Preparation of 3,5-bis-(β-D-glycopyranosyl)-1,2,4-thiadiazoles from C-(β-D-glycopyranosyl)thioformamides

Article abstract of DOI:10.1016/S0040-4020(01)00444-6

Acylated C-glycopyranosyl thioformamides of D-gluco, D-galacto, and D-xylo configuration were obtained by treating the corresponding glycosyl cyanides with hydrogen sulfide in the presence of triethylamine. The thioformamides gave 3,5-bis-(β-D-glycopyranosyl)-1,2,4-thiadiazoles in reactions with potassium bromate and sodium dithionite in dichloromethane-water biphasic solvent mixture. Deprotected derivatives were prepared by Zemple?n deacylation.

Full text of DOI:10.1016/S0040-4020(01)00444-6

TETRAHEDRON
Pergamon
Tetrahedron 57 22001) 5429±5434
Preparation of 3,5-bis-ꢀb-d-glycopyranosyl)-1,2,4-thiadiazoles
from C-ꢀb-d-glycopyranosyl)thioformamides
a
Erzsebet Osz, Katalin Czifrak, Tamas Deim, Laszlo Szilagyi, Attila Benyei
a
a
a
b
Í
Â
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and Laszlo Somsak
Â
a,p
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aDepartment of Organic Chemistry, University of Debrecen, H-4010 Debrecen, Hungary
bDepartment of Physical Chemistry, Laboratory for X-Ray Diffraction, University of Debrecen, H-4010 Debrecen, Hungary
Received 18 January 2001; revised 3 April 2001; accepted 20 April 2001
AbstractÐAcylated C-glycopyranosyl thioformamides of d-gluco, d-galacto, and d-xylo con®guration were obtained by treating the
corresponding glycosyl cyanides with hydrogen sul®de in the presence of triethylamine. The thioformamides gave 3,5-bis-2b-d-glyco-
pyranosyl)-1,2,4-thiadiazoles in reactions with potassium bromate and sodium dithionite in dichloromethane±water biphasic solvent
Â
mixture. Deprotected derivatives were prepared by Zemplen deacylation. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
Since the ®rst observation was encouraging and the product
7a had an interesting asymmetricbis- C-glycosyl hetero-
cyclic structure the reaction was investigated further and
extended to other sugar con®gurations.
Recently we have reported a simple, short synthetic
sequence for the preparation of glycopyranosylidene-
spiro-hydantoins and their thio analogues.1±4 The key step
of these preparations was a ring closure of acylated C-21-
2. Results and discussion
bromo-1-deoxy-b-d-glycopyranosyl)formamides
with
cyanate or thiocyanate ions. The d-gluco spiro-thio-
hydantoin proved to be the best available glucose analogue
inhibitor of muscle and liver glycogen phosphorylase 2GP) a
and b enzymes,2,3 and was also effective in decreasing liver
GPa activity in vivo.5 As a part of this project we set out to
prepare the corresponding spiro-dithiohydantoins in an
analogous way. To this end we investigated the radical-
mediated bromination of C-22,3,4,6-tetra-O-acetyl-b-d-
galactopyranosyl)thioformamide 24a). The new material
obtained from this reaction with high mass recovery con-
tained, however, no bromine, and structure elucidation by
NMR methods and X-ray crystallography established its struc-
ture as 3,5-bis-2b-d-galactopyranosyl)-1,2,4-thiadiazole 7a.
The starting C-2b-d-glycopyranosyl)thioformamides 4a±6a
and 5b were prepared from the corresponding acylated b-d-
glycopyranosyl cyanides 1a,8,9 2a,8,9 3a,10 and 2b,4 respec-
tively, by hydrogen sul®de addition in a chloroform±
ethanol solvent mixture in the presence of catalytic amounts
of triethylamine 2Scheme 1). Surprisingly, from C-glycosyl
thioformamides with pyranoid rings only 6a and its a-l-
arabino analogue have so far been described in the literature
using essentially the same procedure with 4-dimethylamino-
pyridine as the catalyst in 2-propanol for their preparation.11
The ®rst experiments were aimed at the radical-mediated
bromination12 of 4a. In the presence of a catalytic amount
of AIBN in bromotrichloromethane at re¯ux temperature or
at room temperature with irradiation only decomposition
could be observed. With two equivalents of N-bromo-
succinimide in the presence of catalytic AIBN in carbon
tetrachloride at 608C the main product was shown to be
7a by TLC. The best result was achieved with one equiva-
lent of bromine in chloroform solution at room temperature
to give 7a in 80% yield. However, this procedure was not
safely reproducible, therefore, other oxidants were sought
for. With cerium2IV)ammonium nitrate in aqueous aceto-
nitrile three compounds were isolated: 1a 216%), C-22,3,4,6-
tetra-O-acetyl-b-d-galactopyranosyl)formamide 231%), and
7a 244%). Most ef®cient and convenient was the
It has long been known that two molecules of thioamides
can undergo intermolecular cyclization under oxidative
conditions to give 3,5-disubstituted-1,2,4-thiadiazoles by a
mechanism not well understood as yet.6,7 The reaction
has been considered to be limited mainly to arylthioamides
and characterized by variable yields and formation of
by-products such as nitriles and isothiocyanates.7
Keywords: 1,2,4-thiadiazole; thioamide; bromination; carbohydrates;
oxidation.
p
Corresponding author. Tel.: 136-52-512-900; fax: 136-52-453-836;
e-mail: somsak@tigris.klte.hu
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020201)00444-6

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E. Osz et al. / Tetrahedron 57 /2001) 5429±5434
5430
Scheme 1.
preparation of 7a with the reagent system KBrO3±
Na2S2O4 in dichloromethane±water biphasic solvent, a
mixture similar to the ones proposed recently for benzylic
brominations 2actually NaBrO3±NaHSO3 was used in
EtOAc±H2O)13 as well as for deprotection of benzylated
carbohydrate derivatives 2NaBrO3±Na2S2O4 in EtOAc±
H2O).14 In this way crude 7a was obtained as a chromato-
graphically homogeneous product in 94% yield. The
analogous 8a, 8b, and 9a were isolated in 77, 86, and
62% yields, respectively, after recrystallization of the
even after prolonged reaction time. In re¯uxing methanol 10
was obtained in a concurrent elimination reaction.
The structure of 7a could be established by thorough NMR
investigations. The presence of two series of resonances in
1
the H and 13C spectra indicated an asymmetric dimeric
1
structure. The proton assignment was based on a H±1H
COSY experiment. Using 13C±1H HSQC and 13C±1H
HMBC spectra two carbon atoms 2C-3 and C-5) attached
0
to the anomericcarbons 2C-1 and C-100) could be assigned,
while the 15N±1H HMBC spectrum indicated the presence
of two tertiary nitrogen atoms 2N-2 and N-4) displaying
long-range couplings to the anomeric carbons belonging
to a hetero-bond or ring. Long-range 15C±1H and 15N±1H
HMBC correlations crucial for the structure determination
of 7a are listed in Table 1. These observations are com-
patible with the presence of a 3,5-disubstituted-1,2,4-thia-
Â
crude product. Deprotection was performed by the Zemplen
method to give 7c±9c. Applying the same protocol to 8b at
room temperature left one of the benzoyl groups untouched
Table 1. Long-range 13C±1H and 15N±1H HMBC correlations in 7a
diazole moiety as the bridging element in the dimeric
3
0
0
structure. The high values 29.9 and 9.8 Hz) of the JH-1 ,H-2
and 3JH-1 ,H-2 coupling constants are characteristic for b2d)
con®gurations at both anomeric centres. Single crystal
X-ray structure determination provided further con®rmation
of the structure of compound 7a 2Fig. 1). Each of the
other 1,2,4-thiadiazole derivatives 7±9, either protected or
00
00
13C/15N atom
C-3
C-5
N-2
N-4
1H
1H
H-100
H-200
H-10
H-20
H-100
H-10
H-100
Figure 1. ORTEP drawing of thiadiazole 7a.

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E. Osz et al. / Tetrahedron 57 /2001) 5429±5434
5431
unprotected, had similar characteristics with respect to the
anomeric protons as well as the carbons of the heterocycle
in the 1H and 13C spectra 2see Section 4). In compound 10 a
13C±1H HMBC measurement indicated that the unsaturated
sugar moiety was attached to C-5 and the b-d-gluco-
pyranosyl residue to C-3.
yellowish crystals, yield 84%; mp 134±1358C; [a]Dˆ117
2c 1.29, CHCl3); nmax 2KBr) 3428, 3320, 3218, 2968, 1746,
1632, 1448, 1368, 1220, 1098, 1064 cm21 1H NMR
;
2CDCl3): d 7.75 21H, bs, NH2), 7.60 21H, bs, NH2), 5.50
21H, dd, Jˆ3.3, ,1 Hz, H-4), 5.29 21H, quasi t, Jˆ10.2,
9.6 Hz, H-2), 5.15 21H, dd, Jˆ10.2, 3.3 Hz, H-3), 4.39
21H, d, Jˆ9.6 Hz, H-1), 4.26 21H, dd, Jˆ11.5, 7.1 Hz,
H-6), 4.11 21H, dd, Jˆ11.5, 5.6 Hz, H-60), 4.04 21H, ,td,
Jˆ7.1, 5.6, ,1 Hz, H-5), 2.18, 2.08, 2.07, 1.99 212H, 4s,
200.0 2CSNH2,
Some of the deprotected derivatives were assayed as
inhibitors of glycosidase enzymes and showed moderate
effects with Ki values in the millimolar range 27c:
Escherichia coli b-d-galactosidase 0.3 mM; 9c: Aspergillus
carbonarius b-d-xylosidase 12 mM).
4£OAc); 13C NMR 2CDCl3):
d
3JH-1,CSNH2ˆ2.8 Hz), 170.3, 169.9, 169.8, 169.7 2CvO),
83.0 2C-1), 74.0, 71.2, 67.5, 67.2 2C-2 to C-5), 61.4 2C-6),
20.9, 20.5, 20.4, 20.3 2CH3); 15N NMR 2DMSO-d6): d 151.7
2NH2). Anal. calcd for C15H21NO9S 2391.40): C, 46.03; H,
5.41; N, 3.58; S, 8.19; found: C, 46.40; H, 5.46; N, 3.86; S,
8.42.
3. Conclusion
The described method introduces a new reagent system
for the preparation of 1,2,4-thiadiazoles from thioamides,
and offers an easy access to interesting 3,5-bis-C-glycosyl-
1,2,4-thiadiazoles from readily available per-O-acylated
C-2b-d-glycosyl)thioformamides. Some literature examples
of similar but symmetric dimeric structures can be found
with the d-gluco con®guration having a triazin-2,4,6-trione
as the bridging element.15 Although these compounds
proved moderate inhibitors of glycosidase enzymes,
because of the well known biological activities of 1,2,4-
thiadiazole derivatives6 they may deserve further
attention.
4.1.2. C-ꢀ2,3,4,6-Tetra-O-acetyl-b-d-glucopyranosyl)thio-
formamide 5a. By general procedure I from 2a: pale
yellowish crystals, yield 75%; mp 138±1408C; [a]Dˆ215
2c 0.95, CHCl3); nmax 2KBr) 3376, 3330, 3178, 2950, 1752,
1
1716, 1628, 1430, 1374, 1230, 1210, 1094, 1036 cm21; H
NMR 2CDCl3): d 8.00 21H, bs, NH2), 7.80 21H, bs, NH2),
5.24±5.04 23H, 3£t, H-2,3,4), 4.34 21H, d, Jˆ9.5 Hz, H-1),
4.24 21H, dd, Jˆ12.1, 4.4 Hz, H-6), 4.08 21H, dd, Jˆ12.1,
2.2 Hz, H-60) 3.77 21H, m, H-5), 2.04, 2.00, 1.98, 1.94 212H,
4s, 4£OAc); 13C NMR 2CDCl3): d 199.6 2CSNH2), 170.0,
169.8, 169.4 2CvO), 82.8 2C-1), 75.0, 73.2, 70.0, 67.6 2C-2
to C-5) 61.9 2C-6), 20.9, 20.6, 20.3 2CH3). Anal. calcd for
C15H21NO9S 2391.40): C, 46.03; H, 5.41; N, 3.58; found: C,
46.22; H, 5.29; N, 3.65.
4. Experimental
4.1.3. C-ꢀ2,3,4,6-Tetra-O-benzoyl-b-d-glucopyranosyl)thio-
formamide 5b. By general procedure I from 2b: pale
yellowish crystals, yield 74%; mp 198±2008C; [a]Dˆ218
2c 1.02, CHCl3); nmax 2KBr) 3420, 3331, 3250, 3100, 1732,
Melting points were measured in open capillary tubes or on
a Ko¯er hot-stage and are uncorrected. Optical rotations
were determined with a Perkin-Elmer 241 polarimeter at
room temperature. NMR spectra were recorded with Bruker
WP 200 SY 2200/50 MHz for 1H/13C) or Avance DRX 500
1
1602, 1316, 1268, 1178, 1094, 1068, 708 cm21; H NMR
1
2500/125/50 MHz for H/13C/15N) spectrometers. Chemical
2CDCl3) d 8.1±7.8 210H, m, aromatic1NH2), 7.6±7.2 212H,
m, aromatic), 5.97 21H, t, Jˆ9.5, 9.5 Hz), 5.72 21H, t,
Jˆ9.5, ,10 Hz), 5.62 21H, t, Jˆ9.5, 9.5 Hz) 2H-2 to H-4),
4.74 21H, d, Jˆ9.5 Hz, H-1), 4.69 21H, dd, Jˆ12.6, 2.6 Hz,
H-6), 4.55 21H, dd, Jˆ12.6, 5.3 Hz, H-60), 4.24 21H, dd,
Jˆ9.5, 5.3, 2.6 Hz, H-5); 13C NMR 2CDCl3): d 190.6
2CSNH2), 166.3, 165.5, 165.4, 165.1 2CvO), 133±128
2aromaticsignals), 82.72C-1), 75.9, 73.4, 71.2, 69.0 2C-2
to C-5), 62.8 2C-6). Anal. calcd for C35H29NO9S 2639.67):
C, 65.72; H, 4.54; N, 2.19; found: C, 65.44; H, 4.46; N,
2.41.
shifts are referenced to Me4Si 21H), to the residual solvent
signals 213C) or to NH4Cl as external standard 215N). TLC
was performed on DC-Alurolle Kieselgel 60 F254 2Merck),
and the plates were visualised by gentle heating. For column
chromatography Kieselgel 60 2Merck, particle size 0.063±
0.200 mm) was used. Organicsolutions were dried over
anhydrous MgSO4 and concentrated in vacuo at 40±508C
2water bath).
4.1. General procedure I: preparation of per-O-acylated
C-ꢀb-d-glycopyranosyl)thioformamides 4a±6a, and 5b
4.1.4. C-ꢀ2,3,4-Tri-O-acetyl-b-d-xylopyranosyl)thioform-
amide 6a. By general procedure I from 3a: pale yellowish
crystals, yield 55%; mp 179±1818C 2lit.11 mp 179±1818C).
A glycopyranosyl cyanide 21a±3a, or 2b, 2.8 mmol) was
dissolved in chloroform 210 ml) and ethanol 25 ml) was
added. Dry hydrogen sul®de was bubbled through the
reaction mixture at room temperature for 45±50 min to
saturation. Triethylamine 20.1 ml, 0.78 mmol) was then
added and the introduction of hydrogen sul®de continued
for another 3±3.5 h 2until no more starting material could be
detected by TLC, eluent ethyl acetate±hexane 1:1). The
reaction mixture was evaporated under reduced pressure
and the residue crystallised from ethanol.
4.2. General procedure II: preparation of per-O-
acylated 3,5-bis-ꢀb-d-glycopyranosyl)-1,2,4-thiadiazoles
7a±9a and 8b
A per-O-acylated C-2b-d-glycopyranosyl)thioformamide
24a±6a, or 5b, 0.5 mmol) was dissolved in dichloromethane
212 ml), a solution of KBrO3 20.42 g, 2.5 mmol) in water
26 ml) was added and the two phase mixture was vigorously
stirred. A solution of Na2S2O4 20.49 g, 2.8 mmol) in water
26 ml) was added dropwise during ,10 min and stirring
4.1.1. C-ꢀ2,3,4,6-Tetra-O-acetyl-b-d-galactopyranosyl)-
thioformamide 4a. By general procedure I from 1a: pale

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E. Osz et al. / Tetrahedron 57 /2001) 5429±5434
5432
continued until disappearance of the starting material 2TLC,
eluent ethyl acetate±hexane 1:1, ,0.5 h). Dichloromethane
230 ml) was then added, and the organicphase washed with
5% aq. Na2S2O3 220 ml), and water 220 ml), dried, and the
solvent evaporated. The syrupy crude product was crystal-
lized from 96% EtOH.
5b: white crystals, yield 86%; mp 280±2828C; [a]Dˆ210
2c 0.98, CHCl3); nmax 2KBr) 3066, 2954, 2884, 1740, 1602,
1584, 1492, 1452, 1316, 1264, 1178, 1108, 1094, 708 cm21
;
1H NMR 2CDCl3): d 8.1±7.1 240H, m, aromatic), 6.06±5.33
26H, 6£t, H-20 to H-40 and H-200 to H-400), 5.24 21H, d,
Jˆ9.5 Hz, H-10), 4.95 21H, d, Jˆ9.5 Hz, H-100), 4.72 21H,
dd, Jˆ12.6, 2.6 Hz, H-6a0 or H-6a00), 4.53 21H, dd, Jˆ12.6,
4.7 Hz, H-6b0 or H-6b00), 4.42 21H, dd, Jˆ12.6, 2.6 Hz.
H-6a0 or H-6a00), 4.40±4.28 22H, m, H-50 or H-500
and H-6b0 or H-6b00), 4.13 21H, ddd, Jˆ9.5, 4.7, 2.6 Hz,
H-50 or H-500); 13C NMR 2CDCl3): d 188.4 2C-5), 170.5
2C-3), 166.1, 166.0, 165.7, 165.1, 165.0, 164.8, 164.2
2CvO), 134±128 2aromaticsignals), 77.0 2C-1 0), 76.9
2C-100), 76.8, 76.4, 74.5, 73.5, 71.9, 71.4, 69.6, 69.2
2C-20 to C-50 and C-200 to C-500), 63.9, 62.7 2C-60, C-600);
Anal. calcd for C70H54N2O18S 21242.56): C, 67.63; H,
4.35; N, 2.25; S, 2.57; found: C, 67.09; H, 4.36; N, 2.35;
S, 2.56.
4.2.1. 3,5-Bis-ꢀ2,3,4,6-tetra-O-acetyl-b-d-galactopyrano-
syl)-1,2,4-thiadiazole 7a. To a solution of 4a 20.1 g,
,0.26 mmol) in chloroform 26 ml) bromine 20.13 ml,
,0.26 mmol) was added with stirring at room temperature.
The reaction mixture was then immediately evaporated
under reduced pressure, and the yellowish residue crystal-
lised from ethanol to yield crude 7a. Recrystallisation from
hot ethanol gave the title compound 7a 20.077 g, 80%) as
white crystals; mp 203±2048C; [a]Dˆ123 2c 2.10, CHCl3);
n
max 2KBr) 2976, 1756, 1434, 1370, 1234, 1116, 1054 cm21
;
1H NMR 2C6D6): d 6.09 21H, quasi t, Jˆ10.2, 9.9 Hz, H-20),
5.79 21H, quasi t, Jˆ10.2, 10.0 Hz, H-200), 5.66 21H, d,
Jˆ3.3, ,1 Hz, H-40), 5.60 21H, d, Jˆ3.3, ,1 Hz, H-400),
5.42 21H, dd, Jˆ10.2, 3.3 Hz, H-30), 5.34 21H, dd, Jˆ10.2,
3.3 Hz, H-300), 4.90 21H, d, Jˆ10.2 Hz, H-10), 4.61 21H, d,
Jˆ10.2 Hz, H-100), 4.26 22H, strongly coupled AB spin-
system, Jˆ6.5 Hz, H-6a0,6b0), 4.15 22H, strongly coupled
AB spinsystem, Jˆ6.5 Hz, H-6a00,6b00), 3.59 21H, quasi t,
Jˆ6.5, ,1 Hz, H-50), 3.40 21H, quasi t, Jˆ6.5, ,1 Hz,
H-500); in C6D6±CDCl3ˆ1:1 solvent mixture the signals of
the H-6a,6b0 and H-6a,6b00 protons are distinguished: d 4.17
21H, dd, Jˆ11.4, 6.5 Hz, H-6a0), 4.11 21H, dd, Jˆ11.4,
6.5 Hz, H-6b0), 4.09 21H, dd, Jˆ11.4, 6.7 Hz, H-6a00),
4.06 21H, dd, Jˆ11.4, 6.2 Hz, H-6b00), 2.12, 1.76, 1.73,
1.67, 1.62, 1.61, 1.60, 1.56 224H, 8s, 8£CH3); 13C NMR
2C6D6): d 189.9 2C-5), 171.8 2C-3), 170.5, 170.3, 170.1,
170.0, 169.9, 169.7, 169.1 2CvO), 77.7 2C-10), 77.4
2C-100), 75.5 2C-50), 75.5 2C-500), 72.9 2C-30), 72.2 2C-300),
69.3 2C-20), 69.2 2C-200), 68.4 2C-40), 67.8 2C-400), 62.1
4.2.4. 3,5-Bis-ꢀ2,3,4-tri-O-acetyl-b-d-xylopyranosyl)-1,2,
4-thiadiazole 9a. By general procedure II from 6a: white
crystals, yield 62%; mp 198±1998C; [a]Dˆ253 2c 0.50
CHCl3); nmax 2KBr) 2940, 2860, 1752, 1628, 1430, 1374,
1
1226, 1112, 1088, 1058, 1036 cm21; H NMR 2CDCl3): d
5.42±4.98 26H, m, H-20, H-200, H-3, H-300, H-5a, H-5a00),
4.77 21H, d, Jˆ9.5 Hz, H-10), 4.67 21H, d, Jˆ9.5 Hz,
H-100), 4.25 22H, m, H-40, H-400) 3.56±3.40 22H, m, H-5b0
or H-5b00), 2.03, 2.01, 1.97, 1.82 218H, 4s, 6£OAc); 13C
NMR 2CDCl3): d 189.0 2C-5), 170.5, 170.1, 169.9, 169.6,
169.2, 168.8 2CvO), 168.6 2C-3), 76.7 2C-10, C-100), 73.0,
72.5, 71.0, 70.8, 68.6, 68.5 2C-20 to C-40 and C-200 to
C-400), 66.9, 66.8, 2C-50,C-500), 20.5, 20.4, 20.2 2CH3);
Anal. calcd for C24H30N2O14S 2616.56): C, 46.75; H,
4.90; N, 4.54; S, 5.20; found: C, 46.13; H, 4.98; N, 4.45;
S, 5.11.
0
00
2CH2 ), 61.5 2CH2 ), 21.1, 20.7, 20.5, 20.48, 20.42, 20.3,
20.1 2CH3); 15N NMR 2DMSO-d6): d 274.6 2N-4), 240.9
2N-2). Anal. calcd for C30H38N2O18S 2746.70): C, 48.26;
H, 5.13; N, 3.75; S, 4.29; found: C, 47.75; H, 5.15; N,
3.81; S, 4.52.By general procedure II from 4a: yield 94%,
mp 197±1988C, recrystallization from EtOH with 85%
recovery; mp 203±2048C.
4.3. General procedure III: preparation of the
deprotected 3,5-bis-ꢀb-d-glycopyranosyl)-1,2,4-thia-
diazoles 7c±9c
A per-O-acylated 3,5-bis-2b-d-glycopyranosyl)-1,2,4-thia-
diazole 27a±9a or 8b, 0.16 mmol) was dissolved in a
mixture of chloroform 220 ml) and methanol 210 ml), and
20 drops of a 1 M solution of NaOMe in MeOH were added.
The solution was kept at room temperature for deacetyl-
ations or re¯uxed for debenzoylation until completion of
the transformation 2TLC, eluent chloroform±methanol
2:1). Then the solution was treated with Amberlyst 15
2H1 form) ®ltered and the solvent evaporated. The syrupy
residue was puri®ed by column chromatography with
chloroform±methanol 2:1 if necessary.
4.2.2. 3,5-Bis-ꢀ2,3,4,6-tetra-O-acetyl-b-d-glucopyrano-
syl)-1,2,4-thiadiazole 8a. By general procedure II from
5a: white crystals, yield 77%; mp 189±1918C; [a]Dˆ23
2c 1.04, CHCl3); nmax 2KBr) 2948, 1752, 1434, 1370,
1
1226, 1104, 1036 cm21; H NMR 2CDCl3): d 5.40±5.06
26H, m, H-20 to H-40 and H-200 to H-400), 4.88 21H, d,
Jˆ9.5 Hz, H-10), 4.76 21H, d, Jˆ9.5 Hz, H-100), 4.32±4.02
24H, H-6a0, H-6b0, H-6a00, H-6b00), 3.84 22H, m, H-50, H-500),
2.12, 2.05, 2.04, 2.00, 1.95, 1.80 224H, 6s, 8£OAc); 13C
NMR 2CDCl3): d 188.7 2C-5), 170.4, 170.3, 170.2, 170.1,
169.9, 169.3, 168.8, 168,7 2CvO), 169.3 2C-3), 76.8 2C-10),
76.5 2C-100), 76.3, 76.2, 73.9, 73.2, 70.9 two carbons, 68.0,
67.9 2C-20 to C-50 and C-200 to C-500), 62.1, 61.7 2C-60,
C-600), 20.5, 20.4, 20.1 2CH3); Anal. calcd for
C30H38N2O18S 2746.69): C, 48.25; H, 5.09; N, 3.75; S,
4.28; found: C, 48.42; H, 4.98; N, 3.77; S, 4.30.
4.3.1. 3,5-Bis-ꢀb-d-galactopyranosyl)-1,2,4-thiadiazole
7c. By general procedure III from 7a: white crystals,
1
yield 95%; mp 150±1528C; [a]Dˆ153 2c 1.1, MeOH); H
NMR 2CD3OD): d 4.64 21H, d, Jˆ9.6 Hz, H-10), 4.46 21H,
d, Jˆ9.6 Hz, H-100), 4.16 21H, t, Jˆ9.6, 9.5 Hz, H-20 or
H-200), 3.93 22H, t, Jˆ3.20 Hz, H-30, H-300), 3.86-3.55
29H, m, H-20, H-40, H-400,H-50, H-500, H-6a0, H-6a00, H-6b0,
H-6b00); 13C NMR 2CD3OD): d 192.3 2C-5), 173.6 2C-3),
81.4 2C-10), 81.3 2C-100), 80.0, 79.7, 75.9, 75.6, 72.4,
71.5,70.9, 70.5 2C-20 to C-50 and C-200 to C-500), 62.8, 62.7
2C-60, C-600); Anal. calcd for C14H22N2O10S 2410.34):
4.2.3. 3,5-Bis-ꢀ2,3,4,6-tetra-O-benzoyl-b-d-glucopyrano-
syl)-1,2,4-thiadiazole 8b. By general procedure II from

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E. Osz et al. / Tetrahedron 57 /2001) 5429±5434
5433
C, 40.97; H, 5.36; N, 6.83; found: C, 40.51; H, 5.46; N,
6.91.
61.8 2C-60, C-600); Anal. calcd for C14H20N2O9S 2392.38):
C, 42.85; H, 5.14; N 7.14; found: C, 42.92; H, 5.34; N
7.22.
4.3.2. 3,5-Bis-ꢀb-d-glucopyranosyl)-1,2,4-thiadiazole 8c.
By general procedure III from 8a: yield 46%, colourless
syrup; 2Rfˆ0.24, chloroform±methanol 1:1); [a]Dˆ123
2c 0.95, MeOH); 1H NMR 2CD3OD): d 4.72 21H, d,
Jˆ9.4 Hz, H-10), 4.57 21H, d, Jˆ9.4 Hz, H-100), 3.92 21H,
dd, Jˆ12.1 Hz, H-6a0 or H-6a00), 3.90±3.82 22H, m, H-6a0 or
H-6a00, H-20or H-200), 3.76±3.65 22H, m, H-20 or H-200, H-30
or H-300, 3.56±3.44 25H, m, H-30 or H-300, H-40, H-400, H-50,
H-500), 3.40 22H, m, H-6b0, H-6b00); 13C NMR 2CD3OD): d
191.9 2C-5), 173.6 2C-3), 82.7 2C-10), 82.6 2C-100), 79.6,
79.3, 79.2, 79.1, 75.4, 74.2, 71.5, 71.3 2C-20 to C-50 and
C-200 to C-500), 63.0, 62.9 2C-60, C-600); Anal. calcd for
C14H22N2O10S 2410.39): C, 40.97; H, 5.36; N, 6.83; found:
C, 40.47; H, 5.45; N, 6.75.
²
4.6. X-Ray crystallography of 7a
Colourless prism crystals 20.44£0.3£0.23 mm) of
C30H38N2O18S, grown from ethanol Mˆ746.68, orthorhom-
Ê
Ê
Ê
bic, aˆ8,91221) A, bˆ8,90521) A, cˆ46,30821) A, Vˆ
Ê 3
3675,126) A , Zˆ4, space group: P212121, rcalc
ˆ
1.35 g cm23. Data were collected at 29321) K, Enraf
Nonius MACH3 diffractometer, Mo Ka radiation
Ê
lˆ0.71073 A, v ±2u motion, umaxˆ25.478, 3052 re¯ec-
tions of which 1531 were unique with I.2s2I), decay:
1%. The structure was solved using the sir-92 software16
and re®ned on F17 using shelx-9717 program, publication
material was prepared with the wingx-97 suite,18
R2F)ˆ0.10 and wR2F2)ˆ0.31 for 3052 re¯ections, 461
parameters.
4.3.3. 3,5-Bis-ꢀb-d-xylopyranosyl)-1,2,4-thiadiazole 9c.
By general procedure III from 9a: colourless syrup, yield
46%; 2Rfˆ0.24, chloroform±methanol 2:1); [a]Dˆ24 2c
1.0, MeOH); 1H NMR 2CD3OD): d 4.67 21H, d,
Jˆ9.5 Hz, H-10), 4.50 21H, d, Jˆ9.5 Hz, H-100), 4.08 21H,
dd, Jˆ11.1, 5.3 Hz, H-5a0 or H-5a00), 3.99 21H, dd, Jˆ11.1,
5.3 Hz, H-5a0 or H-5a00), 3.93 21H, t, Jˆ9.5, 9.5 Hz), 3.70±
3.62 22H, m, H-40, H-400), 3.54±3.32 25H, m); 13C NMR
2CD3OD): d 192.3 2C-5), 174.0 2C-3), 80.3 2C-10), 80.1
2C-100), 79.4, 79.0, 75.7, 74.4, 71.2, 70.7 2C-20 to C-40 and
C-200 to C-400), 71.6, 71.5 2C-50, C-500); Anal. calcd for
C12H18N2O8S 2350.34): C, 41.14; H, 5.14; N, 8.00; found:
C, 41.31; H, 5.03; N, 8.12.
Acknowledgements
This work was supported by the Hungarian Scienti®c
Research Fund 2Grants: OTKA T23814, T32124, D25136)
and the Ministry of Education 2Grant: FKFP 423/2000).
 Â
Professor Laszlo Kiss is thanked for the enzyme assays.
References
Í
1. Osz, E.; Sos, E.; Somsak, L.; Szilagyi, L.; Dinya, Z.
Â
Â
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4.4. C-ꢀb-d-Galactopyranosyl)thioformamide 4c
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Í
2. Osz, E.; Somsak, L.; Szilagyi, L.; Kovacs, L.; Docsa, T.; Toth,
Â
Â
Â
Â
Compound 4a 20.1 g, 2.55 mmol) was dissolved in MeOH
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overnight at 35±408C. After solvent removal the residue
was puri®ed by column chromatography 2chloroform±
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21H, dd, Jˆ3.2, ,1 Hz, H-4), 3.83 21H, dd, Jˆ11.6, 7.4 Hz,
H-6), 3.72±3.63 23H, m,H-2,5,60), 3.66 21H, dd, Jˆ9.2,
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1
0.8, MeOH); H NMR 2CD3OD): d 6.10 21H, t, Jˆ2.6,
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2.1 Hz, H-5a0 or H-5a00), 4.04±3.68 26H, m, H-200, H-300,
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23H, m, H-50or H-500, H-6a0 or H-6a00, H-6b0 or H-6b00);
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2C-10), 107.6 2C-20), 82.4 2C-100), 82.2, 79.5, 79.3, 74.5,
71.3, 70.1, 70.0 2C-30 to C-50 and C-200 to C-500), 62.6,
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²
Crystallographicdata have been deposited at the Cambridge Crystallo-
graphicData Centre, 12 Union Road, Cambridge CB2 1EZ, UK and
copies can be obtained on request, free of charge, by quoting the publica-
tion citation and the deposition number 156556.

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E. Osz et al. / Tetrahedron 57 /2001) 5429±5434
5434
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