Modified coumarins. 28. Synthesis of spirosubstituted pyranocoumarins

Article abstract of DOI:10.1007/s10600-009-9260-y

Spiropyranobenzopyrandiones were prepared, reduced, and dehydrated to form spirosubstituted pyranocoumarins.

Full text of DOI:10.1007/s10600-009-9260-y

Chemistry of Natural Compounds, Vol. 45, No. 2, 2009
MODIFIED COUMARINS. 28. SYNTHESIS OF
SPIROSUBSTITUTED PYRANOCOUMARINS
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
Spiropyranobenzopyrandiones were prepared, reduced, and dehydrated to form spirosubstituted
pyranocoumarins.
Key words: coumarins, pyranocoumarins, spiropyranocoumarins.
Pyranocoumarins (chromeno-α-pyrones) are widely distributed natural coumarins that contain a 2,2-dimethylpyran
ring annelated to benzopyran-2-one [1]. Pyranocoumarins also include coumarin derivatives containing an annelated
2,2,-dimethyltetrahydropyran-4-one core. Thus, 8,8-dimethyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione (graveolone) was
isolated from parsley [2], Anethum graveolens [3-6], and Pituranthos tortuosus [7] or clausenine (5-hydroxygraveolone) was
isolated from Clausena heptaphylla and C. excavata [8-10].
We synthesized structural analogs of graveolone and spirosubstituted pyranocoumarins, which are presently practically
unstudied [11-13].
Me
Me
Me
HO
O
O
R
O
HO
O
O
Me
O
O
R
O
Ac O, Py
AlCl
3
2
Me
O
R
R
O
3, 4
1, 2
5, 6
Me
R
1
R
1
R
2
Me
Me
2
O
O
R
O
O
O
R
O
R
O
R
O
1
HCl
O
Py
NaBH
4
R
1
OH
O
19, 20
21, 22
7 - 18
1, 3, 5: R = CH CH CH ; 2, 4, 6: R = CH CH CH CH ; 7: R = CH CH CH , R = CH
3
2
2
3
2
2
2
3
2
2
3
1
8: R = CH CH CH CH , R = CH ; 19, 21: R = CH CH CH , R = (CH ) C
3 3
2
2
2
3
1
3
2
2
3
2
20, 22: R = CH CH CH CH CH , R = H
2
2
2
2
3
2
9, 11, 13, 15, 17: R = CH CH CH ; 10, 12, 14, 16, 18: R = CH CH CH CH
2
2
3
2
2
2
3
R
1
R
1
Me
Me
O
C*
C*
11, 12
Me
C*
C*
N
C*
Me
Me
9, 10
13, 14
17, 18
15, 16
C* - Spiroatom
1) Institute of Bioorganic and Petroleum Chemistry, National Academy 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. 135-139, March-April, 2009. Original article
submitted October 29, 2007.
©
152
0009-3130/09/4502-0152 2009 Springer Science+Business Media, Inc.

7-Hydroxy-8-methylcoumarins 1 and 2 that were required for further transformations were prepared by Pechmann
condensation of 2-methylresorcinol with ethylbutyrylacetate or methyl-3-oxoheptanoate in the presence of conc. H SO as
2
4
condensing agent. Hydroxycoumarins 1 and 2 were acetylated by acetic anhydride in pyridine to form 7-acetoxycoumarins 3
and 4. Fries rearrangement of 3 and 4 in the presence of anhydrous AlCl at 120°C produced in high yields 6-acetylcoumarins
3
5 and 6, convenient starting mateirals for annelation of the 2,2-dimethyltetrahydropyran-4-one core.
Kabbe condensation [14] of 5 and 6 with acetone in the presence of pyrrolidine formed 8,8,10-trimethyl-4-alkyl-7,8-
dihydropyrano[3,2-g]chromen-2,6-diones 7 and 8, structural analogs of the natural pyranocoumarin graveolone. The PMR
spectra of 7 and 8 contained resonances characteristic of the coumarin system and an annelated chromanone ring, a 6H singlet
13
for two methyls at 1.50 ppm and a singlet for CH protons at 2.78 ppm. The C NMR spectra of 7 and 8 exhibited a resonance
2
for the spiroatom at 81.20-81.30 ppm.
Using cyclic ketones in the Kabbe condensation produced spiropyranobenzopyrandiones 9-18 in high yields. These
were spiroanalogs of the natural pyranocoumarin graveolone. We used cyclopentanone (9 and 10), cyclohexanone (11 and
12), 4-t-butylcyclohexanone (13 and 14), 3-methylcyclohexanone (15 and 16), and 1-acetylpiperidin-4-one (17 and 18) in this
reaction. The PMR spectra of the spirosubstituted pyranocoumarins showed resonances characteristic of the coumarin ring,
13
the cycloalkyl spirosubstituent, and the formed methylene group at 2.70-3.00 ppm. The C NMR spectra of
spiropyranobenzopyrandiones 11-18 with a cyclohexyl spirosubstituent contained a resonance for the spiroatom at 80-
84 ppm. The spiroatom in cyclopentanespiropyranocoumarin 10 resonated at weaker field at 92 ppm. Doubled proton resonances
for the spirosubstituent and the dihydropyranobenzopyrandione system were noted in the NMR spectra of 15 and 16, which
contain a methyl substituent in the cyclohexane substituent. Obviously such splitting was due to the formation of a mixture of
two diastereomers.
Reduction of 12 and 13 by NaBH in CH OH produced chromanols 19 and 20, dehydration of which under acid-
4
3
catalysis conditions (HCl in dioxane) [15] formed spirosubstituted 4-alkylpyrano[3,2-g]chromen-2-ones 21 and 22, spiroanalogs
of natural linear pyranocoumarins. The PMR spectra of 21 and 22 contained two doublets at 5.73-5.76 and 6.48-6.54 ppm
13
with SSCC J = 9.6 Hz that were characteristic of an annelated pyran ring [16]. The C NMR spectra of 21 and 22 showed a
resonance for the C spiroatom at 78.03-78.43 ppm.
EXPERIMENTAL
The course of reactions and purity of products were monitored by TLC on Merck 60 F
plates with
254
elution by CHCl :CH OH (9:1 and 19:1). Melting points were determined on a Kofler block. NMR spectra were recorded on
3
3
Varian VXR-300 Mercury 400 spectrometers at 300 and 400 MHz, respectively, vs. TMS (internal standard). Elemental
analyses of all compounds agreed with those calculated.
7-Hydroxy-8-methyl-4-propylchrome-2-one (1). A cooled (0°C) solution of 2-methylresorcinol (12.41 g, 0.1 mol)
and ethylbutyrylacetate (15.9 mL, 0.1 mol) in ethanol (20 mL) was stirred vigorously, cooled, and treated dropwise with
conc. H SO (40 mL). The mixture was stirred until thickened, left overnight at room temperature, and poured into icewater
2
4
(500 mL). The resulting precipitate was filtered off and crystallized from aqueous propanol-2 to afford 1, mp 172-173°C (lit.
[17] 165-166°C), C H O .
13 14
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.00 (3H, t, J = 7.2, CH -3′), 1.67 (2H, m, CH -2′), 2.18 (3H, s,
6
3
2
CH -8), 2.69 (2H, t, J = 7.2, CH -1′), 5.98 (1H, s, H-3), 6.83 (1H, d, J = 8.7, H-6), 7.38 (1H, d, J = 8.7, H-5), 10.24 (1H, s,
3
2
OH-7).
7-Hydroxy-8-methyl-4-butylchromen-2-one (2) was prepared analogously to 1 from 2-methylresorcinol (12.41 g,
0.1 mol) and methyl-3-oxoheptanoate (15.9 mL, 0.1 mol). Yield 79%, mp 158-159°C, C H O .
13 14
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 0.92 (3H, t, J = 7.2, CH -4′), 1.37 (2H, m, CH -3′), 1.58 (2H, m,
6
3
2
CH -2′), 2.16 (3H, s, CH -8), 2.72 (2H, t, J = 7.2, CH -1′), 6.07 (1H, s, H-3), 6.89 (1H, d, J = 8.1, H-6), 7.47 (1H, d, J = 8.1,
2
3
2
H-5), 10.39 (1H, s, OH).
7-Acetoxy-8-methyl-4-propylchromen-2-one (3). A mixture of 1 (10.95 g, 50 mmol), freshly distilled acetic anhydride
(9.5 mL, 100 mmol), and anhydrous pyridine (5 mL) was heated for 1 h and left overnight at room temperature. The resulting
precipitate was filtered off and crystallized from propanol-2. Yield 76%, mp 114-116°C (lit. [17] 106-107°C), C H O .
15 16
4
153

PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.98 (3H, t, J = 7.6, CH -3′, 1.64 (2H, m, CH -2′), 2.16 (3H, s,
6
3
2
CH -8), 2.37 (3H, s, CH COO-7), 2.76 (2H, t, J = 7.6, CH -1′), 6.32 (1H, s, H-3), 7.14 (1H, d, J = 8.8, H-6), 7.70 (1H, d,
3
3
2
J = 8.8, H-5).
7-Acetoxy-8-methyl-4-butylchromen-2-one (4) was prepared analogously to 3 from 2 (11.64 g, 50 mmol), acetic
anhydride (9.5 mL, 100 mmol), and anhydrous pyridine (5 mL). Yield 66%, mp 89-90°C, C H O .
16 18
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 0.98 (3H, t, J = 7.2, CH -4′), 1.47 (2H, m, CH -3′), 1.68 (2H, m,
3
3
2
CH -2′), 2.29 (3H, s, CH -8), 2.38 (3H, s, CH COO-7), 2.75 (2H, t, J = 7.2, CH -1′), 6.25 (1H, s, H-3), 7.02 (1H, d, J = 8.8,
2
3
3
2
H-6), 7.49 (1H, d, J = 8.8, H-5).
6-Acetyl-7-hydroxy-8-methyl-4-propylchromen-2-one (5). A ground mixture of coumarin 3 (7.80 g, 30 mmol)
and AlCl (12.00 g, 90 mmol) was held at 120-130°C for 1 h, cooled, and diluted with HCl solution (100 mL, 1 N). The
3
resulting precipitate was filtered off and crystallized from propanol-2. Yield 85%, mp 145-147°C, C H O .
15 16
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.00 (3H, t, J = 7.6, CH -3′), 1.66 (2H, m, CH -2′), 2.15 (3H, s,
6
3
2
CH -8), 2.75 (3H, s, CH CO-6), 2.82 (2H, t, J = 7.6, CH -1′), 6.20 (1H, s, H-3), 8.11 (1H, s, H-5), 12.99 (1H, s, OH).
3
3
2
6-Acetyl-7-hydroxy-8-methyl-4-butylchromen-2-one (6) was prepared analogously to 5 from 4 (8.23 g, 30 mmol)
and AlCl (12.00 g, 90 mmol). Yield 76%, mp 123-125°C, C H O .
3
15 16 4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.96 (3H, t, J = 7.6, CH -4′), 1.40 (2H, m, CH -3′), 1.61 (2H, m,
6
3
2
CH -2′), 2.13 (3H, s, CH -8), 2.74 (3H, s, CH CO-6), 2.82 (2H, t, J = 7.6, CH -1′), 6.18 (1H, s, H-3), 8.08 (1H, s, H-5), 12.95
2
3
3
2
(1H, s, OH).
4-Alkyl-7,8-dihydropyrano[3,2-g]chromen-2,6-diones 7-18. A solution of 6-acetyl-7-hydroxycoumarin 5 or 6
(10 mmol) in CH CN (10 mL) was treated with pyrrolidine (25 mmol, 2.1 mL) and the appropriate ketone (25 mmol) and held
3
at 45C for 8-20 h (end of the reaction determined by TLC). The solvent was removed in vacuo in a rotary evaporator. The solid
was crystallized from propanol-2.
8,8,10-Trimethyl-4-propyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione (7). Yield 72%, mp 119-121°C, C H O .
18 20
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 1.06 (3H, t, J = 7.2, CH -3′), 1.49 (6H, s, 2 × CH -8), 1.73 (2H, m,
3
3
3
CH -2′), 2.31 (3H, s, CH -10), 2.72 (2H, t, J = 7.6, CH -1′), 2.78 (2H, s, CH -7), 6.17 (1H, s, H-3), 8.07 (1H, s, H-5).
2
3
2
2
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.87 (C-6), 159.98 (C-2, C-10a), 157.26 (C-4), 156.72 (C-9a),
6
121.02 (C-4a), 116.97 (C-5), 114.26 (C-5a), 113.37 (C-3), 111.89 (C-10), 81.27 (C-8), 48.26 (C-7), 33.38 (C-1′), 26.89
(CH -8), 21.70 (C-2′), 14.30 (C-3′), 8.71 (CH -10).
3
3
8,8,10-Trimethyl-4-butyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione (8). Yield 65%, mp 176-177°C, C H O .
19 22
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 0.98 (3H, t, J = 7.2, CH -4′), 1.43 (2H, m, CH -3′), 1.51 (6H, s,
3
3
2
2 × CH -8), 1.67 (2H, m, CH -2′), 2.30 (3H, s, CH -10), 2.76 (2H, t, J = 7.6, CH -1′), 2.78 (2H, s, CH -7), 6.17 (1H, s, H-3),
3
2
3
2
2
8.07 (1H, s, H-5).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.83 (C-6), 159.95 (C-2, C-10a), 157.48 (C-4), 156.71 (C-9a),
6
120.99 (C-4a), 116.96 (C-5), 114.26 (C-5a), 113.32 (C-3), 111.81 (C-10), 81.25 (C-8), 48.26 (C-7), 31.19 (C-1′), 30.54
(CH -8), 26.89 (C-2′), 22.59 (C-3′), 14.34 (C-4′), 8.71 (CH -10).
3
3
Spiro[(4-propyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,1′-cyclopentane] (9). Yield 78%, mp 246-247°C,
C H O .
19 20
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 1.05 (3H, t, J = 7,2, CH -3′), 1.60-2.15 (10H, CH -2′, CH -2′,
3
3
2
2
CH -3′, CH -4′, CH -5′), 2.29 (3H, s, CH -10), 2.75 (2H, t, J = 7.5, CH -1′), 2.88 (2H, s, CH -7), 6.17 (1H, s, H-3), 8.07 (1H,
2
2
2
3
2
2
s, H-5).
Spiro[(4-butyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,1′-cyclopentane] (10). Yield 68%, mp 168-169°C,
C H O .
20 22
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.93 (3H, t, J = 7.2, CH -4′), 1.41 (2H, m, CH -3′), 1.50-2.00
6
3
2
(10H, CH -2′, CH -2′, CH -3′, CH -4′, CH -5′), 2.18 (3H, s, CH -10), 2.79 (2H, t, J = 7.6, CH -1′), 2.98 (2H, s, CH -7), 6.26
2
2
2
2
2
3
2
2
(1H, s, H-3), 7.98 (1H, s, H-5).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.63 (C-6), 160.54 (C-2), 160.00 (C-10a), 157.63 (C-4),
6
156.71 (C-9a), 121.25 (C-4a), 117.94 (C-5), 114.76 (C-5a), 111.93 (C-3), 110.06 (C-10), 91.79 (C-8), 46.57 (C-7), 37.60
(C-2′′, C-5′′), 31.09 (C-1′), 30.55 (C-3′′, C-4′′), 23.86 (C-2′), 22.28 (C-3′), 13.91 (C-4′), 8.21 (CH -10).
3
Spiro[(4-propyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,1′-cyclohexane] (11). Yield 73%, mp 197-199°C,
C H O .
20 22
4
154

PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 1.06 (3H, t, J = 7.2, CH -3′), 1.23-2.15 (12H, CH -2′, CH -2′′,
3
3
2
2
CH -3′′, CH -4′′, CH -5′′, CH -6′′), 2.34 (3H, s, CH -10), 2.74 (2H, t, J = 7.6, CH -1′), 2.76 (2H, s, CH -7), 6.17 (1H, s,
2
2
2
2
3
2
2
H-3), 8.05 (1H, s, H-5).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.61 (C-6), 159.98 (C-2), 159.73 (C-10a), 157.32 (C-4),
6
157.10 (C-9a), 121.03 (C-4a), 117.79 (C-5), 114.56 (C-5a), 113.68 (C-3), 111.98 (C-10), 81.91 (C-8), 48.10 (C-7), 34.76
(C-2′′, C-6′′), 33.35 (C-1′), 25.07 (C-4′′), 21.69 (C-3′′, C-5′′), 21.59 (C-2′), 13.93 (C-3′), 8.25 (CH -10).
3
Spiro[(4-butyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,1′-cyclohexane] (12). Yield 82%, mp 200-201°C,
C H O .
21 24
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 0.98 (3H, t, J = 7.2, CH -4′), 1.25-2.11 (14H, CH -2′, CH -3′,
3
3
2
2
CH -2′′, CH -3′′, CH -4′′, CH -5′′, CH -6′′), 2.36 (3H, s, CH -10), 2.74 (2H, s, CH -7), 2.76 (2H, t, J = 7.6, CH -1′), 6.17
2
2
2
2
2
3
2
2
(1H, s, H-3), 8.06 (1H, s, H-5).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.59 (C-6), 159.98 (C-2), 159.73 (C-10a), 157.61 (C-4),
6
157.10 (C-9a), 121.02 (C-4a), 117.80 (C-5), 114.57 (C-5a), 113.66 (C-3), 111.91 (C-10), 81.91 (C-8), 48.10 (C-7), 34.77
(C-2′′, C-6′′), 31.10 (C-1′), 30.56 (C-2′), 25.07 (C-4′′), 22.29 (C-3′), 21.69 (C-3′′, C-5′′), 13.91 (C-4′), 8.25 (CH -10).
3
Spiro[(4-propyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,1′-(4-t-butylcyclohexane)] (13). Yield 81%,
mp 231-232°C, C H O .
24 30
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 0.90 [9H, s, (CH ) -4′′], 1.06 (3H, t, J = 7.2, CH -3′), 1.37-2.20
3
3 3
3
(11H, CH -2′, CH -2′′, CH -3′′, H-4′′, CH -5′′, CH -6′′), 2.36 (3H, s, CH -10), 2.72 (2H, s, CH -7), 2.74 (2H, t, J = 7.6,
2
2
2
2
2
3
2
CH -1′), 6.17 (1H, s, H-3), 8.06 (1H, s, H-5).
2
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.67 (C-6), 159.95 (C-2), 159.64 (C-10a), 157.30 (C-4),
6
157.10 (C-9a), 121.10 (C-4a), 117.89 (C-5), 114.51 (C-5a), 113.73 (C-3), 111.99 (C-10), 81.26 (C-8), 48.56 (C-7), 46.69
(C-4′′), 34.81 (C-2′′, C-6′′), 33.35 (C-1′), 32.59 [C-(CH ) ], 27.77 [(CH ) ], 22.20 (C-3′′, C-5′′), 21.58 (C-2′), 13.92 (C-3′),
3 3
3 3
8.11 (CH -10).
3
Spiro[(4-butyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,1′-(4-t-butylcyclohexane)] (14). Yield 73%,
mp 250-251°C, C H O .
25 32
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 0.90 [9H, s, (CH ) -4′′], 0.98 (3H, t, J = 7.2, CH -4′), 1.36-2.20
3
3 3
3
(13H, CH -2′, CH -3′, CH -2′′, CH -3′′, H-4′′, CH -5′′, CH -6′′), 2.36 (3H, s, CH -10), 2.71 (2H, s, CH -7), 2.77 (2H, t,
2
2
2
2
2
2
3
2
J = 7.6, CH -1′), 6.17 (1H, s, H-3), 8.06 (1H, s, H-5).
2
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.61 (C-6), 159.98 (C-2), 159.68 (C-10a), 157.60 (C-4),
6
157.10 (C-9a), 121.11 (C-4a), 117.85 (C-5), 114.56 (C-5a), 113.73 (C-3), 111.93 (C-10), 81.29 (C-8), 48.59 (C-7), 46.70
(C-4′′), 34.82 (C-2′′, C-6′′), 32.59 [C-(CH ) ], 31.10 (C-1′), 30.56 (C-2′), 27.79 [(CH ) ], 22.29 (C-3′), 22.21 (C-3′′, C-5′′),
3 3
3 3
13.92 (C-4′), 8.21 (CH -10).
3
Spiro[(4-propyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,1′-(3-methylcyclohexane)] (15). Yield 59%,
mp 173-174°C, C H O .
22 26
4
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 0.86 (3H, d, J = 7.2, CH -3′′), 0.99 (3H, t, J = 7.2, CH -3′),
6
3
3
1.05-2.00 (11H, CH -2′, CH -2′′, CH -3′′, H-3′′, CH -5′′, CH -6′′), 2.20 and 2.24 (3H, 2s, CH -10), 2.77 (2H, t, J = 7.6,
2
2
2
2
2
3
CH -1′), 2.82 and 3.00 (2H, s, CH -7), 6.25 (1H, s, H-3), 7.94 and 7.96 (1H, 2s, H-5).
2
2
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.86 (C-6), 159.99 (C-2), 159.36 (C-10a), 157.29 (C-4),
6
156.77 (C-9a), 121.01 (C-4a), 117.53 (C-5), 114.45 (C-5a), 113.47 (C-3), 111.98 (C-10), 83.60 and 82.19 (C-8), 48.61 and
42.86 (C-7), 33.97 and 33.74 (C-2′′, C-6′′), 33.41 (C-1′), 27.84 (C-4′′), 22.75 (C-3′′), 21.73 (CH -3′′), 21.53 (C-2′, C-5′′),
3
14.31 (C-3′), 8.63 (CH -10).
3
Spiro[(4-butyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,1′-(3-methylcyclohexane)] (16). Yield 81%,
mp 155-157°C, C H O .
23 28
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 0.91 (3H, d, J = 7.2, CH -3′′), 0.98 (3H, t, J = 7.2, CH -4′),
3
3
3
1.20-2.15 (13H, CH -2′, CH -3′, CH -2′′, CH -3′′, H-3′′, CH -5′′, CH -6′′), 2.30 and 2.35 (3H, 2s, CH -10), 2.71 and 2.90
2
2
2
2
2
2
3
(2H, s, CH -7), 2.77 (2H, t, J = 7.6, CH -1′), 6.17 (1H, s, H-3), 8.04 and 8.06 (1H, 2s, H-5).
2
2
13
C NMR spectrum (100MHz, DMSO-d , δ, ppm): 191.78 and 191.48 (C-6), 159.94 and 159.93 (C-2), 159.77 and
6
159.33 (C-10a), 157.48 and 156.79 (C-4), 156.73 (C-9a), 120.95 and 120.94 (C-4a), 117.49 and 117.29 (C-5), 114.44 (C-5a),
113.41 (C-3), 111.81 and 111.79 (C-10), 83.60 and 82.17 (C-8), 48.61 and 42.87 (C-7), 33.97 and 33.73 (C-2′′, C-6′′), 31.21
(C-1′), 30.56 (C-2′), 27.82 (C-4′′), 22.56 (C-3′, C-3′′), 21.53 (CH -3′′, C-5′′), 14.34 (C-4′), 8.59 (CH -10).
3
3
155

Spiro[(4-propyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,4′-(1-acetylpiperidine)] (17).
mp 216-217°C, C H NO .
Yield 56%,
21 23
5
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 1.06 (3H, t, J = 7.2, CH -3′), 1.58-1.80 (4H, m, CH -2′, H-3α′′,
3
3
2
H-5α′′), 2.05-2.18 (2H, m, H-3β′′, H-5β′′), 2.13 (3H, s, CH CON-4′′), 2.37 (3H, s, CH -10), 2.74 (2H, t, J = 7.6, CH -1′), 2.79
3
3
2
(2H, s, CH -7), 3.03 and 3.51 (2H, 2m, H-2α′′, H-6α′′), 3.69 and 4.47 (2H, 2m, H-3β′′, H-5β′′), 6.20 (1H, s, H-3), 8.08 (1H,
2
s, H-5).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.30 (C-6), 168.85 (CO–CH ), 159.93 (C-2), 159.01 (C-10a),
6
3
157.27 (C-4), 156.82 (C-9a), 121.11 (C-4a), 117.49 (C-5), 114.70 (C-5a), 113.75 (C-3), 112.16 (C-10), 80.15 (C-8), 47.34
(C-7), 42.09 (C-3′′, C-5′′), 34.61 (C-2′′, C-6′′), 33.40 (C-1′), 21.96 (C-2′), 21.75 (CO–CH ), 14.30 (C-3′), 8.69 (CH -10).
3
3
Spiro[(4-butyl-7,8-dihydropyrano[3,2-g]chromen-2,6-dione)-8,4′-(1-acetylpiperidine)] (18). Yield 71%, mp 197-
198°C, C H NO .
22 25
5
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.98 (3H, t, J = 7.2, CH -4′), 1.40-2.00 (8H, m, CH -2′, CH -3′,
6
3
2
2
CH -3′′, CH -5′′), 2.03 (3H, s, CH CON-4′′), 2.28 (3H, s, CH -10), 2.80 (2H, t, J = 7.6, CH -1′), 2.92 (2H, s, CH -7), 2.92 and
2
2
3
3
2
2
3.65 (2H, 2m, H-2α″, H-6α′′), 3.72 and 4.21 (2H, 2m, H-3β′′, H-5β′′), 6.28 (1H, s, H-3), 7.99 (1H, s, H-5).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 191.56 (C-6), 168.81 (CO–CH ), 159.98 (C-2), 159.72 (C-10a),
6
3
157.47 (C-4), 156.95 (C-9a), 121.10 (C-4a), 117.79 (C-5), 114.61 (C-5a), 113.71 (C-3), 111.96 (C-10), 80.95 (C-8), 47.34 (C-
7), 42.11 (C-3′′, C-5′′), 34.65 (C-2′′, C-6′′), 31.10 (C-1′), 30.56 (C-2′), 22.29 (C-3′), 21.75 (CO–CH ), 13.91 (C-4′), 8.25
3
(CH -10).
3
Spiro[(6-hydroxy-4-alkyl-7,8-dihydropyrano[3,2-g]chromen-2-one)-8,1′-cyclohexanes] 19 and 20. A solution
of 12 or 13 (3 mmol) in CH OH (10 mL) was treated in portions with NaBH (0.46 g, 12 mmol), held at room temperature and
3
4
stirred for 2 h (end of reaction determined by TLC), poured into saturated NaCl solution (100 mL), and extracted with EtOAc
(3 × 20 mL). The organic layer was dried over anhydrous MgSO . Solvent was removed in vacuo in a rotary evaporator. The
4
solid was crystallized from CH OH.
3
Spiro[(6-hydroxy-4-propyl-7,8-dihydropyrano[3,2-g]chromen-2-one)-8,1′-(4-t-butylcyclohexane)] (19). Yield
71%, mp 194-195°C, C
H O .
24 32 4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.86 [9H, s, (CH ) -4′′], 0.98 (3H, t, J = 7.6, CH -3′), 1.00-2.05
6
3 3
3
(13H, CH -7, CH -2′, CH -2′′, CH -3′′, H-4′′, CH -5′′, CH -6′′), 2.18 (3H, s, CH -10), 2.72 (2H, t, J = 7.6, CH -1′), 4.78 (1H,
2
2
2
2
2
2
3
2
m, H-6), 5.63 (1H, d, J = 5.6, OH-6), 6.11 (1H, s, H-3), 7.74 (1H, s, H-5).
Spiro[(6-hydroxy-4-butyl-7,8-dihydropyrano[3,2-g]chromen-2-one)-8,1′-cyclohexane] (20). Yield 92%, mp 140-
141°C, C H O .
21 26
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.93 (3H, t, J = 7.2, CH -4′), 1.25-2.15 (16H, CH -7, CH -2′,
6
3
2
2
CH -3′, CH -2′′, CH -3′′, CH -4′′, CH -5′′, CH -6′′), 2.19 (3H, s, CH -10), 2.74 (2H, t, J = 7.6, CH -1′), 4.76 (1H, m, H-6),
2
2
2
2
2
2
3
2
5.57 (1H, d, J = 5.6, OH-6), 6.11 (1H, s, H-3), 7.71 (1H, s, H-5).
Spiro[(4-alkylpyrano[3,2-g]chromen-2-one)-8,1′-cyclohexanes] 21 and 22. A solution of 19 or 20 (2 mmol) in
dioxane (5 mL) was treated with HCl solution (5 mL, 4 M), held at room temperature and stirred for 4 h (end of reaction
determined using TLC). Solvent was removed in vacuo in a rotary evaporator. The solid was crystallized from CH OH.
3
Spiro[(4-propylpyrano[3,2-g]chromen-2-one)-8,1′-(4-t-butylcyclohexane)] (21). Yield 84%, mp 168-169°C,
C
H
O .
24 30
3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.90 [9H, s, (CH ) -4′′], 0.99 (3H, t, J = 7.6, CH -3′), 1.10-2.00
6
3 3
3
(11H, CH -2′, CH -2′′, CH -3′′, H-4′′, CH -5′′, CH -6′′), 2.21 (3H, s, CH -10), 2.71 (2H, t, J = 7.6, CH -1′), 5.73 (1H, d,
2
2
2
2
2
3
2
J = 9.6, H-7), 6.12 (1H, s, H-3), 6.54 (1H, d, J = 9.6, H-6), 7.40 (1H, s, H-5).
13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 160.80 (C-2), 157.54 (C-10a), 153.80 (C-4), 152.99 (C-9a),
6
131.81 (C-7), 122.72 (C-6), 120.23 (C-4a), 11.78 (C-5), 113.16 (C-5a), 112.93 (C-3), 110.70 (C-10), 78.03 (C-8), 46.74
(C-4′′), 36.27 (C-2′′, C-6′′), 33.48 (C-1′), 32.66 [C–(CH ) ], 27.80 [(CH ) ], 22.02 (C-3′′, C-5′′), 21.77 (C-2′), 13.97 (C-3′),
3 3
3 3
7.93 (CH -10).
3
Spiro[(4-butylpyrano[3,2-g]chromen-2-one)-8,1′-cyclohexane] (22). Yield 86%, mp 114-115°C, C H O .
21 24
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 0.95 (3H, t, J = 7.2, CH -4′), 1.20-1.90 (14H, CH -2′, CH -3′,
6
3
2
2
CH -2′′, CH -3′′, CH -4′′, CH -5′′, CH -6′′), 2.23 (3H, s, CH -10), 2.71 (2H, t, J = 7.5, CH -1′), 5.76 (1H, d, J = 9.6, H-7),
2
2
2
2
2
3
2
6.04 (1H, s, H-3), 6.48 (1H, d, J = 9.6, H-6), 7.29 (1H, s, H-5).
156

13
C NMR spectrum (100 MHz, DMSO-d , δ, ppm): 160.78 (C-2), 157.80 (C-10a), 153.88 (C-4), 153.20 (C-9a),
6
131.43 (C-7), 122.48 (C-6), 120.24 (C-4a), 118.67 (C-5), 112.91 (C-5a), 112.86 (C-3), 110.51 (C-10), 78.43 (C-8), 36.60
(C-2′′, C-6′′), 31.41 (C-1′), 30.80 (C-2′), 25.25 (C-4′′), 22.62 (C-3′), 21.61 (C-3′′, C-5′′), 14.38 (C-4′), 8.46 (CH -10).
3
ACKNOWLEDGMENT
We thank OAO Eximed (Kiev, Ukraine) for help in performing the work.
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157