Synthesis and fungicidal activity of alkaloid-containing carbohydrates

Article abstract of DOI:10.1134/S1070427206030402

N-Glycosylamines, triethylammonium salt of xylosyl- and glucosylbenzyldithiocarbamates, and their derivatives containing fragments of alkaloids were synthesized; some of these substances exhibit fungicidal activity. Pleiades Publishing, Inc., 2006.

Full text of DOI:10.1134/S1070427206030402

ISSN 1070-4272. Russian Journal of Applied Chemistry, 2006, Vol. 79, No. 3, pp. 508 510. Pleiades Publishing, Inc., 2006.
Original Russian Text A.M. Gazaliev, O.A. Nurkenov, I.V. Kulakov, A.A. Ainabaev, D.V. Bessonov, 2006, published in Zhurnal Prikladnoi Khimii,
2006, Vol. 79, No. 3, pp. 517 519.
BRIEF
COMMUNICATIONS
Synthesis and Fungicidal Activity
of Alkaloid-Containing Carbohydrates
A. M. Gazaliev, O. A. Nurkenov, I. V. Kulakov, A. A. Ainabaev, and D. V. Bessonov
Institute of Organic Synthesis and Coal Fuel Chemistry of Kazakhstan Republic, Limited Liability Company,
Karaganda, Kazakhstan
Received December 23, 2005
Abstract N-Glycosylamines, triethylammonium salt of xylosyl- and glucosylbenzyldithiocarbamates, and
their derivatives containing fragments of alkaloids were synthesized; some of these substances exhibit
fungicidal activity.
DOI: 10.1134/S1070427206030402
Among numerous substances comprising the en-
vironment, carbohydrates and their derivatives occupy
an extremely important place and have enormous sig-
nificance in technology and everyday human activity.
Carbohydrates in the form of various derivatives enter
into the cell composition of any living body, playing
the role of structural material, energy source, sub-
1, 2
strates, and regulators of specific and biochemical
processes [1].
Modified derivatives of monosaccharides are of
great scientific and practical interest, since many of
these have pronounced biological activity with a wide
spectrum of effect. A number of derivatives of mono-
saccharides find wide use in medicine, e.g., as effec-
tive anticancer and antiviral agents [2]. All this stimu-
lates an interest in synthetic chemistry of modification
of monosaccharides.
3, 4
where R is H (1, 3), CH OH (2, 4).
2
The synthesized xyloxylbenzylamine (3) and glu-
cosylbenzylamine (4) are hygroscopic white crystal-
line substances darkening in air. Depending on the
synthesis conditions, N-glycosides can crystallize with
1 or 0.5 mol of water. When stored in a desiccator
over P O , they become anhydrous.
In recent years, N-glycosylamides (N-glycosides)
find expanding application for synthesis of natural
glycopeptides, their analogs, and glycoconjugates
used in various biological studies. N-Glycosylamines
are considered as potential pharmaceuticals, since
introduction of carbohydrate group into a molecule
not only increases the solubility but in some cases
alters the biological effect as well [3].
2
5
The IR spectra of the compounds contain an ab-
1
sorption band at 891 7 cm , suggesting -conforma-
tion at the anomeric center. Vibrations of the NH
group appear in the range 2880 2920 cm , and
We obtain a series of new carbohydrate-containing
derivatives based on xylose and glucose for sub-
sequent study of their reactivity and biological ac-
tivity.
1
out-of-plane bending modes of the CH group of
the aromatic ring, in the ranges 745 755 and 695
1
705 cm . The IR spectra of 3 and 4 show that they
Condensation of D-xylose (1) and D-glucose (2)
with benzylamine was performed in alcoholic solution
under heating by the procedure described in [4]:
contain no C=N bonds, i.e., they are not Schiff bases.
According to published data [5], the absorption in
508

SYNTHESIS AND FUNGICIDAL ACTIVITY
509
Physicochemical constants and elemental analyses of compounds 3 12
Found, %
Calculated, %
H N
Compound
Yield, %
mp,
C
Empirical formula
C
H
N
C
3
4
5
6
7
8
9
10
11
12
90.2
91.8
39.7
41.6
40.5
45.3
57.5
70.9
41.8
51.1
105 106
69 70
94 95
60.35
58.09
54.82
53.98
57.26
56.18
57.53
56.55
57.51
56.57
7.18
7.02
7.79
7.60
5.96
6.12
6.69
6.68
6.79
6.86
5.85 C12H17NO4
5.29 C13H19NO5
60.20
57.98
54.76
53.78
57.00
56.05
57.10
56.45
57.10
56.45
7.09
7.11
7.65
7.67
5.72
6.21
6.63
6.71
6.63
6.71
5.80
5.20
6.70
6.27
8.32
7.84
5.80
5.49
5.80
5.49
6.76 C19H32N2O4S2
6.33 C20H34N2O5S2
8.37 C24H29N3O5S2
7.90 C25H33N3O6S2
5.93 C23H32N2O5S2
5.58 C24H34N2O6S2
5.88 C23H32N2O5S2
5.59 C24H34N2O6S2
62 63
129 130
106 107
142 143
68 69
99 100
73 74
1
the range of 1120 1170 cm is characteristic of
cyclic forms of carbohydrates, since sugar alcohols
having the open-chain structure do not absorb in this
range, which is in good agreement with the data ob-
tained.
The synthesized xylosylbenzylamine (3) and glu-
cosylbenzylamine (4) are fairly reactive compounds.
Triethylammonium salts of xylosyl- and glucosylben-
zyldithiocarbamates (5, 6) were synthesized by the
reaction of the corresponding N-glycosides with car-
bon disulfide in ethanol in the presence of triethyl-
amine:
5, 6
7 12
3, 4
(7, 8);
=
(9, 10);
5, 6
where R is H (3, 5), CH OH (4, 6).
2
(11, 12),
The next stage is substitution of alkaloid fragment
for triethylamine by the reaction of triethylammonium
xylosyl- and glucosylbenzyldithiocarbamate with al-
kaloids cytisine, 1-ephedrine, and d-pseudoephedrine
in alcohol:
where R is H (5, 7, 9, 11); CH OH (6, 8, 10, 12).
2
Compounds 7 12 are white powders readily soluble
in water, ethanol, and DMF and insoluble in hydro-
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 79 No. 3 2006

510
GAZALIEV et al.
carbons. The composition and structure of 7 12 were
confirmed by elemental analysis and IR spectroscopy.
The IR spectra of 7 12 contain no absorption bands at
refrigerator. In a few hours, the substance completely
crystallized. The product was washed with anhydrous
ethanol and then with ether and dried in a desiccator
upon P O .
1
844 8 cm , which suggests -conformation of pyra-
2
5
nose ring of the compounds synthesized. In the range
Triethylammonium xylosyl- and glucosylbenzyl-
dithiocarbamates (5, 6). To a 0.01 M solution of
xylosyl- or glucosylbenzylamine in 5 ml of ethanol,
0.01 M of triethylamine was added with stirring, after
which 0.01 M of carbon sulfide in 10 ml of alcohol
was slowly added with cooling (3 5 C), and the mix-
ture was stirred for 60 min at room temperature. After
slight cooling, a precipitate formed. The precipitate
was washed with anhydrous ethanol and then with
anhydrous ether and dried in a desiccator upon P O
1
2900 2930 cm , there are stretching vibration bands
1
of the N H bond; at 1640 1650 cm , the >N C=O
1
bands; and at 1070 1100 cm ; the thiocarbonyl
group (C=S) bands.
There are contradictory opinions on how the im-
portant structural feature of carbohydrates, the pres-
ence of pyranose or furanose ring, is manifested in the
IR spectrum [6]. The presence of several peaks in
1
the range 1010 1090 cm suggests the pyranose
2
5
.
form of the glycoside fragment.
Cytisine xylosyl- and glucosylbenzyldithiocar-
bamates (7, 8). To a stirred 0.001 M solution of com-
pound 5 or 6 in 3 ml of ethanol, a 0.001 M solution of
cytosine in 5 ml of ethanol was added at room tem-
perature, and the mixture was stirred for 60 min. Then
the mixture was heated at 55 58 C for 3 h. The solv-
ent was removed on a water bath. The oily product
was triturated with petroleum ether. The resulting
powder was washed with diethyl ether.
The characteristics of 3 12 are listed in the table.
The spectra of all the compounds studied are charac-
terized by broad strong bands in the range 3250
1
3400 cm , caused by stretching vibrations of OH
groups.
Two synthesized compounds 7 and 8 were tested
for fungicidal activity. Phytopathogenic fungi Fusari-
um oxysporum and Botrytis cinerea were used as test
cultures. The fungicidal activity was estimated from
the intensity of microorganism development in a
nutrient medium in comparison with the reference
tests without addition of the compounds studied.
Compounds 9 12 were obtained similarly (see
table).
CONCLUSIONS
(1) N-Glycosylamines based on xylose and glucose
were synthesized.
We found that cytisine salts of xylosyl- and gluco-
sylbenzyldithiocarbamates tested in vitro have pro-
nounced fungicidal activity against phytopathogenic
fungi Fusarium oxysporum (72 78 and 69 74% sup-
(2) Triethylammonium xylosyl- and glucosylben-
zyldithiocarbamates and their derivatives containing
fragments of alkaloids cytisine, 1-ephedrine, and
d-pseudoephedrine were synthesized.
1
pression of development, respectively).
The results obtained were recorded in a statement
of biological tests.
(3) Cytisine xylosyl- and glucosylbenzyldithiocar-
bamates exhibit pronounced fungicidal activity.
EXPERIMENTAL
REFERENCES
The IR spectra were recorded on an Avatar-320
spectrometer in KBr pellets. Melting points were de-
termined on a Boetius device. The reaction course and
purity of the resulting compounds were monitored by
thin-layer chromatography on Silufol UV-254 plates
in the system isopropanol : ammonia : water = 7:2 :1.
The plates were developed with iodine vapor.
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Radiatsionnaya khimiya uglevodov (Radiation Chemis-
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2. Kochetkov, N.K., Bochkov, A.F., Dmitriev, B.A., et al.,
Khimiya uglevodov (Chemistry of Carbohydrates),
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1944, vol. 76, nos. 9 10, pp. 935 940.
4. Sorokin, W., Ber., 1887, vol. 20, p. 783.
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6. Stepanenko, B.N., Khimiya i biokhimiya uglevodov
(monosakharidy) (Chemistry and Biochemistry of Car-
bohydrates (Monosaccharides)), Moscow: Vysshaya
Shkola, 1977.
Xylosyl- and glucosylbenzylamine (3, 4). To a
0.05 M solution of benzylamine and 8 ml of alcohol,
0.05 M of anhydrous finely ground carbohydrate was
added. The mixture was heated on a water bath at
60 65 C for 20 min, then 10 ml of alcohol was
added, and the solution was left to crystallize in a
1
The studies were carried out at the Research Institute of Plant
Protection (Almaty, Kazakhstan).
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 79 No. 3 2006