Synthesis of 4-cyano- and 4-nitrophenyl 2,5-anhydro-1,6-dithio-α-d-gluco- and -α-L-guloseptanosides carrying different substituents at C-3 and C-4

Article abstract of DOI:10.1016/S0008-6215(00)00190-7

Treatment of 1,6:2,5-dianhydro-3,4-di-O-methanesulfonyl-1-thio-D-glucitol in methanol with sodium hydroxide afforded 1,6:2,5:3,4-trianhydro-1-thio-allitol, 1,4:2,5-dianhydro-6-methoxy-1-thio-D-galactitol, 1,6:2,5-dianhydro-4-O-methyl-1-thio-D-glucitol, 1,6:2,5-dianhydro-3-O-methanesulfonyl-1-thio-D-glucitol and 1,6:2,5-dianhydro-4-deoxy-1-thio-D-erythro-hex-3-ulose (14) in 5, 4, 28, 5.5 and 41% yield, respectively. Formation of these derivatives can be explained via a common sulfonium intermediate. Reduction of 14 with sodium borohydride and subsequent acetylation afforded 3-O-acetyl-1,6:2,5-dianhydro-4-deoxy-1-thio-D-xylo-hexitol, the absolute configuration of which was proved by X-ray crystallography. The 1,6:2,5-dianhydro-1-thio-D-hexitol derivatives in which the free OH groups were protected by acetylation, methylation or mesylation were converted by a Pummerer reaction of their sulfoxides into the corresponding 1-O-acetyl hexoseptanose derivatives which were used as donors for the glycosidation of 4-cyano- and 4-nitrobenzenethiol, respectively. The Pummerer reaction of 1,6:2,5-dianhydro-4-deoxy-3-O-methyl-1-thio-D-xylo-hexitol S-oxide gave, besides 1-O-acetyl-2,5-anhydro-3-deoxy-4-O-methyl-6-thio-α-L- (23) and 1-O-acetyl-2,5-anhydro-4-deoxy-3-O-methyl-6-thio-α-D-xylo-hexose ptanose (25), 1-O-acetyl-4-deoxy-2,6-thioanhydro-D-lyxo-hexopyranose, formed in a rearrangement reaction. The same rearrangement took place, when a mixture of 23 and 25 was used as donor in the glycosidation reaction with 4-cyanobenzenethiol, applying trimethylsilyl triflate as promoter. The oral antithrombotic activity of the obtained α-thioglycosides was determined in rats, using Pescador's model. (C) Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(00)00190-7

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Carbohydrate Research 329 (2000) 269–286
Synthesis of 4-cyano- and 4-nitrophenyl
2,5-anhydro-1,6-dithio-a-
D
-gluco- and
-a-L
-guloseptanosides carrying different substituents at
C-3 and C-4ꢀ
a
b
c
b,
´
Eva Bozo´ , Sa´ndor Boros , La´szlo´ Pa´rka´nyi , Ja´nos Kuszmann *
a Gedeon Richter Chemical Works Ltd., PO Box 17, H-1475 Budapest, Hungary
b Institute for Drug Research, PO Box 82, H-1325 Budapest, Hungary
c Central Research Institute for Chemistry, Hungarian Academy of Sciences, PO Box 17,
H-1525 Budapest, Hungary
Received 9 May 2000; accepted 23 June 2000
Dedicated to Professor Andra´s Lipta´k on the occasion of his 65th birthday
Abstract
Treatment of 1,6:2,5-dianhydro-3,4-di-O-methanesulfonyl-1-thio-
afforded 1,6:2,5:3,4-trianhydro-1-thio-allitol, 1,4:2,5-dianhydro-6-methoxy-1-thio-
O-methyl-1-thio- -glucitol, 1,6:2,5-dianhydro-3-O-methanesulfonyl-1-thio- -glucitol and 1,6:2,5-dianhydro-4-deoxy-
1-thio- -erythro-hex-3-ulose (14) in 5, 4, 28, 5.5 and 41% yield, respectively. Formation of these derivatives can be
explained via a common sulfonium intermediate. Reduction of 14 with sodium borohydride and subsequent
acetylation afforded 3-O-acetyl-1,6:2,5-dianhydro-4-deoxy-1-thio- -xylo-hexitol, the absolute configuration of which
was proved by X-ray crystallography. The 1,6:2,5-dianhydro-1-thio- -hexitol derivatives in which the free OH groups
D
-glucitol in methanol with sodium hydroxide
D
-galactitol, 1,6:2,5-dianhydro-4-
D
D
D
D
D
were protected by acetylation, methylation or mesylation were converted by a Pummerer reaction of their sulfoxides
into the corresponding 1-O-acetyl hexoseptanose derivatives which were used as donors for the glycosidation of
4-cyano- and 4-nitrobenzenethiol, respectively. The Pummerer reaction of 1,6:2,5-dianhydro-4-deoxy-3-O-methyl-1-
thio-
D
-xylo-hexitol S-oxide gave, besides 1-O-acetyl-2,5-anhydro-3-deoxy-4-O-methyl-6-thio-a-
L
- (23) and 1-O-
acetyl-2,5-anhydro-4-deoxy-3-O-methyl-6-thio-a-
D
-xylo-hexoseptanose (25), 1-O-acetyl-4-deoxy-2,6-thioanhydro-D-
lyxo-hexopyranose, formed in a rearrangement reaction. The same rearrangement took place, when a mixture of 23
and 25 was used as donor in the glycosidation reaction with 4-cyanobenzenethiol, applying trimethylsilyl triflate as
promoter. The oral antithrombotic activity of the obtained a-thioglycosides was determined in rats, using Pescador’s
model. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Antithrombotic thioglycosides; Sulfonium intermediates; Pummerer reaction
1. Introduction
ꢀ Orally active antithrombotic thioglycosides, Part XI. For
Part X, see Ref. [1].
* Corresponding author. Tel.: +36-1-3993441; fax: +36-
1-3993356.
In a previous paper [1] we have shown that,
in contrast to the statement of the literature
[2], the oral antithrombotic effect of 4-
cyanophenyl 1,5-dithio-pentopyranosides is
E-mail address: h13757kus@ella.hu (J. Kuszmann).
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00190-7

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E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
270
not restricted to the b-
D
-xylo configuration (1)
(5.5%), epoxide 7 (5%), two monohydroxy–
as e.g., the overbridged, 2,5-anhydro-1,6-
monomethoxy derivatives 9 (4%) and 11
(28%), as well as the ketone 14 (41%) could be
isolated after column chromatography
(Scheme 2). The formation of all these deriva-
tives can be explained via the sulfonium inter-
mediate 5 [3]. Attack of the OH− ion at C-4
will lead with retention of configuration to the
hydroxyꢀmesylate 6 which undergoes a trans
elimination of methanesulfonic acid affording
the known [3] allo epoxide 7. A similar attack
of the MeO− ion at C-4 will result in the
methoxyꢀmesylate 10, the mesyl group of
which will be split off in an E1cB type process
[5] via regeneration of the 3-OH group afford-
ing 11. Furthermore, the MeO− ion can at-
tack the less polar, but less crowded C-6
bridge atom of 5 too, when rearrangement to
the 1,4:2,5-dianhydro-3-O-methanesulfonyl-6-
dithio-D-gluco- (2) and -guloseptanosides (3)
L
possess a much stronger biological activity
(Scheme 1). For checking the structure–activ-
ity relationship in this type of thioglycosides,
the role of the free OH groups at C-3 and/or
C-4 was studied by synthesising analogues of
2 and 3, in which OH-4 was either eliminated,
methylated or exchanged with retention of
configuration with an azido group, while OH-
3 was kept intact or was converted into its
methyl ether or mesyl ester.
2. Results and discussion
For the synthesis of the aforementioned
thioglycosides, the 3,4-dimesylate of the corre-
sponding 1,6-thioanhydro-
D
-glucitol deriva-
methoxy-1-thio- -galactitol isomer 8 takes
D
tive 4 was chosen as starting material, which
place. The mesyl group of the latter will be
split off as mentioned above yielding the iso-
lated methoxyꢀhydroxy derivative 9. The
main attack of the base occurs however either
at H-3 (route a), splitting it off as a proton
resulting in the enolꢀester 12 from which the
can be prepared from 1,6-dibromo-1,6-
dideoxy- -mannitol in seven steps [3,4]. When
D
4 was treated in methanol with 40% aqueous
sodium hydroxide, a complex mixture was
formed, from which the monomesylate 6
Scheme 1.
Scheme 2.

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E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
271
Both the acetate 16 as well as the 3-O-
methyl ether 17, which was obtained from 15
by methylation with methyl iodide in the pres-
ence of sodium hydride, were converted with
hydrogen peroxide in acetic acid into the cor-
responding sulfoxides 20 and 21, respectively.
Pummerer rearrangement of 20 gave a mixture
mesyl group is removed by the base yielding
13 which rearranges immediately to the 3-keto
compound 14. Another possibility would be
an attack of the base on the methyl group of
the mesyloxy substituent (route b) the depro-
tonation of which could trigger a chain reac-
tion in which the mesyl group would be first
eliminated as a sulfene [5] and the formed
3-oxy anion would form directly 14 via migra-
tion of H-3 to C-4 in a pinacoline-type rear-
rangement. The absolute configuration of 14
had to be established, as deprotonation of 4 at
C-4 could not be ruled out and this process
would lead via a similar reaction sequence to
the isomeric 4-keto derivative, indistinguish-
able by NMR spectroscopy from 14. For this
reason 14 was reduced with sodium borohy-
dride, but from the theoretically possible two
isomers 15 and 18 only the former was formed
which was converted into its crystalline ace-
tate 16. The stereoselectivity of the reduction
is a consequence of the steric arrangement of
14, in which the thioether bridge is ‘endo’
related to the keto group, therefore the boro-
hydride ion can approach the latter only from
the less hindered ‘exo’ side, excluding the for-
mation of 18. The hydroxy derivative 15, ob-
tained as a by-product from 4 on reduction
with LAH [5] had probably the same struc-
ture, but as the configuration of this com-
pound was only deduced from the mechanism
suggested for this reaction [5], this structure
from which the 3-deoxy-a-
L
- 22 and the 4-
deoxy-a- -xylo-diacetate 24 could be isolated
D
by column chromatography in a yield of 2 and
71%, respectively. When 24 was applied as
donor in the glycosylation reaction with 4-
cyanobenzenethiol and trimethylsilyl triflate as
promoter, the corresponding a- -septanoside
D
26 was obtained in excellent yield (97%) and
gave, after deacetylation according to Zem-
ple´n, 27 which was submitted to biological
testing. When 4-nitrobenzenethiol was used as
acceptor, and borontrifluoride etherate as pro-
moter, the resulting acetylated thioglycoside
28 afforded 29 after deacetylation (Scheme 3).
When the methoxy derivative 21 was sub-
mitted to the Pummerer reaction, besides a 1:4
mixture of the isomeric monoacetates 23 and
25 the 4-deoxy-2,6-thioanhydro- -lyxo-hexo-
D
pyranose acetate 35 as well as its ethyl pyran-
oside 36a could be isolated in a yield of 40,
9.5 and 5%, respectively. The rearranged
structure of the last two derivatives was estab-
lished by NMR spectroscopy comparing their
data with those of the thioseptanose acetates
23 and 25. Formation of 35 and 36 can be
explained via the isomeric sulfenium ions 32
and 33, which are the hypothetical intermedi-
ates of the Pummerer reaction [6] and are in
equilibrium with each other [1]. However 33 is
probably in an equilibrium with the oxocarbe-
nium ion 34 formed in a pinacoline-type rear-
rangement reaction via a shift of the C-3ꢀC-2
bond to C-1 (Scheme 3). As 34 should be
much more reactive than 33 the acetoxy anion
had still to be established. The absolute -xylo
D
configuration of 16 was finally established by
X-ray crystallography (Fig. 1).
will attack the former yielding the -lyxopyra-
D
nose acetate 35. This was obtained as a single
isomer, the anomeric configuration of which
could not be established by NMR spec-
troscopy. Nevertheless, it is most probably an
a anomer as its optical rotation ([h]D +23°) is
very similar to that of the corresponding ethyl
a-glycoside 36a1 ([h]D +17°).
1 36a is probably formed from 35 during work up (evapora-
tion with EtOH).
Fig. 1. ORTEP plot [15] (using the program PLATON) of 16.
Thermal ellipsoids represent 40% probabilities.

´
272
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
Scheme 3.
and C-3 was evident from the shift of the
corresponding signals in the C NMR spectra
The structure of 36a and 38 was established
13
by NMR spectroscopy by the following data.
According to selective INEPT experiments,
(85.0 and 44.1 ppm) compared to those of 36a
(100.8 and 70.4 ppm). Furthermore, selective
INEPT measurements showed a three-bond
connectivity between H-1 as well as H-3 and
the aromatic C-1% carbon atoms. Besides a
1
there was a three-bond H–13C connectivity in
36a between H-1 (5.26 ppm) and C-3 (70.4
ppm) proving the quasi-equatorial (b) ar-
rangement of H-1. On the other hand, a long
4
4
long range coupling J4a,6b of 2.2 Hz, an inten-
range coupling J4a,6b of 2.3 Hz indicated the
W-arrangement of H-4a and H-6b, enabling
sive cross-peak between H-4b and H-6a could
be detected too in full agreement with the
steric arrangement of these protons in 38. The
inversion of configuration at C-3 was evident
from the change in the value of the J3,4a and
3
their identification. The corresponding J3,4a
and 3J3,4b coupling constants of 9.5 and 2.7 Hz
could be determined accordingly. Location of
the two 4-cyanophenylthio groups in 38 at C-1

´
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
273
both, 4-cyano- and 4-nitrobenzenethiol afford-
ing 45 and 47 which on deacetylation gave 46
and 48, respectively. Similar glycosidation of
the minor component 41 with 4-cyanoben-
zenethiol gave 44 via 43 (Scheme 4).
For checking the influence of the free 3-OH
group of the aforementioned 3-hydroxy-4-
methoxy-thioglycosides on the antithrombotic
activity, the corresponding 3,4-di-O-methyl
derivatives were synthesised too. Theoretically
these derivatives could be obtained by methy-
lating the free 3-OH group of 46 and 48 but,
as shown above, these thioglycosides could be
obtained in a multistep synthesis only, the
overall yield of which was too low for using
them as starting material in any further reac-
tion. For this reason, 2,5-anhydro-6-bromo-
J3,4b coupling constants (9.5“4.8 and 2.7“
11.0 Hz, respectively). In accordance with this
arrangement, no NOE effect was observed
between H-1 and H-3. The anomeric configu-
ration of 38 was deduced further from the
results of the selective INEPT experiments, as
1
no three-band H–13C connectivity could be
detected between H-1 (6.28 ppm) and C-3
(44.1 ppm) and a strong NOE effect was
observed on the aromatic protons on irradiat-
ing H-6b.
The mechanism of the rearrangement, de-
picted in Scheme 3 was further backed by the
fact that, when the isomeric mixture of the
1-O-acetates 23 and 25 was used as donor in
the glycosidation reaction with 4-cyanoben-
zenethiol in the presence of trimethylsilyl tri
-flate as promoter, instead of the correspond-
6-deoxy-3,4-di-O-methyl-
plied as starting material, which can be easily
obtained from -mannitol in few steps [7].
D-glucitol 49 was ap-
ing 4-deoxy-a-
D
-xylo-hexoseptanoside 30, only
the thioglycoside of 2,6-thioanhydro-b-
D
-ara-
D
bino-hexopyranoside 38, carrying a second 4-
cyanothiophenol substituent at C-3 could be
isolated in 26% yield. The formation of 38
might be explained by the same sulfenium ion
intermediate 33 mentioned above, which can
be formed from both, 23 and 25 in the pres-
ence of trimethylsilyl triflate according to the
mechanism depicted in Scheme 3 [1] and re-
acts via the oxocarbenium intermediate 34 to
give first the rearranged thioglycoside 37, the
3-O-methyl group of which is then activated
by trimethylsilyl triflate and undergoes a sub-
stitution reaction via inversion of configura-
tion affording 38. The same glycoside 38 was
obtained in a yield of 97%, when acetate 35
was used as donor. The desired 3-O-methyl
thioseptanosides 30 and 31 were finally syn-
thesised by methylating the 3-OH group of the
corresponding glycosides 27 and 29, respec-
tively, using methyl iodide in the presence of
sodium hydride in N,N-dimethylformamide.
For the synthesis of the 4-O-methyl thiosep-
tanosides 46 and 48, the 3-O-acetyl-4-O-
methyl-glucitol derivative 39, which was
obtained from 11 by acetylation, was con-
verted via oxidation and Pummerer reaction
of the obtained sulfoxide 40 into a 1:9 mixture
of the isomeric acetates 41 and 42. This mix-
ture could be separated by column chro-
matography, and the major component 42
was used as donor for the glycosidation of
Reaction of 49 with potassium thioacetate
afforded 50, which after mesylation and treat-
ment of the obtained mixed ester 51 with
methanolic sodium methoxide, gave the
thioether 52 in excellent yield (Scheme 5). This
was converted into the sulfoxide 53 the Pum-
merer rearrangement of which afforded the
two isomeric acetates 59 and 61 in a ratio of
9:1. They were used without separation for the
glycosylation of both, 4-cyano- and 4-nitro-
benzenethiol and the formed thioglycosides 55
and 56 were isolated by column chromatogra-
phy. By analogy, the corresponding 3,4-di-O-
mesylates 57 and 58 were also synthesised,
using the known [9] sulfoxide 54 as starting
material.
Finally, we decided to synthesise such
analogs, in which the 4-OH group of 2 or 3
is exchanged by azide, as similar substitution
in 1 type compounds led to a substantial
increase in the antithrombotic activity [8]. As
starting
material
1,6-anhydro-3-O-tetra-
-glucitol 63
hydropyranyl-4-O-mesyl-6-thio-
D
[1] was chosen, the mesyloxy group of which
could be exchanged by azide with retention
of configuration affording 64 via an 5 type
(OMs=OTHP)
sulfonium
intermediate
(Scheme 6). After removing the tetra-
hydropyranyl group in methanol with an ion
exchange resin (H+), the resulting hydroxy
derivative 65 was acetylated and the acetate 66

´
274
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
Scheme 4.
Scheme 5.
converted via the Pummerer reaction of its
sulfoxide 68 into a 1:4 mixture of the corre-
sponding 1-O-acetates 70 and 72. This mix-
ture was used as donor in the glycosidation of
4-cyanobenzenethiol and gave, after column
chromatography, the corresponding thioglu-
coside 75. When 4-nitrobenzenethiol was used
as aglycon, besides 78 the corresponding
L
-
gulo isomer 74 could also be isolated in traces.
Deacetylation of 75 and 78 afforded 76 and
79, respectively. For checking the influence of
the 3-OH group of these derivatives on the
biological activity, the corresponding 3-O-me-
syl compounds 77 and 80 were also prepared

´
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
275
Scheme 6.
3. Experimental
applying analogous reactions, i.e., converting
the known [3] 3-O-mesylate 67 via its sulfox-
ide 69 into the 1-O-acetyl isomers 71 and 73
and using this mixture for the glycosylation of
4-cyano- and 4-nitrobenzenethiol.
General methods.—Organic solns were
dried over MgSO4 and concd under dimin-
ished pressure at or below 40 °C. TLC: E.
Merck precoated Silica Gel 60 F254 plates,
with EtOAc (A), EtOAc–hexane mixtures (B,
1:1; C, 1:2; D, 1:4), toluene–MeOH mixture
(E, 9:1), and toluene–acetone mixture (F, 4:1);
detection by spraying the plates with a 0.02 M
soln of I2 and a 0.3 M soln of KI in 10% aq
H2SO4 soln followed by heating at ca. 200 °C.
For column chromatography, Kieselgel 60
was used. The mp are uncorrected. Optical
rotations were determined on 1.0% solns 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 solns in CDCl3 (internal Me4Si) un-
less 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 selective INEPT pulse sequence
was optimised to a heteronuclear coupling
constant of 7 Hz. The ratio of a:b anomeric
Biological results.—The oral antithrom-
botic activity of 27, 29, 30, 31, 38, 44, 46, 48,
55, 56, 57, 58, 76, 77, 79 and 80 was deter-
mined in rats, using Pescador’s model [10] and
2 as reference compound. All compounds
were administered orally 3 h before ligation at
a dose of 2 mg/kg. From the data listed in
Table 1, it can be seen that although there
exists no straightforward structure–activity
relationship in this type of thioglycosides,
blocking of the 4-OH group by methylation
(44, 46, 48) or its substitution by an azido
group (76, 79) seems to have little influence on
the activity when the 3-OH group is still
present. Blocking of the latter by methylation
(31, 55, 56) or mesylation (57, 58, 77) de-
creases the activity in most cases. It is worth-
while mentioning, that the 2,6-thioanhydro- -
D
arabino-hexopyranoside 38, carrying a second
4-cyanothiophenol substituent at C-3 was as
active (38%) as 1.
1
mixtures was determined by H NMR.

´
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
276
X-ray data (see Section 4). Unit cell
parameters were determined by least-squares
of the setting angles of 25 (40.875q544.71°)
reflections. Intensity data were collected on an
Enraf–Nonius CAD4 diffractometer (graphite
monochromator; Cu Ka radiation, u=
,
1.54180 A) at 293(2) K in the range 3.805
q574.52° using ꢀ–2q scans. The intensities
of three standard reflections were monitored
regularly (every 60 min). The intensities of the
standard reflections indicated a crystal decay
Table 2
Crystal data and structure refinement of 16
Empirical formula
Formula weight
Temperature (K)
Radiation
C8H12O3S
188.24
293(2)
Cu Ka
,
Wavelength, u (A)
Crystal system
Space group
1.54180
monoclinic
P21
Unit cell dimensions
,
a (A)
5.529(1)
6.989(1)
11.633(2)
90.20(1)
449.52(13)
2
,
b (A)
,
c (A)
i (°)
3
,
Volume (A )
Z
Dcalc (g/cm3)
Absorption coefficient, v
1.391
2.940
(mm−1
F(000)
)
200
Crystal colour
Crystal description
transparent
prism
Crystal size (mm)
0.40×0.30×0.30
psi-scan
Absorption correction
Max. and min. transmission
q Range for data collection (°)
Index ranges (°)
0.998 and 0.890
3.805q574.52
−65h56, −85k58,
−145l514
2219
Reflections collected
Number of standard reflections
Decay (%)
3
22.00
Independent reflections
Reflections [I\2|(I)]
Refinement method
1811 [Rint=0.0244]
1774
full-matrix least-squares
on F2
Data/restraints/parameters
Goodness-of-fit on F2
1811/1/110
1.1
Final R indices [I\2|(I)]
R1=0.0466,
wR2=0.1190
R1=0.0471,
wR2=0.1199
−0.01(2)
R indices (all data)
Absolute structure parameter
Max. and mean shift/esd
0.004, 0.000
Largest difference peak and hole 0.361 and −0.627
−3
,
(e A
)

´
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
277
Table 3
given in Tables 6 and 7, respectively. Table 8
lists selected 13C NMR data for solns in
CDCl3.
Atomic coordinates (×104) and equivalent isotropic displace-
2
3
a
,
ment parameters (A ×10 ) of 16
Reaction of 1,6:2,5-dianhydro-3,4-di-O-
x
y
z
Ueq
methanesulfonyl-1-thio- -glucitol (4) with
D
S-1
8804(1)
4466(3)
7972(3)
4792(4)
5870(4)
4806(4)
6401(4)
7944(5)
6859(4)
8278(5)
6935(4)
8754(5)
10080.1(7)
7293(4)
7054(3)
7203(4)
9962(4)
7967(4)
6412(4)
5690(4)
6714(4)
8476(4)
7333(4)
7868(6)
3343.1(5)
3789(2)
1206(1)
11(2)
2647(2)
2637(2)
2114(2)
3128(2)
4161(2)
4535(2)
173(2)
48(1)
59(1)
45(1)
67(1)
47(1)
47(1)
46(1)
50(1)
48(1)
47(1)
46(1)
64(1)
NaOH.—A stirred soln of 4 (19.2 g, 60 mmol)
[3,4] in MeOH (400 mL) and 40% aq NaOH
(50 mL) was refluxed for 4 h. After cooling to
rt the mixture was neutralised with solid CO2,
filtered through Celite, concd and the residue
was submitted to column chromatography
(solvent C, then B). Concentration of the first
O-1
O-2
O-3
C-1
C-2
C-3
C-4
C-5
C-6
C-7
C-8
fraction gave 1,6:2,5-dianhydro-4-deoxy- -
D
erythro-hex-3-ulose (14, 3.56 g, 41%): mp 55–
60 °C (hexane); [h]D +72° (c 0.5, CHCl3); Rf
0.7 (solvent C). Anal. Calcd for C6H8O2S: C,
49.98; H, 5.59; S, 22.24. Found: C, 50.03; H,
5.62; S, 22.21.
−716(2)
a U(eq) is defined as one third of the trace of the orthogo-
nalised Uij tensor.
Concentration of the second fraction gave
1,6:2,5:3,4-trianhydro-1-thio-allitol (7, 0.43 g,
5%): mp 104–105 °C (hexane); lit. 105–106 °C
[3]; Rf 0.6 (solvent C).
Table 4
Hydrogen coordinates (×104) and isotropic displacement
2
3
,
parameters of 16 (A ×10 )
x
y
z
Uiso
Concentration of the third fraction gave
1,6:2,5-dianhydro-4-O-methyl-1-thio- -gluci-
D
H-1a
H-1b
H-2
4766
6025
3243
5380
7814
9631
6727
9818
7387
8317
10816
10408
7989
5367
4313
6031
5820
8080
9144
7295
7418
9234
3040
1861
2237
1830
3210
3029
4807
4858
5129
61
61
61
60
66
66
62
61
61
89
89
89
tol (11, 2.97 g, 28%): mp 68–70 °C (ether); lit.
75–76 °C [16]; [h]D +28° (c 0.5, CHCl3); lit.
[h]D +31° [16]; Rf 0.4 (solvent B).
H-3
H-4a
H-4b
H-5
H-6a
H-6b
H-8a
H-8b
H-8c
Concentration of the fourth fraction gave
1,4:2,5-dianhydro-6-methoxy-1-thio- -galacti-
D
tol (9, 425 mg, 4%) as an oil: [h]D −36° (c
0.5, CHCl3); Rf 0.3 (solvent B). Anal. Calcd
for C7H12O3S: C, 47.71; H, 6.86; S, 18.19.
Found: C, 47.75; H, 6.90; S, 18.23.
−1438
−484
−799
10322
8792
Table 5
,
Bond lengths (A) and angles (°) of 16
of 22% (the data were corrected for decay).
An empirical absorption correction (psi-scans)
[11] was applied to the data.
S-1ꢀC-6
O-1ꢀC-2
O-2ꢀC-7
O-3ꢀC-7
C-2ꢀC-3
C-4ꢀC-5
C-7ꢀC-8
1.807(3)
1.433(3)
1.343(3)
1.203(3)
1.528(4)
1.523(4)
1.493(4)
S-1ꢀC-1
O-1ꢀC-5
O-2ꢀC-3
C-1ꢀC-2
C-3ꢀC-4
C-5ꢀC-6
1.813(2)
1.448(3)
1.442(3)
1.513(5)
1.538(3)
1.523(4)
The structure was solved by direct methods
[12] and refined by full-matrix least-squares
anisotropic least-squares on F2 [13]. Crystal
data and refinement details are shown in
Table 2. Hydrogen atomic positions were cal-
culated from assumed geometries. Scattering
factors and their anomalous contributions
were taken from [14]. Final atomic parameters
are given in Tables 3 and 4, bond lengths,
bond angles and torsion angle in Table 5.
C-6ꢀS-1ꢀC-1
C-7ꢀO-2ꢀC-3
O-1ꢀC-2ꢀC-1
C-1ꢀC-2ꢀC-3
O-2ꢀC-3ꢀC-4
C-5ꢀC-4ꢀC-3
O-1ꢀC-5ꢀC-4
C-5ꢀC-6ꢀS-1
O-3ꢀC-7ꢀC-8
99.7(1)
116.4(2)
110.4(2)
115.7(2)
109.3(2)
103.4(2)
104.9(2)
111.5(2)
125.2(2)
C-2ꢀO-1ꢀC-5
C-2ꢀC-1ꢀS-1
O-1ꢀC-2ꢀC-3
O-2ꢀC-3ꢀC-2
C-2ꢀC-3ꢀC-4
O-1ꢀC-5ꢀC-6
C-6ꢀC-5ꢀC-4
O-3ꢀC-7ꢀO-2
O-2ꢀC-7ꢀC-8
104.4(2)
113.1(2)
102.5(2)
114.8(2)
104.3(2)
109.2(2)
113.7(2)
123.1(2)
111.7(2)
1
Selected H NMR chemical shifts (l) and
coupling constants (Hz) for solns of the com-
pounds under investigation in CDCl3 are

´
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
278
Table 6
1
Selected H NMR data for solutions in CDCl3
Compound Chemical shifts (l)
H-1a
2.74
H-1b
2.84
H-2
4.17
H-3
4.55
H-4a
3.33
H-4b
H-5
4.30
H-6a
H-6b
9
14
16
17
20
21
22
24
3.60
3.49
3.30
3.30
2.84
2.88
3.30
3.45
3.49
3.57
3.28
3.58
3.30
3.53
3.55
2.55
2.69
2.82
2.82
3.25
3.45
3.40
3.12
3.50
3.18
3.52
3.21
3.25
3.22
3.22
2.53
3.45
3.50
3.49
3.35
3.45
3.19
3.20
3.22
2.62
2.65
3.33
3.32
3.45
3.47
3.44
3.50
3.20
3.55
3.53
3.20
3.56
3.68
2.27
2.12
2.10
3.50
3.56
2.48
2.10
2.15
2.17
2.26
2.18
2.30
2.15
2.17
3.21
2.93
3.57
3.50
2.25
2.30
2.05
2.35
2.32
2.42
2.32
2.46
3.12
3.08
2.20
3.68
2.24
2.26
2.48
2.70
2.24
2.23
2.23
2.28
3.78
3.85
2.19
2.65
2.30
2.35
2.23
2.35
2.55
2.38
2.37
2.58
2.40
3.13
3.15
3.12
2.84
2.85
6.07
5.37
5.54
4.15
4.59
4.22
4.67
4.36
4.43
6.32
5.26
6.28
2.75
6.00
5.25
4.20
4.90
3.97
4.57
4.03
4.63
3.78–3.88
4.30–4.50
3.12
2.57
4.28
4.35
4.32
4.70
5.51
3.09
3.09
3.14
2.62
2.72
5.43
6.02
5.37
5.50
4.40
4.08
4.58
4.33
4.15
4.65
4.40
2.42
2.20
2.36
3.48
3.64
4.13
4.45
4.30
4.74
4.65
4.38
4.36
4.33
4.55
4.13
4.57
4.18
4.38
4.41
3.15
3.01
3.01
4.84
4.20
4.70
4.35
4.06–4.16
4.83
4.38
4.86
4.43
4.06
4.25
4.56
4.74
4.61
4.63
4.80
4.88
4.55
4.50
4.49
4.70
4.84
4.90
4.27
4.28
4.64
4.64
4.23
4.77
4.25–4.45
4.73
4.80
4.25–4.50
4.75
2.72
2.68
2.50
2.64
2.45
5.18
2.66
2.54
2.73
2.45
2.75
2.46
2.52
2.53
4.95
4.45
4.50
4.57
4.60
4.52
4.54
4.59
4.62
4.48
4.63
4.50
4.61
4.62
4.40
4.27
4.40
4.40
4.81
4.40
4.88
4.45
4.42
4.30
4.44
4.30
3.90
3.94
4.25–4.32
4.40
4.42
4.43
4.64
4.70
4.38
4.24
4.26
4.32
4.45
4.53
4.80
4.70
4.40
4.46
4.83
4.42
4.25–4.45
4.48
4.43
4.25–4.50
4.50
5.17
4.10
5.12
2.21
2.20
1.70
1.68
4.12
c
5.15
4.13
5.19
4.40
5.21
4.42
4.17
4.18
4.05
4.11
4.33
5.07
4.53
5.23
4.38
2.15
2.20
2.22
1.98
2.24
2.00
2.20
2.22
25
26
27 a
28
29 a
30
31
35
36a
38
40
41
42
2.53
2.00–2.20
2.50
2.00–2.20
1.49
2.10
3.72
5.18
4.41
5.20
4.20
4.42
4.10
4.44
4.12
3.58
3.58
2.50
3.24
43
44 a
45
4.06–4.16
5.18
46 a
47
4.25
5.19
4.28
3.79
3.73
3.98
3.87
4.02
4.03
5.28
5.38
3.97
4.32
4.44
5.17
5.03
5.13
4.34
4.85
5.19
5.08
4.49
5.18
48 a
50
3.78–3.88
4.30–4.50
2.28
51
52
4.25–4.32
3.62
4.25–4.32
53 a
55
3.43
4.28
4.30
5.72
5.65
4.27
4.60
4.50
4.53
4.14
4.41
5.19
5.03
4.50
4.72
5.20
4.52
56
57
58 a
59
64 b
64 b
66
2.34
2.47
2.14
3.50
3.58
68 a
69 a
70
71
72
73
74
75
76 a
77
4.25–4.45
5.07
5.18
4.25–4.50
5.08
4.25–4.45
4.72
4.53
4.25–4.50
4.72
4.25–4.45
4.25–4.50
78
79 a
80
a Me2SO-d6.
b Signals of the two THP-diastereomers.
c H-3a 2.60, H-3b 2.38 ppm.

´
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
279
Table 7
1
Selected H NMR data for solutions in CDCl3
Compound Coupling constants (Hz)
J1a,1b
10.9
12.9
13.4
13.4
13.2
13.3
J1a,2
0.8
2.9
3.4
3.4
J1b,2
J2,3
2.5
J3,4a
2.3
J3,4b
J4a,4b J4a,5
2.3
J4b,5
J5,6a
6.3
J5,6b
7.7
ꢀ1
ꢀ1
J6a,6b
9.8
13.4
12.9
12.9
ꢀ13
ꢀ12
13.7
J1b,6b
9
14
16
17
20
21
22
24
1.9
1.2
ꢀ1
ꢀ1
ꢀ1
17.8
13.2
12.7
14.4
7.6
7.7
7.8
8.5
9.5
4.8
7.8
7.9
7.8
7.8
7.6
7.9
7.8
7.8
ꢀ0
B1
1.7
0.7
B1
2.7
2.4
2.7
ꢀ2.5
ꢀ2.5
3.4
2.7
2.7
2.4
2.4
2.4
2.4
2.5
2.4
2.2
ꢀ1
2.3
2.9
3.4
2.9
3.2
3.2
2.4
2.4
2.7
2.4
5.9
6.4
2.7
2.9
ꢀ2
2.7
2.2
ꢀ2.5
3.2
2.4
2.6
ꢀ3
2.9
3.4
3.4
2.9
2.7
2.7
2.7
2.4
2.4
2.6
2.2
2.4
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
B1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
6.4
6.3
6.9
11.2
11.2
11.5
9.5
5.0
5.0
3.4
3.3
4.9
5.0
5.1
4.9
5.1
5.1
5.0
4.9
4.9
ꢀ1
ꢀ3
ꢀ1.5
ꢀ1.5
ꢀ1
3.4
3.4
1.7
1.7
ꢀ1.5
ꢀ7
13.9
b
c
9.7
6.8
6.6
6.4
6.6
6.8
6.6
7.1
6.3
3.5
4.1
2.8
ꢀ7
ꢀ0
6.8
ꢀ0
ꢀ0
10.7
10.3
11.0
11.0
11.0
11.0
10.3
10.3
8.8
13.4
12.9
13.4
12.7
13.2
12.5
13.0
12.7
1.6
1.9
1.5
1.4
1.5
1.5
1.5
1.5
ꢀ1.5
ꢀ1.5
ꢀ1.5
ꢀ1.5
ꢀ1.5
ꢀ1.5
ꢀ1.5
ꢀ1.5
ꢀ3
4.4
ꢀ2
ꢀ1.5
ꢀ1.5
1.7
12.9
12.7
13.2
13.2
13.2
12.9
13.0
12.8
10.8
11.0
11.5
12.5
13.7
12.9
13.9
13.2
13.2
13.2
13.4
13.2
13.7
13.9
13.2
12.5
13.2
13.2
13.7
13.9
13.0
13.2
13.4
12.5
12.2
13.7
14.2
13.4
13.2
13.9
13.8
13.2
13.2
13.7
13.1
13.7
25
26
ꢀ1
27 a
28
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
29 a
30
31
35
36a
38
40
2.9
ꢀ3
2.7
11.0
nd d ꢀ4
ꢀ2
ꢀ1.5
1.2
2.7
2.7
2.9
3.4
9.5
4.8
ꢀ2
14.5
14.9
4.8
5.1
ꢀ0
6.8
nd
13.0
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
41
42
2.9
3.2
2.7
2.6
2.7
2.9
2.9
2.7
2.0
ꢀ2
43
1.3
ꢀ1.5
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ5
4.6
6.6
5.9
nd
ꢀ0
nd
ꢀ0
3.7
2.7
nd
ꢀ0
nd
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ0
ꢀ7
6.8
ꢀ0
ꢀ0
6.6
ꢀ0
nd
ꢀ0
ꢀ0
nd
ꢀ1
ꢀ1
44 a
45
6.6
ꢀ1.5
ꢀ1.5
ꢀ2
ꢀ1.5
6.9
7.1
ꢀ1.5
ꢀ2
ꢀ1.5
ꢀ1.5
ꢀ1.5
ꢀ1.5
ꢀ2
ꢀ1.5
ꢀ1
ꢀ2
46 a
47
7.1
6.8
7.1
4.9
4.1
6.8
6.9
6.8
6.6
6.8
6.8
6.8
6.8
6.8
ꢀ7
7.1
ꢀ0
ꢀ0
7.1
6.8
ꢀ0
6.8
nd
48 a
50
nd
ꢀ5
6.8
ꢀ1
ꢀ2
51
11.0
13.2
12.5
ꢀ1
52
3.2
3.4
3.4
2.2
2.8
2.7
2.7
2.7
2.8
3.2
3.4
ꢀ2.5
2.7
3.2
3.7
3.7
3.7
3.4
3.2
nd
ꢀ1
ꢀ1.5
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ2
2.4
B1
B1
B1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
53 a
55
ꢀ1
ꢀ1
ꢀ1.5
ꢀ1
1.7
3.2
3.2
ꢀ3
3.2
2.7
3.3
2.2
1.9
ꢀ1.5
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
56
57
58 a
59
64
13.2
13.7
ꢀ13
12.9
ꢀ1
ꢀ1
ꢀ2
2.4
66
68 a
69 a
70
2.4
nd
ꢀ1.5
1.7
ꢀ1.5
ꢀ1
71
72
73
74
75
ꢀ2
76 a
77
ꢀ1.5
ꢀ1.5
ꢀ2
ꢀ1
ꢀ1.5
6.6
6.8
nd
6.8
3.7
3.4
nd
78
79 a
80
3.4
ꢀ0
a Me2SO-d6.
b J2,3a 7.3, J2,3b 1.5 Hz.
c J3a,3b 14.1 Hz.
d nd, not determined.

´
E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
280
Table 8
Selected 13C NMR data for solutions in CDCl3
Compound Chemical shifts (l)
C-1
C-2
C-3
C-4
C-5
C-6
Others
9
14
16
17
20
21
22
24
25
26
28
30
31
35
36a
38
40
41
42
43
45
47
50
51
52
55
56
59
64 b
64 b
66
70
71
72
73
75
78
80
34.5
77.7
75.6
75.5
213.7
52.0
40.7
80.2
73.4
73.4
30.5
59.0 (OMe)
26.4
25.2
24.8
52.5
52.1
70.3
68.2
68.4
46.1
45.8
45.5
45.4
91.2
100.8
85.0
51.3
68.2
67.6
49.5
45.4
45.3
61.0
68.5
24.3
45.4
45.4
68.2
24.5
24.6
24.7
73.1 a 73.3 a 34.0
73.4 a 31.4 170.8 (CO); 20.7 (OAc)
73.8
72.7 a 73.2 a 34.8
75.1 80.6 34.6
73.1 a 31.3 73.3 a 74.6 a 27.8 168.9, 170.7 (CO); 20.6, 20.7 (OAc)
81.3
33.9
73.5
74.3 a 56.2 170.3(CO); 20.6 (OAc)
72.9 56.1 58.3 (OMe)
31.7
58.6 (OMe)
76.2
76.6
76.8
76.6
72.6
80.6
74.0
73.9
33.2
32.7
33.8
33.6
33.1
33.1
33.2
33.9
32.4
72.9
72.7
73.8
73.7
29.8 169.8, 170.6 (CO); 20.7, 21.2 (OAc)
29.8 169.8 (CO); 21.1 (OAc); 58.5 (OMe)
30.0 170.8 (CO); 20.9 (OAc); 118.6 (CN)
29.9 170.8 (CO); 20.8 (OAc)
74.0 a 81.5
77.3 a 30.2
58.7 (OMe);118.6 (CN)
58.7 (OMe)
74.0
33.8
36.5
37.7
81.5
76.5
70.4
44.1
77.3
66.0
65.4
65.8
30.2
29.3 169.8 (CO); 21.0 (OAc); 55.9 (OMe)
29.2 62.8, 15.0 (OEt); 55.7 (OMe)
29.7 118.2, 118.6 (CN)
74.4 a 78.2 a 86.6
79.7 a 54.2 169.8 (CO); 20.5 (OAc); 57.0 (OMe)
75.2 a 79.4 a 80.1 a 84.9 a 27.2 168.8, 170.3 (CO); 20.7 (OAc); 57.1 (OMe)
78.2
81.2
79.2
88.1
87.1
79.6
78.0
76.0
27.1 169.8, 170.1 (CO); 20.7, 21.1 (OAc); 57.1 (OMe)
22.9 170.2 CO); 20.7 (OAc); 57.1 (OMe); 118.4 (CN)
78.5 a 78.7 a 87.0
78.5 a 78.8 a 87.0
80.6 a 27.2 170.3 CO); 20.7 (OAc); 57.0 (OMe); 118.4 (CN)
80.6 a 27.2 170.4 (CO); 20.7 (OAc); 57.0 (OMe)
80.8 a 85.6 a 86.7 a 81.5 a 31.9 195.1 (CO); 57.2, 57.4 (OMe); 30.3 (SAc)
78.7 a 84.3 a 86.0 a 82.6 a 31.8 194.9 (CO); 57.3, 57.2 (OMe); 37.3 (Ms); 30.4 (SAc)
75.7 a 88.3 a 88.4 a 78.2 a 29.1
57.0, 58.7 (OMe)
57.1, 58.8 (OMe); 118.5 (CN)
57.2, 58.9 (OMe)
79.2
79.3
88.7
88.8
87.6
87.6
78.4
78.5
27.4
27.5
77.9 a 87.9 a 87.8 a 78.5 a 27.3 169.9 (CO); 21.1 (OAc); 57.1, 58.7 (OMe)
76.2
76.8
85.6
83.4
68.8
68.7
79.8
78.8
29.3
29.2
75.6 a 79.2 a 68.4
80.0 a 29.2 170.4 CO); 20.6 (OAc);
69.4 a 81.5 a 67.8 a 79.3 a 75.2 a 22.8 169.8, 170.2 (CO); 20.7, 21.2 (OAc);
68.2
75.6 a 65.6
80.4 a 82.7 a 27.0 168.6 (CO); 20.6 (OAc); 38.1 (OMs)
67.4 a 78.2 a 79.1 a 68.2 a 79.3 a 27.4 169.8, 170.2 (CO); 20.7, 21.2 (OAc)
67.0 a 78.2 a 78.9 a 67.4 a 81.9 a 27.4 169.6 (CO); 21.1 (OAc); 38.2 (OMs)
45.8
45.7
44.8
78.7 a 79.6 a 68.1
78.7 a 79.7 a 68.1
78.8 a 79.2 a 67.4
80.3 a 27.4 170.2 (CO); 20.6 (OAc); 118.3 (CN)
80.4 a 27.5 170.4 (CO); 20.7 (OAc)
83.4 a 27.7
38.1 (OMs)
a Arbitrary assignment.
b Signals of the two THP-diastereomers.
Concentration of the fifth fraction gave
mixture was neutralised with 4% aq HCl,
1,6:2,5 - dianhydro - 3 - O - methanesulfonyl - 1-
concd and toluene (50 mL) was evaporated
from the residue. The resulting residue was
acetylated in a mixture of pyridine (20 mL)
and Ac2O (10 mL) to give, after the usual
processing and column chromatography (sol-
vent D), 16 (2.88 g, 88%): mp 87–88 °C (ace-
tone); [h]D +5° (c 0.5, CHCl3); Rf 0.4 (solvent
D). Anal. Calcd for C8H12O3S: C, 51.04; H,
6.43; S, 17.03. Found: C, 51.07; H, 6.46; S,
17.08
thio- -glucitol (6, 0.8 g, 5.5%): mp 99–101 °C
D
(hexane); lit. 98–100 °C [3]; [h]D +19° (c 0.5,
CHCl3); lit. [h]D +17.5° (c 1, CHCl3) [3]; Rf
0.2 (solvent B).
3-O-Acetyl-1,6:2,5-dianhydro-4-deoxy-1-
thio- -xylo-hexitol (16).—To a stirred soln
D
of 14 (2.5 g, 17.3 mmol) in EtOH (85 mL),
NaBH4 (2.4 g, 63.5 mmol) was added at rt
and stirring was continued for 30 min. The

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281
1,6:2,5-Dianhydro-4-deoxy-3-O-methyl-1-
thio- -xylo-hexitol (17).—To a stirred soln of
Concentration of the second fraction gave
24 (1.88 g, 71%) as an oil: [h]D +261°; Rf 0.4
(solvent C). Anal. Calcd for C10H14O5S: C,
48.77; H, 5.73; S, 13.02. Found: C, 48.75; H,
5.69; S, 13.06.
D
16 (3.3 g, 17.5 mmol) in MeOH (50 mL), 1 M
NaOMe (0.1 mL) in MeOH was added at rt
and stirring was continued for 1 h. The mix-
ture was neutralised with solid CO2, concd
and toluene (25 mL) was evaporated from the
residue. The residue was dissolved in dry
DMF (25 mL) and 80% NaH (0.65 g, 21.7
mmol) in oil was added. After stirring at rt for
30 min, MeI (1.5 mL, 24 mmol) was added
and stirring was continued for 1 h. The mix-
ture was poured into ice-water, extracted with
CH2Cl2, concd and the residue was submitted
to column chromatography (solvent B) to give
17 (1.91 g, 68%) as an oil: [h]D +46° (c 0.5,
CHCl3); Rf 0.7 (solvent B). Anal. Calcd for
C7H12O2S: C, 52.47; H, 7.55; S, 20.01. Found:
C, 52.44; H, 7.53; S, 19.98.
1 - O - Acetyl - 2,5 - anhydro - 3 - deoxy - 4 - O-
methyl-6-thio-h- -xylo-hexoseptanose (23), 1-
L
O-acetyl-2,5-anhydro-4-deoxy-3-O-methyl-6-
thio-h- -xylo-hexoseptanose (25), 1-O-acetyl-
2,6-anhydro-4-deoxy-3-O-methyl-6-thio-
lyxo-hexopyranose (35) and ethyl 2,6-
anhydro-4-deoxy-3-O-methyl-6-thio-h- -lyxo-
D
D
-
D
hexopyranoside (36a).—A soln of 21 (1.7 g,
9.6 mmol) in Ac2O (20 mL) was stirred at
100 °C for 5 h. The mixture was concd and
EtOH (30 mL) was evaporated from the
residue. The resulting residue was submitted
to column chromatography (solvent C). Con-
centration of the first fraction gave 36a (100
mg, 5%) as an oil: [h]D +17° (c 0.5, CHCl3);
Rf 0.8 (solvent C). Anal. Calcd for C9H16O3S:
C, 52.92; H, 7.89; S, 15.70. Found: C, 52.97;
H, 7.85; S, 15.73.
Concentration of the second fraction gave
35 (200 mg, 9.5%) as an oil: [h]D +23° (c 0.5,
CHCl3); Rf 0.6 (solvent C). Anal. Calcd for
C9H14O4S: C, 49.53; H, 6.47; S, 14.69. Found:
C, 49.56; H, 6.50; S, 14.71.
3-O-Acetyl-1,6:2,5-dianhydro-4-deoxy-1-
thio- -xylo-hexitol S-oxide (20).—To a stirred
D
soln of 16 (2.88 g, 15.3 mmol) in AcOH (45
mL) 33% aq H2O2 (2.2 mL) was added and
the mixture was kept overnight at rt. The
reaction was concd and EtOH (50 mL) was
evaporated from the residue to give, after
crystallisation with ether, 20 (2.62 g, 84%): mp
139–143 °C (ether); [h]D −7° (c 0.5, CHCl3);
Rf 0.3 (solvent A). Anal. Calcd for C8H12O4S:
C, 47.05; H, 5.92; S, 15.70. Found: C, 47.09;
H, 5.98; S, 15.67.
Concentration of the third fraction gave a
1:4 mixture of 23 and 25 (0.85 g, 40%): [h]D
+227° (c 0.5, CHCl3); Rf 0.4 (solvent C).
Anal. Calcd for C9H14O4S: C, 49.53; H, 6.47;
S, 14.69. Found: C, 49.51; H, 6.44; S, 14.65.
4-Cyanophenyl 3-O-acetyl-2,5-anhydro-4-
1,6:2,5-Dianhydro-4-deoxy-3-O-methyl-1-
thio- -xylo-hexitol S-oxide (21).—Oxidation
D
of 17 (1.55 g, 9.67 mmol) was carried out as
described for 20 to give 21 (1.70 g, 100%) as
an oil: [h]D +12°; Rf 0.2 (solvent A). Anal.
Calcd for C8H12O4S: C, 47.71; H, 6.86; S,
18.19. Found: C, 47.69; H, 6.88; S, 18.22.
1,4-Di-O-acetyl-2,5-anhydro-3-deoxy-6-thio-
deoxy-1,6-dithio-h- -xylo-hexoseptanoside
D
(26).—To a soln of 24 (1.3 g, 5.3 mmol) and
4-cyanobenzenethiol (1.43 g, 10.6 mmol) in
dry 1,2-dichloroethane (25 mL) TMSOTf
(0.98 mL, 5.3 mmol) under argon, was added
at −10 °C. After stirring at rt for 1 h, the
reaction was quenched with Et3N, concd and
submitted to column chromatography (solvent
C) to give 26 (1.65 g, 97%): mp 139–144 °C
(EtOAc–hexane); [h]D +389°; Rf 0.5 (solvent
C). Anal. Calcd for C15H15NO3S2: C, 56.05; H,
4.70; N, 4.36; S, 19.95. Found: C, 56.09; H,
4.76; N, 4.40; S, 19.91.
h-
L
-xylo-hexoseptanose (22) and 1,3-di-O-
-xylo-
acetyl-2,5-anhydro-4-deoxy-6-thio-h-
D
hexoseptanose (24).—A soln of 20 (2.2 g,
10.77 mmol) in Ac2O (22 mL) was stirred at
80 °C for 15 h. The mixture was concd and
toluene (30 mL) was evaporated from the
residue. The resulting residue was submitted
to column chromatography (solvent C). Con-
centration of the first fraction gave 22 (60 mg,
2%) as an oil: [h]D +22° (c 0.5, CHCl3); Rf
0.5 (solvent C). Anal. Calcd for C10H14O5S: C,
48.77; H, 5.73; S, 13.02. Found: C, 48.81; H,
5.68; S, 13.07.
4-Cyanophenyl
2,5-anhydro-4-deoxy-1,6-
dithio-h- -xylo-hexoseptanoside (27).—To a
D
soln of 26 (1.65 g, 5.1 mmol) in MeOH (30
mL), 1 M NaOMe (0.1 mL) in MeOH was
added and the mixture was stirred at rt for 1

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4 - Nitrophenyl 2,5 - anhydro - 4 - deoxy - 3 - O-
methyl-1,6-dithio-h- -xylo-hexoseptanoside
h. After neutralising with solid CO2 the mixture
was concd to give, after column chromatogra-
phy (solvent B), 27 (1.0 g, 70%): mp 42–44 °C
(EtOH–water); [h]D +519°(c 0.5 MeOH); Rf
0.4 (solvent B). Anal. Calcd for C13H13NO2S2:
C, 55.89; H, 4.69; N, 5.01; S, 22.95. Found: C,
55.85; H, 4.73; N, 5.05; S, 22.91.
D
(31).—To a soln of 27 (1.3 g, 4.34 mmol) in
DMF (15 mL) 50% NaH (0.25 g, 5.2 mmol) in
oil was added and the mixture was stirred at rt
for 30 min, then MeI (1.5 mL, 24 mmol) was
added and the reaction was stirred at rt
overnight. The mixture was poured into ice-
water, extracted with EtOAc, concd and the
residue was submitted to column chromatogra-
phy (solvent B) to give 31 (0.96 g, 70%): mp
91–93 °C (ether); [h]D +611°(c 0.5 CHCl3); Rf
0.8 (solvent B). Anal. Calcd for C13H15NO4S2:
C, 49.82; H, 4.82; N, 4.47; S, 20.46. Found: C,
49.80; H, 4.86; N, 4.51; S, 20.42.
4 - Nitrophenyl 3 - O - acetyl - 2,5 - anhydro - 4-
deoxy - 1,6 - dithio - h -
D
- xylo - hexoseptanoside
(28).—To a stirred soln of 24 (1.3 g, 5.3 mmol)
and 4-nitrobenzenethiol (80% pure, 1.08 g, 5.5
mmol) in dry 1,2-dichloroethane (25 mL),
BF3·Et2O (0.65 mL, 5.4 mmol) was added.
After stirring at rt for 3 h, the mixture was
poured into ice-cold 6% aq NaHCO3 soln (50
mL), separated and the organic layer was
washed with 6% aq NaHCO3, water, concd and
submitted to column chromatography (solvent
C) to give 28 (1.8 g, 100%) as an oil: [h]D
+398°; Rf 0.5 (solvent C). Anal. Calcd for
C14H15NO5S2: C, 49.25; H, 4.43; N, 4.10; S,
18.78. Found: C, 49.28; H, 4.46; N, 4.07; S,
18.81.
4 - Cyanophenyl 3 - S - (4 - cyanophenyl) - 2,6-
thioanhydro-4-deoxy-2,3-dithio-i- -arabino-
D
hexopyranoside (38).—(i) Glycosidation of
4-cyanobenzenethiol with a 1:4 mixture of 23
and 25 (0.42 g, 1.92 mmol) was carried out as
described for 26 to give, after column chro-
matography (solvent C), 38 (0.2 g, 26%): mp
130–133 °C (ether); [h]D +318° (c 0.5,
CHCl3); Rf 0.5 (solvent C). Anal. Calcd for
C20H16N2OS3: C, 60.58; H, 4.07; N, 7.06; S,
24.26. Found: C, 60.55; H, 4.06; N, 7.03; S,
24.22.
4 - Nitrophenyl 2,5 - anhydro - 4 - deoxy - 1,6-
dithio-h- -xylo-hexoseptanoside (29).—To a
D
soln of 28 (1.8 g, 5.3 mmol) in MeOH (50 mL),
1 M NaOMe (0.1 mL) in MeOH was added
and the mixture was stirred at rt overnight.
After neutralising with solid CO2 the mixture
was concd to give, after column chromatogra-
phy (solvent B), 29 (1.3 g, 82%) as an oil: [h]D
+421°(c 0.5 MeOH); Rf 0.4 (solvent B). Anal.
Calcd for C12H13NO4S2: C, 48.15; H, 4.38; N,
4.68; S, 21.42. Found: C, 48.18; H, 4.33; N,
4.65; S, 21.39.
(ii) To a soln of 35 (0.17 g, 0.78 mmol) and
4-cyanobenzenethiol (0.25 g, 1.85 mmol) in dry
1,2-dichloroethane (10 mL) under argon, TM-
SOTf (0.15 mL, 0.75 mmol) was added at 0 °C.
After stirring at 0 °C for 30 min, the reaction
was quenched with Et3N, concd and submitted
to column chromatography (solvent C) to give
38 (0.3 g, 97%), identical to the compound
described above.
4-Cyanophenyl 2,5-anhydro-4-deoxy-3-O-
3-O-Acetyl-1,6:2,5-dianhydro-4-O-methyl-1-
methyl-1,6-dithio-h- -xylo-hexoseptanoside
D
thio- -glucitol (39).—Acetylation of 11 (2.2 g,
D
(30).—To a soln of 27 (0.9 g, 3.2 mmol) in
DMF (10 mL), 50% NaH (0.2 g, 4.2 mmol) in
oil was added and the mixture was stirred at rt
for 30 min, then MeI (1.5 mL, 24 mmol) was
added and the reaction was stirred at rt
overnight. The mixture was poured into ice-
water, extracted with EtOAc, concd and the
residue was submitted to column chromatogra-
phy (solvent B) to give 30 (0.66 g, 70%): mp
175–183 °C (ether); [h]D +560°(c 0.5 CHCl3);
Rf 0.8 (solvent B). Anal. Calcd for
C14H15NO2S2: C, 57.31; H, 5.15; N, 4.77; S,
21.86. Found: C, 57.34; H, 5.19; N, 4.81; S,
21.90.
12.5 mmol) with Ac2O (5 mL) in pyridine (10
mL) gave, after the usual processing, 39 (2.67
g, 98%): mp 79–80 °C (ether–hexane); lit. 80–
82 °C [16]; Rf 0.7 (solvent C).
3-O-Acetyl-1,6:2,5-dianhydro-4-O-methyl-1-
thio- -glucitol S-oxide (40).—Oxidation of 39
D
(2.67 g, 12.2 mmol) was carried out as de-
scribed for 20 to give 40 (2.46 g, 86%): mp
153–157 °C (ether); [h]D −46° (c 0.5 CHCl3);
Rf 0.3 (solvent A). Anal. Calcd for C9H14O5S:
C, 46.14; H, 6.02; S, 13.69. Found: C, 46.18; H,
6.07; S, 13.71.
1,4-Di-O-acetyl-2,5-anhydro-3-O-methyl-6-
thio - h -
L
- guloseptanose (41) and 1,3 - di - O-

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283
column chromatography (solvent F), 44 (0.9
g, 84%): mp 140–141 °C (ether); [h]D +522°(c
0.5 MeOH); Rf 0.4 (solvent F). Anal. Calcd
for C14H15NO3S2: C, 54.35; H, 4.89; N, 4.53;
S, 20.73. Found: C, 54.31; H, 4.84; N, 4.50; S,
20.76.
acetyl-2,5-anhydro-4-O-methyl-6-thio-h- -glu-
D
coseptanose (42).—A soln of 40 (2.46 g, 10.5
mmol) in Ac2O (25 mL) was stirred at 100 °C
for 10 h. The mixture was concd and toluene
(30 mL) was evaporated from the residue. The
resulting residue was submitted to column
chromatography (solvent C). Concentration of
the first fraction gave 41 (220 mg, 7.5%) as an
oil: [h]D −30° (c 0.3, CHCl3); Rf 0.55 (solvent
C). Anal. Calcd for C11H16O6S: C, 47.82; H,
5.84; S, 11.60. Found: C, 47.81; H, 5.88; S,
11.57.
4-Nitrophenyl 3-O-acetyl-2,5-anhydro-4-O-
methyl-1,6-dithio-h- -glucoseptanoside (47).
D
—Glycosidation of 4-nitrobenzenethiol with
42 (1.2 g, 4.3 mmol) was carried out as de-
scribed for 28 to give, after column chro-
matography (solvent C), 47 (1.6 g, 99%) as an
oil: [h]D +398° (c 0.5, CHCl3); Rf 0.55 (sol-
vent C). Anal. Calcd for C15H17NO6S2: C,
48.51; H, 4.61; N, 3.77; S, 17.26. Found: C,
48.54; H, 4.62; N, 3.80; S, 17.22.
Concentration of the second fraction gave
42 (2.45 g, 84%) as an oil: [h]D +186° (c 0.5,
CHCl3); Rf 0.5 (solvent C). Anal. Calcd for
C11H16O6S: C, 47.82; H, 5.84; S, 11.60. Found:
C, 47.84; H, 5.81; S, 11.63.
4-Nitrophenyl 2,5-anhydro-4-O-methyl-1,6-
4-Cyanophenyl 4-O-acetyl-2,5-anhydro-3-
dithio-h- -glucoseptanoside (48).—Deacetyla-
D
O - methyl - 1,6 - dithio - h -
L
- guloseptanoside
tion of 47 (1.6 g, 4.3 mmol) was performed as
described for 27 to give, after column chro-
matography (solvent F), 44 (1.0 g, 70%): mp
145–147 °C (ether); [h]D +570° (c 0.5
MeOH); Rf 0.4 (solvent F). Anal. Calcd for
C13H15NO5S2: C, 47.40; H, 4.59; N, 4.25; S,
19.47. Found: C, 47.44; H, 4.54; N, 4.20; S,
19.46.
(43).—Glycosidation of 4-cyanobenzenethiol
with 41 (170 mg, 0.6 mmol) was carried out as
described for 26 to give, after column chro-
matography (solvent C), 43 (190 mg, 88%) as
an oil: [h]D −483° (c 0.36, CHCl3); Rf 0.5
(solvent C). Anal. Calcd for C16H17NO4S2: C,
54.68; H, 4.88; N, 3.99; S, 18.25. Found: C,
54.71; H, 4.86; N, 4.03; S, 18.21.
6-S-Acetyl-2,5-anhydro-3,4-di-O-methyl-6-
4-Cyanophenyl
1,6-dithio-h- -guloseptanoside (44).—Deace-
2,5-anhydro-3-O-methyl-
thio- -glucitol (50).—A soln of 49 (5.1 g, 20
D
L
mmol) [7] and potassium thioacetate (2.74 g,
24 mmol) in DMF (25 mL) was stirred at
100 °C for 1 h. The residue obtained on con-
centration was dissolved in CH2Cl2 (50 mL),
washed with water, dried and concd to give,
after column chromatography (solvent B), 50
(4.35 g, 87%): [h]D +68°; Rf 0.4 (solvent B).
Anal. Calcd for C10H18O5S: C, 47.98; H, 7.25;
S, 12.81. Found: C, 47.82; H, 7.30; S, 12.66.
6-S-Acetyl-2,5-anhydro-1-O-methanesul-
tylation of 43 (190 mg, 0.54 mmol) was per-
formed as described for 27 to give, after
column chromatography (solvent E), 44 (130
mg, 78%): mp 166–168 °C (ether); [h]D
−
536°(c 0.3 acetone); Rf 0.4 (solvent E). Anal.
Calcd for C14H15NO3S2: C, 54.35; H, 4.89; N,
4.53; S, 20.73. Found: C, 54.33; H, 4.83; N,
4.55; S, 20.71.
4-Cyanophenyl 3-O-acetyl-2,5-anhydro-4-
O-methyl-1,6-dithio-h- -glucoseptanoside (45).
D
fonyl-3,4-di-O-methyl-6-thio- -glucitol (51).
D
—Glycosidation of 4-cyanobenzenethiol with
42 (1.2 g, 4.3 mmol) was carried out as de-
scribed for 26 to give, after column chro-
matography (solvent C), 45 (1.21 g, 79%) as
an oil: [h]D +364° (c 0.5, CHCl3); Rf 0.55
(solvent C). Anal. Calcd for C16H17NO4S2: C,
54.68; H, 4.88; N, 3.99; S, 18.25. Found: C,
54.65; H, 4.82; N, 4.01; S, 18.22.
—To a stirred soln of 50 (3.25 g, 13 mmol) in
pyridine (15 mL) mesyl chloride (1.23 mL,
15.6 mmol) was added at 0 °C. After 30 min
the mixture was processed the usual way to
give on concentration 51 (4.18 g, 98%) as
syrup, [h]D +49°; Rf 0.6 (solvent B). Anal.
Calcd for C11H20O7S2: C, 40.23; H, 6.14; S,
19.53. Found: C, 40.11; H, 6.22; S, 19.44.
4-Cyanophenyl
2,5-anhydro-4-O-methyl-
(46).—
1,6:2,5-Dianhydro-3,4-di-O-methyl-1-thio- -
D
1,6-dithio-h- -glucoseptanoside
D
glucitol (52).—To a stirred soln of 51 (16.4 g,
50 mmol) in dioxane (160 mL), 4.5 M
Deacetylation of 45 (1.21 g, 3.4 mmol) was
performed as described for 27 to give, after

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284
4 - Nitrophenyl 2,5 - anhydro - 3,4 - di - O-
methanesulfonyl-1,6-dithio-h- -glucoseptano-
methanolic NaOMe (12.2 mL, 55 mmol) was
added and the slurry was heated on a steam
bath for 2 h. The cooled mixture was diluted
with water (300 mL) and extracted with
CH2Cl2. The organic soln was washed with
water, dried, concd, and the residue distilled
at 26.6 Pa to give 52 as colourless liquid (7 g,
78%), bp0.2 75–80 °C; [h]D +5°; Rf 0.8 (sol-
vent B). Anal. Calcd for C8H14O3S: C, 50.50;
H, 7.42; S, 16.85. Found: C, 50.48; H, 7.38; S,
12.82.
D
side (58).—Glycosidation of 4-nitroben-
zenethiol with 60 (0.5 g, 1.33 mmol) was car-
ried out as described for 28 to give 58 (0.58 g,
93%): mp 117–123 °C (ether); [h]D +250° (c
0.5, CHCl3); Rf 0.6 (solvent B). Anal. Calcd
for C14H17NO9S4: C, 35.66; H, 3.63; N, 2.97;
S, 27.20. Found: C, 35.62; H, 3.66; N, 2.95; S,
27.17.
1-O-Acetyl-2,5-anhydro-3,4-di-O-methyl-6-
1,6:2,5-Dianhydro-3,4-di-O-methyl-1-thio-
D-
thio-h-
D
-glucoseptanose (59) and 1-O-acetyl-
glucitol S-oxide (53).—Oxidation of 52 (1.0 g,
5.25 mmol) was carried out as described for 20
to give 53 (0.92 g, 85%): mp 81–83 °C (ether);
[h]D −21° (c 0.5, acetone); Rf 0.2 (solvent A).
Anal. Calcd for C8H14O4S: C, 46.59; H, 6.84;
S, 15.55. Found: C, 46.63; H, 6.88; S, 15.57.
4 - Cyanophenyl 2,5 - anhydro - 3,4 - di - O-
2,5-anhydro-3,4-di-O-methyl-6-thio-h-
L
-gulose
ptanose (61).—A soln of 53 (3.3 g, 16 mmol)
in Ac2O (35 mL) was stirred at 100 °C for 5 h.
The mixture was concd and toluene (30 mL)
was evaporated from the residue to give, after
column chromatography (solvent C), a 9:1
mixture of 59 and 61 (2.66 g, 67%) as an oil:
[h]D +180° (c 0.5, CHCl3); Rf 0.4 (solvent C).
Anal. Calcd for C10H16O5S: C, 48.37; H, 6.50;
S, 12.91. Found: C, 48.41; H, 6.53; S, 12.96.
1,6:2,5 - Dianhydro - 4 - azido - 4 - deoxy - 3 - O-
methyl-1,6-dithio-h- -glucoseptanoside (55).
D
—Glycosidation of 4-cyanobenzenethiol with
a 9:1 mixture of 59 and 61 (0.6 g, 2.4 mmol)
was carried out as described for 26 to give,
after column chromatography (solvent C), 55
(0.7 g, 90%) as an oil: [h]D +440° (c 0.5,
CHCl3); Rf 0.5 (solvent C). Anal. Calcd for
C15H17NO3S2: C, 55.70; H, 5.30; N, 4.33; S,
19.83. Found: C, 55.74; H, 5.27; N, 4.30; S,
19.82.
tetrahydropyranyl-1-thio- -glucitol (64).—To
D
a soln of 63 [1] (5.4 g, 16.6 mmol) in DMF (55
mL) NaN3 (2.5 g, 38.5 mmol) was added and
the mixture was stirred at 110 °C for 1 h.
After cooling to rt the reaction was poured
into ice-water, extracted with ether and concd
to give 64 (4.5 g, 100%) as an oil: Rf 0.8
(solvent C). Anal. Calcd for C11H17N3O3S: C,
48.69; H, 6.32; N, 15.49; S, 11.82. Found: C,
48.71; H, 6.33; N, 15.52; S, 11.86.
4-Nitrophenyl 2,5-anhydro-3,4-di-O-methyl-
1,6-dithio-h-
D
-glucoseptanoside
(56).—Gly-
cosidation of 4-nitrobenzenethiol with a 9:1
mixture of 59 and 61 (0.6 g, 2.4 mmol) was
carried out as described for 28 to give, after
column chromatography (solvent C), 56 (0.73
g, 88%) as an oil: [h]D +378° (c 0.5, CHCl3);
Rf 0.5 (solvent C). Anal. Calcd for
C14H17NO5S2: C, 48.96; H, 4.99; N, 4.08; S,
18.67. Found: C, 48.98; H, 4.96; N, 4.07; S,
18.71.
3 - O- Acetyl - 1,6:2,5 - dianhydro - 4 - azido - 4-
deoxy-1-thio- -glucitol (66).—To a soln of 64
D
(4.27 g, 15.7 mmol) in MeOH (65 mL) Dowex
50WX ion exchange resin (1.5 g) was added
and the mixture was stirred at rt for 24 h.
Then the resin was filtered off, washed with
MeOH and the filtrate was concd. The residue
was acetylated with Ac2O (5 mL) in pyridine
(10 mL) to give, after the usual processing, 66
(2.96 g, 82%): mp 40–46 °C (hexane); [h]D
+39.5° (c 0.5, CHCl3); Rf 0.8 (solvent C).
Anal. Calcd for C8H11N3O3S: C, 41.91; H,
4.84; N, 18.33; S, 13.99. Found: C, 41.94; H,
4.80; N, 18.37; S, 13.95.
4 - Cyanophenyl 2,5 - anhydro - 3,4 - di - O-
methanesulfonyl-1,6-dithio-h- -glucoseptano-
D
side (57).—Glycosidation of 4-cyanoben-
zenethiol with 60 [9] (0.5 g, 1.33 mmol) was
carried out as described for 26 to give, after
column chromatography (solvent B, then A),
57 (0.53 g, 88%): mp 157–163 °C (ether); [h]D
+216° (c 0.5, CHCl3); Rf 0.6 (solvent B).
Anal. Calcd for C15H17NO7S4: C, 39.90; H,
3.79; N, 3.10; S, 28.40. Found: C, 39.88; H,
3.83; N, 3.12; S, 28.44.
3 - O- Acetyl - 1,6:2,5 - dianhydro - 4 - azido - 4-
deoxy-1-thio- -glucitol S-oxide (68).—Oxida-
D
tion of 66 (2.2 g, 9.6 mmol) was carried out as
described for 20 to give 68 (2.1 g, 89%): mp

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E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
285
(75).—Glycosidation of 4-cyanobenzenethiol
with a 1:4 mixture of 70 and 72 (0.5 g, 1.74
mmol) was carried out as described for 26 to
give, after column chromatography (solvent
D), 75 (0.45 g, 71%) as an oil: [h]D +403° (c
0.5, CHCl3); Rf 0.7 (solvent C). Anal. Calcd
for C15H14N4O3S2: C, 49.71; H, 3.89; N, 15.46;
S, 17.69. Found: C, 49.75; H, 3.84; N, 15.42;
S, 17.72.
98–105 °C (ether); [h]D +9° (c 0.5, acetone);
Rf 0.4 (solvent A). Anal. Calcd for
C8H11N3O4S: C, 39.18; H, 4.52; N, 17.13; S,
13.07. Found: C, 39.20; H, 4.57; N, 17.15; S,
13.09.
1,6:2,5 - Dianhydro - 4 - azido - 4 - deoxy - 3 - O-
methanesulfonyl - 1 - thio -
D
- glucitol S-oxide
(69).—Oxidation of 67 [3] (2.5 g, 9.4 mmol)
was carried out as described for 20 to give 69
(2.5 g, 94%): mp 133–138 °C (ether); [h]D
+3° (c 0.5, acetone); Rf 0.3 (solvent A). Anal.
Calcd for C7H11N3O5S2: C, 29.89; H, 3.94; N,
14.94; S, 22.80. Found: C, 29.91; H, 3.92; N,
14.97; S, 22.77.
4-Cyanophenyl 4-azido-4-deoxy-2,5-anhy-
dro-1,6-dithio-h-
D
-glucoseptanoside
(76).—
Deacetylation of 75 (0.45 g, 1.2 mmol) was
performed as described for 27 to give, after
column chromatography (solvent C), 76 (0.36
g, 90%) as an oil: [h]D +456° (c 0.5 MeOH);
Rf 0.3 (solvent C). Anal. Calcd for
C13H12N4O2S2: C, 48.74; H, 3.78; N, 17.49; S,
20.02. Found: C, 48.77; H, 3.75; N, 17.52; S,
19.99.
1,4 - Di - O - acetyl - 2,5 - anhydro - 3 - azido - 3-
deoxy-6-thio-h-
O-acetyl-2,5-anhydro-4-azido-4-deoxy-6-thio-
h- -glucoseptanose (72).—A soln of 68 (2.1 g,
L
-guloseptanose (70) and 1,3-di-
D
7.3 mmol) in Ac2O (20 mL) was stirred at
100 °C for 5 h. The mixture was concd and
toluene (30 mL) was evaporated from the
residue to give, after column chromatography
(solvent C), a 1:4 mixture of 70 and 72 (1.7 g,
81%) as an oil: Rf 0.5 (solvent C). Anal. Calcd
for C10H13N3O5S: C, 41.81; H, 4.56; N, 14.63;
S, 11.16. Found: C, 41.85; H, 4.53; N, 14.66;
S, 11.20.
4-Cyanophenyl 4-azido-4-deoxy-2,5-anhy-
dro - 3 - O - methanesulfonyl - 1,6 - dithio - h - -
D
glucoseptanoside (77).—Glycosidation of 4-
cyanobenzenethiol with 73 (0.7 g, 2.16 mmol)
was carried out as described for 26 to give,
after column chromatography (solvent EH
1:2), 77 (0.58 g, 67%): mp 94–96 °C (ether);
[h]D +344° (c 0.5, CHCl3); Rf 0.6 (solvent C).
Anal. Calcd for C14H14N4O4S3: C, 42.20; H,
3.54; N, 14.06; S, 24.14. Found: C, 42.22; H,
3.51; N, 14.02; S, 24.17.
1-O-Acetyl-2,5-anhydro-3-azido-3-deoxy-4-
O-methanesulfonyl-6-thio-h-
(71) and 1-O-acetyl-2,5-anhydro-4-azido-4-
deoxy-3-O-methanesulfonyl-6-thio-h- -glu-
L
-guloseptanose
4-Nitrophenyl 4-O-acetyl-3-azido-3-deoxy-
D
2,5-anhydro-1,6-dithio-h-
and 4-nitrophenyl 3-O-acetyl-4-azido-4-deoxy-
2,5-anhydro-1,6-dithio-h- -glucoseptanoside
L
-guloseptanoside (74)
coseptanose (73).—A soln of 69 (2.5 g, 8.9
mmol) in Ac2O (25 mL) was stirred at 100 °C
for 5 h. The mixture was concd and toluene
(30 mL) was evaporated from the residue. The
resulting residue was submitted to column
chromatography (solvent C). Concentration of
the first fraction gave 71 (150 mg, 5%) as an
oil: [h]D +14° (c 0.5, CHCl3); Rf 0.45 (solvent
C). Anal. Calcd for C9H13N3O6S2: C, 33.43; H,
4.05; N, 13.00; S, 19.83. Found: C, 33.46; H,
4.03; N, 13.03; S, 19.87.
Concentration of the second fraction gave
73 (1.5 g, 52%) as an oil: [h]D +84° (c 0.5,
CHCl3); Rf 0.4 (solvent C). Anal. Calcd for
C9H13N3O6S2: C, 33.43; H, 4.05; N, 13.00; S,
19.83. Found: C, 33.40; H, 4.08; N, 12.98; S,
19.80.
D
(78).—Glycosidation of 4-nitrobenzenethiol
with a 1:4 mixture of 70 and 72 (0.62 g, 2.16
mmol) was carried out as described for 28 to
give, after column chromatography (solvent
D), 78 (0.4 g, 48%) as an oil: [h]D +394° (c
0.5, CHCl3); Rf 0.7 (solvent C). Anal. Calcd
for C14H14N4O5S2: C, 43.97; H, 3.69; N, 14.65;
S, 16.77. Found: C, 43.93; H, 3.71; N, 14.69;
S, 16.73.
Concentration of the second fraction gave,
after crystallisation with hexane, 74 (20 mg,
2%): mp 174–177 °C (hexane); [h]D −447.5°
(c 0.4 CHCl3); Rf 0.65 (solvent C). Anal.
Calcd for C14H14N4O5S2: C, 43.97; H, 3.69; N,
14.65; S, 16.77. Found: C, 43.95; H, 3.66; N,
14.63; S, 16.79.
4-Cyanophenyl 3-O-acetyl-4-azido-4-deoxy-
2,5-anhydro-1,6-dithio-h- -glucoseptanoside
D

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E. Bozo´ et al. / Carbohydrate Research 329 (2000) 269–286
286
Acknowledgements
4-Nitrophenyl
dro-1,6-dithio-h-
4-azido-4-deoxy-2,5-anhy-
-glucoseptanoside (79).—
D
The authors are very much indebted to Dr
Gabriella Szabo´ for the biological results.
Deacetylation of 78 (0.4 g, 1.04 mmol) was
performed as described for 27 to give, after
column chromatography (solvent C), 79
(0.34 g, 96%): mp 96–101 °C (hexane); [h]D
+476° (c 0.5 MeOH); Rf 0.4 (solvent C).
Anal. Calcd for C12H12N4O4S2: C, 42.34; H,
3.55; N, 16.46; S, 18.84. Found: C, 42.38; H,
3.54; N, 16.49; S, 18.80.
Glycosidation of 4-nitrobenzenethiol with
73 (0.7 g, 2.16 mmol) was carried out as
described for 28 to give, after column chro-
matography (solvent C), 80 (0.49 g, 54%):
mp 77–79 °C (ether); [h]D +324° (c 0.5,
CHCl3); Rf 0.6 (solvent C). Anal. Calcd for
C13H14N4O6S3: C, 37.31; H, 3.37; N, 13.39;
S, 22.99. Found: C, 37.28; H, 3.41; N, 13.42;
S, 23.02.
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Full crystallographic details, excluding
structural features, have been deposited with
the Cambridge Crystallographic Data Centre
(CCDC number for 16: 146871). These data
may be obtained, on request, from: The Di-
rector, CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK (fax: +44-1223-336033; e-
mail: deposit@ccdc.cam.ac.uk or www: http://
www.ccdc.cam.ac.uk).