Modified coumarins. 4. Synthesis and biological properties of cyclopentane-annelated furocoumarins

Article abstract of DOI:10.1023/A:1020423826071

Psoralen and allopsoralen analogs that contain an annelated cyclopentane were synthesized from 7-hydroxy- and 9-hydroxy-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-ones. 9-Phenyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one exhibited low toxicity,

Full text of DOI:10.1023/A:1020423826071

Chemistry of Natural Compounds, Vol. 38, No. 3, 2002
MODIFIED COUMARINS. 4. SYNTHESIS AND
BIOLOGICAL PROPERTIES OF CYCLOPENTANE-
ANNELATED FUROCOUMARINS
M. M. Garazd,1 Ya. L. Garazd,2 S. V. Shilin,2
T. N. Panteleimonova,3 and V. P. Khilya2
UDC 547.814.5
Psoralen and allopsoralen analogs that contain an annelated cyclopentane were synthesized from 7-hydroxy-
and 9-hydroxy-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-ones. 9-Phenyl-1,2,3,4-tetrahydrocyclo-
penta[c]furo[3,2-g]chromen-4-one exhibited low toxicity, acted as a CNS stimulant, and exhibited
cardiotropic activity.
Key words: coumarins, furocoumarins, psoralen, allopsoralen, 1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one.
Furocoumarins are natural compounds of varied structure that are derived from the linear furocoumarin psoralen
(7 -furo[3,2- ]chromen-7-one) or its angular isomer angelicin (2 -furo[2,3- ]chromen-2-one). Other furocoumarin isomers
H
g
H
h
are distributed much less in nature. Thus, allopsoralen (7 -furo[2,3- ]chromen-7-one) was isolated from seeds of
H
f
Psoralea
[2]. Natural furocoumarins and their synthetic analogs exhibit various
Psoralea plicata
[1] and aerial parts of
corylifolia
pharmacological properties due to the presence in them of several pharmacophores. In particular, they are photosensitizers and
increase the sensitivity of humans and animals to sunlight [3]. Furocoumarins can be used as antitumor agents because they
inhibit pathological tissue growth [4]. Derivatives of psoralen and angelicin typically have spasmolytic and cardiotensive
properties [5] and antibacterial [6], antihepatitis [7], anti-infection [8], and anti-HIV [9, 10] activity.
The most well known natural compounds containing the 1,2,3,4-tetrahydrocyclopenta[ ]chromen-4-one moiety are
c
aflatoxins, which are exceedingly toxic and potent carcinogens produced by
[11]. Derivatives of 7-hydroxy-
Aspergillus flavus
1,2,3,4-tetrahydrocyclopenta[ ]chromen-4-one are also interesting because they possess a wide spectrum of biological activity.
c
In particular, they exhibit insecticidal [12], antiallergic [13], antidepressive [14], antifungal [15], neuroprotective and
anticonvulsive [16] properties and act on the CNS [17].
We synthesized furocoumarins containing an annelated cyclopentane moiety by fusing a furan ring to
1,2,3,4-tetrahydrocyclopenta[ ]chromen-4-one and performed pharmacological screening of the prepared compounds. Starting
c
7-hydroxy-1,2,3,4-tetrahydrocyclopenta[ ]chromen-4-one (1), 7-hydroxy-6-methyl-1,2,3,4-tetrahydrocyclopenta[ ]chromen-4-
c
c
one (2), and 9-hydroxy-7-methyl-1,2,3,4-tetrahydrocyclopenta[ ]chromen-4-one (3) were prepared by Pechmann condensation
c
of ethyl-2-oxocyclopentanecarboxylate with resorcinol, 2-methylresorcinol, and orcine, respectively, in the presence of conc.
H SO at 0°C.
2
4
Several approaches to the construction of furocoumarins are known. In particular, psoralen and its isomers are
produced by the method of Spaeth [18] and methods based on Dickman condensation [19], the Perkin reaction [20], and Claisen
rearrangement [21]. In our opinion, the most convenient method for preparing polyfunctional furocoumarin derivatives is the
method of MacLeod [22], which enables the synthesis in high yields of furocoumarins modified on both the coumarin and furan
rings.
The Williamson reaction of furocoumarins 1-3 with α-haloketones forms substituted oxoesters 4-38. The reactions
1) Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of the Ukraine, 02094, Kiev,
ul. Murmanskaya, 1, gmm@i.com.ua; 2) Taras Shevchenko Kiev National University, 01033, the Ukraine, Kiev, ul.
Vladimirskaya, 64; 3) Institute of Gerontology, Academy of Medical Sciences of the Ukraine, 03114, Kiev, ul. Vyshgorodskaya,
67. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 192-202, May-June, 2002. Original article submitted May 14,
2002.
0009-3130/02/3803-0230$27.00 ©2002 Plenum Publishing Corporation
230

4 5 28 10
6 7 29
8 9 30
used α-bromoacetone ( , , ), 3-chloro-2-butanone ( , , ), α-bromopropiophenone ( , , ), α-bromoacetophenone ( ,
11 31 12 13 32 14 15 33
,
), 4-methylphenacylbromide ( ), α-chloro-4-fluoroacetophenone ( ), α-bromo-4-chloroacetophenone
,
,
,
,
16 17 34 18 19 35 20 21 36 22
( , ), 4-bromophenacylbromide ( ), 4-methoxyphenacylbromide ( ), 3-methoxyphenacylbromide ( ,
,
,
,
,
,
23 37
24 25 26 27 38
) and 2-chlorocyclohexanone ( , ,
,
), α-bromo-3,4-methylenedioxyacetophenone (
,
).
R
R
R
O
O
O
O
O
O
O
O
O
Me
R
1
Me
39, 40
41 - 44
45 - 56
R
1
1. 1N NaOH
1. 1N NaOH
1. 1N NaOH
+
+
+
2. H
2. H
2. H
R
R
R
Me
O
O
O
O
O
O
O
O
O
O
R
1
Me
O
O
6 - 9
R
1
4, 5
10 - 21
R CO(Me)CHHal
1
K CO
2
O
3
Hal
K CO
3
2
MeCOCH Br
2
R
K CO
3
2
HO
O
O
R
1
O
1, 2
O
Cl
MeO
O
K CO
Br
2
3
K CO
2
3
Br
K CO
2
O
3
R
R
R
O
O
O
O
O
O
O
O
O
O
O
O
MeO
O
O
O
22, 23
26, 27
24, 25
1. 1N NaOH
1. 1N NaOH
1. 1N NaOH
+
+
2. H
+
2. H
2. H
R
R
R
O
O
O
O
O
O
O
O
O
MeO
O
O
57, 58
61, 62
59, 60
4, 22, 24, 26, 39, 57, 59, 61: R = H; 5, 23, 25, 27, 40, 58, 60, 62: R = Me; 6, 41: R = H, R = Me;
1
7, 42: R = R = Me; 8, 43: R = H, R = Ph; 9, 44: R = Me, R = Ph; 10, 45: R = R = H;
1
1
1
1
11, 46: R = Me, R = H; 12, 47: R = H, R = Me; 13, 48: R = R = Me; 14, 49: R = H, R = F;
1
1
1
1
15, 50: R = Me, R = F; 16, 51: R = H, R = Cl; 17, 52: R = Me, R = Cl; 18, 53: R = H, R = Br;
1
1
1
1
19, 54: R = Me, R = Br; 20, 55: R = H, R = OMe; 21, 56: R = Me, R = OMe
1
1
1
The PMR spectra of the prepared ketones contain signals characteristic of the coumarin ring and alkoxyl. The IR
spectra have two bands in the range 1690-1730 cm-1, typical for C O stretching of the coumarin ring and the alkoxyl carbonyl
[23]. The UV spectra of 4-38 contain three strong maxima at 203-206, 250-260, and 310-330 nm, characteristic of this type
of compounds [23].
231

Me
Me
O
O
Me
Me
O
O
Me
Me
O
O
O
O
O
Me
64
63
65
1. 1N NaOH
1. 1N NaOH
1. 1N NaOH
+
+
+
2. H
2. H
2. H
Me
O
O
O
Me
O
O
O
Me
O
O
O
O
O
O
Me
Me
29
Me
30
K CO
28
Me
PhCOCH(Me)Br
MeCOCH(Me)Cl K CO
2
3
MeCOCH Br K CO
2
2
3
2
3
Me
O
O
O
O
Cl
OH
O
K CO
2
3
Hal
3
K CO
2
3
R
1
Br
MeO
K CO
2
3
Me
O
O
O
Me
O
O
O
Me
O
O
O
O
O
MeO
O
R
1
38
31 - 36
37
1. 1N NaOH
1. 1N NaOH
1. 1N NaOH
+
+
+
2. H
2. H
2. H
Me
O
O
Me
O
O
Me
O
O
MeO
R
1
O
O
O
73
66 - 71
72
29, 64: R = Me; 30, 65: R = Ph; 31, 66: R = H; 32, 67: R = Me;
1
1
1
1
33, 68: R = F; 34, 69: R = Cl; 35, 70: R = Br; 36, 71: R = OMe
1
1
1
1
4 38
Ketones - cyclize readily into the corresponding 1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-ones
39 62
-
63 73
(psoralen-type furocoumarins) and 7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-ones
-
(allopsoralen-type
furocoumarins) upon heating with 1 N NaOH. Construction of the furan ring at the 7,8-positions of 1,2,3,4-
39 62 63 73
tetrahydrocyclopenta[c]chromen-4-one ( ) or the 8,9-positions of this same system ( ) was confirmed by PMR
-
-
39 62
have simple splitting for the aromatic protons owing to a lack of coupling to H-8 of
spectroscopy. The PMR spectra of
-
the ring of 1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one. As a result, aromatic proton H-10 of furocoumarin appears as a
63 73
singlet. An analogous picture develops for furocoumarins
-
. Proton H-5 of the furocoumarin resonates as a singlet owing
to a lack of coupling to H-8 of the starting coumarin. Furthermore, a 1-H singlet is observed at 7.8-8.5 ppm for furocoumarins
39 40
,
45 62
63
66 72
, which are unsubstituted at the 2-position.
, and
-
, which are unsubstituted at the 8-position, and for
and
-
232

This is also characteristic of formation of the furocoumarin ring. The UV spectra have strong absorption bands in the range
250-270 nm that are stronger than in the starting ketones. This also provides evidence that the furan ring was added to the
coumarin [23].
The pharmacological screening of 9-phenyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (45) using Wistar
rats has shown that 45 has low toxicity. The LD50 is greater than 3300 mg/kg. Compound 45 at a dose of 400 mg/kg caused
rats to move stereotypically in one direction in elongated circles around the cage without other visual symptons, i.e., it has
features of a CNS stimulant. Furthermore, 45 at a dose of 100 mg/kg showed cardiotropic activity. The bioelectric activity of
the rat myocardium typically had a decreased frequency of cardiac contractions.
Thus, the pharmacological screening revealed that further investigations of furocoumarin derivatives is promising for
finding new biologically active compounds.
EXPERIMENTAL
The course of the reactions and purity of the products were monitored by TLC on Merck 60 F254 plates using
CHCl —CH OH (9:1) and (95:5). IR and UV spectra were measured on Nicolet FTIR Nexus 475 and Specord M40
3
3
spectrometers, respectively. PMR spectra were taken on a Varian VXR-300 spectrometer relative to TMS (internal standard).
Elemental analyses of all compounds agreed with those calculated.
7-Hydroxy-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (1). A cooled (0°C) solution of resorcinol (22 g,
0.2 mole) and ethyl-2-oxocyclopentanecarboxylate (29 mL, 0.2 mole) in absolute ethanol (50 mL) was vigorously stirred and
cooled, treated dropwise with conc. H SO (20 mL), stirred until congealed, left overnight at room temperature, and poured into
2
4
500 mL of icewater. The resulting solid was filtered off and crystallized from isopropanol (75%). Yield 68%, C12H10O3, mp
246-247°C (lit. 224°C [15], 243.5°C [24], 250-252°C [25]). IR spectrum (KBr, cm-1): 3209, 2967, 2928, 1677, 1621, 1561,
1517, 1460, 1392, 1350, 1307, 1266, 1147, 1132, 1075, 851, 827, 754, 718. UV spectrum (CH CN, λmax, nm, log ε): 204
3
(4.72), 218 (4.26), 321 (4.24). PMR spectrum (300 MHz, DMSO-d, δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.71 (2H, m, CH -1),
2
2
2.99 (2H, m, CH -3), 6.69 (1H, d, J = 2.1, H-6), 6.73 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 7.32 (1H, d, J = 8.4, H-9), 10.20 (1H,
2
br.s, OH-7).
7-Hydroxy-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (2). Prepared analogously to 1 from 2-
methylresorcinol (24.8 g). Yield 74%, C13H12O3, mp 290-292°C (dec.) (lit. 257°C [26], 259°C [27]). IR spectrum (KBr, cm-1):
3365, 2962, 2924, 1683, 1605, 1579, 1509, 1378, 1364, 1299, 1084, 808, 758. UV spectrum (EtOH, λmax, nm, log ε): 205
(4.74), 221 (4.29), 328 (4.28). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.08 (2H, m, CH -2), 2.17 (3H, s, CH -6),
6
2
3
2.71 (2H, m, CH -1), 3.00 (2H, m, CH -3), 6.86 (1H, d, J = 8.4, H-8), 7.24 (1H, d, J = 8.4, H-9), 10.30 (1H, br.s, OH-7).
2
2
9-Hydroxy-7-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (3). Prepared analogously to 1 from orcine
monohydrate (28.4 g). Crystallized from isopropanol (60%). Yield 67%, C13H12O3, mp 253-255°C (dec.) (lit. 253-254°C [28],
255°C [15]). IR spectrum (KBr, cm-1): 3340, 2955, 2862, 1686, 1611, 1567, 1516, 1441, 1391, 1337, 1283, 1146, 1113, 1076,
1030, 984, 829, 740. UV spectrum (EtOH, λmax, nm, log ε): 206 (4.71), 213 (4.59), 256 (4.05), 311 (4.27). PMR spectrum
(300 MHz, DMSO-d , δ, ppm): 2.01 (2H, m, CH -2), 2.28 (3H, s, CH -7), 2.63 (2H, m, CH -1), 3.25 (2H, m, CH -3), 6.54 (1H,
6
2
3
2
2
s, H-8), 6.63 (1H, s, H-6), 10.38 (1H, br.s, OH-7).
General Synthetic Method for Ketones 4-25 and 28-37. A hot solution of coumarin 1, 2, or 3 (10 mmole) in absolute
acetone (50 mL) was treated with freshly calcined potash (2.76 g, 20 mmole), stirred vigorously, heated (50-56°C), and treated
with the appropriate -haloketone (11 mmole). The reaction mixture was held for 1-3 h with heating and vigorous stirring
(completion of the reaction was determined by TLC) and treated with H SO (300 mL, 1 N). The resulting solid was filtered
2
4
off and crystallized from isopropanol (75%).
7-(2-Oxopropoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (4). Yield 85%, C15H14O4, mp 145°C (lit. 139°C
[25]). IR spectrum (KBr, cm-1): 3447, 3069, 2911, 1721, 1612, 1509, 1422, 1396, 1281, 1246, 1163, 1132, 1073, 1028, 953,
880, 832, 753. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.79), 220 (4.38), 223 (4.32), 321 (4.34). PMR spectrum
3
(300 MHz, deuteroacetone, δ, ppm, J/Hz): 2.12 (2H, m, CH -2), 2.24 (3H, s, CH -3 ), 2.77 (2H, m, CH -1), 3.08 (2H, m,
2
3
2
CH -3), 4.89 (2H, s, CH -1 ), 6.89 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 6.95 (1H, d, J = 2.1, H-6), 7.46 (1H, d, J = 8.4, H-9).
2
2
6-Methyl-7-(2-oxopropoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (5). Yield 92%, C16H16O4, mp 163-
165°C. IR spectrum (KBr, cm-1): 3437, 2954, 2897, 1734, 1704, 1615, 1574, 1504, 1460, 1432, 1420, 1377, 1286, 1186, 1120,
233

1057, 1036, 805, 756. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.69), 219 (4.29), 322 (4.25). PMR spectrum (300 MHz,
3
deuteroacetone, δ, ppm, J/Hz): 2.16 (2H, m, CH -2), 2.26 (3H, s, CH -3′), 2.33 (3H, s, CH -6), 2.80 (2H, m, CH -1), 3.06 (2H,
2
3
3
2
m, CH -3), 4.86 (2H, s, CH -1′), 6.88 (1H, d, J = 8.4, H-8), 7.35 (1H, d, J = 8.4, H-9).
2
2
7-(1-Methyl-2-oxopropoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (6). Yield 78%, C16H16O4, mp 102-
103°C. IR spectrum (KBr, cm-1): 3415, 2956, 2920, 1721, 1628, 1613, 1510, 1428, 1398, 1360, 1277, 1244, 1162, 1138, 1125,
1091, 1062, 1023, 994, 834, 752. UV spectrum (CH CN, λmax, nm, log ε): 206 (5.06), 223 (4.75), 248 (4.63), 294 (4.53), 308
3
(4.60). PMR spectrum (300 MHz, deuteroacetone, δ, ppm, J/Hz): 1.53 (3H, d, J = 6.9, CH -4′), 2.10 (2H, m, CH -2), 2.22 (3H,
3
2
s, CH -1′), 2.79 (2H, m, CH -1), 3.08 (2H, m, CH -3), 5.00 (1H, q, H-3′), 6.85 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 6.96 (1H,
3
2
2
d, J = 2.1, H-6), 7.49 (1H, d, J = 8.4, H-9).
6-Methyl-7-(1-methyl-2-oxopropoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (7). Yield 84%, C17H18O4,
mp 149-151°C. IR spectrum (KBr, cm-1): 3434, 2966, 2919, 2854, 1729, 1703, 1603, 1570, 1499, 1430, 1375, 1281, 1262,
1123, 1109, 1083, 1041, 811, 757. UV spectrum (EtOH, λmax, nm, log ε): 206 (4.73), 220 (4.35), 321 (4.34). PMR spectrum
(300 MHz, deuteroacetone, δ, ppm, J/Hz): 1.55 (3H, d, J = 6.9, CH -4′), 2.13 (2H, m, CH -2), 2.20 (3H, s, CH -1′), 2.34 (3H,
3
2
3
s, CH -6), 2.79 (2H, m, CH -1), 3.08 (2H, m, CH -3), 4.99 (1H, q, H-3 ), 6.84 (1H, d, J = 8.4, H-8), 7.38 (1H, d, J = 8.4, H-9).
3
2
2
7-(1-Methyl-2-oxo-2-phenylethoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (8). Yield 85%, C21H18O4,
mp 159.5-160.5°C. IR spectrum (KBr, cm-1): 3435, 3061, 2978, 2934, 1708, 1696, 1625, 1611, 1515, 1448, 1404, 1298, 1280,
1251, 1233, 1164, 1134, 1116, 1066, 1028, 968, 698. UV spectrum (CH CN, λmax, nm, log ε): 203 (4.83), 223 (4.35), 245
3
(4.27), 294 (4.07), 321 (4.36). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.60 (3H, d, J = 6.9, CH -3 ), 2.10 (2H,
6
3
m, CH -2), 2.71 (2H, m, CH -1), 3.01 (2H, m, CH -3), 6.22 (1H, q, H-2 ), 6.92 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 6.96 (1H,
2
2
2
d, J = 2.1, H-6), 7.47 (1H, d, J = 8.4, H-9), 7.60 (2H, m, H-3″, H-5″), 7.73 (1H, m, H-4″), 8.10 (2H, m, H-2″, H-6″).
6-Methyl-7-(1-methyl-2-oxo-2-phenylethoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (9). Yield 87%,
C22H20O4, mp 152-154°C. IR spectrum (KBr, cm-1): 3432, 2918, 2852, 1703, 1606, 1576, 1501, 1452, 1428, 1376, 1279, 1255,
1227, 1133, 1099, 1036, 964, 810, 758, 704. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.89), 223 (4.40), 245 (4.41), 319
3
(4.36). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.63 (3H, d, J = 6.9, CH -3 ), 2.07 (2H, m, CH -2), 2.26 (3H, s,
6
3
2
CH -6), 2.72 (2H, m, CH -1), 2.98 (2H, m, CH -3), 6.19 (1H, q, H-2 ), 6.88 (1H, d, J = 8.4, H-8), 7.30 (1H, d, J = 8.4, H-9),
3
2
2
7.57 (2H, m, H-3″, H-5″), 7.70 (1H, m, H-4″), 8.06 (2H, m, H-2″, H-6″).
7-(2-Oxo-2-phenylethoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (10). Yield 90%, C20H16O4, mp 194°C.
IR spectrum (KBr, cm-1): 3433, 2906, 1701, 1626, 1563, 1515, 1449, 1427, 1393, 1295, 1228, 1154, 1084, 1057, 986, 836, 751,
686. UV spectrum (CH CN, λmax, nm, log ε): 203 (3.83), 224 (3.31), 244 (3.26), 322 (3.24). PMR spectrum (300 MHz,
3
DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.74 (2H, m, CH -1), 3.05 (2H, m, CH -3), 5.69 (2H, s, CH -2 ), 7.00 (1H,
6
2
2
2
2
dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 7.10 (1H, d, J = 2.1, H-6), 7.50 (1H, d, J = 8.4, H-9), 7.57 (2H, m, H-3″, H-5″), 7.70 (1H, m,
H-4″), 8.01 (2H, m, H-2″, H-6″).
6-Methyl-7-(2-oxo-2-phenylethoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (11). Yield 91%, C21H18O4,
mp 202-203°C. IR spectrum (KBr, cm-1): 3417, 2920, 1715, 1602, 1578, 1503, 1449, 1432, 1377, 1283, 1223, 1127, 1061,
1037, 971, 762, 688. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.78), 220 (4.27), 243 (4.24), 320 (4.24). PMR spectrum
3
(300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.30 (3H, s, CH -6), 2.74 (2H, m, CH -1), 3.03 (2H, m, CH -3),
6
2
3
2
2
5.72 (2H, s, CH -2 ), 7.01 (1H, d, J = 8.4, H-8), 7.34 (1H, d, J = 8.4, H-9), 7.57 (2H, m, H-3″, H-5″), 7.70 (1H, m, H-4″), 8.01
2
(2H, m, H-2″, H-6″).
7-[2-(4-Methylphenyl)-2-oxoethoxy]-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (12). Yield 91%, C21H18O4,
mp 178.5-179.5°C. IR spectrum (KBr, cm-1): 3442, 2918, 1712, 1699, 1625, 1562, 1514, 1444, 1427, 1396, 1295, 1234, 1156,
1058, 996, 835, 809, 750. UV spectrum (CH CN, λmax, nm, log ε): 206 (5.03), 222 (4.56), 252 (4.53), 292 (4.31), 319 (4.49).
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.41 (3H, s, CH -4 ), 2.73 (2H, m, CH -1), 3.05
6
2
3
2
(2H, m, CH -3), 5.67 (2H, s, CH -2 ), 7.01 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 7.08 (1H, d, J = 2.1, H-6), 7.39 (2H, d, J = 8.4,
2
2
H-3″, H-5″), 7.50 (1H, d, J = 8.4, H-9), 7.92 (2H, J = 8.4, H-2″, H-6″).
7-[2-(4-Methylphenyl)-2-oxoethoxy]-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (13). Yield 94%,
C22H20O4, mp 211.5-212.5°C. IR spectrum (KBr, cm-1): 3421, 2968, 2921, 1715, 1701, 1609, 1574, 1503, 1458, 1431, 1284,
1231, 1129, 1061, 1037, 972, 801, 758. UV spectrum (CH CN, λmax, nm, log ε): 207 (4.83), 254 (4.36), 319 (4.32). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.30 (3H, s, CH -6), 2.41 (3H, s, CH -4″), 2.77 (2H, m,
6
2
3
3
CH -1), 3.03 (2H, m, CH -3), 5.67 (2H, s, CH -2′), 6.99 (1H, d, J = 8.4, H-8), 7.34 (1H, d, J = 8.4, H-9), 7.38 (2H, d, J = 8.4,
2
2
2
H-3″, H-5″), 7.91 (2H, d, J = 8.4, H-2″, H-6″).
234

7-[2-(4-Fluorophenyl)-2-oxoethoxy]-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (14). Yield 92%, C20H15FO4,
mp 214-215°C. IR spectrum (KBr, cm-1): 3431, 2916, 1719, 1702, 1625, 1600, 1510, 1413, 1396, 1296, 1233, 1155, 1086,
1059, 993, 858, 834, 812, 750, 583. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.95), 223 (4.45), 247 (4.36), 292 (4.16),
3
319 (4.39). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.11 (2H, m, CH -2), 2.74 (2H, m, CH -1), 3.07 (2H, m,
6
2
2
CH -3), 5.72 (2H, s, CH -2′), 7.03 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 7.12 (1H, d, J = 2.1, H-6), 7.43 (2H, m, H-3″, H-5″), 7.53
2
2
(1H, d, J = 8.4, H-9), 8.13 (2H, m, H-2″, H-6″).
7-[2-(4-Fluorophenyl)-2-oxoethoxy]-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (15). Yield 93%,
C21H17FO4, mp 186-187°C. IR spectrum (KBr, cm-1): 3437, 3049, 2931, 1729, 1703, 1633, 1602, 1508, 1431, 1379, 1289,
1233, 1135, 838, 800, 757, 583. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.93), 222 (4.42), 246 (4.39), 323 (4.40). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.30 (3H, s, CH -6), 2.74 (2H, m, CH -1), 3.03 (2H, m,
6
2
3
2
CH -3), 5.73 (2H, s, CH -2′), 7.01 (1H, d, J = 8.4, H-8), 7.34 (1H, d, J = 8.4, H-9), 7.42 (2H, m, H-3″, H-5″), 8.11 (2H, m, H-2″,
2
2
H-6″).
7-[2-(4-Chlorophenyl)-2-oxoethoxy]-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (16). Yield 94%, C20H15ClO4,
mp 202.5-203.5°C. IR spectrum (KBr, cm-1): 3434, 2913, 1702, 1623, 1589, 1403, 1294, 1232, 1158, 1092, 1060, 991, 835,
823. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.94), 223 (4.44), 252 (4.46), 291 (4.20), 320 (4.39). PMR spectrum
3
(300 MHz, DMSO-d , δ, ppm, J/Hz): 2.11 (2H, m, CH -2), 2.74 (2H, m, CH -1), 3.07 (2H, m, CH -3), 5.67 (2H, s, CH -2′),
6
2
2
2
2
7.00 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 7.08 (1H, d, J = 2.1, H-6), 7.52 (1H, d, J = 8.4, H-9), 7.64 (2H, d, J = 7.2, H-3″, H-5″),
8.05 (2H, d, J = 7.2, H-2″, H-6″).
7-[2-(4-Chlorophenyl)-2-oxoethoxy]-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (17). Yield 89%,
C21H17ClO4, mp 223-224°C. IR spectrum (KBr, cm-1): 3424, 2921, 1717, 1612, 1430, 1376, 1285, 1224, 1130, 1091, 1036,
978, 971, 827, 800, 757. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.25), 255 (3.76), 321 (3.70). PMR spectrum (300 MHz,
3
DMSO-d , δ, ppm, J/Hz): 2.13 (2H, m, CH -2), 2.31 (3H, s, CH -6), 2.76 (2H, m, CH -1), 3.04 (2H, m, CH -3), 5.67 (2H, s,
6
2
3
2
2
CH -2′), 7.03 (1H, d, J = 8.4, H-8), 7.39 (1H, d, J = 8.4, H-9), 7.64 (2H, d, J = 7.2, H-3 , H-5 ), 8.05 (2H, d, J = 7.2, H-2″,
2
H-6″).
7-[2-(4-Bromophenyl)-2-oxoethoxy]-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (18). Yield 91%, C20H15BrO4,
mp 204-205°C. IR spectrum (KBr, cm-1): 3424, 2919, 1720, 1702, 1625, 1586, 1402, 1296, 1233, 1159, 1072, 991, 817. UV
spectrum (CH CN, λmax, nm, log ε): 205 (5.12), 215 (4.77), 257 (4.66), 291 (4.40), 319 (4.59). PMR spectrum (300 MHz,
3
DMSO-d , δ, ppm, J/Hz): 2.17 (2H, m, CH -2), 2.76 (2H, m, CH -1), 3.08 (2H, m, CH -3), 5.60 (2H, s, CH -2′), 6.97 (1H, dd,
6
2
2
2
2
J8,6 = 2.1, J8,9 = 8.4, H-8), 7.05 (1H, d, J = 2.1, H-6), 7.44 (1H, d, J = 8.4, H-9), 7.74 (2H, d, J = 8.4, H-3″, H-5″), 7.94 (2H, d,
J = 8.4, H-2″, H-6″).
7-[2-(4-Bromophenyl)-2-oxoethoxy]-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (19). Yield 95%,
C21H17BrO4, mp 229-230°C. IR spectrum (KBr, cm-1): 3433, 2926, 1698, 1625, 1604, 1588, 1501, 1446, 1376, 1296, 1226,
1122, 1072, 1048, 979, 970, 815, 758. UV spectrum (dioxane, λmax, nm, log ε): 213 (4.67), 256 (4.40), 296 (4.22), 319 (4.30).
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.29 (3H, s, CH -6), 2.75 (2H, m, CH -1), 3.04 (2H,
6
2
3
2
m, CH -3), 5.70 (2H, s, CH -2′), 7.02 (1H, d, J = 8.4, H-8), 7.34 (1H, d, J = 8.4, H-9), 7.80 (2H, d, J = 8.4, H-3″, H-5″), 7.93
2
2
(2H, d, J = 8.4, H-2″, H-6″).
7-[2-(4-Methoxyphenyl)-2-oxoethoxy]-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (20). Yield 88%, C21H18O5,
mp 198-199°C. IR spectrum (KBr, cm-1): 3434, 3069, 2963, 1711, 1684, 1624, 1612, 1602, 1514, 1428, 1404, 1373, 1284,
1267, 1233, 1164, 1078, 1057, 1025, 978, 831, 814. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.94), 219 (4.67), 285 (4.56),
3
320 (4.49). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.73 (2H, m, CH -1), 3.04 (2H, m, CH -
6
2
2
2
3), 3.87 (3H, s, OCH -4 ), 5.64 (2H, s, CH -2 ), 6.99 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 7.06 (1H, d, J = 2.1, H-6), 7.09 (2H,
3
2
d, J = 8.4, H-3″, H-5″), 7.49 (1H, d, J = 8.4, H-9), 8.00 (2H, J = 8.4, H-2″, H-6″).
7-[2-(4-Methoxyphenyl)-2-oxoethoxy]-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (21). Yield 92%,
C22H20O5, mp 208°C. IR spectrum (KBr, cm-1): 3420, 2918, 2849, 1717, 1697, 1602, 1574, 1504, 1459, 1425, 1378, 1315,
1285, 1265, 1240, 1189, 1129, 1023, 973, 832, 800, 757, 606. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.84), 220 (4.56),
3
282 (4.45), 319 (4.36). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.30 (3H, s, CH -6), 2.74
6
2
3
(2H, m, CH -1), 3.04 (2H, m, CH -3), 3.86 (3H, s, OCH -4″), 5.67 (2H, s, CH -2 ), 6.98 (1H, d, J = 8.4, H-8), 7.10 (2H, d,
2
2
3
2
J = 8.4, H-3″, H-5″), 7.35 (1H, d, J = 8.4, H-9), 7.99 (2H, J = 8.4, H-2″, H-6″).
7-[2-(3-Methoxyphenyl)-2-oxoethoxy]-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (22). Yield 91%, C21H18O5,
mp 173-174°C. IR spectrum (KBr, cm-1): 3433, 3066, 2910, 1723, 1701, 1611, 1510, 1487, 1469, 1453, 1428, 1402, 1336,
235

1268, 1253, 1221, 1199, 1169, 1068, 1028, 1011, 880, 828, 804, 787, 755, 686. UV spectrum (CH CN, λmax, nm, log ε): 205
3
(4.76), 220 (4.63), 250 (4.07), 292 (4.05), 319 (4.29). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.13 (2H, m, CH -
6
2
2), 2.75 (2H, m, CH -1), 3.05 (2H, m, CH -3), 3.85 (3H, s, OCH -3″), 5.63 (2H, s, CH -2 ), 6.97 (1H, dd, J8,6 = 2.4, J8,9 = 8.4,
2
2
3
2
H-8), 7.06 (1H, d, J = 2.1, H-6), 7.23 (1H, dd, J = 2.7, J = 8.4, H-4″), 7.44 (1H, d, J = 8.4, H-5″), 7.47 (1H, d, J = 8.4, H-9), 7.51
(1H, d, J = 2.7, H-2″), 7.65 (1H, J = 8.4, H-6″).
7-[2-(3-Methoxyphenyl)-2-oxoethoxy]-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (23). Yield 93%,
C22H20O5, mp 195-196°C. IR spectrum (KBr, cm-1): 3424, 2925, 2860, 1718, 1707, 1632, 1599, 1490, 1471, 1435, 1377, 1338,
1320, 1288, 1260, 1207, 1182, 1134, 1069, 1043, 1013, 975, 871, 824, 793, 757, 687, 618. UV spectrum (dioxane, λmax, nm,
log ε): 204 (4.71), 219 (4.68), 248 (4.01), 292 (4.00), 321 (4.32). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.11
6
(2H, m, CH -2), 2.30 (3H, s, CH -6), 2.75 (2H, m, CH -1), 3.03 (2H, m, CH -3), 3.84 (3H, s, OCH -3 ), 5.70 (2H, s, CH -2′),
2
3
2
2
3
2
7.00 (1H, d, J = 8.4, H-8), 7.25 (1H, dd, J = 2.7, J = 8.4, H-4″), 7.35 (1H, d, J = 8.4, H-9), 7.47 (1H, d, J = 8.4, H-5″), 7.51 (1H,
d, J = 2.7, H-2″), 7.60 (1H, J = 8.4, H-6″).
7-[2-(1,3-Benzodioxol-5-yl)-2-oxoethoxy]-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (24). Yield 88%,
C21H16O6, mp 187-188°C. IR spectrum (KBr, cm-1): 3434, 2920, 1711, 1688, 1624, 1562, 1503, 1457, 1428, 1399, 1296, 1266,
1156, 1140, 1114, 1075, 1047, 998, 936, 835, 805, 750. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.88), 224 (4.61), 231
3
(4.55), 279 (4.25), 294 (4.30), 319 (4.53). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.74 (2H,
6
2
m, CH -1), 3.06 (2H, m, CH -3), 5.61 (2H, s, CH -2′), 6.16 (2H, s, CH -2 ), 6.99 (1H, dd, J8,6 = 2.4, J8,9 = 8.4, H-8), 7.07 (1H,
2
2
2
2
d, J = 2.1, H-6), 7.10 (1H, d, J = 8.4, H-7″), 7.50 (1H, d, J = 8.4, H-9), 7.53 (1H, d, J = 2.1, H-4″), 7.69 (1H, dd, J6",4" = 2.1, J6",7"
= 8.4, H-6″).
7-[2-(1,3-Benzodioxol-5-yl)-2-oxoethoxy]-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (25). Yield
92%, C22H18O6, mp 234-235°C. IR spectrum (KBr, cm-1): 3423, 2918, 1721, 1694, 1604, 1502, 1449, 1438, 1378, 1277, 1253,
1136, 1108, 1034, 997, 975, 924, 817, 801, 757. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.75), 226 (4.45), 231 (4.40),
3
286 (4.12), 319 (4.42). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.11 (2H, m, CH -2), 2.29 (3H, s, CH -6), 2.75
6
2
3
(2H, m, CH -1), 3.10 (2H, m, CH -3), 5.67 (2H, s, CH -2′), 6.13 (2H, s, CH -2 ), 6.95 (1H, J = 8.4, H-8), 7.05 (1H, d, J = 8.4,
2
2
2
2
H-7″), 7.34 (1H, d, J = 8.4, H-9), 7.48 (1H, d, J = 2.1, H-4″), 7.65 (1H, dd, J6",4" = 2.1, J6",7" = 8.4, H-6″).
7-Methyl-9-(2-oxopropoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (28). Yield 78%, C16H16O4, mp 143-
145°C. IR spectrum (KBr, cm-1): 3436, 2951, 2918, 1714, 1705, 1615, 1497, 1441, 1421, 1384, 1253, 1157, 1139, 1075, 828,
739. UV spectrum (EtOH, λmax, nm, log ε): 207 (4.50), 247 (3.75), 314 (4.11). PMR spectrum (300 MHz, deuteroacetone, δ,
ppm): 2.17 (2H, m, CH -2), 2.25 (3H, s, CH -1′), 2.37 (3H, s, CH -7), 2.77 (2H, m, CH -1), 3.41 (2H, m, CH -3), 4.91 (2H,
2
3
3
2
2
s, CH -3′), 6.66 (1H, s, H-8), 6.76 (1H, d, H-6).
2
7-Methyl-9-(1-methyl-2-oxopropoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (29). Yield 75%, C17H18O4,
mp 146-148°C. IR spectrum (KBr, cm-1): 3416, 2974, 2928, 2860, 1721, 1615, 1560, 1498, 1456, 1429, 1380, 1292, 1257,
1163, 1128, 1097, 1065, 1047, 1029, 988, 830. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.84), 246 (4.35), 305 (4.45).
3
PMR spectrum (300 MHz, deuteroacetone, δ, ppm, J/Hz): 1.58 (3H, d, J = 6.9, CH -4′), 2.10 (2H, m, CH -2), 2.21 (3H, s,
3
2
CH -1′), 2.36 (3H, s, CH -7), 2.75 (2H, m, CH -1), 3.45 (2H, m, CH -3), 5.03 (1H, q, H-3′), 6.54 (1H, s, H-8), 6.78 (1H, s, H-6).
3
3
2
2
7-Methyl-9-(1-methyl-2-oxo-2-phenylethoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (30). Yield 82%,
C22H20O4, mp 195-196°C. IR spectrum (KBr, cm-1): 3434, 2918, 1717, 1688, 1612, 1496, 1439, 1380, 1257, 1237, 1223, 1139,
1114, 1061, 962, 837, 705. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.99), 247 (4.56), 310 (4.45). PMR spectrum (300
3
MHz, DMSO-d , δ, ppm, J/Hz): 1.61 (3H, d, J = 6.9, CH -3 ), 2.03 (2H, m, CH -2), 2.28 (3H, s, CH -7), 2.68 (2H, m, CH -1),
6
3
2
3
2
3.32 (2H, m, CH -3), 6.22 (1H, q, H-2′), 6.68 (1H, s, H-8), 6.81 (1H, s, H-6), 7.59 (2H, m, H-3″, H-5″), 7.71 (1H, m, H-4″),
2
8.08 (2H, m, H-2″, H-6″).
7-Methyl-9-(2-oxo-2-phenylethoxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (31). Yield 89%, C21H18O4,
mp 213-215°C. IR spectrum (KBr, cm-1): 3434, 2904, 1719, 1696, 1614, 1499, 1448, 1424, 1232, 1160, 1139, 1076, 998. UV
spectrum (CH CN, λmax, nm, log ε): 204 (4.84), 244 (4.40), 308 (4.30). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz):
3
6
2.07 (2H, m, CH -2), 2.36 (3H, s, CH -7), 2.70 (2H, m, CH -1), 3.40 (2H, m, CH -3), 5.59 (2H, s, CH -2′), 6.76 (1H, s, H-8),
2
3
2
2
2
6.80 (1H, d, H-6), 7.55 (2H, m, H-3″, H-5″), 7.67 (1H, m, H-4″), 8.03 (2H, d, J = 8.4, H-2″, H-6″).
9-[2-(4-Methylphenyl)-2-oxoethoxy]-7-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (32). Yield 90%,
C22H20O4, mp 209-211°C. IR spectrum (KBr, cm-1): 3434, 2920, 1701, 1612, 1497, 1421, 1236, 1139, 1074, 1054, 1027, 997,
813. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.40), 253 (4.00), 328 (3.88). PMR spectrum (300 MHz, DMSO-d , δ, ppm,
3
6
J/Hz): 2.04 (2H, m, CH -2), 2.35 (3H, s, CH -7), 2.40 (3H, s, CH -4 ), 2.69 (2H, m, CH -1), 3.38 (2H, m, CH -3), 5.60 (2H,
2
3
3
2
2
236

s, CH -2′), 6.75 (1H, s, H-8), 6.82 (1H, s, H-6), 7.39 (2H, d, J = 8.4, H-3″, H-5″), 7.92 (2H, d, J = 8.4, H-2″, H-6″).
2
9-[2-(4-Fluorophenyl)-2-oxoethoxy]-7-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (33). Yield 89%,
C21H17FO4, mp 212-214°C. IR spectrum (KBr, cm-1): 3433, 2915, 2856, 1702, 1611, 1560, 1498, 1459, 1445, 1424, 1385,
1342, 1263, 1232, 1155, 1139, 1075, 1054, 1025, 993, 830, 592, 568. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.79), 245
3
(4.38), 308 (4.26). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.08 (2H, m, CH -2), 2.68 (2H, m, CH -1), 3.39 (2H, m,
6
2
2
CH -3), 5.65 (2H, s, CH -2′), 6.84 (1H, s, H-8), 6.88 (1H, s, H-6), 7.41 (2H, m, H-3″, H-5″), 8.13 (2H, m, H-2″, H-6″).
2
2
9-[2-(4-Chlorophenyl)-2-oxoethoxy]-7-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (34). Yield 94%,
C21H17ClO4, mp 221-222°C. IR spectrum (KBr, cm-1): 3433, 2912, 1703, 1613, 1590, 1499, 1429, 1401, 1232, 1156, 1139,
1091, 1076, 992, 820. UV spectrum (dioxane, λmax, nm, log ε): 214 (4.66), 252 (4.42), 311 (4.24). PMR spectrum (300 MHz,
DMSO-d , δ, ppm, J/Hz): 2.06 (2H, m, CH -2), 2.35 (3H, s, CH -7), 2.70 (2H, m, CH -1), 3.36 (2H, m, CH -3), 5.61 (2H, s,
6
2
3
2
2
CH -2′), 6.81 (1H, s, H-8), 6.84 (1H, s, H-6), 7.62 (2H, d, J = 7.2, H-3″, H-5″), 8.05 (2H, d, J = 7.2, H-2″, H-6″).
2
9-[2-(4-Bromophenyl)-2-oxoethoxy]-7-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (35). Yield 88%,
C21H17BrO4, mp 236-237°C. IR spectrum (KBr, cm-1): 3434, 2922, 1702, 1612, 1586, 1500, 1459, 1430, 1401, 1261, 1229,
1157, 1139, 1076, 1056, 992, 818. UV spectrum (dioxane, λmax, nm, log ε): 215 (4.67), 254 (4.43), 306 (4.31). PMR spectrum
(300 MHz, DMSO-d , δ, ppm, J/Hz): 2.08 (2H, m, CH -2), 2.35 (3H, s, CH -7), 2.69 (2H, m, CH -1), 3.38 (2H, m, CH -3),
6
2
3
2
2
5.64 (2H, s, CH -2′), 6.84 (1H, s, H-8), 6.87 (1H, s, H-6), 7.81 (2H, d, J = 8.4, H-3″, H-5″), 7.96 (2H, d, J = 8.4, H-2″, H-6″).
2
9-[2-(4-Methoxyphenyl)-2-oxoethoxy]-7-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (36). Yield 94%,
C22H20O5, mp 193-194°C. IR spectrum (KBr, cm-1): 3433, 2950, 2849, 1709, 1695, 1611, 1599, 1560, 1513, 1502, 1460, 1421,
1383, 1320, 1306, 1268, 1237, 1170, 1153, 1137, 1076, 1058, 1025, 990, 829. UV spectrum (CH CN, λmax, nm, log ε): 206
3
(4.79), 215 (4.68), 258 (4.26), 286 (4.49), 310 (4.36). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.04 (2H, m, CH -
6
2
2), 2.34 (3H, s, CH -7), 2.68 (2H, m, CH -1), 3.38 (2H, m, CH -3), 3.87 (3H, s, CH O-4 ), 5.58 (2H, s, CH -2′), 6.81 (1H, s,
3
2
2
3
2
H-8), 6.85 (1H, s, H-6), 7.11 (2H, d, J = 8.4, H-3″, H-5″), 8.01 (2H, d, J = 8.4, H-2″, H-6″).
9-[2-(3-Methoxyphenyl)-2-oxoethoxy]-7-methyl-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (37). Yield 91%,
C22H20O5, mp 169-170°C. IR spectrum (KBr, cm-1): 3434, 2920, 1719, 1708, 1613, 1585, 1560, 1497, 1459, 1432, 1384, 1263,
1138, 1075, 1052, 1026, 992, 789, 686. UV spectrum (EtOH, λmax, nm, log ε): 207 (4.03), 217 (4.00), 251 (3.53), 313 (3.64).
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.04 (2H, m, CH -2), 2.35 (3H, s, CH -7), 2.68 (2H, m, CH -1), 3.38 (2H,
6
2
3
2
m, CH -3), 3.85 (3H, s, OCH -3″), 5.63 (2H, s, CH -2 ), 6.82 (1H, s, H-8), 6.87 (1H, s, H-6), 7.25 (1H, dd, J = 2.7, J = 8.4,
2
3
2
H-4″), 7.48 (1H, d, J = 8.4, H-5″), 7.53 (1H, d, J = 2.7, H-2″), 7.63 (1H, J = 8.4, H-6″).
7-(2-Oxocyclohexyloxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (26). A solution of coumarin (1, 3.03 g,
15 mmole) in dry DMF (50 mL) was treated with freshly calcined potash (6.2 g, 45 mmole) and 2-chlorocyclohexanone
(3.43 mL, 30 mmole). The reaction mixture was stirred vigorously and heated (75-80 C) for 24 h and treated with H SO
2
4
(300 mL, 1 N). The solid was filtered off and crystallized from isopropanol. Yield 59%, C18H18O4, mp 180 C. IR spectrum
(KBr, cm-1): 3417, 2946, 2868, 1714, 1709, 1624, 1558, 1435, 1393, 1320, 1292, 1255, 1151, 1133, 1074, 1057, 1024,
860, 819. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.70), 220 (4.30), 224 (4.28), 293 (4.05), 321 (4.31). PMR spectrum
3
(300 MHz, DMSO-d , δ, ppm, J/Hz): 2.09 (2H, m, CH -2), 1.60-2.66 (8H, m, CH -3′, CH -4′, CH -5′, CH -6′), 2.71 (2H, m,
6
2
2
2
2
2
CH -1), 3.04 (2H, m, CH -3), 5.20 (1H, m, H-1′), 6.88 (1H, dd, J8,6 = 2.1, J8,9 = 8.4, H-8), 6.95 (1H, d, J = 2.1, H-6), 7.46 (1H,
2
2
d, J = 8.4, H-9).
6-Methyl-7-(2-oxocyclohexyloxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (27). Prepared analogously to
26. Yield 63%, C19H20O4, mp 224-226 C. IR spectrum (KBr, cm-1): 3432, 2950, 2859, 1724, 1701, 1605, 1573, 1502, 1445,
1374, 1313, 1284, 1263, 1120, 1104, 1073, 1044, 811, 758, 533. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.65), 220
3
(4.23), 323 (4.23). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.09 (2H, m, CH -2), 2.25 (3H, s, CH -6), 1.60-2.66
6
2
3
(8H, m, CH -3′, CH -4′, CH -5′, CH -6′), 2.74 (2H, m, CH -1), 3.02 (2H, m, CH -3), 5.14 (1H, m, H-1′), 6.86 (1H, d, J = 8.4,
2
2
2
2
2
2
H-8), 7.29 (1H, d, J = 8.4, H-9).
7-Methyl-9-(2-oxocyclohexyloxy)-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-one (38). Prepared analogously to
26. Yield 52%, C19H20O4, mp 170-171 C. IR spectrum (KBr, cm-1): 3424, 2943, 2863, 1716, 1613, 1494, 1445, 1383, 1290,
1254, 1169, 1127, 1109, 1072, 841, 821. UV spectrum (CH CN, λmax, nm, log ε): 207 (4.61), 246 (3.91), 254 (3.86), 310
3
(4.21). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.32 (3H, s, CH -7), 1.60-2.60 (8H, m,
6
2
3
CH -3′, CH -4′, CH -5′, CH -6′), 2.68 (2H, m, CH -1), 3.30 (2H, m, CH -3), 5.19 (1H, m, H-1′), 6.62 (1H, s, H-8), 6.78 (1H,
2
2
2
2
2
2
s, H-6).
237

General Synthetic Method for Furocoumarins 39-73. A solution or suspension of ketone 4-38 (6 mmole) in
isopropanol (50 mL) was treated with NaOH (50 mL, 1 N). The reaction mixture was heated for 3-4 h until the starting ketone
dissolved completely (course of the reaction monitored by TLC) and treated with H SO (300 mL, 1 N). The solid was filtered
2
4
off and crystallized from isopropanol.
9-Methyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (39). Yield 86%, C15H12O3, mp 232-233 C
(lit. 237 C [25]). IR spectrum (KBr, cm-1): 3422, 3119, 2919, 1716, 1637, 1599, 1578, 1459, 1446, 1402, 1385, 1345, 1258,
1128, 1067, 1052, 944, 865, 816, 752. UV spectrum (CH CN, λmax, nm, log ε): 210 (4.58), 250 (4.48), 296 (4.16), 328 (4.06).
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.14 (2H, m, CH -2), 2.25 (3H, s, CH -9), 2.75 (2H, m, CH -1), 3.13 (2H, m,
6
2
3
2
CH -3), 7.64 (1H, s, H-6), 7.76 (1H, s, H-10), 7.86 (1H, s, H-8),
2
6,9-Dimethyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (40). Yield 89%, C16H14O3, mp 204-205 C.
IR spectrum (KBr, cm-1): 3414, 2962, 2923, 2861, 1719, 1638, 1621, 1597, 1459, 1444, 1395, 1354, 1264, 1102, 1059, 1038,
984, 855, 814, 758. UV spectrum (CH CN, λmax, nm, log ε): 212 (4.62), 251 (4.54), 300 (4.24), 328 (4.05). PMR spectrum
3
(300 MHz, DMSO-d , δ, ppm): 2.12 (2H, m, CH -2), 2.25 (3H, s, CH -9), 2.45 (3H, s, CH -6), 2.75 (2H, m, CH -1), 3.10 (2H,
6
2
3
3
2
m, CH -3), 7.52 (1H, s, H-10), 7.86 (1H, s, H-8).
2
8,9-Dimethyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (41). Yield 78%, C16H14O3, mp 211.5-
212.5 C. IR spectrum (KBr, cm-1): 3409, 3055, 2963, 2921, 2587, 1718, 1643, 1581, 1460, 1441, 1403, 1384, 1347, 1298,
1267, 1175, 1142, 1074, 1060, 952, 878, 861, 752. UV spectrum (CH CN, λmax, nm, log ε): 211 (4.57), 253 (4.56), 295 (4.16),
3
302 (4.15), 335 (4.04). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.12 (2H, m, CH -2), 2.16 (3H, s, CH -9), 2.38 (3H,
6
2
3
s, CH -8), 2.77 (2H, m, CH -1), 3.14 (2H, m, CH -3), 7.44 (1H, s, H-6), 7.52 (1H, s, H-10).
3
2
2
6,8,9-Trimethyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (42). Yield 84%, C17H16O3, mp 215-
216 C. IR spectrum (KBr, cm-1): 3418, 2952, 2922, 2861, 1716, 1642, 1599, 1461, 1438, 1407, 1386, 1354, 1267, 1176, 1148,
1098, 1038, 984, 955, 852, 820, 757. UV spectrum (CH CN, λmax, nm, log ε): 212 (4.40), 254 (4.39), 299 (4.01), 305 (4.00),
3
337 (3.81). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.09 (2H, m, CH -2), 2.12 (3H, s, CH -9), 2.38 (3H, s, CH -8), 2.40
6
2
3
3
(3H, s, CH -6), 2.73 (2H, m, CH -1), 3.07 (2H, m, CH -3), 7.29 (1H, s, H-10).
3
2
2
8-Methyl-9-phenyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (43). Yield 86%, C21H16O3, mp 205-
206 C. IR spectrum (KBr, cm-1): 3427, 3051, 2952, 2917, 2852, 1718, 1635, 1581, 1572, 1497, 1456, 1438, 1403, 1345, 1197,
1137, 1064, 1019, 956, 942, 894, 865, 835, 774, 751, 707. UV spectrum (CH CN, λmax, nm, log ε): 201 (4.36), 207 (4.32), 225
3
(4.12), 254 (4.27), 296 (3.94), 299 (3.93), 335 (3.72). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.11 (2H, m, CH -2),
6
2
2.54 (3H, s, CH -8), 2.77 (2H, m, CH -1), 3.12 (2H, m, CH -3), 7.44 (1H, m, H-4′), 7.56 (4H, m, H-2′, H-3′, H-5′, H-6′), 7.59
3
2
2
(1H, s, H-6), 7.64 (1H, s, H-10).
6,8-Dimethyl-9-phenyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (44). Yield 86%, C22H18O3, mp
242-244 C. IR spectrum (KBr, cm-1): 3420, 2960, 2922, 1729, 1634, 1598, 1438, 1401, 1341, 1175, 1103, 1033, 982, 952,
773, 756, 705. UV spectrum (CH CN, λmax, nm, log ε): 212 (4.69), 255 (4.67), 299 (4.35), 305 (4.33), 338 (4.04). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm): 2.09 (2H, m, CH -2), 2.50 (3H, s, CH -6), 2.54 (3H, s, CH -8), 2.76 (2H, m, CH -1),
6
2
3
3
2
3.06 (2H, m, CH -1), 7.39 (1H, s, H-10), 7.43 (1H, m, H-4′), 7.54 (4H, m, H-2′, H-3′, H-5′, H-6′).
2
9-Phenyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (45). Yield 85%, C20H14O3, mp 203-204 C.
IR spectrum (KBr, cm-1): 3406, 2948, 1714, 1632, 1610, 1578, 1457, 1440, 1420, 1400, 1349, 1150, 1103, 1089, 1067, 941,
840, 818, 749, 694. UV spectrum (EtOH, λmax, nm, log ε): 203 (4.57), 213 (4.55), 227 (4.40), 250 (4.42), 305 (4.21), 337
(4.00). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.12 (2H, m, CH -2), 2.77 (2H, m, CH -1), 3.18 (2H, m, CH -3), 7.43
6
2
2
2
(1H, m, H-4′), 7.54 (2H, m, H-3′, H-5′), 7.75 (1H, s, H-6), 7.79 (2H, m, H-2′, H-6′), 7.92 (1H, s, H-10), 8.44 (1H, s, H-8).
6-Methyl-9-phenyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (46). Yield 92%, C21H16O3, mp 237-
238 C. IR spectrum (KBr, cm-1): 3403, 2967, 1710, 1632, 1594, 1565, 1394, 1355, 1259, 1114, 1088, 1054, 1035, 982, 915,
812, 770, 757, 699. UV spectrum (CH CN, λmax, nm, log ε): 215 (4.39), 251 (4.29), 306 (4.10). PMR spectrum (300 MHz,
3
DMSO-d , δ, ppm): 2.11 (2H, m, CH -2), 2.50 (3H, s, CH -6), 2.77 (2H, m, CH -1), 3.14 (2H, m, CH -3), 7.42 (1H, m, H-4′),
6
2
3
2
2
7.53 (2H, m, H-3′, H-5′), 7.74 (1H, s, H-10), 7.76 (2H, m, H-2′, H-6′), 8.42 (1H, s, H-8).
9-(4-Methylphenyl)-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (47). Yield 82%, C21H16O3, mp 189-
190 C. IR spectrum (KBr, cm-1): 3429, 2919, 1723, 1705, 1633, 1585, 1576, 1509, 1450, 1402, 1349, 1152, 1097, 1069, 941,
819. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.72), 227 (4.48), 246 (4.51), 250 (4.52), 297 (4.31), 304 (4.32), 328 (4.08).
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.11 (2H, m, CH -2), 2.38 (3H, s, CH -4 ), 2.78 (2H, m, CH -1), 3,19
6
2
3
2
(2H, m, CH -3), 7.36 (2H, d, J = 8.4, H-3″, H-5″), 7.65 (2H, d, J = 8.4, H-2″, H-6″), 7.76 (1H, d, H-6), 7.92 (1H, s, H-10), 8.41
2
238

(1H, s, H-8).
9-(4-Methylphenyl)-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (48).
Yield 86%,
C22H18O3, mp 229-231 C. IR spectrum (KBr, cm-1): 3423, 2967, 2916, 1724, 1636, 1598, 1457, 1394, 1354, 1113, 1083, 1033,
983, 917, 805. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.68), 251 (4.56), 304 (4.34), 333 (3.97). PMR spectrum (300
3
MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.38 (3H, s, CH -4″), 2.50 (3H, s, CH -6), 2.75 (2H, m, CH -1), 3.11
6
2
3
3
2
(2H, m, CH -3), 7.33 (2H, d, J = 8.4, H-3″, H-5″), 7.61 (2H, d, J = 8.4, H-2″, H-6″), 7.67 (1H, s, H-10), 8.34 (1H, s, H-8).
2
9-(4-Fluorophenyl)-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (49). Yield 81%, C20H13FO3, mp
252-253 C. IR spectrum (KBr, cm-1): 3434, 2931, 1714, 1634, 1579, 1504, 1457, 1421, 1402, 1350, 1329, 1220, 1152, 1104,
1085, 1068, 942, 840, 818, 803. UV spectrum (CH CN, λmax, nm, log ε): 203 (4.59), 212 (4.52), 249 (4.44), 301 (4.20). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm): 2.12 (2H, m, CH -2), 2.76 (2H, m, CH -1), 3.17 (2H, m, CH -3), 7.36 (2H, m, H-3″,
6
2
2
2
H-5″), 7.74 (1H, s, H-6), 7.81 (2H, m, H-2″, H-6″), 7.89 (1H, s, H-10), 8.43 (1H, s, H-8).
9-(4-Fluorophenyl)-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (50).
Yield 84%,
C21H15FO3, mp 246-247 C. IR spectrum (KBr, cm-1): 3432, 2930, 1712, 1633, 1599, 1576, 1505, 1393, 1219, 1117, 1088,
1052, 839, 804. UV spectrum (CH CN, λmax, nm, log ε): 200 (4.67), 210 (4.59), 248 (4.49), 304 (4.28). PMR spectrum
3
(300 MHz, DMSO-d , δ, ppm): 2.12 (2H, m, CH -2), 2.45 (3H, s, CH -6), 2.73 (2H, m, CH -1), 3.09 (2H, m, CH -3), 7.33 (2H,
6
2
3
2
2
m, H-3″, H-5″), 7.63 (1H, s, H-10), 7.76 (2H, m, H-2′, H-6″), 8.38 (1H, s, H-8).
9-(4-Chlorophenyl)-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (51). Yield 90%, C20H13ClO3, mp
199-200 C. IR spectrum (KBr, cm-1): 3434, 2923, 1736, 1634, 1583, 1490, 1476, 1401, 1349, 1154, 1090, 1060, 1012, 940,
819, 798. UV spectrum (CH CN, λmax, nm, log ε): 203 (4.70), 251 (4.52), 302 (4.30), 329 (4.08). PMR spectrum (300 MHz,
3
DMSO-d , δ, ppm, J/Hz): 2.15 (2H, m, CH -2), 2.79 (2H, m, CH -1), 3.20 (2H, m, CH -3), 7.57 (2H, d, J = 7.2, H-3′, H-5′),
6
2
2
2
7.76 (1H, s, H-6), 7.80 (2H, d, J = 7.2, H-2′, H-6′), 7.94 (1H, s, H-10), 8.46 (1H, s, H-8).
9-(4-Chlorophenyl)-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (52).
Yield 93%,
C21H15ClO3, mp 242-244 C. IR spectrum (KBr, cm-1): 3423, 2970, 2916, 1725, 1637, 1597, 1580, 1492, 1392, 1353, 1114,
1093, 1082, 1030, 1015, 982, 915, 839, 804. UV spectrum (CH CN, λmax, nm, log ε): 204 (4.70), 213 (4.62), 249 (4.61), 302
3
(4.38), 335 (4.00). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.11 (2H, m, CH -2), 2.50 (3H, s, CH -6), 2.76 (2H,
6
2
3
m, CH -1), 3.14 (2H, m, CH -3), 7.56 (2H, d, J = 7.2, H-3′, H-5′), 7.72 (1H, s, H-10), 7.77 (2H, d, J = 7.2, H-2′, H-6′), 8.48 (1H,
2
2
s, H-8).
9-(4-Bromophenyl)-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (53). Yield 88%, C20H13BrO3, mp
192-193 C. IR spectrum (KBr, cm-1): 3434, 2921, 1727, 1635, 1603, 1582, 1475, 1448, 1398, 1348, 1151, 1106, 1081, 1061,
1008, 941, 821, 810. UV spectrum (EtOH, λmax, nm, log ε): 203 (4.81), 213 (4.70), 249 (4.64), 302 (4.42), 335 (4.16). PMR
spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.18 (2H, m, CH -2), 2.82 (2H, m, CH -1), 3.22 (2H, m, CH -3), 7.65 (2H, d,
6
2
2
2
J = 8.4, H-3′, H-5′), 7.69 (1H, s, H-6), 7.72 (2H, d, J = 8.4, H-2′, H-6′), 7.92 (1H, s, H-10), 8.41 (1H, s, H-8).
9-(4-Bromophenyl)-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (54).
Yield 91%,
C21H15BrO3, mp 229-230 C. IR spectrum (KBr, cm-1): 3421, 2961, 1723, 1637, 1596, 1577, 1488, 1392, 1353, 1115, 1083,
1030, 1011, 983, 915, 837, 804. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.69), 212 (4.60), 249 (4.59), 301 (4.35). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm): 2.13 (2H, m, CH -2), 2.48 (3H, s, CH -6), 2.78 (2H, m, CH -1), 3.16 (2H, m, CH -3),
6
2
3
2
2
7.71 (5H, m, H-10, H-2′, H-3′, H-5′, H-6′), 8.48 (1H, s, H-8).
9-(4-Methoxyphenyl)-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (55). Yield 89%, C21H16O4, mp
189-190 C. IR spectrum (KBr, cm-1): 3449. 2972, 2838, 1713, 1633, 1585, 1507, 1465, 1402, 1350, 1272, 1245, 1179, 1151,
1113, 1091, 1067, 1035, 941, 874, 836, 819, 795, 753. UV spectrum (EtOH, λmax, nm, log ε): 206 (4.70), 232 (4.53), 252
(4.56), 310 (4.34). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.13 (2H, m, CH -2), 2.79 (2H, m, CH -1), 3.20 (2H,
6
2
2
m, CH -3), 7.11 (2H, d, J = 8.4, H-3′, H-5′), 7.71 (2H, d, J = 8.4, H-2′, H-6′), 7.77 (1H, s, H-6), 7.92 (1H, s, H-10), 8.37 (1H,
2
s, H-8).
9-(4-Methoxyphenyl)-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (56). Yield 83%,
C22H18O4, mp 195-196 C. IR spectrum (KBr, cm-1): 3421, 2967, 1722, 1585, 1509, 1449, 1393, 1332, 1301, 1250, 1179, 1112,
1082, 1027, 983, 916, 836, 806. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.80), 252 (4.72), 305 (4.49). PMR spectrum
3
(300 MHz, DMSO-d , δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.48 (3H, s, CH -6), 2.75 (2H, m, CH -1), 3.12 (2H, m, CH -3),
6
2
3
2
2
7.09 (2H, d, J = 8.4, H-3′, H-5′), 7.67 (2H, d, J = 8.4, H-2′, H-6′), 7.70 (1H, s, H-10), 8.36 (1H, s, H-8).
9-(3-Methoxyphenyl)-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (57). Yield 92%, C21H16O4, mp
226-227° C. IR spectrum (KBr, cm-1): 3433, 3097, 3084, 2966, 2918, 1709, 1635, 1603, 1577, 1498, 1465, 1451, 1425, 1406,
239

1353, 1265, 1248, 1221, 1159, 1101, 1069, 1013, 870, 843, 822, 792. UV spectrum (CH CN, λmax, nm, log ε): 212 (4.76), 251
3
(4.49), 301 (4.32), 328 (4.06). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.16 (2H, m, CH -2), 2.79 (2H, m, CH -1),
6
2
2
3.17 (2H, m, CH -3), 3.86 (3H, s, OCH -3′), 6.95 (1H, dd, J = 2.7, J = 8.4, H-4′), 7.22 (1H, d, J = 2.7, H-2′), 7.28 (1H, d,
2
3
J = 8.4, H-5′), 7.41 (1H, J = 8.4, H-6′), 7.59 (1H, s, H-6), 7.84 (1H, s, H-10), 8.29 (1H, s, H-8).
9-(3-Methoxyphenyl)-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (58). Yield 87%,
C22H18O4, mp 225.5-226.5° C. IR spectrum (KBr, cm-1): 3435, 2929, 1707, 1603, 1491, 1475, 1456, 1419, 1392, 1218, 1115,
1056, 1027, 857, 838, 793. UV spectrum (CH CN, λmax, nm, log ε): 214 (5.00), 250 (4.66), 301 (4.49), 333 (4.21). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.16 (2H, m, CH -2), 2.54 (3H, s, CH -6), 2.80 (2H, m, CH -1), 3.15 (2H, m,
6
2
3
2
CH -3), 3.86 (3H, s, OCH -3′), 6.95 (1H, dd, J = 2.7, J = 8.4, H-4′), 7.22 (1H, d, J = 2.7, H-2′), 7.28 (1H, d, J = 8.4, H-5′), 7.40
2
3
(1H, J = 8.4, H-6′), 7.69 (1H, s, H-10), 8.31 (1H, s, H-8).
9-(1,3-Benzodioxol-5-yl)-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (59). Yield 86%, C21H14O5,
mp 189.5-190.5° C. IR spectrum (KBr, cm-1): 3432, 3103, 2901, 1713, 1634, 1577, 1502, 1489, 1477, 1435, 1402, 1344, 1236,
1165, 1137, 1097, 1068, 1037, 929, 867, 819. UV spectrum (CH CN, λmax, nm, log ε): 211 (4.77), 253 (4.55), 308 (4.42). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.13 (2H, m, CH -2), 2.77 (2H, m, CH -1), 3.18 (2H, m, CH -3), 6.09 (2H, s,
6
2
2
2
CH -2′), 7.04 (1H, d, J = 8.4, H-7′), 7.23 (1H, dd, J = 2.1, J = 8.4, H-6′), 7.29 (1H, d, J = 2.1, H-4′), 7.69 (1H, s, H-6), 7.86 (1H,
2
s, H-10), 8.32 (1H, s, H-8).
9-(1,3-Benzodioxol-5-yl)-6-methyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one (60). Yield 91%,
C22H16O5, mp 220-221° C. IR spectrum (KBr, cm-1): 3427, 2901, 1711, 1633, 1597, 1574, 1504, 1490, 1474, 1437, 1393, 1347,
1270, 1238, 1120, 1103, 1084, 1038, 985, 931, 865, 810, 789. UV spectrum (CH CN, λmax, nm, log ε): 214 (4.78), 250 (4.56),
3
302 (4.40), 328 (4.05). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.11 (2H, m, CH -2), 2.48 (3H, s, CH -6), 2.76
6
2
3
(2H, m, CH -1), 3.14 (2H, m, CH -3), 6.09 (2H, s, CH -2 ), 7.04 (1H, d, J = 8.4, H-7′), 7.23 (1H, dd, J = 2.1, J = 8.4, H-6′),
2
2
2
7.28 (1H, d, J = 2.1, H-4′), 7.67 (1H, s, H-10), 8.33 (1H, s, H-8).
1,2,3,4,8,9,10,11-Octahydrobenzo[4,5]furo[3,2-g]cyclopenta[c]chromen-4-one (61). Yield 79%, C18H16O3, mp 223-
224° C. IR spectrum (KBr, cm-1): 3403, 3059, 2936, 2859, 1711, 1647, 1634, 1579, 1461, 1439, 1406, 1344, 1130, 1113, 1068,
1024, 942, 867, 751. UV spectrum (CH CN, λmax, nm, log ε): 212 (4.37), 254 (4.43), 295 (4.00), 301 (3.99), 338 (3.87). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm): 1.85 (4H, m, CH -9, CH -10), 2.13 (2H, m, CH -2), 2.61 (2H, m, CH -11), 2.74 (4H,
6
2
2
2
2
m, CH -1, CH -8), 3.12 (2H, m, CH -3), 7.53 (1H, s, H-6), 7.56 (1H, s, H-10).
2
2
2
6-Methyl-1,2,3,4,8,9,10,11-octahydrobenzo[4,5]furo[3,2-g]cyclopenta[c]chromen-4-one (62). Yield 82%, C19H18O3,
mp 238-239° C. IR spectrum (KBr, cm-1): 3433, 2943, 2854, 1708, 1642, 1596, 1440, 1412, 1340, 1181, 1137, 1100, 1088,
1042, 984. UV spectrum (CH CN, λmax, nm, log ε): 202 (4.57), 210 (4.55), 255 (4.55), 299 (4.15), 338 (3.91). PMR spectrum
3
(300 MHz, DMSO-d , δ, ppm): 1.84 (2H, m, CH -10), 1.94 (2H, m, CH -9), 2.15 (2H, m, CH -2), 2.45 (3H, s, CH -6), 2.60
6
2
2
2
3
(2H, m, CH -11), 2.74 (4H, m, CH -1, CH -8), 3.07 (2H, m, CH -3), 7.28 (1H, s, H-10).
2
2
2
2
3,4-Dimethyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (63). Yield 81 %, C16H14O3, mp 241-
243° C. IR spectrum (KBr, cm-1): 3436, 3114, 2964, 2933, 1704, 1632, 1585, 1569, 1447, 1392, 1172, 1114, 1095, 1075, 1051,
981, 961, 849, 819. UV spectrum (CH CN, λmax, nm, log ε): 204 (4.41), 226 (4.43), 253 (4.46), 301 (4.21), 307 (4.22), 331
3
(3.97). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.15 (2H, m, CH -9), 2.36 (3H, s, CH -4), 2.65 (3H, s, CH -3), 2.74
6
2
3
3
(2H, m, CH -10), 3.31 (2H, m, CH -8), 7.03 (1H, s, H-5), 7.75 (1H, s, H-2).
2
2
2,3,4-Trimethyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (64). Yield 73%, C17H16O3, mp 209-
210° C. IR spectrum (KBr, cm-1): 3432, 2958, 2916, 1706, 1631, 1611, 1567, 1441, 1424, 1391, 1166, 1105, 1069, 1057, 989,
878. UV spectrum (CH CN, λmax, nm, log ε): 202 (4.64), 227 (4.46), 257 (4.43), 302 (4.27), 308 (4.26), 338 (3.88). PMR
3
spectrum (300 MHz, DMSO-d , δ, ppm): 2.12 (2H, m, CH -9), 2.26 (3H, s, CH -3), 2.36 (3H, s, CH -4), 2.59 (3H, s, CH -2),
6
2
3
3
3
2.70 (2H, m, CH -10), 3.22 (2H, m, CH -8), 7.03 (1H, s, H-5).
2
2
2,4-Dimethyl-3-phenyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (65). Yield 85%, C22H18O3,
mp 181-182° C. IR spectrum (KBr, cm-1): 3433, 2965, 2921, 1713, 1633, 1610, 1561, 1491, 1451, 1396, 1206, 1153, 1106,
1073, 990, 945, 881, 759, 714. UV spectrum (CH CN, λmax, nm, log ε): 204 (4.63), 225 (4.50), 254 (4.55), 301 (4.30), 307
3
(4.29), 337 (3.93). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.09 (3H, s, CH -2), 2.15 (2H, m, CH -9), 2.32 (3H, s, CH -
6
3
2
3
4), 2.74 (2H, m, CH -10), 3.32 (2H, m, CH -8), 7.00 (1H, s, H-5), 7.38-7.55 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′).
2
2
4-Methyl-3-phenyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-g]chromen-7-one (66). Yield 86%, C21H16O3, mp
215-217° C. IR spectrum (KBr, cm-1): 3435, 2972, 2923, 1708, 1633, 1607, 1573, 1450, 1396, 1382, 1181, 1115, 1083, 1057,
1007, 939, 847, 764, 708. UV spectrum (CH CN, λmax, nm, log ε): 204 (4.64), 230 (4.54), 249 (4.47), 298 (4.27), 307 (4.28),
3
240

329 (4.02). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.17 (2H, m, CH -9), 2.28 (3H, s, CH -4), 2.76 (2H, m, CH -10),
6
2
3
2
3.35 (2H, m, CH -8), 7.09 (1H, s, H-5), 7.45 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 8.08 (1H, s, H-2).
2
3-(4-Methylphenyl)-4-methyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (67). Yield 89%,
C22H18O3, mp 233-234° C. IR spectrum (KBr, cm-1): 3421, 2920, 2854, 1717, 1633, 1612, 1581, 1568, 1450, 1385, 1179, 1116,
1083, 1052, 981, 937, 860, 827, 798, 747. UV spectrum (CH CN, λmax, nm, log ε): 206 (4.59), 223 (4.55), 248 (4.46), 300
3
(4.24), 307 (4.25). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.16 (2H, m, CH -9), 2.23 (3H, s, CH -4), 2.38 (3H,
6
2
3
s, CH -4′), 2.75 (2H, m, CH -10), 3.34 (2H, m, CH -8), 7.05 (1H, s, H-5), 7.28 (2H, d, J = 8.4, H-3″, H-5″), 7.34 (2H, d,
3
2
2
J = 8.4, H-2″, H-6″), 8.00 (1H, s, H-2).
3-(4-Fluorophenyl)-4-methyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (68).
Yield 85%,
C21H15FO3, mp 224-225° C. IR spectrum (KBr, cm-1): 3404, 2919, 1708, 1631, 1579, 1500, 1451, 1227, 1113, 1086, 1056,
939, 842, 793. UV spectrum (EtOH, λmax, nm, log ε): 201 (4.59), 226 (4.55), 254 (4.42), 308 (4.25), 335 (4.00). PMR spectrum
(300 MHz, DMSO-d , δ, ppm, J/Hz): 2.15 (2H, m, CH -9), 2.23 (3H, s, CH -4), 2.74 (2H, m, CH -10), 3.29 (2H, m, CH -8),
6
2
3
2
2
7.10 (1H, s, H-5), 7.32 (2H, d, J = 8.4, H-3′, H-5′), 7.54 (2H, d, J = 8.4, H-2′, H-6′), 8.14 (1H, s, H-2).
3-(4-Chlorophenyl)-4-methyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (69). Yield 91%,
C21H15ClO3, mp 265-266°C. IR spectrum (KBr, cm-1): 3412, 2952, 2853, 1715, 1632, 1572, 1484, 1450, 1398, 1382, 1181,
1118, 1089, 1050, 1016, 937, 857, 846, 831. UV spectrum (dioxane, λmax, nm, log ε): 215 (4.51), 224 (4.58), 252 (4.54), 298
(4.28), 306 (4.28), 331 (4.04). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 2.18 (2H, m, CH -9), 2.25 (3H, s, CH -4), 2.78
6
2
3
(2H, m, CH -10), 3.37 (2H, m, CH -8), 7.10 (1H, s, H-5), 7.51 (4H, s, H-2′, H-3′, H-5 , H-6′), 8.09 (1H, s, H-2).
2
2
3-(4-Bromophenyl)-4-methyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (70). Yield 89%,
C21H15BrO3, mp 285-286°C. IR spectrum (KBr, cm-1): 3404, 2952, 2923, 1710, 1631, 1569, 1481, 1450, 1397, 1382, 1117,
1087, 1050, 1011, 980, 937, 857, 843, 831. UV spectrum (dioxane, λmax, nm, log ε): 215 (4.56), 235 (4.62), 252 (4.60), 298
(4.32), 306 (4.31), 329 (4.05). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.22 (2H, m, CH -9), 2.28 (3H, s, CH -4),
6
2
3
2.80 (2H, m, CH -10), 3.41 (2H, m, CH -8), 7.11 (1H, s, H-5), 7.42 (2H, d, J = 8.1, H-3′, H-5′), 7.63 (2H, d, J = 8.1, H-2′, H-6′),
2
2
8.02 (1H, s, H-2).
3-(4-Methoxyphenyl)-4-methyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (71). Yield 91%,
C22H18O4, mp 212-214°C. IR spectrum (KBr, cm-1): 3434, 2953, 1711, 1632, 1580, 1502, 1448, 1289, 1246, 1176, 1116, 1083,
1051, 1035, 937, 839, 796, 748. UV spectrum (CH CN, λmax, nm, log ε): 225 (4.58), 239 (4.62), 298 (4.27), 308 (4.28), 336
3
(4.00). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.16 (2H, m, CH -9), 2.24 (3H, s, CH -4), 2.74 (2H, m, CH -10),
6
2
3
2
3.33 (2H, m, CH -8), 3.82 (3H, s, CH O-4′), 7.04 (2H, d, J = 8.4, H-3′, H-5′), 7.10 (1H, s, H-5), 7.38 (2H, d, J = 8.4, H-2′, H-6′),
2
3
8.03 (1H, s, H-2).
3-(3-Methoxyphenyl)-4-methyl-7,8,9,10-tetrahydrocyclopenta[c]furo[2,3-f]chromen-7-one (72). Yield 94%,
C22H18O4, mp 222-224°C. IR spectrum (KBr, cm-1): 3436, 2920, 1710, 1633, 1610, 1589, 1570, 1481, 1452, 1437, 1328, 1288,
1259, 1221, 1116, 1082, 1056, 953, 855, 826, 791, 708. UV spectrum (CH CN, λmax, nm, log ε): 227 (4.61), 250 (4.47), 300
3
(4.28), 307 (4.28), 329 (4.02). PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.19 (2H, m, CH -9), 2.28 (3H, s, CH -4),
6
2
3
2.77 (2H, m, CH -10), 3.36 (2H, m, CH -8), 3.85 (3H, s, CH O-3′), 7.00 (3H, m, H-2′, H-4′, H-5′), 7.10 (1H, s, H-5), 7.36 (1H,
2
2
3
J = 8.4, H-6′), 7.97 (1H, s, H-2).
7-Methyl-1,2,3,4,8,9,10,11-octahydrobenzo[4,5]furo[2,3-f]cyclopenta[c]chromen-4-one (73). Yield 76%, C19H18O3,
mp 234-235°C. IR spectrum (KBr, cm-1): 3434, 2952, 2842, 1706, 1637, 1610, 1570, 1428, 1399, 1363, 1286, 1178, 1153,
1122, 1101, 1069, 1027, 985, 886. UV spectrum (CH CN, λmax, nm, log ε): 205 (4.44), 226 (4.34), 230 (4.35), 259 (4.53), 302
3
(4.22), 342 (3.82). PMR spectrum (300 MHz, DMSO-d , δ, ppm): 1.84 (4H, m, CH -9, CH -10), 2.15 (2H, m, CH -2), 2.59
6
2
2
2
(3H, s, CH -7), 2.74 (4H, m, CH -1, CH -8), 2.83 (2H, m, CH -11), 3.31 (2H, m, CH -3), 7.01 (1H, s, H-6).
3
2
2
2
2
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