Synthesis of hydrophilic and lipophilic 4-arylcoumarin phosphates

Article abstract of DOI:10.1007/s11172-011-0304-7

Novel hydrophilic and lipophilic prodrugs, sodium 4-arylcoumarin dialkylphosphates and 4-arylcoumarin dioleyl phosphates, were synthesized by phosphorylation of 4-arylcoumarins with dialkylphosphites.

Full text of DOI:10.1007/s11172-011-0304-7

Russian Chemical Bulletin, International Edition, Vol. 60, No. 10, pp. 2003—2009, October, 2011
2003
Synthesis of hydrophilic and lipophilic 4ꢀarylcoumarin phosphates
A. N. Selikhov,a Y. B. Malysheva,a A. V. Nyuchev,a N. S. Sitnikov,a E. A. Sharonova,a
A. S. Shavyrin,b S. Combes,c and A. Yu. Fedorova
aN. I. Lobachevsky Nizhny Novgorod State University,
23 prosp. Gagarina, 603950 Nizhny Novgorod, Russian Federation.
Fax: +7 (831) 462 3085. Eꢀmail: afnn@rambler.ru
bG. A. Razyvaev Institute of Organometallic Chemistry, Russian Academy of Sciences,
49 ul. Tropinina, 603600 Nizhny Novgorod, Russian Federation.
Fax: +7 (831) 462 7497. Eꢀmail: andrew@imoc.sinn.ru
cUniversites AixꢀMarseille 1, 2 et 3, Faculte des Sciences SaintꢀJerome, case 521,
UMR 6264, 13397 Marseille Cedex 20, France.
Fax: +33 (049) 128 8758. Eꢀmail: Sebastien.Combes@univꢀprovence.fr
Novel hydrophilic and lipophilic prodrugs, sodium 4ꢀarylcoumarin dialkylphosphates and
4ꢀarylcoumarin dioleyl phosphates, were synthesized by phosphorylation of 4ꢀarylcoumarins
with dialkylphosphites.
Key words: 4ꢀarylcoumarins, water soluble prodrugs, lipophilic prodrugs, phosphorylation.
Natural1 and synthetic2 4ꢀarylcoumarins 1 possess high
level of antitumor activity, e.g., suppress mitotic spindle
formation in the tumor cells thus inhibiting tubulin polyꢀ
merization.3 Two nonꢀcoplanar syn aryl moieties A and B
linked by rigid C—C bond make structure of these derivaꢀ
tives similar to combretastatin Aꢀ4 (CAꢀ4) 2a, cisꢀstilbene
separated from African plant Combretum cafrum, which
exhibited significant antimitotic activity.4 Low water solꢀ
ubility of 4ꢀarylcoumarins 1 and CAꢀ4 makes difficult their
evaluation in vivo. Conversion of CAꢀ4 and its analogs into
water soluble prodrug forms5 (2b) and amino acid derivaꢀ
tives6 (2c) improve their pharmacokinetic profile, namely,
make it possible to reach higher concentration of the therꢀ
apeutic agent in blood, decrease the dose levels and, thereꢀ
fore, decrease its general toxicity.7 Currently, fosbretabuꢀ
lin 2b and ombrabulin 2c are in phase III clinical trials.8
A serious drawback of CAꢀ4 derivatives is that they are
prone to Z,Eꢀisomerization during storage and use, which
significantly decrease antitumor activity.4,9 This encourꢀ
age us to synthesize a number of novel water soluble nonꢀ
isomerizable neoflavonoid analogs of CAꢀ4 phosphate deꢀ
rivatives, compounds 3 (Scheme 1).
The key step in the synthesis of 4ꢀarylcoumarins 3 is
Suzuki—Miyaura crossꢀcoupling reaction10 of coumarin
triflates 4a—f (see Ref. 11) with 3ꢀhydroxyꢀ4ꢀmethoxyꢀ
phenylboronic acid bearing the methoxymethyl protectꢀ
ing group (see Scheme 1). Application of catalytic system
Pd(dppf)Cl2 (0.05 equiv.)—K3PO4 (3.0 equiv.)—Bu4NBr
(0.1 equiv.) (see Ref. 12) serves for the synthesis of target
4ꢀarylcoumarins 5a—f in high yields (58—95%) regardless
of the number and position of the methoxy groups in the
coumarin framework (see Scheme 1).
The methoxymethyl (MOM) protecting groups in
compounds 5a—f were cleaved by acid hydrolysis in aceꢀ
tone at 40 °C. Derivatives 6a—f were obtained in 81—94%
yields (see Scheme 1). Phosphorylation13 of compounds
6a—f by dibenzyl phosphite resulted in dibenzyl phosꢀ
phates 7a—f in good yields (59—81%). Debenzylation14
of the latter by subsequent treatment with Me3SiBr and
MeONa afforded target products 3a—f in 54—89% yields.
It is of note that water soluble prodrugs 3a—f upon
enzymatic dephosphorylation15 in the cells can form
4ꢀarylcoumarins 6a—f exhibiting marked antitumor
activity.2a,b
Along with hydrophilic coumarins 3a—f, we syntheꢀ
sized lipophilic phosphate derivatives of 4ꢀarylcoumarins,
compounds 8a,d,f, by the reaction of 6a,d,f with dioleyl
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1968—1973, October, 2011.
1066ꢀ5285/11/6010ꢀ2003 © 2011 Springer Science+Business Media, Inc.

2004
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
Selikhov et al.
Схема 1
R1
H
OMe
H
R2
H
H
R3
H
H
R1
H
OMe
OMe
R2
H
H
R3
OMe
OMe
OMe
a
b
c
d
e
f
OMe
H
OMe
Reagents and conditions: i. Pd(dppf)Cl2 (0.05 equiv.), K3PO4 (3.0 equiv.), Bu4NBr (0.1 equiv.), MeCN, 3 h, 80 °C; ii. HCl, acetone,
0.2—0.5 h, 40 °C; iii. (BnO)2P(O)H (1.7 equiv.), MeCN—CCl4 (1 : 1), DIPEA (2.1 equiv.), DMAP (0.1 equiv.), 1 h, –10 °C;
iv. 1) Me3SiBr (6 equiv.), CH2Cl2, 1 ч, 20 °C; 2) MeONa (2 equiv.), MeOH, 0.5 h, 25 °C.
phosphite16 (Scheme2). Lipophilic compounds 8a,d,f were
isolated in the yields of 61—69%.
Currently, hydrophilic (3a—f) and hydrophobic (8a,d,f)
prodrug forms of 4ꢀarylcoumarins are in evaluation of
in vitro cytotoxicity.
Scheme 2
Experimental
1
H and 13C NMR spectra were recorded on a Bruker ARX
400 in CDCl3 at 400 and 101 MHz, respectively. The chemical
shifts are given in the δ scale relative to Mе4Si. All commercially
available reagents (Aldrich, Alfa Aesar) were used as purchased.
The solvents were purified prior to use according to the standard
procedures. Petroleum ether with b.p. 40—70 °C was used.
4ꢀArylcoumarin trifluoromethanesulfonates 4a—f were syntheꢀ
sized by the known procedure.19
Compounds 5a—f (general procedure). A solution of couꢀ
marin 4ꢀtrifluoromethanesulfonate 4 (1 equiv.), arylboronic acid
(1.3 equiv.), K3PO4 (3 equiv.), Bu4NBr (0.1 equiv.), and
Pd(dppf)Cl2 (0.05 equiv.) in MeCN (1 mL per 0.086 mmol of
compound 4) was stirred at 80 °C for 3 h under argon. The solꢀ
vent was removed in vacuo, purification of the residue by silica
gel column chromatography yielded the target product.
Oleyl is Me(CH2)7CH=CH(CH2)8
Reagents and conditions: i. (OleylO)2P(O)H, CCl4—MeCN—CHCl3
(1 : 1 : 1), DIPEA (7 equiv.), DMAP (0.3 equiv.), 2 h, –10 °C.
4ꢀ(3´ꢀMethoxymethoxymethylꢀ4´ꢀmethoxyphenyl)chromenꢀ
2ꢀone (5a) was synthesized from coumarin 4ꢀtrifluoromethaneꢀ
sulfonate (121 mg, 0.41 mmol), 3ꢀmethoxymethoxymethylꢀ4ꢀ
methoxyphenylboronic acid (112 mg, 0.53 mmol), Pd(dppf)Cl2
(17 mg, 0.021 mmol), K3PO4 (261 mg, 1.23 mmol), and Bu4NBr
Lipid prodrugs 8 can effectively be inserted into the
lipid bilayer of targeted therapeutic liposome transport
systems,17 which could increase selectivity of therapeutic
effect and reduce general toxicity18 of 4ꢀarylcoumarins 6.

Synthesis of 4ꢀarylcoumarin phosphates
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2005
(13 mg, 0.041 mmol). Elution with ethyl acetate—petroleum
ether (3 : 2) afforded compound 5a in a yield of 111 mg (86%),
light yellow crystals, m.p. 142 °C. 1H NMR (CDCl3), δ: 3.52,
3.96 (both s, 3 H each, OCH3); 5.26 (s, 2 H, CH2); 6.36 (s, 1 H,
H(3)); 7.02 (d, 1 H, H(5´), J = 8.4 Hz); 7.12 (dd, 1 H, H(6´),
J = 8.4 Hz, J = 2.0 Hz); 7.23 (m, 2 H, H(2´), H(6)); 7.39 (d, 1 H,
H(8), J = 7.6 Hz); 7.55 (m, 2 H, H(5), H(7)). 13C NMR (CDCl3),
δ: 56.0, 56.3, 95.6, 111.8, 114.7, 116.9, 117.3, 119.0, 122.9, 124.0,
126.9, 127.7, 131.8, 146.5, 151.0, 154.2, 155.0, 160.8.
4ꢀ(3´ꢀMethoxymethoxymethylꢀ4´ꢀmethoxyphenyl)ꢀ7ꢀmethꢀ
oxychromenꢀ2ꢀone (5b) was synthesized from 7ꢀmethoxycouꢀ
marin 4ꢀtrifluoromethanesulfonate (4b) (133 mg, 0.41 mmol),
3ꢀmethoxymethoxymethylꢀ4ꢀmethoxyphenylboronic acid (112 mg,
0.53 mmol), Pd(dppf)Cl2 (17 mg, 0.021 mmol), K3PO4 (261 mg,
1.23 mmol), and Bu4NBr (13 mg, 0.041 mmol). Elution with
ethyl acetate—petroleum ether (3 : 2) afforded compound 5b in
a yield of 121 mg (86%), light yellow crystals, m.p. 135 °C.
1H NMR (CDCl3), δ: 3.53, 3.89, 3.96 (all s, 3 H each, OCH3);
5.26 (s, 2 H, OCH2O); 6.21 (s, 1 H, H(3)); 6.81 (dd, 1 H, H(6),
J = 8.9 Hz, J = 2.4 Hz); 6.89 (d, 1 H, H(8), J = 2.4 Hz); 7.02
(d, 1 H, H(5´), J = 8.3 Hz); 7.11 (dd, 1 H, H(6´), J = 8.3 Hz,
J = 1.5 Hz); 7.27 (d, 1 H, H(2´), J = 1.5 Hz); 7.48 (d, 1 H, H(5),
J = 8.9 Hz). 13C NMR (CDCl3), δ: 55.94, 56.20, 56.50, 95.78,
101.25, 111.67, 111.93, 112.44, 112.75, 117.05, 123.03, 128.12,
128.30, 135.37, 143.21, 151.16, 156.24, 161.60, 162.88.
4ꢀ(3´ꢀMethoxymethoxymethylꢀ4´ꢀmethoxyphenyl)ꢀ6ꢀmethꢀ
oxychromenꢀ2ꢀone (5c) was synthesized from 6ꢀmethoxycouꢀ
marin 4ꢀtrifluoromethanesulfonate (4c) (133 mg, 0.41 mmol),
3ꢀmethoxymethoxymethylꢀ4ꢀmethoxyphenylboronic acid (112 mg,
0.53 mmol), Pd(dppf)Cl2 (17 mg, 0.021 mmlo), K3PO4 (261 mg,
1.23 mmlo), and Bu4NBr (13 mg, 0.041 mmol). Elution with
ethyl acetate—petroleum ether (3 : 2) afforded compound 5c in
a yield of 81 mg (58%), light yellow crystals, m.p. 155 °C.
1H NMR (CDCl3), δ: 3.52, 3.76, 3.97 (all s, 3 H each, OCH3);
5.27 (s, 2 H, OCH2O); 6.37 (s, 1 H, H(3)); 7.04 (d, 1 H, H(5´),
J = 11.0 Hz); 7.05 (s, 1 H, H(5)); 7.09—7.16 (m, 2 H, H(7),
H(8)); 7.30 (d, 1 H, H(2´), J = 1.8 Hz); 7.33 (d, 1 H, H(6´),
J = 9.0 Hz). 13C NMR (CDCl3), δ: 55.8, 56.0, 56.3, 95.6, 101.1,
111.8, 113.6, 116.9, 117.1, 122.9, 128.1, 128.4, 135.4, 139.6,
143.0, 144.2, 150.9, 156.1, 162.7.
4ꢀ(3´ꢀMethoxymethoxymethylꢀ4´ꢀmethoxyphenyl)ꢀ5ꢀmethꢀ
oxychromenꢀ2ꢀone (5d) was synthesized from 5ꢀmethoxycouꢀ
marin 4ꢀtrifluoromethanesulfonate (4d) (133 mg, 0.41 mmol),
3ꢀmethoxymethoxymethylꢀ4ꢀmethoxyphenylboronic acid (112 mg,
0.53 mmol), Pd(dppf)Cl2 (17 mg, 0.021 mmol), K3PO4 (261 mg,
1.23 mmol), Bu4NBr (13 mg, 0.041 mmol). Elution with ethyl
acetate—petroleum ether (3 : 2) afforded compound 5d in a yield
of 111 mg (79%), light yellow crystals, m.p. 150 °C. 1H NMR
(CDCl3), δ: 3.51, 3.54, 3.94 (all s, 3 H each, OCH3); 5.22 (s, 2 H,
OCH2O); 6.18 (s, 1 H, H(3)); 6.69 (d, 1 H, H(6), J = 8.3 Hz);
6.91 (d, 1 H, H(5´), J = 8.3 Hz); 6.96 (dd, 1 H, H(6´), J = 8.3 Hz,
J = 1.3 Hz); 7.02 (d, 1 H, H(8), J = 8.3 Hz); 7.10 (d, 1 H, H(2´),
J = 1.3 Hz); 7.46 (t, 1 H, H(7), J = 8.3 Hz). 13C NMR (CDCl3),
δ: 55.72, 56.09, 56.37, 95.78, 106.78, 109.42, 110.16, 110.77,
116.16, 116.55, 121.53, 132.38, 132.55, 145.58, 150.02, 154.96,
155.65, 157.46, 160.70.
1.77 mmol), and Bu4NBr (19 mg, 0.059 mmol). Elution with
ethyl acetate—petroleum ether (3 : 2) afforded compound 5e in
a yield of 209 mg (95%), light yellow crystals, m.p. 135 °C.
1H NMR (CDCl3), δ: 3.51 (s, 6 H, OCH3); 3.87, 3.93 (both s,
3 H each, OMe); 5.21 (s, 2 H, CH2); 6.01 (s, 1 H, H(3)); 6.25
(d, 1 H, H(6), J = 2.2 Hz); 6.52 (d, 1 H, H(8), J = 2.2 Hz); 6.92
(m, 2 H, H(5´), H(6´)); 7.09 (d, 1 H, H(2´), J = 1.6 Hz).
13C NMR (CDCl3), δ: 55.5, 55.7, 55.9, 56.2, 93.6, 95.6, 95.8,
103.5, 110.6, 112.7, 116.6, 121.4, 132.5, 145.4, 150.0, 155.1,
157.2, 158.2, 160.9, 163.3.
4ꢀ(3´ꢀMethoxymethoxymethylꢀ4´ꢀmethoxyphenyl)ꢀ5,6,7ꢀtriꢀ
methoxychromenꢀ2ꢀone (5f) was synthesized from 5,6,7ꢀtriꢀ
methoxycoumarin 4ꢀtrifluoromethanesulfonate (4f) (100 mg,
0.26 mmol), 3ꢀmethoxymethoxymethylꢀ4ꢀmethoxyphenylborꢀ
onic acid (72 mg, 0.34 mmol), Pd(dppf)Cl2 (11 mg, 0.013 mmol),
K3PO4 (165 mg, 0.78 mmol), and Bu4NBr (8 mg, 0.026 mmol).
Elution with ethyl acetate—petroleum ether (1 : 1) afforded
compound 5e in a yield of 86 mg (82%), light yellow crysꢀ
1
tals, m.p. 141 °C. H NMR (CDCl3), δ: 3.32, 3.49, 3.79, 3.93,
3.93 (all s, 3 H each, OCH3); 5.23 (s, 2 H, OCH2O); 6.07
(s, 1 H, H(3)); 6.71 (s, 1 H, H(8)); 6.92 (d, 1 H, H(5´),
J = 8.3 Hz); 6.98 (dd, 1 H, H(6´), J = 8.3 Hz, J = 2.0 Hz); 7.16
(d, 1 H, H(2´), J = 2.0 Hz). 13C NMR (CDCl3), δ: 56.08, 56.30,
56.40, 61.21, 61.26, 95.78, 96.40, 107.41, 110.77, 114.20, 116.48,
121.64, 131.67, 139.63, 145.56, 149.88, 151.28, 151.88, 155.00,
156.90, 160.89.
Compounds 6a—f (general procedure). To a solution of couꢀ
marin 5 in acetone (3 mL of acetone per 0.45 mmol of 5), conc.
HCl (10 drops per 0.15 mmol of 5) was added dropwise over
a period of 30 min at 40 °C. The solvent was removed in vacuo,
the residue was dissolved in ethyl acetate, the organic layer was
washed with saturated aqueous NaHCO3 (three times). The orꢀ
ganic layer was separated and dried with anh. Na2SO4. The
product was purified by silica gel column chromatography. The
NMR spectra of compounds 6a—f are in agreement with that
published earlier.20
4ꢀ(3´ꢀHydroxyꢀ4´ꢀmethoxy)chromenꢀ2ꢀone (6a) was syntheꢀ
sized from compound 5a (94 mg, 0.3 mmol), acetone (2 mL),
and conc. HCl (20 drops). Elution with ethyl acetate—petroꢀ
leum ether (1 : 1) afforded compound 6a in a yield of 76 mg
(94%), light yellow crystals, m.p. 193 °C.
4ꢀ(3´ꢀHydroxyꢀ4´ꢀmethoxy)ꢀ7ꢀmethoxychromenꢀ2ꢀone (6b)
was synthesized from compound 5b (103 mg, 0.3 mmol), aceꢀ
tone (2 mL), and conc. HCl (20 drops). Elution with ethyl aceꢀ
tate—petroleum ether (1 : 1) afforded compound 6b in a yield of
72 mg (81%), light yellow crystals, m.p. 173 °C.
4ꢀ(3´ꢀHydroxyꢀ4´ꢀmethoxy)ꢀ6ꢀmethoxychromenꢀ2ꢀone (6c)
was synthesized from compound 5c (68 mg, 0.2 mmol), acetone
(1.5 mL), and conc. HCl (15 drops). Elution with ethyl aceꢀ
tate—petroleum ether (1 : 1) afforded compound 6c in a yield of
49 mg (83%), light yellow crystals, m.p. 167 °C.
4ꢀ(3´ꢀHydroxyꢀ4´ꢀmethoxy)ꢀ5ꢀmethoxychromenꢀ2ꢀone (6d)
was synthesized from compound 5d (103 mg, 0.3 mmol), aceꢀ
tone (2 mL), and conc. HCl (20 drops). Elution with ethyl aceꢀ
tate—petroleum ether (1 : 1) afforded compound 6d in a yield of
73 mg (82%), light yellow crystals, m.p. 180 °C.
4ꢀ(3´ꢀMethoxymethoxymethylꢀ4´ꢀmethoxyphenyl)ꢀ5,7ꢀdiꢀ
methoxychromenꢀ2ꢀone (5e) was synthesized from 5,7ꢀdimethoxyꢀ
coumarin 4ꢀtrifluoromethanesulfonate (4e) (209 mg, 0.59 mmol),
3ꢀmethoxymethoxymethylꢀ4ꢀmethoxyphenylboronic acid (163 mg,
0.77 mmol), Pd(dppf)Cl2 (24 mg, 0.03 mmol), K3PO4 (375 mg,
4ꢀ(3´ꢀHydroxyꢀ4´ꢀmethoxy)ꢀ5,7ꢀdimethoxychromenꢀ2ꢀone
(6e) was synthesized from compound 5e (112 mg, 0.3 mmol),
acetone (2 mL), and conc. HCl (20 drops). Elution with ethyl
acetate—petroleum ether (1 : 1) afforded compound 6e in a yield
of 87 mg (88%), light yellow crystals, m.p. 148 °C.

2006
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
Selikhov et al.
4ꢀ(3´ꢀHydroxyꢀ4´ꢀmethoxy)ꢀ5,6,7ꢀtrimethoxychromenꢀ2ꢀ
one (6f) was synthesized from compound 5f (80 mg, 0.2 mmol),
acetone (1.5 mL), and conc. HCl (15 drops). Elution with ethyl
acetate—petroleum ether (1 : 1) afforded compound 6f in a yield
of 65 mg (91%), light yellow crystals, m.p. 157 °C.
Compounds 7a—f (general procedure). To a solution of comꢀ
pound 6 (1 equiv.), DIPEA (2.1 equiv.), and DMAP (0.1 equiv.)
in CH3CN, equal volume of CCl4 was added at –10 °C under
argon. Then dibenzyl phosphite (1.7 equiv.) was slowly added by
drops and the reaction mixture was stirred for 1 h. After compleꢀ
tion of the reaction, the mixture was washed with 2 M KH2PO4,
extracted with ethyl acetate, organic layer was washed with
brine, and dried with anh. Na2SO4. The solvent was removed
in vacuo. The product was purified by silica gel column chromatoꢀ
graphy.
(d, J = 7.1 Hz); 148.69, 152.06 (d, J = 5.2 Hz); 153.96, 156.10,
161.01. 31P NMR (CDCl3), δ: –5.92.
Dibenzyl[2ꢀmethoxyꢀ5ꢀ(5ꢀmethoxyꢀ2ꢀoxochromenꢀ4ꢀyl)ꢀ
phenyl]phosphate (7d) was synthesized from compound 6d
(73 mg, 0.245 mmol), dibenzyl phosphite (109 mg, 0.417 mmol),
DIPEA (66 mg, 0.515 mmol), and DMAP (3 mg, 0.025 mmol).
Elution with ethyl acetate—petroleum ether (1 : 1) afforded comꢀ
pound 7d in a yield of 97 mg (71%), yellowish oil. 1H NMR
(CDCl3), δ: 3.47, 3.86 (both s, 3 H each, OCH3); 5.18 (d, 4 H,
J = 8.0 Hz); 6.09 (s, 1 H, H(3)); 6.64 (d, 1 H, H(6), J = 8.3 Hz);
6.93 (d, 1 H, H(8), J = 8.3 Hz); 6.98—7.04 (m, 2 H, H(5´),
H(2´)); 7.07 (d, 1 H, H(6´), J = 8.2 Hz); 7.41—7.22 (m, 10 H,
Ph); 7.46 (t, 1 H, H(7), J = 8.3 Hz). 13C NMR (CDCl3), δ:
55.80, 56.10, 70.01 (d, J = 5.8 Hz); 106.73, 109.10, 109.97,
111.63, 116.17, 121.38 (d, J = 3.1 Hz), 124.60, 128.02, 128.67,
128.70, 132.32 (d, J = 1.7 Hz); 132.48, 135.71 (d, J = 7.2 Hz);
138.84 (d, J = 7.3 Hz); 150.84 (d, J = 5.0 Hz); 154.04, 155.55,
157.39, 160.49. 31P NMR (CDCl3), δ: –6.02.
Dibenzyl[2ꢀmethoxyꢀ5ꢀ(5,7ꢀdimethoxyꢀ2ꢀoxochromenꢀ4ꢀ
yl)phenyl]phosphate (7e) was synthesized from compound 6e
(87 mg, 0.265 mmol), dibenzyl phosphite (118 mg, 0.451 mmol),
DIPEA (72 mg, 0.557 mmol), and DMAP (3.3 mg, 0.027 mmol).
Elution with ethyl acetate—petroleum ether (1 : 1) afforded comꢀ
pound 7e in a yield of 105 mg (67%), yellowish oil. 1H NMR
(CDCl3), δ: 3.43, 3.86, 3.87 (both s, 3 H each, OMe); 5.18 (d, 4 H,
OCH2, J = 8.0 Hz); 5.93 (s, 1 H, H(3)); 6.19 (d, 1 H, H(6),
J = 1.8 Hz); 6.51 (d, 1 H, H(8), J = 1.8 Hz); 6.92 (d, 1 H, H(5´),
J = 8.4 Hz); 7.02 (s, 1 H, H(2´)); 7.06 (d, 1 H, H(6´), J = 8.4 Hz);
7.22—7.40 (m, 10 H, Ph). 13C NMR (CDCl3), δ: 55.69, 55.89,
56.09, 69.97, 70.03, 93.64, 95.82, 103.40, 111.59, 112.87, 121.44
(d, J = 3.1 Hz); 124.63, 128.02, 128.67, 128.69, 132.41, 132.42,
135.72 (d, J = 7.3 Hz); 138.78 (d, J = 7.3 Hz); 150.78 (d, J = 4.9 Hz);
154.34, 157.31, 158.31, 160.89, 163.51. 31P NMR (CDCl3),
δ: –6.03.
Dibenzyl[2ꢀmethoxyꢀ5ꢀ(5,6,7ꢀtrimethoxyꢀ2ꢀoxochromenꢀ4ꢀ
yl)phenyl]phosphate (7f) was synthesized from compound 6f
(65 mg, 0.182 mmol), dibenzyl phosphite (82 mg, 0.309 mmol),
DIPEA (49 mg, 0.382 mmol), and DMAP (2.2 mg, 0.018 mmol).
Elution with ethyl acetate—petroleum ether (1 : 1) afforded comꢀ
pound 7f in a yield of 74 mg (66%), yellowish oil. 1H NMR
(CDCl3), δ: 3.26, 3.76, 3.86, 3.94 (all s, 3 H each, OMe); 5.17
(d, 4 H, OCH2, J = 8.1 Hz); 5.98 (s, 1 H, H(3)); 6.71 (s, 1 H,
H(8)); 6.94 (d, 1 H, H(5´), J = 8.7 Hz); 7.10 (dd, 1 H, H(6´),
J = 8.7 Hz, J = 0.7 Hz); 7.11 (d, 1 H, H(2´), J = 0.7 Hz); 7.27—7.35
(m, 10 H, Ph). 13C NMR (CDCl3), δ: 56.13, 56.42, 61.22, 70.01,
70.07, 96.37, 107.21, 111.72, 114.38, 121.18 (d, J = 3.0 Hz);
125.07 (d, J = 1.2 Hz); 128.06, 128.68, 128.71, 131.49 (d,
J = 1.5 Hz); 135.72 (d, J = 7.1 Hz); 138.81 (d, J = 7.2 Hz);
139.58 (d, J = 5.1 Hz); 150.78, 151.16, 151.81, 154.04, 157.02,
160.67. 31P NMR (CDCl3), δ: –5.97.
Compounds 3a—f (general procedure). To a solution of couꢀ
marin dibenzyl phosphite 7 (1 equiv.) in CH2Cl2 (1 mL per
0.07 mmol of 7), trimethylsilyl bromide (6 equiv.) was added
over a period of 40 min. Then 25% MeONa in MeOH (2 equiv.)
was added and the reaction mixture was stirred for 30 min. Reꢀ
moval of the solvent in vacuo and precipitation of the resulted
crystals with acetone from a solution in water resulted in pure
product.
Dibenzyl[2ꢀmethoxyꢀ5ꢀ(2ꢀoxochromenꢀ4ꢀyl)phenyl]phosphꢀ
ate (7a) was synthesized from compound 6a (76 mg, 0.283 mmol),
dibenzyl phosphite (126 mg, 0.482 mmol), DIPEA (77 mg,
0.594 mmol), and DMAP (3.4 mg, 0.028 mmol). Elution with
ethyl acetate—petroleum ether (1 : 1) afforded compound 7a in
a yield of 88 mg (59%), yellowish oil. 1H NMR (CDCl3), δ: 3.88
(s, 3 H, OCH3); 5.19 (dd, 4 H, OCH2, J = 8.3 Hz, J = 3.0 Hz);
6.26 (s, 1 H, H(3)); 7.04 (d, 1 H, H(5´), J = 8.2 Hz); 7.25—7.15
(m, 3 H, H(7), H(8), H(2´)); 7.27—7.37 (m, 10 H, Ph); 7.40
(dd, 1 H, H(6´), J = 8.2 Hz, J = 1.0 Hz); 7.48 (dd, 1 H, H(5),
J = 8.0 Hz, J = 1.4 Hz); 7.54 (dt, 1 H, H(7), J = 8.0 Hz, J = 1.4 Hz).
13C NMR (CDCl3), δ: 56.19, 70.15, 70.20, 112.95, 115.07,
117.43, 118.86, 122.02 (d, J = 3.0 Hz); 124.36, 126.31,
126.99, 127.63, 128.07, 128.69, 128.76, 132.03, 135.53, 135.56
(d, J = 7.0 Hz); 139.85 (d, J = 7.2 Hz); 152.05 (d, J = 5.1 Hz);
154.26 (d, J = 2.3 Hz); 160.78. 31P NMR (CDCl3), δ: –5.93.
Dibenzyl[2ꢀmethoxyꢀ5ꢀ(7ꢀmethoxyꢀ2ꢀoxochromenꢀ4ꢀyl)ꢀ
phenyl]phosphate (7b) was synthesized from compound 6b
(72 mg, 0.242 mmol), dibenzyl phosphite (108 mg, 0.411 mmol),
DIPEA (66 mg, 0.508 mmol), and DMAP (3 mg, 0.028 mmol).
Elution with ethyl acetate—petroleum ether (1 : 1) afforded comꢀ
pound 7b in a yield of 110 mg (81%), yellowish oil. 1H NMR
(CDCl3), δ: 3.87, 3.88 (both s, 3 H each, OCH3); 5.19 (dd, 2 H,
OCH2, J = 8.3 Hz, J = 2.1 Hz); 6.10 (s, 1 H, H(3)); 6.75 (dd, 1 H,
H(6), J = 8.9 Hz, J = 2.1 Hz); 6.88 (d, 1 H, H(8), J = 2.1 Hz);
7.03 (d, 1 H, H(5´), J = 8.4 Hz); 7.19 (s, 1 H, H(2´)); 7.22
(d, 1 H, H(6´), J = 8.4 Hz); 7.35—7.28 (m, 10 H, Ph); 7.37
(d, 1 H, H(5), J = 8.9 Hz). 13C NMR (CDCl3), δ: 55.95, 56.21,
70.16, 70.22, 101.30, 111.79, 112.45, 112.94, 122.00 (d, J = 3.1 Hz);
126.25, 128.00, 128.10, 128.72, 128.79, 135.61 (d, J = 7.0 Hz);
139.84 (d, J = 7.1 Hz); 151.98 (d, J = 4.9 Hz); 154.42, 156.13,
161.29, 162.92. 31P NMR (CDCl3), δ: –5.93.
Dibenzyl[2ꢀmethoxyꢀ5ꢀ(6ꢀmethoxyꢀ2ꢀoxochromenꢀ4ꢀyl)ꢀ
phenyl]phosphate (7c) was synthesized from compound 6c
(49 mg, 0.164 mmol), dibenzyl phosphite (73 mg, 0.279 mmol),
DIPEA (44 mg, 0.344 mmol), and DMAP (2 mg, 0.028 mmol).
Elution with ethyl acetate—petroleum ether (1 : 1) afforded comꢀ
pound 7c in a yield of 57 mg (62%), yellowish oil. 1H NMR
(CDCl3), δ: 3.73, 3.88 (both s, 3 H each, OMe); 5.19 (dd, 4 H,
OCH2, J = 8.3 Hz); 6.27 (s, 1 H, H(3)); 6.95 (d, 1 H, H(5),
J = 2.8 Hz); 7.05 (d, 1 H, H(5´), J = 8.4 Hz); 7.13 (dd, 1 H,
H(7), J = 9.0 Hz, J = 2.8 Hz); 7.21 (s, 1 H, H(2´)); 7.25 (d, 1 H,
H(8), J = 9.0 Hz); 7.28—7.36 (m, 11 H, H(6´), Ph). 13C NMR
(CDCl3), δ: 55.94, 56.18, 70.17, 70.23, 109.37, 113.07, 115.44,
118.40, 119.23, 119.72, 121.98 (d, J = 3.0 Hz); 126.20, 127.73,
127.74, 128.09, 128.71, 128.80, 135.58 (d, J = 6.9 Hz); 139.88
Disodium [2ꢀmethoxyꢀ5ꢀ(2ꢀoxochromenꢀ4ꢀyl)phenyl]phosphꢀ
ate (3a) was synthesized from compound 7a (56 mg, 0.106 mmol),
trimethylsilyl bromide (97 mg, 0.636 mmol), and 25% MeONa

Synthesis of 4ꢀarylcoumarin phosphates
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2007
in MeOH (48 μL) in a yield of 23 mg (54%), colorless crystals,
m.p. 156 °C. 1H NMR (MeOD), δ: 3.93 (s, 3 H, OMe); 6.45
(s, 1 H, H(3)); 7.13 (s, 2 H, H(5´), H(8)); 7.32 (t, 1 H, H(6),
J = 7.7 Hz); 7.39 (d, 1 H, H(6´), J = 8.2 Hz); 7.60 (t, 1 H, H(7),
J = 7.7 Hz); 7.70—7.89 (m, 2 H, H(2´), H(5)). 13C NMR
(MeOD), δ: 56.59 (d, J = 6.9 Hz); 113.29, 115.00 (d, J = 3.5 Hz);
117.97, 120.25, 121.96 (d, J = 2.5 Hz); 123.90, 125.68, 128.58,
128.80, 133.13, 145.16 (d, J = 6.2 Hz); 153.37 (d, J = 5.9 Hz);
155.41, 157.73, 163.06. 31P NMR (MeOD), δ: –0.82.
Disodium [2ꢀmethoxyꢀ5ꢀ(7ꢀmethoxyꢀ2ꢀoxochromenꢀ4ꢀyl)ꢀ
phenyl]phosphate (3b) was synthesized from compound 7b
(76 mg, 0.136 mmol), trimethylsilyl bromide (125 mg, 0.816 mmol),
and 25% MeONa in MeOH (62 μL) in a yield of 51 mg (88%),
colorless crystals, m.p. 195 °C (decomp.). 1H NMR (MeOD),
δ: 3.86, 3.90 (both s, 3 H each, OMe); 6.29 (s, 1 H, H(3));
6.89—6.91 (m, 2 H, H(6), H(8)); 7.03 (d, 1 H, H(5´), J = 8.3 Hz);
7.07 (d, 1 H, H(6´), J = 8.3 Hz); 7.68 (d, 1 H, H(5), J = 8.6 Hz);
7.87 (s, 1 H, H(2´)). 13C NMR (MeOD), δ: 56.41 (d, J = 6.6 Hz);
56.59 (d, J = 6.6 Hz); 101.99, 111.58 (d, J = 4.4 Hz); 112.76,
113.52, 113.81, 121.30, 122.81, 129.13, 126.30, 130.04 (d, J =
= 2.2 Hz); 145.96 (d, J = 5.3 Hz); 152.78 (d, J = 6.7 Hz); 157.22,
158.37, 163.76, 164.49. 31P NMR (MeOD), δ: 1.77.
Disodium [2ꢀmethoxyꢀ5ꢀ(6ꢀmethoxyꢀ2ꢀoxochromenꢀ4ꢀyl)ꢀ
phenyl]phosphate (3c) was synthesized from compound 7c
(55 mg, 0.098 mmol), trimethylsilyl bromide (90 mg, 0.588 mmol),
and 25% MeONa in MeOH (45 μL) in a yield of 33 mg (80%),
colorless crystals, m.p. 195 °C (decomp.). 1H NMR (MeOD),
δ: 3.74, 3.91 (both s, 3 H each, OMe); 6.47 (s, 1 H, H(3));
7.04—7.09 (m, 2 H, H(5´), H(8)); 7.17 (s, 2 H, H(7), H(5)); 7.30
(d, 1 H, H(6´), J = 9.6 Hz); 7.89 (s, 1 H, H(2´)). 13C NMR
(MeOD), δ: 56.35 (d, J = 3.3 Hz); 56.59 (d, J = 3.3 Hz); 110.96,
112.77, 115.44 (d, J = 1.5 Hz); 119.00, 120.69, 120.82, 121.32,
122.72, 128.79, 146.20 (d, J = 5.4 Hz); 149.70, 152.89 (d, J= 6.8 Hz);
157.64, 157.82, 163.41. 31P NMR (MeOD), δ: 1.75.
Disodium [2ꢀmethoxyꢀ5ꢀ(5ꢀmethoxyꢀ2ꢀoxochromenꢀ4ꢀyl)ꢀ
phenyl]phosphate (3d) was synthesized from compound 7d
(50 mg, 0.089 mmol), trimethylsilyl bromide (82 mg, 0.534 mmol),
and 25% MeONa in MeOH (41 μL) in a yield of 32 mg (86%),
colorless crystals, m.p. 201 °C (decomp.). 1H NMR (MeOD),
δ: 3.46, 3.81 (both s, 3 H each, OMe), 6.39 (d, 1 H, H(6´),
J = 8.7 Hz); 6.44 (d, 1 H, H(6), J = 8.3 Hz); 6.58 (d, 1 H, H(8),
J = 8.3 Hz); 6.67—6.77 (m, 2 H, H(3), H(5´)); 7.11 (t, 1 H,
H(7), J = 8.3 Hz); 7.87 (s, 1 H, H(2´)). 13C NMR (MeOD),
δ: 56.04 (d, J = 5.8 Hz); 56.45 (d, J = 9.3 Hz); 104.28 (d, J = 2.0 Hz);
111.69, 113.00, 118.60 (d, J = 3.7 Hz); 120.52, 121.51 (d,
J = 1.7 Hz); 127.61, 129.70, 136.85, 139.78, 144.94 (d, J = 6.0 Hz);
150.87 (d, J = 6.4 Hz); 158.00, 159.97, 177.11. 31P NMR
(MeOD), δ: 2.06.
Disodium [2ꢀmethoxyꢀ5ꢀ(5,6,7ꢀtrimethoxyꢀ2ꢀoxochromenꢀ
4ꢀyl)phenyl]phosphate (3f) was synthesized from compound 7f
(70 mg, 0.113 mmol), trimethylsilyl bromide (104 mg,
0.678 mmol), and 25% MeONa in MeOH (52 μL) in a yield of
48 mg (89%), colorless crystals, m.p. 187 °C (decomp.). 1H MNR
(MeOD), δ: 3.40, 3.66 (both s, 3 H each, OMe); 3.82 (s, 6 H,
OMe); 6.37 (s, 1 H, H(3)); 6.50 (dd, 1 H, H(6´); J = 8.5 Hz,
J = 1.8 Hz); 6.66 (s, 1 H, H(8)); 6.77 (d, 1 H, H(5´), J = 8.5 Hz);
7.80 (d, 1 H, H(2´), J = 1.8 Hz). 13C NMR (MeOD), δ: 56.20,
56.27, 61.19, 61.25, 100.13 (d, J = 5.0 Hz); 111.85, 117.91,
118.34, 119.13, 121.89, 127.76, 137.64, 140.12, 145.09 (d,
J = 5.0 Hz); 151.07 (d, J = 6.5 Hz); 153.21, 154.71, 161.46,
177.05. 31P NMR (MeOD), δ: 2.20.
Dioleyl phosphite. To a stirred solution of oleyl alcohol (2.001 g,
7.5 mmol) and pyridine (0.395 g, 5 mmol, distilled prior to use)
in CH2Cl2, PCl3 (0.343 g, 2.5 mmol) was added dropwise at
0—5 °C. The reaction mixture was stirred for 1.5 h with slow
warming up to ambient temperature. After completion of the
reaction, the mixture was washed with 2 M KH2PO4 and exꢀ
tracted with ethyl acetate, the organic layer was washed with
brine, and dried with anh. Na2SO4. The solvent was removed
in vacuo. Purification of the residue by column chromatography
(silica gel, elution with diethyl ether—petroleum ether, 1 : 1)
afforded dioleyl phosphite in a yield of 1.02 g (70%), transparent
oil. 1H NMR (CDCl3), δ: 0.84 (t, 6 H, Me, J = 6.6 Hz);
1.13—1.44 (m, 44 H, CH2); 1.52—1.75 (m, 4 H, OCH2CH2);
1.82—2.04 (m, 8 H, CH2CH=CHCH2); 4.01 (dd, 4 H, OCH2,
J = 7.3 Hz, J = 14.2 Hz); 5.16—5.41 (m, 4 H, CH=CH); 6.74
(d, 1 H, H—P, JP,H = 692.4 Hz). 13C NMR (CDCl3), δ: 14.1,
22.6, 25.5, 27.1, 27.2, 29.0, 29.1, 29.3, 29.4, 29.5, 29.7, 29.7, 30.3,
30.4, 31.9, 65.7, 129.7, 129.9. 31P NMR (CDCl3), δ: 7.65.
Compounds 8a,d,f (general procedure). A mixture of couꢀ
marin 5 (1 equiv.), DIPEA (7 equiv.), DMAP (0.3 equiv.), and
CCl4 was dissolved in MeCN—CHCl3 (1 : 1) at –10 °C under
argon. Then dioleyl phosphite (5 equiv.) was added dropwise
and the reaction mixture was stirred for 2 h. After completion of the
reaction, the mixture was washed with 2 M KH2PO4, extracted
with ethyl acetate, the organic layer was washed with water,
brine, dried with anh. Na2SO4, and the solvent was removed
in vacuo. The product was purified by column chromatography
(silica gel, elution with petroleum ether—ethyl acetate, 2 : 1).
Dioleyl[2ꢀmethoxyꢀ5ꢀ(2ꢀoxochromenꢀ4ꢀyl)phenyl]phosphate
(8a) was synthesized from compound 5a (89 mg, 0.332 mmol),
dioleyl phosphite (968 mg, 1.66 mmol), DIPEA (300 mg, 2.324
mmol), DMAP (12 mg, 0.01 mmol), CCl4 (0.75 mL), MeCN
0.75 mL), and CHCl3 (0.75 mL) in a yield of 189 mg (67%),
yellowish oil. 1H NMR (CDCl3), δ: 0.87 (t, 6 H, Me(Oleyl),
J = 6.8 Hz); 1.17—1.45 (m, 44 H, CH2(Oleyl)); 1.64—1.76
(m, 4 H, OCH2CH2); 1.92—2.07 (m, 8 H, CH2CH=CHCH2);
3.95 (s, 3 H, OMe); 4.12—4.24 (m, 4 H, OMe); 5.27—5.42 (m, 4 H,
CH=CH); 6.36 (s, 1 H, H(3)); 7.08 (d, 1 H, H(5´), J = 8.5 Hz);
7.21—7.30 (m, 2 H, H(6), H(8)); 7.39—7.42 (m, 2 H, H(7),
H(6´)); 7.51—7.61 (m, 2 H, H(2´), H(5)). 13C NMR (CDCl3),
δ: 14.25, 22.81, 25.56, 27.34 (d, J = 3.5 Hz); 29.00—30.03 (m);
30.34, 30.41, 32.04, 32.73 (d, J = 2.9 Hz); 56.26, 68.87 (d, J =
= 6.3 Hz); 113.00, 115.14, 117.52, 118.95, 121.98 (d, J = 2.8 Hz);
127.73 (d, J = 1.6 Hz); 124.37, 126.17, 127.04, 129.87, 130.13,
132.07, 140.22, 152.16, 154.38 (d, J = 4.0 Hz); 160.83. 31P NMR
(CDCl3), δ: –5.7.
Disodium [2ꢀmethoxyꢀ5ꢀ(5,7ꢀdimethoxyꢀ2ꢀoxochromenꢀ4ꢀ
yl)phenyl]phosphate (3e) was synthesized from compound 7e
(48 mg, 0.081 mmol), trimethylsilyl bromide (74 mg, 0.486 mmol),
and 25% MeONa in MeOH (37 μL) in a yield of 29 mg (79%),
colorless crystals, m.p. 257 °C (decomp.). 1H NMR (MeOD), δ:
3.44, 3.75, 3.81 (all s, 3 H each, OMe); 5.98 (s, 1 H, H(6)); 6.13
(s, 1 H, H(8)); 6.47 (d, 1 H, H(5´), J = 8.4 Hz); 6.66 (s, 1 H,
H(3)); 6.72 (d, 1 H, H(6´), J = 8.4 Hz); 7.84 (s, 1 H, H(2´)).
13C NMR (MeOD), δ: 55.53 (d, J = 7.8 Hz); 56.01 (d, J = 5.1 Hz);
56.50 (d, J = 8.3 Hz); 91.30, 98.03—97.84 (m); 111.79, 113.20,
118.64, 121.70, 127.31, 137.33, 140.29, 144.90 (d, J = 6.0 Hz);
150.81 (d, J = 6.5 Hz); 160.52, 162.22, 177.32. 31P NMR
(MeOD), δ: 2.19.
Dioleyl[2ꢀmethoxyꢀ5ꢀ(5ꢀmethoxyꢀ2ꢀoxochromenꢀ4ꢀyl)ꢀ
phenyl]phosphate (8d) was synthesized from compound 5d

2008
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
Selikhov et al.
(44 mg, 0.148 mmol), dioleyl phosphite (431 mg, 0.74 mmol),
DIPEA (134 mg, 1.036 mmol), DMAP (5.4 mg, 0.044 mmol),
CCl4 (0.3 mL), MeCN (0.3 mL), and CHCl3 (0.3 mL) in a yield
of 79 mg (61%), yellowish oil. 1H NMR (CDCl3), δ: 0.87 (t, 6 H,
Me(Oleyl), J = 6.8 Hz); 1.18—1.43 (m, 44 H, CH2(Oleyl)); 1.68
(dt, 4 H, OCH2CH2, J = 13.7 Hz, J = 6.8 Hz); 1.91—2.07 (m, 8 H,
CH2CH=CHCH2); 3.56, 3.92 (both s, 3 H each, OMe); 4.09—4.22
(m, 4 H, OCH2); 5.27—5.41 (m, 4 H, CH=CH); 6.16 (s, 1 H,
H(3)); 6.68 (d, 1 H, H(6), J = 8.3 Hz); 6.95 (d, 1 H, H(8),
J = 8.3 Hz); 7.00 (d, 1 H, H(5´), J = 8.4 Hz); 7.09 (dd, 1H,
H(6´), J = 8.4 Hz, J = 1.7 Hz); 7.22 (s, 1 H, H(2´)); 7.45 (t, 1 H,
H(7), J = 8.3 Hz). 13C NMR (CDCl3), δ: 14.26, 22.82, 25.59,
27.34 (d, J = 3.1 Hz); 29.28—29.90 (m); 30.34, 30.41, 32.04,
55.89, 56.12, 68.71 (d, J = 6.5 Hz); 106.70, 110.04, 111.59,
116.25, 121.33 (d, J = 2.8 Hz); 124.49, 129.87, 130.13, 132.51,
139.07 (d, J = 7.0 Hz); 150.89 (d, J = 5.2 Hz); 154.19, 155.59,
157.45, 160.54. 31P NMR (CDCl3), δ: –5.77.
Dioleyl[2ꢀmethoxyꢀ5ꢀ(5,6,7ꢀtrimethoxyꢀ2ꢀoxochromenꢀ4ꢀ
yl)phenyl]phosphate (8f) was synthesized from compound 5f
(53 mg, 0.148 mmol), dioleyl phosphite (431 mg, 0.74 mmol),
DIPEA (134 mg, 1.036 mmol), DMAP (5.4 mg, 0.044 mmol),
CCl4 (0.3 mL), MeCN (0.3 mL), and CHCl3 (0.3 mL) in a yield
of 96 mg (69%), yellowish oil. 1H NMR (CDCl3), δ: 0.87 (t, 6 H,
Me(Oleyl), J = 6.8 Hz); 1.14—1.45 (m, 44 H, CH2(Oleyl)); 1.68
(dt, 4 H, OCH2CH2, J = 14.1 Hz, J = 6.9 Hz); 1.93—2.04 (m, 8 H,
CH2CH=CHCH2); 3.33, 3.79, 3.91, 3.93 (all s, 3 H each, OMe);
4.11—4.21 (m, 4 H, OCH2); 5.27—5.40 (m, 4 H, CH=CH);
6.04 (s, 1 H, H(3)); 6.70 (s, 1 H, H(8)); 6.96 (d, 1 H, H(5´),
J = 8.4 Hz); 7.11 (dd, 1 H, H(6´), J = 8.4 Hz, J = 2.0 Hz); 7.28
(s, 1 H, H(2´)). 13C NMR (CDCl3), δ: 14.24, 22.81, 25.57, 27.33
(d, J = 2.4 Hz); 29.01—30.08 (m); 30.33, 30.40, 32.03, 56.15,
56.38, 61.23 (d, J = 5.7 Hz); 68.75 (d, J = 6.2 Hz); 96.40, 107.25,
111.70, 114.41, 121.11 (d, J = 2.9 Hz); 124.93, 129.87, 130.11,
131.54, 151.21, 151.83, 154.18, 157.02, 160.68. 31P NMR
(CDCl3), δ: –5.80.
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This work was financially supported by the Russian
Foundation for Basic Research (Projects Nos 09ꢀ03ꢀ
00647ꢀa and № 11ꢀ03ꢀ97034ꢀp_povolzhie_a), and the
Council for Grants at the President of the Russian Federꢀ
ation (the Program for the State Support of Young Scienꢀ
tistsꢀDoctors of Sciences, Grant MDꢀ5606.2010.3).
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Received May 5, 2011;
in revised form September 4, 2011