Synthesis and properties of 2-cyanoethoxy derivatives of dammarane triterpenoids

Article abstract of DOI:10.1134/S1070428015110184

Cyanoethylation of dammaran-3β-ols and 3-oxime dammarene, semisynthetic derivatives of the natural dipterocarpol, afforded a series of new dammarane triterpenoids containing 2-cyanoethoxy fragment at the carbon atom in the position 3 of the tetracyclic scaffold. A notable antiviral activity was found in 20(S)-3-[(2-cyanoethoxy)imino]-dammar-24-en-20-ol and 20(S)-3-O-(2-cyanoethyl)-25,26,27-trinor-20,24-olidedammarane.

Full text of DOI:10.1134/S1070428015110184

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 11, pp. 1627–1632. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © A.S. Kaledina, A.D. Zorina, V.V. Zarubaev, V.V. Anokhina, E.B. Erkhitueva, R.E. Trifonov, 2015, published in Zhurnal
Organicheskoi Khimii, 2015, Vol. 51, No. 11, pp. 1656–1661.
Synthesis and Properties of 2-Cyanoethoxy Derivatives
of Dammarane Triterpenoids
A. S. Kaledinaa, A. D. Zorinaa, V. V. Zarubaevb, V. V. Anokhinaa,
E. B. Erkhituevaa, and R. E. Trifonova
a St. Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg, 199034 Russia
e-mail: rost_trifonov@mail.ru; r.trifonov@spbu.ru
b Research Institute of Influenza, St. Petersburg, Russia
Received September 15, 2015
Abstract—Cyanoethylation of dammaran-3β-ols and 3-oxime dammarene, semisynthetic derivatives of the
natural dipterocarpol, afforded a series of new dammarane triterpenoids containing 2-cyanoethoxy fragment at
the carbon atom in the position 3 of the tetracyclic scaffold. A notable antiviral activity was found in 20(S)-3-
[(2-cyanoethoxy)imino]-dammar-24-en-20-ol and 20(S)-3-О-(2-cyanoethyl)-25,26,27-trinor-20,24-olide-
dammarane.
DOI: 10.1134/S1070428015110184
Naturally occurring triterpenoids of oleanane and
lupane family as well as their semisynthetic derivatives
exhibit various types of biological activity and are
utilized in development of new drugs, in particular,
antiviral means [1, 2]. Lately the antiviral action was
studied of glycyrrhetic acid and betulin. It was shown
that the introduction of substituents of various
electronic nature resulted in formation of new meta-
bolically stable candidate substances. For instance, the
succinate of 18β-glycyrrhetic acid [3], as well as
dimethyl succinate and dimethyl glutarate (at С3 and
С28) of betulin proved to be promising compounds
with a high anti-HIV action. Betulinic acid dimethyl
succinate became the basic compound of antiviral
pharmaceutical bevirimat used in the treatment of
AIDS and enteroviruses [2, 3]. It is also known that
amides, hydrazones, hydrazides, oxazoles, cyanalkyl
and other nitrogen-containing betulin and oleanane
acids derivatives are capable to suppress the
reproduction of viruses of influenza, papilloma,
enterovirus ECHO6, and herpes [4–13].
According to published information natural tri-
terpenoids of dammarane series exhibit a wide range of
biologic action [14–17], yet few data on preparation
and properties of semisynthetic derivatives of this
series are reported. We showed formerly that the damma-
rane triterpenoid alninkanone [20(S),24(R)-20,24-epoxy-
24-methyldammaran-3-one] 1 exhibited a pronounced
inhibiting activity with respect to influenza viruses of
types А (Н3N2) and В (Hong Kong flu) [18].
2,3- and 3,4-Seco acids obtained from alninkanone
1 proved to be active against type A flu virus
(protection index 60%) [19].
OH
O
O
O
1
2
1627

KALEDINA et al.
1628
Scheme 1.
O
O
O
O
30% KOH,
[(C3H7)4N]+OH ,
_
NaBH4_BF3 Et2O
.
CrO3, AcOH
CH2=CHCN
2
THF
HO
O
O
3
4
5
CN
In continuation of research on looking for new
NMR spectrum, and also by chromatographic and
spectral data.
biologically active semisynthetic derivatives of natural
dipterocarpol (20S-hydroxydammaran-24-en-3-one) 2
and its analogs we obtained in this study a series of 2-
cyanoethoxy-substituted dammarane triterpenoids and
their antiviral activity was tested.
The syntheses of 3-cyanoethoxy derivatives of
dammarane 7 (Scheme 2) and 9 (Scheme 3) we
succeeded to perform in two stages. In the first stage
the keto group at С3 of triterpenoid 2 and lactone 3 was
reduced to the 3β-hydroxy group with sodium
tetrahydroborate in ethanol to obtain dammaranediol 6
(Scheme 2) and 3β-hydroxylactone 8 (Scheme 3). The
structure of compounds 6 and 8 was confirmed by the
presence of the signal of the proton Н3α at 3β-hydroxyl
[δ 3.20 ppm (1Н, С3Н)]. Further in similar conditions
20(S)-3-О-(2-cyanoethyl)dammar-24-en-20-ol 7 and
20(S)-3-О-(2-cyanoethyl)-25,26,27-trinor-20,24-olide-
dammarane 9 were synthesized.
In the first stage we synthesized dammarane
triterpenoid 3 containing a lactone fragment in the
position 17 by oxidation of dipterocarpol 2 with chro-
mic anhydride along procedure [20, 21] (Scheme 1).
Further the reduction of 20(S)-25,26,27-trinor-20,24-
olidedammaran-3-one 3 with boron trifluoride etherate
and sodium tetrahydroborate afforded 20(S)-25,26,27-
trinor-20,24-epoxydammaran-3β-ol 4 [21].
Cyanoethylation of epoxy compound 4 with acrylo-
nitrile in dioxane in the presence of tetrapropylammo-
nium hydroxide at room temperature led to the
formation of cyanoethyl derivative of epoxydammara-
ne 5 in a good yield (Scheme 1). The structure of 20(S)-
3-О-(2-cyanoethyl)-25,26,27-trinor-20,24-epoxydam-
marane 5 was confirmed by the presence of an
absorption band of the stretching vibrations of СN
group at 2252 cm–1 in the IR spectrum, by the signals
of the methylene protons of the cyanoethyl fragment at
The structures of compounds 7 and 9 were
confirmed by the presence of the absorption band of
the cyano group stretching vibrations at 2250 cm–1 in
the IR spectra, by characteristic signals of the
methylene protons of the cyanoethyl fragment at δ
2.58, 3.55, 3.72 ppm in the 1Н NMR spectrum, and by
the signal of the carbon atom of the cyano group at δ
118.2 ppm in the 13С NMR spectra. The reaction of
compound 6 occurred selectively at the secondary
hydroxy group at the atom С3 not affecting the tertiary
hydroxyl at the atom С20.
1
δ 2.59, 3.57, 3.77 ppm in the Н NMR spectrum, of
carbon atom of cyano group at δ 118.2 ppm in the 13С
Scheme 2.
OH
OH
[(C3H7)4N]+OH_,
30% KOH,
CH2=CHCN
NaBH4, EtOH
2
NC
HO
O
6
7
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

SYNTHESIS AND PROPERTIES OF 2-CYANOETHOXY DERIVATIVES OF DAMMARANE
1629
Scheme 3.
O
O
O
[(C3H7)4N]+OH_,
O
O
O
30% KOH,
CH2=CHCN
NaBH4, EtOH
HO
NC
O
O
9
3
8
Yields of compounds 5, 7, and 9 were 45, 22, and
boiling substrate 2 with hydroxylamine hydrochloride
in pyridine (Scheme 4). In the 13С NMR spectrum of
3-oxime 10 the signal of the carbonyl carbon atom at
δ 218.03 ppm is absent, and a signal of the C=NOH
group appears at 167.24 ppm. The cyanoethylation
of compound 10 in the above described conditions
led to the formation in a good yield of 20(S)-3-N-
(2-cyanoethoxyimino)dammar-24-en-20-ol 11
(Scheme 4).
81% respectively. We failed to increase the yields by
varying the reaction duration and the other conditions.
Besides the target products the reaction mixture
contained the initial hydroxy derivatives 4, 6, and 8
due apparently to the reversibility of Michael reaction.
The individual cyanoethoxy derivatives were isolated
by column chromatography.
We also synthesized 2-cyanoethoxy derivative of
dipterocarpol 10, where the cyanoethyl group is
attached to the oxygen atom of the oxime fragment
involving the atom С3. According to published data the
triterpene oximes showed often a high biologic
activity; for instance, oxime of betulonic acid turned
out to be more active than the acid proper with respect
to viruses of flu type A and herpes [8, 9]. Oxime of
dipterocarpol 10 was obtained in a good yield by
The structure of 20(S)-3-(2-cyanoethoxyimino)
dammar-24-en-20-ol 11 was confirmed by the
presence of the absorption band of СN group in the IR
spectrum, and also by the signals of protons of the
1
methylene groups at δ 3.72 and 4.23 ppm in the Н
NMR spectrum and by the only carbon atom signal in
the downfield region at 118.00 ppm in the 13С NMR
spectrum. No splitting of the CN group signal in the
Scheme 4.
OH
OH
NH2OH, Py
HO
O
N
2
10
OH
[(C3H7)4N]+OH_,
CN
30% KOH,
CH2=CHCN
O
N
11
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

KALEDINA et al.
1630
13С NMR spectrum, and also published data on the
formation of exclusively E-isomer at the C=N bond in
oximes and cyanoethoxyimines at С3 in the А ring of
lupane and oleanane triterpenoids [13], made it
possible to ascribe to the structure of compound 11 just
Е-configuration.
(3Н, С19Н3), 0.89 s (3Н, С18Н3), 0.98 s (3Н, С28Н3),
1.01 s (3Н, С29Н3), 1.14 s (3Н, С21Н3), 1.11–1.62 m
(12Н, СН, СН2), 1.63–1.95 m (1Н, С13Н), 1.96–2.04
m (8Н, СН, СН2), 2.05–2.11 m (4Н, СН, СН2), 2.57 t
(2Н, С2'Н2, J 6.5 Hz), 3.57 m (1Н, С1'Н2), 3.78 m (1Н,
С1'Н2), 3.81 m (2Н, С24Н2). 13С NMR spectrum
(СDCl3), δ, ppm: 15.52, 15.89, 16.05, 16.12, 16.20,
19.28 (С2'), 21.63, 22.98, 24.94, 25.78, 26.47, 26.95,
28.09, 31.22, 35.04, 35.28, 37.08, 38.82, 38.99, 40.40,
43.08, 49.81, 49.96, 50.72, 56.29, 64.16 (С1'Н2), 66.75,
85.96 (С20), 87.73 (С3Н), 118.19 (CN). Mass spectrum
(ESI), m/z (Irel, %): 478.3682 [M + Na]+. С30Н49NO2.
Calculated M 455.3763.
All compounds synthesized in this study were
tested for antiviral activity with respect to influenza
virus A/Puerto Rico/8/34 (H1N1) on MDCK cells.
Among the cyanoethoxy derivatives of dammarane
triterpenoids a considerable activity was shown by
lactone 9 (selectivity index SI 10) and cyano-
ethoxyimine 11 (selectivity index SI 9).
20(S)-Dammar-24-en-20,3β-diol (6). To 4 g
(0.009 mol) of 20(S)-hydroxydammar-24-en-3-one 2
dissolved in 70 mL of ethanol was added 470 mg
(0.012 mol) of sodium tetrahydroborate, and the
mixture was refluxed for 24 h at 80°C. Then the
reaction mixture was diluted with water and acidified
to рН 2. The precipitate was filtered off, washed,
dried, and recrystallized from a mixture petroleum
ether–ethyl acetate. Yield 2.4 g (60%), mp 132–134°C
(134–135°С [16]).
EXPERIMENTAL
TLC was performed on Silufol plates, eluent
hexane (petroleum ether)–ethyl acetate, 4 : 1 and 2 : 1;
the development by spraying with a 5% solution of
anisaldehyde and sulfuric acid in ethanol followed by
heating to 100–120°C for 2–3 min. Melting points
were measured on a small heating block PHMK VEB
Wagetechnik Rapido. IR spectra were recorded on a
spectrophotometer Perkin Elmer Spectrum BX from
20(S)-25,26,27-Trinor-20,24-olidedammaran-3β-
ol (8) was obtained from lactone 3 analogously to
compound 6. Reduced lactone 8 melted at 200–201°C
(203–206°С [21]). No depression was observed at
melting a mixed sample with an authentic compound.
The spectral data were consistent with the published
information [21].
1
pellets with KBr. Н and 13С NMR spectra were
registered on a spectrometer Bruker Avance II 400
(operating frequencies 400 and 100 МHz respectively).
Mass spectra were obtained on an instrument maXis
Bruker. Rotation angles were measured on an
Automatic polarimeter AA-55.
Dipterocarpol 2 was obtained by extraction with
ethyl acetate from latex of Dipterocarpus alatus
followed by recrystallization from a mixture ethyl
acetate–hexane [20].
20(S)-3-О-(2-Cyanoethyl)-dammar-24-en-20-ol
(7) was obtained similarly to compound 5. Yield 1.24 g
(45%), mp 251–253°C, [α]D22.7 +53.7° (c 1.0, CHCl3).
1Н NMR spectrum (СDCl3), δ, ppm: 0.78 s (3Н,
С30Н3), 0.86 s (3Н, С19Н3), 0.88 s (3Н, С18Н3), 0.96 s
(3Н, С28Н3), 0.98 s (3Н, С29Н3), 1.15 s (С21Н3), 1.63 s
(3Н, С26Н3), 1.69 s (3Н, С27Н3), 1.10–1.19 m (8Н, СН,
СН2), 1.20–1.60 m (11Н, СН, СН2), 1.63–1.83 m (1Н,
С13Н), 1.98–2.20 m (5Н, СН, СН2), 2.55 t (2Н, С2'Н2,
J 6.6 Hz), 3.55 m (1Н, С1'Н2), 3.71 m (1Н, С1'Н2), 5.20
t (1Н, С24Н, J 6.7 Hz). 13С NMR spectrum (СDCl3), δ,
ppm: 16.11, 16.20, 16.42, 17.70, 18.17, 18.40, 19.05
(C2'H2), 21.55, 22.54, 22.96, 24.08, 25.38, 25.73,
27.52, 28.08, 31.16, 35.22, 37.05, 38.78, 38.98,
40.40, 40.48, 42.25, 49.84, 50.27, 50.63, 56.28, 64.15
(C1'H2), 75.39, 87.70 (С3Н), 118.19 (СN), 124.73
(C24H), 131.54 (C25). Mass spectrum (ESI), m/z (Irel,
%): 520.4146 [M + Na]+, С33Н55NO2. Calculated M
497.4232.
20(S)-3-О-(2-Cyanoethyl)-25,26,27-trinor-20,24-
epoxydammarane (5). A mixture of 0.52 g (0.0013 mol)
of 20(S)-25,26,27-trinor-20,24-epoxydammaran-3β-ol
4, 1.71 mL (0.026 mol) of acrylonitrile, 0.65 mL of
tetrapropylammonium hydroxide, and 1.7 mL of 30%
KОН solution in 10 mL of dioxane was stirred at room
temperature in an argon atmosphere for 2 h. Then the
reaction mixture was poured in a beaker containing
100 mL of ice and 1 mL of 15% hydrochloric acid.
The precipitate was filtered off, washed with water till
neutral washings, and dried in air. The reaction product
was purified by flash-chromatography on silica gel.
Eluent hexane–ethyl acetate. Yield 0.42 g (81%), mp
193–195°C, [α]D23.5 +48.7° (c 1.0, CHCl3). Н NMR
1
spectrum (СDCl3), δ, ppm: 0.80 s (3Н, С30Н3), 0.90 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

SYNTHESIS AND PROPERTIES OF 2-CYANOETHOXY DERIVATIVES OF DAMMARANE
1631
20(S)-3-О-(2-Cyanoethyl)-25,26,27-trinor-20,24-
olidedammarane (9) was obtained similarly to com-
pound 5. Yield 0.108 g (22%), mp 197–199°C, [α]D22.8
+208.32° (c 1.0, CHCl3). 1Н NMR spectrum (СDCl3), δ,
ppm: 0.79 s (3H, С30Н3), 0.86 s (3H, С19Н3), 0.90 s (3H,
С18Н3), 0.97 s (3H, С28Н3), 1.00 s (3H, С29Н3), 1.38 s
(3H, С21Н3), 1.11–1.62 m (12Н, СН, СН2), 1.63–1.83
m (1Н, С13Н), 1.84–2.04 m (8Н, СН, СН2), 2.05–2.20
m (4Н, СН, СН2), 2.59 t (2Н, С2'H2, J 6.4 Hz), 3.56 m
(1H, C3'H2), 3.81 m (1H, C3'H2). 13С NMR spectrum
(СDCl3), δ, ppm: 15.48, 16.05, 16.11, 16.17, 16.22,
19.28 (С2'Н2), 21.44, 22.94, 25.05, 25.48, 26.8, 28.09,
29.20, 31.02, 31.18, 35.19, 37.06, 38.78, 38.99, 49.35,
40.41, 43.17, 50.16, 50.57, 56.27, 64.15 (С1'Н2), 87.67
(С3Н), 90.12(С20), 118.17 (СN), 176.73 (С24). Mass
spectrum (ESI), m/z (Irel, %): 492.3459 [M + Na]+.
С30Н47NO3. Calculated M 469.35559.
СН2), 1.59–1.75 m (8Н, СН, СН2), 1.80–2.11 m (4Н,
СН, СН2), 2.25–2.33 m (1Н, С13Н), 3.71 t (2H, C1'H2,
J 6.5 Hz), 4.23 t (2Н, С2'H2, J 6.4 Hz), 5.14 t (1Н,
С24Н, J 6.8 Hz). 13С NMR spectrum (СDCl3), δ, ppm:
15.36, 15.48, 16.20, 16.35, 17.71, 18.03, 18.38 (C2'H2),
19.04, 21.81, 22.56, 24.79, 25.44, 25.75, 27.48, 27.52,
31.13, 34.78, 37.06, 39.01, 40.44, 40.48, 40.51, 42.32,
49.80, 50.19, 50.29, 55.93, 67.29 (C1'H2), 75.36,
118.00 (CN), 124.71 (C24H), 131.60 (C25), 168.27 (C3).
Mass spectrum (ESI), m/z (Irel, %): 533.4103 [M + Na]+.
С33Н54N2O2. Calculated М 510.41853.
Examination of cytotoxicity in vitrо. The cyto-
toxicity of compounds was estimated in experiments
on cell culture MDCK that was incubated for 48 h at
37°C in a carbon dioxide incubator in an atmosphere
of 5% of CO2. From the studied compounds a double
dilution series was prepared of concentrations from
500 to 3 µg/mL in supporting medium Eagle MEM
and the microtetrazolium (MTT) test was carried out
on 96-well plate templates [22]. The cells were twice
washed with physiological solution (0.9% NaCl), and
in each well was added 100 of МТТ solution [3-(4,5-
dimethylthiazole-2)-2,5-diphenyltetrazolium bromide]
in a concentration 0.5 µg/mL in physiological solution.
The templates were incubated for 1 h at 37°C, then the
liquid was removed, and in each well was added
0.1 mL of dimethyl sulfoxide. The optical density of cells
was measured on a spectrophotometer Victor 2 1440 at
the wavelength of 535 nm. From the findings obtained
the concentration of the compound destructing 50% of
cell in the culture (CND50) was calculated.
Oxime of 20(S)-hydroxydammar-24-en-3-one (10).
In 10 mL of pyridine was dissolved 4 g (0.009 mol) of
20(S)-hydroxydammar-24-en-3-one 2, 2.4 g (0.0345 mol)
of hydroxylamine hydrochloride, and the mixture was
boiled for 2 h, cooled, poured in 50 mL of water, and
acidified to рН 2. The separated precipitate was
filtered off, washed with water till neutral reaction, and
purified by chromatography (eluent hexane–ethyl
acetate), then recrystallized from ethyl acetate. Yield
1
3.71 g (93%), mp 185–186°C. Н NMR spectrum, δ,
ppm: 0.88 s (3H, CH3), 0.96 s (3H, CH3), 1.00 s (3H,
CH3), 1.08 s (3H, CH3), 1.16 s (3H, CH3), 1.21–1.60 m
(11H, CH, CH2), 1.64 s (3H, CH3), 1.70 s (3H, CH3),
1.71–1.89 m (11H, CH, CH2), 2.01–2.12 m (2H, CH,
CH2), 2.20–2.39 m (1H, CH), 5.12 t (1H, C24H, J 6.9 Hz),
7.69 br.s (1H, NOH). 13С NMR spectrum (СDCl3), δ,
ppm: 15.40, 15.87, 16.33, 17.32, 17.71, 19.04, 21.80,
22.56, 22.86, 24.78, 25.42, 25.74, 27.35, 27.52, 31.17,
34.82, 37.18, 39.05, 40.39, 40.47, 42.31, 42.61, 49.70,
50.25, 50.27, 56.03, 75.43 (С20), 124.71 (C24H),
131.57 (C25), 167.24 (C3).
Estimation of antiviral activity in vitro. The
monolayer culture of MDCK cells was infected by the
following procedure: in each well of the templates was
added 100 µL of the tested compound dissolved in
supporting medium, and the incubation was carried out
for 1 h at 37°C in a carbon dioxide incubator in an
atmosphere of 5% of CO2. Then into each well was
added 100 µL of 10-fold (10–1–10–7) dilutions of virus
and all was left for 2 days at 37°C in the atmosphere of
5% of CO2. After 48 h 100 µL of the culture fluid was
sampled from each well, transferred to the plate
template for immunological reaction, and the
hemagglutination assay was performed. To this end in
the wells with sampled culture fluid was added an
equal amount of 1% suspension of hen erythrocytes in
physiological solution. The results were estimated after
40 min incubation at room temperature. As infectious
titre of the virus the reciprocal value was regarded of
the maximum virus dilution that caused complete
20(S)-3-(2-Cyanoethoxyimino)dammar-24-en-
20-ol (11). A mixture of 1.16 g (0.0025 mol) of com-
pound 10, 3.34 mL (0.05 mol) of acrylonitrile, 1.27 mL
of tetrapropylammonium hydroxide, and 1.7 mL of
30% solution of KОН was stirred in 10 mL of dioxane
for 2 h, the reaction product was isolated as described
for compounds 5, 7, and 9, and recrystallized from ethyl
acetate. Yield 1.04 g (90%), mp 124–125°C, [α]D23.1
1
+138.93° (c 1.0, CHCl3). Н NMR spectrum (СDCl3),
δ, ppm: 0.89 s (3H, С30Н3), 0.94 s (С19Н3), 1.00 s
(С18Н3), 1.06 s (С28Н3), 1.15 s (С21Н3), 1.16 s (С29Н3),
1.64 s (С26Н3), 1.71 s (С27Н3), 1.20–1.58 m (12Н, СН,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 11 2015

KALEDINA et al.
1632
Baltina, L.A., Galin, F.Z., and Tolstikov, G.A., Russ.
J. Bioorg. Chem., 2003, vol. 29, p. 296.
agglutination of erythrocytes. The titre was expressed in
logarithm of the 50% of the infective dose (log ID50).
The antiviral activity of a compound was estimated
from the decreased infective titre of the virus. From the
data obtained the 50% effective concentration was
calculated, or the concentration of the compound
which caused the two-fold reduction of the virus titre
(by 0.3 log ID50) (EC50), and then the selectivity index
SI was calculated (the ratio CTD50/EC50).
9. Flekhter, O.B., Boreko, E.I., Nigmatullina, L.R.,
Pavlova, N.I., Medvedeva, N.I., Nikolaeva, S.N.,
Tret’yakova, E.V., Savinova, O.V., Baltina, L.A.,
Karachurina, L.T., Galin, F.Z., Zarudii, F.S., and
Tolstikov, G.A., Pharm. Chem. J., 2004, vol. 38, p. 148.
10. Flekhter, O.B., Medvedeva, N.I., Tolstikov, G.A.,
Savinova, O.V., Boreko, E.I., and Dolgushin, F.M.,
Russ. J. Bioorg. Chem., 2009, vol. 35, p. 118.
Spectral measurements were performed in the
Resource centers “Magnetic Resonance Research
Centre” and “Chemical Analysis and Materials Research
Centre” of the St. Petersburg State University.
11. Kazakova, O.B., Giniyatullina, G.V., and Tolstikov, G.A.,
Russ. J. Bioorg. Chem., 2011, vol. 37, p. 619.
12. Kazakova, O.B., Giniyatullina, G.V., Tolstikov, G.A.,
Baikova, I.P., Zaprutko, L., and Apryshko, G.N., Russ.
J. Bioorg. Chem., 2011, vol. 37, p. 369.
13. Antimonova, A.N., Uzenkova, N.V., Petrenko, N.I.,
Shakirov, M.M., Shul’ts, E.E., and Tolstikov, G.A.,
Russ. J. Org. Chem., 2011, vol. 47, p. 589.
The study was carried out under the financial
support of the Russian Science Foundation (project
no. 14-50-00069).
14. Ukiya, M., Kikuchi, T., Tokuda, H., Tabata, K.,
Kimura, Y., Arai, T., Ezaki, Y., Oseto, O., Suzuki, T.,
and Akihisa, T., Chem. Biodiv., 2010, vol. 7, p. 1871.
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