Assessment of synthetic methods for the preparation of N-β-d-glucopyranosyl-N′-substituted ureas, -thioureas and related compounds

Article abstract of DOI:10.1016/j.carres.2008.01.045

Preparation of O-peracetylated N-β-d-glucopyranosyl-N′-acyl urea derivatives resulted in the formation of anomeric mixtures under the following conditions: acylation of O-peracetylated β-d-glucopyranosyl urea by acyl chlorides in the presence of ZnCl₂ in refluxing CHCl₃; addition of O-peracetylated β-d-glucopyranosylamine to acyl isocyanates in acetonitrile at rt; addition of carboxamides to in situ prepared O-peracetylated β-d-glucopyranosyl isocyanate in refluxing toluene. Deprotection of O-peracetylated N-β-d-glucopyranosyl-N′-acyl ureas either under base (NaOMe in MeOH at or below rt) or under acid (KHSO₄ or AcCl in MeOH at rt) catalyzed transesterification conditions resulted in unavoidable partial cleavage of the N′-acyl moieties. Reaction of β-d-glucopyranosylammonium carbamate with an isocyanate, isothiocyanate or isoselenocyanate in dry pyridine at rt appears as a general method for the preparation of the corresponding β-d-glucopyranosyl ureas, -thio- and -selenoureas, respectively, inclusive N′-acyl derivatives.

Full text of DOI:10.1016/j.carres.2008.01.045

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 2083–2093
Assessment of synthetic methods for the preparation
of N-b-D-glucopyranosyl-N0-substituted ureas, -thioureas
and related compounds
*
´
´
´
´
´
´
´
Laszlo Somsak, Nora Felfoldi, Balint Konya, Csaba Huse, Katalin Telepo,
¨
¨
´
´
Eva Bokor and Katalin Czifrak
Department of Organic Chemistry, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary
Received 21 September 2007; received in revised form 24 January 2008; accepted 29 January 2008
Available online 7 February 2008
Presented at Eurocarb 14th Lubeck, Germany, September 2007
¨
Abstract—Preparation of O-peracetylated N-b-D-glucopyranosyl-N0-acyl urea derivatives resulted in the formation of anomeric
mixtures under the following conditions: acylation of O-peracetylated b-D-glucopyranosyl urea by acyl chlorides in the presence
of ZnCl2 in refluxing CHCl3; addition of O-peracetylated b-D-glucopyranosylamine to acyl isocyanates in acetonitrile at rt; addition
of carboxamides to in situ prepared O-peracetylated b-D-glucopyranosyl isocyanate in refluxing toluene. Deprotection of O-per-
acetylated N-b-D-glucopyranosyl-N0-acyl ureas either under base (NaOMe in MeOH at or below rt) or under acid (KHSO4 or AcCl
in MeOH at rt) catalyzed transesterification conditions resulted in unavoidable partial cleavage of the N0-acyl moieties. Reaction of
b-D-glucopyranosylammonium carbamate with an isocyanate, isothiocyanate or isoselenocyanate in dry pyridine at rt appears as a
general method for the preparation of the corresponding b-D-glucopyranosyl ureas, -thio- and -selenoureas, respectively, inclusive
N0-acyl derivatives.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Glucosylurea; Acyl urea; Thiourea; Selenourea
1. Introduction
of a large aromatic group (R = 2-naphthyl) rendered
these inhibitors into the nanomolar range. In this paper,
we summarize our experience in the preparation of N-b-
D-glucopyranosyl-N0-acyl urea derivatives, and propose
a simple way for the synthesis of N-b-D-glucopyran-
osyl-N0-substituted ureas II and III as well as some
thio and seleno analogues, which were needed to
establish structure–activity relationships. The enzymatic
and structural studies will be published elsewhere.7,8
Inhibition of human liver glycogen phosphorylase is
under extensive study with the hope to provide a poten-
tial new therapy for type 2 diabetes mellitus. The most
populated class of inhibitors comprises glucose deriva-
tives1,2 most of which bind at the catalytic site as
evidenced by X-ray crystallography.3
The first potent glucose analogue inhibitors of rabbit
muscle glycogen phosphorylase b (RMGPb) were some
N-acyl-b-D-glucopyranosylamines I (Chart 1). Later,
it was demo- nstrated that the elongation of the aglycon6
especially with another NHCO moiety as in N-b-D-glu-
copyranosyl-N0-acyl ureas III together with the presence
2. Results and discussion
The first acyl ureas III (R = Me, Ph) tested as inhibitors
of GP were those for which the O-peracetylated deriva-
tives were known in the literature.9 For the preparation
of other derivatives, acylation of urea 110 by ZnCl2
*
Corresponding author. Tel.: +36 52 512 900; fax: + 36 52 453 836;
e-mail: somsak@tigris.unideb.hu
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.01.045

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L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
acyl isocyanates (Route c) obtained from acyl chlorides
Ki [μM]
324
R
with NaOCN catalyzed by SnCl4.11 In these reactions,
too, anomerization was observed in several cases
(although, we speculate, probably to a lesser extent as
revealed by the higher isolated yields for the b-anomers;
compare Routes a and c for 3h and 3i). Reactions of the
prepared glucopyranosyl isocyanate12 6 with carboxam-
ides (Route d) also gave anomeric mixtures from which
the b-anomers of 3h and 3i could be isolated in satisfac-
tory yields together with some a-3h and a-3i. At first
sight, these anomerizations were surprising since N-acyl-
ated glycosylamines and similar derivatives were consid-
ered to be configurationally stable (precisely, more
stable than glycosylamines).13 However, it was pointed
out that glycosyl ureas underwent both acid- and base-
catalyzed anomerization.14 Loss of anomeric configura-
tional integrity was also reported for an O-perbenzylat-
ed glucosyl urea under slightly acidic conditions,15 and
HO
HO
Me
Ph
O
H
N
R
HO
I
OH
814
O
O
HO
HO
O
H
N
H
N
HO
II
R
O
OH
3055
HO
HO
Me
Ph
O
H
N
H
N
R
HO
III
OH
4.65
O
0.351
2-Naphthyl
Chart 1. Some representative inhibitors of rabbit muscle glycogen
phosphorylase.4,5
´
for glucosyl thioureas under slightly basic Zemplen
deacetylation conditions.16 Anomerizations of glycosyl
ureas and -carbamates were also observed during forma-
tion of glycosyl isocyanates to be reacted with amines.17
In the light of these literature reports, our observations
may be unravelled. The Lewis acidic ZnCl2 may not
only activate acid chlorides but can also catalyze imini-
um ion formation13,18 and, thereby, anomerization in
the reactions of 1. During the addition of 5 to acyl
isocyanates, the glucosylamine itself may anomerize,
but even traces of it may act as basic catalysts for the
anomerization of the formed ureas. The most difficult
is to understand the reaction of 6 with carboxamides be-
cause the latter are probably neither acidic nor basic en-
ough to elicit anomerization; since 6 was not purified
but used as the crude product of the transformation of
5, some unreacted glucosylamine might have remained
in the mixture to act as a basic catalyst for the
anomerization.
catalyzed reaction of the corresponding acyl chlorides to
give 3 was investigated first7,8 (Scheme 1, Table 1, Route
a). In most of these reactions formation of an anomeric
mixture was observed, the separation of which by silica
gel column chromatography allowed only the b-anomers
to be isolated in low yields because of the very similar
mobilities of the isomers. From a larger scale prepara-
tion of the 2-naphthoyl urea, it was possible to isolate
a small amount of the a-anomer a-3m, which was unam-
bigously characterized by MS and NMR methods (see
Section 3). To avoid the formation of the undesired
by-product, glucopyranosylamine 5 was reacted with
RO
O
H
RO
1 R = Ac
2 R = H
N
NH2
RO
OR
Deprotection of compound 3 was complicated by the
propensity of the acyl urea moiety towards splitting off
O
the acyl part.7,8 Thus, deacetylation under Zemplen con-
´
a
ditions at or below room temperature in most cases gave
4 together with 2 within 0.5–1 h. Acid catalyzed transe-
sterification either by using KHSO4 or by using a cata-
lytic amount of AcCl in MeOH slowed down the
reaction to 5–12 days, and thus it became easier to
follow the transformation by TLC and to detect the
optimal time to get the highest yield for 4. However,
even in these reactions, the formation of 2 was to be
observed.
Because of the above difficulties, we sought for a
more simple and direct way of preparation of the target
N-(b-D-glucopyranosyl)-N0-acyl ureas 4. The choice of
reacting glucopyranosylamines with acyl isocyanates
seemed straightforward, since the feasibility of analo-
gous reactions with iso(thio)cyanates had been demon-
strated.19,20 However, glycosylamines13 are available
RO
RO
3 R = Ac
O
H
H
N
RO
b
N
R'
d
OR
4 R = H +
2
O
O
c
AcO
AcO
AcO
AcO
AcO
AcO
O
O
e
NH2
NCO
OAc
OAc
6
5
Scheme 1. Reagents and conditions: (a) R0–COCl, ZnCl2, CHCl3,
reflux; (b) deprotection, see text; (c) R0–CONCO, CH3CN, Ar, rt; (d)
R0–CONH2, PhCH3, reflux; (e) (Cl3CO)2CO, NaHCO3, CH2Cl2,
water, rt.

L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
2085
Table 1. Preparation of N-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-N0-acyl ureas 3 by methods indicated in Scheme 17,8
R0 in 3
Route a
Isolated
Route c
Route d
Isolated
Observed
Observed
Isolated
Observed
a
b
c
d
e
f
c-C6H11
b
ab
40% b
60% b
4-NO2–C6H4
4-Cl–C6H4
3-Cl–C6H4
4-AcO–C6H4
4-Ph–C6H4
4-Me–C6H4
4-tBu–C6H4
4-CF3–C6H4
PhCH2
b
b
b
ab
65% b
67% b
90% b
20% b
b
72% b
43% b
34% b
36% b
Failed
57% b
14% b
73% b
32% b 1% a
41% b
47% b
ab
ab
ab
ab
b
ab
b
ab
b
g
h
i
ab
ab
40% b
40% b
ab
ab
51% b 10% a
69% b 9% a
j
k
l
Ph2CH
1-Naphthyl
2-Naphthyl
2-Indolyl
m
n
o
2-Pyridyl
ab
by rather lengthy and laborious methods involving, for
example, several days or even weeks reaction time, the
need for large amounts of reagents, evaporating large
volumes of water, using ion exchange and lyophiliza-
tion.18,21,22 On the other hand, these compounds can
be obtained by a recent new method23–25 in which the
monosaccharide is reacted with ammonium carbamate
in methanol, and the glycosylammonium carbamate
crystals can be isolated by a simple filtration after 1
day. Thus, b-D-glucopyranosylammonium carbamate
(8) was obtained from D-glucose (7) in 91% yield
(Scheme 2) and the salt could be stored in a refrigerator
for at least one month.
Although the liberation of the free glucopyranosyl-
amine from the carbamate salt was feasible,23 the more
simple direct use of the salt was envisaged (N-bromo-
acetylation of the salt was reported26). To this end, the
reaction of 8 with phenyl isocyanate was investigated
in several solvents such as MeOH, acetone, MeOH–
Py, acetone–Py and MeOH–Et3N at rt but satisfactory
conversion was to be observed only in dry pyridine.
Therefore, reactions of 8 with a series of cyanates and
thiocyanates were performed in pyridine at rt to give 9
and 10, respectively (Table 2). For these reactions, the
acyl isocyanates were obtained by oxalyl chloride from
the corresponding carboxamides.27 It has to be noted
that the conversions were not complete even after rather
long (1 week) reaction times. The yields refer to the
amount of the starting carbamate salt 8 without taking
into account the incomplete conversion because recov-
ery of 8 was not reasonable. Thus, the real yields must
be higher than those given in Table 2. Some thioureas
(10a,b,f,i,k) were obtained by the reaction of acetylated
glucopyranosylamine 12 with the corresponding isothio-
cyanates to give 13a,b,f,i,k, which were deprotected by
´
the Zemplen protocol to give the corresponding com-
pounds 10.
Carbamate salt 8 was also reacted with phenyl iso-
selenocyanate to give selenourea 1128 in 65% yield (again
without taking into account the incomplete conversion
of 8) exhibiting spectral data identical with the reported
ones.
HO
HO
HO
HO
HO
HO
HO
H
H
O
O
O
a
b
d
HO
NH2
.
HO2CNH2
N
N
HO
OH
R
OH
OH
OH
X
7
5
8 (91%)
9 X = O
10 X = S
11 X = Se, R = Ph
(65%)
AcO
AcO
AcO
AcO
AcO
AcO
H
H
N
R
c
O
O
NH2
N
OAc
OAc
S
12a(68%)
b (57%)
f (79%)
i (80%)
k (92%)
for yields and/or R of 9, 10, and 12
see Table 2
Scheme 2. Reagents and conditions: (a) NH4O2CNH2 (4 equiv), abs MeOH, 37 °C, 1 day; (b) R–NCX, abs pyridine, rt; (c) R–NCS, CH2Cl2, rt;
(d) NaOMe, MeOH, rt.

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L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
Table 2. N-(b-D-glucopyranosyl)-N0-substituted ureas 9 and -thioureas 10 prepared from carbamate salt 8
R
9
10
Reaction time (day)
Yield (%)
Reaction time (day)
Yield (%)
a
b
C6H5
2-Cl–C6H4
3
1
60
53
86 from 12
64 from 8
20 from 12
5
c
d
e
f
3-Cl–C6H4
4-Cl–C6H4
2-F–C6H4
4-F–C6H4
3
1
1
42
54
76
20 from 8
97 from 12
g
h
i
4-Br–C6H4
2
1
2
3
70
76
63
46
4-NO2–C6H4
4-MeO–C6H4
3-CF3–C6H4
4-CF3–C6H4
3-CN–C6H4
8
44 from 12
98 from 12
j
k
l
3
3
3
3
5
45
45
42
60
19
m
n
o
p
C10H7 (1-naphthyl)
C10H7 (2-naphthyl)
C
10H7CO (2-naphthyl)a
4-tBu–C6H4COb
a 9o corresponds to 4 (R = C10H7, 2-naphthyl).
b 9p corresponds to 4 (R = 4-tBu–C6H4).
In conclusion, the easy availability of glucopyranosyl-
ammonium carbamate allowed the preparation of N-(b-
D-glucopyranosyl)-N0-substituted ureas, -thioureas and
a selenourea in two steps from D-glucose. Thus, the syn-
thesis of the highly efficient glycogen phosphorylase
inhibitors N-(b-D-glucopyranosyl)-N0-acyl ureas has
been significantly improved facilitating further struc-
ture–activity studies.
3.2. General procedure I for the preparation of N-b-D-
glucopyranosyl-N0-aryl or acyl ureas 9 and -thioureas 10
Carbamate salt 8 was dissolved in dry pyridine (10 mg/
˚
2 mL) containing molecular sieves (3 A), then 1–2 equiv
of the corresponding isocyanate, isothiocyanate or acyl
isocyanate was added in one portion. The reaction mix-
ture was stirred at rt and monitored by TLC (7:3 or 1:1
CHCl3–MeOH). When TLC showed no more change
(conversions were incomplete), the solvent was evapo-
rated. The obtained crude mixture was purified by
column chromatography.
3. Experimental
3.1. General methods
3.3. General procedure II for the preparation of
N-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-N0-aryl
thioureas 12
Melting points were measured in open capillary tubes
or on a Kofler hot-stage and are uncorrected. Optical
rotations were determined with a Perkin–Elmer 241
polarimeter at room temperature. NMR spectra were
recorded with BRUKER 360 (360/90 MHz for
1H/13C) or Avance DRX 500 (500/125 MHz for
1H/13C) spectrometers. Chemical shifts are referenced
to Me4Si (1H), or to the residual solvent signals
(13C). TLC was performed on DC-Alurolle Kieselgel
60 F254 (Merck), and the plates were visualized under
UV light and by gentle heating. For column chromato-
graphy, Kieselgel 60 (Merck, particle size 0.063–
0.200 mm) was used. Organic solutions were dried over
anhydrous MgSO4 and concentrated under diminished
pressure at 40–50 °C (water bath). Aryl isocyanates and
-isothiocyanates were purchased from Aldrich or pre-
pared from the corresponding amines,12 acyl isocya-
nates27 and phenyl isoselenocyanate28 obtained by the
literature methods.
2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosylamine29 (5)
was dissolved and stirred in dry CH2Cl2 (1 g/20 mL)
˚
containing molecular sieves (3 A). After 20 min, 1–
1.5 equiv aryl isothiocyanate was added. The mixture
was stirred at rt for 1–10 days (TLC, 1:1 EtOAc–
hexane). After completion of the reaction, the mixture
was filtered over a Celite pad and the solvent evapo-
rated. The residue was purified by crystallization or
column chromatography.
´
3.4. General procedure III for the Zemplen-deacetylation
To a soln of an O-acetyl protected compound in dry
MeOH (0.10 g/5 mL), 1–2 drops of a ꢀ1 M methanolic
NaOMe soln were added, and the reaction mixture was
kept at rt until completion of the transformation (TLC,

L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
2087
1:1 or 7:3 CHCl3–MeOH). Amberlyst 15 (H+ form) was
then added to remove sodium ions, the resin was filtered
off and the solvent removed. If the residue was chro-
matographically not uniform, it was purified by column
chromatography or crystallization.
Section 3.4.1. Reaction time 5 h. Column chromato-
graphic purification (1:5 EtOAc–hexane) gave as the
first fraction 222 mg (69%) of N-(2,3,4,6-tetra-O-
acetyl-b-D-glucopyranosyl)-N0-(4-trifluoromethyl-benz-
oyl)urea (3i) as a white powder. Mp: 109–112 °C; [a]D
1
ꢁ37 (c 1.46, CHCl3); H NMR (CDCl3, 360 MHz): d
3.4.1. N-(2,3,4,6-Tetra-O-acetyl-b- and a-D-glucopyrano-
syl)-N0-(4-tert-butylbenzoyl)urea (3h and a-3h). 2,3,4,6-
Tetra-O-acetyl-b-D-glucopyranosylamine29 (5, 50 mg,
0.14 mmol) was transformed into the corresponding iso-
cyanate 6 according to the literature method,12 and this
was boiled in dry toluene with 4-tert-butylbenzamide
(51 mg, 0.28 mmol) for 1 day. The solvent was then
removed and the residue purified by column chromato-
graphy (1:5 EtOAc–hexane) to give 35 mg (44%) N-(2,3,
4,6-tetra-O-acetyl-b-D-glucopyranosyl)-N0-(4-tert-butyl-
benzoyl)urea 3h, as the first fraction. Mp: 117–119 °C;
[a]D ꢁ39 (c 0.20, CHCl3); 1H NMR (CDCl3,
360 MHz): d (ppm) 9.48 (1H, d, J 8.9 Hz, NHCONHC-
OAr), 9.00 (1H, s, NHCONHCOAr), 7.87 (2H, d, J
8.3 Hz, Ar), 7.51 (2H, d, J 8.3 Hz, Ar), 5.35 (1H, pseudo
t, J 9.6, 9.9 Hz, H-3), 5.32 (1H, pseudo t, J 8.9, 9.6 Hz,
H-1), 5.14 (1H, pseudo t, J 8.9, 9.9 Hz, H-4), 5.12 (1H,
pseudo t, J 9.6, 9.9 Hz, H-2), 4.27 (1H, dd, J 4.0,
12.3 Hz, H-6), 4.07 (1H, dd, J 1.2, 12.3 Hz, H-60), 3.81
(1H, ddd, J 1.2, 4.0, 8.9 Hz, H-5), 2.06, 2.04, 2.03
(12H, 3s, 4 ꢂ OCOCH3), 1.35 (9H, s, PhC(CH3)3); 13C
NMR (CDCl3, 90 MHz): d (ppm) 170.6, 170.1, 169.8,
169.4, 167.3 (CO), 157.3 (NHCONH), 154.1, 128.8,
127.7, 125.8 (aromatics), 79.0 (C-1), 73.5, 73.0, 70.0,
68.0 (C-2–C-5), 61.6 (C-6), 35.1 (C(CH3)3), 31.0
(C(CH3)3), 20.7, 20.6, 20.5 (OCOCH3). Anal. Calcd
for C26H34N2O11 (550.57): C, 56.72; H, 6.22; N, 5.09.
Found: C, 56.38; H, 5.96; N, 5.17. The next fraction
gave 8 mg (10%) of the title compound a-3h, as colour-
less crystals. Mp: 70–72 °C; [a]D +88 (c 3.89, CHCl3); 1H
NMR (CDCl3, 360 MHz): d (ppm) 10.16 (1H, s,
NHCONHCOAr), 10.05 (1H, d, J 7.9 Hz, NHCONHC-
OAr), 8.01 (2H, d, J 7.9 Hz, Ar), 7.56 (2H, d, J 7.9 Hz,
Ar), 6.04 (1H, dd, J 5.3, 7.9 Hz, H-1), 5.43 (1H, pseudo
t, J 9.6, 10.5 Hz, H-3), 5.23 (1H, dd, J 5.3, 10.5 Hz, H-2),
5.16 (1H, pseudo t, J 9.6, 9.6 Hz, H-4), 4.37 (1H, dd, J
1.8, 12.3 Hz, H-6), 4.04 (1H, dd, J 3.5, 12.3 Hz, H-60),
4.00 (1H, ddd, J 1.8, 3.5, 9.6 Hz, H-5), 2.06, 2.05, 2.04
(12H, 3s, 4 ꢂ OCOCH3), 1.37 (9H, s, C(CH3)3); 13C
NMR (CDCl3, 90 MHz): d (ppm) 170.5, 169.8, 169.5,
169.4, 168.5 (CO), 157.5 (NHCONH), 154.9, 128.4,
127.9, 125.9 (aromatics), 75.1 (C-1), 70.2, 68.7, 68.3,
68.0 (C-2–C-5), 61.6 (C-6), 35.1 (C(CH3)3), 30.9
(C(CH3)3), 20.5 (OCOCH3).
(ppm) 10.16 (1H, s, NHCONHCOAr), 9.49 (1H, d, J
8.9 Hz, NHCONHCOAr), 8.15 (2H, d, J 8.0 Hz, Ar),
7.79 (2H, d, J 8.3 Hz, Ar), 5.38 (1H, pseudo t, J 9.2,
9.6 Hz, H-3), 5.27 (1H, t, J 8.9, 9.2 Hz, H-1), 5.17 (1H,
t, J 9.2, 9.6 Hz, H-4), 5.12 (1H, t, J 9.2, 9.6 Hz, H-2),
4.25 (1H, dd, J 4.3, 12.6 Hz, H-6), 4.02 (1H, dd, J 2.2,
12.6 Hz, H-60), 3.78 (1H, ddd, J 2.2, 4.3, 9.6 Hz, H-5),
2.06, 2.05, 2.04, 2.03 (12H, 4s, 4 ꢂ OCOCH3). 13C
NMR (CDCl3, 90 MHz): d (ppm) 170.5, 170.1, 169.9,
169.4, 166.9 (CO), 154.5 (NHCONH), 134.8 (q, J
32 Hz, CCF3), 135.1, 128.7, 125.7 (aromatics), 123.4 (q,
J 273 Hz, CF3), 79.1 (C-1), 73.6, 72.8, 70.1, 68.1 (C-2–
C-5), 61.6 (C-6), 20.5 (OCOCH3). Anal. Calcd for
C23H25F3N2O11 (562.45): C, 49.12; H, 4.48; N, 4.98.
Found: C, 49.33; H, 4.26; N, 4.58. The next fraction gave
28 mg (9%) of the title compound a-3i as a white powder.
1
Mp: 155–158 °C; [a]D +75 (c 0.84, CHCl3); H NMR
(CDCl3, 360 MHz): d (ppm) 10.39 (1H, s, NHCONH-
COAr), 9.87 (1H, d, J 7.9 Hz, NHCONHCOAr), 8.22
(2H, d, J 8.8 Hz, Ar), 7.83 (2H, d, J 8.8 Hz, Ar),
6.02 (1H, dd, J 5.3, 7.9 Hz, H-1), 5.41 (1H, pseudo t,
J 9.6, 10.5 Hz, H-3), 5.22 (1H, dd, J 5.3, 10.5 Hz,
H-2), 5.18 (1H, pseudo t, J 9.6, 9.6 Hz, H-4), 4.35 (1H,
dd, J 3.5, 12.3 Hz, H-6), 4.01 (1H, dd, J 2.6, 12.3 Hz,
H-60), 3.97 (1H, ddd, J 2.6, 3.5, 9.6 Hz, H-5), 2.07,
2.06, 2.05 (12H, 3s, 4 ꢂ OCOCH3); 13C NMR (CDCl3,
90 MHz): d (ppm) 170.6, 169.9, 169.5, 169.4, 167.5
(CO), 154.7 (NHCONH), 135.1 (q, J 34 Hz, CCF3),
134.5, 128.6, 126.0 (aromatics), 123.2 (q, J 289 Hz,
CF3), 75.3 (C-1), 70.1, 68.7, 68.5, 67.9 (C-2–C-5), 61.4
(C-6), 20.6 (CH3).
3.4.3. N-(2,3,4,6-Tetra-O-acetyl-b- and a-D-glucopyrano-
syl)-N0-(2-naphthoyl)urea (3m and a-3m). To a soln of
2-naphthoyl-chloride (2.93 g, 15 mmol) in dry CHCl3
(40 mL), anhydrous ZnCl2 (160 mg, 1.20 mmol) and
2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl urea10 (1,
2 g, 5.1 mmol) were added with stirring. The reaction
mixture was refluxed until TLC (1:1 EtOAc–hexane)
showed complete transformation of 1. Then, the reac-
tion mixture was poured into ice-water and extracted
with chloroform (2ꢂ). The organic phases were com-
bined and washed with satd aq Na2CO3 soln and water.
After drying, the solvent was evaporated and the residue
was purified by column chromatography (1:2 EtOAc–
hexane). The main product was 0.88 g (32%) N-
(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-N0-(2-naph-
thoyl)urea. Mp: 184–185 °C; [a]D ꢁ64 (c 1.2, CHCl3); 1H
NMR (CDCl3 + Me2SO-d6, 360 MHz): d (ppm) 10.23
(1H, s, NHCONHCOAr), 9.65 (1H, d, J 8.5 Hz,
3.4.2. N-(2,3,4,6-Tetra-O-acetyl-b- and a-D-glucopyrano-
syl)-N0-(4-trifluoromethyl-benzoyl)urea (3i and a-3i). Pre-
pared from 2,3,4,6-tetra-O-acetyl-b-D-glucopyranos-
ylamine29 (5, 200 mg, 0.58 mmol) and 4-trifluoro-
methyl-benzamide (218 mg, 1.15 mmol) as described in

2088
L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
NHCONHCOAr), 8.57 (1H, s, Ar), 8.10–7.6 (6H, m
unres., Ar), 5.34 (1H, pseudo t, J 9.1 Hz, H-1), 5.33,
5.16, 5.09 (3 ꢂ 1H, 3 pseudo t, J 9.6 Hz, H-2–H-4),
4.17 (1H, dd, J 3.7, 12.6 Hz, H-6), 3.95 (1H, broad d,
J 12.6 Hz, H-60), 3.64 (1H, m unres., H-5), 2.03, 2.00
(12H, 2s, 4 ꢂ OCOCH3); 13C NMR (CDCl3 + Me2SO-
d6, 90 MHz): d (ppm) 170.54, 170.03, 169.74, 169.31,
168.11 (CO), 155.04 (NHCONH), 135.47, 132.24,
129.47, 129.25, 128.83, 128.69, 128.56, 127.76, 127.04,
123.79 (aromatics), 78.94 (C-1), 73.46, 72.95, 70.14,
67.99 (C-2–C-5), 61.47 (C-6), 20.53, 20.45 (OCOCH3).
Anal. Calcd for C26H28N2O11 (544.52): C, 57.35; H,
5.18; N, 5.14. Found: C, 57.38; H, 5.32; N, 5.17. We also
isolated 0.03 g (1%) N-(2,3,4,6-tetra-O-acetyl-a-D-gluco-
pyranosyl)-N0-(2-naphthoyl)urea a-3m as a colourless
oil. Rf = 0.82 (2:1 EtOAc–hexane); [a]D +16 (c 0.96,
CHCl3); 1H NMR (CDCl3): d (ppm) 10.57 (1H, s, CON-
HCO), 10.18 (1H, d, J 6.8 Hz, NH), 8.77–8.75, 8.18–
7.93, 7.72–7.58 (10H, m, aromatics), 6.11 (1H, pseudo
t, J 5.9, 6.8 Hz, H-1), 5.51 (1H, pseudo t, J 9.9,
9.9 Hz, H-4), 5.31 (1H, dd, J 9.6, 5.9 Hz, H-2), 5.23
(1H, pseudo t, J 9.9, 9.2 Hz, H-3), 4.40 (1H, dd, J
12.0, 3.4 Hz, H-6), 4.13 (1H, dd, J 12.0, 1.5 Hz, H-60),
4.09 (1H, ddd, J 9.9, 3.4, 1.5 Hz, H-5), 2.14, 2.11,
2.10, 2.09 (4 ꢂ 3H, 4s, CH3); 13C NMR (CDCl3): d
(ppm) 171.2, 170.6, 169.9, 169.5, 168.9 (CO), 155.4
(NHCONH), 135.9, 135.7, 132.5, 129.6, 129.5, 128.9,
128.2, 127.8, 127.1, 123.6 (aromatics), 75.3 (C-1), 70.4,
68.7, 68.5, 68.2 (C-2–C-5), 61.2 (C-6), 20.6 (CH3);
ESIMS: m/z 567.09 ([M+Na]+).
(aromatics), 80.7 (C-1), 78.1, 77.5, 72.9, 70.0 (C-2–C-5),
60.9 (C-6). Anal. Calcd for C13H18N2O6 (298.30):
C, 52.35; H, 6.08; N, 9.39. Found: C, 52.15; H, 5.98; N,
9.56.
3.4.6. N-(b-D-Glucopyranosyl)-N0-(2-chlorophenyl)urea
(9b). From 8 (0.16 g, 0.66 mmol) and 2-chlorophenyl
isocyanate (0.10 g, 0.66 mmol) according to General
procedure I. Purified by column chromatography (2:1
CHCl3–MeOH) to yield 0.12 g (53%) yellowish crystal-
line product. Mp: 196–198 °C; [a]D +39 (c 0.20, Me2SO);
1H NMR (D2O/CD3OD): d (ppm) 7.77–7.75 (4H, m,
aromatics), 5.17 (1H, d, J 9.3 Hz, H-1), 4.22 (1H, dd,
J 11.9, 1.3 Hz, H-6), 4.05 (1H, dd, J 11.9, 5.3 Hz,
H-60), 3.85 (1H, t, J 10.6, 9.3 Hz, H-2), 3.80–3.55 (3H,
m, H-3, H-4, H-5); 13C NMR (D2O/CD3OD): d
(ppm): 160.4 (NHCONH), 137.2, 133.8, 130.3, 130.0,
129.8, 128.2 (aromatics), 82.3 (C-1), 78.3, 78.0, 73.3,
70.8 (C-2–C-5), 62.0 (C-6). Anal. Calcd for C13H17-
ClN2O6 (332.74): C, 46.93; H, 5.15; N, 9.39. Found:
C, 46.60; H, 4.98; N, 9.56.
3.4.7. N-(b-D-Glucopyranosyl)-N0-(3-chlorophenyl)urea
(9c). From 8 (0.16 g, 0.67 mmol) and 3-chlorophenyl
isocyanate (0.10 g, 0.67 mmol) according to General
procedure I. Purified by column chromatography (2:1
CHCl3–MeOH) to yield 0.09 g (42%) white crystalline
product. Mp: 203–205 °C; [a]D ꢁ18 (c 0.10, Me2SO);
1H NMR (CD3OD): d (ppm) 8.65 (1H, s, NH), 7.66–
7.26 (4H, m, aromatics), 7.03 (1H, d, J 6.6 Hz NH),
4.79 (1H, pseudo t, J 9.2, 6.6 Hz, H-1), 3.83 (1H, dd, J
11.9, 2.6 Hz, H-6), 3.62 (1H, dd, J 11.9, 2.8 Hz, H-60),
3.44–3.27 (4H, m, H-2, H-3, H-4, H-5); 13C NMR
(CD3OD): d (ppm): 157.6 (NHCONH), 142.1, 135.4,
131.1, 126.7, 121.1, 118.2 (aromatics), 82.5 (C-1), 79.4,
78.9, 74.1, 71.5 (C-2–C-5), 62.8 (C-6). Anal. Calcd for
C13H17ClN2O6 (332.74): C, 46.93; H, 5.15; N, 9.39.
Found: C, 46.68; H, 5.08; N, 9.49.
3.4.4. b-D-Glucopyranosylammonium carbamate (8). D-
Glucose (3.0 g, 17 mmol) was dissolved in dry MeOH
(84 mL) and ammonium carbamate (5.2 g, 84 mmol)
was added. The reaction mixture was stirred for 16 h
at 37 °C, then stored at 0 °C for an hour. The product
crystallized from the soln. After filtration, it was dried
in a vacuum desiccator at ꢀ60 mbar. Yield: 3.64 g
(91%), mp: 124–126 °C; [a]D +17 (c 1, water), lit.23
[a]D +5.3 (c 1, water). NMR data for H-1 and soln
behaviour matched those reported.23
3.4.8. N-(b-D-Glucopyranosyl)-N0-(4-chlorophenyl)urea
(9d). From 8 (0.16 g, 0.66 mmol) and 4-chlorophenyl
isocyanate (0.10 g, 0.66 mmol) according to General
procedure I. Purified by column chromatography (2:1
CHCl3–MeOH) to yield 0.12 g (54%) white crystalline
product. Mp: 240–242 °C; [a]D +23 (c 0.28, Me2SO);
1H NMR (Me2SO-d6): d (ppm) 8.69 (1H, s, NH), 7.42
(2H, d, J 8.0 Hz, aromatics), 7.28 (2H, d, J 8.0 Hz, aro-
matics), 6.71 (1H, d, J 9.2 Hz, NH), 5.06–5.05 (2H, m,
OH), 4.92 (1H, d, J 8.9 Hz, OH), 4.65 (1H, pseudo t,
J 9.2, 8.0 Hz, H-1), 4.52 (1H, s, OH), 3.62 (1H, dd, J
11.9, 4.0 Hz, H-6), 3.19 (1H, dd, J 11.9, 1.3 Hz, H-60),
3.10–2.93 (4H, m, H-2, H-3, H-4, H-5); 13C NMR
(Me2SO-d6): d (ppm) 154.4 (NHCONH), 138.9, 135.5,
128.5, 128.1, 124.9, 119.3 (aromatics), 80.6 (C-1), 78.2,
77.5, 72.8, 69.9 (C-2–C-5), 60.9 (C-6). Anal. Calcd for
3.4.5. N-(b-D-Glucopyranosyl)-N0-phenyl urea (9a).
From 8 (0.10 g, 0.41 mmol) and phenyl isocyanate
(50 lL, 0.41 mmol) according to General procedure I.
Purified by column chromatography (2:1 CHCl3–
MeOH) to yield 0.07 g (60%) white crystalline product.
Mp: 193–195 °C (lit.30 mp: 223 °C dec); [a]D ꢁ33 (c
1
0.42, Me2SO) (lit.30 [a]D ꢁ55, water); H NMR (D2O):
d (ppm) 7.41–7.16 (5H, m, aromatics), 4.92 (1H, d, J
8.9 Hz, H-1), 3.89 (1H, dd, J 12.3, 2.2 Hz, H-6), 3.72
(1H, dd, J 12.3, 5.2 Hz, H-60), 3.56 (1H, pseudo t, J 9.2,
8.9 Hz, H-3), 3.53 (1H, ddd, J 8.9, 5.2, 2.2 Hz, H-5),
3.41 (1H, t, J 8.9, 8.9 Hz, H-4), 3.41 (1H, pseudo t, J
9.2, 8.9 Hz, H-2); 13C NMR (Me2SO-d6): d (ppm) 154.5
(NHCONH), 137.8, 129.0, 128.3, 125.2, 123.8, 120.2

L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
2089
C13H17ClN2O6 (332.74): C, 46.93; H, 5.15; N, 9.39.
Found: C, 46.75; H, 4.92; N, 9.15.
3.4.12. N-(b-D-Glucopyranosyl)-N0-(4-methoxyphenyl)-
urea (9i). From 8 (0.10 g, 0.42 mmol) and 4-methoxy-
phenyl isocyanate (60 lL, 0.46 mmol) according to
General procedure I. Purified by column chromatogra-
phy (2:1 CHCl3–MeOH) to yield 0.09 g (63%) white
crystalline product. Mp: 192–194 °C; [a]D +14 (c 0.16,
3.4.9. N-(b-D-Glucopyranosyl)-N0-(2-fluorophenyl)urea
(9e). From 8 (0.18 g, 0.75 mmol) and 2-fluorophenyl
isocyanate (0.10 g, 0.75 mmol) according to General
procedure I. Purified by column chromatography (2:1
CHCl3–MeOH) to yield 0.18 g (76%) white crystalline
product. Mp: 199–201 °C; [a]D ꢁ10 (c 0.20, Me2SO);
1H NMR (Me2SO-d6): d (ppm) 8.51 (1H, s, NH),
8.08–6.93 (4H, m, aromatics), 7.38 (1H, d, J 9.2 Hz,
NH), 5.14–5.10 (2H, m, OH, H-1), 5.00 (1H, t, J 5.3,
5.3 Hz, OH), 4.64 (1H, pseudo t, J 6.6, 5.3 Hz, OH),
3.61 (1H, dd, J 11.9, 5.3 Hz, H-6), 3.20 (1H, dd, J
11.9, 1.3 Hz, H-60), 3.15–3.00 (3H, m, H-2, H-3, H-5),
2.95 (1H, t, J 9.3, 9.3 Hz, H-4); 13C NMR: (Me2SO-
d6): d (ppm) 154.4 (NHCONH), 151.8 (d, CF, J 242.4
Hz), 127.9, 124.4, 122.1, 120.5, 115.0 (aromatics), 80.7
(C-1), 78.2, 77.6, 73.0, 69.9 (C-2–C-5), 60.9 (C-6). Anal.
Calcd for C13H17FN2O6 (316.29): C, 49.37; H, 5.42; N,
8.86. Found: C, 49.20; H, 5.58; N, 8.56.
1
Me2SO); H NMR (Me2SO-d6): d (ppm) 8.43 (1H, s,
NH), 7.30 (2H, d, J 9.2 Hz, aromatics), 6.74 (2H, d, J
9.2 Hz, aromatics), 6.78 (1H, d, J 9.3 Hz, NH), 5.04
(1H, d, J 8.9 Hz, OH), 4.92 (1H, d, J 8.9 Hz, OH),
4.65 (1H, pseudo t, J 9.2, 8.9 Hz, OH), 4.52 (1H, pseudo
t, J 9.2, 8.9 Hz, OH), 3.69 (4H, m, OCH3, H-1), 3.61
(1H, dd, J 11.9, 3.0 Hz, H-6), 3.38 (1H, dd, J 11.9,
1.3 Hz, H-60), 3.21 (1H, pseudo t, J 10.6, 9.3 Hz, H-2),
3.09–2.92 (3H, m, H-3, H-4, H-5); 13C NMR (Me2SO-
d6): d (ppm) 154.7 (NHCONH), 154.1, 133.1, 119.8,
119.5, 115.6, 113.3 (aromatics), 80.8 (C-1), 78.1, 77.6,
72.9, 69.9 (C-2–C-5), 60.9 (C-6), 55.1 (OCH3). Anal.
Calcd for C14H20N2O7 (328.32): C, 51.22; H, 6.14; N,
8.53. Found: C, 51.02; H, 6.48; N, 8.68.
3.4.13.
N-(b-D-Glucopyranosyl)-N0-(3-trifluoromethyl-
3.4.10. N-(b-D-Glucopyranosyl)-N0-(4-bromophenyl)urea
(9g). From 8 (0.14 g, 0.58 mmol) and 4-bromophenyl
isocyanate (0.11 g, 0.58 mmol) according to General
procedure I. Purified by column chromatography (2:1
CHCl3–MeOH) to yield 0.15 g (70%) white crystalline
product. Mp: 187–189 °C; [a]D +27 (c 0.20, Me2SO);
1H NMR (Me2SO-d6): d (ppm) 8.62 (1H, s, NH), 7.43
(2H, d, J 7.9 Hz, aromatics), 7.31 (2H, d, J 7.9 Hz, aro-
matics), 6.82 (1H, d, J 9.2 Hz, NH), 5.11–5.06 (2H, m,
OH), 4.95 (1H, d, J 8.9 Hz, OH), 4.70 (1H, pseudo t,
J 9.2, 9.2 Hz, H-1), 4.52 (1H, s, OH), 3.54 (1H, dd, J
11.8, 4.0 Hz, H-6), 3.22 (1H, dd, J 11.9, 1.3 Hz, H-60),
3.15–2.93 (4H, m, H-2, H-3, H-4, H-5); 13C NMR
(Me2SO-d6): d (ppm) 154.5 (NHCONH), 131.9, 131.5,
126.8, 125.6, 122.3, 118.7 (aromatics), 80.6 (C-1), 78.0,
77.3, 72.5, 69.8 (C-2–C-5), 61.1 (C-6). Anal. Calcd for
C13H17BrN2O6 (377.19): C, 41.40; H, 4.54; N, 7.43.
Found: C, 41.12; H, 5.68; N, 7.56.
phenyl)urea (9j). From 8 (0.12 g, 0.50 mmol) and 3-tri-
fluoromethylphenyl isocyanate (0.09 g, 0.50 mmol)
according to General procedure I. Purified by column
chromatography (4:1 CHCl3–MeOH) to yield 0.08 g
(46%) white crystalline product. Mp: 189–191 °C; [a]D
1
+17 (c 0.21, Me2SO); H NMR (Me2SO-d6): d (ppm)
7.95 (1H, s, NH), 7.57–7.20 (4H, m, aromatics), 7.28
(1H, d, J 9.3 Hz, NH), 5.12–5.04 (2H, m, OH), 4.68
(1H, t, J 9.3, 9.3 Hz, H-1), 4.62 (1H, s, OH), 4.19 (1H,
d, J 8.9 Hz, OH), 3.99 (1H, dd, J 12.1, 2.3 Hz, H-6),
3.58 (1H, dd, J 12.1, 4.0 Hz, H-60), 3.21–2.96 (4H, m,
H-2, H-3, H-4, H-5); 13C NMR (Me2SO-d6): d (ppm):
154.8 (NHCONH), 141.2, 129.5, 129.4 (q, C-CF3
J
31.7 Hz), 124.9 (2), 121.1 (aromatics), 117.3 (q, CF3 J
265.3 Hz), 80.6 (C-1), 78.3, 77.6, 72.8, 69.9 (C-2–C-5),
60.8 (C-6). Anal. Calcd for C14H17F3N2O6 (366.30): C,
45.91; H, 4.68; N, 7.65. Found: C, 45.51; H, 4.58; N, 7.36.
3.4.14. N-(b-D-Glucopyranosyl)-N0-(3-cyanophenyl)urea
(9l). From 8 (0.1 g, 0.83 mmol) and 3-cyanophenyl
isocyanate (0.12 g, 0.83 mmol) according to General
procedure I. Purified by column chromatography (4:1
CHCl3–MeOH) to yield 0.12 g (45%) white crystalline
3.4.11. N-(b-D-Glucopyranosyl)-N0-(4-nitrophenyl)urea
(9h). From 8 (0.05 g, 0.21 mmol) and 4-nitrophenyl
isocyanate (0.035 g, 0.21 mmol) according to General
procedure I. Purified by column chromatography (2:1
CHCl3–MeOH) to yield 0.05 g (76%) white crystalline
product. Mp: 169–171 °C; [a]D ꢁ44 (c 0.21, Me2SO); 1H
NMR (D2O): d (ppm) 8.03 (2H, d, J 9.3 Hz, aromatics),
7.40 (2H, d, J 9.3 Hz, aromatics), 4.87 (1H, d, J 9.3 Hz,
H-1), 3.83 (1H, dd, J 11.9, 1.3 Hz, H-6), 3.67 (1H, dd, J
11.9, 5.3 Hz, H-60), 3.65–3.39 (4H, m, H-2, H-3, H-4,
H-5); 13C NMR (D2O): d (ppm) 156.9 (NHCONH),
145.6, 142.8, 125.8, 125.1, 123.4, 119.3 (aromatics), 81.4
(C-1), 77.9, 77.2, 72.5, 69.9 (C-2–C-5), 61.2 (C-6). Anal.
Calcd for C13H17N3O8 (343.30): C, 45.48; H, 4.99; N,
12.24. Found: C, 45.18; H, 5.18; N, 12.36.
1
product. Mp: 219–221 °C; [a]D +1 (c 0.21, Me2SO); H
NMR (Me2SO-d6): d (ppm) 8.50 (1H, s, NH), 7.35–
6.78 (4H, m, aromatics), 6.61 (1H, d, J 9.3 Hz, NH),
5.03 (1H, d, J 8.9 Hz, OH), 4.89 (1H, d, J 8.9 Hz,
OH), 4.67 (1H, pseudo t, J 9.2, 8.9 Hz, OH), 4.51 (1H,
pseudo t, J 9.2, 8.9 Hz, OH), 3.61 (1H, dd, J 11.9,
2.3 Hz, H-6), 3.42 (1H, dd, J 11.9, 2.3 Hz, H-60), 3.33
(1H, t, J 9.3, 9.3 Hz, H-1), 3.20 (1H, pseudo t, J 10.6,
9.3 Hz, H-2), 3.10–3.02 (2H, m, H-3, H-5), 2.96 (1H, t,
J 9.3, 9.3 Hz, H-4); 13C NMR (Me2SO-d6): d (ppm)
154.5 (NHCONH), 133.6, 132.7, 119.4, 119.2, 113.9,

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L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
113.7 (aromatics), 110.5 (CN), 80.7 (C-1), 78.0, 77.5,
72.8, 69.9 (C-2–C-5), 60.8 (C-6). Anal. Calcd for
C14H17N3O6 (323.31): C, 52.01; H, 5.30; N, 13.00.
Found: C, 51.90; H, 5.28; N, 13.26.
77.3, 73.2, 69.70 (C-2–C-5), 60.8 (C-6). Anal. Calcd for
C13H18N2O6 (298.30): C, 52.35; H, 6.08; N, 9.39. Found:
C, 52.55; H, 6.26; N, 9.16.
3.4.18. N-(b-D-Glucopyranosyl)-N0-(4-tert-butylbenzoyl)-
urea (9p). From 8 (0.68 g, 2.80 mmol) and 4-tert-butyl-
benzoyl isocyanate (0.28 g, 1.40 mmol) according to
General procedure I. Purified by column chromato-
graphy (9:1 CHCl3–MeOH) to yield 0.10 g (19%) pale
yellowish oil, Rf 0.08, CHCl3–MeOH, 9:1; [a]D ꢁ31 (c
0.16, Me2SO); 1H NMR (Me2SO-d6): d (ppm) 10.78
(1H, s, NH), 9.14 (1H, d, J 9.2 Hz, NH), 7.92 (2H, d,
J 9.2 Hz, aromatics), 7.53 (2H, d, J 9.2 Hz, aromatics),
5.25 (1H, d, J 5.3 Hz, OH), 5.02 (1H, d, J 4.0 Hz,
OH), 4.94 (1H, d, J 5.3 Hz, OH), 4.82 (1H, t, J 9.2,
9.2 Hz, H-1), 4.52 (1H, t, J 5.3, 5.3 Hz, OH), 3.65 (1H,
dd, J 11.9, 5.3 Hz, H-6), 3.46 (1H, dd, J 11.9, 2.6 Hz,
H-60), 3.32–3.01 (4H, m, H-2, H-3, H-4, H-5), 1.30
(9H, s, C(CH3)3); 13C NMR (Me2SO-d6): d (ppm)
168.2 (NHCOAr) 156.0 (NHCONH), 153.5, 129.5,
128.0 (2), 125.3 (2) (aromatics), 80.2 (C-1), 78.5, 77.2,
73.1, 69.7 (C-2–C-5), 62.8 (C-6), 34.7 (C(CH3)3), 30.7
(C(CH3)3). Anal. Calcd for C18H26N2O7 (382.42): C,
56.54; H, 6.85; N, 7.33. Found: C, 56.40; H, 6.18; N,
7.26.
3.4.15.
N-(b-D-Glucopyranosyl)-N0-(1-naphthyl)urea
(9m). From 8 (0.05 g, 0.21 mmol) and 1-naphthyl
isocyanate (35 lL, 0.21 mmol) according to General
procedure I. Purified by column chromatography (4:1
CHCl3–MeOH) to yield 0.03 g (45%) mildly brown crys-
talline product. Mp: 220–222 °C; [a]D ꢁ24 (c 0.20,
1
Me2SO); H NMR (Me2SO-d6 + D2O): d (ppm) 8.00–
7.41 (7H, m, aromatics), 4.70 (1H, d, J 8.9 Hz, H-1),
3.66 (1H, dd, J 12.3, 1.5 Hz, H-6), 3.43 (1H, dd, J
12.3, 4.0 Hz, H-60), 3.26 (1H, pseudo t, J 9.6, 8.9 Hz,
H-3), 3.21 (1H, ddd, J 8.9, 4.0, 1.5 Hz, H-5), 3.12 (1H,
t, J 8.9, 8.9 Hz, H-4), 3.07 (1H, pseudo t, J 9.6,
8.9 Hz, H-2); 13C NMR (Me2SO-d6 + D2O): d (ppm)
154.8 (NHCONH), 134.6, 133.6, 128.4, 125.8, 125.7,
125.5, 125.4, 122.3, 121.1, 116.4 (aromatics), 80.8
(C-1), 78.1, 77.5, 73.1, 69.9 (C-2–C-5), 60.9 (C-6). Anal.
Calcd for C17H20N2O6 (348.36): C, 58.61; H, 5.79; N,
8.04. Found: C, 58.40; H, 5.58; N, 8.26.
3.4.16.
N-(b-D-Glucopyranosyl)-N0-(2-naphthyl)urea
(9n). From 8 (0.17 g, 0.69 mmol) and 2-naphthyl iso-
cyanate (0.11 g, 0.69 mmol) according to General pro-
cedure I. Purified by column chromatography (2:1
CHCl3–MeOH) to yield 0.10 g (42%) mildly brown crys-
talline product. Mp: 238–239 °C; [a]D ꢁ24 (c 0.20,
3.4.19.
N-(b-D-Glucopyranosyl)-N0-phenyl
thiourea
(10a). From 12a (0.13 g, 0.27 mmol) according to Gen-
eral procedure III. Yield: 0.07 g (86%) pale yellow crys-
tals. Mp: 119–121 °C (lit.30 mp: 121 °C), [a]D ꢁ24 (c
1
1
Me2SO); H NMR (Me2SO-d6 + D2O): d (ppm) 7.92–
0.23, water); H NMR (D2O): d (ppm) 7.48–7.24 (5H,
7.30 (7H, m, aromatics), 4.70 (1H, d, J 9.2 Hz, H-1),
3.67 (1H, dd, J 12.3, 1.9 Hz, H-6), 3.44 (1H, dd, J
12.3, 5.5 Hz, H-60), 3.28 (1H, pseudo t, J 9.2, 8.9 Hz,
H-3), 3.22 (1H, ddd, J 8.9, 5.5, 1.9 Hz, H-5), 3.10 (1H,
t, J 8.9, 8.9 Hz, H-4), 3.09 (1H, pseudo t, J 9.2,
8.9 Hz, H-2); 13C NMR (CDCl3): d (ppm) 154.6
(NHCONH), 137.6, 133.7, 128.9, 128.3, 127.4, 126.8,
126.2, 123.7, 119.4, 113.0 (aromatics), 80.8 (C-1), 78.2,
77.6, 72.9, 70.0 (C-2–C-5), 60.9 (C-6). Anal. Calcd for
C17H20N2O6 (348.36): C, 58.61; H, 5.79; N, 8.04. Found:
C, 58.55; H, 5.66; N, 8.06.
m, aromatics), 5.50 (1H, d, J 9.2 Hz, H-1), 3.85 (1H,
dd, J 11.9, 1.0 Hz, H-6), 3.70 (1H, dd, J 11.9, 6.6 Hz,
H-60), 3.51 (1H, ddd, J 9.2, 6.6, 1.0 Hz, H-5), 3.54,
3.40, 3.37 (3 ꢂ 1H, 3 ꢂ pseudo t, J 9.2, 9.2 Hz, H-2,
H-3, H-4); 13C NMR (D2O): d (ppm) 182.9 (CS),
130.2 (2), 129.2, 128.3 (2), 127.0 (aromatics), 84.6
(C-1), 77.9, 77.1, 72.5, 69.7 (C-2–C-5), 61.1 (C-6). Anal.
Calcd for C13H18N2O5S (314.36): C, 49.67; H, 5.77; N,
8.91; S, 10.20. Found: C, 49.22; H, 5.95; N, 8.45; S,
10.33.
3.4.20. N-(b-D-Glucopyranosyl)-N0-(2-chlorophenyl)thio-
urea (10b). From 8 (0.20 g, 0.80 mmol) and 2-chloro-
phenyl isothiocyanate (0.13 mL, 1.04 mmol) or from
13b (0.23 g, 0.44 mmol) according to General proce-
dures I and III, respectively. Purified by column
chromatography (1:1 CHCl3–MeOH). Yield: 0.29 g
(64%) from 8 or 0.07 g (20%) from 12b pale yellow crys-
tals. Mp: 165–167 °C; [a]D +71 (c 0.05, Me2SO); 1H
NMR (CD3OD): d (ppm) 7.36–7.19 (4H, m, aromatics),
5.37 (1H, d, J 9.2 Hz, H-1), 4.33 (1H, dd, J 11.9, 1.0 Hz,
H-6), 4.18 (1H, dd, J 11.9, 6.6 Hz, H-60), 3.56 (1H, ddd,
J 9.2, 6.6, 1.0 Hz H-5), 3.44 (1H, pseudo t, J 9.2, 9.2 Hz,
H-2), 3.35–3.30 (2H, m, H-3, H-4); 13C NMR (CD3OD):
d (ppm) 173.6 (CS), 130.7 (2), 130.5, 129.1, 128.2 (2)
3.4.17.
N-(b-D-Glucopyranosyl)-N0-(2-naphthoyl)urea
(9o). From 8 (0.13 g, 0.54 mmol) and 2-naphthoyl
isocyanate (0.11 g, 0.54 mmol) according to General
procedure I. Purified by column chromatography (2:1
CHCl3–MeOH) to yield 0.10 g (60%) white crystalline
product. Mp: 213–214 °C; [a]D +6.5 (c 0.18, Me2SO);
1H NMR (Me2SO-d6): d (ppm) 11.02 (1H, s, NH),
9.15 (1H, d, J 9.5 Hz, NH), 8.2–7.5 (7H, m, aromatics),
4.84 (1H, pseudo t, J 9.5, 8.6 Hz, H-1), 4.01–3.08
(10H, m, 4 ꢂ OH, H-2, H-3, H-4, H-5, H-6, H-60); 13C
NMR (Me2SO-d6) d (ppm) 168.5 (NHCOAr), 153.5
(NHCONH), 134.7, 134.6, 132.1, 130.0, 129.6, 129.4,
129.2, 127.8, 127.6, 126.5 (aromatics), 80.3 (C-1), 78.6,

L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
2091
(aromatics), 91.4 (C-1), 78.6, 76.5, 73.9, 71.8 (C-2–
C-5), 68.4 (C-6). Anal. Calcd for C13H17ClN2O5
(348.81): C, 40.77; H, 4.91; N, 8.03; S, 9.19. Found: C,
40.55; H, 5.18; N, 8.21; S, 9.01.
(382.36): C, 43.98; H, 4.48; N, 7.33; S, 8.39. Found: C,
43.75; H, 4.38; N, 7.51; S, 8.45.
3.4.24. N-(b-D-Glucopyranosyl)-N0-phenyl selenourea
(11). b-D-Glucopyranosylammonium carbamate
8
3.4.21. N-(b-D-Glucopyranosyl)-N0-(4-fluorophenyl)thio-
urea (10f). From 8 (0.20 g, 0.80 mmol) and 4-fluoro-
phenyl isothiocyanate (0.12 mL, 0.82 mmol) or from
12f (0.15 g, 0.30 mmol) according to General procedures
I and III, respectively. Purified by column chromato-
graphy (4:1 CHCl3–MeOH). Yield: 0.13 g (20%) from
8 or 0.09 g (97%) from 12f yellow crystalline product.
was suspended in dry pyridine (0.20 g, 0.83 mmol/
˚
8 mL) containing molecular sieves (3 A). To the sus-
pension (0.15 g, 0.83 mmol), phenyl-isoselenocyanate
was added and the mixture was stirred at rt in the
dark for 1 day under argon atmosphere (TLC, 4:1
CHCl3–MeOH). Then, the mixture was filtered over
a Celite pad and the solvent evaporated. The crude
product was purified by column chromatography (4:1
CHCl3–MeOH) to yield 0.15 g (65%) red oil, Rf 0.84
(1:1 CHCl3–MeOH); [a]D ꢁ23 (c 0.022, Me2SO)
(lit.28 [a]D ꢁ19 (c 1.4, MeOH)); 1H NMR (D2O): d
(ppm) 7.43–7.23 (4H, d, J 7.9 Hz, ArH), 5.59 (1H, d,
J 9.2 Hz, H-1), 3.83 (1H, dd, J 11.9, 1.0 Hz, H-6),
3.79 (1H, dd, J 11.9, 6.6 Hz, H-60) 3.69–3.36 (4H, m,
H-2, H-3, H-4, H-5); 13C NMR (D2O): d (ppm)
181.6 (CSe), 149.7, 133.1, 129.5, 127.8, 126.2, 125.1
(aromatics), 87.5 (C-1), 78.1, 77.2, 72.5, 69.8 (C-2–
C-5), 61.2 (C-6). ESIMS: m/z 385.03 ([M+Na]+),
C13H18N2NaO5Se.
1
Mp: 120–122 °C; [a]D ꢁ182 (c 0.08, water); H NMR
(D2O): d (ppm) 7.26 (d, 2H, J 7.9 Hz, aromatics), 7.14
(d, 2H, J 7.9 Hz, aromatics), 5.49 (1H, d, J 9.2 Hz,
H-1), 3.84 (1H, dd, J 11.9, 1.0 Hz, H-6), 3.81 (1H, dd,
J 11.9, 5.3 Hz, H-60), 3.70 (1H, ddd, J 9.2, 5.3, 1.0 Hz
H-5), 3.67 (1H, pseudo t, J 9.2, 9.2 Hz H-2), 3.54–3.48
(2H, m, H-3, H-4); 13C NMR (D2O): d (ppm) 182.2
(CS), 162.0 (d, CF, J 245.3 Hz), 129.3 (2) 116.9, 116.7,
111.9 (aromatics), 78.0 (C-1), 77.9, 77.1, 72.6, 69.8
(C-2–C-5), 61.2 (C-6). Anal. Calcd for C13H17FN2O5S
(332.35): C, 46.98; H, 5.16; N, 8.43; S, 9.65. Found: C,
46.75; H, 5.38; N, 8.31; S, 9.45.
3.4.22. N-(b-D-Glucopyranosyl)-N0-(4-methoxyphenyl)-
thiourea (10i). From 12i (0.81 g, 1.58 mmol) according
to General procedure III. Purified by column chroma-
tography (1:1 CHCl3–MeOH) to yield 0.23 g (44%) pale
yellow crystalline product. Mp: 119–121 °C; [a]D ꢁ109
3.4.25. N-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-
N0-phenyl thiourea (12a). From 5 (0.50 g, 1.44 mmol)
and phenyl isothiocyanate (0.26 mL, 1.5 equiv) accord-
ing to General procedure II. Purified by column
chromatography (1:1 EtOAc–hexane) to yield 0.47 g
(68%) white crystalline product. Mp: 131–133 °C (lit.29
mp: 135 °C), [a]D ꢁ19 (c 0.31, CHCl3); 1H NMR
(CDCl3): d (ppm) 9.08 (1H, s, NH), 7.48–7.18 (5H, m,
aromatics), 6.90 (1H, d, J 6.6 Hz, NH), 5.86 (1H, pseudo
t, J 9.2, 9.2 Hz), 5.35 (1H, pseudo t, J 10.5, 9.2 Hz), 5.03
(1H, pseudo t, J 10.5, 9.2 Hz), 4.95 (1H, pseudo t, J 9.2,
9.2 Hz), (H-1, H-2, H-3, H-4), 4.32 (1H, dd, J 13.2,
4.0 Hz, H-6), 4.08 (1H, dd, J 13.2, 1.2 Hz, H-60), 3.86
(1H, ddd, J 9.2, 4.0, 1.2 Hz, H-5), 2.06, 2.04, 2.01,
1.99 (4 ꢂ 3H, 4s, CH3); 13C NMR (CDCl3): d (ppm)
181.7 (CS), 170.5, 170.5, 169.6, 169.4 (CO), 135.6,
129.5, 129.5, 127.1, 124.9, 124.9, (aromatics), 82.5
(C-1), 73.1, 72.5, 70.1, 67.9 (C-2–C-5), 61.4 (C-6), 20.4,
20.3 (3) (CH3). Anal. Calcd for C21H26N2O9S (482.51):
C, 52.28; H, 5.43; N, 5.81; S, 6.65. Found: C, 52.20;
H, 5.35; N, 5.90; S, 6.71.
1
(c 0.24, water); H NMR (D2O): d (ppm) 7.15 (d, 2H,
J 7.9 Hz, aromatics), 6.89 (d, 2H, J 7.9 Hz, aromatics),
5.48 (1H, d, J 9.2 Hz, H-1), 3.82 (1H, dd, J 11.9,
1.0 Hz, H-6), 3.67 (1H, dd, J 11.9, 5.3 Hz, H-60), 3.47
(1H, ddd, J 9.2, 5.3, 1.0 Hz H-5), 3.52 (1H, pseudo t,
J 9.2, 9.2 Hz, H-2), 3.41–3.39 (2H, m, H-3, H-4); 13C
NMR (D2O): d (ppm) 180.2 (CS), 128.5 (3), 127.6,
115.2 (2) (aromatics), 83.1 (C-1), 77.9, 77.1, 72.6, 69.8
(C-2–C-5), 61.2 (C-6) 56.1 (OCH3). Anal. Calcd for
C14H20N2O6S (344.39): C, 48.83; H, 5.85; N, 8.13; S,
9.31. Found: C, 48.62; H, 5.58; N, 8.26; S, 9.05.
3.4.23.
N-(b-D-Glucopyranosyl)-N0-(4-trifluoromethyl-
phenyl)thiourea (10k). From 12k (0.15 g, 0.26 mmol)
according to General procedure III. Purified by column
chromatography (1:1 CHCl3–MeOH) to yield 0.10 g
(98%) pale yellow crystalline product. Mp: 190–192 °C;
[a]D ꢁ57 (c 0.14, water); 1H NMR (D2O): d (ppm)
7.90 (2H, d, J 7.9 Hz, ArH), 7.70 (2H, d, J 7.9 Hz,
ArH), 5.22 (1H, d, J 9.2 Hz, H-1), 3.83 (1H, dd, J
13.2, 1.5 Hz, H-6), 3.66 (1H, dd, J 13.2, 4.0 Hz, H-60),
3.48–3.37 (4H, m, H-2, H-3, H-4, H-5); 13C NMR
(D2O): d (ppm) 174.7 (CS), 140.3, 132.3 (q, J 31.9 Hz,
CCF3), 129.6 (2), 125.7 (2) (aromatics), 124.5 (q, J
272.9 Hz CF3), 82.7 (C-1), 73.9, 72.7, 70.3, 68.1 (C-2–
C-5), 61.5 (C-6). Anal. Calcd for C14H17F3N2O5S
3.4.26. N-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-
N0-(2-chlorophenyl)thiourea (12b). From
5
(0.50 g,
1.44 mmol)
and
2-chlorophenyl
isothiocyanate
(0.37 mL, 1.5 equiv) according to General procedure
II. Purified by column chromatography (2:3 EtOAc–
hexane) to yield 0.59 g (79%) white crystalline product.
1
Mp: 144–146 °C; [a]D +48, (c 0.31, CHCl3); H NMR
(CDCl3): d (ppm) 8.14 (1H, s, NH), 7.51–7.23 (4H, m,
aromatics), 6.71 (1H, d, J 9.2 Hz, NH), 5.76 (1H, t, J

2092
L. Somsa´k et al. / Carbohydrate Research 343 (2008) 2083–2093
9.2, 9.2 Hz), 5.35 (1H, pseudo t, J 10.5, 9.2 Hz), 5.05
(1H, t, J 10.5, 9.2 Hz), 4.90 (1H, t, J 9.2, 9.2 Hz),
(H-1, H-2, H-3, H-4), 4.33 (1H, dd, J 13.2, 4.0 Hz,
H-6), 4.10 (1H, dd, J 13.2, 1.2 Hz, H-60), 3.87 (1H,
ddd, J 9.2, 4.0, 1.2 Hz, H-5), 2.06, 2.05, 2.03, 2.00
(4 ꢂ 3H, 4s, CH3); 13C NMR (CDCl3): d (ppm) 182.5
(CS), 171.1, 170.6, 169.8, 169.6 (CO), 132.8, 130.5,
130.4, 129.1, 128.1, 128.0 (aromatics), 83.1 (C-1), 73.5,
72.5, 70.4, 68.2 (C-2–C-5), 61.6 (C-6), 20.7, 20.6, 20.5
(2) (CH3). Anal. Calcd for C21H25ClN2O9S (516.96):
C, 48.79; H, 4.87; N, 5.42; S, 6.20. Found: C, 48.65;
H, 5.02; N, 5.22; S, 6.07.
C22H25F3 N2O9S (550.51): C, 48.00; H, 4.58; N, 5.09;
S, 5.82. Found: C, 48.22; H, 4.78; N, 5.36; S, 5.47.
3.4.29. N-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-
N0-(4-methoxy-phenyl)thiourea (12i). From 5 (1.00 g,
2.88 mmol) and 4-methoxy-phenylisocyanate (0.33 mL,
4.32 mmol) according to General procedure II. Purified
by column chromatography (1:1 EtOAc–hexane) to
yield 0.81 g (57%) colourless oil, Rf 0.27 (1:1 EtOAc–
1
hexane); [a]D +14 (c 0.19, CHCl3); H NMR (CDCl3):
d (ppm) 8.65 (1H, s, NH), 7.12 (2H, d, J 7.9 Hz, aromat-
ics), 6.93 (2H, d, J 7.9 Hz, aromatics), 6.57 (1H, d, J
9.2 Hz, NH), 5.83 (1H, pseudo t, J 9.2, 9.2 Hz), 5.34
(1H, pseudo t, J 9.2, 9.2 Hz), 5.02 (1H, pseudo t, J
9.2, 9.2 Hz), 4.91 (1H, pseudo t, J 9.2, 9.2 Hz), (H-1,
H-2, H-3, H-4), 4.30 (1H, dd, J 11.9, 4.0 Hz, H-6),
4.10 (1H, dd, J 11.9, 2.4 Hz, H-60), 3.84–3.80 (4H, m,
H-5, OCH3), 2.05, 2.04, 2.02, 1.99 (4 ꢂ 3H, 4s, CH3);
13C NMR (CDCl3): d (ppm) 182.1 (CS), 171.0, 170.5,
169.6, 169.4 (CO), 127.3 (3), 126.7, 114.8 (2) (aromatics),
82.8 (C-1), 73.3, 72.5, 70.3, 68.0 (C-2–C-5), 60.2 (C-6),
55.3 (OCH3), 20.8, 20.4, 20.3 (2) (CH3). Anal. Calcd
for C22H28N2O10S (512.54): C, 51.56; H, 5.51; N, 5.47;
S, 6.26. Found: C, 51.35; H, 5.19; N, 5.28; S, 6.09.
3.4.27. N-(2,3,4,6-Tetra-O-acetyl-b-D-glucopranosyl)-N0-
(4-fluorophenyl)thiourea
1.44 mmol) and
(12f). From
4-fluorophenyl
5
(0.50 g,
isothiocyanate
(0.22 mL, 2.16 mmol) according to General procedure
II. Purified by column chromatography (1:1 EtOAc–
hexane) to yield 0.67 g (92%) white crystalline product.
1
Mp: 191–193 °C; [a]D +18 (c 0.29, CHCl3); H NMR
(CDCl3): d (ppm) 8.63 (1H, s, NH), 7.20 (2H, d, J
7.9 Hz, aromatics), 7.12 (2H, d, J 7.9 Hz, aromatics),
6.68 (1H, d, J 9.2 Hz, NH), 5.81 (1H, t, J 9.2, 9.2 Hz),
5.36 (1H, t, J 9.2, 9.2 Hz), 5.06 (1H, t, J 9.2, 9.2 Hz),
4.93 (1H, t, J 9.2, 9.2 Hz), (H-1, H-2, H-3, H-4), 4.32
(1H, dd, J 11.9, 4.0 Hz, H-6), 4.09 (1H, dd, J 11.9,
1.5 Hz, H-60), 3.86 (1H, ddd, J 9.2, 4.0, 1.5 Hz, H-5),
2.07, 2.03, 2.01 (2) (4 ꢂ 3H, 4s, CH3); 13C NMR
(CDCl3): d (ppm) 182.2 (CS), 170.9, 170.6, 169.7,
169.4 (CO), 162.0 (d, CF, J 246.1 Hz), 132.1, 127.8,
127.6, 116.7, 116.5 (aromatics), 82.9 (C-1), 73.5, 72.4,
70.4, 68.1 (C-2–C-5), 61.5 (C-6), 20.6 (2), 20.4 (2)
(CH3). Anal. Calcd for C21H25FN2O9S (500.50): C,
50.40; H, 5.03; N, 5.60; S, 6.41. Found: C, 50.15; H,
5.33; N, 5.36; S, 6.17.
Acknowledgement
Financial support for this work was provided by the
Hungarian Scientific Research Fund (OTKA 46081
and 61336).
References
´
1. Somsak, L.; Nagy, V.; Hadady, Z.; Docsa, T.; Gergely, P.
3.4.28. N-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-
Curr. Pharm. Design 2003, 9, 1177–1189.
N0-(4-trifluoromethyl-phenyl)thiourea (12k). From
5
´
2. Somsak, L.; Nagy, V.; Hadady, Z.; Felfo¨ldi, N.; Docsa,
(1.00 g, 2.88 mmol) and 4-trifluoromethylphenyl isothio-
cyanate (0.46 mL, 2.88 mmol) according to General pro-
cedure II. Purified by column chromatography (1:1
EtOAc–hexane) to yield 1.81 g (80%) white crystalline
product. Mp: 112–114 °C; [a]D +32 (c 0.15, CHCl3);
1H NMR (CDCl3): d (ppm) 11.08 (1H, d, J 9.2 Hz,
NH), 9.21 (1H, s, NH), 7.99 (2H, d, J 7.9 Hz, aromat-
ics), 7.78 (2H, d, J 7.9 Hz, aromatics), 5.78 (1H, pseudo
t, J 9.2, 9.2 Hz), 5.39 (1H, pseudo t, J 10.6, 9.2 Hz), 5.20
(1H, pseudo t, J 10.6, 9.2 Hz), 5.13 (1H, t, J 9.2, 9.2 Hz),
(H-1, H-2, H-3, H-4), 4.32 (1H, dd, J 13.2, 5.3 Hz, H-6),
4.14 (1H, dd, J 13.2, 1.2 Hz, H-60), 3.87 (1H, ddd, J 9.2,
5.3, 1.2 Hz, H-5), 2.07, 2.04, 2.03, 1.99 (4 ꢂ 3H, 4s,
CH3); 13C NMR (CDCl3): d (ppm) 182.4 (CS), 170.6,
170.1, 170.0, 169.9 (CO), 134.8 (q, C-CF3, J 31.7 Hz),
128.2 (2), 126.1 (2), 121.7 (aromatics), 123.2 (q, CF3, J
272.9 Hz), 77.8 (C-1), 77.8, 77.2, 72.9, 69.9 (C-2–C-5),
61.2 (C-6), 20.7, 20.5 (3) (CH3). Anal. Calcd for
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Leonidas, D. D.; Somsak, L.; Nagy, V.; Praly, J.-P.;
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Docsa, T.; Toth, B.; Gergely, P. Eur. J. Biochem. 2002,
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´
6. Gyo¨rgydeak, Z.; Hadady, Z.; Felfo¨ldi, N.; Krakomperger,
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