Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio-D-ribopyranosides as well as their 2-deoxy and 2,3-dideoxy derivatives possessing antithrombotic activity

Article abstract of DOI:10.1016/S0008-6215(99)00175-5

1,2,3,4-Tetra-O-acetyl-5-thio-D-ribopyranose as well as its 1-bromide were used as donors in the reaction with 4-cyano- and 4-nitrobenzenethiol, to give the corresponding thioglycosides in different anomeric ratios depending on the reaction conditions. Zemplen deacetylation afforded 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-α- and β-D-ribopyranosides, respectively. 1,3,4-Tri-O-acetyl-2-deoxy-5-thio-D-erythro-pentopyranose was synthesized from methyl 2-deoxy-D-erythro-pentofuranoside and was coupled with 4-cyano- and 4-nitrobenzenethiol to give anomeric mixtures from which 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-β-D-erythro-pentopyranosides were isolated after deacetylation. 1,4-Di-O-acetyl-2,3-dideoxy-5-thio-D-glycero-pentopyranose was obtained starting from 1,2;5,6-di-O-isopropylidene-D-mannitol and used as the donor in the glycosylation reaction with 4-cyano- and 4-nitrobenzenethiol. The resulting anomeric mixtures were separated to give, after deacetylation, 4-cyanophenyl as well as 4-nitrophenyl 2,3-dideoxy-1,5-dithio-β-D-glycero-pentopyranosides. All of these thioglycosides showed significant antithrombotic activity on rats after oral administration. Copyright (C) 1999 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(99)00175-5

www.elsevier.nl/locate/carres
Carbohydrate Research 321 (1999) 52–66
Synthesis of 4-cyanophenyl and 4-nitrophenyl
1,5-dithio- -ribopyranosides as well as their 2-deoxy and
D
2,3-dideoxy derivatives possessing antithrombotic
activityꢀ
´
Eva Bozo´, Sa´ndor Boros, Ja´nos Kuszmann *
Institute for Drug Research, PO Box 82, H-1325 Budapest, Hungary
Received 5 May 1999; accepted 30 June 1999
Abstract
1,2,3,4-Tetra-O-acetyl-5-thio-
D
-ribopyranose as well as its 1-bromide were used as donors in the reaction with
4-cyano- and 4-nitrobenzenethiol, to give the corresponding thioglycosides in different anomeric ratios depending on
the reaction conditions. Zemple´n deacetylation afforded 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-a- and
b-
methyl 2-deoxy-
mixtures from which 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-b-
after deacetylation. 1,4-Di-O-acetyl-2,3-dideoxy-5-thio- -glycero-pentopyranose was obtained starting from 1,2;5,6-
di-O-isopropylidene- -mannitol and used as the donor in the glycosylation reaction with 4-cyano- and 4-nitrobenz-
enethiol. The resulting anomeric mixtures were separated to give, after deacetylation, 4-cyanophenyl as well as
4-nitrophenyl 2,3-dideoxy-1,5-dithio-b- -glycero-pentopyranosides. All of these thioglycosides showed significant
antithrombotic activity on rats after oral administration. © 1999 Elsevier Science Ltd. All rights reserved.
D-ribopyranosides, respectively. 1,3,4-Tri-O-acetyl-2-deoxy-5-thio-D-erythro-pentopyranose was synthesized from
D
-erythro-pentofuranoside and was coupled with 4-cyano- and 4-nitrobenzenethiol to give anomeric
-erythro-pentopyranosides were isolated
D
D
D
D
Keywords: 5-Thio-D-ribose, 5-thio-2-deoxy-D-erythro-pentose, and 5-thio-2,3-dideoxy-D-glycero-pentose derivatives; Glycosidation
reactions; Thioglycosides; Oral antithrombotic activity
logical activity. In order to check the influence
of the configuration of the pentose unit, the
1. Introduction
synthesis of the corresponding 5-thio- -ri-
D
In a previous paper [2], we have shown that
in contrast to a statement in the literature [3]
the oral antithrombotic effect of 4-cyano-
phenyl 1,5-dithio-pentopyranosides is not re-
stricted to the b-
anomers of the corresponding
binopyranosides show a remarkably high bio-
bopyranosides was decided upon. Further-
more, as the presence of the hydroxyl group at
C-2 in the xylopyranosides is not essential for
the antithrombotic activity either [4], the syn-
thesis of the 2-deoxy and 2,3-dideoxy-ribopyr-
anosides was also considered.
D
-xylo configuration, as both
- and -ara-
D
L
ꢀ Orally active antithrombotic thioglycosides, Part VIII.
For Part VII, see Ref. [1].
2. Results and discussion
* Corresponding author. Tel.: +36-1-399-3441; fax: +36-
1-399-3356.
E-mail address: h13757kus@ella.hu (J. Kuszmann)
Synthesis of the 5-thio-
D
-ribopyranosides 8
and 9.— -Ribose was converted, according to
D
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00175-5

´
E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
53
the literature [5,6], via its 5-O-tosylate 1 into
the S-acetate 2, deacetylation of which was
carried out with sodium methoxide in
methanol at the boiling temperature in the
presence of sodium borohydride to avoid the
formation of disulfides. Hydrolysis of the re-
sulting 5-thio-derivative 3 was carried out with
0.05 M sulfuric acid at 100 °C to give, after
acetylation, an a,b anomeric mixture (ratio
ꢀ3:2) of tetraacetate 4 in high yield (81%).
From this mixture, 4b could be separated
upon crystallization, and 4a by column chro-
matography, but for further experiments the
mixture was used. When this mixture was
treated with hydrogen bromide in acetic acid,
an a,b anomeric mixture (ratio ꢀ1:3) of bro-
mide 5 was formed. It is interesting to note
but the yield and the a:b ratio of the thiogly-
cosides 7 were practically the same (see Table
1, entries 1 and 2). To get higher ratios of the
b anomers, the acetobromo derivative 5 was
used as donor in a mixture of acetonitrile and
toluene, and zinc oxide as promoter for the
condensation with 4-cyanobenzenethiol. The
reaction was carried out at 50 °C, 5 was con-
sumed in 1 h and the corresponding thiogly-
cosides 6 were formed in 61% yield with an
a:b ratio of 3:7. No significant change in the
speed and outcome of the reaction was ob-
served when potassium carbonate was used as
promoter and acetone as solvent (see Table 1,
entries 3 and 4). When 4-nitrobenzenethiol
was used as acceptor in the zinc oxide-pro-
moted reaction, the corresponding thiogly-
cosides 7 were obtained in 74% yield (see
Table 1, entry 5) with the same 3:7 a:b ratio as
the 4-cyano-analogues 6. From these mixtures,
6b, 7a and 7b could be separated by crystal-
lization. The crystalline glycosides 8a, 8b, 9a
and 9b, obtained on deacetylation, were sub-
mitted to biological testing (Scheme 1).
4
that both anomers of 4 and 5 adopt the C1
conformation (J4,5axꢀ12 Hz); this means that
the anomeric effect, which forces the C-1 sub-
stituents into axial position, is operating only
in the cases of the a anomers. However, in this
configuration an energetically unfavored 1,3-
diaxial interaction does exist.
For the synthesis of the target thiogly-
cosides, tetraacetate 4 was used as donor in
1,2-dichloroethane and trimethylsilyl triflate
was used as promoter for the condensation
with 4-cyanobenzenethiol. The reaction was
carried out at 20 °C, 4 was consumed in 1 h
and the corresponding thioglycosides 6 were
formed in excellent yield (98%) containing the
a,b anomers in a ratio of 17:3. When 4-ni-
trobenzenethiol was glycosylated with 4 in the
presence of boron trifluoride etherate as pro-
moter, the reaction was much slower (24 h),
Synthesis of the 2-deoxy-5-thio- -erythro-
D
pentopyranosides 25 and 27.—For the synthe-
sis of the corresponding thioglycosides,
1,3,4-tri-O-acetyl-2-deoxy-5-thio- -erythro-
D
pentopyranose (11) was needed as donor. This
derivative had been obtained by Wong et al.
[7] in 1995, in moderate yield (33%) using an
enzyme-catalyzed aldol reaction of 3-thio- -
D
glyceraldehyde (10). As this method seemed to
be unsuitable for the preparation of larger
quantities, the classical approach of Ingles and
Whistler [8], who converted 2-deoxy-
D
-ribose
Table 1
Influence of the reaction conditions on the glycosidation reactions
a
Entry
Donor
Acceptor
Promoter
Solvent
Time
Temperature
(°C)
Product
Yield (%)
a:b
ratio
1
2
3
4
5
6
7
8
9
4
CN
NO2
CN
CN
NO2
CN
NO2
CN
NO2
TMSOTf
BF3·Et2O
ZnO
K2CO3
ZnO
TESOTf
TMSOTf
TESOTf
TESOTf
1,2-dichloroethane
1,2-dichloroethane
MeCN, toluene
acetone
MeCN, toluene
1,2-dichloroethane
1,2-dichloroethane
1,2-dichloroethane
1,2-dichloroethane
1 h
24 h
1 h
1 h
30 min
1 h
1 h
30 min
30 min
20
20
50
60
50
20
20
−10
−10
6
98
99
61
52
74
98
99
86
99
17:3
9:1
3:7
1:9
3:7
1:3
1:2
1:3
3:7
4
7
5
6
5
6
5
7
11
11
28
28
24
26
46
47
a Substituent of the 4-substituted thiophenol.

´
54
E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
Scheme 1.
in a four-step process into an anomeric mix-
ture of methyl 2-deoxy-5-thio- -erythro-pen-
long-range coupling for the anomeric proton.
The pyranose ring of 11a was evident from
the chemical shift of C-1 (being attached to a
sulfur atom) but the conformation is uncertain
as the coupling constants could not be deter-
mined due to the overlapping of the signals.
Isolation of the methyl pyranoside 18b means
that, even in aqueous solution, besides the
hydrolysis the furanoside 12“pyranoside 17
isomerization also takes place, i.e. protonation
of 12 can lead via the two isomeric oxonium
ions 19 and 20 to the cyclic 21 or acyclic 22
oxocarbenium ions. However, while attack of
the thiol group at C-1 of 21 led via a rear-
rangement to the hydrolyzed thiosugar 23, the
same attack at C-1 of 22 gave the methyl
pyranoside 17. Theoretically, protonation of
the methoxy group of 17 could lead after
hydrolysis directly to 23, but because of the
enhanced sensitivity of 2-deoxy-5-thio sugars
towards acids [4] the yield of 23 decreased
dramatically on prolonged hydrolysis or ap-
plying a more acidic pH. For the same reason,
attempts to convert 18 by acetolysis into 11
were also unsuccessful (Scheme 2). Triacetate
11 is acid sensitive and can be stored only at
temperatures below 5 °C, as at room tempera-
ture a slow decomposition takes place.
Condensation of triacetate 11 with 4-
cyanobenzenethiol was carried out in 1,2-
dichloroethane in the presence of triethylsilyl
triflate as promoter at 20 °C, yielding a mix-
ture of anomers 24a and 24b in excellent yield
(98%) in a ratio of 1:3. A similar yield (99%)
was achieved when 4-nitrobenzenethiol was
used as aglycon and trimethylsilyl triflate as
promoter, but the anomeric ratio of 26a and
26b obtained as a mixture was 1:2 (see Table
1, entries 6 and 7). The pure b anomers 25b
and 27b, which crystallized after deacetylation
D
tofuranosides (12), was considered. This could
be transformed into a mixture of the corre-
sponding methyl pyranosides 17 on treatment
with methanolic hydrochloric acid. Hydrolysis
of the latter at 75 °C with 0.25 M hydrochloric
acid in 50% aqueous methanol was supposed
to give the free thiosugar 23. Only 17b was
characterized in the literature [8]. We repeated
this reaction sequence with the following
slight modifications. Tosylation of methyl 2-
deoxy- -ribofuranoside [8] gave, besides some
D
unchanged starting material, the monotosylate
13 and ditosylate 14 in 72 and 21% yields,
respectively, after separation by column chro-
matography. Both derivatives were unstable
and decomposed on storage at room tempera-
ture. Acetylation of 13 gave 15, which was
converted immediately into the stable 16 by
treatment with potassium thioacetate in N,N-
dimethylformamide. The two anomers could
be separated by column chromatography and
their anomeric configuration was assigned ac-
cording to the optical rotation. Deacetylation
of 16 was carried out in boiling methanol with
1 equivalent of sodium methoxide and hydrol-
ysis of the resulting crude thiol 12 was carried
out by boiling its acidified (pH 4) aqueous
solution. The products were isolated after
acetylation by column chromatography, af-
fording the triacetate 11 as an anomeric mix-
ture (18.7%) as well as the methyl pyranoside
18b (13.2%). Their structure was proved by 1H
NMR spectroscopy according to the following
1
data. The C4 conformation of the pyranose
rings in 11b and 18b was evident from the
presence of the large J2ax,3ax 12 Hz coupling,
and the axial orientation of the anomeric sub-
stituent from the presence of the J1eq,5eq 1.7 Hz

´
E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
55
from the above anomeric mixtures, were sub-
mitted to biological testing.
via hydrogenation of the 2-ene derivative 31
into 32, which after hydrolysis and reaction
with benzyl mercaptan yielded the antipode of
29 in an overall yield of ꢀ7%. However, in
our hands, hydrogenation of crude 31 [10]
over Pd/C led to a complex mixture from
which, after acetylation, besides the 1,5-anhy-
dro-pentitol acetate 33 only the open-chain
diacetate 34 could be isolated in 47 and 32%
yields, respectively (Scheme 3). Analogous
products were already described in the glucal
Synthesis of the 2,3-dideoxy-5-thio- -glyc-
D
ero-pentopyranosides 50 and 51.—For the syn-
thesis of the corresponding thioglycosides,
1,4-di-O-acetyl-2,3-dideoxy-5-thio- -pentopyr-
D
anose (28) was needed as donor; this could be
prepared from 2,3-dideoxy- -glycero-pentose
(30) via its open-chain derivative 29. The
isomer of the latter was prepared by Allerton
et al. in 1951 [9] by conversion of -arabinose
D
L
-
L
Scheme 2.

´
56
E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
Scheme 3.
series depending on the quality of the applied
Pd catalysts [10,11].
tose 39, which was obtained as a solid mixture
containing the a- and b-pyranose isomers in a
ratio of 2:1. The absence of any furanose
structure is in accordance with the tendency of
5-thio sugars to form pyranosides exclusively
[19]. After acetylation, the two crystalline
anomers 28a and 28b could be separated by
column chromatography, but they were not
stable at room temperature and could be
stored without decomposition only below
5 °C. According to their NMR spectra, in
both anomers the 1-O-acetyl group is axially
In 1968 Goodman published another 12-
step synthesis of 29 starting from
D-xylose
[12], but because of the low overall yield of
this approach we turned our attention to the
intermediate 30. This was prepared by Diek-
man et al. in 1989 [13] by conversion of
1,2:5,6-di-O-isopropylidene-
D
-mannitol into
2,3-O-isopropylidene- -glyceraldehyde
D
and
Wittig-type chain elongation followed by hy-
drogenation and subsequent hydrolysis. We
4
used 1,2:5,6-di-O-isopropylidene-
D
-threo-hex-
oriented, i.e. 28a adopts the C1, while 28b the
3-enitol (35) [14–16] as starting material,
1C4 conformation. This means that the energy
gained by the anomeric effect is enough to
compensate the sterically unfavored diaxial
arrangement of the two acetoxy groups in the
latter conformer (Scheme 4).
which could be converted, in a yield of 71%,
into 3,4-dideoxy- -threo-hexitol (37) [17] by
D
first saturating the double bond of 35 in the
presence of triethylamine, and afterwards re-
moving the isopropylidene groups from the
resulting 36 by hydrochloric acid in methanol.
Periodate oxidation of 37 afforded the 2,3-
dideoxy-pentose 38 as a complex mixture of
its anomeric furanose and pyranose forms [13]
in nearly quantitative yield, but 38 could be
converted without purification into the diben-
zyl dithioacetal 42 in high yield. Tosylation
and subsequent acetylation of 42 afforded di-
acetate 44 besides the mixed ester 45, the
primary tosyloxy group of which was ex-
changed by potassium thiobenzoate in N,N-
dimethylformamide to give 41. The mercapto
groups of the latter were removed in aqueous
tetrahydrofuran in the presence of mercuric
oxide with boron trifluoride etherate [18]. The
obtained aldehyde 40 gave, after Zemple´n
deacylation, the free 2,3-dideoxy-5-thiopen-
Condensation of a mixture of the anomeric
peracetates (28a and 28b) with 4-cyano- and
4-nitrobenzenethiol was performed in 1,2-
dichloroethane at −10 °C in the presence of
triethylsilyl triflate as promoter affording the
corresponding glycosides 46 and 47 in 1:3 and
3:7 a:b ratios, respectively (see Table 1, entries
8 and 9). From these mixtures, the pure b
isomers 46b and 47b could be obtained by
crystallization and gave, on deacetylation, 50b
and 51b, respectively, which were both sub-
mitted to biological testing. When the cou-
pling reaction with the cyanobenzenethiol was
carried out at 20 °C, a rearrangement took
place and instead of the thiopyranosides only
a
5-substituted-1,4,5-trithiofuranoside
49
could be isolated (see Scheme 5). Despite the
fact that the absolute configuration of this

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
57
Scheme 4.
Scheme 5.
derivative could not be determined (only the
furanoid structure by selective INEPT NMR
measurements, proving the location of one of
the thiophenol moieties at C-5), it is probable
that, according to the depicted reaction mech-
anism, an inversion at C-4 took place. A
further indirect proof of this mechanism was
obtained when the isolated mixture of the
thiopyranosides 46 was treated under the same
reaction conditions as used for the glycosida-
tion at 20 °C, affording the aforementioned
rearranged product 49.
botic activity of 8a, 8b, 9a, 9b, 25b, 27b, 49,
50b and 51b 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
all compounds apart from the 4-nitrophenyl
thioglycoside 27b were more active than beci-
parcil [2], used as the reference compound.
This means that the antithrombotic activity is
not restricted to the
D
-xylo configuration and
that the presence of the hydroxyl groups at
C-2 and C-3 is not essential for the biological
effect either.
Biological results.—The oral antithrom-

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
58
Table 2
Oral antithrombotic activity of 8a, 8b, 9a, 9b, 25b, 27b, 49b and 50b in rats using Pescador’s model [20] compared with beciparcil
a
Compound
Ref
25
8a
8b
9a
9b
25b
27b
49
50b
51b
ED50 (mg/kg)
3
10
10
2
3
25
3
3
1
a Ref, reference compound (beciparcil=4-cyanophenyl 1,5-dithio-b-
D-xylopyranoside) [2].
3. Experimental
residue (27 g, 81%) was obtained, which ac-
cording to NMR spectroscopy contained 4a
and 4b in a ratio of 3:2. Crystallization from
ether–hexane afforded crystalline 4b (9.5 g,
28.5%) mp 121–123 °C; lit. 123–124 °C [6]; Rf
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, 1:1; B, 2:1;
C, 3:1; D, 4:1), EtOAc–EtOH mixture (E 3:1),
EtOAc (F) and toluene–MeOH mixture (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 followed by
heating at ca. 200 °C. For column chromatog-
raphy, 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. Multiplicities of the 13C
NMR spectra were obtained from DEPT ex-
periments. The assignment of the protons was
based on homonuclear decoupling experi-
ments. The ratio of a:b anomeric mixtures was
1
0.55 (solvent B); H NMR: l 5.97 (d, 1 H, J1,2
8.5 Hz, H-1), 5.45 (dd, 1 H, J3,4 ꢀ2.5 Hz,
H-3), 5.12 (dd, 1 H, J2,3 ꢀ2 Hz, H-2), 5.10
(ddd, 1 H, J4,5ax 9.8, J4,5eq 3.6 Hz, H-4), 3.04
(dd, 1 H, J5ax,5eq 13.4 Hz, H-5ax), 2.71 (dd, 1
H, H-5eq), 1.90–2.10 (4s, 12 H, 4 OAc); 13C
NMR: l 170.0–169.0 (4 CꢀO), 71.0, 69.8,
69.3, 68.9 (C-1,2,3,4), 26.6 (C-5), 20.8–20.2 (4
OAc).
Column chromatography (solvent A) of the
mother liquor gave, besides a further crop of
4b (0.7 g, 2.1%), the a anomer 4a (16.7 g,
50%); [h]D +217°; lit. [h]D+221° (c 0.77,
1
MeOH) [6]; Rf 0.45 (solvent B); H NMR: l
5.90 (d, 1 H, J1,2 4.7 Hz, H-1), 5.52 (dd, 1 H,
J3,4ꢀ2.5 Hz, H-3), 5.12 (dd, 1 H, J2,3 ꢀ2 Hz,
H-2), 5.10 (ddd, 1 H, J4,5ax 11.9, J4,5eq 3.4 Hz,
H-4), 3.16 (dd, 1 H, J5ax,5eq 12.9 Hz, H-5ax),
2.44 (dd, 1 H, H-5eq), 1.90–2.10 (4s, 12 H, 4
OAc); 13C NMR: l 170.0–169.0 (4 CꢀO),
70.1, 70.0, 68.8, 68.4 (C-1,2,3,4), 21.8 (C-5),
20.8–20.2 (4 OAc).
1
determined by H NMR.
1,2,3,4-Tetra-O-acetyl-5-thio- -ribopyranose
D
(4).—To a stirred solution of 2 [6] (16 g, 0.1
mol) in MeOH (100 mL), 4 M NaOMe (2 mL)
and NaBH4 (0.05 g) were added and the mix-
ture was boiled for 10 min; (Rf 0.55“0.65,
solvent D). The solution was concentrated
and hot 0.05 M H2SO4 was added to the
residue. The mixture was stirred on a steam
bath for 1 h whereupon a clear solution was
obtained. This was cooled, neutralized with
NaHCO3, filtered with charcoal and concen-
trated. Toluene (3×100 mL) was added and
evaporated from the residue, which was then
treated with Ac2O (150 mL) in pyridine (200
mL). After the usual processing, a semisolid
2,3,4-Tri-O-acetyl-5-thio- -ribopyranosyl
D
bromide (5).—To a stirred solution of a 3:2
anomeric mixture of tetraacetates 4a and 4b
(3.3 g, 10 mmol) in CH2Cl2 (30 mL), HBr in
AcOH (33%, 15 mL) was added and stirring
was continued for 1 h at rt. Then the mixture
was poured into ice-water, extracted with
CH2Cl2, washed with 6% aq NaHCO3, water
and concentrated to yield, according to NMR
spectroscopy, a 1:3 anomeric mixture of 5a
1
and 5b (3.3 g, 95%): Rf 0.65 (solvent B); H
NMR: a anomer, l 5.61 (dd, 1 H, H-3),
5.4–5.0 (m, 3 H, J4,5ax 12.0 Hz, H-1,2,4), 3.31
(dd, 1 H, J5ax,5eq 12.7 Hz, H-5ax), 2.62 (dd, 1

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
59
column chromatography (solvent B) to yield 6
(0.7 g, 61%) as a 3:7 mixture of a and b
anomers.
H, H-5eq), 2.20, 2.08, 2.04 (3s, 9 H, 3 OAc);
13C NMR: l 169.5–169.0 (3 CꢀO), 70.4, 69.9,
68.2 (C-2,3,4), 47.6 (C-1), 23.1 (C-5), 20.9–
20.4 (3 OAc). 1H NMR: b anomer, l 5.55 (dd,
1 H, J3,4ꢀ2.5 Hz, H-3), 5.2 (m, 2 H, J2,3ꢀ2,
J4,5ax 10.5, J4,5eq 4.2 Hz, H-2,4), 4.96 (d, 1 H,
J1,2 9.8 Hz, H-1), 3.10 (dd, 1 H, J5ax,5eq 13.2
Hz, H-5ax), 2.65 (dd, 1 H, H-5eq), 2.14, 2.07,
2.03 (3s, 9 H, 3 Oac); 13C NMR: l 169.5–
169.0 (3 CꢀO), 74.2, 69.4, 69.3 (C-2,3,4), 43.4
(C-1), 29.4 (C-5), 20.9–20.4 (3 OAc). Anal.
Calcd for C11H15BrO6S: C, 37.20; H, 4.26; Br,
22.50; S, 9.03. Found: C, 37.10; H, 4.38; Br,
22.32; S, 8.91.
(iii) To a stirred suspension of 5 (1.0 g, 2.8
mmol) and potassium carbonate (0.6 g, 4.3
mmol) in acetone (50 mL), 4-cyanobenz-
enethiol (0.45 g, 3.3 mmol) was added and the
mixture was refluxed for 1 h. After cooling to
rt, the precipitated salts were filtered off and
washed with acetone. The filtrate was concen-
trated and submitted to column chromatogra-
phy (solvent B) to yield 6 (0.6 g, 52%) as a 1:9
mixture of a and b anomers. Recrystallization
from diethyl ether yielded 6b (0.34 g, 29%):
mp 112–115 °C (diethyl ether); [h]D +70° (c
0.5, CHCl3).
4-Cyanophenyl 2,3,4-tri-O-acetyl-1,5-dithio-
D
-ribopyranoside (6).—(i) To a stirred solu-
tion of
4
(0.73 g, 2.2 mmol) and
4-Nitrophenyl 2,3,4-tri-O-acetyl-1,5-dithio-
4-cyanobenzenethiol (0.6 g, 4.4 mmol) in dry
1,2-dichloroethane (20 mL), under argon
Me3SiOTf (0.4 mL, 2.2 mmol) was added at
−10°C. After stirring at rt for 1 h, the reac-
tion was quenched with Et3N, concentrated
and submitted to column chromatography
(solvent B) to yield 6 (0.88 g, 98%) as a 17:3
mixture of a and b anomers: Rf 0.4 (solvent
D
-ribopyranoside (7).—(i) To a stirred solu-
tion of
4
(0.73 g, 2.2 mmol) and
4-nitrobenzenethiol (0.45 g, 2.9 mmol) in dry
1,2-dichloroethane (20 mL), BF3·EtO2 (0.27
mL, 2.2 mmol) was added. The mixture was
kept at rt for 24 h, then poured into ice-cold
6% aq NaHCO3 solution (25 mL). The sepa-
rated organic layer was washed with water,
6% aq NaHCO3 and concentrated to yield 7
(0.93 g, 99%) as a 9:1 mixture of a and b
anomers. Recrystallization from diethyl ether
yielded 7a (0.42 g, 45%): mp 112–115 °C (di-
ethyl ether); [h]D +407° (c 0.5, CHCl3); Rf 0.4
1
B); H NMR: a anomer, l 7.58–7.46 (m, 4 H,
aromatic), 5.60 (dd, 1 H, J3,4 2.4 Hz, H-3),
5.33 (dd, 1 H, J2,3 2.4 Hz, H-2), 5.14 (ddd, 1
H, J4,5ax 11.5, J4,5eq 3.9 Hz, H-4), 4.68 (d, 1 H,
J1,2 5.1 Hz, H-1), 3.32 (dd, 1 H, J5ax,5eq 13.2
Hz, H-5ax), 2.58 (dd, 1 H, H-5eq), 2.25, 2.08,
2.02 (3s, 9 H, 3 OAc); b anomer, l 7.65–7.50
(m, 4 H, aromatic), 5.60 (dd, 1 H, J3,4ꢀ2.5
Hz, H-3), 5.14 (m, 2 H, J2,3ꢀ2, J4,5ax 11.3,
J4,5eq 3.9 Hz, H-2,4), 4.41 (d, 1 H, J1,2 10.7 Hz,
H-1), 3.10 (dd, 1 H, J5ax,5eq 13.0 Hz, H-5ax),
2.56 (dd, 1 H, H-5eq), 2.16, 2.04, 2.00 (3s, 9
H, 3 OAc); 13C NMR: l 170.0–169.0 (3 CꢀO),
139.5, 132.4, 130.9, 111.0 (aromatic) 118.1
(CN), 71.8, 70.1, 69.8 (C-2,3,4), 46.1 (C-1),
28.0 (C-5), 21.0–20.4 (3 OAc). Anal. Calcd
for C18H19NO6S2: C, 52.80; H, 4.68; N, 3.42;
S, 15.66. Found: C, 52.69; H, 4.58; N, 3.50; S,
15.71.
1
(solvent B); H NMR: l 8.16–7.60 (m, 4 H,
aromatic), 5.62 (dd, 1 H, J3,4 2.7 Hz, H-3),
5.35 (dd, 1 H, J2,3 2.7 Hz, H-2), 5.15 (ddd, 1
H, J4,5ax 11.5, J4,5eq 4.2 Hz H-4), 4.74 (d, 1 H,
J1,2 4.9 Hz, H-1), 3.32 (dd, 1 H, J5ax,5eq 13.2
Hz, H-5ax), 2.60 (dd, 1 H, H-5eq), 2.25, 2.08,
2.02 (3s, 9 H, 3 OAc); 13C NMR: l 169.5 (3
CꢀO), 145.2, 144.0 129.4, 124.0 (aromatic),
71.8, 70.2, 69.1 (C-2,3,4), 50.4 (C-1), 22.8 (C-
5), 20.9–20.7 (3 OAc). Anal. Calcd for
C17H19NO8S2: C, 47.55; H, 4.46; N, 3.26; S,
14.93. Found: C, 47.63; H, 4.48; N, 3.30; S,
14.87.
(ii) To a suspension of 5 (1.0 g, 2.8 mmol)
and ZnO (0.3 g, 3.7 mmol) in MeCN (10 mL)
and toluene (10 mL), 4-nitrobenzenethiol (0.5
g, 3.2 mmol) was added and the mixture was
stirred at 50 °C for 30 min. The reaction mix-
ture was filtered through Celite, washed with
CH2Cl2, concentrated and submitted to
column chromatography (solvent B) to yield 7
(ii) To a suspension of 5 (1.0 g, 2.8 mmol)
and ZnO (0.3 g, 3.7 mmol) in MeCN (10 mL)
and toluene (10 mL), 4-cyanobenzenethiol
(0.45 g, 3.3 mmol) was added and the mixture
was stirred at 50 °C for 1 h. The reaction
mixture was filtered through Celite, washed
with CH2Cl2, concentrated and submitted to

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
60
yielded, after neutralization with solid CO2
and column chromatography (solvent G), 9a
(0.2 g, 71%): mp 76–80 °C (ether); [h]D +440°
(0.9 g, 74%) as a 3:7 mixture of a and b
anomers. Recrystallization from diethyl ether
yielded 7b (0.45 g, 37%): mp 143–146 °C (di-
ethyl ether); [h]D +83° (c 0.5, CHCl3); Rf 0.4
1
(c 0.5, MeOH); Rf 0.2 (solvent G); H NMR
1
(solvent B); H NMR: l 8.16–7.60 (m, 4 H,
(Me2SO-d6): l 8.12–7.55 (m, 4 H, aromatic),
5.34, 5.15, 5.05 (3d, 3 H, OH), 4.73 (d, 1 H,
J1,2 3.6 Hz, H-1), 4.02 (m, 1 H, J2,3 2.0 Hz,
aromatic), 5.62 (dd, 1 H, J3,4 ꢀ2.5 Hz, H-3),
5.16 (dd, 1 H, J2,3ꢀ2 Hz, H-2), 5.15 (ddd, 1
H, J4,5ax 11.5, J4,5eq 4.1 Hz, H-4), 4.46 (d, 1 H,
J1,2 10.7 Hz, H-1), 3.12 (dd, 1 H, J5ax,5eq 12.7
Hz, H-5ax), 2.58 (dd, 1 H, H-5eq), 2.18, 2.02,
2.00 (3s, 9 H, 3 OAc). Anal. Calcd for
C17H19NO8S2: C, 47.55; H, 4.46; N, 3.26; S,
14.93. Found: C, 47.47; H, 4.51; N, 3.32; S,
14.97.
H-2), 3.80–3.65 (m, 2 H, J4,5ax 10.0, J4,5eq
ꢀ
3.5 Hz, H-3,4), 2.85 (dd, 1 H, J5ax,5eq 12.9 Hz,
H-5ax), 2.48 (dd, 1 H, H-5eq). Anal. Calcd for
C11H13NO5S2: C, 43.55; H, 4.32; N, 4.62; S,
21.14. Found: C, 43.61; H, 4.38; N, 4.68; S,
21.22.
4-Nitrophenyl 1,5-dithio-i- -ribopyranoside
D
4-Cyanophenyl
1,5-dithio-h- -ribopyran-
D
(9b).—Deacetylation of 7b (0.45 g, 1.0 mmol)
with 1 M NaOMe (0.1 mL) in MeOH (25 mL)
yielded, after neutralization with solid CO2
and column chromatography (solvent G), 9b
(0.22 g, 71%): mp 155–160 °C (ether); [h]D
oside (8a).—Deacetylation of 6 (a:b=17:3;
0.88 g, 2.1 mmol) with 1 M NaOMe (0.1 mL)
in MeOH (20 mL) yielded, after neutralization
with solid CO2, 8a (0.29 g, 48%) which crys-
tallized from the solution: mp 195–197 °C
(ether); [h]D+446° (c 0.5, MeOH); Rf 0.3
1
+8° (c 0.5, MeOH); Rf 0.2 (solvent G); H
NMR (Me2SO-d6): l 8.15–7.65 (m, 4 H, aro-
matic), 5.50, 5.08, 5.05 (3d, 3 H, OH), 4.52 (d,
1 H, J1,2 10.3 Hz, H-1), 3.88 (m, 1 H, J3,4 ꢀ2.5
Hz, H-3), 3.72 (m, 1 H, J4,5ax 10.0, J4,5eq 3.7
Hz, H-4), 3.58 (m, 1 H, J2,3 1.9 Hz, H-2), 2.93
(dd, 1 H, J5ax,5eq 12.5 Hz, H-5ax), 2.28 (dd, 1
H, H-5eq). Anal. Calcd for C11H13NO5S2: C,
43.55; H, 4.32; N, 4.62; S, 21.14. Found: C,
43.59; H, 4.28; N, 4.59; S, 21.11.
1
(solvent G); H NMR (Me2SO-d6): l 7.72–
7.46 (m, 4 H, aromatic), 5.24, 5.08, 5.05 (3brs,
3 H, OH), 4.66 (d, 1 H, J1,2 3.7 Hz, H-1), 4.00
(m, 1 H, J2,3 2.2 Hz, H-2), 3.72 (m, 1 H, J4,5ax
9.0, J4,5eq ꢀ3.5 Hz, H-4), 3.68 (m, 1 H, J3,4ꢀ
2.5 Hz, H-3), 2.82 (dd, 1 H, J5ax,5eq 13.1 Hz,
H-5ax), 2.48 (dd, 1 H, H-5eq). Anal. Calcd for
C12H13NO3S2: C, 50.87; H, 4.62; N, 4.94; S,
22.63. Found: C, 50.81; H, 4.58; N, 4.88; S,
22.72.
Methyl 2-deoxy-5-O-p-tolylsulfonyl-
thro-pentofuranoside (13) and methyl 2-deoxy-
3,5-di-O-p-tolylsulfonyl- -erythro-pentofuran-
oside (14).—Crude methyl 2-deoxy- -erythro-
pentofuranoside, obtained from 2-deoxy-
D-ery-
4-Cyanophenyl
1,5-dithio-i- -ribopyran-
D
D
oside (8b).—Deacetylation of 6b (0.34 g, 0.8
mmol) with 1 M NaOMe (0.1 mL) in MeOH
(10 mL) yielded, after neutralization with solid
CO2 and column chromatography (solvent F),
8b (0.17 g, 72%): mp 154–157 °C (ether);
[h]D−11° (c 0.5, MeOH); Rf 0.6 (solvent F);
1H NMR (Me2SO-d6): l 7.78–7.60 (m, 4 H,
aromatic), 5.47, 5.07, 5.00 (3d, 3 H, OH), 4.46
(d, 1 H, J1,2 10.0 Hz, H-1), 3.88 (m, 1 H,
J3,4 ꢀ2.5 Hz, H-3), 3.70 (m, 1 H, J4,5ax 10.7,
J4,5eq ꢀ3.9 Hz, H-4), 3.55 (m, 1 H, J2,3 2.0 Hz,
H-2), 2.91 (dd, 1 H, J5ax,5eq 12.5 Hz, H-5ax),
2.28 (dd, 1 H, H-5eq). Anal. Calcd for
C12H13NO3S2: C, 50.87; H, 4.62; N, 4.94; S,
22.63. Found: C, 50.92; H, 4.56; N, 4.98; S,
22.68.
D
D-
erythro-pentopyranose (10 g) according to
Ref. [7] was dissolved with stirring in pyridine
(100 mL) and tosyl chloride (21.2 g, 1.5 equiv)
was added at 0 °C. After 1 h the temperature
was raised to 20 °C and after 1 h the mixture
was worked up in the usual way to give after
column chromatography (solvent A) and con-
centration of the first fraction 14 (6.5 g, 21%)
as an unstable syrup: Rf 0.8 (solvent A). Anal.
Calcd for C20H24O8S2: C, 52.62; H, 5.30; S,
14.05. Found: C, 52.50; H, 5.44; S, 13.88.
Concentration of the second fraction gave
13 (14.7 g, 72%) as an unstable syrup: Rf 0.4
(solvent A). Anal. Calcd for C13H18O6S: C,
51.64; H, 6.00; S, 10.60. Found: C, 51.56; H,
6.12; S, 10.42.
4-Nitrophenyl 1,5-dithio-h- -ribopyranoside
D
(9a).—Deacetylation of 7a (0.4 g, 0.9 mmol)
with M NaOMe (0.1 mL) in MeOH (20 mL)

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
61
1,3,4-Tri-O-acetyl-2-deoxy-5-thio-
D
-erythro-
Methyl 3-O-acetyl-2-deoxy-5-O-p-tolylsul-
fonyl- -erythro-pentofuranoside (15).—Acetyl-
pentopyranose (11) and methyl 3,4-di-O-acetyl-
D
2-deoxy-5-thio-i- -erythro-pentopyranoside
D
ation of 13 (12.1 g, 40 mmol) in pyridine (30
mL) with Ac2O (10 mL) gave, after the usual
processing, 15 (13.1 g, 95%): Rf 0.6 (solvent
A); 13C NMR: l 170.8 and 170.3 (CꢀO),
144.9, 132.7 129.8 and 127.8 (aromatic), 105.5
and 105.0 (C-1) 81.1, 80.7, 74.3 and 73.8
(C-3,4), 70.3 and 69.5 (C-5), 54.9 (OMe), 38.7
and 38.6 (C-2), 21.5 (TsꢁMe), 20.8 and 20.7
(OAc). Anal. Calcd for C15H20O7S: C, 52.32;
H, 5.85; S, 9.31. Found: C, 52.28; H, 5.98; S,
9.24.
(18b).—To a stirred solution of 16 (14.5 g, 58
mmol) in MeOH (150 mL), 4 M NaOMe (14.5
mL) and NaBH4 (0.05 g) were added and the
mixture was boiled for 10 min (Rf 0.55“0.30,
solvent B). The mixture was concentrated af-
ter neutralization with solid CO2. The residue
was dissolved in water (100 mL) and the pH
was adjusted to 4 by addition of 5 M HCl
(ꢀ11 mL). The solution was boiled for 90
min (Rf 0.80“0.2–0.3, solvent F), filtered
with charcoal, and concentrated. The residue
was coevaporated with toluene (3×50 mL),
then pyridine (50 mL) and Ac2O (30 mL) were
added. After 20 h, the mixture was processed
in the usual way and the residue obtained on
concentration was separated by column chro-
matography (solvent B). Concentration of the
first fraction gave 18b (1.9 g, 13.2%): [h]D −
Methyl
3-O-acetyl-5-S-acetyl-2-deoxy- -
D
erythro-pentofuranoside (16).—To a stirred
solution of 15 (17.2 g, 50 mmol) in DMF (50
mL), KSAc (7.4 g, 65 mmol) was added and
stirring was continued at 100 °C for 1 h. The
mixture was concentrated, the residue was dis-
solved in CH2Cl2, and washed with water. The
residue obtained on concentration was sub-
mitted to column chromatography (solvent
B), to give 16 (12 g, 97%). From this mixture,
the two anomers could be separated by re-
peated column chromatography (solvent C),
1
330°; Rf 0.75 (solvent A); H NMR: l 5.28
(ddd, 1 H, J4,5ax 1.7, J4,5eq 4.9 Hz, H-4), 5.20
(ddd, 1 H, J3,4 2.7 H-3), 4.59 (dd, 1 H, J1,2ax
2.7, J1,2eq 3.9, J1,5eq 1.7 Hz, H-1), 3.38 (s, 3 H,
OMe), 3.12 (dd, 1 H, J5ax,5eq 14.4 Hz, H-5ax),
2.72 (dd, 1 H, H-5eq), 2.40 (ddd, 1 H, J2ax,2eq
12.9, J2ax,3 12.0, J2eq,3 2.8, Hz, H-2ax), 2.15
(ddd, 1 H, H-2eq), 2.12, 2.00 (2s, 2×3 H,
OAc); 13C NMR: l 170.1, 169.5 (CꢀO), 81.3
(C-1), 67.2, 66.4 (C-3,4), 56.0 (OMe), 4.0 (C-
2), 26.8 (C-5), 20.8, 20.7 (OAc). Anal. Calcd
for C10H16O5S: C, 48.37; H, 6.50; S, 12.91.
Found: C, 48.31; H, 6.52; S, 12.85.
1
to give 16a [h]D +99°; Rf 0.55 (solvent B); H
NMR: l 5.04 (dd, 1 H, J1,2a 5.4, J1,2b 1.0 Hz,
H-1), 4.86 (ddd, 1 H, J3,4 5.4 Hz, H-3), 4.22
(ddd, 1 H, J4,5a 5.2, J4,5b 5.6 Hz, H-4), 3.36 (s,
3 H, OMe), 3.24 (dd, 1 H, J5a,5b 13.8 Hz,
H-5a), 3.18 (dd, 1 H, H-5b), 2.38 (ddd, 1 H,
J2a,2b 14.6, J2a,3 8.3, J2b,3 2.4 Hz, H-2a), 2.35 (s,
3 H, SAc), 2.05, (s, 3 H, OAc), 1.94 (ddd, 1 H,
H-2b); 13C NMR: l 194.5 (SꢁCꢀO), 170.6
(CꢀO), 104.4 (C-1), 80.5, 75.5 (C-3,4), 54.9
(OMe), 39.0 (C-2), 31.2 (C-5), 30.3 (SAc), 20.8
(OAc) and 16b [h]D −53°; Rf 0.55 (solvent B);
1H NMR: l 5.2–5.05 (m, 2 H, J1,2a 2.4, J1,2b
4.4, J3,4 ꢀ5 Hz, H-1,3), 4.10 (ddd, 1 H, J4,5a
6.3, J4,5b 7.8 Hz, H-4), 3.25 (dd, 1 H, J5a,5b
13.7 Hz, H-5a), 3.24 (s, 3 H, OMe), 3.03 (dd,
1 H, H-5b), 2.40 (ddd, 1 H, J2a,2b 14.4, J2a,3 7.1
Hz, H-2a), 2.33 (s, 3 H, SAc), 2.03, (s, 3 H,
Concentration of the second fraction gave
11 (3.0 g, 18.7%), which according to NMR
spectroscopy contained the a,b anomers in a
1
2:3 ratio; Rf 0.6 (solvent A); H NMR: a
anomer, l 5.78 (dd, 1 H, J1,2ax 3.5, J1,2eq 3.5
Hz, H-1), 5.30–5.15 (m, 2 H, H-3,4), 3.45–
3.20 (m, 2 H, H-5ax,5eq), 2.70–2.20 (m, 2 H,
H-2ax,2eq), 2.11, 2.09, 2.02 (3s, 9 H, OAc);
13C NMR: l 170.0–168.8 (CꢀO), 69.9, 68.5,
67.1 (C-1,3,4), 35.5 (C-2), 22.4 (C-5), 20.8–
20.4 (OAc); 1H NMR: b anomer, l 6.01 (dd, 1
H, J1,2ax ꢀ2.5, J1,2eq ꢀ3.5, J1,5eq 1.7 Hz, H-1),
5.35 (ddd, 1 H, J4,5ax 1.8, J4,5eq 4.9 Hz, H-4),
5.10 (ddd, 1 H, J3,4 ꢀ2.5 Hz, H-3), 3.26 (dd, 1
H, J5ax,5eq 14.7 Hz, H-5ax), 2.85 (dd, 1 H,
H-5eq), 2.70–2.20 (m, 2 H, J2ax,3 ꢀ12.0,
J2eq,3ꢀ2.5 Hz, H-2ax,2eq), 2.12, 2.10, 2.01
13
OAc), 1.93 (ddd, 1 H, J2b,3 4.4 Hz, H-2b); C
NMR: l 194.5 (SꢁCꢀO), 170.0 (CꢀO), 105.3
(C-1), 82.4, 76.4 (C-3,4), 54.9 (OMe), 38.8
(C-2), 32.5 (C-5), 30.1 (SAc), 20.6 (OAc).
Anal. Calcd for C10H16O5S: C, 48.37; H, 6.50;
S, 12.91. Found for 16a: C, 48.28; H, 6.57; S,
12.83; Found for 16b: C, 48.30; H, 6.62; S,
12.79.

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
62
(3s, 9 H, OAc); 13C NMR: l 170.0–168.8
(CꢀO), 72.0, 67.0, 65.6 (C-1,3,4), 32.1 (C-2),
27.9 (C-5), 20.8–20.4 (OAc). Anal. Calcd for
C11H16O6S: C, 47.82; H, 5.84; S, 11.60. Found:
C, 47.80; H, 5.89; S, 11.51.
4-Nitrophenyl 3,4-di-O-acetyl-2-deoxy-1,5-
dithio- -erythro-pentopyranoside (26).—To a
D
stirred solution of 11 (0.4 g, 1.4 mmol) and
4-nitrobenzenethiol (0.48 g, 3 mmol) in dry
1,2-dichloroethane (15 mL) under argon,
Me3SiOTf (0.3 mL, 1.4 mmol) was added at
−10 °C. After stirring at rt for 1 h, the reac-
tion was quenched with Et3N, concentrated
and the residue was submitted to column
chromatography (solvent B) to yield 26 (0.53
g, 99%) as a 1:2 mixture of a and b anomers:
4-Cyanophenyl
3,4-di-O-acetyl-2-deoxy-
1,5-dithio- -erythro-pentopyranoside (24).—
D
To a stirred solution of 11 (0.4 g, 1.4 mmol)
and 4-cyanobenzenethiol (0.4 g, 2.9 mmol) in
dry 1,2-dichloroethane (15 mL) under argon,
Et3SiOTf (0.35 mL, 1.4 mmol) was added at
−10 °C. After stirring at rt for 1 h, the reac-
tion was quenched with Et3N. The mixture
was concentrated and submitted to column
chromatography (solvent B) to yield 24 (0.5 g,
98%) as a 1:3 mixture of a and b anomers: Rf
1
Rf 0.4 (solvent B); H NMR: a anomer, l
8.15–7.55 (m, 4 H, aromatic), 5.25–5.05 (m, 2
H, J3,4 ꢀ3, J4,5ax 7.8, J4,5eq 3.4 Hz, H-3,4), 4.46
(t, 1 H, J1,2ax 5.8, J1,2eq 5.8 Hz, H-1), 3.23 (dd,
1 H, J5ax,5eq 13.9 Hz, H-5ax), 2,80 (dd, 1 H,
H-5eq), ꢀ2.60 (m, 1 H, J2ax,2eq ꢀ14, J2ax,3 ꢀ3
Hz, H-2eq), ꢀ2.20 (m, 1 H, H-2ax), 2.13,
1
0.4 (solvent B); H NMR: a anomer, l 7.65–
7.50 (m, 4 H, aromatic), 5.25–5.05 (m, 2 H,
J4,5ax 7.6, J4,5eq 3.0 Hz, H-3,4), 4.40 (dd, 1 H,
J1,2eq 5.7, J1,2ax 5.7 Hz, H-1), 3.20 (dd, 1 H,
J5ax,5eq 13.9 Hz, H-5ax), 2,79 (dd, 1 H, H-5eq),
2.57 (ddd, 1 H, J2ax,2eq ꢀ14 Hz, H-2eq), 2.18
(ddd, 1 H, H-2ax), 2.13, 2.03 (2s, 6 H, OAc);
1H NMR: b anomer, l 7.65–7.50 (m, 4 H,
aromatic), 5.38 (ddd, 1 H, H-3), ꢀ5.15 (m, 1
H, J4,5ax 9.5, J4,5eq 3.0 Hz, H-4), 4.54 (dd, 1 H,
J1,2ax 9.5, J1,2eq 2.8 Hz, H-1), 3.12 (dd, 1 H,
J5ax,5eq 13.7 Hz, H-5ax), 2,79 (dd, 1 H, H-5eq),
2.49 (ddd, 1 H, J2ax,2eq ꢀ14 Hz, H-2eq), ꢀ
2.20 (m, 1 H, H-2ax), 2.11, 2.05 (2s, 6 H,
OAc). Anal. Calcd for C16H17NO4S2: C, 54.68;
H, 4.88; N, 3.99; S, 18.25. Found: C, 54.73; H,
4.91; N, 3.90; S, 18.33.
1
2.05 (2s, 6 H, OAc); H NMR: b anomer, l
8.15–7.55 (m, 4 H, aromatic), 5.40 (ddd, 1 H,
J3,4 ꢀ3 Hz, H-3), ꢀ5.15 (m, 1 H, J4,5ax 9.3,
J4,5eq 3.4 Hz, H-4), 4.58 (dd, 1 H, J1,2ax 9.8,
J1,2eq 3.2 Hz, H-1), 3.11 (dd, 1 H, J5ax,5eq 13.5
Hz, H-5ax), 2,80 (dd, 1 H, H-5eq), 2.52 (ddd,
1 H, J2ax,2eq ꢀ14, J2ax,3 ꢀ3, J2eq,3 ꢀ5 Hz, H-
2eq), ꢀ2.20 (m, 1 H, H-2ax), 2.11, 2.06 (2s, 6
H, OAc). Anal. Calcd for C15H17NO6S2: C,
48.51; H, 4.61; N, 3.77; S, 17.26. Found: C,
48.57; H, 4.66; N, 3.80; S, 17.33.
4-Nitrophenyl 2-deoxy-1,5-dithio-i- -ery-
D
thro-pentopyranoside (27b).—Deacetylation of
26 (a:b 1:2, 0.53 g, 1.4 mmol) with 1 M
NaOMe (0.1 mL) in MeOH (20 mL) yielded,
after neutralization with solid CO2, 27b (0.12
g, 29%), which crystallized from the solution:
mp 132–134 °C (MeOH); [h]D −77° (c 0.5,
MeOH); Rf 0.7 (solvent F); 1H NMR (Me2SO-
d6): l 8.16–7.60 (m, 4 H, aromatic), 4.94 and
4.88 (2d, 2 H, OH), 4.85 (dd, 1 H, J1,2ax 10.0,
J1,2eq 2.7 Hz, H-1), 3.87 (m, 1 H, J3,4 ꢀ3 Hz,
H-3), 3.72 (m, 1 H, J4,5ax 9.5, J4,5eq 3.4 Hz,
H-4), 2.95 (dd, 1 H, J5ax,5eq 12.9 Hz, H-5ax),
2,51 (dd, 1 H, H-5eq), 2.35 (ddd, 1 H, J2ax,2eq
13.4, J2ax,3 2.2 J2eq,3 6.6 Hz, H-2eq), 2.01 (ddd,
1 H, H-2ax). Anal. Calcd for C11H13NO4S2: C,
45.98; H, 4.56; N, 4.87; S, 22.31. Found: C,
45.89; H, 4.63; N, 4.91; S, 22.40.
4-Cyanophenyl 2-deoxy-1,5-dithio-i- -ery-
D
thro-pentopyranoside (25b).—Deacetylation of
24 (a:b 1:3, 0.45 g, 1.3 mmol) with 1 M
NaOMe (0.1 mL) in MeOH (10 mL) yielded,
after neutralization with solid CO2, 25b (0.1 g,
26%), which crystallized from the solution: mp
188–190 °C (MeOH); [h]D −134° (c 0.5,
MeOH); Rf 0.3 (solvent G); 1H NMR
(Me2SO-d6): l 7.78–7.55 (m, 4 H, aromatic),
4.90 and 4.85 (2d, 2 H, OH), 4.78 (dd, 1 H,
J1,2ax 10.0, J1,2eq 2.7 Hz, H-1), 3.85 (m, 1 H,
J3,4 3.4 Hz, H-3), 3.71 (m, 1 H, J4,5ax 9.3, J4,5eq
3.4 Hz, H-4), 2.93 (dd, 1 H, J5ax,5eq 13.0 Hz,
H-5ax), 2,49 (dd, 1 H, H-5eq), 2.32 (ddd, 1 H,
J2ax,2eq 13.3, J2eq,3 6.3, J2ax,3 2.4 Hz, H-2eq),
1.98 (ddd, 1 H, H-2ax). Anal. Calcd for
C12H13NO2S2: C, 53.91; H, 4.90; N, 5.24; S,
23.98. Found: C, 53.87; H, 4.86; N, 5.16; S,
23.85.
4-O-Acetyl-1,5-anhydro-2,3-dideoxy-
ero-pentitol (33) and 4,5-di-O-acetyl-2,3-
dideoxy- -glycero-pentose (34).—A solution
of the crude diacetate 31 (5 g, 25 mmol) [9] in
L
-glyc-
L

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
63
MeOH (50 mL) was hydrogenated in the pres-
ence of 10% Pd/C (250 mg) for 3 h. The
filtered solution was concentrated and the
residue separated by column chromatography
(solvent B). The fraction having Rf 0.6 (sol-
vent A) contained 33 (1.7 g, 47%): [h]D −17°;
1H NMR: l 4.80 (m, 1 H, J4,5a 3.1, J4,5b 5.9
Hz, H-4), 3.76 (dd, 1 H, J5a,5b 11.7 Hz, H-5a),
3.65 (m, 2 H, H-1a,b), 3.58 (dd, 1 H, H-5b),
2,3-Dideoxy-
D
-glycero-pentose
dibenzyl
dithioacetal (42).—To a stirred solution of 37
(15 g, 0.1 mol) in water (160 mL), a solution
of NaIO4 (22.5 g, 0.105 mol) in water (250
mL) was added at 0 °C over a period of 15
min. The starting material was gradually con-
verted into 38 (Rf 0.35“0.65, solvent E) while
NaIO3 precipitated. The mixture was filtered
after 30 min, the filtrate was concentrated and
the residue was coevaporated with EtOH (2×
200 mL). The residue was passed through a
short column (solvent E) to give upon concen-
tration a syrup (11.8 g, 100%) containing an
anomeric mixture of the corresponding fura-
nose and pyranose structures. This was dis-
solved in concd HCl (35 mL) and benzyl
mercaptan (31 mL, 0.25 mol) was added with
stirring. The mixture turned dark blue. After 1
h, it was poured into a mixture of water (300
mL) and CH2Cl2 (200 mL), the aq solution
was extracted with CH2Cl2 (200 mL) and the
combined extracts were washed with 5% aq
NaHCO3 and water. Upon concentration, the
residue was purified by column chromatogra-
phy (solvent A) to yield 42 (25.1 g 72%) as
syrup: [h]D −23°; lit. [h]D −23° [11]; Rf 0.3
13
2.10–1.50 (m, 4 H, H-2a,b,3a,b); C NMR: l
170.2 (CꢀO), 69.4, 67.6 (C-1,5), 67.8 (C-4),
27.9, 22.7 (C-2,3), 20.9 (OAc). Anal. Calcd for
C7H12O3: C, 58.32; H, 8.39. Found: C, 58.28;
H, 8.31.
Concentration of the fraction having Rf 0.4
(solvent A) gave 34 (1.6 g, 32%): [h]D +27°;
1H NMR: l 9.77 (dd, 1 H, J1,2a 1.1, J1,2b 1.1
Hz, H-1), 5.10 (m, 1 H, J4,5a 3.8, J4,5b 6.0 Hz,
H-4), 4.25 (dd, 1 H, J5a,5b 11.9 Hz, H-5a), 4.05
(dd, 1 H, H-5b), 2.55 (m, 2 H, H-2a,b), ꢀ2.0
(m, 2 H, H-3a,b), 2.05, 2.04 (2s, 6 H, OAc);
13C NMR: l 200.6 (C-1), 170.6, 170.4 (CꢀO),
70.5 (C-4), 64.6 (C-5), 39.4 (C-2), 23.0 (C-3),
20.8, 20.6 (OAc). Anal. Calcd for C9H14O5: C,
53.46; H, 6.98. Found: C, 56.28; H, 7.11.
3,4-Dideoxy-1,2:5,6-di-O-isopropylidene- -
D
threo-hexitol (36).—A solution of 35 [14–16]
(22.8 g, 0.1 mol) in MeOH (250 mL) and Et3N
(5 mL) was hydrogenated in the presence of
10% Pd/C (1 g) for 2 h. Concentration of the
filtered solution gave 36 (23 g, 100%). An
aliquot part (1 g) was purified by column
chromatography: Rf 0.55 (solvent C); [h]D
1
(solvent A); H NMR: l 7.30–7.10 (m, 10 H,
aromatic), 3.78 (d, 2 H, CH2Ph), 3.70 (d, 1 H,
CH2Ph), 3.68 (d, 1 H, CH2Ph), 3.48 (m, 1 H,
H-1), 3.42 (m, 2 H, J4,5b 8.1, J5a,5b 11.6 Hz,
H-4,5a), 3.26 (dd, 1 H, H-5b), 2.00–1.35 (m, 4
H, H-2a,b,3a,b); 13C NMR: l 138.8, 137.8,
128.7, 128.2, 126.7 (aromatic), 71.4 (C-4), 66.2
(C-5), 50.2 (C-1), 34.5, 34.4 (CH2Ph), 31.2,
30.2 (C-2,3).
1
+22°; H NMR: l 4.22 (m, 2 H, H-2,5), 4.12
(dd, 2 H, J1a,2 6.0, J1b,2 7.0, J1a,1b 7.5 Hz,
H-1a,6a), 3.55 (dd, 2 H, H-1b,6b), 1.80–1.50
(m, 4 H, H-3a,b,4a,b), 1.40, 1.32 (2s, 12 H,
CMe2); 13C NMR: l 108.7 (CMe2), 75.4 (C-
2,5), 69.1 (C-1,6), 29.4 (C-3,4), 26.8, 25.6
(CMe2). Anal. Calcd for C12H22O4: C, 62.58;
H, 9.63. Found: C, 62.68; H, 9.70.
4,5-Di-O-acetyl-2,3-dideoxy-
tose dibenzyl dithioacetal (44) and 4-O-acetyl-
2,3-dideoxy-5-O-p-toluenesulfonyl- -glycero-
D
-glycero-pen-
D
pentose dibenzyl dithioacetal (45).—To a
stirred solution of 42 (3.5 g, 10 mmol) in
pyridine (20 mL), a solution of tosyl chloride
(2.8 g, 15 mmol) in pyridine (15 mL) was added
at 0 °C during 10 min. Stirring was continued
at 20 °C for 1 h when the starting material was
converted into 43 (Rf 0.3“0.7, solvent A).
Then Ac2O (4 mL) was added and after 1 h the
mixture was processed the usual way to give,
after column chromatography (solvent D) and
concentration of the fraction having Rf 0.3
3,4-Dideoxy- -threo-hexitol (37).—A solu-
D
tion of crude 36 (22 g) in MeOH (250 mL)
and 1 M HCl (50 mL) was kept at 20 °C for 1
h. After neutralization with solid NaHCO3,
the mixture was concentrated and the residue
coevaporated with EtOH (2×100 mL). The
residue was extracted with hot EtOH (2×50
mL), the filtrate was concentrated to 30 mL
and was diluted with EtOAc (100 mL) to give
37 (10.2 g, 71%): mp 91–93 °C; lit. mp 92–
94 °C [18].
1
(solvent D), 44 (0.5 g, 11.6%): [h]D −7°; H
NMR: l 7.35–7.15 (m, 10 H, aromatic), 4.90

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
64
(7.5 mL), BF3·Et2O (48%, 1.6 mL) and subse-
quently a solution of 41 (5.1 g, 10 mmol) in
THF (10 mL) were added at 10 °C. Stirring
was continued at 20 °C for 2 h, then the
mixture was poured onto a stirred slurry of
Na2CO3 (5 g) in Et2O (200 mL). The separated
organic solution was washed with 10% aq
K2CO3, 10% aq KI and water. The residue
obtained upon concentration gave, after
column chromatography (solvent C), 40 (1.85
(m, 1 H, J4,5a 3.3, J4,5b 6.4 Hz, H-4), 4.11 (dd,
1 H, J5a,5b 11.9 Hz, H-5a), 3.91 (dd, 1 H,
H-5b), 3.82 (d, 2 H, CH2Ph), 3.73 (d, 1 H,
CH2Ph), 3.72 (d, 1 H, CH2Ph), 3.48 (m, 1 H,
H-1), 2.08, 2.04 (2s, 6 H, OAc), 1.85–1.60 (m,
4 H, H-2a,b,3a,b); 13C NMR: l 169.9, 169.7
(CꢀO), 137.7, 137.6, 128.5, 128.1, 126.6 (aro-
matic), 70.4 (C-4), 64.3 (C-5), 49.6 (C-1), 34.3,
34.2 (CH2Ph), 30.5, 27.8 (C-2,3), 20.5, 20.2
(OAc). Anal. Calcd for C23H28O4S2: C, 63.86;
H, 6.52; S, 14.82. Found: C, 63.70; H, 6.57; S,
14.73.
1
g, 66%): [h]D −2°; Rf 0.5 (solvent B); H
NMR: l 7.95–7.45 (m, 5 H, aromatic), 9.76
(t, 1 H, J1,2a 1.0, J1,2b 1.0 Hz, H-1), 5.08 (m, 1
H, J4,5a 4.5, J4,5b 6.1 Hz, H-4), 3.42 (dd, 1 H,
J5a,5b 14.2 Hz, H-5a), 3.22 (d, 1 H, H-5b), 2.55
(m, 2 H, J2,3.7.3 Hz, H-2a,b), 2.05 (s, 3 H,
OAc), 2.04 (m, 2 H, H-3a,b); 13C NMR: l
200.8 (C-1), 190.6 (SꢁCꢀO), 170.3 (CꢀO),
136.4, 133.5, 128.6, 127.2 (aromatic), 71.6 (C-
4), 39.6, 32.0, 25.4 (C-2,3,5), 20.8 (OAc).
Anal. Calcd for C14H16O4S: C, 59.98; H, 5.76;
S, 11.42. Found: C, 59.93; H, 5.67; S, 11.22.
Concentration of the fraction having Rf 0.6
(solvent B) gave 45 (3.7 g, 68%): [h]D −17°;
1H NMR: l 7.75–7.15 (m, 14 H, aromatic),
4.76 (m, 1 H, J4,5a 3.5, J4,5b 5.2 Hz, H-4), 4.07
(dd, 1 H, J5a,5b 10.9 Hz, H-5a), 3.89 (dd, 1 H,
H-5b), 3.79 (d, 2 H, CH2Ph), 3.72 (d, 1 H,
CH2Ph), 3.70 (d, 1 H, CH2Ph), 3.43 (m, 1 H,
H-1), 2.42 (s, 3 H, Me), 1.92 (s, 3 H, OAc),
13
1.75–1.55 (m, 4 H, H-2a,b,3a,b); C NMR: l
170.1 (CꢀO), 144.9, 137.9, 137.8, 132.6, 129.8,
128.9, 128.5, 127.8, 127.0 (aromatic), 70.2 (C-
4), 69.6 (C-5), 50.0 (C-1), 34.3, 34.2 (CH2Ph),
30.8, 27.8 (C-2,3), 21.6 (Me), 20.7 (OAc).
Anal. Calcd for C28H32O5S3: C, 61.74; H, 5.92;
S, 17.66. Found: C, 61.68; H, 5.99; S, 17.55.
2,3-Dideoxy-5-thio- -glycero-pentopyranose
D
(39).—To a solution of 40 (2.8 g, 10 mmol) in
MeOH (20 mL), 4 M NaOMe (0.2 mL), and
after 24 h an additional 4 M NaOMe (0.2 mL)
were added. The mixture was neutralized with
solid CO2 after 48 h and the residue obtained
on concentration was partitioned between wa-
ter and CH2Cl2. The aq solution was concen-
trated and the residue filtered through a short
column with EtOAc to give, on concentration,
39 (1.03 g, 77%) containing the a,b anomers in
a 2:1 ratio: mp 68–71 °C; [h]D +71°; Rf 0.5
4-O-Acetyl-5-S-benzoyl-2,3-dideoxy- -glyc-
D
ero-pentose dibenzyl dithioacetal (41).—A so-
lution of 45 (4.9 g, 9 mmol) and KSBz (2.5 g,
14.2 mmol) in DMF (25 mL) was stirred at
50 °C for 2 h. The residue obtained upon
concentration was purified by column chro-
matography (solvent C) to give 41 (4 g, 88%):
1
[h]D−6°; Rf 0.55 (solvent C); H NMR: l
1
(solvent F); H NMR (Me2SO-d6): a anomer,
7.95–7.10 (m, 14 H, aromatic), 4.92 (m, 1 H,
J4,5a 4.6, J4,5b 6.6 Hz, H-4), 3.83 (d, 2 H,
CH2Ph), 3.76 (d, 1 H, CH2Ph), 3.74 (d, 1 H,
CH2Ph), 3.48 (m, 1 H, H-1), 3.33 (dd, 1 H,
J5a,5b 13.9 Hz, H-5a), 3.10 (dd, 1 H, H-5b),
2.00 (s, 3 H, OAc), 1.85–165 (m, 4 H, H-
l 5.70, 4.90 (2d, 2 H, OH), 4.72 (dd, 1 H, J1,2ax
2.7, J1,2eq 2.7, J1,5eq ꢀ1 Hz, H-1), 3.58 (m, 1 H,
J4,5ax 10.5, J4,5eq 3.9 Hz, H-4), 2.70 (dd, 1 H,
J5ax,5eq 12.4 Hz, H-5ax), 2,40 (dd, 1 H, H-5eq),
13
2.10–1.75 (m, 4 H, H-2a,b,3a,b); C NMR: l
13
68.6, 68.3 (C-1,4), 35.6, 30.4, 29.2 (C-2,3,5).
2a,b,3a,b); C NMR: l 190.2 (SꢁCꢀO), 169.8
1
10.9. H NMR (Me2SO-d6): b anomer, l 5.70,
(CꢀO), 137.6, 137.5, 136.2, 133.2, 128.6, 128.2,
128.1, 126.8, 126.6 (aromatic), 71.3 (C-4), 49.8
(C-1), 34.3, 34.3 (CH2Ph), 31.8, 30.7, 30.4
(C-2,3,5), 20.6 (OAc). Anal. Calcd for
C23H30O3S3: C, 65.85; H, 5.92; S, 18.83.
Found: C, 65.77; H, 5.90; S, 18.58.
4.80 (2d, 2 H, OH), 4.68 (dd, 1 H, J1,2ax 9.0,
J1,2eq 2.7 Hz, H-1), 3.60 (m, 1 H, J4,5ax 9.0,
J4,5eq 3.2 Hz, H-4), 2.64 (dd, 1 H, J5ax,5eq 13.5
Hz, H-5eq), 2,44 (dd, 1 H, H-5ax), 2.15–1.25
13
(m, 4 H, H-2a,b,3a,b); C NMR: l 72.7, 66.7
(C-1,4), 39.0, 34.1, 32.3 (C-2,3,5). Anal. Calcd
for C5H10O2S: C, 44.75; H, 7.51; S, 23.89.
Found: C, 44.77; H, 7.48; S, 23.84.
4-O-Acetyl-5-S-benzoyl-2,3-dideoxy- -glyc-
D
ero-pentose (40).—To a stirred slurry of yel-
low HgO (2.5 g) in THF (50 mL) and water

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E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
65
(OAc); 1H NMR: b anomer, l 7.60–7.50 (m, 4
H, aromatic), 4.98 (m, 1 H, J4,5ax 8.6, J4,5eq
ꢀ2.5 Hz, H-4), 4.28 (dd, 1 H, J1,2ax 8.8, J1,2eq
2.7 Hz, H-1), 2.96 (dd, 1 H, J5ax,5eq 13.4 Hz,
H-5eq), 2.74 (dd, 1 H, H-5ax), 2.48 (m, 1 H,
H-2a), 2.10 (m, 1 H, H-2b), 2.07 (s, 3 H,
OAc), 2.05 (m, 1 H, H-3a), 1.65 (m, 1 H,
1,4-Di-O-acetyl-2,3-dideoxy-5-thio- -glyc-
D
ero-pentopyranose (28).—Acetylation of 39
(1.8 g, 13.4 mmol) with Ac2O (8 mL) in
pyridine (10 mL) gave, after the usual process-
ing, 28 (2.43 g, 83%) containing the a,b
anomers in a ꢀ1:1 ratio: mp 72–74 °C
(ether–hexane). They could be partly sepa-
rated by column chromatography (solvent D)
to give 28a: mp 64–66 °C; [h]D +207°; Rf 0.4
13
H-3b); C NMR: l 170.0 (CꢀO), 140.5, 132.2,
129.6, 109.8 (aromatic), 118.4 (CN), 68.5 (C-
4), 47.0 (C-1), 32.2, 31.7, 29.7 (C-2,3,5). 21.0
(OAc). Anal. Calcd for C14H15NO2S2: C,
57.31; H, 5.15; N, 4.77; S, 21.85. Found: C,
57.39; H, 5.22; N, 4.83; S, 21.91.
1
(solvent D); H NMR: l 5.75 (t, 1 H, J1,2ax
3.2, J1,2eq 3.2, J1,5eq ꢀ1 Hz, H-1), 4.97 (dddd, 1
H, J4,5ax 10.7, J4,5eq 4.0 Hz, H-4), 2.92 (dd, 1
H, J5ax,5eq 12.4 Hz, H-5ax), 2.65 (dd, 1 H,
H-5eq), 2.35–1.75 (m, 4 H, J3ax,4 11.0, J3eq,4
4.2 Hz, H-2a,b,3a,b), 2.12, 2.06 (2s, 6 H,
OAc); 13C NMR: l 169.5, 169.4 (CꢀO), 70.8,
69.8 (C-1,4), 32.9, 27.4, 26.1 (C-2,3,5). 21.2,
21.1 (OAc); and 28b: mp 123–125 °C; [h]D−
When the same reaction was carried out at
20 °C, a mixture was formed containing 46
only in traces and after column chromatogra-
phy (solvent D) and subsequent crystallization
from MeOH, 4-cyanophenyl 2,3-dideoxy-
1
315°; Rf 0.3 (solvent D); H NMR: l 5.84 (t, 1
1,4,5 - trithio - 5 - (4 - cyanophenyl) - - glycero -
L
H, J1,2ax ꢀ2.5, J1,2eq ꢀ2.5, J1,5eq ꢀ1 Hz, H-1),
5.08 (ddd, 1 H, J4,5ax 2.2, J4,5eq 4.6 Hz, H-4),
3.17 (dd, 1 H, J5ax,5eq 14.4 Hz, H-5ax), 2.74
pentofuranoside (49, 0.39 g, 23%) could be
isolated: mp 123–125 °C (MeOH); [h]D −369°
1
(c 0.5, CHCl3); H NMR: l 7.60–7.50 (m, 4
(dd, 1 H, H-5eq), 2.40–1.75 (m, 4 H, J3ax,4
ꢀ
H, aromatic), 7.40–7.30 (m, 4 H, aromatic),
5.01 (t, 1 H, J1,2a 4.9, J1,2b 4.9 Hz, H-1), 3.80
(m, 1 H, J4,5a 6.6, J4,5b 7.8 Hz, H-4), 3.18 (dd,
1 H, J5a,5b 13.2 Hz, H-5a), 3.13 (dd, 1 H,
H-5b), 2.45 (m, 2 H, H-2a,3a), 2.18 (m, 1 H,
H-2b), 2.05 (m, 1 H, H-3b); 13C NMR: l
143.6, 143.1, 132.4, 132.4, 128.6, 127.7, 109.5,
109.1 (aromatic), 118.6, 118.5 (CN), 54.1 (C-
1), 48.4 (C-4), 38.6, 36.6 (C-2,5). 33.9 (C-3).
Anal. Calcd for C19H16N2S3: C, 61.92; H, 4.38;
N, 7.60; S, 26.10. Found: C, 61.88; H, 4.35; N,
4.30; S, 25.92.
3, J3eq,4 ꢀ3 Hz, H-2a,b,3a,b), 2.13, 2.11 (2s, 6
H, OAc); 13C NMR: l 170.3, 169.3 (CꢀO),
70.6, 65.1 (C-1,4), 27.9, 26.8, 24.1 (C-2,3,5).
21.0, 20.9 (OAc). Anal. Calcd for C9H14O4S:
C, 49.53; H, 6.47; S, 14.69. Found for 28a: C,
49.47; H, 6.48; S, 14,58. Found for 28b: C,
49.51; H, 6.49; S, 14,63.
4-Cyanophenyl 4-O-acetyl-2,3-dideoxy-1,5-
dithio- -glycero-pentopyranoside (46).—To a
D
stirred solution of 28 (1.0 g, 4.6 mmol) and
4-cyanobenzenethiol (1.25 g, 9.2 mmol) in dry
1,2-dichloroethane (30 mL) under argon,
Et3SiOTf (1.15 mL, 4.6 mmol) was added at
−10 °C. After stirring at −10 °C for 30 min,
the reaction was quenched with Et3N, concen-
trated and submitted to column chromatogra-
phy (solvent D) to yield 46 (1.15 g, 86%) as a
1:3 mixture of a and b anomers. Rf 0.4 (sol-
vent D). Recrystallization from ether gave 46b
(0.44 g, 33%); mp 108–110 °C (ether); [h]D
4-Nitrophenyl 4-O-acetyl-2,3-dideoxy-1,5-
dithio- -glycero-pentopyranoside (47).—To a
D
stirred solution of 28 (1.0 g, 4.6 mmol) and
4-nitrobenzenethiol (1.4 g, 9.2 mmol) in dry
1,2-dichloroethane (30 mL) under argon,
Et3SiOTf (1.15 mL, 4.6 mmol) was added at
−10 °C. After stirring at −10 °C for 30 min,
the reaction was quenched with Et3N, concen-
trated and submitted to column chromatogra-
phy (solvent D) to yield 47 (1.42 g, 99%) as a
3:7 mixture of a and b anomers: Rf 0.4 (sol-
vent D). Recrystallization from ether gave 47b
(0.88 g, 61%): mp 127–130 °C (ether); [h]D
1
−275° (c 0.5, CHCl3); H NMR: a anomer, l
7.60–7.40 (m, 4 H, aromatic), 4.97 (m, 1 H,
J4,5ax 9.8, J4,5eq ꢀ2.5 Hz, H-4), 4.47 (t, 1 H,
J1,2ax 3.2, J1,2eq 3.2 Hz, H-1), 3.06 (dd, 1 H,
J5ax,5eq ꢀ13 Hz, H-5ax), 2.72 (dd, 1 H, H-5eq),
2.40–1.80 (m, 4 H, H-2a,b,3a,b), 2.0.5 (s, 3 H,
OAc); 13C NMR: l 170.0 (CꢀO), 69.9 (C-4),
47.0 (C-1), 32.5, 28.4, 27.1 (C-2,3,5). 21.0
1
−192° (c 0.5, CHCl3); H NMR: a anomer, l
8.14–7.48 (m, 4 H, aromatic), 4.98 (m, 1 H,
J4,5ax 9.8, J4,5eq 3.9 Hz, H-4), 4.52 (t, 1 H, J1,2ax

´
E. Bozo´ et al. / Carbohydrate Research 321 (1999) 52–66
66
3.9, J1,2eq 3.9 Hz, H-1), 3.06 (dd, 1 H, J5a,5eq
13.2 Hz, H-5ax), 2.74 (dd, 1 H, H-5eq), 2.38
(m, 2 H, H-2a,b), 2.05 (s, 3 H, OAc), 1.92 (m,
10.2, J1,2eq 2.9 Hz, H-1), 3.68 (m, 1 H, J4,5ax
8.3, J4,5eq ꢀ2.5 Hz, H-4), 2.68 (dd, 1 H, J5ax,5eq
12.9 Hz, H-5eq), 2.64 (dd, 1 H, H-5ax), 2.45
(m, 1 H, J3ax,4ꢀ8.2, J3eq,4 ꢀ3.8 Hz, H-3a),
2.35 (m, 1 H, H-2a), 1.85 (m, 1 H, H-2b), 1.50
(m, 1 H, H-3b). Anal. Calcd for C11H13NO3S2:
C, 48.69; H, 4.83; N, 5.16; S, 23.63. Found: C,
48.75; H, 4.79; N, 5.11; S, 23.57.
13
2 H, H-3a,b); C NMR: l 170.1 (CꢀO),146.6,
144.7, 129.2, 124.0 (aromatic), 70.0 (C-4), 47.0
(C-1), 32.7, 28.6, 27.3 (C-2,3,5). 21.2 (OAc);
1H NMR: b anomer, l 8.15–7.50 (m, 4 H,
aromatic), 4.98 (m, 1 H, J4,5ax 8.6, J4,5eq ꢀ3
Hz, H-4), 4.35 (dd, 1 H, J1,2ax 9.0, J1,2eq 2.9
Hz, H-1), 2.98 (dd, 1 H, J5ax,5eq 13.4 Hz,
H-5eq), 2.76 (dd, 1 H, H-5ax), 2.72 (m, 1 H,
H-3a), 2.52 (m, 1 H, H-2a), 2.15 (m, 1 H,
H-2b), 2.08 (m, 1 H, H-3b), 2.08 (s, 3 H,
Acknowledgements
The authors are indebted to Dr Gabriella
Szabo´ for the biological results.
13
OAc); C NMR: l 170.1 (CꢀO), 145.9, 144.2,
128.8 123.8 (aromatic), 68.5 (C-4), 46.9 (C-1),
32.2, 31.7, 29.7 (C-2,3,5). 21.1 (OAc). Anal.
Calcd for C13H15NO4S2: C, 49.82; H, 4.82; N,
4.47; S, 20.46. Found: C, 49.90; H, 4.86; N,
4.51; S, 20.43.
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ation of 46b (0.42 g, 1.4 mmol) with 1 M
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(0.27 g, 75%): mp 133–135 °C (ether); [h]D−
164° (c 0.4, MeOH); Rf 0.3 (solvent G); [h]D−
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1
275° (c 0.5, CHCl3); H NMR (Me2SO-d6): l
7.76–7.56 (m, 4 H, aromatic), 5.03 (d, 1 H,
OH), 4.64 (dd, 1 H, J1,2ax 10.6, J1,2eq 2.9 Hz,
H-1), 3.67 (m, 1 H, J4,5ax 8.3, J4,5eq ꢀ2.5 Hz,
H-4), 2.66 (dd, 1 H, J5ax,5eq 12.9 Hz, H-5eq),
2.63 (dd, 1 H, H-5ax), 2.34 (m, 1 H, H-2a),
1.95 (m, 1 H, J3ax,4 ꢀ8.2, J3eq,4 ꢀ3.8 Hz, H-
3a), 1.83 (m, 1 H, H-2b), 1.48 (m, 1 H, H-3b).
Anal. Calcd for C12H13NOS2: C, 57.34; H,
5.21; N, 5.57; S, 25.51. Found: C, 57.43; H,
5.16; N, 5.50; S, 25.59.
4-Nitrophenyl 2,3-dideoxy-1,5-dithio-i-
D
-
glycero-pentopyranoside (51b).—Deacetyl-
ation of 47b (0.86 g, 2.7 mmol) with 1 M
NaOMe (0.1 mL) in MeOH (30 mL) yielded,
after neutralization with solid CO2 and
column chromatography (solvent G), 51b
(0.52 g, 70%): mp 142–145 °C (ether); [h]D1−
119° (c 0.5, MeOH); Rf 0.3 (solvent G); H
NMR (Me2SO-d6): l 8.18–7.65 (m, 4 H, aro-
matic), 5.05 (d, 1 H, OH), 4.69 (dd, 1 H, J1,2ax
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.