Hydroxyamino sugar derivatives: Sugar nitrones

Article abstract of DOI:10.1016/S0014-827X(98)00069-X

We describe in this paper the preparation of 46 new sugar nitrone derivatives and their antibacterial activity against Escherichia coli and Bacillus subtilis.

Full text of DOI:10.1016/S0014-827X(98)00069-X

Il Farmaco 53 (1998) 623±625
New Compounds
Hydroxyamino sugar derivatives: sugar nitrones
G. Zosimo-Landolfo1, J.M.J. Tronchet, N. Bizzozero, F. Habashi, A. Kamatari
Department of Pharmaceutical Chemistry, Sciences II University, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland
Received 11 May 1998; accepted 20 September 1998
Abstract
We describe in this paper the preparation of 46 new sugar nitrone derivatives and their antibacterial activity against Escherichia coli and
Bacillus subtilis. q 1998 Elsevier Science S.A. All rights reserved.
Keywords: Nitrones; Carbohydrates; Antibacterial
Nitrones are very useful synthons, as upon reduction they
afford hydroxylamines [1], upon cycloaddition oxazolidines
and can rearrange to amides [2]. Carbohydrate derivatives
bearing a nitrone function were ®rst prepared in our labora-
tory [3]. They result from the reaction of a keto or aldehydo
sugar with a N-alkylhydroxylamine [4].
We report here on the preparation of 46 new N-glycosyl
nitrones (Figs. 1±4) obtained from the condensation of an
aldehyde with a hydroxyamino sugar [5,6]. The acidic
hydrolysis of the acetonide protection will be described
elsewhere.
The nitrones 1±45 were submitted to antibacterial screen-
ing tests against Escherichia coli and Bacillus subtilis as
part of a systematic screening program. Compound 46
was not tested. The results are listed in Table 1. They
show a poor antibacterial activity, except for compound
32 which presents a MIC of 50 mg/ml for both E. coli and
B. subtilis (Table 1).
The synthetic route explored here led to di- and trisac-
charide derivatives, linked through a nitrone function [7].
1. Experimental
All chemicals are from commercial grade Fluka and
Merck. The melting points were observed on a Mettler
FP 52 apparatus. The optical rotations were measured in
chloroform on a Schmidt-Haensch polarimeter. The UV
spectra were observed on a Uvikon 810 spectrophot-
ometer. The IR spectra were obtained on a Perkin-Elmer
1 Present address: Elsevier Science S.A., 50 Avenue de la Gare, 1001
Fig. 1.
Lausanne, Switzerland.
0014-827X/98/$ - see front matter q 1998 Elsevier Science S.A. All rights reserved.
PII S0014-827X(98)00069-X

624
G. Zosimo-Landolfo et al. / Il Farmaco 53 (1998) 623±625
Fig. 4.
357 and the PMR spectra were observed on a Bruker
SP200 apparatus. The antibacterial tests were performed
according to Ref. [8].
Fig. 2.
One millimole of a hydroxyamino sugar [5,6] was
allowed to react with an aldehyde in an appropriate solvent.
When the reaction was completed (TLC), the mixture was
evaporated to dryness and puri®ed by column chromatogra-
phy on silicagel 60F254 from Merck. The general synthetic
conditions are shown in Table 2.
Melting points of compounds 1±46 are listed in Table 2.
All the prepared sugar nitrones present elemental analysis,
UV, IR, SM and PMR spectra in accordance with their
structure (details may be obtained from the authors (GZL)).
Table 1
Antimicrobial activity in mg/ml
Nitrone
E. coli
B. subtilis
Nitrone
E. coli
B. subtilis
1
2
NAa
225
. 500
. 500
. 500
. 500
400
27
28
29
30
32
33
34
35
36
37
38
39
40
41
43
44
45
NA
NA
NA
250
5
NA
NA
. 500
NA
. 500
. 200
50
6
7
400
50
8
NA
NA
NA
NA
9
. 500
. 500
NA
. 500
. 500
NA
NA
NA
. 400
. 400
. 400
NA
11
12
13
14
15
20
22
23
24
25
26
NA
400
400
175
. 500
. 500
NA
. 500
. 500
. 500
200
. 400
NA
NA
. 400
125
125
200
400
NA
. 400
NA
NA
. 400
NA
400
. 400
NA
. 400
NA
400
400
NA
NA
a NA, no activity.
Fig. 3.

G. Zosimo-Landolfo et al. / Il Farmaco 53 (1998) 623±625
625
Table 2
General synthetic conditions and melting points in 8C
Nitrone
Solvent
Reaction temperature (8C)
Reaction time (h)
Yield (%)
M.p. (8C)
83.7±85.3
1
2
Methanol
Pyridine
Benzaldehyde
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
65
20
0.5
12
12
5
65
87
76
55
79
75
70
70
70
68
84
93
80
72
85
70
82
95
90
60
68
60
72
82
64
77
64
78
78
39
78
85
94
61
75
73
57
90
71
38
78
40
34
76
98
81
129.0±129.7
145.0±145.5
183.4±185.5
131.4±132.5
230.6±230.7
171.1±171.5
159.3±162.5
175.0±176.0
159.0±160.0
188.3±189.5
162.4±167.4
119.0±121.1
116.2±116.5
129.6±130.9
120.9±121.4
45.9±46.0
3
20
4
110
20
5
12
2
6
110
110
110
110
20
7
2
8
2
9
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
12
4
Toluene
Furfuraldehyde
Toluene
Toluene
Toluene
Toluene
THF
110
20
4
110
110
110
110
20
2
2
2
2
12
12
12
12
2
Ethanol
Benzene
Benzaldehyde
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
75
82.5±83.3
80
20
41.0±42.0
118.2±119.2
108.0±109.3
100.5±103.1
128.3±130.0
50.9±52.4
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
2
2
2
2
109.9±111.5
62.0±63.5
2
1
139.0±141.0
104.5±106.5
51.9±53.9
2
1
3
117.2±119.2
85.5±85.7
1
0.5
1
147.1±148.7
118.5±119.4
247.5±248.5
125.1±125.8
138.2±139.9
108.9±110.6
114.6±115.3
141.1±142.4
226.0±228.0
57.7±59.2
2
1
1
1
1
2
2
0.5
1
53.4±54.3
Syrup
2
1
74.3±75.7
1
0.5
71.9±73.6
71.7±73.1
[5] J.M.J. Tronchet, G. Zosimo-Landolfo, N. Bizzozero, D. Cabrini, F.
Habashi, E. Jean, M. Geoffroy, Terminal deoxy hydroxyaminosugars,
Carbohydr. Chem. 7 (1988) 169±186.
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