Synthesis of N-Derivatives of Cytisine, Anabasine, and Salsoline Alkaloids with Pharmacophore 3-Aminopyridine-2(1H)-one and 5-Methyl-7-phenyloxazole[5,4-b]pyridine Cycles

Article abstract of DOI:10.1134/S1070363219120259

The reaction of nucleophilic substitution of 2-chloro-N-(6-methyl-2-oxo-4-phenyl-1,2-dihydropyridin-3-yl)acetamide and 2-(chloromethyl)-5-methyl-7-phenyloxazolo[5,4-b]pyridine with cytisine, anabasine, and salsoline alkaloids has afforded the corresponding derivatives. Structure of the obtained compounds has been confirmed by means of ¹H and ¹³C NMR spectroscopy.

Full text of DOI:10.1134/S1070363219120259

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 12, pp. 2487–2491. © Pleiades Publishing, Ltd., 2019.
Synthesis of N-Derivatives of Cytisine, Anabasine, and Salsoline
Alkaloids with Pharmacophore 3-Aminopyridine-2(1H)-one
and 5-Methyl-7-phenyloxazole[5,4-b]pyridine Cycles
I. V. Palamarchuka,*, D. N. Ogurtsovab, T. M. Seilkhanovc, and I. V. Kulakova
a Institute of Chemistry, Tyumen State University, Tyumen, 625003 Russia
b Omsk O.M. Dostoevskii State University, Omsk, 644077 Russia
c Ualikhanov Kokshetau State University, Kokshetau, 020000 Kazakhstan
*e-mail: i.v.palamarchuk@utmn.ru
Received November 11, 2019; revised December 20, 2019; accepted December 25, 2019
Abstract—The reaction of nucleophilic substitution of 2-chloro-N-(6-methyl-2-oxo-4-phenyl-1,2-dihydropyridin-
3-yl)acetamide and 2-(chloromethyl)-5-methyl-7-phenyloxazolo[5,4-b]pyridine with cytisine, anabasine, and
salsoline alkaloids has afforded the corresponding derivatives. Structure of the obtained compounds has been
confirmed by means of 1Н and 13С NMR spectroscopy.
Keywords: alkaloid, cytisine, anabasine, salsoline, 3-amino-4-phenylpyridine-2(1Н)-one, chloroacetamide,
oxazolo[5,4-b]pyridine, nucleophilic substitution
DOI: 10.1134/S1070363219120259
Combination of two or more pharmacophore frag-
ments (one of them being a natural compound) in a single
molecule is a main route to the design of novel biologi-
cally active compounds. Basic synthetic pharmacophores
include derivatives of pyridine which are components
of vital vitamins (В5 and В6), drugs exhibiting diverse
therapeutic activity (antibacterial, antituberculous, an-
tidepressant, antihistaminic, analgesic, psychotropic,
nootropic, etc.) [1–3], and agricultural chemicals (ef-
ficient fungicides, herbicides, and growth promotors)
[4, 5]. Structural features are important in determining
the pharmacological effect of the active substances, since
the change in the fragments position or the formation of
additional bonds can alter the range of the activity. The
presence of electron-donating hydroxyl and alkyl groups
in pyridine derivatives leads to the antioxidant activity.
For example, the Mexidol drug (3-oxy-6-methyl-2-ethyl-
pyridinium succinate 1, see the figure) shows antioxidant
and membrane-protecting action. Exchange of the OH
group with the NH2 one alters its biological activity. For
example, the 3-aminopyridine-2(1Н)-ones include the
drugs likeAmrinon 2 (see the figure) [6]. The presence of
an amino acid fragment makes 3-aminopyridine-2(1Н)-
ones promising as building blocks for the synthesis of
peptidomimetics [7, 8].
Derivatives of pyridine fused at the С2 and С3 posi-
tions, for example, bicyclic oxazolo[5,4-b]pyridines
also exhibit wide range of biological activity including
antimicrobial, antitumor, anti-inflammatory, and anal-
gesic [9–11].
The synthetic routes to oxazolo[5,4-b]pyridines 5
[12–14] include condensation of benzamides 4 in an
acidic medium (polyphosphoric acid or phosphorus
oxychloride); the benzamides 4 being obtained from
N
OH
NH2
HOOC(CH COOꢀ
N
H
N
O
)
2 2
H
2
1
Structures of Mexidol 1 and Amrinon 2.
2487

2488
PALAMARCHUK et al.
Scheme 1.
H
N
R
NH2
X
POCl3
or PPA
N
O
RC(O)Cl
R
O
N
X
N
N
3
4
5
X = OH; Hal; R = Ar.
Scheme 2.
Ph
Ph
Ph
N
O
H
N
NH2
O
N
C(O)Cl
ClCH2
POCl
O
5
3 + P2
Cl
110°C, 4 h
/Py,
CH2Cl2
Cl
N
H
N
O
20°C
O
H
7
8
6
the corresponding 3-amino-2-hydroxy- or 3-amino-
2-halopyridines 3 (Scheme 1).
and 2-(chloromethyl)-5-methyl-7-phenyloxazolo[5,4-b]-
pyridine 8 [16, 17] (Scheme 2).
The derivatives containing bicyclic oxazolo[5,4-b]
pyridine moiety and physiologically active alkaloids
(cytisine, anabasine, salsoline) as substituents have not
been reported in the literature.
The use of compound 7 in the synthesis of 2-methyl-
amino-substituted oxazolo[5,4-b]pyridine via nucleo-
philic substitution with different amines has been earlier
demonstrated [17].
The following substrates were used as the starting
materials for the modification with natural alkaloids:
3-aminopyridine-2(1Н)-one 6 [15], 2-chloro-N-(6-meth-
yl-2-oxo-4-phenyl-1,2-dihydropyridin-3-yl)acetamide 7,
Extending our studies on the synthesis of novel
derivatives based on cytisine, anabasine, and salsoline
alkaloids [18–21], we used the classical reaction of nu-
Scheme 3.
Ph
Ph
O
O
H
N
H
N
HN
N
aceton + DMF, KI,
Cl
N
H
O
N
H
O
q
25 C, K
2CO3
ꢀ
9a 9c
7
Ph
N
Ph
N
HN
N
O
N
Cl
N
q
DMF, KI, 25
C,
O
K
2CO3
ꢀ
10a 10c
8
11
13
12
4
1
5
10
9
5
7
HO
N
4
4
3
3
7
3
5
8
=
11
N
N
(a),
(b),
(c).
N
N
9
H
3CO
6
2
8
10
N
O
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

SYNTHESIS OF N-DERIVATIVES OF CYTISINE, ANABASINE, AND SALSOLINE ALKALOIDS
2489
pyrido[1,2-a][1,5]diazocin-3(4H)-yl)acetamide (9a).
Yield 153 mg (71%), white crystals, mp 157–160°С.
1Н NMR spectrum (СDCl3), δ, ppm: 1.77 and 1.86 two
br. d [2Н, Н-8, J8,7, J8,9 = 12.2 Hz], 2.35 s (3H, CH3),
2.38–2.48 m (4Н, Н-9, H-7,H-11a, Н-13а), 2.92–3.01 m
cleophilic substitution of chlorine atom in compounds 7
and 8 (Scheme 3).
The reaction in a mixture of the alkylating agent and
alkaloid (anabasine was used as the hydrochloride) was
performed at room temperature (for compounds 9а–9с) or
at reflux (for compounds 10а–10с) in anhydrous acetone
in the presence of potassium carbonate, 10 vol% of DMF,
and small amount of potassium iodide. The addition of
DMF allowed dissolution of anabasine hydrochloride
and significantly accelerated the nucleophilic substitu-
tion. The target products were isolated from the reaction
mixture in the form of the bases. The use of DMF only at
heating (60°C) for the synthesis of compounds 9а–9с led
to the formation of 1H-pyrido[2,3-b][1,4]oxazine-2(3H)-
one via cyclization of compound 7 as side product. The
formation of that compound in basic medium has been
described previously [16].
(4Н,N-СН2,H-11е,Н-13е),3.80d.d[1Н,Н-10а,2J10a,10e
=
=
2
15.3 Hz, J10a,9 = 6.1 Hz), 4.01 d [1Н, Н-10е, J10е,10а
15.3 Hz], 5.72 d [1H, Н-5, J5,4 = 7.0 Hz], 6.02 s (1H,
Н-5'), 6.34 d [1H, Н-3, J3,4 = 9.2 Hz], 7.13 d. d [1H, Н-4,
J4,5 = 7.0, J4,3 = 9.2 Hz], 7.29–7.40 m (6H, 5Н Ph, NH),
12.61 br. s (1Н, NH). 13С NMR spectrum, δ, ppm: 18.9,
25.3, 27.9, 35.1, 49.6, 59.9, 60.2, 61.3, 105.0, 107.9,
116.8, 119.8, 127.7 (2С Ph), 128.2 (2С Ph), 128.3, 137.6,
138.6, 143.5, 150.0, 151.0, 161.8, 163.2, 169.8. Found,
%: C 69.42; H 6.48; N 13.43. C25H26N4O3. Calculated,
%: C, 69.75; H, 6.09; N, 13.01.
N-(6-Methyl-2-oxo-4-phenyl-1,2-dihydropyridin-
3-yl)-2-(2-(pyridin-3-yl)piperidin-1-yl)acetamide (9b).
Yield 90 mg (45%), pale beige crystals, mp 131–134°С.
1Н NMR spectrum (СDCl3), δ, ppm: 1.40–1.87 m [6Н,
Н-10, Н-11, Н-12], 2.18–2.25 m (1Н, Н-9а), 2.36 s (3H,
6-CH3), 2.53 d [1Н, N-СНa, 2Jab = 16.8 Hz], 2.98 d [1Н,
N-СНb, 2Jba = 16.8 Hz], 3.22 br. d (1Н, Н-9е, J = 10.7 Hz),
3.28 br. d (1Н, Н-7, J = 9.2 Hz), 6.13 s (1Н, Н-5'), 7.23 d. d
(1Н, Н-5, 3J5,4 = 7.6 Hz, 3J5,6 = 4.6 Hz), 7.29–7.36 m (5Н,
Structure of the obtained compounds was confirmed
by means of 1Н and 13С NMR spectroscopy. The spec-
tra of compounds 9а–9с and 10а–10с contained the
products of the alkaloid fragments in the characteristic
ranges as well as diastereotropic bridging methylene
protons (as two doublets with high spin-spin interaction
constants) and the protons of aromatic 3-aminopyridine
and 7-phenyloxazolo[5,4-b]pyridine cycles. The obtained
derivatives are interesting objects with potential anti-
inflammatory activity.
Ph), 7.71 d (1Н, Н-4, 3J4,5 = 7.6 Hz), 8.52 d (1Н, Н-6, 3J6,5
=
4.6 Hz), 8.57 s (1Н, Н-2), 8.88 s (1Н, NH), 13.31 br. s
(1Н, NH). 13С NMR spectrum (СDCl3), δ, ppm: 18.7,
24.6, 26.0, 36.6, 55.2, 58.7, 65.4, 108.23, 120.3, 123. 8,
127.1 (2C Ph), 128.2, 128.3 (2C Ph), 134.6, 138.2, 139.2,
142.0, 148.5, 148.9, 149.2, 162.4, 169.1. Found, %: C
72.03; H 6.13; N 13.49. C24H26N4O2. Calculated, %: C
71.62; H 6.51; N 13.92.
EXPERIMENTAL
1H and 13С NMR spectra were recorded using a Jeol
JNM-ECA 400 instrument (400 and 100 MHz, respec-
tively) in CDCl3 with TMS as internal reference. TLC
analysis was performed using Sorbfil plates with propa-
nol-2–benzene–ammonia (10 : 5 : 2) as eluent and iodine
vapor as developer.
2-(6-Hydroxy-7-methoxy-1-methyl-3,4-dihydroiso-
quinolin-2(1H)-yl)-N-(6-methyl-2-oxo-4-phenyl-1,2-
dihydropyridin-3-yl)acetamide (9с). Yield 89 mg
Compounds 9а–9с (general procedure). Amixture of
138 mg (0.5 mmol) of compound 7, 0.5 mmol of the cor-
responding alkaloid (cytisine, anabasine hydrochloride,
or salsoline), 20 mg of potassium iodide, and 138 mg
(1.0 mmol) of potassium carbonate in 5 mL of acetone
and 0.5–1.0 mL of DMF was stirred at room tempera-
ture during 10–15 h. The reaction course was monitored
by means of TLC. The reaction mixture was filtered to
separate salts precipitate, washed with acetone, and re-
crystallized from a hexane : methylene chloride mixture
(3 : 1) after the solvent removal.
1
(41%), pale beige crystals, mp 248–251°С. Н NMR
spectrum (СDCl3), δ, ppm: 1.27 d [1H, 1-CH3, J = 6.4 Hz],
2.31 s (3H, 6-CH3), 2.52–2.57 m (1Н, На-4), 2.68–2.71 m
(2Н, Не-4, На-3), 2.96–3.03 m (1Н, Не-3), 3.13 d [1Н,
N-СНa, 2Jab = 16.5 Hz], 3.17 d [1Н, N-СНb, 2Jba = 16.5 Hz],
3.73 q [1Н, СH-СН3, J = 6.4 Hz], 3.84 s (1Н, ОСН3),
5.29 s (1Н, ОН), 6.07 s (1Н, Н-5'), 6.44 s (1Н, Н-5),
6.59 s (1Н, Н-8), 7.35–7.39 m (5Н, Ph), 8.82 br. s (1Н,
NH), 11.45 br. s (1Н, NH). 13С NMR spectrum (СDCl3),
δ, ppm: 16.8, 18.3, 24.7, 43.0, 54.0, 54.6, 56.3, 104.3,
108.8, 113.3, 119.2, 123.8, 125.7 (2С Ph), 126.1, 126.3
(2С Ph), 128.0, 136.6, 140.5, 143.0, 144.2, 146.2, 159.0,
N-(6-Methyl-2-oxo-4-phenyl-1,2-dihydropyridin-
3-yl)-2-(8-oxo-1,5,6,8-tetrahydro-2H-1,5-methanol-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

2490
PALAMARCHUK et al.
167.8. Found, %: C 68.83; H 5.88; N 9.32. C25H27N3O4.
Calculated, %: C 69.27; H 6.28; N 9.69.
6.67; N 14.14. C24H24N4O. Calculated, %: C 74.97; H
6.29; N 14.57.
Compounds 10а–10с (general procedure).Amixture
of 130 mg (0.5 mmol) of compound 8, 0.5 mmol of the
corresponding alkaloid (cytisine, anabasine hydrochlo-
ride, or salsoline), and 70 mg (0.5 mmol) of potassium
carbonate in 5 mL of DMF was stirred at room tempera-
ture during 5 h. The reaction course was monitored by
means of TLC. The reaction mixture was treated with
150 mL of icy water, filtered to separate the precipitate,
washed with water, and recrystallized from a propanol-2 :
hexane mixture (1 : 5) after drying in air.
7-Methoxy-1-methyl-2-{(5-methyl-7-phenyl-
oxazolo[5,4-b]pyridin-2-yl)methyl}-1,2,3,4-tetrahy-
droisoquinolin-6-ol (10c). Yield 91 mg (44%), white
crystals, mp 157–159°С. 1Н NMR spectrum (СDCl3), δ,
ppm: 1.47 d [3H, 1-CH3, J = 6.1 Hz), 2.69 s (3H, 5-CH3),
2.71–2.74 m (1Н, На-4), 2.79–2.86 m (1Н, Не-4), 2.99 d.
d. d [1Н, На-3, 2J = 11.8 Hz, 3J = 5.7 Hz, 3J = 5.3 Hz],
3.27 d. d. d [1Н, Не-3, 2J = 12.2 Hz, 3J = 7.6 Hz, 3J =
4.6 Hz], 3.83 s (1Н, ОСН3), 3.97 q (1Н, СH-СН3, J =
6.1 Hz), 4.11 d [1Н, N-СHа, J = 15.2 Hz], 4.21 d [1Н,
N-СНb, J = 15.2 Hz], 5.54 br. s (1Н, ОН), 6.53 s (1Н,
Н-5), 6.63 s (1Н, Н-8), 7.38 s (1Н, Н-6'), 7.47 t [1H,
H-4 Ph J = 6.1 Hz], 7.53 t [2Н, Н-3,5 Ph, J = 6.9 Hz],
8.07 d [2H, Н-2,6, Ph, J = 6.1 Hz]. 13С NMR spectrum,
δ, ppm: 20.8, 24.3, 26.7, 45.9, 51.5, 56.0, 56.2, 109.4,
114.1, 118.2, 126.6, 127.9, 128.9 (4C Ph), 129.4, 130.7,
134.8, 140.8, 143.9, 145.0, 154.5, 160.5, 163.4. Found,
%: C 71.86; H 6.50; N 9.73. C25H25N3O3. Calculated, %:
C 72.27; H 6.07; N 10.11.
3-{(5-Methyl-7-phenyloxazolo[5,4-b]pyridin-
2-yl)methyl}-1,2,3,4,5,6-hexahydro-8H-1,5-methano-
pyrido[1,2-a][1,5]diazocine-8-one (10а). Yield 113 mg
(55%), white crystals, mp 143–146°С. 1Н NMR spectrum
(СDCl3), δ, ppm: 1.73, 1.87 two br. d [2Н, Н-8, J8,7,J8,9
=
12.8Hz], 2.46 br. s (1Н, Н-9), 2.69 s (3H, 5'-CH3), 2.73 br. d
[1H, H-7, J = 11.0 Hz], 2.79 d. d [1H, H-11a, J11a,11e
10.8 Hz, J11a,9 = 2.1 Hz], 2.97 br. d [1H, Н-13а, J13a,7
=
=
1.8 Hz], 3.03–3.11m (2H, H-11е, Н-13е), 3.84 d [1Н,
N-СНа, 1J = 15.6 Hz], 3.91 d [1Н,N-СНb, 1J = 15.6 Hz],
3.93 d [1Н, Н-10а, J10a,10e = 15.5 Hz], 4.08 d [1Н, Н-10е,
FUNDING
J10е,10а = 15.5 Hz], 5.99 d. d [1H, Н-5, J5,4 = 6.9 Hz, J5,3
=
This study was financially supported by the Russian Foun-
1.4 Hz), 6.46 d. d [1H, Н-3, J3,4 = 9.2 Hz, J3,5 = 1.4 Hz],
7.27 d. d [1H, Н-4, J4,5 = 6.9 Hz, J4,3 = 9.2 Hz], 7.38 s
(1H, Н-6'), 7.47 m (1H, Н-4, Ph), 7.54 t [2H, Н-3,5 Ph,
J = 7.5 Hz], 8.05 d. d (2H, Н-2,6 Ph, J = 8.5 Hz, 1.1 Hz).
13С NMR spectrum, δ, ppm: 24.3, 25.2, 27.9, 35.4, 49.8,
54.6, 58.8, 59.3, 104.6, 116.9, 118.3, 127.6, 128.8 (2С
Ph), 128.9 (2С Ph), 129.5, 134.7, 138.6, 140.9, 151.0,
154.6, 160.4, 162.0, 163.6. Found, %: C 72.38; H 6.21;
N 13.17. C25H24N4O2. Calculated, %: C 72.80; H 5.86;
N 13.58.
dation for Basic Research (project no. 18-33-01143).
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
REFERENCES
1. Soldatenkov, A.T., Kolyadina, N.M., and Shendrik, I.V.,
Osnovy organicheskoi khimii lekarstvennykh veshchestv
(Fundamentals of Organic Chemistry of Medicinal Sub-
stances), Moscow: Khimiya, 2001.
5-Methyl-7-phenyl-2-{[2-(pyridin-3-yl)piperidin-
1-yl]methyl}oxazolo[5,4-b]pyridine (10b). Yield 44 mg
(23%), beige crystals, mp 106–110°С. 1Н NMR spectrum
(СDCl3), δ, ppm: 1.30–1.83 m [6Н, Н-10, Н-11, Н-12],
2.26–2.38 m (1Н, Н-9а), 2.71 s (3H, 6-CH3), 3.18 br. d
(1Н, Н-9е, J = 12.2 Hz), 3.53 br. d (1Н, Н-7, J = 10.7 Hz),
3.62 d [1Н, N-СНa, 2Jab = 15.3 Hz], 3.87 d [1Н, N-СНb,
2. Mashkovskii, M.D., Lekarstva XX veka (20th Century
Medicine), Moscow: Novaya Volna, 1998.
3. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Moscow: Novaya Volna, 2007.
4. Mel’nikov, N.N., Pestitsidy. Khimiya, tekhnologiya i
primenenie (Pesticides. Chemistry, Technology, and Ap-
plication), Moscow: Khimiya, 1987.
2Jba = 15.3 Hz], 7.21 d. d (1Н, Н-5, 3J5,4 = 7.6 Hz, 3J5,6
=
4.6 Hz), 7.38 s (1Н, Н-6'), 7.42–7.55 m (3Н, Н-3,4,5, Ph),
7.97 d (1Н, Н-4, 3J4,5 = 7.6 Hz), 8.04 d (2H, Н-2, 6 Ph,
J = 7.6 Hz), 8.54 d (1Н, Н-6, 3J6,5 = 4.6 Hz), 8.71 s (1Н,
Н-2). 13С NMR spectrum (СDCl3), δ, ppm: 22.7, 24.3,
25.8, 36.6, 52.1, 53.7, 64.4, 118.3, 124.0, 127.5, 128.8
(2C, Ph), 128.9 (2C Ph), 129.5, 129.6, 134.7, 135.8, 139.7,
140.8, 148.5, 149.2, 154.5, 162.8. Found, %: C 74.53; H
5. Shimanskaya, M.V. and Leitis, L.Ya., Chem. Heterocycl.
Compd., 1989, vol. 25, no. 5, p. 477.
https://doi.org/10.1007/BF00482487
6. Ward, A., Brogden, R.N., Heel, R.C., Speight, T.M., and
Avery, G.S., Drugs, 1983, vol. 26, no. 6, p. 468.
https://doi.org/10.2165/00003495-198326060-00002
7. Verissimo, E., Berry, N., Gibbons, P., Lurdes, S.,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019

SYNTHESIS OF N-DERIVATIVES OF CYTISINE, ANABASINE, AND SALSOLINE ALKALOIDS
2491
Cristiano, M., Rosenthal, P.J., Gut, J., Ward, S.A.,
and O’Neill, P.M., Bioorg. Med. Chem. Lett., 2008,
vol. 18, no. 14, p. 4210.
15. Kulakov, I.V., Matsukevich, M.V., Shulgau, Z.T., Ser-
gazy, S., Seilkhanov, T.M., Puzari, A., and Fisyuk, A.S.,
Chem. Heterocycl. Compd., 2015, vol. 51, p. 991.
https://10.1007/s10593-016-1809-7
https://10.1016/j.bmcl.2008.05.068
8. Ettari, R., Bonaccorso, C., Micale, N., Heindl, C., Schir-
meister, T., Calabrò, M.L., Grasso, S., and Zappalà, M.,
ChemMedChem., 2011, vol. 6, no. 7, p. 1228.
https://10.1002/cmdc.201100093
16. Fisyuk, A.S., Kulakov, I.V., Goncharov, D.S., Nikitina, O.S.,
Bogza, Y.P., and Shatsauskas, A.L., Chem. Heterocycl.
Compd., 2014, vol. 50, no. 2, p. 217.
https://10.1007/s10593-014-1464-9
9. Yildiz-Oren, I., Yalcin, I.,Aki-Sener, E., and Ucarturk, N.,
Eur. J. Med. Chem., 2004, vol. 39, no. 3, p. 291.
https://10.1016/j.ejmech.2003.11.014
17. Palamarchuk, I.V., Matsukevich, M.V., Kulakov, I.V.,
Seilkhanov, T.M., and Fisyuk, A.S., Chem. Heterocycl.
Compd., 2019, vol. 55, no. 8, p. 788.
10. Clark, R.L., Pessolano, A.A., Witzel, B., Lanza, T., and
Shen, T.Y., J. Med. Chem., 1978, vol. 21, p. 1158.
https://10.1021/jm00209a014
https://10.1007/s10593-019-02537-y
18. Kulakov, I.V., Nurkenov, O.A., Turdybekov, D.M.,
and Turdybekov, K.M., Chem. Nat. Compd., 2010,
vol. 46, no. 2, p. 257.
11. Boger, D.L., Miyauchi, H., Du, W., Hardouin, C., Fe-
cik, R.A., Cheng, H., Hwang, I., Hedrick, M.P., Leung, D.,
Acevedo, O., Guimarães, C.R.W., Jorgensen, W.L.,
and Cravatt, B.F., J. Med. Chem., 2005, vol. 48, no. 6,
p. 1849.
https://10.1007/s10600- 010-9582-9
19. Kulakov, I.V., Nurkenov, O.A., Turdybekov, D.M., Aina-
baev, A.A., Turdybekov, K.M., and Gazaliev, A.M., Chem.
Nat. Compd., 2009, vol. 45, no. 1, p. 66.
https://10.1021/jm049614v
https://10.1007/s10600-009-9251-z
12. Doise, M., Blondeau, D., and Sliwa, H., Synth. Commun.,
1992, vol. 22, no. , 20, p. 2891.
20. Kulakov, I.V., Nurkenov, O.A., Turdybekov, D.M.,
Ibragimov, B.T., Talipov, S.A., Zhambekov, Z.M., Ai-
nabaev, A.A., and Turdybekov, K.M., Chem. Nat.
Compd., 2009, vol. 45, no. 2, p. 209.
https://10.1080/00397919208021112
13. Myllymäki, M.J. and Koskinen, A.M.P., Tetrahedron
Lett., 2007, vol. 48, no. 13, p. 2295.
https://10.1007/ s10600-009-9284-3
https://10.1016/j.tetlet.2007.01.161
21. Kulakov, I.V., Nurkenov, O.A., Arinova, A.E., Turdy-
bekov, D.M., Talipov, S.A., and Ibragimov, B.T., Chem.
Nat. Compd., 2011, vol. 47, no. 5, p. 777.
14. Dan Xu, Xianfang Xu, Zongliang Liu, Li-Ping Sun, and
Qidong You., Synlett., 2009, vol. 7, p. 1172.
https://10.1055/s-0028-1088149
https://10.1007/s10600-011-0056-5
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 12 2019