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V. L. Gein et al.
(3.71 – 3.96 ppm), a broad signal from protons of the enol
hydroxy groups (9.31 – 9.75 ppm), and a signal of protons in
the phenol hydroxy group (8.82 – 8.84 ppm) in compounds
XXI, XXII, X, XI (Table 2).
EXPERIMENTAL BIOLOGICAL PART
The synthesized compounds were tested for
bacteriostatic activity using a conventional method of double
serial dilutions in a beef-infusion broth. A daily culture
grown in the broth was washed off with a sterile physiologi-
cal solution of sodium chloride and used to prepare the stock
solution with a bacterial load of 500 ´ 106 microbial cells per
ml (as determined according to the bacterial standard). The
stock solution was diluted to 1/100 with sterile broth to ob-
tain a working solution, and 0.1 ml of this solution (with a
microbial load of 5 ´ 106 per ml) was introduced into 2 ml of
the broth. The bacterial load in the sample was 250,000 mi-
crobes per ml. The bacteriostatic effect was assessed by the
presence or absence of the growth of test microbes upon in-
cubation for 18 – 20 h at 36 – 37°C. The acting dose was es-
timated as the minimum concentration (MIC, mg/ml) inhibit-
The data of 1H NMR spectroscopy and the reaction with
iron(III) chloride suggest that the synthesized compounds
I – XXVIII occur predominantly in the enolic form.
EXPERIMENTAL CHEMICAL PART
1
The H NMR spectra were measured on Bruker DRX
500 (working frequency, 500.13 MHz) and WM-250
(250.13 MHz) spectrometers (Germany) using DMSO-d6 as
the solvent and HMDS as the internal standard. The IR ab-
sorption spectra were recorded on the UR-20 and Specord
M-80 spectrophotometers (Germany) using samples pre-
pared as nujol mulls. The course of the reactions was fol-
lowed and purity of the reaction products was checked by
TLC on Silufol UV-254 plates eluted with a ben-
zene – acetonitrile – ethyl acetate (2 : 1 : 1) mixture. The
spots of 4-acetylpyrrolin-2-ones (I – XI) were revealed by
exposure to iodine vapor, while the spots of compounds
XII – XXVIII were detected under UV illumination. The
data of elemental analyses agree with the results of calcula-
tions using the empirical formulas.
General procedure for the synthesis of 5-aryl-4-acyl-
1-(N,N-dimethylaminoethyl)-3-hydroxy-3-pyrrolin-2-ones
(I – XXVIII). To a warm solution of 0.01 mole of an aro-
matic aldehyde and 0.01 mole of a 2,4-dioxobutanoic acid
methyl ether in 10 ml of 96% ethyl alcohol was added
N,N-dimethylethylenediamine (0.01 mole) and the reaction
mixture was allowed to stand for 24 h at room temperature.
The precipitate was separated by filtration and recrystallized
(see Table 1).
ing microbial growth.
It was established that all the synthesized compounds ex-
hibited a weak antimicrobial activity with MIC ranging from
250 to 1000 mg/ml.
REFERENCES
1. V. L. Gein, L. F. Gein , N. Yu. Porseva, et al., Khim.-Farm. Zh.,
25(12), 37 – 40 (1991).
2. V. L. Gein, O. V. Voronina, T. E. Ryumina, et al., Khim.-Farm.
Zh., 30(2), 25 – 26 (1996).
3. V. L. Gein, A. V. Popov, V. É. Kolla, et al., Khim.-Farm. Zh.,
27(5), 42 – 45 (1993).
4. M. D. Mashkovskii, Drugs [in Russian], Vol. 2, Kharkov (1997),
pp. 331, 375, 422.
Gein
