Synthesis and biological activity of certain derivatives of selenoglucosides

Article abstract of DOI:10.1007/s10593-009-0371-y

The condensation of 1-Se-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose with trimethylchlorosilane, triphenylchlorosilane, dibutylchloroarsine, and diphenylchloroarsine has been studied. New derivatives of selenoglucosides have been synthesized. The biocidal pr

Full text of DOI:10.1007/s10593-009-0371-y

Chemistry of Heterocyclic Compounds, Vol. 45, No. 8, 2009
SYNTHESIS AND BIOLOGICAL
ACTIVITY OF CERTAIN DERIVATIVES
OF SELENOGLUCOSIDES
N. N. Sidamonidze1, R. A. Gakhokidze1, L. G. Arabuli1*, and Z. Sh. Lomtatidze1
The condensation of 1-Se-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose with trimethylchlorosilane,
triphenylchlorosilane, dibutylchloroarsine, and diphenylchloroarsine has been studied. New derivatives
of selenoglucosides have been synthesized. The biocidal properties of the synthesized compounds have
been studied.
Keywords: Se-glucose, dibutylchloroarsine, diphenylchloroarsine, trimethylchlorosilane, triphenyl-
chlorosilane.
For some time past wide opportunities have arisen for the use of organic compounds containing sulfur,
selenium, arsenic, and other heteroatoms in agriculture, medicine, and industry. It is known that organosilicon
compounds serve for the prophylaxis of the formation and growth of tumors (various forms of leukemia,
Ehrlich’s tumor, sarcoma 180, etc.) [1, 2]. At the present time various organic and inorganic arsenic-containing
compounds have been approved. These possess bactericidal and fungicidal properties and are successfully
applied against a series of pathogenic microorganisms participating in biodegradation [3, 4]. The biocidal
properties of selenium-containing organic compounds have been studied comparatively little.
The application of glycosides for the modification of biologically active organic compounds of silicon,
selenium, and arsenic may, on the one hand, change their biological and physiological action, and on the other,
may reduce their toxicity.
The synthesis of derivatives of selenoglucosides has been carried out and their bactericidal action has
been investigated in the present work.
1-Selenotrimethylsilyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (2), 1-selenotriphenylsilyl-2,3,4,6-tetra-
O-acetyl-β-D-glucopyranose (3), 1-selenodibutylarsinyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (4), and
1-selenodiphenylarsinyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (5) have been synthesized by the
condensation of 1-Se-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (1) with chlorotrimethylsilane, chlorotriphenyl-
silane, dibutylchloroarsine, and chlorodiphenylarsine.
To clarify the bactericidal properties of the compounds 2-5 synthesized by us their effect was tested on
the growth and development of certain microorganisms.
_______
* To whom correspondence should be addressed, e-mail: L.Arabuli@yahoo.com.
1 Tbilisi State University, Tbilisi 0128, Georgia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1167-1170, August, 2009. Original
article submitted October 25, 2007; revision submitted July 2, 2008.
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0009-3122/09/4508-0926©2009 Springer Science+Business Media, Inc.

The synthesized compounds displayed a selective effect on the growth and development of various
microorganisms. Thus, at concn. = 1.0 g/liter compounds 3 and 5 possess high activity in relation to
Actinomyces griseus (suppression zones 7.0 and 10.0 mm respectively).
R
CH2OAc
O
R
Se
Si
R3SiCl
Et3N
R
OAc
CH2OAc
O
Ac O
SeH
OAc
2, 3
OAc
Ac O
CH2OAc
O
R
As
Se
OAc
R2AsCl
Et3N
R
1
OAc
Ac O
OAc
4, 5
2 R = Me, 3, 5 R = Ph, 4 R = Bu
Moderate activity in relation to Actinomyces streptomicini was detected for compounds 2, 4, and 5
(suppression zone 4.0 mm). In relation to the phytopathogenic bacterium Xanthomonas compestris only
compound 5 proved to be active, although the activity was low (suppression zone 2 mm). Compounds 3 and 5,
possessing high activity, contain phenyl groups in their molecules.
The results of the investigation make it possible to show the biologically active groups in the
compounds investigated and to establish a certain correlation between structure and biological activity, which is
promising for the purpose-directed search for new compounds with their biological properties previously
designed.
EXPERIMENTAL
The IR spectra were obtained on an AVAKA 250 spectrometer in KBr disks. Optical rotation was measured
on a SU-3 universal saccharimeter. 13C NMR spectra were recorded on a Bruker AM-300 (75 MHz) in CDCl3,
internal standard was TMS.
TABLE 1. Effect of Compounds 2-5 on the Growth and Development of
Microorganisms
2
3
4
5
Control
Test microorganism
Suppression zone of microorganism, mm at concn., g/liter
1.0
3.0
4.0
0.5
0.1
2.0
1.5
0
1.0
7.0
3.5
1.0
0.1
4.0
2.5
0.5
1.0
3.0
4.0
0
0.1
1.0
0.1
7.0
2.5
0.0
0.0
0.5
0.4
0.1
Actynomyces
griseus
1.0 10.0
Actynomyces
streptomicini
Xanthomonas
compestris
1.5
0
4.0
2.0
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1-Seleno-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (1). Yield was 67.5%, mp 94-95oC, Rf 0.9 (hexane–
ethyl acetate, 6:4), [α]D +21o (c 0.62, chloroform). IR spectrum, ν, cm-1: 2580 (Se-H); 1720 (C=O); 1010, 1040 (C–
O–C). Found, %: C 40.02; H 5.11. C14H20O9Se. Calculated, %: C 40.87; H 4.6.
1-Seleno-R3Si-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoses 2, 3 and 1-Seleno-R2As-2,3,4,6-tetra-
O-acetyl-β-D-glucopyranoses 4, 5 (General Method). An ether solution of the appropriate R3SiCl or R2AsCl
(1.8 mmol) was added dropwise with stirring and heating (50-60oC) to a solution of selenoglucose 1 (0.62 g,
1.4 mmol) in chloroform (25 ml) and triethylamine (0.32 ml). Stirring was continued for 2 h (compound 2) or 1 h
(compound 3) and left for 18 h at ~20oC (compounds 4 and 5 were left without additional stirring). The separated
solid triethylamine hydrochloride was filtered off, and washed with ether. The combined filtrates were treated with
activated carbon, and concentrated in vacuum until the start of crystallization. The precipitated crystals were filtered
off and recrystallized twice from ethanol. Chromatographically pure compounds were obtained.
1-Selenotrimethylsilyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (2). White crystals, yield 0.44 g
(60%); mp 96-97oC, [α]D +13.4o (c 0.32, chloroform), Rf 0.51 (benzene–dioxane, 3:1). 13C NMR spectrum, δ,
ppm: 91.8 (C-1); 84.7 (C-2); 74.5 (C-3); 70.8 (C-4); 71.9 (C-5); 69.2 (C-6); 168.2-170.6 (C=O); 10.2-27.5
(CH3). Found, %: C 42.60; H 6.00; Si 6.10. C17H28O9SeSi. Calculated, %: C 42.20; H 5.80; Si 5.80.
1-Selenotriphenylsilyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (3). Yield 0.63
g (63%); mp
192-193oC, Rf 0.63 (chloroform–methanol, 4:1), [α]D +22.7o (c 0.4, chloroform). 13C NMR spectrum, δ, ppm: 95.5
(C-1); 71.2 (C-2); 73.6 (C-3); 66.8 (C-4); 77.0 (C-5); 62.5 (C-6); 170.4-175.6 (C=O); 20.6-29.7 (CH3); 127.1-133.6
(C6H5). Found, %: C 57.40; H 5.10; Si 4.23. C32H34O9SeSi. Calculated, %: C 57.40; H 5.08; Si 4.20.
1-Selenodibutylarsinyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (4). Yield 0.82 g (55%); mp
13
114-115oC, Rf 0.82 (petroleum ether–benzene, 1:1), [α]D +20.1o (c 0.3, chloroform). C NMR spectrum, δ, ppm:
92.5 (C-1); 71.2 (C-2); 73.4 (C-3); 69.0 (C-4); 76.8 (C-5); 62.8 (C-6); 167.5-172.5 (C=O); 35.4-42.0 (CH2);
13.6-22.2 (CH3). Found, %: C 44.35; H 6.20; As 14.11. C22H37AsO9Se. Calculated, %: C 44.10; H 6.18; As 12.50.
1-Selenodiphenylarsinyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (5). Yield 0.49 g (51%); mp
131-132.5oC, Rf 0.31 (petroleum ether–benzene, 1:1), [α]D +15.7o (c 0.47, chloroform). 13C NMR spectrum, δ,
ppm: 95.5 (C-1); 71.2 (C-2); 73.5 (C-3); 68.8 (C-4); 73.7 (C-5); 62.5 (C-6); 168.0-171.0 (C=O); 20.0-21.9
(CH3); 136.0-137.0 (C6H5). Found, %: C 49.20; H 4.90; As 12.40. C26H29AsO9Se. Calculated, %: C 48.80;
H 4.50; As 11.70.
Determination of Bactericidal Activity. As test microorganisms actinomycetes producing
physiologically active substances were used, viz. Actinomyces griseus, Actinomyces streptomicini, and the
phytogenic bacterium Xanthomonas compestris. Solid nutrient media were used for incubating test organisms:
Krasil'nikov medium (1 g KNO3, 0.5 g K2HPO4, 0.5 g NaCl, 0.5 g MgSO4, traces of FeSO4, 1 g CaCO3, 20 g
starch, water) was used for actinomycetes and meat-peptone agar (MPA) for bacteria. The effect of the
synthesized compounds on the growth and development of microorganisms was studied by the Egorov method
(alveolar method) [5]. The size of the toxic action was determined from the sterility zone around a hole. A
solvent mixture of ethyl alcohol–chloroform, 1:1 served as control. Substances of concentration 1.0 and 0.1 g/l
were placed in the hole. The results of the investigations are given in Table 1.
REFERENCES
1.
E. Ya. Lukevics and Z. Ya. Zelmene, Biological Activity of Silicon Compounds [in Russian], Riga
(1984), 301 pp.
2.
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M. A. Ignatenko, Khim.-farm. Zh., 28, 401 (1984).
L. P. Asatiani and Z. Sh. Lomtatidze, Khim.-farm. Zh., 28, 576 (1984).
Z. Sh. Lomtatidze and K. A. Laperashvili, Gruz. Mikrobiol. Obshchest., 2, 93 (1992).
D. S. Egorov, Handbook of Microbiology [in Russian], Izd. MGU, Moscow (1976), p. 245.
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