Modified coumarins. 12. Synthesis of 3,4-cycloannelated coumarin β-d-glucopyranosides

Article abstract of DOI:10.1023/B:CONC.0000025455.68950.36

O-β-D-Glucopyranosides were synthesized using 3,4-cycloannelated hydroxycoumarins as aglycons. Phenolic hydroxyls were O-glycosylated via condensation of coumarin potassium salts with acetobromoglucose in homogeneous medium and in a liquid-liquid system using a phase-transfer catalyst.

Full text of DOI:10.1023/B:CONC.0000025455.68950.36

Chemistry of Natural Compounds, Vol. 40, No. 1, 2004
MODIFIED COUMARINS. 12. SYNTHESIS OF 3,4-CYCLOANNELATED
COUMARIN β-D-GLUCOPYRANOSIDES
Ya. L. Garazd,1 M. M. Garazd,2 and V. P. Khilya1
UDC 547.814.5
O-β-D-Glucopyranosides were synthesized using 3,4-cycloannelated hydroxycoumarins as aglycons.
Phenolic hydroxyls were O-glycosylated via condensation of coumarin potassium salts with
acetobromoglucose in homogeneous medium and in a liquid—liquid system using a phase-transfer catalyst.
Key words: coumarins, glucosides, glucosylation, phase-transfer catalyst, synthesis.
Coumarins with bound sugars are widelydistributedin nature. Themost common ofthesecompounds are O-glycosides
with the sugar in various positions on the benzopyran ring [1]. Compared with the aglycons, they are more soluble in water
and blood plasma. Their acetates and methyl ethers are highly soluble in lipids and other slightly polar media. Therefore,
introducing carbohydrates into the coumarin structure can significantly change the hydrophilic-lipophilic balance and,
consequently, affect its transport in biological systems. The biological activity of coumarin O-glycosides is of great interest
owing to the high and varied pharmacological activity of coumarins. The synthesis of glycosides provides an additional
capability to introduce into the coumarin core a variety of substituents that are promising from the viewpoint of biological
activity. Therefore, we synthesized β-D-glucopyranosides of 5- and 7-hydroxy-3,4-cycloannelated coumarins.
Hydroxycoumarins 1-6 and 9 and 10, which were necessary for further transformations, were prepared by
Pechmann condensation of polyphenols (resorcinol, 2-methylresorcinol, orcine) and ethyl-2-oxocyclopentanecarboxylate,
ethyl-2-oxocyclohexanecarboxylate, or methyl-2-oxo-1-cycloheptanecarboxylate in the presence of conc. H SO [2,
2
4
3]. 3-Hydroxybenzo[c]chromen-6-one (7) and 3-hydroxy-4-methylbenzo[c]chromen-6-one (8) were synthesized bythe Hurtley
method via condensation in NaOH solution of 2-bromobenzoic acid with resorcinol or 2-methylresorcinol, respectively, using
copper sulfate solution (10%) as a catalyst [4].
The glycosylation methods used in the chemistry of benzopyrans are primarily modifications of the Koenigs—Knorr
method [5]. The first method is based on glycosylation of phenol hydroxyls with acetobromosugars in the presence of silver
carbonate or oxide [6, 7]. The second method consists of glycosylation of sodium or potassium salts of phenols with
acetobromosugars in aqueous acetone [8, 9] or aqueous DMF [10]. Methods for synthesizing glycosides of benzopyrans under
phase-transfer catalytic conditions in liquid—liquid or liquid—solid systems using phase-transfer crown ethers or quaternary
ammonium salts as catalysts have been developed [11-14].
3,4-Annelated coumarins were glucosylated bytwo methods. The first was based on condensation of a glucosyl donor,
acetobromoglucose (Ac GlupBr)with potassium saltsofhydroxycoumarinsin aqueous acetone with cooling (0°C) bya modified
4
Michael method [15]. Solutions of these salts were prepared using equivalent amounts of KOH solution (10%) and twice
(relative to the base volume) the amount of acetone. Under such conditions the target per-O-acetylglucopyranosides 11-20 that
contain the carbohydrate in the 5- or 7-position of the coumarin were prepared in yields of 24-56%.
1)TarasShevchenkoKievNational University, 01033, Ukraine, Kiev, ul. Vladimirskaya, 64; 2) InstituteofBioorganic
and Petroleum Chemistry, National Academy of Sciences of Ukraine, 02094, Ulraine, Kiev, ul. Murmanskaya, 1, e-mail:
gmm@i.com.ua. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 7-12, January-February, 2004. Original article
submitted December 12, 2003.
0009-3130/04/4001-0006 ©2004 Plenum Publishing Corporation
6

R
2
R
2
R
2
AcO
HO
OH
HO
O
R
O
R
O
O
R
O
R
O
O
R
O
R
A or B
O
MeONa
O
OAc
OAc
OH
1
1
1
OAc
OH
1 - 8
11 - 18
21 - 28
Me
O
R
O
Me
O
R
O
Me
O
R
O
R
MeONa
A or B
R
1
R
1
AcO
HO
O
O
O
1
O
OH
OAc
OAc
OH
OH
OAc
OH
9, 10
19, 20
29, 30
A:
B:
p
Ac4Glu Br, KOH, H2O-CH3COCH3
p
Ac4Glu Br, KOH, TBAB, H2O-CH2Cl2
1, 11, 21:
4, 14, 24:
7, 17, 27:
9, 19, 29:
2, 12, 22:
3, 13, 23:
6, 16, 26:
RR1 = (CH2)3, R2 = H;
RR1 = (CH2)3, R2 = CH3;
RR1 = (CH2)4, R2 = H;
5, 15, 25:
RR1 = (CH2)4, R2 = CH3;
RR1 = (CH2)5, R2 = H;
8, 18, 28:
RR1 = (CH2)5, R2 = CH3;
RR1 = -CH=CH-CH=CH-, R2 = H;
RR1 = -CH=CH-CH=CH-, R2 = CH3;
10, 20, 30:
RR1 = (CH2)3;
RR1 = (CH2)4
The low glucosylation yields are explained by the fact that a side reaction occurs during the reaction, i.e., elimination
of HBr from the acetobromoglucose to form 2-acetoxyglucal [15]. In our opinion, the second important hindrance during the
synthesis is the poor solubility of the phenol salts in the aqueous acetone mixture. This creates heterogeneous reaction
conditions. The potassium salts of hydroxycoumarins 1, 2, 7, and 8 are poorly soluble in aqueous acetone. Therefore, the yields
of glucosides 11, 12, 17, and 18 under these conditions are low (24-30%).
The second method of glycosylating coumarins 1, 2, 7, and 8 was effective. It is based on phase-transfer catalysis in
a two-phase liquid—liquid system. Dichloromethane was used as the organic solvent; KOH solution (10%), as the base. The
reaction between equivalent amounts of hydroxycoumarin, base, and acetobromoglucose was performed at room temperature
in the presence of an equivalent amount of tetrabutylammonium bromide (TBAB) as phase-transfer catalyst [12]. Using this
method, tetraacetylglucopyranosides 11, 12, 17, and 18 were prepared in the highest yields (46-51%). In our opinion, this is
explained by performing the reaction under homogeneous conditions. It should be noted that the yields of the glucosides did
not increase substantially compared with the modified Michael method if this method was used for glucosylation of
hydroxycoumarins 3, 4, 9, and 10, the potassium salts of which are sufficiently soluble in aqueous acetone.
Signals for protons of the coumarin aglycons and carbohydrates were unambiguously identified in the PMR spectra
of the synthesized tetra-O-acetylglucopyranosides 11-20. The configuration ofthe anomeric center was determined using PMR
data. The presence of a doublet for the anomeric proton H-1 at 5.09-5.27 ppm with SSCC 7.6 Hz is consistent with
formation of a 1,2-trans-glycoside bond (β-configuration) [16]. The IR spectra of 11-20 contain two bands at 1748-1758 and
-1
1700-1732 cm that are typical of stretching vibrations of the C=O bond of acetyls and coumarin rings, respectively.
Deacetylation of O-acetylglucopyranosides 11-20 by a modified Zemplen method (sodium methoxide in methanol)
produced β-D-glucopyranosides 21-30 in high yields (83-97%). The PMR spectra ofthe synthesized glucosides contain signals
for carbohydrate and aglycon fragments and, in contrast with the starting peracetates, lack signals for acetyls. Retention of the
β-configuration was confirmed by the presence in the PMR spectra of a doublet for the anomeric proton H-1′ at 4.87-5.03 ppm
with SSCC 7.6 Hz. The signal for the primary alcohol proton OH-6 resonates as a triplet at 4.45-4.62 ppm with SSCC 5.6 Hz;
the secondary alcohol protons OH-2, OH-3, and OH-4, as doublets with SSCC 3.2-5.6 Hz at 5.05-5.42 ppm. The IR spectra
-1
of glucosides 21-30 exhibit two bands at 3384-3468 and 1692-1722 cm that are typical of stretching vibrations of alcohol
hydroxyls and coumarin C=O bonds, respectively.
7

EXPERIMENTAL
The course of reactions and purity of products were monitored using TLC on Merck 60 F254 plates with elution by
CHCl :CH OH (9:1). Melting points were determined on a Kofler block. IRand UV spectra were measured on a Nicolet Nexus
3
3
475 FTIR spectrometer and a Specord M40 spectrophotometer, respectively. PMR spectra were recorded on Varian VXR-300
and Mercury-400 spectrometers at 300 and 400 MHz working frequencies, respectively, relative to TMS (internal standard).
Elemental analyses of all compounds agreed with those calculated.
The syntheses of 1-4 and 7-10 have been described [2, 3, 17]. 2,3,4,6-Tetraacetyl-α-D-glucopyranosylbromide was
prepared as before [18].
3-Hydroxy-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-6-one (5). A cooled (0°C) solution of resorcinol
(11.0 g, 100 mmol) and methyl-2-oxo-1-cycloheptanecarboxylate (15.6 mL, 100 mmol) in absolute CH OH (20 mL) was
3
vigorously stirred, cooled, treated dropwise with conc. H SO (10 mL), stirred until thickened, left overnight at room
2
4
temperature, and transferred intoicewater (200 mL). The resulting precipitate was filtered offand crystallizedfrom propan-2-ol
(60%). Yield 59%, C H O , mp 198-199°C (lit. 188.5-189.5°C [19], 189-190°C [20]).
14 14
3
-1
IR spectrum (KBr, cm ): 3219, 2929, 1679, 1614, 1568, 1514, 1385, 1324, 1311, 1236, 1150, 1097, 1075, 867, 779.
UV spectrum (CH CN, λmax, nm, log ε): 219 (4.20), 324 (4.20).
3
PMRspectrum (300 MHz, DMSO-d6, δ, ppm, J/Hz): 1.52 (2H, m, CH -9), 1.61 (2H, m, CH -10), 1.86 (2H, m, CH -8),
2
2
2
2.74 (2H, m, CH -11), 2.90 (2H, m, CH -7), 6.65 (1H, d, J = 2.4, H-4), 6.73 (1H, dd, J = 2.4, J = 8.7, H-2), 7.60 (1H, d, J = 8.7,
2
2
H-1), 10.23 (1H, s, OH-3).
3-Hydroxy-4-methyl-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-6-one (6) waspreparedanalogouslyto5 from
2-methylresorcinol (12.4 g, 100 mmol) and methyl-2-oxo-1-cycloheptanecarboxylate (15.6 mL, 100 mmol). Yield 64%,
C H O , mp 224-225°C.
15 16
3
-1
IR spectrum (KBr, cm ): 3221, 2912, 1675, 1604, 1569, 1508, 1457, 1376, 1321, 1271, 1248, 1102, 1086, 808, 778.
UV spectrum (EtOH, λmax, nm, log ε): 206 (4.81), 223 (4.41), 331 (4.32).
PMRspectrum (300 MHz, DMSO-d6, δ, ppm, J/Hz): 1.51 (2H, m, CH -9), 1.59 (2H, m, CH -10), 1.86 (2H, m, CH -8),
2
2
2
2.17 (3H, s, CH -4), 2.74 (2H, m, CH -11), 2.90 (2H, m, CH -7), 6.81 (1H, d, J = 8.7, H-2), 7.45 (1H, d, J = 8.7, H-1), 10.15
3
2
2
(1H, s, OH-3).
General Method for Glucosylation by Method A. A solution of hydroxycoumarin (1-10, 10 mmol) in acetone
(10 mL) and KOH solution (5.6 mL, 10%, 10 mmol) was vigorously stirred, cooled (0°C) for 30 min, and treated in portions
over 1 h with acetobromoglucose (4.11 g, 10 mmol). The resulting solution or suspension was stirred for 4 h with cooling (0°C),
left overnight at room temperature, treated with CHCl (50 mL), transferred toa separatoryfunnel, and treated successivelywith
3
KOH solution (1 N, 2 × 50 mL) and water (50 mL). Acidification of the combined alkaline extracts regenerated unreacted
hydroxycoumarin. The organic phase was dried over anhydrous MgSO . The solvent was removed in vacuum in a rotary
4
evaporator. The oily product was crystallized from propan-2-ol.
General Method for Glucosylation by Method B. A mixture of hydroxycoumarin (1-10, 10 mmol), KOH solution
(5.6 mL, 10%, 10 mmol), CH Cl (10 mL), acetobromoglucose (4.11 g, 10 mmol), and TBAB (3.22 g) was held at room
2
2
temperature, stirred vigorously for 1 h, and treated with CHCl (50 mL), transferred to separatory funnel, and treated
3
successively with NaCl saturated solution (50 mL), KOH solution (1 N, 2 × 50 mL), and water (50 mL). Acidification of the
alkaline solution regenerated unreacted hydroxycoumarin. The organic phase was dried over anhydrous MgSO . Solvent was
4
removed in vacuum in a rotary evaporator. The oily product was crystallized from propan-2-ol.
7-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-2,3-dihydrocyclopenta[c]chromen-4-one (11). Yield26% (by
method A), 51% (by method B), C H O , mp 172-173.5°C.
26 28 12
-1
IR spectrum (KBr, cm ): 2928, 1758, 1700, 1630, 1618, 1438, 1372, 1244, 1172, 1088. UV spectrum (EtOH,
λ
max, nm, log ε): 204 (4.65), 218 (4.22), 319 (4.13).
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 2.04, 2.06, 2.07, 2.12 (12H, four s, four CH COO), 2.21 (2H, m,
3
3
CH -2), 2.91 (2H, m, CH -1), 3.06 (2H, m, CH -3), 3.91 (1H, ddd, J = 10.0, J = 5.6, J = 2.4, H-5′), 4.19 (1H, dd, J = 12.0,
2
2
2
J = 2.4, H-6′α), 4.31 (1H, dd, J = 12.0, J = 5.6, H-6′β), 5.13 (1H, d, J = 7.6, H-1′), 5.17 (1H, dd, J = 10.0, J = 9.6, H-4′), 5.28-
5.35 (2H, m, H-2′, H-3′), 6.92 (1H, dd, J = 2.4, J = 8.8, H-8), 7.00 (1H, d, J = 2.4, H-6), 7.37 (1H, d, J = 8.8, H-9).
7-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-6-methyl-2,3-dihydrocyclopenta[c]chromen-4-one (12). Yield
24% (by method A), 46% (by method B), C H O , mp 173.5-175°C.
27 30 12
8

-1
IR spectrum (KBr, cm ): 2960, 1756, 1705, 1612, 1428, 1374, 1242, 1132, 1076, 1046. UV spectrum (EtOH,
λ
max, nm, log ε): 206 (4.67), 220 (4.22), 318 (4.12).
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 2.05, 2.06, 2.07, 2.12 (12H, four s, four CH COO), 2.21 (2H, m,
3
3
CH -2), 2.26 (3H, s, CH -6), 2.92 (2H, m, CH -1), 3.05 (2H, m, CH -3), 3.89 (1H, ddd, J = 10.0, J = 5.6, J = 2.4, H-5′), 4.20
2
3
2
2
(1H, dd, J = 12.0, J = 2.4, H-6′α), 4.30 (1H, dd, J = 12.0, J = 5.6, H-6′β), 5.11 (1H, d, J = 7.6, H-1′), 5.20 (1H, dd, J = 10.0,
J = 9.6, H-4′), 5.27-5.36 (2H, m, H-2′, H-3′), 6.98 (1H, d, J = 8.8, H-8), 7.24 (1H, d, J = 8.8, H-9).
3-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-7,8,9,10-tetrahydrobenzo[c]chromen-6-one (13). Yield 48%
(by method A), 51% (by method B), C H O , mp 135.5-137°C.
27 30 12
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 1.76-1.90 (4H, m, CH -8, CH -9), 2.05, 2.06, 2.07, 2.12 (12H, four
2
2
3
s, four CH COO), 2.53-2.59 (2H, m, CH -7), 2.72-2.79 (2H, m, CH -10), 3.92 (1H, ddd, J = 10.0, J = 5.6, J = 2.4, H-5′), 4.19
3
2
2
(1H, dd, J = 12.0, J = 2.4, H-6′α), 4.30 (1H, dd, J = 12.0, J = 5.6, H-6′β), 5.14 (1H, d, J = 7.6, H-1′), 5.17 (1H, dd, J = 10.0,
J = 9.6, H-4′), 5.28-5.35 (2H, m, H-2′, H-3′), 6.91 (1H, dd, J = 8.8, J = 2.4, H-2), 6.94 (1H, d, J = 2.4, H-4), 7.48 (1H, d,
J = 8.8, H-1).
3-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-4-methyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one (14).
Yield 52% (by method A), 49% (by method B), C H O , mp 210-211.5°C.
28 32 12
-1
IR spectrum (KBr, cm ): 2940, 1758, 1710, 1608, 1378, 1242, 1072, 1060, 1048. UV spectrum (EtOH, λmax, nm,
log ε): 207 (4.65), 222 (4.13), 318 (4.15).
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 1.75-1.91 (4H, m, CH -8, CH -9), 2.05, 2.06, 2.08, 2.09 (12H, four
2
2
3
s, four CH COO), 2.26 (3H, s, CH -4), 2.54-2.60 (2H, m, CH -7), 2.72-2.78 (2H, m, CH -10), 3.89 (1H, ddd, J = 10.0, J = 5.6,
3
3
2
2
J = 2.4, H-5′), 4.20 (1H, dd, J = 12.0, J = 2.4, H-6′α), 4.31 (1H, dd, J = 12.0, J = 5.6, H-6′β), 5.09 (1H, d, J = 7.6, H-1′), 5.20
(1H, dd, J = 10.0, J = 9.2, H-4′), 5.32 (1H, dd, J = 9.6, J = 8.8, H-3′), 5.37 (1H, dd, J = 9.6, J = 7.2, H-2′), 6.96 (1H, d, J = 8.8,
H-2), 7.36 (1H, d, J = 8.8, H-1).
3-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-6-one (15).
Yield 56% (by method A), C H O , mp 188-189°C.
28 32 12
-1
IR spectrum (KBr, cm ): 2932, 1756, 1710, 1608, 1380, 1224, 1076, 1060, 1044. UV spectrum (EtOH, λmax, nm,
log ε): 205 (4.55), 218 (4.13), 321 (4.12).
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 1.56-1.72 (4H, m, CH -8, CH -10), 1.83-1.97 (2H, m, CH -9), 2.05,
2
2
2
3
2.07, 2.13 (12H, three s, four CH COO), 2.86-2.96 (4H, m, CH -7, CH -11), 3.90 (1H, ddd, J = 10.0, J = 5.6, J = 2.4, H-5′),
3
2
2
4.18 (1H, dd, J = 12.4, J = 2.4, H-6′α), 4.31 (1H, dd, J = 12.4, J = 6.0, H-6′β), 5.15 (1H, d, J = 7.6, H-1′), 5.17 (1H, dd, J = 10.0,
J = 9.6, H-4′), 5.27-5.36 (2H, m, H-2′, H-3′), 6.91 (1H, dd, J = 8.8, J = 2.4, H-2), 6.95 (1H, d, J = 2.4, H-4), 7.59 (1H, d,
J = 8.8, H-1).
3-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-4-methyl-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-6-one
(16). Yield 51% (by method A), C H O , mp 192.5-194°C.
29 34 12
-1
IR spectrum (KBr, cm ): 2924, 1758, 1708, 1602, 1444, 1370, 1224, 1134, 1046. UV spectrum (EtOH, λmax, nm,
log ε): 206 (4.76), 220 (4.31), 326 (4.19).
PMRspectrum (400 MHz, CDCl , δ, ppm, J/Hz): 1.56-1.71 (4H, m, CH -8, CH -10), 1.86-1.95 (2H, m, CH -9), 2.05,
2
2
2
3
2.06, 2.08, 2.10 (12H, four s, four CH COO), 2.27 (3H, s, CH -4), 2.84-2.96 (4H, m, CH -7, CH -11), 3.89 (1H, ddd, J = 10.0,
3
3
2
2
J = 5.2, J = 2.4, H-5′), 4.20 (1H, dd, J = 12.4, J = 2.4, H-6′α), 4.31 (1H, dd, J = 12.4, J = 6.0, H-6′β), 5.10 (1H, d, J = 7.6, H-1′),
5.20 (1H, dd, J = 10.0, J = 9.2, H-4′), 5.32 (1H, dd, J = 9.6, J = 8.8, H-3′), 5.37 (1H, dd, J = 9.6, J = 7.6, H-2′), 6.97 (1H, d,
J = 8.8, H-2), 7.47 (1H, d, J = 8.8, H-1).
3-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)benzo[c]chromen-6-one (17). Yield 30% (by method A), 46%
(by method B), C H O , mp 173-174.5°C.
27 26 12
-1
IR spectrum (KBr, cm ): 1748, 1722, 1620, 1460, 1380, 1248, 1240, 1236, 1178, 1100, 1066. UV spectrum (EtOH,
λ
max, nm, log ε): 208 (4.51), 215 (4.52), 224 (4.50), 232 (4.49), 265 (4.18), 275 (4.26), 291 (4.01), 301 (4.07), 322 (3.94).
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 2.05, 2.07, 2.09, 2.14 (12H, four s, four CH COO), 3.92 (1H, ddd,
3
3
J = 9.6, J = 6.0, J = 2.0, H-5′), 4.21 (1H, dd, J = 12.0, J = 2.4, H-6′α), 4.32 (1H, dd, J = 12.0, J = 5.6, H-6′β), 5.17 (1H, d,
J = 7.6, H-1′), 5.19 (1H, dd, J = 10.0, J = 9.6, H-4′), 5.30-5.37 (2H, m, H-2′, H-3′), 6.99 (1H, dd, J = 8.8, J = 2.4, H-2), 7.02 (1H,
d, J = 2.4, H-4), 7.56 (1H, t, J = 8.0, H-8), 7.82 (1H, t, J = 8.0, H-9), 7.98 (1H, d, J = 8.8, H-1), 8.04 (1H, d, J = 8.0, H-10), 8.38
(1H, d, J = 8.0, H-7).
9

3-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-4-methylbenzo[c]chromen-6-one (18). Yield 25% (bymethod
A), 49% (by method B), C H O , mp 220.5-222°C.
28 28 12
-1
IR spectrum (KBr, cm ): 1758, 1740, 1732, 1612, 1468, 1382, 1276, 1242, 1230, 1216, 1116, 1072. UV spectrum
(EtOH, λmax, nm, log ε): 210 (4.49), 222 (4.59), 248 (4.21), 272 (4.23), 278 (4.26), 301 (3.95), 324 (3.93).
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 2.06, 2.07, 2.10, 2.11 (12H, four s, four CH COO), 2.31 (3H, s,
3
3
CH -4), 3.92 (1H, ddd, J = 10.0, J = 5.6, J = 2.4, H-5′), 4.22 (1H, dd, J = 12.0, J = 2.4, H-6′α), 4.32 (1H, dd, J = 12.0, J = 5.6,
3
H-6′β), 5.13 (1H, d, J = 7.6, H-1′), 5.22 (1H, dd, J = 10.0, J = 9.6, H-4′), 5.34 (1H, dd, J = 9.6, J = 8.8, H-3′), 5.39 (1H, dd,
J = 9.6, J = 7.6, H-2′), 7.04 (1H, d, J = 8.8, H-2), 7.55 (1H, t, J = 8.0, H-8), 7.81 (1H, t, J = 8.0, H-9), 7.86 (1H, d, J = 8.8, H-1),
8.04 (1H, d, J = 8.0, H-10), 8.38 (1H, d, J = 8.0, H-7).
9-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-7-methyl-2,3-dihydrocyclopenta[c]chromen-4-one (19). Yield
46% (by method A), 49% (by method B), C H O , mp 186.5-188°C.
27 30 12
-1
IR spectrum (KBr, cm ): 1760, 1710, 1620, 1370, 1238, 1076. UV spectrum (EtOH, λmax, nm, log ε): 207 (4.63), 242
(3.84), 304 (4.21).
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 2.05, 2.06, 2.07 (12H, three s, four CH COO), 2.10 (2H, m, CH -2),
3
2
3
2.42 (3H, s, CH -7), 2.82 (2H, m, CH -3), 3.00-3.11 (1H, m, H-1α), 3.28-3.38 (1H, m, H-1β), 3.93 (1H, ddd, J = 9.6, J = 6.0,
3
2
J = 2.0, H-5′), 4.17 (1H, dd, J = 12.0, J = 2.4, H-6′α), 4.26 (1H, dd, J = 12.0, J = 5.6, H-6′β), 5.17-5.35 (4H, m, H-1′, H-2′, H-3′,
H-4′), 6.65 (1H, s, H-8), 6.91 (1H, s, H-6).
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-3-methyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one (20).
Yield 48% (by method A), 44% (by method B), C H O , mp 183.5-184.5°C.
28 32 12
PMR spectrum (400 MHz, CDCl , δ, ppm, J/Hz): 1.66-1.77 (4H, m, CH -8, CH -9), 2.04, 2.05, 2.06, 2.07 (12H, four
2
2
3
s, four CH COO), 2.39 (3H, s, CH -3), 2.50-2.59 (2H, m, CH -7), 2.72-2.82 (1H, m, H-10α), 3.00-3.12 (1H, m, H-10β), 3.92
3
3
2
(1H, ddd, J = 10.0, J = 5.6, J = 2.4, H-5′), 4.18 (1H, dd, J = 12.0, J = 2.4, H-6′α), 4.25 (1H, dd, J = 12.0, J = 6.0, H-6′β), 5.18
(1H, dd, J = 10.0, J = 8.8, H-4′), 5.27 (1H, d, J = 7.6, H-1′), 5.32 (1H, dd, J = 9.6, J = 8.8, H-3′), 5.36 (1H, dd, J = 9.6, J = 7.6,
H-2′), 6.66 (1H, s, H-2), 6.85 (1H, s, H-4).
GeneralMethodfor Deacetylationof2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosides11-20. Asolution ofperacetate
(11-20, 5 mmol) in absolute CH OH (20 mL) was treated with sodium methoxide (50 mg) and boiled for 10-30 min (completion
3
ofthe reaction determined byTLC). The precipitate that formed on cooling (0°C) was filtered off and washed with cold CH OH.
3
The mother liquor was concentrated in vacuum in a rotaryevaporator. An additional portion ofglucopyranoside (21-30) formed
upon cooling.
7-(β-D-Glucopyranosyloxy)-2,3-dihydrocyclopenta[c]chromen-4-one (21). Yield 85%, C H O , mp 252.5-
18 20
8
253.5°C.
IR spectrum (KBr, cm ): 3440, 2932, 1704, 1626, 1392, 1298, 1256, 1168, 1088, 1074, 1036. UV spectrum (EtOH,
max, nm, log ε): 205 (4.77), 218 (4.33), 321 (4.28).
PMR spectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 2.10 (2H, m, CH -2), 2.74 (2H, m, CH -1), 3.06 (2H, m, CH -3),
-1
λ
2
2
2
3.16 (1H, m, H-4′), 3.28 (2H, m, H-2′, H-3′), 3.44 (2H, m, H-5′, H-6′α), 3.70 (1H, dd, J = 11.6, J = 4.8, H-6′β), 4.60 (1H, t,
J = 5.6, OH-6), 5.01 (1H, d, J = 7.6, H-1′), 5.06 (1H, d, J = 4.4, OH), 5.13 (1H, d, J = 4.0, OH), 5.40 (1H, d, J = 4.4, OH), 7.02
(1H, d, J = 2.4, H-6), 7.08 (1H, dd, J = 2.4, J = 8.8, H-8), 7.54 (1H, d, J = 8.8, H-9).
7-(β-D-Glucopyranosyloxy)-6-methyl-2,3-dihydrocyclopenta[c]chromen-4-one (22). Yield 97%, C H O ,
19 22
8
mp 172-173.5°C.
-1
IR spectrum (KBr, cm ): 3436, 2932, 1702, 1608, 1378, 1286, 1248, 1172, 1074. UV spectrum (EtOH, λmax, nm,
log ε): 206 (4.56), 219 (4.10), 321 (4.13).
PMR spectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 2.14 (2H, m, CH -2), 2.29 (3H, s, CH -4), 2.79 (2H, m, CH -1),
2
3
2
3.05 (2H, m, CH -3), 3.15-3.30 (4H, m, H-2′, H-3′, H-4′, H-5′), 3.48 (1H, m, H-6′α), 3.69 (1H, dd, J = 11.6, J = 4.8, H-6′β),
2
4.45 (1H, t, J = 5.6, OH-6), 4.87 (1H, d, J = 7.6, H-1′), 4.95 (1H, d, J = 4.4, OH), 5.05 (1H, d, J = 4.0, OH), 5.29 (1H, d, J = 4.4,
OH), 7.11 (1H, d, J = 8.8, H-8), 7.34 (1H, d, J = 8.8, H-9).
3-(β-D-Glucopyranosyloxy)-7,8,9,10-tetrahydrobenzo[c]chromen-6-one (23). Yield 88%, C H O , mp 214-
19 22
8
215°C.
-1
IR spectrum (KBr, cm ): 3412, 2940, 1692, 1610, 1392, 1284, 1262, 1176, 1080, 1052, 1042. UV spectrum (EtOH,
max, nm, log ε): 204 (4.66), 216 (4.23), 316 (4.21).
λ
10

PMRspectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 1.67-1.82 (4H, m, CH -8, CH -9), 2.40(2H, m, CH -7), 2.78 (2H,
2
2
2
m, CH -10), 3.17 (1H, m, H-4′), 3.27 (2H, m, H-2′, H-3′), 3.39-3.48 (2H, m, H-5′, H-6′α), 3.70 (1H, dd, J = 11.6, J = 4.8,
2
H-6′β), 4.59 (1H, t, J = 5.6, OH-6), 5.00 (1H, d, J = 7.6, H-1′), 5.06 (1H, d, J = 4.4, OH), 5.13 (1H, d, J = 4.0, OH), 5.38 (1H,
d, J = 4.0, OH), 7.00 (1H, dd, J = 8.8, J = 2.0, H-2), 7.02 (1H, d, J = 2.0, H-4), 7.64 (1H, d, J = 8.8, H-1).
3-(β-D-Glucopyranosyloxy)-4-methyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one (24). Yield 92%, C H O ,
20 24
8
mp 233-234.5°C.
-1
IR spectrum (KBr, cm ): 3388, 2932, 1704, 1608, 1382, 1282, 1266, 1132, 1104, 1084, 1040. UV spectrum (EtOH,
max, nm, log ε): 205 (4.72), 221 (4.24), 318 (4.20).
λ
PMR spectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 1.66-1.83 (4H, m, CH -8, CH -9), 2.24 (3H, s, CH -4), 2.41 (2H,
2
2
3
m, CH -7), 2.77 (2H, m, CH -10), 3.20 (1H, m, H-4′), 3.29 (2H, m, H-2′, H-3′), 3.46 (2H, m, H-5′, H-6′α), 3.69 (1H, dd,
2
2
J = 11.6, J = 4.8, H-6′β), 4.57 (1H, t, J = 5.6, OH-6), 4.93 (1H, d, J = 7.6, H-1′), 5.05 (1H, d, J = 4.4, OH), 5.12 (1H, d, J = 4.0,
OH), 5.41 (1H, m, OH), 7.12 (1H, d, J = 8.8, H-2), 7.51 (1H, d, J = 8.8, H-1).
3-(β-D-Glucopyranosyloxy)-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-6-one (25). Yield 83%, C H O ,
20 24
8
mp 219-220.5°C.
-1
IR spectrum (KBr, cm ): 3468, 2928, 1686, 1618, 1608, 1388, 1286, 1262, 1238, 1180, 1100, 1080, 1012.
UV spectrum (EtOH, λmax, nm, log ε): 205 (4.75), 219 (4.30), 324 (4.24).
PMR spectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 1.42-1.64 (4H, m, CH -8, CH -10), 1.78-1.89 (2H, m, CH -9),
2
2
2
2.75-2.81 (2H, m, CH -7), 2.94-3.00 (2H, m, CH -11), 3.16-3.48 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′α), 3.70 (1H, dd, J = 11.2,
2
2
J = 5.2, H-6′β), 4.59 (1H, t, J = 5.6, OH-6), 5.01 (1H, d, J = 7.6, H-1′), 5.06 (1H, d, J = 5.6, OH), 5.13 (1H, d, J = 4.4, OH), 5.39
(1H, d, J = 4.4, OH), 7.00 (1H, dd, J = 8.8, J = 2.4, H-2), 7.03 (1H, d, J = 2.4, H-4), 7.82 (1H, d, J = 8.8, H-1).
3-(β-D-Glucopyranosyloxy)-4-methyl-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-6-one (26). Yield 89%,
C H O , mp 136.5-138°C.
21 26
8
-1
IR spectrum (KBr, cm ): 3348, 2924, 1700, 1602, 1370, 1268, 1074. UV spectrum (EtOH, λmax, nm, log ): 207
(4.69), 221 (4.19), 328 (4.16).
PMR spectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 1.39-1.68 (4H, m, CH -8, CH -10), 1.77-1.90 (2H, m, CH -9),
2
2
2
2.24 (3H, s, CH -4), 2.73-2.84 (2H, m, CH -7), 2.91-3.02 (2H, m, CH -11), 3.15-3.26 (2H, m, H-2′, H-3′, H-4′), 3.41 (1H, m,
3
2
2
H-5′), 3.46 (1H, m, H-6′α), 3.69 (1H, dd, J = 11.2, J = 5.6, H-6′β), 4.58 (1H, t, J = 5.6, OH-6), 4.95 (1H, d, J = 7.6, H-1′), 5.06
(1H, d, J = 4.4, OH), 5.13 (1H, d, J = 4.0, OH), 5.41 (1H, d, J = 4.4, OH), 7.12 (1H, d, J = 8.8, H-2), 7.70 (1H, d, J = 8.8, H-1).
3-(β-D-Glucopyranosyloxy)benzo[c]chromen-6-one (27). Yield 92%, C H O , mp 258-259.5°C.
19 18
8
-1
IR spectrum (KBr, cm ): 3388, 1722, 1620, 1458, 1396, 1280, 1184, 1090, 1040. UV spectrum (EtOH, λmax, nm,
log ε): 210 (4.59), 217 (4.59), 225 (4.56), 232 (4.56), 267 (4.25), 275 (4.32), 292 (4.11), 302 (4.17), 328 (4.03).
PMR spectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 3.16 (1H, m, H-4′), 3.29 (2H, m, H-2′, H-3′), 3.39-3.51 (2H, m,
H-5′, H-6′α), 3.71 (1H, dd, J = 11.6, J = 4.8, H-6′β), 4.62 (1H, t, J = 5.6, OH-6), 5.03 (1H, d, J = 7.6, H-1′), 5.07 (1H, d,
J = 5.2, OH), 5.14 (1H, d, J = 4.4, OH), 5.40 (1H, d, J = 4.4, OH), 7.08 (2H, m, H-2, H-4), 7.62 (1H, t, J = 8.0, H-8), 7.93 (1H,
t, J = 8.0, H-9), 8.22 (1H, d, J = 8.8, H-1), 8.29 (1H, d, J = 8.0, H-10), 8.36 (1H, d, J = 8.0, H-7).
3-(β-D-Glucopyranosyloxy)-4-methylbenzo[c]chromen-6-one (28). Yield 87%, C H O , mp 303-304.5°C.
20 20
8
-1
IR spectrum (KBr, cm ): 3384, 1716, 1606, 1468, 1404, 1280, 1196, 1168, 1076. UV spectrum (EtOH, λmax, nm,
log ε): 210 (4.41), 222 (4.49), 249 (4.09), 280 (4.15), 302 (3.85), 329 (3.78).
PMR spectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 2.30 (3H, s, CH -4), 3.20 (1H, m, H-4′), 3.29 (2H, m, H-2′, H-3′),
3
3.38 (1H, m, H-5′), 3.48 (1H, m, H-6′α), 3.71 (1H, dd, J = 11.6, J = 4.8, H-6′β), 4.61 (1H, t, J = 5.6, OH-6), 4.98 (1H, d,
J = 7.6, H-1′), 5.06 (1H, d, J = 4.8, OH), 5.13 (1H, d, J = 4.0, OH), 5.42 (1H, d, J = 4.0, OH), 7.20 (1H, d, J = 8.8, H-2), 7.61
(1H, t, J = 8.0, H-8), 7.91 (1H, t, J = 8.0, H-9), 8.17 (1H, d, J = 8.8, H-1), 8.23 (1H, d, J = 8.0, H-10), 8.37 (1H, d, J = 8.0, H-7).
9-(β-D-Glucopyranosyloxy)-7-methyl-2,3-dihydrocyclopenta[c]chromen-4-one (29). Yield 83%, C H O ,
19 22
8
mp 200-201.5°C.
-1
IR spectrum (KBr, cm ): 3408, 2920, 1706, 1680, 1620, 1556, 1498, 1460, 1384, 1260, 1148, 1080. UV spectrum
(EtOH, λmax, nm, log ε): 207 (4.50), 243 (3.72), 308 (4.10).
PMR spectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 2.02 (2H, m, CH -2), 2.36 (3H, s, CH -7), 2.67 (2H, m, CH -3),
2
3
2
3.15-3.59 (7H, m, CH -1, H-2′, H-3′, H-4′, H-5′, H-6′α), 3.69 (1H, dd, J = 10.8, J = 5.2, H-6′β), 4.60 (1H, t, J = 5.6, OH-6), 5.00
2
(1H, d, J = 7.6, H-1′), 5.06 (1H, d, J = 4.8, OH), 5.14 (1H, d, J = 4.4, OH), 5.34 (1H, d, J = 5.6, OH), 6.88 (1H, s, H-8), 6.89
(1H, s, H-6).
11

1-(β-D-Glucopyranosyloxy)-3-methyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one (30). Yield 89%, C H O ,
20 24
8
mp 210-211.5°C.
PMRspectrum (400 MHz, DMSO-d6, δ, ppm, J/Hz): 1.59-1.74 (4H, m, CH -8, CH -9), 2.34 (3H, s, CH -3), 2.41 (2H,
2
2
3
m, CH -7), 2.96-3.01 (1H, m, H-10α), 3.14-3.52 (6H, m, H-10β, H-2′, H-3′, H-4′, H-5′, H-6′α), 3.70 (1H, dd, J = 11.2, J = 5.2,
2
H-6′β), 4.60 (1H, t, J = 5.6, OH-6), 5.00 (1H, d, J = 7.6, H-1′), 5.06 (1H, d, J = 4.4, OH), 5.14 (1H, d, J = 3.2, OH), 5.36 (1H,
d, J = 5.2, OH), 6.82 (1H, s, H-2), 6.90 (1H, s, H-4).
ACKNOWLEDGMENT
We thank OAO "Eximed" (Kiev, Ukraine) for help in performing the work.
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12