Modified Coumarins. 36. Synthesis of Linear and Angular Dihydropyranocoumarincarboxylic Acids

Article abstract of DOI:10.1007/s10600-016-1658-8

The syntheses of linear and angular dihydropyranocoumarincarboxylic acids, modified structural derivatives of dihydroxanthyletin and dihydroseselin, were described.

Full text of DOI:10.1007/s10600-016-1658-8

DOI 10.1007/s10600-016-1658-8
Chemistry of Natural Compounds, Vol. 52, No. 3, May, 2016
MODIFIED COUMARINS. 36. SYNTHESIS OF LINEAR AND
ANGULAR DIHYDROPYRANOCOUMARINCARBOXYLIC ACIDS
Ya. L. Garazd and M. M. Garazd*
The syntheses of linear and angular dihydropyranocoumarincarboxylic acids, modified structural derivatives
of dihydroxanthyletin and dihydroseselin, were described.
Keywords: coumarins, pyranocoumarins, dihydropyranocoumarins, dihydroxanthyletin, dihydroseselin.
The benzopyran-2-one moiety is a structural fragment of many important natural secondary metabolites [1] and
compounds with potent pharmacological activity [2]. Pyranocoumarins are broadly distributed in nature and contain a
2,2-dimethylpyran ring annelated to benzopyran-2-one [1]. The majority of natural pyranocoumarins are derived from the
linear pyranone xanthyletin. Pyranocoumarins also include coumarin derivatives containing an annelated
2,2-dimethyldihydropyran ring. Typical representatives of linear natural dihydropyranocoumarins are dihydroxanthyletin (1),
which is produced by the plants Cassia pumila Lam. [3], Seseli tortuosum L.B.S. Eur. [4], Ammi majus [5], and Ficus tsiangii
[6] and 5-methoxydihydroxanthyletin (dihydroxanthoxyletin) (2), which was isolated from Glycyrrhiza uralensis [7]. Angular
dihydropyranocoumarins 3 and 4 were dihydroseselin derivatives and were isolated from leaves of Marila pluricostata [8].
Me
Me
O
O
O
Me
Me
O
O
O
R
OH
3, 4
R
1, 2
1, 3: R = H; 2: R = OMe; 4: R = C(O)CH CH
2
3
It is also noteworthy that dihydropyranocoumarin derivatives inhibited acetylcholinesterase [9] and exhibited anticancer
activity [10].
The goal of the present work was to functionalize the dihydropyranocoumarin system by adding a carboxylic acid to
its structure.
2,2-Dimethylchroman-7-ol (5) that was required to synthesize the linear dihydropyranocoumarins was prepared by
Kabbe condensation [11] of 2,4-dihydroxyacetophenone with acetone in the presence of pyrrolidine followed by Clemmensen
reduction of the chromanone by Zn dust in HCl [12]. Pechmann condensation of chromanol 5 and the corresponding acetoacetic
esters in the presence of conc. H SO gave esters 6–8 of linear dihydropyranocoumaric acids. The splitting pattern of the
2
4
aromatic protons in PMR spectra of 6–8 was simplified compared with that of the starting 2,2-dimethylchromane
because proton H-6 did not couple with the dihydropyran ring. Protons H-5 and H-10 of the 8,8-dimethyl-7,8-
dihydropyrano[3,2-g]chromen-2-one system appeared as two 1H singlets at 7.44–7.57 and 6.70 ppm, respectively. The PMR
spectrum of 8 also had a 1H singlet at 6.25 ppm for the dihydroxanthyletin H-3 proton. Furthermore, PMR spectra of 6–8
contained resonances characteristic of a 2,2-dimethyldihydropyran ring (a 6H singlet at 1.31 ppm and two triplets at 1.80 and
2.80 ppm with SSCC 6.4 Hz) and an ester.
Eximed, 50 Kharꢀkovskoe Shosse, Kiev, 02160, Ukraine, e-mail: gmm@i.com.ua. Translated from Khimiya Prirodnykh
Soedinenii, No. 3, May–June, 2016, pp. 351–355. Original article submitted October 26, 2015.
©
0009-3130/16/5203-0399 2016 Springer Science+Business Media New York
399

10
5
Me
Me
8
O
O
O
3
7
4
6
Me COOR
6, 9
6: R = Me
d
9: R = H
OH
a
Me
Me
Me
Me
Me
Me
O
O
O
O
O
O
O
b
c
3'
2'
5
7, 10
Me
8, 11
COOR
COOR
8: R = Et
11: R = H
7: R = Et
10: R = H
d
d
a. Dimethylacetylsuccinate, MeOH, H SO ; b. diethyl 2-acetylglutarate, EtOH, H SO ;
2
4
2
4
c. diethyl 1,3-diacetonedicarboxylate, EtOH, H SO ; d. 1. NaOH (1 N), 2. H SO (1 N)
2
4
2
4
Alkaline hydrolysis of 6–8 formed the corresponding linear dihydropyranocoumarincarboxylic acids 9–11. Alkaline
hydrolysis of 8 was associated with a side decarboxylation reaction that resulted in partial (at room temperature) or full (with
heating) formation of 4,8,8-trimethyldihydropyrano[3,2-g]chromen-2-one. Therefore, alkaline hydrolysis of 8 was carried
13
out with cooling (0–5°C). The C NMR spectrum of 9 showed resonances at 174.92 and 160.29 ppm that were characteristic
of a carboxylic acid and coumarin carbonyl [13], respectively, in addition to resonances of a linearly annelated
2,2-dimethyldihydropyran ring (74.98, 32.35, 26.67, 26.61, and 23.32 ppm).
Angular dihydropyranocoumarincarboxylic acids were synthesized from starting ethyl (5-hydroxy-2,2-
dimethylchroman-7-yloxy)acetate (12), which was obtained via alkylation of 5,7-dihydroxy-2,2-dimethylchroman-4-one by
ethylbromoacetate followed by Clemmensen reduction of the chromanone by Zn dust in HCl [14]. Pechmann condensation of
12 and the appropriate ethyl acetoacetates in the presence of conc. H SO as a condensing agent and subsequent alkaline
2
4
hydrolysis of the ester gave substituted [(8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]acetic acids
(13–21).
PMR spectra of 13–21 showed a simplified splitting pattern for the aromatic protons compared with
starting 2,2-dimethylchromane because pyran proton H-6 did not couple. As a result, H-6 of 8,8-dimethyl-9,10-
dihydropyrano[2,3-f]chromen-2-one was observed as a 1H singlet at 6.18–6.27 ppm. PMR spectra of 13–17 also exhibited 1H
singlets at 5.86–5.96 ppm that belonged unambiguously to H-3 and were characteristic for a 4-substituted coumarin ring.
Furthermore, PMR spectra of 13–21 contained resonances characteristic of a 2,2-dimethyldihydropyran ring, a hydroxyacetic
13
group, and substituents of the synthesized coumarin ring. C NMR spectra of 13 had resonances at 171.56 and 161.41 ppm
that were characteristic of a carboxylic acid and coumarin carbonyl, respectively, in addition to resonances for an angular
annelated 2,2-dimethyldihydropyran ring (75.96, 31.75, 26.56, 26.43, and 16.38 ppm) [8].
Me
O
Me
7 O
9
Me
10
5
Me
OH
O
O
R
a
3
6
2
4
EtOOC
O
HOOC
O
R
1
12
13: R = CH , R = H; 14: R = CH CH , R = H; 15: R = (CH ) CH , R = H
13 - 21
1
3
2
1
2
3
2
1
2 2
3
2
16: R = (CH ) CH , R = H; 17: R = Ph, R = H; 18: R = R = CH
1
2 3
3
2
1
2
1
2
3
19: R = CH , R = CH Ph; 20: R R = (CH ) ; 21: R R = (CH )
1
3
2
2
1
2
2 3
1
2
2 4
a. 1. R COCHR COOEt, H SO ; 2. NaOH (1N) ; 3. H SO (1N)
1
2
2
4
2
4
Angular dihydropyranocoumarincarboxylic acids were also synthesized using 7-methoxy-5-hydroxy-2,2-
dimethylchromane (22) as starting material [12]. Pechmann condensation of chromanol 22 and the appropriate acetoacetic
esters in the presence of conc. H SO gave esters 23–25, PMR spectra of the pyranocoumarins of which showed H-6 of the
2
4
8,8-dimethyl-9,10-dihydropyrano[2,3-f]chromen-2-one systems as 1H singlets at 6.32–6.34 ppm. The PMR spectrum of 25
400

also had a 1H singlet at 6.11 ppm that was assigned unambiguously to H-3 and was a characteristic resonance for a 4-substituted
coumarin ring. Furthermore, PMR spectra of 23–25 showed resonances characteristic of a 2,2-dimethyldihydropyran ring and
an ester.
Me
Me
Me
9
Me
Me
Me
10
8
O
O
O
O
O
O
O
O
O
3
6
4
5
OMe Me COOR
OMe Me
OMe
25, 28
c
a
COOR
b
COOR
23, 26
24, 27
23: R = Me
26: R = H
24: R = Et
27: R = H
25: R = Et
28: R = H
Me
Me
d
d
d
O
OH
22
OMe
a. Dimethylacetylsuccinate, MeOH, H SO ; b. diethyl 2-acetylglutarate, EtOH, H SO ;
2
4
2
4
c. diethyl 1,3-diacetonedicarboxylate, EtOH, H SO ; d. 1. NaOH (1 N), 2. H SO (1 N)
2
4
2
4
Alkaline hydrolysis of esters 23–25 gave the corresponding angular dihydropyranocoumarincarboxylic acids 26–28.
Alkaline hydrolysis of 25, analogously to ester 8, was also associated with a side decarboxylation reaction. Therefore, it was
13
also hydrolyzed with cooling (0–5°C). The C NMR spectrum of 26 had resonances at 175.06 and 161.53 ppm that were
characteristic of carboxylic acid and coumarin carbonyl, respectively, in addition to resonances of an angular annelated
2,2-dimethyldihydropyran ring (75.98, 31.87, 26.69, 26.47, and 16.41 ppm).
The synthesized linear and angular dihydropyranocoumarincarboxylic acids are interesting as multi-faceted organic
synthons because they act as an activated ester or carboxylic acid. This opens new possibilities for further modification of
pyranocoumarin derivatives.
EXPERIMENTAL
The course of reactions and purity of products were monitored by TLC on Merck 60 F254 plates using CHCl –
3
MeOH (9:1 and 95:5) as eluents. Melting points were determined on a Kofler block. NMR spectra were measured on Varian
VXR-300 and Mercury 400 spectrometers at 300 and 400 MHz, respectively, vs. TMS (internal standard). Elemental analyses
of all compounds agreed with those calculated.
The syntheses of 2,2-dimethylchroman-7-ol (5), ethyl (5-hydroxy-2,2-dimethylchroman-7-yloxy)acetate (12), and
7-methoxy-5-hydroxy-2,2-dimethylchromane (22) were reported before [12, 14, 15].
4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromenes 6–8 and 5-Methoxy-4,8,8-trimethyl-2-oxo-9,10-
dihydropyrano[2,3-f]chromenes 23–25. A cooled (0°C) solution of 2,2-dimethylchroman-7-ol (17.8 g, 0.1 mol, for 6–8) or
7-methoxy-5-hydroxy-2,2-dimethylchromane (20.8 g, 0.1 mol, for 23–25) and the appropriate acetoacetic ester (0.1 mol) in
MeOH (30 mL) (for 6 and 23) or EtOH (30 mL) (for 7, 8, 24, and 25) was stirred vigorously, cooled, treated dropwise with
conc. H SO (30 mL), stirred for 8 h, and left overnight at room temperature. The mixture was poured into ice water (500 mL).
2
4
The resulting precipitate was filtered off and crystallized from aqueous MeOH (for 6 and 23) or aqueous EtOH (for 7, 8, 24,
and 25).
Methyl (4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)acetate (6). Ñ Í Î . Yield 74%,
18 20
5
1
mp 172–173ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 7.57 (1Í, s, Í-5), 6.69 (1Í, s, Í-10), 3.64 (2Í, s,
6
ÑÍ -3), 3.61 (3Í, s, ÑÎÎÑÍ ), 2.82 (2Í, t, J = 6.4, Í-6), 2.35 (3Í, s, ÑÍ -4), 1.81 (2Í, t, J = 6.4, Í-7), 1.31 (6Í, s, ÑÍ -8).
2
3
3
3
Ethyl 3-(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)propionate (7). Ñ Í Î . Yield 65%,
20 24
5
1
mp 123–124ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 7.54 (1Í, s, Í-5), 6.68 (1Í, s, Í-10), 4.02 (2Í, q,
6
J = 7.2, Í-1ꢀꢀ), 2.81 (2Í, t, J = 6.4, Í-6), 2.76 (2Í, t, J = 8.0, Í-2ꢀ), 2.37 (2Í, t, J = 8.0, Í-3ꢀ), 2.35 (3Í, s, ÑÍ -4), 1.81 (2Í,
3
t, J = 6.4, Í-7), 1.31 (6Í, s, ÑÍ -8), 1.15 (3Í, t, J = 7.2, Í-2ꢀꢀ).
3
401

Ethyl (8,8-Dimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-4-yl)acetate (8). Ñ Í Î . Yield 75%,
18 20
5
1
mp 167–168ꢁÑ. H NMR spectrum (300 MHz, DMSO-d , ꢂ, ppm, J/Hz): 7.44 (1Í, s, Í-5), 6.71 (1Í, s, Í-10), 6.25 (1Í, s,
6
Í-3), 4.12 (2Í, q, J = 7.2, Í-1ꢀ), 3.93 (2Í, s, ÑÍ -4), 2.78 (2Í, t, J = 6.4, Í-6), 1.88 (2Í, t, J = 6.4, Í-7), 1.31 (6Í, s,
2
ÑÍ -8), 1.19 (3Í, t, J = 7.2, Í-2ꢀ).
3
Methyl (5-Methoxy-4,8,8-trimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-3-yl)acetate (23). Ñ Í Î .Yield
19 22
6
1
78%, mp 183–184ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 6.32 (1Í, s, Í-6), 3.79 (3Í, s, 5-OÑÍ ), 3.63
6
3
(2Í, s, ÑÍ -3), 3.62 (3Í, s, ÑÎÎÑÍ ), 2.63 (2Í, t, J = 6.4, Í-10), 2.45 (3Í, s, ÑÍ -4), 1.78 (2Í, t, J = 6.4, Í-9), 1.31 (6Í,
2
3
3
s, ÑÍ -8).
3
Ethyl 3-(5-Methoxy-4,8,8-trimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-3-yl)propionate (24). Ñ Í Î .
21 26
6
1
Yield 64%, mp 130–131ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 6.33 (1Í, s, Í-6), 4.04 (2Í, q, J = 7.2,
6
Í-1ꢀꢀ), 3.79 (3Í, s, 5-OÑÍ ), 2.76 (2Í, t, J = 8.0, Í-2ꢀ), 2.64 (2Í, t, J = 6.4, Í-10), 2.47 (3Í, s, ÑÍ -4), 2.40 (2Í, t, J = 8.0,
3
3
Í-3ꢀ), 1.79 (2Í, t, J = 6.4, Í-9), 1.29 (6Í, s, ÑÍ -8), 1.16 (3Í, t, J = 7.2, Í-2ꢀꢀ).
3
Ethyl (5-Methoxy-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-4-yl)acetate (25). Ñ Í Î . Yield
19 22
6
1
73%, mp 172–173ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 6.34 (1Í, s, Í-6), 6.11 (1Í, s, Í-3), 4.07 (2Í,
6
q, J = 7.2, Í-1ꢀ), 3.83 (2Í, s, ÑÍ -4), 3.71 (3Í, s, 5-OÑÍ ), 2.68 (2Í, t, J = 6.4, Í-10), 1.80 (2Í, t, J = 6.4, Í-9), 1.31 (6Í, s,
2
3
ÑÍ -8), 1.17 (3Í, t, J = 7.2, Í-2ꢀ).
3
Dihydropyranocoumarincarboxylic Acids 9, 10, 26, and 27. A solution of ester 6, 7, 23, or 24 (50 mmol) in
i-PrOH (50 mL) was treated with NaOH solution (150 mmol, 150 mL, 1 M), stirred vigorously, and heated for 1 h (course of
reaction monitored by TLC). When the reaction was complete, the mixture was cooled, poured into water (200 mL) and
acidified to pH 5–6. The resulting precipitate was filtered off and crystallized from aqueous i-PrOH.
(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)acetic Acid (9). Ñ Í Î . Yield 88%,
17 18
5
1
mp 181–182ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.27 (1Í, br.s, ÑÎÎÍ), 7.56 (1Í, s, Í-5), 6.69 (1Í,
6
s, Í-10), 3.54 (2Í, s, ÑÍ -3), 2.82 (2Í, t, J = 6.4, Í-6), 2.33 (3Í, s, ÑÍ -4), 1.81 (2Í, t, J = 6.4, Í-7), 1.31 (6Í, s, ÑÍ -8).
2
3
3
13
C NMR spectrum (100 MHz, DMSO-d , ꢂ, ppm): 174.92, 160.29, 158.41, 150.46, 149.15, 127.91, 122.06, 118.35, 114.65,
6
101.49, 74.98, 32.90, 32.35, 26.67, 26.61, 23.32, 15.24.
3-(4,8,8-Trimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-3-yl)propionic Acid (10). Ñ Í Î . Yield 81%,
18 20
5
1
mp 151–152ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.16 (1Í, br.s, ÑÎÎÍ), 7.51 (1Í, s, Í-5), 6.69 (1Í,
6
s, Í-10), 2.73–2.81 (4Í, m, Í-2ꢀ, 6), 2.37 (3Í, s, ÑÍ -4), 2.37 (2Í, t, J = 8.0, Í-3ꢀ), 1.81 (2Í, t, J = 6.4, Í-7), 1.30 (6Í, s,
3
ÑÍ -8).
3
(5-Methoxy-4,8,8-trimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-3-yl)acetic Acid (26). Ñ Í Î . Yield
18 20
6
1
83%, mp 195–196ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.25 (1Í, br.s, ÑÎÎÍ), 6.30 (1Í, s, Í-6),
6
3.81 (3Í, s, 5-OÑÍ ), 3.61 (2Í, s, ÑÍ -3), 2.64 (2Í, t, J = 6.4, Í-10), 2.47 (3Í, s, ÑÍ -4), 1.78 (2Í, t, J = 6.4, Í-9), 1.31 (6Í,
3
2
3
13
s, ÑÍ -8). C NMR spectrum (100 MHz, DMSO-d , ꢂ, ppm): 175.06, 161.53, 160.13, 159.84, 154.57, 149.22, 121.16,
3
6
102.73, 99.29, 88.73, 75.98, 56.41, 32.77, 31.87, 26.69, 26.47, 16.41, 16.19.
(5-Methoxy-4,8,8-trimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-3-yl)proprionic Acid (27). Ñ Í Î .
19 22
6
1
Yield 75%, mp 149–150ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.17 (1Í, br.s, ÑÎÎÍ), 6.33 (1Í, s,
6
Í-6), 3.80 (3Í, s, 5-OÑÍ ), 2.74 (2Í, t, J = 8.0, Í-2ꢀ), 2.65 (2Í, t, J = 6.4, Í-10), 2.48 (3Í, s, ÑÍ -4), 2.33 (2Í, t, J = 8.0,
3
3
Í-3ꢀ), 1.79 (2Í, t, J = 6.4, Í-9), 1.30 (6Í, s, ÑÍ -8).
3
Dihydropyranocoumarincarboxylic Acids 11 and 28. A solution of NaOH (150 mmol, 150 mL, 1 M) was cooled
to 0–5°C, treated with a solution of ester 8 or 25 in i-PrOH (50 mL), held at 0–5°C, and stirred vigorously for 1 h (course of
reaction monitored by TLC). When the reaction was finished, the mixture was cooled (0–5°C) and acidified to pH 5–6. The
resulting precipitate was filtered off and crystallized from aqueous i-PrOH.
(8,8-Dimethyl-2-oxo-7,8-dihydropyrano[3,2-g]chromen-4-yl)acetic Acid (11). Ñ Í Î . Yield 72%, mp 150ꢁÑ
16 16
5
1
(dec.). H NMR spectrum (300 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.20 (1Í, br.s, ÑÎÎÍ), 7.41 (1Í, s, Í-5), 6.70 (1Í, s,
6
Í-10), 6.23 (1Í, s, Í-3), 3.85 (2Í, s, ÑÍ -4), 2.77 (2Í, t, J = 6.4, Í-6), 1.86 (2Í, t, J = 6.4, Í-7), 1.30 (6Í, s, ÑÍ -8).
2
3
(5-Methoxy-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-4-yl)aceticAcid (28). Ñ Í Î .Yield 68%,
17 18
6
1
mp 165ꢁÑ (dec.). H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.24 (1Í, br.s, ÑÎÎÍ), 6.29 (1Í, s, Í-6), 6.00
6
(1Í, s, Í-3), 3.75 (3Í, s, 5-OÑÍ ), 3.74 (2Í, s, ÑÍ -4), 2.72 (2Í, t, J = 6.4, Í-10), 1.82 (2Í, t, J = 6.4, Í-9), 1.33 (6Í, s,
3
2
ÑÍ -8).
3
[(8,8-Dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]acetic Acids 13–21. A solution of chromanol
12 (21.02 g, 75 mmol) and the appropriate ethyl acetoacetate (75 mmol) in EtOH (20 mL) was cooled (0°C), stirred vigorously,
402

treated dropwise with conc. H SO (50 mL), stirred for 8 h, left overnight at room temperature, and poured into ice water
2
4
(500 mL). The resulting oily precipitate was dissolved in i-PrOH (100 mL), diluted with NaOH solution (9.6 g, 240 mmol) in
H O (100 mL), stirred vigorously, and heated at 90–100°C for 2 h (course of reaction monitored by TLC). When the reaction
2
was finished, the mixture was cooled to room temperature and acidified to pH 4. The resulting precipitate was filtered off and
crystallized from aqueous EtOH.
[(4,8,8-Trimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]acetic Acid (13). Ñ Í Î . Yield 76%,
17 18
6
1
mp 192–193ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 13.02 (1Í, br.s, ÑÎÎÍ), 6.22 (1Í, s, Í-6), 5.91 (1Í,
6
s, Í-3), 4.68 (2Í, s, 5-ÎÑÍ ), 2.66 (2Í, t, J = 6.8, Í-10), 2.57 (3Í, s, ÑÍ -4), 1.81 (2Í, t, J = 6.8, Í-9), 1.32 (6Í, s, ÑÍ -8).
2
3
3
13
C NMR spectrum (100 MHz, DMSO-d , ꢂ, ppm): 171.56, 161.41, 160.12, 154.81, 154.52, 154.17, 111.67, 102.95, 99.63,
6
87.88, 75.96, 68.35, 31.75, 26.56, 25.43, 20.69, 16.38.
[(4-Ethyl-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]acetic Acid (14). Ñ Í Î . Yield
18 20
6
1
72%, mp 185–186ꢁÑ. H NMR spectrum (300 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.95 (1Í, br.s, ÑÎÎÍ), 6.21 (1Í, s, Í-6),
6
5.91 (1Í, s, Í-3), 4.69 (2Í, s, 5-ÎÑÍ ), 3.02 (2Í, q, J = 7.2, Í-1ꢀ), 2.71 (2Í, t, J = 6.6, Í-10), 1.82 (2Í, t, J = 6.6, Í-9), 1.33
2
(6Í, s, ÑÍ -8), 1.19 (3Í, t, J = 7.2, Í-2ꢀ).
3
[(8,8-Dimethyl-2-oxo-4-propyl-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]acetic Acid (15). Ñ Í Î . Yield
19 22
6
1
65%, mp 174–175ꢁÑ. H NMR spectrum (300 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.98 (1Í, br.s, ÑÎÎÍ), 6.21 (1Í, s, Í-6),
6
5.88 (1Í, s, Í-3), 4.68 (2Í, s, 5-ÎÑÍ ), 2.95 (2Í, q, J = 7.2, Í-1ꢀ), 2.71 (2Í, t, J = 6.6, Í-10), 1.82 (2Í, t, J = 6.6, Í-9),
2
1.53–1.66 (2H, m, Í-2ꢀ), 1.33 (6Í, s, ÑÍ -8), 0.97 (3Í, t, J = 7.2, Í-3ꢀ).
3
[(4-Butyl-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]acetic Acid (16). Ñ Í Î . Yield
20 24
6
1
68%, mp 162–163ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 13.09 (1Í, br.s, ÑÎÎÍ), 6.27 (1Í, s, Í-6),
6
5.96 (1Í, s, Í-3), 4.76 (2Í, s, 5-ÎÑÍ ), 2.95 (2Í, q, J = 7.6, Í-1ꢀ), 2.67 (2Í, t, J = 6.4, Í-10), 1.79 (2Í, t, J = 6.4, Í-9),
2
1.50–1.55 (2H, m, Í-2ꢀ), 1.30–1.39 (2H, m, Í-3ꢀ), 1.30 (6Í, s, ÑÍ -8), 0.87 (3Í, t, J = 7.2, Í-4ꢀ).
3
[(8,8-Dimethyl-2-oxo-4-phenyl-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]acetic Acid (17). Ñ Í Î . Yield
22 20
6
1
78%, mp 184–186ꢁÑ. H NMR spectrum (300 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.93 (1Í, br.s, ÑÎÎÍ), 7.29–7.36 (5Í, m,
6
Ph-4), 6.18 (1Í, s, Í-6), 5.86 (1Í, s, Í-3), 4.19 (2Í, s, 5-ÎÑÍ ), 2.78 (2Í, t, J = 6.6, Í-10), 1.86 (2Í, t, J = 6.6, Í-9), 1.35
2
(6Í, s, ÑÍ -8).
3
[(3,4,8,8-Tetramethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]aceticAcid (18). Ñ Í Î .Yield 81%,
18 20
6
1
mp 195–196ꢁÑ. H NMR spectrum (300 MHz, DMSO-d , ꢂ, ppm, J/Hz): 13.06 (1Í, br.s, ÑÎÎÍ), 6.20 (1Í, s, Í-6), 4.67 (2Í,
6
s, 5-ÎÑÍ ), 2.70 (2Í, t, J = 6.6, Í-10), 2.59 (3Í, s, ÑÍ -4), 2.06 (3Í, s, ÑÍ -3), 1.81 (2Í, t, J = 6.6, Í-9), 1.32 (6Í, s,
2
3
3
ÑÍ -8).
3
[(3-Benzyl-4,8,8-trimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-5-yl)oxy]aceticAcid (19). Ñ Í Î .Yield
24 24
6
1
65%, mp 159–160ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 12.90 (1Í, br.s, ÑÎÎÍ), 7.13–7.27 (5Í, m,
6
Ph), 6.27 (1Í, s, Í-6), 4.72 (2Í, s, 5-ÎÑÍ ), 3.93 (2Í, s, ÑÍ -3), 2.67 (2Í, t, J = 7.2, Í-10), 2.57 (3Í, s, ÑÍ -4), 1.79 (2Í,
2
2
3
t, J = 7.2, Í-9), 1.29 (6Í, s, ÑÍ -8).
3
[(2,2-Dimethyl-6-oxo-3,4,6,7,8,9-hexahydrocyclopenta[c]pyrano[2,3-h]chromen-10-yl)oxy]acetic Acid (20).
1
Ñ Í Î . Yield 67%, mp 193–194ꢁÑ. H NMR spectrum (300 MHz, DMSO-d , ꢂ, ppm, J/Hz): 13.01 (1Í, br.s, ÑÎÎÍ), 6.19
19 20
6
6
(1Í, s, Í-11), 4.64 (2Í, s, 10-ÎÑÍ ), 3.31 (2Í, t, J = 7.2, Í-7), 2.71 (2Í, t, J = 7.2, Í-2), 2.66 (2Í, t, J = 7.2, Í-9), 1.99–2.10
2
(2Í, m, Í-8), 1.81 (2Í, t, J = 7.2, Í-3), 1.32 (6Í, s, ÑÍ -2).
3
[(2,2-Dimethyl-6-oxo-3,4,7,8,9,10-hexahydrobenzo[c]pyrano[2,3-h]chromen-11-yl)oxy]acetic Acid (21).
1
Ñ Í Î . Yield 76%, mp 181–182ꢁÑ. H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 13.09 (1Í, br.s, ÑÎÎÍ), 6.23
20 22
6
6
(1Í, s, Í-12), 4.74 (2Í, s, 11-ÎÑÍ ), 3.07 (2Í, m, Í-7), 2.66 (2Í, t, J = 7.2, Í-3), 2.37 (2Í, m, Í-10), 1.78 (2Í, t, J = 7.2,
2
Í-4), 1.64 (4Í, m, Í-8, 9), 1.28 (6Í, s, ÑÍ -2).
3
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