Synthesis of 4-cyano and 4-nitrophenyl 1,6-dithio-D-manno-, L-ido- and D-glucoseptanosides possessing antithrombotic activity.

Article abstract of DOI:10.1016/S0008-6215(02)00128-3

1,6-Anhydro-3,4-O-isopropylidene-1-thio-D-mannitol was converted into its sulfoxide which after hydrolysis, acetylation and subsequent Pummerer rearrangement gave the penta-O-acetyl-1-thio-D-mannoseptanose anomers in excellent yield. This anomeric mixture was used as donor for the glycosylation of 4-nitro- and 4-cyanobenzenethiol in the presence of boron trifluoride etherate and trimethylsilyl triflate, respectively, to yield the corresponding thioseptanosides in high yield. The same strategy was applied for the synthesis of the corresponding L-idothioseptanosides using 1,6-anhydro-3,4-O-isopropylidene-1-thio-L-iditol as starting material. The penta-O-acetyl-D-glucothioseptanose donors could not be synthesised the same way, as the Pummerer reaction of the corresponding tetra-O-acetyl-1,6-thioanhydro-1-thio-D-glucitol sulfoxides led to an inseparable mixture of the corresponding L-gulo- and D-glucothioseptanose anomers. Therefore, D-glucose diethyl dithioacetal was converted via its 2,3,4,5-tetra-O-acetyl-6-S-acetyl derivative into an anomeric mixture of its 6-thio-septanose and -furanose peracetates which could be separated by column chromatography. Condensation of the 6-thio-glucoseptanose peracetates with 4-cyano- and 4-nitrobenezenethiol in the presence of boron trifluoride etherate afforded anomeric mixtures of the corresponding thioseptanosides. The D-manno-, L-ido- and D-glucothioseptanosides obtained after Zemplen deacetylation of these mixtures were tested for their oral antithrombotic activity.

Full text of DOI:10.1016/S0008-6215(02)00128-3

Carbohydrate Research 337 (2002) 1351–1365
www.elsevier.com/locate/carres
Synthesis of 4-cyano and 4-nitrophenyl 1,6-dithio-
D
-manno-, -ido-
L
and
D
-glucoseptanosides possessing antithrombotic activityꢀ,ꢀꢀ
a
b
a
c,
´
´
Eva Bozo´, Tama´s Ga´ti, Ada´m Demeter, Ja´nos Kuszmann *
aChemical Works of Gedeon Richter Ltd., PO Box 27, H-1475 Budapest, Hungary
bTechnical Uni6ersity of Budapest, Institute of General and Analytical Chemistry, Szt. Gelle´rt te´r 4, H-1111 Budapest, Hungary
cInstitute for Drug Research, PO Box 82, H-1325 Budapest, Hungary
Received 19 March 2002; accepted 28 May 2002
Abstract
1,6-Anhydro-3,4-O-isopropylidene-1-thio-
subsequent Pummerer rearrangement gave the penta-O-acetyl-1-thio-
D
-mannitol was converted into its sulfoxide which after hydrolysis, acetylation and
-mannoseptanose anomers in excellent yield. This anomeric
D
mixture was used as donor for the glycosylation of 4-nitro- and 4-cyanobenzenethiol in the presence of boron trifluoride etherate
and trimethylsilyl triflate, respectively, to yield the corresponding thioseptanosides in high yield. The same strategy was applied
for the synthesis of the corresponding
material. The penta-O-acetyl- -glucothioseptanose donors could not be synthesised the same way, as the Pummerer reaction of
the corresponding tetra-O-acetyl-1,6-thioanhydro-1-thio- -glucitol sulfoxides led to an inseparable mixture of the corresponding
-gulo- and -glucothioseptanose anomers. Therefore, -glucose diethyl dithioacetal was converted via its 2,3,4,5-tetra-O-acetyl-6-
L-idothioseptanosides using 1,6-anhydro-3,4-O-isopropylidene-1-thio-L-iditol as starting
D
D
L
D
D
S-acetyl derivative into an anomeric mixture of its 6-thio-septanose and -furanose peracetates which could be separated by column
chromatography. Condensation of the 6-thio-glucoseptanose peracetates with 4-cyano- and 4-nitrobenezenethiol in the presence
of boron trifluoride etherate afforded anomeric mixtures of the corresponding thioseptanosides. The
-glucothioseptanosides obtained after Zemple´n deacetylation of these mixtures were tested for their oral antithrombotic activity.
© 2002 Published by Elsevier Science Ltd.
D-manno-, L-ido- and
D
Keywords: 6-Thiosugars;
D
-manno-,
L
-ido- and
D
-glucothioseptanose peracetates; Thioseptanosides; Oral antithrombotic activity
1. Introduction
2. Results and discussion
In our previous papers,2,3 we showed that 4-substi-
tuted phenyl 2,5-anhydro-1,6-dithio- -glucosep-
tanosides (1) possess oral antithrombotic activity. For
our further structure–activity studies, we decided to
check the influence of the 2,5-anhydro bridge on the
biological activity, i.e., to synthesise the corresponding
Synthesis of the
thesis of the required donor molecule, 1,6-anhydro-3,4-
O-isopropylidene-1-thio-
-mannitol (5)4 was chosen as
starting material the isopropylidene group of which was
hydrolysed with aqueous trifluoroacetic acid (Scheme
2). Acetylation of the crude product resulted, however,
in a relatively low yield (30%) of an inseparable mixture
containing the needed tetra-O-acetate 8 and its ring-
D-mannoseptanosides.—For the syn-
D
D
D
-manno- (2),
L
-ido- (3), and
D-gluco-6-thiosep-
tanosides (4) (Scheme 1).
contracted 2,6-anhydro- -glucitol isomer 6 in a 1:1
D
ratio. The latter is formed during hydrolysis via a
transannular attack of the sulfur atom on the C-2(5)
carbon atom§ and subsequent hydrolysis of the formed
episulfonium intermediate.4,5 The mixture of the tetra-
ꢀ Orally active antithrombotic thioglycosides, Part XV. For
Part XIV, see Ref. 1.
ꢀꢀ Presented in part at the XXth International Carbohy-
drate Symposium, Hamburg, 27 August–1 September, 2000,
Abstr. B128.
* Corresponding author. Tel.: +36-1-399-3300; fax: +36-
1-399-3356
E-mail address: h13757@ella.hu (J. Kuszmann).
§ Because of the C2 symmetry of the molecule, C-2 and C-5
are equivalent, consequently attack of the sulfur atom on
either of them will lead to the same isomer.
0008-6215/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0008-6215(02)00128-3

´
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E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
Scheme 1.
Scheme 2. (i) TFA/H2O. (ii) Ac2O/Py. (iii) NaOMe/MeOH. (iv) NCS. (v) HSC6H4pNO2/ZnO. (vi) NaIO4. (vii) Ac2O. (viii)
HSC6H4pNO2/BF3·Et2O. (ix) HSC6H4pCN/TMSOTf.
15a was obtained. When 4-cyanobenzenethiol was used
as aglycon and trimethylsilyl triflate as promoter, the
corresponding acetylated a-thioglycoside 19 was
formed which afforded the thioseptanoside 20 after
deacetylation. Both 15a and 20 were submitted to
biological testing.
acetates 6 and 8 was deacetylated, but from the result-
ing mixture of the tetrahydroxy compounds 7 and 9
only the latter could be partially separated. Reacetyla-
tion of 9 afforded 8. Treatment of a mixture of the
tetraacetates 6 and 8 with N-chlorosuccinimide in
toluene2 afforded the corresponding chlorides 10 and
11, which gave 13 and 15 on treatment with 4-nitroben-
zenethiol in the presence of zinc oxide and subsequent
Zemple´n deacetylation of the intermediate derivatives
12 and 14 in a yield of 12.5 and 6%, respectively.
Although the low yield of 15a could be increased to
26% using pure 9 as donor, because of this relatively
low yield as well as the difficulties in separating the
mixtures of 6 and 8, another approach was tried. For
avoiding the ring contraction reaction mentioned
above, the thioether 5 was converted into its sulfoxide
16 prior to hydrolysis. Hydrolysis of the O-isopropyli-
dene group of 16 and subsequent acetylation afforded
the tetraacetate 17 in excellent yield. Pummerer rear-
rangement of 17 gave a 1:1 mixture of the correspond-
ing a- and b-pentaacetates (18ab) and this was used
without separation for the glycosidation of 4-nitroben-
zenethiol in the presence of boron trifluoride etherate to
give a 95:5 a,b-anomeric mixture of the thiosep-
tanosides 14 in excellent yield (98%). After deacetyla-
tion according to Zemple´n, the crystalline a anomer
Synthesis of the
the aforementioned synthesis, 1,6-thioanhydro-3,4-O-
isopropylidene-
-iditol (21)4 was chosen as starting ma-
L-idoseptanosides.—By analogy to
L
terial for the donor molecule (Scheme 3). Hydrolysis of
the isopropylidene group with aqueous trifluoroacetic
acid and subsequent acetylation led, however, not to
22, but to a mixture from which the 1,5-thioanhydro-
glucitol¶ pentaacetate 25 was isolated as the main com-
ponent (51%) and the 1,4-thioanhydro-
-altritol¶ 26
(3%) as well as the 2,5-thioanhydro- -mannitol pen-
D-
D
D
taacetate 29 as by-products (3%). That means that
during hydrolysis, the ring sulfur atom can attack not
only C-2(5) by forming an episulfonium intermediate
(23) but C-3(4) as well, and the more strained four
membered ring of the bicyclic sulfonium ion 27 so
¶ Due to the C2 symmetry of the starting material attack of
the sulfur atom at C-2 leads to 2,6-thioanhydro-
that at C-3 to 3,6-thioanhydro- -talitol, but both are equiva-
lent with the mentioned structures 25 and 26.
L-gulitol and
L

´
E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1353
Scheme 3. (i) TFA/H2O. (ii) Ac2O/Py.
Scheme 4. (i) NCS. (ii) HSC6H4pNO2/ZnO.
Scheme 5. (i) NaIO4. (ii) TFA/H2O. (iii) Ac2O/Py. (iv) Ac2O. (v) HSC6H4pCN/BF3·Et2O. (vi) HSC6H4pNO2/BF3·Et2O. (vii)
NaOMe/MeOH.
formed will be opened at the less hindered carbon
atom, yielding after acetylation 26. On the other hand,
the tetrahydrothiopyrane ring of 24 can undergo a
further ring contraction via the episulfonium ion 28
leading, after acetylation, to 29. Similar ring-transfor-
mation reactions were described for hydroxy containing
thiepane derivatives using Mitsunobu conditions.5
When the tetraacetate 25 was treated with N-chloro-
succinimide in toluene, the resulting anomeric chlorides
(30) were too unstable to be separated and were there-
fore converted directly into their thioglycosides using
4-nitrobenzenethiol in the presence of zinc oxide
(Scheme 4). Similarly to the aforementioned mannitol
derivatives chlorination took place at the tertiary car-
bon atom, as only the two anomeric 2,6-dithio-L-xylo-
hex-2-ulopyranosides 31 and 32 were formed and could
be separated in yields of 33 and 3%, respectively.
For avoiding the unwanted rearrangement reactions
which occurred during the acidic treatment of 21, the
strategy used successfully for the synthesis of the donor
18 was applied, i.e., 21 was converted via its sulfoxide
33 into the tetraacetate 34 the Pummerer rearrangement

´
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E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
Scheme 6. (i) NaIO4. (ii) TFA/H2O. (iii) Ac2O/Py.
couplings (Table 3), as well as the observed downfield
shift of the H-2 and H-5 protons (Table 2) of the
b-sulfoxides (the sulfoxide oxygen assumes an axial
orientation in the dominant conformation) relative to
the a-sulfoxides (oxygen is equatorial) are diagnostic of
the sulfoxide configuration. When a mixture of in 42a
and 42b was treated with aqueous trifluoroacetic acid,
an unexpected ring closure reaction took place, as after
acetylation only the triacetate of the corresponding
1,4-anhydro-derivative 47 could be isolated.ꢀꢀ This is
most probably formed via protonation of the sulfoxide
group (43) and subsequent elimination of water. Hy-
drolysis of the resulting S-C(1) ylide 44 would give 49,
the polarised C-1 atom of which can be attacked by the
OH-4 group (48) resulting in the overbridged structure
46. The latter gives on acetylation the isolated triacetate
47. As the sulfoxide group in 42 is flanked by two
of which afforded a 1:1 anomeric mixture of the corre-
sponding pentaacetates 35 (Scheme 5). This mixture
was used without separation for the glycosidation of
4-cyanobenzenethiol in the presence of trimethylsilyl
triflate, but the anomeric mixture of the corresponding
thioglycosides (37) was accompanied by several insepa-
rable by-products. However, when boron trifluoride
etherate was applied as promoter, 37 was obtained in
satisfactory yield as a 1:1.5 mixture of the a and b
anomers which could not be separated even by repeated
column chromatography. In an analogous way the
condensation of 35 with 4-nitrobenzenethiol afforded
39a and 39b in a similar ratio which could be separated
by column chromatography. Zemple´n deacetylation of
the anomeric mixture of 37 afforded an inseparable
mixture of 38a+38b and the unsaturated 2-deoxy-1-
ene derivative 36 which could be separated as a by-
product. They were submitted to biological testing
together with the 4-nitrobenzene anomers 40a and 40b,
obtained on Zemple´n deacetylation of 39a and 39b,
respectively.
methylene groups, theoretically the L-gulofuranose iso-
mer 45 could be formed in an analogous reaction via an
S-C(6) ylide, but in 45 all three acetoxy groups would
be cis related which is
a sterically unfavoured
arrangement.
Synthesis of the
thesis of these thioglycosides di-O-isopropylidene-1,6-
thioanhydro-
-glucitol 416 was chosen as starting
D-glucoseptanosides.—For the syn-
For overcoming the above mentioned difficulties,
1,6-thioanhydro-
-glucitol tetraacetate 5011 was used as
D
D
starting material for the synthesis of the glycosyl donor
(Scheme 7). As this molecule does not belong to the C2
symmetry group, on oxidation with sodium periodate
two sulfoxide isomers 51 and 52 were formed, which
could be separated by column chromatography. Their
structure was assigned by NMR spectroscopy as de-
scribed for the isomers of 42. Pummerer rearrangement
of both isomers resulted, according to NMR spec-
troscopy, in a mixture of four compounds: the two
material, but for avoiding any rearrangement during
hydrolysis of the isopropylidene groups, the compound
was converted with sodium periodate into its sulfoxide
42 (Scheme 6). The two diastereomers, differing in the
chirality of the sulfoxide group, i.e., the (S)-S-oxide
42a and the (R)-S-oxide 42b could be separated, and
their stereochemistry was established by NMR, as ac-
cording to the literature7–10 an axial sulfoxide is associ-
ated with a larger geminal coupling constant of the
a-methylene protons as compared to an equatorial one.
Moreover, the significant deshielding of the protons
that are in a syn–axial arrangement to an axial sulfox-
ide can be used to assign the configuration of the SꢀO
L
-gulothioseptanose 53 and 54 as well as the two D-glu-
ꢀꢀ The synthesis of 47 was recently published by Hughes and
Todhunter12 using a different route. This compound can be
regarded as a 1,6-anhydro-6-thio-b-D-glucofuranose deriva-
tive.
2
2
centre. The measured larger geminal J1a,1b and J6a,6b

´
E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1355
latter with mercury oxide/mercury chloride in aqueous
acetone and subsequent treatment with hydrogen
sulfide in the presence of pyridine led, after acetylation,
to a mixture containing according to GLC and NMR
spectroscopy, the two anomers of the glucofuranoside
64a and 64b as well as the required anomeric mixture of
the thioseptanoside acetates 55+56 in a ratio of
1:1:2:4. While the former two anomers could not be
separated from each other by column chromatography,
we succeeded in separating 55 and 56. Formation of the
furanose isomers 64 means that, during the hydrolysis
of the mercapto groups of 59, not only the expected
S-deacetylation takes place, but the thiol intermediate
60 undergoes a partial acetyl migration, resulting in the
2,3,5,6-tetraacetate 62 which undergoes a cyclisation to
the furanose derivative 63 yielding on acetylation 64. It
is worthwhile mentioning that, when all acetyl groups
cothioseptanose anomers 55 and 56, and differed only
in their ratio. Attempts to separate these four pentaac-
etate isomers by column chromatography failed, as
only a mixture of the two 1,2-trans-glycosides 54+56
could be partly separated from the mixture of the
1,2-cis-glycosides 53+55. For this reason the approach
applied by Whistler and Campbell13 for the synthesis of
the analogous 6-thio-
adopted next for the synthesis of the donor
tanose pentaacetates 55+56. Accordingly
D
-galactoseptanose acetates was
-glucosep-
-glucose
D
D
diethyl dithioacetal was treated with 1.1 equiv of p-
toluenesulfonyl chloride in pyridine and subsequently
with acetic anhydride, affording a 9:1 mixture of the
6-O-tosylate 58 and the pentaacetate 57, which were
separated by column chromatography. Conversion of
58 with potassium thioacetate in acetone afforded the
6-S-acetate 59 in ꢀquantitative yield. Reaction of the
Scheme 7. (i) NaIO4. (ii) Ac2O. (iii) KSAc. (iv) HgCl2/HgO/H2O. (v) Ac2O/Py. (vi) NaOMe/MeOH.

´
1356
E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
Scheme 8. (i) HSC6H4pX, BF3·Et2O. (ii) NaOMe/MeOH.
Table 1
Oral antithrombotic activity of 4-substituted phenyl 1,6-dithio-hexoseptanosides in rats using Pescador’s model14
Configuration
D
-glucoa
D
-manno
L
-ido
D-gluco
Compound
1
1
15a
20
36b
38c
40a
40b
68b
70a
70b
Rd
CN
37
NO2
50
NO2
37
CN
43
CN
30
CN
26
NO2
48
NO2
29
CN
27
NO2
24
NO2
19
Inhibitione (%)
a Reference compounds: 2,5-anhydro-derivatives.2
b 1-en-
D-arabino.
c a,b Anomer ratio 1:1.6.
d Substituent of the phenyl aglycon.
e Inhibition % at an oral dose of 2 mg/kg.
transannular participation reaction of the ring sulfur
atom, forming the sulfonium intermediate 71 with in-
version of configuration at C-2. Attack of this episulfo-
nium ion by a 4-cyanobenezenethiol molecule will lead,
via a second inversion at C-2, to the trithio derivatives
72 which on deacetylation affords 73. When 4-nitroben-
zenethiol was used as aglycon in the aforementioned
glycosidation reaction, a mixture was obtained, con-
taining besides a 1:2 mixture of the a and b anomers of
69 the corresponding trithio derivative 74 as by-
product. From this mixture 69b as well as 74 could be
separated by column chromatography and crystallisa-
tion. Zemple´n deacetylation of the anomeric mixture of
69 afforded 70a and 70b, respectively, which could be
separated. The thioseptanosides 68b, 70a and 70b were
submitted to biological testing.
of 64 are removed by Zemple´n deacetylation, a fura-
nose“pyranose isomerisation takes place, and after
acetylation only a 1:1 mixture of the corresponding
pentaacetate pyranose anomers 66a and 66b can be
isolated. That means that, during the demercaptalisa-
tion process, only the 4-O-acetyl group migrates to the
6-thiol group while the 5-O-acetyl group remains intact.
Otherwise the pyranose pentaacetates 66 should be
formed as by-products instead of the furanose anomers
64.
As, during the glycosidation reactions with the ap-
propriate thiols, a,b-anomeric mixtures were formed
even when the pure b-pentaacetate 56 was used as
donor, in further experiments the a,b-anomeric pen-
taacetate mixture was used for this purpose. Condensa-
tion of
a
1:2 a,b-anomeric mixture of the
glucoseptanose pentaacetates 55+56 with 4-cyanoben-
zenethiol in the presence of boron trifluoride etherate
afforded, besides a 1:2 mixture of the a and b anomers
of 67, some further by-products (Scheme 8). From this
mixture, pure 67b could be isolated after column chro-
matography and subsequent crystallisation which gave
68b after Zemple´n deacetylation. Deacetylation of the
residue, obtained after separation of 67b, afforded a
mixture from which 68a as well as the 1,2,6-trithio
derivative 73 could be separated by column chromatog-
raphy in low yield. That means that, during the glycosi-
dation reaction, the boron trifluoride can activate the
2-O-acetyl group of 67, which is eliminated via a
Deacetylation of the trithio-derivative 74 afforded 75.
Although the anomeric configuration of 73 and 75 was
suggested to be a by comparing its NMR data with
those of the two pentaacetate anomers 55 and 56, the
large negative value of their optical rotation ([h]D
−
560 and −562°, respectively) indicated rather the pres-
ence of a b anomer.
Biological results.—The oral antithrombotic activity
of 15a, 20, 36, 38, 40a, 40b, 73a, 73b, 75a and 75b was
determined on rats, using Pescador’s model.14 All com-
pounds were administered orally 3 h before ligation.
From the data listed in Table 1, it can be seen that the
biological activity of the -mannoseptanosides 15a and
D

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E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1357
20 and the a-
L
-idoseptanoside 40a was in the range of
1,6-Anhydro-1-thio-
D
-mannitol (9).—Deacetylation
the corresponding 2,5-anhydro-glucoseptanosides
1
of a 1:1 mixture of 6 and 8 (2.5 g, 7.2 mmol) with 3 M
NaOMe (0.1 mL) in MeOH (50 mL) yielded, after
neutralisation with solid CO2 and column chromatogra-
phy (solvent E) 9 (0.5 g, 39%): mp 122–124 °C (ether),
Lit.4 mp 120–122 °C; Rf 0.4 (solvent E). Anal. Calcd
for C6H12O4S: C, 39.99; H, 6.71; S, 17.79. Found: C,
39.91; H, 6.78; S, 17.83.
which were used as reference compounds, but no gener-
ally valid structure activity relationship could be
established.
Concentration of the second fraction gave a 4:1
3. Experimental
mixture of 2,6-anhydro-2-thio-
D
-glucitol 7 and 9 (0.77
g, 60%).
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), EtOAc (D), toluene–MeOH mixtures (E,
4:1), CH2Cl2–MeOH mixtures (F, 95:5; G, 9:1), tolu-
ene–acetone mixtures (H, 2:1) and EtOAc–EtOH mix-
tures (I, 9:1); detection by spraying the plates with a
0.02 M solution of I2 and a 0.30 M solution of KI in
10% aq H2SO4 solution followed by heating at ca.
200 °C. For column chromatography, Kieselgel 60 was
used. Mp are uncorrected. Optical rotations were deter-
mined at 20 °C. The NMR spectra were recorded on a
Varian INOVA™ spectrometer operating at 500 MHz
Acetylation of 9 (0.6 g) with Ac2O (5 mL) in pyridine
(10 mL) afforded 8 (0.92 g, 79%) as a syrup: [h]D
−74.5° (c 0.6, CHCl3); Rf 0.4 (solvent B). Anal. Calcd
for C14H20O8S: C, 48.27; H, 5.79; S, 9.20. Found: C,
48.32; H, 5.78; S, 9.24.
Con6ersion of the mixture of 6+ 8 into the thiogly-
cosides 12 and 14.—To a slurry of a 1:1 mixture of
6+8 (1.0 g, 2.87 mmol) in toluene (10 mL), NCS (0.38
g, 2.85 mmol) was added and the mixture was stirred
for 1 h at 20 °C. During this period, 6+8 was gradu-
ally dissolved and succinimide precipitated. This was
filtered off and was washed with toluene (5 mL). The
filtrate, containing 10 and 11 (Rf 0.6 (solvent B) was
added dropwise over a period of 30 min to a stirred
slurry of freshly fused ZnO (0.3 g, 3.7 mmol) and
4-nitrobenzenethiol (purity 80%) (0.67 g, 3.45 mmol) in
MeCN (15 mL). Stirring was continued for 30 min at
20 °C, then the mixture was filtered through Celite. The
residue obtained on concentration of the filtrate was
dissolved in MeOH (20 mL) and deacetylated with 3 M
NaOMe (0.1 mL). After neutralisation with solid CO2,
the mixture was concentrated and submitted to column
chromatography (solvent F, then G). Concentration of
1
(1H) by using a Varian 5 mm H{13C/15N} PFG Indi-
1
rect·nmr™ probe. H chemical shifts are given relative
to TMS (lTMS 0.00 ppm) as measured in Me2SO-d6 and
1
CDCl3 at 30 °C. H assignments were straightforward
by a concerted use of standard high-field one- and
two-dimensional (2D) NMR methods: 1D DPFGSE-
NOE (selective excitation by I-Burp2 shaped pulses)
and 2D 1H–1H shift correlations (PFG-DQFCOSY,
PFG-HSQC, PFG-HMBC). The obtained scalar and
NOE connectivities provided abundant information to
ensure unambiguous spectral assignments. Chemical
shifts are given in Table 2 and coupling constants in
Table 3. A detailed conformational analysis of the
prepared glucoseptanosides will be published in a forth-
coming paper.
the first fraction yielded 4-nitrophenyl 1,6-dithio-D-
mannoseptanoside (15a, 60 mg, 6%): mp 162–164 °C
(ether); [h]D +75° (c 0.5, pyridine); Rf 0.7 (solvent G).
Anal. Calcd for C12H15NO6S2: C, 43.23; H, 4.54; N,
4.20; S, 19.24. Found: C, 43.29; H, 4.57; N, 4.16; S,
19.22.
GLC was conducted with a Chrompack CP-9000
Gaschromatograph, using a glass capillary column RH-
5ms+ (30 m×0.25 mm) coated with polyimide; temper-
ature 12 °C×min−1 from 185 to 325 °C; carrier gas
nitrogen, 6lin 16.8 cm×s−1, 6split 24.9 cm×s−1, inlet
pressure 60 kPa, make up gas nitrogen; detection by
FID.
Concentration of the second fraction gave 4-nitro-
phenyl 1,6-dithio-b- -fructopyranoside (13, 120 mg,
D
12.5%): mp 98–102 °C; [h]D −234° (c 0.5, pyridine); Rf
0.6 (solvent G). The b configuration was proved by
NMR, as there was a NOE effect between the aromatic
H-2%, H-6(b) and H-4, as well as between H-1 and H-3.
Anal. Calcd for C12H15NO6S2: C, 43.23; H, 4.54; N,
4.20; S, 19.24. Found: C, 43.21; H, 4.57; N, 4.23; S,
19.24.
1,3,4,5-Tetra-O-acetyl-2,6-anhydro-2-thio-
D-glucitol
(6) and 2,3,4,5-tetra-O-acetyl-1,6-anhydro-1-thio-
D
-
mannitol (8).—A solution of 54 (9.1 g, 41.3 mmol) in
0.1 M aq trifluoroacetic acid (90 mL) was refluxed for
2 h, then concentrated and the residue was acetylated in
2:1 pyridine–Ac2O (120 mL) overnight. After usual
work-up, the residue was submitted to column chro-
matography (solvent B) to yield, according to NMR
spectroscopy, a 1:1 mixture of 6 and 8 (4.3 g, 30%).
4-Nitrophenyl
2,3,4,5-tetra-O-acetyl-1,6-dithio-D-
mannoseptanoside (14).—(i) To a slurry of 8 (0.7 g, 2.0
mmol) in toluene (10 mL), NCS (0.27 g, 2.0 mmol) was
added and the mixture was stirred for 2 h at 20 °C.
During this period, 8 gradually dissolved and succin-
imide precipitated. This was filtered off and was washed
with toluene (5 mL). The filtrate, containing 11 (Rf 0.6

´
1358
E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
Table 2
a
1H NMR data for 6–75 as measured in CDCl3 and bMe2SO-d6 at 30 °C at 500 MHz
Compound Chemical shifts (l)
H-1a H-1b H-2 H-3 H-4 H-5 H-6a H-6b Others
6a,c
8a,c
9b,§
4.06 4.13
2.80–2.90
2.43 2.79
3.60 3.91
4.52
3.44 5.27 5.19 5.25 2.91 2.64
5.37–5.39 2.80–2.90
3.92 3.74 3.74 3.92 2.43 2.79
4.18 3.75 4.06 2.43 2.90
5.52 5.74 5.57 5.43 3.10 2.94
4.00 4.09 3.81 4.00 2.84 2.72
4.56 4.04 4.28 4.47 3.54 3.13
5.77 5.39 5.19 5.24 3.46 3.38
5.67 5.44 5.53 5.33 3.26 2.74
1.98, 2.01, 2.05, 2.07 (OAc)
2.00, 2.04 (OAc)
4.67 br (2-OH, 3-OH)
13b
5.14 (1-OH), 5.17 (3-OH), 4.66 (4-OH, 5-OH)
2.12 (2-OAc), 2.06 (3-OAc), 2.14 (4-OAc), 2.07 (5-OAc)
5.54 (2-OH), 4.83 (3-OH), 4.59 (4-OH), 4.84 (5-OH)
2.87 br s (2-OH, 5-OH), 1.42 C(CH3)2
2.05 (2-OAc), 2.12 (3-OAc), 2.17 (4-OAc), 2.10 (5-OAc)
2.09 (1-OAc), 2.07 (2-OAc), 2.13 (3-OAc), 2.13 (4-OAc),
2.08 (5-OAc)
2.10 (1-OAc), 2.14 (2-OAc), 2.04 (3-OAc), 2.05 (4-OAc),
2.17 (5-OAc)
2.05, 2.06, 2.11, 2.13 (OAc)
14aa
15ab
16a
4.60
3.54 3.04
3.14 3.66
5.91
17a
18aa
18ba
6.08
5.77 5.50
5.38–5.42 2.98 3.37
19a
4.45
4.55
5.49 5.73 5.56 5.42 3.07 2.94
3.98 4.10 3.82 4.00 2.82 2.75
4.94–5.02 5.14 3.11 4.07 4.18
5.26 5.29 3.44 5.20 4.09 4.36
3.57 5.29 5.29 3.57 4.08 4.22
5.33 5.39 4.94 2.71 3.04
20b
5.55 (2-OH), 4.85 (3-OH), 4.62 (4-OH), 4.88 (5-OH)
1.95 (2-OAc), 1.94 (3-OAc), 1.96 (4-OAc), 2.00 (6-OAc)
2.00, 2.02, 2.04, 2.04 (OAc)
25a
2.83 2.60
3.23 2.94
4.08 4.22
4.32 4.95
4.02 4.52
2.80 3.55
3.52 3.21
5.87
26a,c
29a,c
31a
2.01, 2.02 (OAc)
2.19 (1-OAc), 2.11 (3-OAc), 1.98 (4-OAc), 2.00 (5-OAc)
1.80 (1-OAc), 2.06 (3-OAc), 2.01 (4-OAc), 2.07 (5-OAc)
5.68 (2-OH), 5.46 (5-OH), 1.32 C(CH3)2
2.04, 2.09, 2.11, 2.14 (OAc)
2.01, 2.02, 2.03, 2.05, 2.08, (OAc)
1.99, 2.02, 2.04, 2.08, 2.18 (OAc)
32a
5.64 5.75 5.14 2.90 3.27
33b
3.96 3.49
5.68 5.26–5.30 5.41 3.51 3.21
5.33–5.45 5.06 2.72 3.06
3.84–3.92 3.27 2.89
34a
35aa,c
35ba,c
36b
6.08
5.34 5.40 5.44 5.22 3.40 2.83
6.43 4.18 3.30 3.58 3.01 2.66
5.10 br (3-OH, 4-OH, 5-OH)
38ab,c
38bb,c
39aa
39ba
40ab
40bb
42ab
42bb
47a
4.55
4.85
4.41
4.78
4.62
3.44
3.47–3.51 3.56 2.87 2.68
5.43 (2-OH), 5.09 (3-OH), 4.97 (4-OH), 4.99 (5-OH)
5.69 (2-OH), 5.06 (3-OH), 4.90 (4-OH), 4.95 (5-OH)
2.02, 2.03, 2.03, 2.03 (OAc)
2.06 (2-OAc), 2.06 (3-OAc), 2.04 (4-OAc), 2.04 (5-OAc)
5.11 (2-OH), 5.47 (3-OH), 5.00 (4-OH), 5.00 (5-OH)
5.10 br (2-OH, 3-OH, 4-OH, 5-OH)
1.33, 1.36 C(CH3)2, 1.27, 1.39 C(CH3)2
1.35, 1.37 C(CH3)2, 1.30, 1.39 C(CH3)2
2.13 (2-OAc), 2.17 (3-OAc), 2.18 (5-OAc)
2.08 (2-OAc), 2.10 (3-OAc), 2.18 (4-OAc), 2.09 (5-OAc)
2.04 (2-OAc), 2.12 (3-OAc), 2.14 (4-OAc), 2.06 (5-OAc)
2.05 (1-OAc), 2.21 (2-OAc), 2.06 (3-OAc), 2.05 (4-OAc),
2.04 (5-OAc)
2.13 (1-OAc), 2.16 (2-OAc), 2.03 (3-OAc), 2.04 (4-OAc),
2.05 (5-OAc)
2.18 (1-OAc), 2.02 (2-OAc), 2.04 (3-OAc), 2.05 (4-OAc),
2.12 (5-OAc)
2.10 (1-OAc), 2.04 (2-OAc), 2.10 (3-OAc), 2.11 (4-OAc),
2.10 (5-OAc)
3.89 3.57 3.42 3.49 2.87 2.71
5.31 5.39 5.50 5.15 2.86 3.01
5.55 5.38 5.39 5.28 3.37 2.81
3.44–3.54
3.57 2.89 2.70
4.90
3.92 3.59 3.44 3.51 2.89 2.76
3.81 4.23 4.15 4.52 3.56 3.00
4.23 4.09 4.29 4.78 3.06 3.20
5.61 5.36 4.65 4.81 2.79 3.59
5.12 5.27 5.22 5.32 3.48 3.41
5.73 5.26 5.34 5.69 3.21 3.15
5.71 5.27 5.54 5.07 3.48 2.66
3.13 3.75
2.90 3.41
5.00
3.62 3.32
3.26–3.30
6.07
51a
52a
53a,c
54a,c
55a
5.75
6.05
6.01
5.37 5.25 5.73 5.20 2.79 3.30
5.35 5.61 5.42 5.44 3.18 2.87
5.26 5.44 5.32 5.36 2.92–3.02
56a
67aa,c
67ba
68ab
68bb
69ab,c
69bb
70ab,c
70bb
73b
4.52
4.46
4.74
4.74
4.58
4.51
4.79
4.80
5.78
4.89
5.89
5.60 5.73 5.24 5.44 3.16 2.90
5.18 5.54 5.42 5.37 2.96 3.02
3.87 4.00 3.63 4.10 2.69 3.01
2.09 (2-OAc), 2.04 (3-OAc), 2.06 (4-OAc), 2.17 (5-OAc)
2.06 (2-OAc), 2.12 (3-OAc), 2.13 (4-OAc), 2.08 (5-OAc)
5.61 (2-OH), 5.17 (3-OH), 4.47 (4-OH), 4.94 (5-OH)
5.46 (2-OH), 5.12 (3-OH), 4.89 (4-OH), 4.94 (5-OH)
2.05, 2.06, 2.10, 2.17 (OAc)
2.06 (2-OAc), 2.13 (3-OAc), 2.14 (4-OAc), 2.09 (5-OAc)
5.64 (2-OH), 5.17 (3-OH), 4.46 (4-OH), 4.94 (5-OH)
5.10 (2-OH), 5.14 (3-OH), 4.92 (4-OH), 4.96 (5-OH)
3.40 br s (3,4,5-OH)
3.60
3.77–3.88 4.01 2.88 2.62
5.61 5.74 5.26 5.45 3.17 2.92
5.20 5.55 5.43 5.38 2.95–3.06
3.87 4.01 3.63 4.10 2.69 3.04
3.63
3.80–3.88 4.28 2.94 2.63
3.30 3.96 3.20 4.00 2.58 2.90
3.51 5.88 4.86 5.41 2.92–2.95
3.35 3.96 3.22 3.99 2.80 2.91
74a
2.02 (3-OAc), 2.01 (4-OAc), 2.21 (5-OAc)
5.44 (3-OH), 4.73 (4-OH), 4.71 (5-OH)
75b
§cMeasured at 300 MHz.
Chemical shifts are determined from the mixture of the respective isomers (6+8, 26+29, 35a+35b, 38a+38b, 53+55, 54+56,
67a+67b, 69a+69b, 70a+70b).

´
E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1359
Table 3
a
1H–1H coupling data for 6–75 as measured in CDCl3 and bMe2SO-d6 at 30 °C at 500 MHz
Compound Coupling constants (Hz)
3J1a,2 3J1b,2 J2,3 3J3,4 3J4,5 3J5,6a J5,6b J6a,6b J1a,1b Others
3
3
2
2
6a,c
9b,§
7.1
3.3
6.8
8.9
3.0
n.r.
6.3
2.9
9.7
3.7
13.8 11.1
13.4
3
13b
9.2
8.2
7.3
2.9
3.1
2.7
4.3
7.5
7.5
1.8
4.5
3.4
13.9 11.6 3J1a,1-OH=3.9, J1b,1-OH=4.3
14aa
15ab
7.2
7.8
2.1
2.1
15.7
14.7
3J2,2-OH=5.5, J3,3-OH=5.4, J4,4-OH=4.6,
3
3
3J5,5-OH=4.7
16a
ꢀ8.0 7.8
1.0
3.3
1.5
1.4
2.8
1.9
1.7
9.2
6.4
7.1
8.9
8.1
7.3
2.4
1.7
3.2
n.d. 7.2
2.9
2.4
n.d. 3.3
9.6
8.8
13.9 13.6
14.6 14.9
15.7
15.2
15.6
17a
9.7
1.7
4.5
2.0
7.2
6.5
18aa
18ba
19a
8.1
2.9
7.3
7.8
4.6
3.7
20b
14.6
3J2,2-OH=5.4, J3,3-OH=5.4, J4,4-OH=4.6,
3
3
3J5,5-OH=4.4
25a
10.8
2.9
6.7
3.9
4.9
7.9
n.d. 10.6 9.2
2.9
3.0
3.4
5.8
2.6
12.0 13.4
12.3 12.1
11.4
26a,c
29a,c
31a
2.0
10.3 5.0
9.8
9.9
8.6
3.3
9.6
9.7
n.d. 9.5
8.9 1.9
4.9
4.7
11.2 13.5 12.1
11.2 13.3 12.1
4.8
9.3
32a
33b
3.0
7.5
4.6
1.9
7.4
3.1
8.6
7.4
12.6 13.9 3J2,2-OH=4.2, J5,5-OH=4.2
14.1 14.2
3
34a
35aa,c
35ba,c
36b
n.d. n.d. n.d. 4.0
ꢀ9 ꢀ9 ꢀ9 3.4
3.7
11.3 15.4
3.7
8.4
6.0
16.3
14.4
15.3
9.6
7.6
3.2
38ab,c
7.9
3.4
ꢀ8 n.d. n.d. 4.4
3J2,2-OH=4.4, J3,3-OH=2.9, J4,4-OH=3.8,
3
3
3J5,5-OH=4.4
38bb,c
6.8
8.5
8.5
4.4
9.3
14.4
3J2,2-OH=5.7, J3,3-OH=4.1, J4,4-OH=3.5,
3
3
3J5,5-OH=3.5
39aa
39ba
40ab
40bb
42ab
42bb
47a
8.2
4.1
7.8
3.6
8.4
8.8
9.2
8.2
8.5
8.3
4.3
4.0
7.7
5.7
6.1
9.3
15.7
15.8
15.4
14.5
12.8 11.1
14.5 13.8
14.9
13.2 13.6
14.5 14.6
15.2
16.6
15.4
n.d.
15.5
14.7
14.5
3
n.d. n.d. n.d. 3.9
3J2,2-OH=1.9, J3,3-OH=4.3
6.9
8.9
8.9
2.7
7.1
7.9
0.9
1.4
9.2
4.6
7.6
4.0
6.5
8.5
8.4
7.8
7.5
5.2
4.3
9.4
8.7
7.8
8.6
8.6
8.4
8.3
8.1
6.8
6.4
2.7
1.3
1.0
7.3
7.4
2.8
1.8
2.0
1.8
1.7
4.5
12.0 2.3
11.4 2.1
11.8
11.3
2.3
2.4
0.6
3.3
3.6
51a
10.1
9.4
2.3
1.8
10.0 2.8
10.1 2.5
10.8 3.8
3.4
8.2
52a
53a,c
54a,c
55a
4.9
5.2
2.9
7.0
4.1
8.4
3.1
3.8
5.0
56a
3J5,6a+3J5,6b=12.0
67aa,c
67ba
68ab
6.1
8.9
5.0
4.0
4.5
2.5
3J2,2-OH=6.6, J3,3-OH=5.0, J4,4-OH=3.8,
3
3
3J5,5-OH=4.1
68bb
8.3
5.2
7.0
1.5
8.9
4.3
14.1
3J2,2-OH=6.6, J3,3-OH=4.6, J4,4-OH=4.1,
3
3
3J5,5-OH=4.7
69ab,c
69bb
4.1
8.6
3.1
7.6
3.8
6.5
8.6
8.4
8.3
2.1
1.8
1.5
6.1
8.7
5.0
4.0
4.6
2.6
15.5
14.7
14.4
70ab,c
3J2,2-OH=6.6, J3,3-OH=5.0, J4,4-OH=3.8,
3
3
3J5,5-OH=4.1
70bb
8.4
5.2
ꢀ7 1.5
8.9
4.3
4.4
4.2
1.7
1.8
14.0
3J2,2-OH=6.6, J3,3-OH=4.5, J4,4-OH=4.1,
3
3
3J5,5-OH=4.7
73b
74a
75b
2.5
3.2
2.7
9.6
9.7
9.6
9.0
9.5
8.8
2.8
2.9
2.8
13.9
n.d.
13.9
3J5,6a+3J5,6b=5.8
3J3,3-OH=5.5, J4,4-OH=5.8, J5,5-OH=3.7
3
3
§cMeasured at 300 MHz.
Chemical shifts are determined from the mixture of the respective isomers (6+8, 26+29, 35a+35b, 38a+38b, 53+55, 54+56,
67a+67b, 69a+69b, 70a+70b).
n.d., not determined; n.r., not resolved.

´
E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1360
(solvent B) was added dropwise over a period of 30 min
to a stirred slurry of freshly fused ZnO (0.21 g, 2.6
mmol) and 4-nitrobenzenethiol (purity 80%) (0.47 g, 2.4
mmol) in MeCN (15 mL). Stirring was continued for 30
min at 20 °C, then the mixture was filtered through
Celite. The residue obtained on concentration of the
filtrate was submitted to column chromatography (sol-
vent B, then A) to yield 14a (320 mg, 26%) as an oil:
[h]D +72° (c 0.55, CHCl3); Rf 0.4 (solvent B). Anal.
Calcd for C20H23NO10S2: C, 47.90; H, 4.62; N, 2.79; S,
12.79. Found: C, 47.93; H, 4.59; N, 2.82; S, 12.75.
(ii) Under argon, to a stirred solution of 18 (1.32 g,
3.25 mmol) and 4-nitrobenzenethiol (purity 80%) (0.66
g, 3.4 mmol) in dry 1,2-dichloroethane (20 mL)
BF3·Et2O (0.4 mL, 3.0 mmol) was added at 20 °C. The
mixture was kept at 20 °C for 2 h and then poured into
an ice-cold 6% aq NaHCO3 solution (50 mL). The
separated organic layer was washed with water, 6% aq
NaHCO3 and concentrated. The residue was submitted
to column chromatography (solvent B, then A) to yield
14 (1.6 g, 98%) as an oil which, according to NMR
spectroscopy, contained 14a and 14b in a ratio of 19:1.
to column chromatography (solvent B). Concentration
of the first fraction gave 18a (200 mg, 2%) as an oil:
[h]D +139° (c 0.5, CHCl3); Rf 0.4 (solvent B). Anal.
Calcd for C16H22O10S: C, 47.29; H, 5.46; S, 7.89.
Found: C, 47.33; H, 5.45; S, 7.83.
Concentration of the second fraction gave a 1:1
mixture of 18a and 18b (8.44 g, 95%).
Concentration of third fraction gave 18b (130 mg,
1.5%) as an oil: [h]D −196° (c 0.5, CHCl3); Rf 0.35
(solvent B). Anal. Calcd for C16H22O10S: C, 47.29; H,
5.46; S, 7.89. Found: C, 47.27; H, 5.41; S, 7.85.
4-Cyanophenyl
2,3,4,5-tetra-O-acetyl-1,6-dithio-D-
mannoseptanoside (19).—Under argon, to a stirred so-
lution of 18 (203 mg, 0.5 mmol) and 4-cyano-
benzenethiol (140 mg,
1
mmol) in dry 1,2-
dichloroethane (10 mL), TMSOTf (0.12 mL, 0.6 mmol)
was added at −10 °C. After stirring at −10 °C for 30
min, the reaction was quenched with Et3N, concen-
trated and the residue submitted to column chromatog-
raphy (solvent B) to give 19 (200 mg, 83%) as a syrup
which, according to NMR spectroscopy, was a 19:1
mixture of the a and b anomers: [h]D +55° (c 1,
CHCl3); Rf 0.35 (solvent B). Anal. Calcd for
C21H23NO8S2: C, 52.38; H, 4.81; N, 2.91; S, 13.32.
Found: C, 52.65; H, 5.03; N, 2.61; S, 13.21.
4-Nitrophenyl 1,6-dithio-h- -mannoseptanoside (15a).
D
—To a solution of a 19:1 a:b mixture of 14 (1.6 g, 3.2
mmol) in MeOH (50 mL), 3 M NaOMe in MeOH (0.1
mL) was added at rt. The solution was made neutral
after 1 h with solid CO2 and the precipitated material
was filtered and washed with ether to give 15a (0.68 g,
64%) identical with that obtained above.
4-Cyanophenyl 1,6-dithio-h- -mannoseptanoside (20).
D
—To a solution of 19 (400 mg) in CHCl3 (10 mL) and
MeOH (10 mL), 1 M NaOMe in MeOH (0.05 mL) was
added at rt. The solution was made neutral after 1 h
with solid CO2, and the residue of the concentrated
solution was submitted to column chromatography
(solvent I) to yield 20 (120 mg, 46%): mp 158–160 °C
(ether); [h]D +69° (c 0.5, pyridine); Rf 0.6 (solvent I).
Anal. Calcd for C13H15NO4S2: C, 49.82; H, 4.82; N,
4.47; S, 20.46. Found: C, 49.80; H, 4.77; N, 4.42; S,
20.31.
1,6-Anhydro-3,4-O-isopropylidene-1-thio-D-mannitol
S-oxide (16).—To a solution of NaIO4 (6.5 g, 30.4
mmol) in water (20 mL), a solution of 5 (6.66 g, 30.2
mmol) in acetone (120 mL) was added dropwise and
the resulting mixture was stirred at 20 °C for 2 h. The
precipitated crystals were filtered off and washed with
acetone. The residue obtained on concentration of the
filtrate was submitted to column chromatography (sol-
vent E) to yield 16 (7.1 g, 99%): mp 77–80 °C (ether–
hexane); [h]D −76° (c 0.5, MeOH); Rf 0.3 (solvent E).
Anal. Calcd for C9H16O5S: C, 45.75; H, 6.83; S, 13.57.
Found: C, 45.72; H, 6.80; S, 13.55.
2,3,4,6-Tetra-O-acetyl-1,5-anhydro-1-thio-
(25), 2,3,5,6-tetra-O-acetyl-1,4-anhydro-1-thio-
tol (26) and 1,3,4,6-tetra-O-acetyl-2,5-anhydro-2-thio-
-mannitol (29).—A solution of 214 (2.5 g, 11.3 mmol)
D
-glucitol
D
-altri-
D
in 0.1 M aq trifluoroacetic acid (25 mL) was refluxed
for 2 h, then concentrated and the residue was acety-
lated in 2:1 pyridine–Ac2O (45 mL) overnight. After
usual work-up, the residue was submitted to column
chromatography (solvent B). Concentration of the first
fraction gave a 1:1 mixture of 26 and 29 (235 mg, 6%):
Rf 0.4 (solvent B).
Concentration of the second fraction gave 25 (2.02 g,
51%): mp 108–110 °C (ether); [h]D +44° (c 0.5,
CHCl3); Rf 0.3 (solvent B). Anal. Calcd for C14H20O8S:
C, 48.27; H, 5.79; S, 9.20. Found: C, 48.30; H, 5.77; S,
9.16.
2,3,4,5-Tetra-O-acetyl-1,6-anhydro-1-thio-D-manni-
tol S-oxide (17).—A solution of 16 (7.1 g, 41.3 mmol)
in 0.1 M aq trifluoroacetic acid (70 mL) was refluxed
for 2 h, then concentrated and the residue was acety-
lated in 2:1 pyridine–Ac2O (100 mL) overnight. After
usual work-up, the residue was recrystallised from
ether–hexane to yield 17 (8.37 g, 82%): mp 130–
133 °C; [h]D −3° (c 0.5, MeOH); Rf 0.3 (solvent D).
Anal. Calcd for C14H20O9S: C, 46.15; H, 5.53; S, 8.80.
Found: C, 46.18; H, 5.55; S, 8.83.
1,2,3,4,5-Penta-O-acetyl-1-thio-D-mannoseptanose
(18).—A solution of 17 (8.0 g, 22 mmol) in Ac2O (80
mL) was stirred at 140 °C for 17 h. The mixture was
concentrated and toluene (100 mL) was evaporated
from the residue. The obtained residue was submitted
4-Nitrophenyl 1,3,4,5-tetra-O-acetyl-2,6-dithio-i-
xylo-hex-2-ulopyranoside (31) and 4-nitrophenyl 1,3,4,5-
tetra-O-acetyl-2,6-dithio-h- -xylo-hex-2-ulopyranoside
(32).—To a slurry of 25 (1.25 g, 3.6 mmol) in toluene
L-
L

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1361
(15 mL), NCS (0.48 g, 3.6 mmol) was added and the
mixture was stirred for 1 h at 20 °C. During this period
25 was gradually dissolved and succinimide precipi-
tated. This was filtered off and was washed with toluene
(5 mL). The filtrate, containing 30 (Rf 0.7, solvent B)
was added dropwise over a period of 30 min to a stirred
slurry of freshly fused ZnO (0.38 g, 4.7 mmol) and
4-nitrobenzenethiol (purity 80%) (0.85 g, 4.4 mmol) in
MeCN (20 mL). Stirring was continued for 1 h at
20 °C, then the mixture was filtered through Celite. The
residue obtained on concentration of the filtrate was
submitted to column chromatography (solvent B). Con-
centration of the first fraction gave 32 (50 mg, 3%): mp
128–132 °C (ether); [h]D −101° (c 0.3, CHCl3); Rf 0.6
(solvent B); The b configuration was proved by NMR,
as there was a NOE effect between the aromatic H-2%,
H-6(b) and H-4, as well as between H-1 and H-3. Anal.
Calcd for C20H23NO10S2: C, 47.90; H, 4.62; N, 2.79; S,
12.79. Found: C, 47.88; H, 4.64; N, 2.77; S, 12.76.
Concentration of the second fraction gave 31 (0.6 g,
33%) as an oil: [h]D +89° (c 0.3, CHCl3); Rf 0.5
(solvent B); The a configuration was proved by NMR,
as there was a NOE effect between the aromatic H-2%,
and H-3, as well as between H-1, H-4 and H-6(b). Anal.
Calcd for C20H23NO10S2: C, 47.90; H, 4.62; N, 2.79; S,
12.79. Found: C, 47.87; H, 4.63; N, 2.76; S, 12.80.
A). Anal. Calcd for C16H22O10S: C, 47.29; H, 5.46; S,
7.89. Found: C, 47.27; H, 5.43; S, 7.87.
4-Cyanophenyl 2-deoxy-1,6-dithio-
septanoside (36) and 4-cyanophenyl 1,6-dithio-
L
-xylo-hex-1-eno-
-idosep-
L
tanoside (38).—To a solution of 37 (500 mg, 1.04
mmol) in MeOH (50 mL), 3 M NaOMe in MeOH (0.05
mL) was added at rt. The solution was made neutral
after 1 h with solid CO2, and the residue of the concen-
trated solution was submitted to column chromatogra-
phy (solvent E). Concentration of the first fraction gave
36 (35 mg, 11%): mp 118–120 °C (ether); [h]D −268°
(c 0.4, pyridine); Rf 0.4 (solvent E). Anal. Calcd for
C13H13NO3S2: C, 52.86; H, 4.44; N, 4.74; S, 21.71.
Found: C, 52.81; H, 4.46; N, 4.72; S, 21.77.
Concentration of the second fraction gave 38 (190
mg, 58%) as a 1:1.5 mixture of a:b anomers: Rf 0.3
(solvent E). Anal. Calcd for C13H15NO4S2: C, 49.82; H,
4.82; N, 4.47; S, 20.46. Found: C, 52.81; H, 4.46; N,
4.72; S, 21.77.
4-Cyanophenyl
2,3,4,5-tetra-O-acetyl-1,6-dithio-L-
idoseptanoside (37).—Under argon, to a stirred solution
of 34 (2.03 g, 5 mmol) and 4-cyanobenzenethiol (0.81 g,
6 mmol) in dry 1,2-dichloroethane (30 mL), BF3·Et2O
(0.65 mL, 5.3 mmol) was added at rt. After 2 h, the
reaction was poured into ice-cold 6% aq NaHCO3
solution (60 mL). The separated organic solution was
washed with water, dried, concentrated and the residue
submitted to column chromatography (solvent B) to
give 37 (1.7 g, 69%) which, according to 1H NMR
spectroscopy, was a 1:1.5 mixture of the a and b
anomers: l 4.36 (1 H, d, J1,2 8.1 Hz, H-1b) and 4.73 (1
H, d, J1,2 4.1 Hz, H-1a) Rf 0.3 (solvent B). Anal. Calcd
for C21H23NO8S2: C, 52.38; H, 4.81; N, 2.91; S, 13.32.
Found: C, 52.65; H, 5.03; N, 2.61; S, 13.21.
1,6-Anhydro-3,4-O-isopropylidene-1-thio-L-iditol S-
oxide (33).—To a solution of NaIO4 (12.5 g, 58.44
mmol) in water (260 mL), a solution of 21 (12.2 g,
55.38 mmol) in acetone (220 mL) and water (100 mL)
was added dropwise and the resulted mixture was
stirred at 20 °C for 2 h. The precipitated crystals were
filtered off and washed with acetone. The residue ob-
tained on concentration of the filtrate was submitted to
column chromatography (solvent E) to yield 33 (12.95
g, 99%): mp 235–240 °C; [h]D +35° (c 0.5, pyridine);
Rf 0.3 (solvent E). Anal. Calcd for C9H16O5S: C, 45.75;
H, 6.83; S, 13.57. Found: C, 45.78; H, 6.85; S, 13.60.
4-Nitrophenyl
2,3,4,5-tetra-O-acetyl-1,6-dithio-L-
idoseptanoside (39).—The reaction of 4-nitroben-
zenethiol (0.66 g, 80% purity, 3.4 mmol) with 35 (1.32
g, 3.25 mmol) was carried out as described for 37 to
give after column chromatography (solvent B) 39 (1.53
g, 94%) which, according to NMR spectroscopy, was a
2:3 mixture of the a and b anomers: Rf 0.3 (solvent B).
They could be separated by repeated column chro-
matography (solvent B). Concentration of the first frac-
tion gave 39b (0.82 g): mp 165–168 °C (ether); [h]D
+225° (c 1.0, CHCl3); Rf 0.6 (solvent A). Anal. Calcd
for C20H23NO10S2: C, 47.90; H, 4.62; N, 2.79; S, 12.79.
Found: C, 47.93; H, 4.65; N, 2.82; S, 12.83.
Concentration of the second fraction gave 39a (0.55
g): mp 155–158 °C (ether); [h]D −80° (c 1.0, CHCl3);
Rf 0.55 (solvent A). Anal. Calcd for C20H23NO10S2: C,
47.90; H, 4.62; N, 2.79; S, 12.79. Found: C, 47.88; H,
4.60; N, 2.77; S, 12.75.
2,5-Anhydro-2,3,4,5-tetra-O-acetyl-1-thio-L-iditol S-
oxide (34).—A solution of 33 (7.5 g, 31.7 mmol) in 0.1
M aq trifluoroacetic acid (90 mL) was refluxed for 2 h,
then concentrated and the residue was acetylated in 2:1
pyridine–Ac2O (100 mL) overnight. After usual work-
up, the residue was submitted to column chromatogra-
phy (solvent E) to yield 34 (8.54 g, 74%): mp
133–135 °C (ether); [h]D −13° (c 1.0, MeOH); Rf 0.5
(solvent E). Anal. Calcd for C14H20O9S: C, 46.15; H,
5.53; S, 8.80. Found: C, 46.12; H, 5.51; S, 8.78.
1,2,3,4,5-Penta-O-acetyl-1-thio- -idoseptanose (35).
L
—A solution of 34 (6.7 g, 18.4 mmol) in Ac2O (70 mL)
was stirred at 100 °C for 20 h. The mixture was concen-
trated and toluene (100 mL) was evaporated from the
residue. The residue was submitted to column chro-
matography (solvent A) to yield, according to NMR
spectroscopy, a 1:1 mixture of 35a and 35b (6.85 g,
92%): mp 105–107 °C (EtOAc–hexane); Rf 0.6 (solvent
4-Nitrophenyl 1,6-dithio-h- -idoseptanoside (40a).—
L
To a solution of a 39a (0.55 g, 1.0 mmol) in MeOH (50
mL), 3 M NaOMe in MeOH (0.1 mL) was added at rt.
The solution was made neutral after 1 h with solid CO2,

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E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1362
concentrated and the residue was washed with water to
yield 40a (234 mg, 64%): mp 75–77 °C (ether); [h]D
−240° (c 0.5, pyridine); Rf 0.3 (solvent E). Anal. Calcd
for C12H15NO6S2: C, 43.23; H, 4.54; N, 4.20; S, 19.24.
Found: C, 43.20; H, 4.62; N, 4.19; S 19.19.
to NMR spectroscopy, the solid residue contained 51
and 52 in a ratio of 1:3. It was dissolved in hot EtOAc
(50 mL) and hexane (30 mL) was added. After cooling,
the precipitated crystals were filtered and washed with
hexane to give 52 (3.1 g, 58%), mp 174–177 °C, [h]D
−58° (c 1, CHCl3), Rf 0.4 (solvent C). The residue (2 g)
obtained on concentration of the filtrate was submitted
to column chromatography (solvent D). Eluted first
was unchanged 50 (0.6 g, 11.5%). Concentration of the
second fraction gave 51 (0.8 g, 15%) mp 137–141
(EtOAc–hexane); [h]D −18° (c 1, CHCl3); Rf 0.45
(solvent D). Anal. Calcd for C14H20O9S: C, 46.15; H,
5.53; S, 8.80. Found for 51: C, 46.11; H, 5.62; S 8.72.
Found for 52: C, 46.09; H, 5.59; S, 8.82.
Pummerer reaction of 51 and 52.—A solution of
51+52 (2.6 g, 18.4 mmol) in Ac2O (26 mL) was stirred
at 100 °C for 7 h. The mixture was concentrated and
toluene (50 mL) was evaporated from the residue. The
obtained residue was submitted to column chromatog-
raphy (solvent A). Concentration of the first fraction
gave, according to NMR spectroscopy, a 1:1 mixture of
54 and 56 (0.78 g, 27%): Rf 0.5 (solvent A). Anal. Calcd
for C16H22O10S: C, 47.29; H, 5.46; S, 7.89. Found: C,
47.23; H, 5.49; S, 7.82.
Concentration of the second fraction gave, according
to NMR spectroscopy, a 1.2:2.8:1:1.7 mixture of 53, 54,
55 and 56 (1.9 g, 65.5%): Rf 0.50+0.45 (solvent A).
Anal. Calcd for C16H22O10S: C, 47.29; H, 5.46; S, 7.89.
Found: C, 47.19; H, 5.43; S, 7.92.
Concentration of the third fraction gave, according
to NMR spectroscopy, a 3:7 mixture of 53 and 55 (180
mg, 6%): Rf 0.45 (solvent A). Anal. Calcd for
C16H22O10S: C, 47.29; H, 5.46; S, 7.89. Found: C, 47.25;
H, 5.45; S, 7.84.
4-Nitrophenyl 1,6-dithio-i- -idoseptanoside (40b).—
L
Deacetylation of 39b (0.59 g, 1.2 mmol) was performed
as described for 39a to yield 40b (325 mg, 83%): mp
181–184 °C (ether); [h]D −27° (c 1.0, pyridine); Rf 0.3
(solvent E). Anal. Calcd for C12H15NO6S2: C, 43.23; H,
4.54; N, 4.20; S, 19.24. Found: C, 43.27; H, 4.57; N,
4.16; S 19.29.
2,3:4,5-Di-O-isopropylidene-1,6-anhydro-1-thio-D-glu-
citol S-oxide (42).—To a solution of NaIO4 (1.95 g,
9.12 mmol) in water (60 mL), a solution of 416 (2.33 g,
8.95 mmol) in acetone (50 mL) was added dropwise and
the resulted mixture was stirred at 20 °C for 1 h. The
precipitated crystals were filtered off and washed with
acetone. The residue obtained on concentration of the
filtrate was submitted to column chromatography (sol-
vent H). Concentration of the first fraction yielded 42b
(R)-S-oxide (0.51 g, 21%): mp 229–232 °C (ether); [h]D
+72° (c 0.5, acetone); Rf 0.4 (solvent H). Anal. Calcd
for C12H20O5S: C, 52.16; H, 7.29; S, 11.60. Found: C,
52.19; H, 7.31; S, 11.57.
Concentration of the second fraction gave a 1.7:1
mixture of 42b (R)-S-oxide and 42a (S)-S-oxide (1.75
g, 71%).
Concentration of the third fraction yielded 42a (S)-
S-oxide (90 mg, 3.6%): mp 222–226 °C (ether); [h]D
+2° (c 0.5, acetone); Rf 0.3 (solvent H). Anal. Calcd
for C12H20O5S: C, 52.16; H, 7.29; S, 11.60. Found: C,
52.13; H, 7.25; S, 11.62.
2,3,5-Tri-O-acetyl-1,6-anhydro-1-thio-i-D-glucofura-
nose (47).—A solution of a 1.7:1 mixture of 42(R)- and
(S)-S-oxide (1.75 g, 6.3 mmol) in 0.1 M aq trifl-
uoroacetic acid (20 mL) was refluxed for 1.5 h, then
concentrated and the residue was acetylated in 2:1
pyridine–Ac2O (30 mL) overnight. After usual work-
up, the residue was submitted to column chromatogra-
phy (solvent B) to yield 47 (0.78 g, 40%) as an oil: [h]D
−114° (c 1.0, CHCl3); Rf 0.4 (solvent B); Lit.12 [h]D
1,2,3,4,5-Penta-O-acetyl-6-thio-h-
glucoseptanose (56) as well as 1,2,3,5-O-acetyl-6-S-ace-
tyl- -glucofuranose (64).—To a stirred solution of 59
D
- (55) and -i-D-
D
(10.5 g, 20 mmol) in acetone (200 mL) and water (25
mL), HgCl2 (25 g) and yellow HgO (25 g) were added.
The slurry was stirred for 36 h at rt, filtered and the
residue was washed with hot acetone (100 mL). Pyri-
dine (37 mL) was added to the filtrate and thereafter a
stream of H2S was passed through it until all mercury
salts precipitated. The formed dark brown precipitate
was removed by filtration and the filtrate was concen-
trated at 25 °C. The residue was dissolved in chloro-
form (200 mL), washed three times with water (3×30
mL), dried and concentrated. The remaining syrup was
dissolved in pyridine (100 mL) and concentrated to half
of its volume at 30 °C. The remaining solution was kept
under argon for 24 h at rt, then cooled to 0 °C and
treated with Ac2O (20 mL). The mixture was kept at rt
for 24 h to give after usual processing a syrup (7.8 g,
94%), which on TLC (solvent C) showed two distin-
guished set of spots at Rf ꢀ0.4 and ꢀ0.3. According
to GLC and NMR, this mixture contained 55, 56, 64a
1
−90° (c 1.0, CHCl3). Both, the H as well as the 13C
12
NMR data were identical with those given in Lit.
.
Anal. Calcd for C12H16O7S: C, 39.56; H, 4.43; S, 8.80.
Found: C, 39.60; H, 4.47; S, 8.77.
2,3,4,5-Tetra-O-acetyl-1,6-anhydro-1-thio-D-glucitol
(S)-S-oxide (51) and (R)-S-oxide (52).—To a stirred
solution of 508 (5.2 g, 15 mmol) in acetone (100 mL), a
solution of NaIO4 (5.5 g, 25.7 mmol) in water (35 mL)
was added at rt. After 2 h further NaIO4 (0.5 g, 2.3
mmol) was added to the formed slurry and stirring was
continued for 20 h. The precipitate was filtered off and
washed with acetone (50 mL). The combined filtrate
was concentrated, the residue was dissolved in CH2Cl2,
washed with water, dried and concentrated. According

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E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1363
and 64b in a ratio of 2:4:1:1 and was submitted to
column chromatography (solvent C).
2.90–2.45 (m, 4 H, S-CH2CH3), 2.15, 2.09, 2.08, 2.06
and 2.05 (5 s, 5×3 H, OAc) 1.33 and 1.23 (2 t, 2×3
H, S-CH2CH3); 13C NMR: l 72.1, 70.0, 68.4, 68.3
(C-2,3,4,5), 61.4 (C-6), 50.7 (C-1)
Concentration of the first fraction (Rf 0.4) gave a
syrup (1.6 g, 19%) which according to GLC and NMR
1
contained 64a and 64b in a ratio of ꢀ1:1. H NMR
Concentration of the second fraction gave 58 (23.1 g,
(CDCl3): 64a l 6.44 (d, J1,2 4.4, 1 H, H-1), 5.52 (dd, J2,3
3.3, J3,4 4.9 Hz, 1 H, H-3), 5.20 (ddd, J4,5 5.1, J5.6a 6.8,
J5.6b 3.4 Hz, 1 H, H-5), 5.18 (dd, 1 H, H-2), 4.44 (dd, 1
H, H-4), 3.54 (dd, J6a,6b 14.0 Hz, 1 H, H-6b), 3.02 (dd,
1 H, H-6a), 2.33 (s, 3 H, SAc), 2.12–1.96 (OAc); 13C
NMR: l 93.4 (C-1), 30.2 (S-Ac), 29.9 (C-6), 64b l 6.10
(s, J1,2 ꢀ0, 1 H, H-1), 5.39 (d, J2,3 ꢀ0, J3,4 4.6 Hz, 1
H, H-3), 5.28 (ddd, J4,5 5.1, J5.6a 6.4, J5.6b 3.4 Hz, 1 H,
H-5), 5.10 (s, 1 H, H-2), 4.47 (dd, 1 H, H-4), 3.60 (dd,
J6a,6b 14.0 Hz, 1 H, H-6b), 3.00 (dd, 1 H, H-6a), 2.33 (s,
3 H, SAc), 2.12–1.96 (OAc); 13C NMR: l 98.6 (C-1),
30.4 (C-6), 30.2 (S-Ac). Anal. Calcd for C16H22O10S: C,
47.29; H, 5.46; S, 7.89. Found: C, 47.42; H, 5.62; S,
7.53.
76%) as a syrup, [h]D +9°. Lit.16 [h]D +8° (c 4,
1
CHCl3). H NMR (CDCl3): l 7.78 and 7.38 (2 d, 4 H,
aromatic) 5.71 (dd, J2,3 7.6, J3,4 2.6 Hz, 1 H, H-3), 5.38
(dd, J4,5 8.1 Hz, 1 H, H-4), 5.23 (dd, J1,2 4.2, 1 H, H-2),
5.01 (ddd, J5.6a 4.2, J5.6b 2.9 Hz, 1 H, H-5), 4.18 (dd,
J6a,6b 11.2 Hz, 1 H, H-6b), 4.11 (d, 1 H, H-1), 4.10 (dd,
1 H, H-6a), 2.85–2.45 (m, 4 H, S-CH2CH3), 2.45 (s, 3
H, TsCH3), 2.09, 2.07, 2.02 and 2.01 (4 s, 4×3 H,
OAc) 1.29 and 1.23 (2 t, 2×3 H, S-CH2CH3); 13C
NMR: l 72.0, 69.8, 67.9, 67.8 (C-2,3,4,5), 66.4 (C-6),
50.6 (C-1).
2,3,4,5-Tetra-O-acetyl-6-S-acetyl-D-glucose diethyl
dithioacetal (59).—To a stirred solution of 58 (12.2 g,
20 mmol) in acetone (250 mL), KSAc (2.96 g, 26 mmol)
was added and the slurry was boiled for 5 h when
according to TLC the reaction was completed. The
residue of the concentrated mixture was dissolved in
CHCl3, washed with water, dried and concentrated to
give 59 (10 g, 98%) as a syrup. [h]D +25°. Anal. Calcd
for C20H32O9S3: C, 46.86; H, 6.29; S, 18.76. Found: C,
The second fraction (Rf 0.35) afforded on concentra-
tion 56 (1,7 g, 20.5%): mp 95–97 °C (ether–hexane),
1
[h]D −59°; H NMR (CDCl3): l 6.01 (d, J1,2 6.8, 1 H,
H-1), 5.53 (dd, J2,3 4.6, J3,4 8.5 Hz, 1 H, H-3), 5.40–
5.27 (m, 2 H, H-4,5), 5.24 (dd, 1 H, H-2), 2.98 (d,
J5,6aꢀJ5,6b 5.8 Hz, 2 H, H-6a,6b), 2.12, 2.11, 2.11, 2.10,
2.04 (5 s, 5×3 H, OAc); 13C NMR: l 75.9, 74.9, 70.7,
69.6, 68.9 (C-1,2,3,4,5), 28.0 (C-6). Anal. Calcd for
C16H22O10S: C, 47.29; H, 5.46; S, 7.89. Found: C, 47.21;
H, 5.45; S, 7.78.
1
46.72; H, 6.11; S, 18.52. H NMR (CDCl3): l 5.78 (dd,
J2,3 7.1, J3,4 3.2 Hz, 1 H, H-3), 5.35 (dd, J4,5 7.1 Hz, 1
H, H-4), 5.29 (dd, J1,2 4.6, 1 H, H-2), 5.01 (ddd, J5.6a
6.6, J5.6b 3.2 Hz, 1 H, H-5), 4.07 (d, 1 H, H-1), 3.33 (dd,
J6a,6b 14.6 Hz, 1 H, H-6b), 2.99 (dd, 1 H, H-6a),
2.90–2.40 (m, 4 H, S-CH2CH3), 2.33 (s, 3 H, SAc),
2.16, 2.09, 2.05 and 2.03 (4 s, 4×3 H, OAc) 1.32 and
1.23 (2 t, 2×3 H, S-CH2CH3); 13C NMR: l 71.9, 70.1,
69.9, 69.2 (C-2,3,4,5), 50.8 (C-1), 29.0 (C-6).
The third fraction (Rf 0.30) gave on concentration 55
1
(0.58 g, 7%) as a syrup, [h]D +109° H NMR (CDCl3):
l 6.05 (d, J1,2 2.9, 1 H, H-1), 5.62 (dd, J2,3 9.3, J3,4 7.6
Hz, 1 H, H-3), 5.48–5.38 (m, 2 H, H-4,5), 5.35 (dd, 1
H, H-2), 3.18 (dd, J5,6b 8.1, J6a,6b 15.1 Hz, 1 H, H-6b),
2.86 (dd, J5,6a 4.6 Hz, 1 H, H-6a), 2.18, 2.13, 2.05, 2.04,
2.02 (5 s, 5×3 H, OAc); 13C NMR: l 74.7, 71.1, 71.0,
70.4, 67.8 (C-1,2,3,4,5), 26.8 (C-6). Anal. Calcd for
C16H22O10S: C, 47.29; H, 5.46; S, 7.89. Found: C, 47.39;
H, 5.65; S, 7.62.
1,2,3,4-Tetra-O-acetyl-6-S-acetyl-D-glucopyranose
(66).—To a solution of a 1:1 a,b-anomeric mixture of
the furanose compound 64 (3.2 g) in MeOH (30 mL), 3
M methanolic NaOMe (3.5 mL) was added at rt. The
mixture was neutralised after 30 min with solid CO2
and kept for 20 h at rt. The residue obtained on
concentration was dissolved in pyridine (15 mL) and
Ac2O (10 mL) was added. After 20 h at rt, the mixture
was processed by the usual way to give on concentra-
tion of the CH2Cl2 solution a syrup (2.75 g, 86%)
which, according to NMR spectroscopy and GLC mea-
surements, contained 66a and 66b in a ratio of ꢀ1:1.
After column chromatography (solvent B), the same
mixture solidified and was filtered with ether–hexane
(2.4 g, 75%), mp 88–92 °C (ether–hexane); Rf 0.45
2,3,4,5,6-Penta-O-acetyl- (57) and 2,3,4,5-tetra-O-
acetyl-6-O-p-toluenesulfonyl-
D
-glucose diethyl dithioac-
etal (58).—To a stirred solution of
D
-glucose diethyl
dithioacetal (14.3 g, 50 mmol), TsCl (10.5 g, 55 mmol)
was added at 0 °C. After 30 min the temperature was
raised to 20 °C, after 20 min the mixture was cooled
with ice and Ac2O (50 mL) was added. The mixture was
kept at rt overnight to give after usual processing a
syrup (30 g) which was submitted to column chro-
matography using solvent C for elution.
1
Concentration of the first fraction gave 57 (2.3 g,
9.2%), mp 43–45 °C (EtOH–water), Rf 0.3 (solvent C).
(solvent B). H NMR (CDCl3): 66a l 6.26 (d, J1,2 3.6,
1 H, H-1), 5.43 (dd, J2,3 10.2, J3,4 9.5 Hz, 1 H, H-3),
5.05 (dd, 1 H, H-2), 5.01 (dd, J4,5 10.0 Hz, 1 H, H-4),
4.02 (dd, J5,6bꢀJ5,6a 4.4 Hz, 1 H, H-5), 3.18 (d, 2 H,
H-6a,6b), 2.33 (s, 3 H, SAc), 2.17, 2.08, 2.01, 2.00 (4 s,
4×3 H, OAc); 13C NMR: l 88.8 (C-1), 70.6, 69.8, 69.7,
69.1 (C-2,3,4,5), 29.6 (C-6), 66b l 5.68 (d, J1,2 8.0, 1 H,
1
Lit.15 mp 45–47 °C. H NMR (CDCl3): l 5.76 (dd, J2,3
7.3, J3,4 2.9 Hz, 1 H, H-3), 5.43 (dd, J4,5 8.1 Hz, 1 H,
H-4), 5.28 (dd, J1,2 4.2, 1 H, H-2), 5.06 (ddd, J5.6a 4.8,
J5.6b 3.2 Hz, 1 H, H-5), 4.23 (dd, J6a,6b 12.7 Hz, 1 H,
H-6b), 4.11 (dd, 1 H, H-6a), 4.07 (d, 1 H, H-1),

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E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1364
H-1), 5.20 (m, J2,3ꢀJ3,4 9.5 Hz, 1 H, H-3), 5.15–4.95
(m, 2 H, H-2,4), 3.81 (dd, J5,6b 3.5, J5,6a 5.9 Hz, 1 H,
H-5), 3.20 (dd, J6a,6b 14.4 Hz, 1 H, H-6b), 3.16 (dd, 1
H, H-6a), 2.33 (s, 3 H, SAc), 2.10, 2.09, 2.02, 2.01 (4 s,
4×3 H, OAc); 13C NMR: l 91.5 (C-1), 73.6, 72.6, 70.2,
69.7 (C-2,3,4,5), 29.6 (C-6). Anal. Calcd for
C16H22O10S: C, 47.29; H, 5.46; S, 7.89. Found: C, 47.35;
H, 5.65; S, 7.68.
From this mixture, 66a could be separated after
repeated column chromatography, mp 114–118 °C
(ether–hexane); Lit.17 mp 102–104 °C, Rf 0.40 (solvent
B); [h]D +80°; Lit.16 [h]D +38° (c 1.1, CHCl3). Anal.
Calcd for C16H22O10S: C, 47.29; H, 5.46; S, 7.89.
Found: C, 47.30; H, 5.55; S, 7.81.
Concentration of the third fraction gave 68b (50 mg,
2%), identical with that, described above.
4-Nitrophenyl 2,3,4,5-tetra-O-acetyl-1,6-dithio-
coseptanoside (69) and 4-nitrophenyl 3,4,5-tri-O-acetyl-2
- S - (4 - nitrophenyl) - 1,2,6 - trithio - - glucoseptanoside
D-glu-
D
(74).—The reaction of 4-nitrobenzenethiol (1.2 g, 80%
purity, 3 mmol) with 1:2 mixture of 55+56 (2 g, 5
mmol) was carried out as described for 37 to give after
column chromatography (Rf 0.35, solvent B) a solid
material (2.1 g, 84%) which contained, according to
NMR spectroscopy, besides different by-products 69a
and 69b as the main components in a ratio of 1:9.
Recrystallisation of this mixture from MeOH (20 mL)
gave 69b (1.5 g, 58%), mp 149–151 °C; [h]D −9°; Rf
0.30 (solvent E). Anal. Calcd for C20H23NO10S2: C,
47.90; H, 4.62; N, 2.79; S, 12.79. Found: C, 47.87; H,
4.71; N, 2.62; S, 12.83.
The residue obtained on concentration of the mother
liquor gave, after repeated column chromatography
(solvent B), 74 (140 mg, 4.6%) as a syrup; [h]D −168°
(c 0.8, CHCl3); Rf 0.35 (solvent B). Anal. Calcd for
C24H24N2O10S3: C, 48.31; H, 4.05; N, 4.70; S, 16.12.
Found: C, 48.55; H, 4.26; N, 4.62; S, 15.95.
4-Cyanophenyl
2,3,4,5-tetra-O-acetyl-1,6-dithio-D-
glucoseptanoside (67).—The reaction of 4-cyanoben-
zenethiol (950 mg, 7 mmol) with 1:2 mixture of 55+56
(2.45 g, 6 mmol) was carried out in the presence of
BF3·Et2O (0.8 mL, 6.5 mmol) as described for 37 to
give after column chromatography (solvent B, Rf 0.35)
a semisolid material (2.7 g) which, according to NMR
spectroscopy, was a mixture containing besides differ-
ent by-products 67a and 67b as the main components in
a ratio of 1:2.5. On treatment with ether–hexane, 67b
(1.6 g, 55.4%) was obtained; mp 160–163 °C (MeOH),
[h]D −20° (c 1, CHCl3); Rf 0.35 (solvent B). Anal.
Calcd for C21H23NO8S2: C, 52.38; H, 4.81; N, 2.91; S,
13.32. Found: C, 52.40; H, 4.85; N, 2.88; S, 13.27.
The residue (1 g) obtained on concentration of the
mother liquor contained, according to NMR spec-
troscopy, besides different by-products 67a and 67b in a
ratio of 3:1 which could not be separated.
Concentration of the further fractions gave a mixture
(1.1 g) which, according to NMR spectroscopy, con-
tained 69a and 69b in a ratio of 1:2, but these two
anomers could not be separated.
4-Nitrophenyl 1,6-dithio- -glucoseptanoside (70).—(i)
D
Deacetylation of 69b (500 mg) was carried out as
described for 15a to give after column chromatography
(solvent E) 70b (252 mg, 75%), mp 145–149 °C (ether);
[h]D −98° (c 1, pyridine); Rf 0.30 (solvent E). Anal.
Calcd for C12H15NO6S2: C, 43.23; H, 4.54; N, 4.20; S,
19.24. Found: C, 43.27; H, 4.62; N, 4.12; S, 19.17.
(ii) When the residue (1 g) obtained after separation
of 74 was submitted to deacetylation, as described for
15a, a mixture (620 mg, 73%) was obtained which,
according to NMR spectroscopy, contained 69a and
69b in a ratio of 1:2 which could not be separated; mp
129–134 °C (ether); [h]D −56° (c 1, pyridine); Rf 0.30
(solvent E). Anal. Calcd for C12H15NO6S2: C, 43.23; H,
4.54; N, 4.20; S, 19.24. Found: C, 43.19; H, 4.60; N,
4.10; S, 19.09.
4-Cyanophenyl 1,6-dithio-
4-cyanophenyl 2-S-(4-cyanophenyl)-1,2,6-trithio-
D
-glucoseptanoside (68) and
-glu-
D
coseptanoside (73).—(i) Deacetylation of 67b (270 mg)
was performed as described for 20 to give after column
chromatography (solvent E) 68b (150 mg, 85.3%), mp
130–133 °C; [h]D −113° (c 0.8, pyridine); Rf 0.30
(solvent E). Anal. Calcd for C13H15NO4S2: C, 49.82; H,
4.82; N, 4.47; S, 20.46. Found: C, 49.88; H, 4.87; N,
4.40; S, 20.32
(ii) When the residue (900 mg), obtained on concen-
tration of the mother liquor of 67b was deacetylated in
a similar way a mixture (380 mg) containing 68a, 68b
and 73 was obtained which could be separated by
column chromatography (solvent E).
Concentration of the first fraction gave 73 (60 mg,
2.3%), mp 100–105 °C (ether); [h]D −560° (c 0.4,
pyridine); Rf 0.40 (solvent E). Anal. Calcd for
C20H18N2O3S3: C, 55.79; H, 4.21; N, 6.51; S, 22.34.
Found: C, 55.63; H, 4.27; N, 6.57; S, 22.31.
4-Nitrophenyl 2-S-(4-nitrophenyl)-1,2,6-trithio-D-glu-
coseptanoside (75).—Deacetylation of 74 (100 mg) was
performed as described for 15a to give after column
chromatography (solvent E) 75 (70 mg, 91%), mp 196–
205 °C (ether); [h]D −562° (c 0.5, pyridine); Rf 0.40
(solvent E). Anal. Calcd for C18H18N2O7S3: C, 45.95;
H, 3.86; N, 5.95; S, 20.44. Found: C, 45.87; H, 3.60; N,
5.77; S, 20.09.
Concentration of the second fraction gave 68a (205
mg, 10.7%), mp 165–170 °C (ether); [h]D −18° (c 0.25,
pyridine); Rf 0.35 (solvent E). Anal. Calcd for
C13H15NO4S2: C, 49.82; H, 4.82; N, 4.47; S, 20.46.
Found: C, 49.76; H, 4.80; N, 4.42; S, 20.23.
Acknowledgements
The authors are very much indebted to Dr. Ferenc
Szederke´nyi for the GLC analysis, to Sa´ndor Boros for

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E. Bozo´ et al. / Carbohydrate Research 337 (2002) 1351–1365
1365
7. Buchanan, G. W.; Durst, T. Tetrahedron Lett. 1975, 21,
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recording and evaluating some of the NMR spectra for
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