC)
Product Yield (%) ꢁ,ꢀ ratio
1
2
3
4
5
6
7
8
6
6
7
17
17
20
20
20
CN
NO2
CN
CN
NO2
CN
K2CO3
K2CO3
.
BF3 Et2O
TMSOTf
.
BF3 Et2O
K2CO3
ZnO
K2CO3
Acetone
Acetone
1,2-Dichloroethane
1,2-Dichloroethane
1,2-Dichloroethane
Acetone
2 h
60
60
15
20
20
60
20
60
24
25
24
26
27
26
26
27
64
61
92
87
81
55
64
42
1:1b
1:1b
1:4
1:2
1:2
1.3:1
1.3:1
1.3:1
1 h
15 min
2 h
24 h
1 h
CN
NO2
Acetonitrile/toluene
Acetone
30 min
2 h
a
Substituent of the 4-substituted thiophenol.
Unseparable mixture.
b

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E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
195
and trimethylsilyl tri¯ate as promoter the ꢁ:ꢀ ratio
of the corresponding thioglycoside 26 was 1:2 and
the reaction reached completion within 2 h at 20 ꢁC.
Essentially the same anomeric ratio of 27 was
obtained when 4-nitrobenzenethiol was used as
aglycon and boron tri¯uoride etherate as pro-
moter, but the reaction was much slower and was
mixtures (F, 4:1; G, 9:1); detection by spraying the
plates with a 0.02 M solution of I2 and a 0.3 M
solution of KI in 10% aq H2SO4 solution fol-
lowed by heating at ca. 200 ꢁC. For column
chromatography, Kieselgel 60 was used. The mp
are uncorrected. Optical rotations were deter-
mined on 1.0% solutions in CHCl3 at 20 ꢁC unless
stated otherwise. NMR spectra were recorded
with a Bruker AC 250 spectrometer at 250 MHz
(1H) and 62.9 MHz (13C) for solutions in CDCl3
(internal Me4Si) unless stated otherwise (Tables 3
and 4). Multiplicities of the 13C NMR spectra
were obtained from DEPT experiments. The
assignment of the protons were based on homo-
nuclear decoupling experiments. The ratio of ꢁ:ꢀ
ꢁ
completed after 24 h at 20 C. For comparison,
both 26 and 27 were synthesized also by using the
corresponding bromide 20 as donor. The ratio of
the anomers (ꢁ,ꢀ=1.3:1) did not depend on the
aglycon or the applied promoter, but the highest
yield and fastest reaction was obtained in the pre-
sence of zinc oxide.
The ester groups of all separated isomers could
be removed under Zemplen's condition and the
resulting thioglycosides 28ꢀ, 28ꢁ, 29ꢀ and 29ꢁ were
obtained in crystalline state. In solution (CDCl3),
1
anomeric mixtures was determined by H NMR
spectroscopy. Structural formulas of the corre-
sponding intermediates refer to the l-isomers, the
data of the corresponding d-enantiomers are indi-
cated by the addition of -D to the number of the
formulas.
4
all acylated glycosides (24±27) adopted the C1(l)
conformation, independently of the con®guration
of the anomeric center. However, in the case of the
4
1
deacylated derivatives 28 and 29, a C1(l)$ C4(l)
equilibrium could be detected for both anomers by
NMR spectroscopy which in the case of the ꢀ-
5-S-Benzoyl-2,3-O-isopropylidene-5-thio-l-arab-
inose (11).ÐTo a stirred slurry of HgO (18 g) in
.
THF (400 mL) and water (45 mL), BF3 Et2O (48%,
anomers was strongly shifted towards the C4(l)
12 mL) was added at 0 ꢁC. Thereafter, a solution of
10 [3] (16.6 g, 40 mmol) in THF (40 mL) was added
over a period of 30 min. Stirring was continued at
20 ꢁC for 1 h, then the reaction mixture was poured
into a stirred slurry of ether (500 mL) and Na2CO3
(20 g). The organic solution was washed with 10%
aq K2CO3 until a pH of ꢀ 9 was reached and then
with water to give on concentration 11 (12.4 g,
ꢀ100%) containing, according to NMR spectro-
scopy, some 11-hydrate. Therefore, no correct
analytical data could be obtained; [ꢁ]d +145ꢁ; Rf
0.5 (solvent A); 1H NMR: ꢂ 9.85 (d, 1 H, H-1), 4.52
(dd, 1 H, H-2), 4.30 (dd, 1 H, H-3), 1.40, 1.46 (2s, 6
H, CMe2); J1,2 1,2; J2,3 6.5; J3,4 4.2 Hz; 13C NMR: ꢂ
201.4 (aldehyde), 96.0 (aldehyde±hydrate).
1
conformation. In methanol-d4 at low temperature
(203 K), the two conformers of 28ꢁ gave separated
signals and their ratio was 2:8.
All reactions mentioned above were repeated
with the corresponding d-isomers too, a€ording
the thioglycosides 30ꢀ, 30ꢁ, 31ꢀ and 31ꢁ which
were submitted together with their enantiomers to
biological testing (Scheme 5).
Biological results.ÐThe oral antithrombotic
activity of 1, 28ꢀ, 28ꢁ, 29ꢀ, 29ꢁ, 30ꢀ, 30ꢁ, 31ꢀ and
31ꢁ was determined in rats, using Pescador's model
[20]. All compounds were administered orally 3 h
before ligation. From the data listed in Table 2, it
can be seen that while the 28ꢀ isomer was only
slightly more active than the reference compound
(beciparcil 1) all other isomers showed a much
stronger anticoagulant activity.
5-S-Benzoyl-2,3-O-isopropylidene-5-thio-d-arab-
inose (11-D). [ꢁ]d 147ꢁ.
4-O-Benzoyl-2,3-O-isopropylidene-5-thio-l-arab-
inopyranose (12).ÐA solution of crude 11 (10.9 g,
35 mmol) in MeOH (50 mL) was treated with
methanolic 4 M NaOMe (1 mL) at room tempera-
ture. The mixture was neutralized with solid CO2
after 15 min, ®ltered and concentrated to give
crude 12 (10.5 g, 97%) as an anomeric mixture
(ꢁ:ꢀꢀ15:85). Column chromatography (solvent B)
a€orded 12ꢁ (5.19 g, 48%) as syrup; [ꢁ]d +215ꢁ;
Rf 0.5 (solvent B). Anal. Calcd for C15H18O5S: C,
58.05; H, 5.85; S, 10.33. Found: C, 58.00; H, 5.89;
3. Experimental
General methods.ÐOrganic solutions were dried
over MgSO4 and concentrated under diminished
ꢁ
pressure at or below 40 C. TLC used E. Merck
precoated Silica Gel 60 F254 plates, with hexane±
EtOAc mixtures (A, 1:2; B, 2:1; C, 3:1; D, 5:1),
EtOAc±EtOH mixture (E 9:1) and toluene±MeOH

Â
E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
196
Scheme 5.
S, 10.25. The same compound could be obtained in
95% yield when acetate 14 was used as starting
material.
4-O-Benzoyl-2,3-O-isopropylidene-5-thio-d-arab-
inopyranose (12-D). [a]d 217ꢁ. Anal. Calcd for
C15H18O5S: C, 58.05; H, 5.85; S, 10.33. Found: C,
57.95; H, 5.90; S, 10.27.
14 (1.75 g, 5 mmol) in CH2Cl2 (10 mL) and MeOH
(10 mL) was boiled in the presence of methanolic
M NaOMe (0.3 mL) for 1 h to give after neutraliza-
tion with solid CO2, ®ltration and concentration 13
(0.95 g, 93%): mp 123±125 ꢁC (ether±hexane) as an
anomeric mixture (ꢁ:ꢀ ꢀ 1:9); [ꢁ]d +190ꢁ; mutar-
otation: [ꢁ]d +252ꢁ (5 min) !+230ꢁ (24 h, c 1,
pyridine); Rf 0.5 (solvent D). Anal. Calcd for
C8H14O4S: C, 46.59; H, 6.85; S, 15.52. Found: C,
46.48; H, 6.90; S, 15.42.
2,3-O-Isopropylidene-5-thio-l-arabinopyranose
(13).ÐA solution of crude 12 (1.35 g, 5 mmol) or
2,3-O-Isopropylidene-5-thio-l-arabinopyranose
(13-D). mp 122±125 C (ether±hexane) anomeric
mixture (ꢁ:ꢀ ꢀ 1:9); [ꢁ]d 192ꢁ; mutarotation: [ꢁ]d
+254ꢁ (5 min)! +235ꢁ (24 h, c 1, pyridine). Anal.
Calcd for C8H14O4S: C, 46.59; H, 6.85; S, 15.52.
Found: C, 46.52; H, 6.92; S, 15.48.
Table 2
Oral antithrombotic activity of 1, 28ꢀ, 28ꢁ, 29ꢀ, 29ꢁ, 30ꢀ,
30ꢁ, 31ꢀ, and 31ꢁ in rats using Pescador's model [20]
ꢁ
Compound
1 28ꢀ 28ꢁ 29ꢀ 29ꢁ 30ꢀ 30ꢁ 31ꢀ 31ꢁ
25 15 1.5 3.5 3.5 3.5
ED50 (mg/kg)
5
2
1

Â
E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
197
Table 3
Selected H NMR data for solutions in CDCl3
1
Compound
Chemical shifts (ꢂ)
Coupling constants (Hz)
H-1
H-2
H-3
H-4
H-5ax
H-5eq
J1,2
J2,3 J3,4 J4,5ax
J4,5eq
J5ax,5eq
J1,5eq
12ꢁ
13ꢁ
14ꢀ
14ꢁ
15ꢀ
15ꢁ
17ꢀ
5.42 4.55 4.18 5.85
5.35 4.35 4.02 4.64
6.02 4.52 3.68 5.78
6.28 4.62 4.12 5.88
4.42 5.15±5.80
3.32
3.25
3.20
3.26
3.18
3.22
3.31
3.43
2.75±3.10
3.03
3.50
3.24
3.24
3.20
3.34
2.88
3.18
2.90
3.18
2.98±3.20
3.36
3.00±3.20
3.36
2.70
2.94
3.00
2.20
nd
2.65±2.85
2.96
2.95
2.73
3.08
2.98
2.68
2.74
2.81
2.88
2.7
2.6
9.2
2.8
5.0
2.5
4.7
9.5 2.2
9.5 2.2
9.3 2.9
9.7 2.3
1.8
1.9
3.4
1.9
3.5
3.6
4.0
3.4
3.0
4.2
3.3
4.3
nd
5.8
4.3
3.7
3.4
3.4
3.7
6.6
6.0
6.8
5.8
5.6
5.5
ꢀ6
5.6
nd
14.9
14.3
14.9
14.8
13.4
14.7
13.5
14.9
nd
13.9
15.0
15.0
14.8
14.9
14.9
14.2
14.4
14.4
14.4
ꢀ1
ꢀ1
Ð
ꢀ1
ndb
nd
nd
nd
nd
ꢀ8
Ð
4.73 5.15±5.80
1.4
9.4
1.4
1.6
Ð
1.6
Ð
5.80 5.45 5.28 5.63
6.24 5.65 5.43 5.85
4.60 3.90 3.65 5.35
4.96 3.95 3.88 5.42
5.68 5.28 5.49 5.79
5.62 4.72 3.75 5.85
5.80 4.76 4.38 5.92
4.50 4.22 3.63 5.80
4.92 4.84 4.11 5.85
4.24 5.45 5.05 5.45
4.85 5.55 5.35 5.46
4.38 5.45 5.06 5.45
4.91 5.58 5.36 5.45
4.38 5.56 5.15 5.68
4.96 5.67 5.48 5.76
4.42 5.58 5.18 5.70
5.02 5.70 5.48 5.75
4.42 3.88 3.44 4.02
4.75 4.06 3.66 4.00
4.80 4.25 3.82 4.16
4.82 4.19 3.85 4.12
4.94 4.38 3.60 4.20
4.50 3.95 3.48 4.04
4.82 4.12 3.70 4.05
nd
17ꢁ
3.0 10.8 2.9
6.7
2.3
18ꢀa
18ꢁa
20
nd nd
8.7 2.4
nd
2.81
3.00
3.16
3.02
2.96
3.00
3.03
2.85
3.06
2.85
1.4
1.5
2.9
1.8
1.9
1.7
2.6
1.7
2.7
1.7
2.9
ꢀ2
ꢀ3
1.5
nd
9.6
9.8
ꢀ1
3.4 10.2 2.9
2.2
Ð
22ꢀ
22ꢁ
23ꢀ
23ꢁ
24ꢀ
24ꢁ
25ꢀ
25ꢁ
8.8
2.6
10.4
4.0
7.8
3.9
7.8
3.7
8.3
3.9
8.1
3.9
7.3
2.0
2.5
nd
9.1 2.6
9.6 2.3
8.9 2.2
9.4 2.4
7.7 2.8
9.3 2.7
7.8 2.9
9.3 2.9
8.3 2.8
9.5 2.9
8.1 2.6
9.5 3.0
7.2 2.6
5.3 1.8
6.1 2.4
4.4 nd
ꢀ1
Ð
1.0
Ð
1.2
Ð
1.4
Ð
26ꢀ
26ꢁ
27ꢀ
ꢀ14
2.95
2.96
14.6
ꢀ14.5
14.5
nd
ꢀ1
Ð
1.4
Ð
27ꢁ
28ꢀa
28ꢁa
28ꢁc
28ꢁ,(1C4)c,d
28ꢁ,(4C1)c,d
29ꢀa
29ꢁa
2.26
2.54
2.30
2.52
3.5
3.4
nd
nd
nd
12.5
13.0
12.2
12.5
nd
nd
12.2
nd
nd
10.3
3.9 10.3 nd
7.0
1.9
6.8 2.5
5.0 2.3
Ð
nd
2.32
3.3
12.6
a
Me2SO-d6.
nd, Not determined.
b
c MeOH-d4.
d
203 K.
1-O-Acetyl-4-O-benzoyl-2,3-O-isopropylidene-5-
thio-l-arabinopyranose (14).ÐAcetylation of crude
12 (11 g, 35.5 mmol) in pyridine (20 mL) with Ac2O
(15 mL) gave, after usual processing and column
chromatography (solvent D), 14 (9 g, 72%) as a
semisolid anomeric mixture (ꢁ:ꢀ ꢀ4:6). Recrys-
tallization from methanol a€orded an ꢁ:ꢀ ꢀ 1:1
mixture (3.2 g, 26%): mp 118±120ꢁ; [ꢁ]d +230ꢁ; Rf
0.6 (solvent C). Anal. Calcd for C8H14O4S: C,
46.59; H, 6.85; S, 15.52. Found: C, 46.48; H, 6.90;
S, 15.42.
1-O-Acetyl-4-O-benzoyl-2,3-O-isopropylidene-5-
thio-d-arabinopyranose (14-D). ꢁ:ꢀ ꢀ1:1 mixture,
mp 117±119ꢁ. Anal. Calcd for C8H14O4S: C, 46.59;
H, 6.85; S, 15.52. Found: C, 46.51; H, 6.79; S,
15.39.
(0.5 mL) was boiled for 15 min, cooled, neutralized
with NaHCO3, ®ltered and concentrated. The resi-
due was dissolved in pyridine (10 mL) and Ac2O
(7 mL) to give after usual processing and column
chromatography (solvent D) 15 (2.3 g, 58%) as an
anomeric mixture (ꢁ:ꢀ ꢀ1:6); Rf 0.6 (solvent C).
Anal. Calcd for C17H20O7S: C, 55.43; H, 5.47; S,
8.70. Found: C, 55.25; H, 5.66; S, 8.52.
Methyl 2,3-di-O-acetyl-4-O-benzoyl-5-thio-d-arab-
inopyranoside (15-D). ꢁ:ꢀ ꢀ1:5 mixture. Anal.
Calcd for C17H20O7S: C, 55.43; H, 5.47; S, 8.70.
Found: C, 55.29; H, 5.60; S, 8.58.
Methyl 5-thio-b-l-arabinopyranoside (16).ÐDea-
cylation of 15 (1.5 g, 4 mmol) with methanolic M
NaOMe (0.1 mL) in MeOH (10 mL) at room tem-
perature a€orded after 24 h crystalline 16 (0.24 g,
38%). The residue of the concentrated mother
liquor gave, after column chromatography (solvent
E), a second crop of 16 (0.21 g, 33%): mp 178±180 ꢁC;
Methyl 2,3-di-O-acetyl-4-O-benzoyl-5-thio-l-arab-
inopyranoside (15).ÐA solution of crude 12 (3.5 g,
10 mmol) in MeOH (20 mL) and concd HCl

Â
E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
198
Table 4
Selected 13C NMR data for solutions in CDCl3
Compound
Chemical shifts (ꢂ)
C-1
C-2
C-3
C-4
C-5
Others
12ꢁ
14ꢀ
14ꢁ
15ꢀ
15ꢁ
18ꢁb
20
22ꢀ
22ꢁ
23ꢀ
23ꢁ
26ꢀ
26ꢁ
27ꢀ
27ꢁ
28ꢀb
28ꢁb
74.6a
77.8a
72.9a
81.7
81.9
73.9a
55.4
80.9a
79.0a
50.7
52.8
50.4
51.4
50.3
51.3
51.0
48.9
73.3a
74.6a
72.9a
70.8a
71.6a
72.9a
70.9a
77.9a
73.9a
67.8a
68.4a
69.0a
68.5a
69.0a
68.5a
75.9a
65.9a
71.8a
74.5a
72.6a
69.7a
69.7a
72.8a
69.3a
75.3a
72.6a
73.8a
73.9a
70.6a
69.1a
70.6a
69.0a
72.3a
72.6a
69.1a
67.0a
68.5a
68.8a
68.3a
68.6a
69.0a
67.1a
68.5a
79.6a
74.3a
71.7a
71.4a
71.6a
71.4a
73.8a
73.6a
28.5
31.5
29.5
23.8
26.5
26.0
29.5
31.7
29.4
33.8
29.5
29.6
28.1
29.5
28.2
30.9
29.4
108.1 (CMe2)
110.8 (CMe2)
108.6 (CMe2)
57.1 (OMe)
56.4 (OMe)
110.1 (CMe2)
108.8 (CMe2)
108.8 (CMe2)
109.0 (CMe2)
a
Arbitrary assignment.
Me2SO-d6.
b
[ꢁ]d +457ꢁ (c 0.5, water); Rf 0.4 (solvent E). Anal.
Calcd for C6H12O4S: C, 39.99; H, 6.71; S, 17.79.
Found: C, 40.0; H, 6.75; S, 17.66.
4-O-Benzoyl-5-thio-d-arabinopyranose
(18-D).
ꢁ
mp 138±140 C (acetone±ether) [ꢁ]d 299ꢁ (c 1,
acetone), mutarotation: [ꢁ]d
330ꢁ (5 min)!
Methylꢁ 5-thio-b-d-arabinopyranoside (16-D). mp
250ꢁ (4 h, c 1, pyridine). Anal. Calcd for C12H14
O5S: C, 53.32; H, 5.22; S, 11.86. Found: C, 53.29;
H, 5.27; S, 11.80.
ꢁ
ꢁ
180±182 C, lit. 185±186 C [15], lit. 176±178 C
[16]; [ꢁ]d 457ꢁ (c 0.5, water); lit. 452ꢁ (c 0.6,
MeOH) [15].
5-Thio-b-l-arabinose (19).ÐTo a solution of 18
(0.8 g, 2 mmol) in CHCl3 (5 mL) and MeOH
(5 mL), a solution of methanolic M NaOMe
(0.1 mL) was added at room temperature. The
mixture was neutralized with solid CO2 after 1 h to
yield, on concentration and crystallization with
1,2,3-Tri-O-acetyl-4-O-benzoyl-5-thio-l-arabino-
pyranose (17).ÐAcetylation of 18 (2.7 g, 10 mmol)
with Ac2O (10 mL) in pyridine (15 mL) gave, after
usual processing, 17 (3.44 g, 87%) as an anomeric
mixture (ꢁ:ꢀ ꢀ1:4); Rf 0.6 (solvent C). Anal. Calcd
for C18H20O8S: C, 54.54; H, 5.09; S, 8.09. Found:
C, 54.50; H, 5.12; S, 7.98.
1,2,3-Tri-O-acetyl-4-O-benzoyl-5-thio-d-arabino-
pyranose (17-D). ꢁ:ꢀ ꢀ1:5 mixture. Anal. Calcd for
C18H20O8S: C, 54.54; H, 5.09; S, 8.09. Found: C,
54.48; H, 5.02; S, 7.95.
ꢁ
EtOH, 19 (0.24 g, 72%): mp 172±174 C (EtOH);
[ꢁ]d +303ꢁ (5 min)! +281ꢁ (24 h, c 0.5, H2O).
Anal. Calcd for C5H10O4S: C, 36.14; H, 6.06; S,
19.29. Found: C, 36.03; H, 6.12; S, 18.88.
5-Thio-b-d-arabinose (19-D). mp 173±175 ꢁC
ꢁ
(EtOH); lit. 172±175 C [15]; [ꢁ]d 300ꢁ (5 min)!
4-O-Benzoyl-5-thio-l-arabinopyranose (18).ÐA
solution of 12 (3.1 g, 10 mmol) in AcOH (30 mL)
and H2O (10 mL) was heated on a steam bath for
30 min to give after concentration, and subsequent
coevaporation of the residue with toluene 18ꢁ
285ꢁ (24 h, c 0.5, H2O); lit. 250ꢁ (c 0.6, H2O)
[15].
1,2,3,4-Tetra-O-acetyl-5-thio-b-l-arabinopyranose
(5).ÐAcetylation of 19 (8.3 g, 50 mmol) with Ac2O
(45 mL) in pyridine (60 mL) gave, after usual pro-
ꢁ
ꢁ
(1.7 g, 63%); mp 136±138 C (acetone±ether); [ꢁ]d
cessing, 5 (16.0 g, 93%): mp 120±122 C (EtOH);
+295ꢁ (c 1, acetone); mutarotation: [ꢁ]d +326ꢁ
(5 min)! +250ꢁ (4 h, c 1, pyridine). Concentration
of the ®ltrate gave 18 (0.9 g, 34%) as an anomeric
mixture (ꢁ:ꢀ ꢀ1:3); Rf 0.4 (solvent C). Anal. Calcd
for C12H14O5S: C, 53.32; H, 5.22; S, 11.86. Found:
C, 53.25; H, 5.25; S, 11.81.
[ꢁ]d +299ꢁ; Rf 0.45 (solvent B). Anal. Calcd for
C13H18O8S: C, 46.70; H, 5.43; S, 9.59. Found: C,
46.67; H, 5.40; S, 9.52.
1,2,3,4-Tetra-O-acetyl-5-thio-b-d-arabinopyranose
(5-D).Ðmp 120±124 C (EtOH); lit. 118±120 C
ꢁ
ꢁ
[15], [ꢁ]d 300ꢁ; lit. 308ꢁ [15].

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E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
199
2,3-Di-O-acetyl-4-O-benzoyl-5-thio-b-l-arabino-
pyranosyl bromide (20).ÐTo a stirred solution of
17 (1.0 g, 2.5 mmol) in dry CH2Cl2 (10 mL), 33%
hydrogen bromide in acetic acid (5 mL) was added.
After 1 h at room temperature, the mixture was
poured into ice-water, extracted with CH2Cl2,
washed with 6% aq NaHCO3, brine and con-
centrated to yield 20 (1.0 g, 95%): [ꢁ]d +367ꢁ (c
0.4, CHCl3); Rf 0.7 (solvent B). Anal. Calcd for
C16H17BrO6S: C, 46.70; H, 5.43; S, 9.59. Found: C,
46.67; H, 5.40; S, 9.52.
4-Cyanophenyl 4-O-benzoyl-2,3-O-isopropylidene-
1,5-dithio-l-arabinopyranoside (23).ÐUnder argon,
to a solution of 14 (0.35 g, 1 mmol) and 4-cyano-
benzenethiol (0.26 g, 1.85 mmol) in dry CH2Cl2
(15 mL) TMSOTf (0.2 mL, 1.1 mmol) was adꢁded at
ꢁ
10 C and the mixture was stirred at 10 C for
30 min. The reaction was quenched with Et3N,
concentrated and the residue was submitted to
column chromatography (solvent C). Concentra-
tion of thꢁe ®rst fraction gave 23ꢁ (30 mg, 7%): mp
145±150 C (EtOAc±hexane); [ꢁ]d +392ꢁ (c 0.5,
CHCl3); Rf 0.7 (solvent C). Anal. Calcd for
C22H21NO4S2: C, 61.81; H, 4.95; N, 3.28; S, 15.00.
Found: C, 61.72; H, 5.07; S, 15.11.
Concentration of the second fraction gave 23ꢀ
(70 mg, 17%): mp 90±95 ꢁC (EtOAc±hexane);
[ꢁ]d +55ꢁ (c 0.5, CHCl3); Rf 0.5 (solvent C). Anal.
Calcd for C22H21NO4S2: C, 61.81; H, 4.95; N, 3.28;
S, 15.00. Found: C, 61.93; H, 4.79; S, 15.05.
Glycosidation of 4-cyanobenzenethiol with 6.Ð
To a stirred suspension of 6 [7] (1.5 g, 4.2 mmol)
and potassium carbonate (0.85 g, 6.15 mmol) in
acetone (85 mL), 4-cyanobenzenethiol (0.8 g,
5.9 mmol) was added and the mixture was re¯uxed
for 2 h. After cooling to room temperature, the
precipitated salts were ®ltered o€, washed with
acetone, the ®ltrate was concentrated and sub-
mitted to column chromatography (solvent B) to
yield 4-cyanophenyl 2,3,4-tri-O-acetyl-1,5-dithio-l-
arabinopyranoside (24, 1.1 g, 64%) as a 1:1
anomeric mixture. Rf 0.5 (solvent B). Anal. Calcd
for C18H19NO6S2: C, 52.80; H, 4.68; N, 3.42; S,
15.66. Found: C, 52.91; H, 4.75; N, 3.50; S, 15.72.
Glycosidation of 4-nitrobenzenethiol with 6.ÐTo
a stirred suspension of 6 (1.0 g, 2.8 mmol) and
potassium carbonate (0.56 g, 4.05 mmol) in acetone
(45 mL), 4-nitrobenzenethiol (0.6 g, 3.9 mmol) was
added and the mixture was re¯uxed for 1 h. After
cooling to room temperature, the precipitated salts
were ®ltered o€, washed with acetone, the ®ltrate
was concentrated and submitted to column chro-
matography (solvent B) to yield 4-nitrophenyl
2,3,4-tri-O-acetyl-1,5-dithio-l-arabinopyranoside
(25, 0.74 g, 61%) as a 1:1 anomeric mixture. Rf 0.4
(solvent B). Anal. Calcd for C17H19NO8S2: C,
47.55; H, 4.46; N, 3.26; S, 14.93. Found: C, 47.48;
H, 4.40; N, 3.17; S, 14.88.
O-(2,3,4-Tri-O-acetyl-5-thio-b-l-arabinopyrano-
syl) trichloroacetimidate (7).ÐUnder argon, hydra-
zine acetate (0.4 g, 4.3 mmol) was added to a
stirred solution of 5 (1.0 g, 3.0 mmol) in DMF
(30 mL) at room temperature. After 1 h, EtOAc
(50 mL) and CH2Cl2 (50 mL) were added, the
organic layer was washed with brine, con-
centrated, and the residue submitted to column
chromatography (solvent B) to yield 2,3,4-tri-O-
acetyl-5-thio-l-arabinopyranose (21, 0.58 g, 66%):
Rf 0.3 (solvent B). This was dissolved in CH2Cl2
(10 mL), CCl3CN (2.05 mL, 20 mmol) and K2CO3
(2.8 g, 20 mmol) were added under argon, and the
mixture was stirred at room temperature for 24 h.
Then the reaction was diluted with ether, ®ltered
through Celite, concentrated, and the residue was
submitted to column chromatography (solvent B)
ꢁ
to yield 7 (0.74 g, 86%): mp 148±153 C (ether);
[ꢁ]d +313ꢁ (c 0.47, CHCl3); Rf 0.7 (solvent B).
Anal. Calcd for C13H16Cl3NO7S: C, 35.76; H,
3.69; N, 3.21; S, 7.34. Found: C, 35.63; H, 3.82; ꢁN,
3.15; S, 7.42. lit. data for 7-D mp 143±148 C
(ether-petroleum ether); [ꢁ]d 326ꢁ [10].
4-Nitrophenyl 4-O-benzoyl-2,3-O-isopropylidene-
5-thio-l-arabinopyranoside (22).ÐA solution of 12
(0.31 g, 1 mmol), PPh3 (0.34 g, 1.3 mmol), 4-nitro-
phenol (0.22 g, 1.6 mmol) and DEAD (0.25 mL,
1.6 mmol) in toluene (10 mL) was stirred under N2
for 72 h, concentrated and submitted to column
chromatography (solvent D). Concentration of the
®rst ꢁfraction gave 22ꢁ (80 mg, 18.6%): mp 108±
111 C (ether±hexane); [ꢁ]d +327ꢁ (c 0.5, CHCl3);
Rf 0.6 (solvent C). Anal. Calcd for C21H21NO7S:
C, 58.46; H, 4.91; N, 3.25; S, 7.43. Found: C,
58.33; H, 5.00; N, 3.33; S, 7.35.
Concentration of the second fraction gave 22ꢀ
ꢁ
(150 mg, 35%). mp 93±95 C (ether±hexane); [ꢁ]d
Glycosidation of 4-cyanobenzenethiol with 7.Ð
Under argon, a suspension of 7 (1.8 g, 4.12 mmol),
4-cyanobenzenethiol (1.3 g, 9.7 mmol) and 4 A
molecular sieve (2.4 g) in 1,2-dichloroethane
(80 mL) was stirred at room temperature for
38ꢁ (c 0.5, CHCl3); Rf 0.4 (solvent C). Anal.
Calcd for C21H21NO7S: C, 58.46; H, 4.91; N,
3.25; S, 7.43. Found: C, 58.30; H, 5.07; N, 3.36; S,
7.39.

Â
E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
200
ꢁ
.
30 min. After cooling to 15 C, 0.1 M BF3 Et2O
in 1,2-dichloroethane (5 mL) ꢁwas added, and stir-
ring was continued at 15 C for 15 min. After
addition of Et3N (0.5 mL), the mixture was ®ltered
through Celite, washed with 1,2-dichloroethane,
the ®ltrate was concentrated and submitted to col-
umn chromatography (solvent B) to yield 24
(1.56 g, 92%) as a 1:4 mixture of ꢁ and ꢀ anomers.
Rf 0.5 (solvent B). Recrystallization from ether
yielded 4-cyanophenyl 2,3,4-tri-O-acetyl-1,5-dithio-
ꢀ-l-arabinopyranoside (24ꢁ, 1.1 g, 65%): mp 167±
Concentration of the ®rst fraction gave 4-nitro-
phenyl 2,3-di-O-acetyl-4-O-benzoyl-1,5-dithio-ꢀ-l-
arabꢁinopyranoside (27ꢁ, 0.75 g, 53%): mp 173±
176 C (ether); [ꢁ]d +363ꢁ (c 0.4, CHCl3); Rf 0.6
(solvent B). Anal. Calcd for C22H21NO8S2: C,
53.76; H, 4.31; N, 2.85; S, 13.04. Found: C, 53.88;
H, 4.40; N, 2.91; S, 13.14.
Concentration of the second fraction gave 4-
nitrophenyl 2,3-di-O-acetyl-4-O-benzoyl-1,5-dithio-
ꢁ-l-arabinopyranoside (27ꢀ, 0.4 g, 28%): [ꢁ]d +1ꢁ
(c 0.5, CHCl3); Rf 0.5 (solvent B). Anal. Calcd for
C22H21NO8S2: C, 53.76; H, 4.31; N, 2.85; S, 13.04.
Found: C, 53.90; H, 4.35; N, 3.01; S, 13.16.
169 C (ether); [ꢁ]d +375ꢁ (c 0.5, CHCl3); Rf 0.5
(solvent B). Anal. Calcd for C18H19NO6S2: C,
52.80; H, 4.68; N, 3.42; S, 15.66. Found: C, 52.73;
H, 4.61; N, 3.33; S, 15.58.
ꢁ
The corresponding d-isomers were obtained
under identical conditions and had the following
ꢁ
Glycosidation of 4-cyanobenzenethiol with 17.Ð
Under argon, to a stirred solution of 17 (0.8 g,
2 mmol) and 4-cyanobenzenethiol (0.54 g, 4 mmol)
in 1,2-dichloroethane (20 mL) TMSOTf (0.4 mL,
data: 27ꢁ-D: mp 173±176 C (ether); [ꢁ]d 374ꢁ (c
0.5, CHCl3); Rf 0.6 (solvent B). 27ꢀ-D: [ꢁ]d 5ꢁ (c
0.5, CHCl3); Rf 0.5 (solvent B).
Glycosidation of 4-cyanobenzenethiol with 20.Ð
(a) To a stirred suspension of 20 (1.0 g, 2.4 mmol)
and potassium carbonate (0.5 g, 3.6 mmol) in
acetone (45 mL) 4-cyanobenzenethiol (0.45 g,
3.3 mmol) was added and the mixture was re¯uxed
for 1 h. After cooling to room temperature, the
precipitated salts were ®ltered o€, washed with
acetone, the ®ltrate was concentrated and sub-
mitted to column chromatography (solvent B).
Concentration of the ®rst fraction gave 26ꢁ
(250 mg, 22%), identical with the compound
described above.
ꢁ
2.2 mmol) was added at 10 C. After stirring at
room temperature for 2 h, the reaction was quen-
ched with Et3N, concentrated and submitted to
column chromatography (solvent B). Concentra-
tion of the ®rst fraction gave 4-cyanophenyl 2,3-
di-O-acetyl-4-O-benzoyl-1,5-dithio-ꢀ-l-arabinopyr-
anoside (26ꢁ, 0.55 g, 58%): mp 161±163 ꢁC (ether);
[ꢁ]d +386ꢁ (c 0.5, CHCl3); Rf 0.6 (solvent B). Anal.
Calcd for C23H21NO6S2: C, 58.58; H, 4.49; N, 2.97;
S, 13.60. Found: C, 58.67; H, 4.40; N, 2.83; S,
13.55.
Concentration of the second fraction gave 4-
cyanophenyl 2,3-di-O-acetyl-4-O-benzoyl-1,5-dithio-
ꢁ-l-arabinopyranoside (26ꢀ, 0.27 g, 29%): [ꢁ]d
+15ꢁ (c 0.5, CHCl3); Rf 0.5 (solvent B). Anal.
Calcd for C23H21NO6S2: C, 58.58; H, 4.49; N, 2.97;
S, 13.60. Found: C, 58.65; H, 4.53; N, 3.07; S,
13.52.
Concentration of the second fraction gave 26ꢀ
(375 mg, 33%), identical with the compound
described above.
(b) To a suspension of 20 (1.0 g, 2.4 mmol) and
ZnO (0.3 g) in acetonitrile (10 mL) and toluene
(10 mL), 4-cyanobenzenethiol (0.45 g, 3.3 mmol)
was added and the mixture was stirred at room
temperature for 30 min. The reaction was ®ltered
through Celite, washed with CH2Cl2, concentrated
and submitted to column chromatography (solvent
B). Concentration of the ®rst fraction gave 26ꢁ
(320 mg, 28%), identical with the compound
described above.
The corresponding d-isomers, obtained under
identical conditions, had the following data: 26ꢁ-D:
ꢁ
mp 161±163 C (ether); [ꢁ]d 383ꢁ (c 0.5, CHCl3);
Rf 0.6 (solvent B). 26ꢀ-D: [ꢁ]d 15ꢁ (c 0.5, CHCl3);
Rf 0.5 (solvent B).
Glycosidation of 4-nitrobenzenethiol with 17.Ð
To a stirred solution of 17 (1.14 g, 2.9 mmol) and
4-nitrobenzenethiol (0.5 g, 3.2 mmol) in 1,2-
Concentration of the second fraction gave 26ꢀ
(410 mg, 36%), identical with the compound
described above.
.
dichloroethane (15 mL), BF3 Et2O (0.36 mL,
2.9 mmol) was added. The mixture was kept at
room temperature for 24 h, then poured into
ice-cold 6% aq NaHCO3 solution (25 mL), sepa-
rated, and the organic layer was washed with
water, 6% aq NaHCO3, concentrated and sub-
mitted to column chromatography (solvent B).
Glycosidation of 4-nitrobenzenethiol with 20.Ð
To a stirred suspension of 20 (1.0 g, 2.4 mmol) and
potassium carbonate (0.5 g, 3.6 mmol) in acetone
(45 mL) 4-nitrobenzenethiol (0.51 g, 3.3 mmol) was
added and the mixture was re¯uxed for 2 h. After
cooling to room temperature, the precipitated salts

Â
E. Bozo et al./Carbohydrate Research 311 (1998) 191±202
201
were ®ltered o€, washed with acetone, the ®ltrate
was concentrated and submitted to column chro-
matography (solvent B). Concentration of the ®rst
fraction gave 27ꢁ (220 mg, 19%), identical with the
compound described above.
Concentration of the second fraction gave 27ꢀ
(280 mg, 24%), identical with the compound
described above.
N, 4.62; S, 21.14. Found: C, 43.51; H, 4.25; N,
4.57; S, 21.19.
4-Cyanophenyl 1,5-dithio-a-d-arabinopyranoside
(30ꢀ).ÐDeacylation of 26ꢀ-D (1.3 g, 2.8 mmol)
with M NaOMe (0.1 mL) in MeOH (70 mL) yiel-
ded, after processing as described for 28ꢀ in
ꢁ
method (b), 30ꢀ (0.69 g, 89%): mp 219±221 C
(ether); [ꢁ]d +106ꢁ (c 0.5, pyridine); Rf 0.3 (solvent
F). Anal. Calcd for C12H13NO3S2: C, 50.87; H,
4.62; N, 4.94; S, 22.63. Found: C, 50.92; H, 4.63;
N, 4.79; S, 22.72.
4-Cyanophenyl 1,5-dithio-a-l-arabinopyranoside
(28ꢀ).Ð(a) Deacetylation of 24 (ꢁ:ꢀ ꢀ1:1; 1.1 g,
2.7 mmol) with M NaOMe (0.1 mL) in MeOH
(25 mL) yielded, after neutralization with solid
CO2, 28ꢀ (200 mg, 26%) which crystallized from
4-Cyanophenyl 1,5-dithio-b-d-arabinopyranoside
(30ꢁ).ÐDeacylation of 26ꢁ-D (1.0 g, 2.15 mmol)
with M NaOMe (0.1 mL) in MeOH (50 mL) yiel-
ded, after processing as described for 28ꢀ in
ꢁ
the solution; mp 220±222 C (MeOH); [ꢁ]d 108ꢁ
(c 0.5, pyridine); Rf 0.3 (solvent F). Anal. Calcd for
C12H13NO3S2: C, 50.87; H, 4.62; N, 4.94; S, 22.63.
Found: C, 50.76; H, 4.53; N, 4.91; S, 22.70.
ꢁ
method (b), 29ꢁ (0.53 g, 88%): mp 181±183 C
(ether); [ꢁ]d 161ꢁ (c 0.5, pyridine); Rf 0.3 (solvent
F). Anal. Calcd for C12H13NO3S2: C, 50.87; H,
4.62; N, 4.94; S, 22.63. Found: C, 50.81; H, 4.58;
N, 4.90; S, 22.68.
(b) Deacylation of 26ꢀ (410 mg, 0.87 mmol) with
M NaOMe (0.1 mL) in MeOH (15 mL) yielded,
after neutralization with solid CO2 and column
chromatography (solvent F), 28ꢀ (230 mg, 95%),
identical with the compound described above.
4-Cyanophenyl 1,5-dithio-b-l-arabinopyranoside
(28ꢁ).Ð(a) Deacetylation of 24ꢁ (1.1 g, 2.7 mmol)
with M NaOMe (0.1 mL) in MeOH (25 mL) yiel-
ded after processing as described for 28ꢀ in
4-Nitrophenyl 1,5-dithio-a-d-arabinopyranoside
(31ꢀ).ÐDeacylation of 27ꢀ-D (0.53 g, 1.1 mmol)
with M NaOMe (0.1 mL) in MeOH (25 mL) yiel-
ded, after processing as described for 28ꢀ in
ꢁ
method (b), 31ꢀ (0.26 g, 79%): mp 175±177 C
(ether); [ꢁ]d +106ꢁ (c 0.5, pyridine); Rf 0.2 (solvent
G). Anal. Calcd for C11H13NO5S2: C, 43.55; H,
4.32; N, 4.62; S, 21.14. Found: C, 43.63; H, 4.40;
N, 4.68; S, 21.19.
ꢁ
method (b), 28ꢁ (0.66 g, 87%): mp 182±184 C
(ether); [ꢁ]d +162ꢁ (c 0.5, pyridine); Rf 0.3 (solvent
F). Anal. Calcd for C12H13NO3S2: C, 50.87; H,
4.62; N, 4.94; S, 22.63. Found: C, 50.76; H, 4.53;
N, 4.91; S, 22.70.
4-Nitrophenyl 1,5-dithio-b-d-arabinopyranoside
(31ꢁ).ÐDeacylation of 27ꢁ-D (390 mg, 0.79 mmol)
with M NaOMe (0.1 mL) in MeOH (20 mL) yiel-
ded, after processing as described for 28ꢀ in
(b) Deacylation of 26ꢁ (250 mg, 0.53 mmol) with
M NaOMe (0.1 mL) in MeOH (10 mL) yielded,
after processing as described for 28ꢀ in method
(b), 28ꢁ (140 mg, 95%), identical with the com-
pound described above.
ꢁ
method (b), 29ꢁ (200 mg, 83%): mp 183±185 C
(ether); [ꢁ]d 165ꢁ (c 0.5, pyridine); Rf 0.2 (solvent
G). Anal. Calcd for C11H13NO5S2: C, 43.55; H,
4.32; N, 4.62; S, 21.14. Found: C, 43.52; H, 4.28;
N, 4.59; S, 21.17.
4-Nitrophenyl 1,5-dithio-a-l-arabinopyranoside
(29ꢀ).ÐDeacylation of 27ꢀ (280 mg, 0.57 mmol)
with M NaOMe (0.1 mL) in MeOH (15 mL) yiel-
ded, after processing as described for 28ꢀ in
Acknowledgements
ꢁ
method (b), 29ꢀ (140 mg, 81%): mp 175±177 C
(ether); [ꢁ]d 106ꢁ (c 0.5, pyridine); Rf 0.2 (solvent
G). Anal. Calcd for C11H13NO5S2: C, 43.55; H,
4.32; N, 4.62; S, 21.14. Found: C, 43.62; H, 4.43;
N, 4.71; S, 21.20.
The authors are very much indebted to Dr.
Gabriella Szabo for the biological tests.
References
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(29ꢁ).ÐDeacylation of 27ꢁ (220 mg, 0.45 mmol)
with M NaOMe (0.1 mL) in MeOH (15 mL) yielded,
after processing as described for 28ꢀ in method
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