Modified coumarins. 30. Synthesis of 6-heteroarylcoumarins

Article abstract of DOI:10.1007/s10600-009-9262-9

Heteroarylcoumarins containing 2-indole, 3-pyrazole, and 4-pyrimidine substituents in the 6-position of the coumarin ring were synthesized.

Full text of DOI:10.1007/s10600-009-9262-9

Chemistry of Natural Compounds, Vol. 45, No. 2, 2009
MODIFIED COUMARINS. 30. SYNTHESIS OF
6-HETEROARYLCOUMARINS
1
1
1*
I. V. Nagorichna, A. A. Tkachuk, M. M. Garazd,
UDC 547.814.5
2
2
Ya. L. Garazd, and V. P. Khilya
Heteroarylcoumarins containing 2-indole, 3-pyrazole, and 4-pyrimidine substituents in the 6-position of
the coumarin ring were synthesized.
Key words: coumarins, heteroarylcoumarins, enaminones, heterocyclization.
The benzopyran-2-one moiety is found in the molecular structure of many important natural secondary metabolites
[1] and compounds with high pharmacological activity [2]. Modification of the benzopyran-2-one moiety by judicious
introduction of a heterocyclic ring into the molecule has recently become an active topic in coumarin chemistry [3, 4]. This
research is interesting to the theory of organic synthesis and the targeted synthesis of new biologically active compounds
based on the coumarin core.
In most instances the hetaryl substituent is introduced at the 3- or 4-position of the coumarin ring judging from
syntheses of coumarins containing heterocyclic rings in the benzene ring of the benzopyran-2-one [4]. Herein we report the
synthesis of coumarins with indole, pyrazole, and pyrimidine rings in the 6-position of the benzopyran-2-one moiety.
Me
Me
Me
1
O
HO
N
O
R
O
HO
O
O
R
O
7
HO
O
PhNHNH
2
Me
PhNH
3
Me
2''
H N
2
N
4''
5
NH
NH
N
R
14, 15
1, 2
3, 4
6''
H N
2
2
DMFDMA
Me
H PO
3
4
Me
HO
O
O
Me
HO
O
R
O
1
O
Me
PhNHNH
2
HO
O
7
N
N
Ph
N
Me
2''
3
4''
Bu
O
5
13
7, 8
NH
R
NH NH
2
2
Ac O
2
6''
5, 6
Me
Me
10
1
O
1
O
7
HO
O
O
O
NH NH
2
2
N
3
3
7
HN
3''
5
5
R
O
R
5''
11, 12
9, 10
1, 3, 5, 7, 9, 11, 14: R = CH CH CH ; 2, 4, 6, 8, 10, 12, 15: R = CH CH CH CH
3
2
2
3
2
2
2
1) Institute of Bioorganic and Petroleum Chemistry, NationalAcademy of Sciences of Ukraine, 02094, Ukraine, Kiev,
ul. Murmanskaya, 1, e-mail: gmm@i.com.ua; 2) Taras Shevchenko Kiev National University, 01033, Ukraine, Kiev, ul.
Vladimirskaya, 64. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 145-148, March-April, 2009. Original article
submitted January 14, 2008.
©
164
0009-3130/09/4502-0164 2009 Springer Science+Business Media, Inc.

The 6-acetyl-7-hydroxy-8-methyl-4-alkylchromen-2-ones (1) and (2) required for further transformations were prepared
by Fries rearrangement of the corresponding 7-acetoxycoumarins [5]. Condensation of 7-acetoxycoumarins 1 and 2 with
N-phenylhydrazine produced phenylhydrazones 3 and 4, intramolecular heterocyclization of which under Fisher synthesis
conditions using polyphosphoric acid at 120°C [6] formed 7-hydroxy-6-(indol-2-yl)-8-methyl-4-alkylchromen-2-ones 5 and
6. NMR spectra of 5 and 6 showed resonances characteristic of the coumarin system and the formed indole ring.
We used enaminones 7 and 8, which were prepared by condensation of the dimethylacetal of N,N-dimethylformamide
(DMFDMA) with 6-acetylcoumarins 1 and 2, as convenient starting materials for the synthesis of coumarins with pyrazole and
pyrimidine substituents [7, 8].
Brief heating of enaminones 7 and 8 in acetic anhydride led to annelation of the pyran-4-one ring [9, 10] in the
coumarin system to form 10-methyl-4-alkylpyrano[3,2-g]chromen-2,6-diones 9 and 10. The PMR spectra of these compounds
showed resonances for the coumarin system and two doublets with SSCC J = 6.0 Hz at 6.38 and 8.34 ppm that were characteristic
13
of an annelated pyran-4-one ring [11]. C NMR spectra of 9 and 10 had resonances at 176 and 159 ppm that were characteristic
of carbonyl groups of the chromone and coumarin ring, respectively.
Hydrazine is known to react with compounds with a chromone ring to open the pyranone ring and close a pyrazole
ring [12]. Brief heating of alcoholic solutions of 9 and 10 with an excess of hydrazine led to recyclization of the pyrano
[3,2-g]chromen-2,6-dione system into 7-hydroxy-8-methyl-4-alkyl-6-(pyrazol-3-yl)chromen-2-ones (11 and 12). In contrast
with starting pyranocoumarins 9 and 10, coumarins 11 and 12 form with an alcoholic solution of FeCl a characteristic blue-
3
green chelate complex due to the phenolic hydroxyl and the pyrazole nitrogen. PMR spectra of 11 and 12 showed resonances
for the coumarin system and two doublets with SSCC J = 2.4 Hz at 7.12 and 8.00 ppm that were characteristic of H-4 and H-5
of the formed pyrazole ring and two broad singlets for the NH- and OH-protons at 12.20 and 13.30 ppm, respectively. The
presence of a hydroxyl proton resonance at weak field (13.30 ppm) was consistent with the presence of an intramolecular
interaction between the hydroxyl and the pyrazole nitrogen.
6-(Pyrazol-3-yl)chromen-2-ones 11 and 12 were also prepared by treatment of an alcoholic solution of
enaminones 7 and 8 with an excess of hydrazone [7, 8]. Enaminone 8 was reacted analogously with phenylhydrazine
to form 6-(1-phenylpyrazol-3-yl)chromen-2-one 13.
Reaction of enaminones 7 and 8 with guanidinium hydrochloride in pyridine resulted in the formation of the
pyrimidine ring [7] and led to the formation of 6-(2-aminopyrimidin-4-yl)chromen-2-ones 14 and 15. Coumarins 14 and 15
and an alcoholic solution of FeCl formed a characteristic blue-green chelate complex due to the phenolic hydroxyl and the
3
pyrimidine nitrogen. PMR spectra of 14 and 15 showed resonances for the coumarin system and two doublets with SSCC
J = 5.6 Hz at 7.40 and 8.40 ppm that were characteristic of H-5 and H-6 of the pyrimidine ring. A characteristic feature of the
PMR spectra of 14 and 15 was the separate absorption of the NH and OH protons. A 2H broad singlet for the amino group
2
appeared at 7.10-7.20 ppm. The resonance of the hydroxy proton at weak field (15.20 ppm) was consistent with a strong
intramolecular H-bond between the hydroxyl and the pyrimidine nitrogen.
EXPERIMENTAL
The course of reactions and the purity of products were monitored by TLC on Merck 60 F254 plates with elution by
CHCl :CH OH (9:1 and 95:5). Melting points were determined on a Kofler block. NMR spectra were measured on Varian
3
3
VXR-300 and Varian Mercury 400 spectrometers at 300 and 400 MHz, respectively, relative to TMS (internal standard).
Elemental analyses of all compounds agreed with those calculated.
The syntheses of 6-acetyl-7-hydroxycoumarins 1 and 2 have been reported [5].
Phenylhydrazones 3 and 4. A solution of 1 or 2 (10 mmol) and phenylhydrazine (0.25 mL, 25 mmol) in ethanol
(10 mL) was refluxed for 1 h and cooled. The resulting precipitate was filtered off and crystallized from propanol-2.
7-Hydroxy-8-methyl-6-(N-phenylethanehydrazonoyl)-4-propylchromen-2-one (3). Yield 95%, mp 273-274°C,
C H N O .
21 22
2 3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.04 (3H, t, J = 7.2, CH -3′), 1.73 (2H, m, CH -2′), 2.25 (3H, s,
6
3
2
CH -8), 2.47 (3H, s, CH CN-6), 2.81 (2H, t, J = 7.2, CH -1′), 6.06 (1H, s, H-3), 6.85 (1H, m, H-4′′), 7.07 (2H, d, J = 7.8, H-3′′,
3
3
2
H-5′′), 7.28 (2H, t, J = 7.8, H-2′′, H-6′′), 7.62 (1H, s, H-5), 9.55 (1H, s, NH), 13.99 (1H, s, OH).
165

4-Butyl-7-hydroxy-8-methyl-6-(N-phenylethanehydrazonoyl)chromen-2-one (4). Yield 90%, mp 262-263°C,
C H N O .
22 24
2 3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 0.98 (3H, t, J = 7.2, CH -4′), 1.44 (2H, m, CH -3′), 1.65 (2H, m,
6
3
2
CH -2′), 2.25 (3H, s, CH -8), 2.45 (3H, s, CH CN-6), 2.81 (2H, t, J = 7.2, CH -1′), 6.04 (1H, s, H-3), 6.85 (1H, m, H-4′′), 7.06 (2H,
2
3
3
2
d, J = 7.8, H-3′′, H-5′′), 7.28 (2H, t, J = 7.8, H-2′′, H-6′′), 7.63 (1H, s, H-5), 9.57 (1H, s, NH), 14.00 (1H, s, OH).
6-(Indol-2-yl)coumarins 5 and 6. A mixture of phenylhydrazone 3 or 4 (5 mmol) and polyphosphoric acid (20 mL)
was held at 120•C for 1 h, cooled, poured into icewater (300 mL), and neutralized with NaHCO solution (10%). The resulting
3
precipitate was filtered off and crystallized from propanol-2.
7-Hydroxy-6-(indol-2-yl)-8-methyl-4-propylchromen-2-one (5). Yield 62%, mp 243-244°C, C H NO .
21 19
3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.02 (3H, t, J = 7.2, CH -3′), 1.73 (2H, m, CH -2′), 2.33 (3H, s,
6
3
3
CH -8), 2.87 (2H, t, J = 7.2, CH -1′), 6.18 (1H, s, H-3), 7.02 (1H, t, J = 7.6, H-6′′), 7.04 (1H, s, H-3′′), 7.11 (1H, t, J = 7.6, H-5′′),
3
2
7.47 (1H, d, J = 7.6, H-7′′), 7.56 (1H, d, J = 7.6, H-4′′), 7.92 (1H, s, H-5), 9.81 (1H, s, NH), 11.35 (1H, s, OH).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 160.96 (C-2), 157.76 (C-4), 156.15 (C-8a), 152.40 (C-7), 134.79
6
(C-7′′), 129.05 (C-2′′), 122.03 (C-4a), 121.72 (C-5′′), 120.63 (C-6), 119.76 (C-3′′), 118.63 (C-4′′), 113.45 (C-5), 112.72 (C-8),
110.62 (C-6′′), 110.58 (C-3), 102.9 (C-1′′), 33.34 (C-1′), 21.84 (C-2′), 14.41 (C-3′), 8.75 (CH -8).
3
4-Butyl-7-hydroxy-6-(indol-2-yl)-8-methylchromen-2-one (6). Yield 71%, mp 221-223°C, C H NO .
22 21
3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.95 (3H, t, J = 7.2, CH -4′), 1.45 (2H, m, CH -3′), 1.66 (2H, m,
6
3
2
CH -2′), 2.32 (3H, s, CH -8), 2.89 (2H, t, J = CH -1′), 6.16 (1H, s, H-3), 7.00 (1H, t, J = 7.6, H-6′′), 7.02 (1H, s, H-3′′), 7.11 (1H,
2
3
2
t, J = 7.6, H-5′′), 7.47 (1H, d, J = 7.6, H-7′′), 7.56 (1H, d, J = 7.6, H-4′′), 7.91 (1H, s, H-5), 9.75 (1H, s, NH), 11.38 (1H, s, OH).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 161.12 (C-2), 158.05 (C-4), 157.65 (C-8a), 152.57 (C-7), 135.42
6
(C-7′′), 129.03 (C-2′′), 121.84 (C-4a), 121.61 (C-5′′), 120.50 (C-6), 119.71 (C-3′′), 118.51 (C-4′′), 113.42 (C-5), 111.87 (C-8),
109.92 (C-6′′), 109.58 (C-3), 102.11 (C-1′′), 31.18 (C-1′), 30.80 (C-2′), 22.60 (C-3′), 14.48 (C-4′), 9.74 (CH -8).
3
Enaminones 7 and 8. A mixture of coumarin 1 or 2 (10 mmol) and DMFDMA (2 mL, 15 mmol) in anhydrous toluene
(20 mL) was refluxed for 24 h (end of reaction determined using TLC). The resulting precipitate was filtered off and crystallized
from propanol-2.
6-[3-(Dimethylamino)prop-2-enoyl]-7-hydroxy-8-methyl-4-propylchromen-2-one (7). Yield 84%, mp 197-198°C,
C H NO .
18 21
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.99 (3H, t, J = 7.2, CH -3′), 1.67 (2H, m, CH -2′), 2.14 (3H, s,
6
3
2
CH -8), 2.85 (2H, t, J = 7.2, CH -1′), 3.08 (3H, s, NCH ), 3.25 (3H, s, NCH ), 6.01 (1H, d, J = 11.6, H-2′′), 6.12 (1H, s, H-3), 7.99
3
2
3
3
(1H, d, J = 11.6, H-3′′), 8.01 (1H, s, H-5), 12.15 (1H, s, OH).
4-Butyl-6-[3-(dimethylamino)prop-2-enoyl]-7-hydroxy-8-methylchromen-2-one (8). Yield 63%, mp 185-186°C,
C H NO .
19 23
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.96 (3H, t, J = 7.2, CH -4′), 1.42 (2H, m, CH -3′), 1.60 (2H, m,
6
3
2
CH -2′), 2.15 (3H, s, CH -8), 2.87 (2H, t, J = 7.2, CH -1′), 3.06 (3H, s, NCH ), 3.25 (3H, s, NCH ), 5.99 (1H, d, J = 11.6, H-2′′),
2
3
2
3
3
6.14 (1H, s, H-3), 7.99 (1H, d, J = 11.6, H-3′′), 8.01 (1H, s, H-5), 11.90 (1H, s, OH).
10-Methyl-4-alkylylpyrano[3,2-g]chromen-2,6-diones 9 and 10. A solution of enaminone 7 or 8 (3 mmol) in
freshly distilled acetic anhydride (5 mL) was refluxed for 5 h (end of reaction determined using TLC) and cooled. The
resulting precipitate was filtered off and crystallized from propanol-2.
10-Methyl-4-propylpyrano[3,2-g]chromen-2,6-dione (9). Yield 68%, mp 181-182°C, C H O .
16 14
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.03 (3H, t, J = 7.2, CH -3′), 1.73 (2H, m, CH -2′), 2.44 (3H, s,
6
3
2
CH -10), 2.85 (2H, t, J = 7.2, CH -1′), 6.38 (1H, d, J = 6.0, H-7), 6.40 (1H, s, H-3), 8.21 (1H, s, H-5), 8.34 (1H, d, J = 6.0, H-8).
3
2
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 176.47 (C-6), 159.52 (C-2), 157.98 (C-10a), 156.57 (C-4), 155.83
6
(C-8), 154.24 (C-9a), 120.83 (C-5a), 119.73 (C-5), 117.14 (C-4a), 115.1 (C-10), 113.99 (C-7), 112.51 (C-3), 33.37 (C-1′), 21.39
(C-2′), 14.30 (C-3′), 8.75 (CH -8).
3
4-Butyl-10-methylpyrano[3,2-g]chromen-2,6-dione (10). Yield 84%, mp 156-157°C, C H O .
17 16
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.95 (3H, t, J = 7.2, CH -4′), 1.44 (2H, m, CH -3′), 1.63 (2H, m,
6
3
2
CH -2′), 2.42 (3H, s, CH -10), 2.86 (2H, t, J = 7.2, CH -1′), 6.41 (1H, d, J = 6.0, H-7), 6.42 (1H, s, H-3), 8.18 (1H, s, H-5), 8.40
2
3
2
(1H, d, J = 6.0, H-7).
166

13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 176.37 (C-6), 159.44 (C-2), 157.9 (C-10a), 156.71 (C-4), 155.75
6
(C-8), 154.32 (C-9a), 120.83 (C-5a), 119.73 (C-5), 117.05 (C-4a), 115.03 (C-10), 113.85 (C-7), 112.48 (C-3), 31.15 (C-1′),
30.12 (C-2′), 22.57 (C-3′), 14.36 (C-4′), 8.69 (CH -8).
3
6-(Pyrazol-3-yl)chromen-2-ones 11 and 12. MethodA. A solution of dione 9 or 10 (2 mmol) in ethanol (5 mL) was
treated with hydrazine monohydrate (0.49 mL, 10 mmol), refluxed for 1 h (end of reaction determined using TLC), and cooled.
The resulting precipitate was filtered off and dried.
Method B. A solution of enaminone 7 or 8 (2 mmol) in ethanol (5 mL) was treated with hydrazine monohydrate
(0.30 mL, 6 mmol), refluxed for 1-2 h (end of reaction determined using TLC), and cooled. The resulting precipitate was
filtered off and dried.
7-Hydroxy-8-methyl-4-propyl-6-(pyrazol-3-yl)chromen-2-one (11). Yield 88%, mp 194-195°C, C H N O .
16 16
2 3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.00 (3H, t, J = 7.2, CH -3′), 1.68 (2H, m, CH -2′), 2.24 (3H, s,
6
3
2
CH -8), 2.83 (2H, t, J = 7.2, CH -1′), 6.12 (1H, s, H-3), 7.12 (1H, d, J = 2.4, H-4′′), 7.93 (1H, s, H-5), 8.00 (1H, d, J = 2.4, H-5′′),
3
2
12.20 (1H, br.s, NH), 13.30 (1H, br.s, OH).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 160.92 (C-2), 157.59 (C-4), 157.29 (C-8a), 152.43 (C-7), 150.43
6
(C-3′′), 130.9 (C-5′′), 120.30 (C-4a), 114.29 (C-6), 112.27 (C-5), 112.01 (C-8), 110.17 (C-3), 102.72 (C-4′′), 33.21 (C-1′), 21.78
(C-2′), 14.31 (C-3′), 8.74 (CH -8).
3
4-Butyl-7-hydroxy-8-methyl-6-(pyrazol-3-yl)chromen-2-one (12). Yield 84%, mp 181-182°C, C H N O .
17 18
2 3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.94 (3H, t, J = 7.2, CH -4′), 1.42 (2H, m, CH -3′), 1.60 (2H, m,
6
3
2
CH -2′), 2.23 (3H, s, CH -8), 2.83 (2H, t, J = 7.2, CH -1′), 6.11 (1H, s, H-3), 7.08 (1H, d, J = 2.4, H-4′′), 7.91 (1H, s, H-5), 8.00 (1H,
2
3
2
d, J = 2.4, H-5′′), 12.25 (1H, br.s, NH), 13.20 (1H, br.s, OH).
4-Butyl-7-hydroxy-8-methyl-6-(1-phenylpyrazol-3-yl)chromen-2-one (13). A solution of enaminone 8 (0.66 g,
2 mmol) in ethanol (5 mL) was treated with phenylhydrazine (0.59 mL, 6 mmol), refluxed for 2 h (end of reaction determined
using TLC), and cooled. The resulting precipitate was filtered and dried. Yield 64%, mp 194-195°C, C H N O .
23 22
2 3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.96 (3H, t, J = 7.2, CH -4′), 1.44 (2H, m, CH -3′), 1.64 (2H, m,
6
3
2
CH -2′), 2.29 (3H, s, CH -8), 2.90 (2H, t, J = 7.2, CH -1′), 6.18 (1H, s, H-3), 7.39 (1H, t, J = 7.6, H-4′″), 7.44 (1H, d, J = 2.8,
2
3
2
H-4′′), 7.58 (2H, t, J = 7.6, H-3′″, H-5′″), 7.91 (2H, d, J = 7.6, H-2′″, H-6′″), 8.05 (1H, s, H-5), 8.77 (1H, d, J = 2.4, H-5′′), 11.65 (1H,
s, OH).
6-(2-Aminopyrimidin-4-yl)chromen-2-ones 14 and 15. A mixture of enaminone 7 or 8 (2 mmol) and guanidinium
hydrochloride (0.29 g, 3 mmol) in pyridine (5 mL) was refluxed for 8-10 h (end of reaction determined using TLC), poured into
water (100 mL), and acidified with acetic acid. The resulting precipitate was filtered off and crystallized from propanol-2.
6-(2-Aminopyrimidin-4-yl)-7-hydroxy-8-methyl-4-propylchromen-2-one (14). Yield 82%, mp 203-204°C,
C H N O .
17 17
3 3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.01 (3H, t, J = 7.2, CH -3′), 1.67 (2H, m, CH -2′), 2.21 (3H, s,
6
3
2
CH -8), 2.83 (2H, t, J = 7.2, CH -1′), 6.11 (1H, s, H-3), 7.16 (2H, br.s, NH ), 7.40 (1H, d, J = 5.6, H-5′′), 8.08 (1H, s, H-5), 8.45 (1H,
3
2
2
d, J = 5.6, H-6′′), 15.15 (1H, br.s, OH).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 161.36 (C-2), 160.52 (C-2′′, C-4′′), 157.43 (C-4, C-8a), 154.42
6
(C-7), 152.03 (C-6′′), 110.03 (C-3), 121.95 (C-4a), 113.84 (C-6), 113.04 (C-5), 111.52 (C-8), 104.65 (C-5′′), 33.02 (C-1′), 21.50
(C-2′), 14.34 (C-3′), 8.50 (CH -8).
3
6-(2-Aminopyrimidin-4-yl)-4-butyl-7-hydroxy-8-methylchromen-2-one (15). Yield 87%, mp 196-197°C,
C H N O .
18 19
3 3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 0.95 (3H, t, J = 7.2, CH -4′), 1.42 (2H, m, CH -3′), 1.63 (2H, m,
6
3
2
CH -2′), 2.22 (3H, s, CH -8), 2.86 (2H, t, J = 7.2, CH -1′), 6.11 (1H, s, H-3), 7.14 (2H, br.s, NH ), 7.38 (1H, d, J = 5.6, H-5′′), 8.08
2
3
2
2
(1H, s, H-5), 8.41 (1H, d, J = 5.6, H-6′′), 15.19 (1H, br.s, OH).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 161.47 (C-2), 160.69 (C-2′′), 159.87 (C-4′′), 157.88 (C-4, C-8a),
6
154.46 (C-7), 152.03 (C-6′′), 122.19 (C-4a), 113.84 (C-6), 113.14 (C-5), 110.19 (C-3), 104.75 (C-5′′), 111.64 (C-8), 30.9
(C-1′′), 30.58 (C-2′), 22.26 (C-3′), 14.43 (C-4′), 8.57 (CH -8).
3
167

ACKNOWLEDGMENT
We thank OAO Eximed (Kiev, Ukraine) for help in performing the work.
REFERENCES
1.
2.
R. D. H. Murray, Progress in the Chemistry of Organic Natural Products. The Naturally Occurring Coumarins,
Springer, Vienna, NewYork (2002).
R. O’Kennedy and R. D. Thornes, Coumarins - Biology, Applications and Mode of Action, John Wiley & Sons
Ltd., Chichester (1997).
3.
4.
S. M. Kovalenko, I. E. Bylov, K. M. Sytnik, and V. P. Chernykh, Molecules, 1146 (2000).
V. P. Khilya, O. V. Shablykina, and V. V. Ishchenko, Selected Methods of Heterocycle Synthesis and Modification
[in Russian], Vol. 2, V. G. Kartsev, ed., IBS PRESS, Moscow (2003), p. 518.
I. V. Nagorichna, M. M. Garazd,Ya. L. Garazd, and V. P. Khilya, Khim. Prir. Soedin., 135 (2009).
A. H. Abdel-Rahman, A. M. Khalil, S. I. El-Desoky, and E. M. Keshk, Chem. Pap., 53, 323 (1999).
K. M. Al-Zaydi, Molecules, 541 (2003).
5.
6.
7.
8.
E. M. Keshk, Heteroat. Chem., 15, 85 (2004).
9.
B. Fohlisch, Chem. Ber., 104, 348 (1971).
10.
H.Yoshimura, M. Nagai, S. Hibi, K. Kikuchi, S. Abe, T. Hida, S. Higashi, I. Hishinuma, and T.Yamanaka, J. Med.
Chem., 38, 3163 (1996).
11.
12.
M. E. Perel′son, Yu. N. Sheinker, and A. A. Savina, Spectra and Structure of Coumarins, Chromones, and
Xanthones [in Russian], Meditsina, Moscow (1975).
V. V. Arkhipov, M. M. Garazd, M. N. Smirnov, and V. P. Khilya, Khim. Geterotsikl. Soedin., 218 (2004).
168