Synthetic transformations of higher terpenoids: XXXII.*synthesis of 16-alkenyl-substituted labdatrienes by oxidative coupling of methyl phlomisoate with alkenes

Article abstract of DOI:10.1134/S1070428013110225

Reactions of methyl phlomisoate with methyl acrylate, phenyl acrylate, methyl vinyl ketone, phenyl vinyl ketone, or N-substituted acrylamides catalyzed by Pd(OAc)2 in the presence of Cu(OAc)2, p-benzoquinone in the mixture of propionic acid and acetonitrile proceed regio- and stereoselectively with the formation of (E)- 16-vinyl labdatrienoates. The oxidative coupling under these conditions of the methyl phlomisoate with styrene results in a mixture of 15,16-distyryl-, 16-styryl-, and 16-(1-phenylvinyl)-derivatives of furanolabdanoid. Pleiades Publishing, Ltd., 2013.

Full text of DOI:10.1134/S1070428013110225

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 11, pp. 1690−1702. © Pleiades Publishing, Ltd., 2013.
Original English Text © Yu.V. Kharitonov, O.I. Kremenko, E.E. Shults, M.M. Shakirov, G.A. Tolstikov, 2013, published in Zhurnal Organicheskoi Khimii, 2013,
Vol. 49, No. 11, pp. 1707−1718.
Synthetic Transformations of Higher Terpenoids: XXXII.*
Synthesis of 16-Alkenyl-Substituted Labdatrienes
by Oxidative Coupling of Methyl Phlomisoate with Alkenes
Yu. V. Kharitonov, O. I. Kremenko, E. E. Shults, M. M. Shakirov, and G. A. Tolstikov†
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences,
Novosibirsk, 630090 Russia
e-mail: schultz@nioch.nsc.ru
Received April 24, 2013
Abstract—Reactions of methyl phlomisoate with methyl acrylate, phenyl acrylate, methyl vinyl ketone, phenyl
vinyl ketone, or N-substituted acrylamides catalyzed by Pd(OAc)2 in the presence of Cu(OAc)2, p-benzoquinone
in the mixture of propionic acid and acetonitrile proceed regio- and stereoselectively with the formation of (E)-
16-vinyl labdatrienoates. The oxidative coupling under these conditions of the methyl phlomisoate with styrene
results in a mixture of 15,16-distyryl-, 16-styryl-, and 16-(1-phenylvinyl)-derivatives of furanolabdanoid.
DOI: 10.1134/S1070428013110225
We formerly demonstrated by an example of the oxi- mixture of propionic acid and acetonitrile, 1 : 1, in the
dative coupling of methyl phlomisoate (I) with styrene presence of Pd(OAc)2/Cu(OAc)2/ BQ/O2 (35°C, 10 h) led
(II) (2 equiv) or with excess methyl acrylate (III) the to the formation of a mixture of methyl 15,16-distyryl-
possibility to modify labdanoid I at the furan fragment (IV), 16-(1-phenylvinyl )- (V), and 16-styryl-15,16-ep-
with the introduction of an alkenyl substituent in the po- oxylabdatrienoates (VI) in a ratio 1 : 4.5 : 1. Compounds
sitions С15 and С16 labdane skeleton. The reaction with IV (yield 4%) and VI (yield 4%) were isolated in an
styrene (II) in the presence of 0.1 equiv of Pd(OAc)2, individual state. The main reaction product V (yield 18%,
0.5 equiv of Cu(OAc)2, and 0.1 equiv of 1,4-benzoqui- according to 1Н NMR data) suffered further transforma-
none (BQ) in a mixture of propionic acid and ether, 1 : 1 tions in the course of the column chromatography. At the
(35°C, 10 h) in an oxygen atmosphere afforded methyl reaction in the mixture of the propionic acid and DMF, 1 :
(E)-15,16-distyryl-15,16-epoxylabdatrienoate (IV) (yield 1, (35°С, 15 h) the conversion reached 68%, compounds
63%) (Scheme 1) [2]. The yield of the products of the IV and VI were isolated in an individual state (yield 5
Pd-catalyzed cross-coupling reaction of the substituted and 7% respectively).
furans with styrene (II) and the other alkenes is consider-
ably affected by the nature of the solvent [3, 4] and by
the composition of the oxidizing system [5, 6]. It seemed
therefore reasonable to investigate the effect of the co-
solvent, the composition of the oxidation system, and
the alkene nature on the yield and the composition of the
products of the oxidative coupling of methyl phlomisoate
acid (I) with terminal alkenes and to obtain new alkenyl-
substituted furanolabdanoids.
The replacement of the cosolvent made it possible to
change the selectivity of the reaction between labdatriene I
and methyl acrylate (III). Whereas at the reaction of com-
pounds I and III in the mixture of propionic acid and ether,
1 : 1, (35°C, 80 h) in the presence of 0.1 equiv of Pd(OAc)2,
0.5 equiv of Cu(OAc)2, 0.1 equiv of (BQ) in the atmo-
sphere of O2 methyl ethers were isolated of 15,16-bis(2-
methoxycarbonylvinyl)- (VII), 16-(2-methoxycarbonyl-
vinyl)- (VIII), and 15-(2-methoxycarbonylvinyl)-15,16-
The reaction of compound I with styrene (II) in a epoxylabdatrien-18-oic acid (IX) (yield 27, 17, and 7%,
___________
* For Communication XXXI, see [1].
respectively) [2], the reaction carried out in the solvents
mixture propionic acid–acetonitrile, 1 : 1, afforded com-
†
Deceased.
1690

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XXXII.
1691
pounds VIII and VII (yield 54 and 5%).
(calculated with respect of two stages) by the formylation
of methyl phlomisoate (I) followed by the condensation
of 16-formyllabdatrienoate with acetone.
By an example of the reaction of furanolabdanoid I
with methyl acrylate (III) we found the significant ef-
fect of the composition of the oxidative system on the
products yield and the selectivity of the reaction. The
reaction of compound I with 1 equiv of methyl acrylate
(III) in the mixture of propionic acid and ether in an argon
atmosphere in the presence of 0.05 equiv of Pd(OAc)2,
2 equiv of Cu(OAc)2, and 0.1 equiv of BQ resulted in the
formation of the alkenyl derivatives VII, VIII, IX in the
ratio 1 : 5 : 1. The replacement of the cosolvent (ethyl
ether for acetonitrile) the regioselectivity of the reaction
increased. Under the identical experimental conditions
(40°С, 80 h) 18-methyl-16-(2-methoxycarbonylvinyl)
labdatrienoate (VIII) was obtained as a single reaction
product (yield 34% after the column chromatography;
besides, 7% of initial compound I was isolated).
We explored the reaction of labdanoid I with acryl-
amides XVI–XXI. The corresponding 18-methyl-16-
(E)-[3-(R-amino)-3-oxoprop-1-en-1-yl]labdatrienoates
XXIII–XXVII were isolated as individual substances
by column chromatography on silica gel. The maxi-
mum yield was obtained by the oxidative coupling of
furanolabdanoid I with N-arylacrylamides XVI, XVII;
the yield of compounds XXII, XXIII was 59 and 42%.
In the reactions of diterpenoid I with amides prepared
from the methyl esters of amino acids XIX–XXI, and
also with N-acryloylmorpholine (XXVIII) the consider-
able decrease in the yield was observed of the products
of 16-alkenylation XXV–XXVII, XXIX (16–25 and
8%). The replacement of the cosolvent in the reaction
of compound I with amides XIX–XXI did not result in
the increase of the overall yield of the reaction products.
The oxidative coupling of compound I with phenyl
acrylate (X), methyl vinyl ketone (XI), or phenyl vinyl
ketone (XII) in the presence of 0.05 equiv of Pd(OAc)2,
2 equiv of Cu(OAc)2, and 0.1 equiv of BQ in propionic
acid and acetonitrile, 1 : 1, (35°C, 80 h) led to the forma-
tion of 18-methyl-16-(E)-(2-R-carbonylvinyl)labdatrie-
noates XIII–XV in 29–54% yield (Scheme 2). Compound
XIV was obtained previously [7] in a comparable yield
Taking into consideration valuable pharmacological
properties of 2,5-dialkenylfurans [8, 9], we investigated
the possibility of successive introducing vinyl groups into
labdanoid derivatives with various alkenyl substituents.
The reaction of 16-(2-methoxycarbonylvinyl)labdatrieno-
ate (VIII) with styrene (II) in the presence of 0.1 equiv of
Scheme 1.
R
R
16
12
13
14
O
11
20
15
17
1
4
a_г
9
O
10
5
2
3
8
+
R
7
6
H
19
CO2Me
H
18
CO2Me
II, III
I
IV, VII
R1
R2
1'
2'
O
+
O
+
CO2Me
H
CO2Me
H
CO2Me
IX
V, VI, VIII
R = Ph (II, IV), CO2Me (III, VII); R1 = Ph, R2 = H (V); R1 = H, R2 = Ph (VI), CO2Me (VIII); a. Pd(OAc)2, Cu(OAc)2,
BQ, O2, EtCO2H–Et2O, 1 : 1; b. Pd(OAc)2, Cu(OAc)2, BQ, O2, EtCO2H–MeCN, 1 : 1; c. Pd(OAc)2, Cu(OAc)2, BQ, Et-
CO2H–Et2O, 1 : 1; г. Pd(OAc)2, Cu(OAc)2, BQ, EtCO2H–MeCN, 1 : 1.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

KHARITONOV et al.
1692
Scheme 2.
O
O
NHR'
R
NHR'
R
O
O
X_XII, XXVIII
XVI_XXI
O
O
I
a, b
a, b
H
H
CO2CH3
CO2CH3
XIII_XV, XXIX
XXII_XXVII
R = OPh (X, XIII), Me (XI, XIV), Ph (XII, XV), morpholin-4-yl (XXVIII, XXIX); R' = Ph (XVI, XXII), 4-MeC6H4
(XVII, XXIII), Bn (XVIII, XXIV), CH(Me)CO2Me (XIX, XXV), CH(Ph)CH2CO2Me (XX, XXVI), CH(Et)CO2Me (XXI,
XXVII); a. Pd(OAc)2, Cu(OAc)2, BQ, EtCO2H–MeCN, 35°C; b. Pd(OAc)2, Cu(OAc)2, BQ, O2, EtCO2H–Et2O, 35°C.
Pd(OAc)2, 0.5 equiv of Cu(OAc)2, and 0.1 equiv of BQ
in the mixture of propionic acid and ether, 1 : 1, (35°C,
80 h) in the atmosphere of O2 furnished 15-styryl-16-
(2-methoxycarbonylvinyl)labdatrienoate (XXX) (yield
10%) (Scheme 3). The conversion of compound VIII was
50%. As seen, the presence of an acceptor substituent in
the position 2 of the furan ring imparts the subsequent
introduction of a substituent into the position 5.
of pentane-1,5-diyl diacrylate (XXXI) in the presence
of 0.1 equiv of Pd(OAc)2, 0.5 equiv of Cu(OAc)2, and
0.1 equiv of BQ in the mixture of propionic acid and ether,
1 : 1, (35°C, 80 h) in the oxygen atmosphere led to the
formation of monocoupling product XXХII isolated by
column chromatography in 10% yield. The reaction of
diterpenoid I with N,N'-hexane-1,6-diyl(bisacrylamide)
(XXXIII) under similar conditions gave besides 16-ac-
ryloylamino derivative (XXXIV) (yield 26%) a coupling
The reaction of methyl phlomisoate (I) with 1 equiv
Scheme 3.
O
1'
2'
a
O
VIII
+
II
2"
1"
Ph
H
CO2CH3
XXX
O
CONH(CH2)6NH
O
O
X
1"
1''
2"
2''
X
X
(CH2)n
X
( )n
1'
2'
16
15
16'
13'
14'
12
12'
13
14
11
O
O
O
20
11'
O
20'
15'
O
XXXI, XXXIII
17
17'
1
1'
4'
9
6
I
9'
10
2
3
2'
3'
a
10'
5'
8
7
8'
7'
5
4
6'
H
H
H
19'
19
CO2Me
CO2CH3
CO2Me
18'
18
XXXII, XXXIV
XXXV
X = O, n = 5 (XXXI, XXXII); X = NH, n = 6 (XXXIII, XXXIV); a. Pd(OAc)2/BQ/Cu(OAc)2/O2, EtCO2H/Et2O, 35°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XXXII.
1693
1
product by both double bonds XXXV (yield 2%).
hexane linker in the Н NMR spectrum and the proton
signals of the 16-(N-alkenyl)furanolabdane fragment in
the product of double coupling XXXV equals 1 : 2.
The structure and composition of compounds synthe-
sized were confirmed by IR, UV, NMR, and mass spectra
and by elemental analysis. The introduction of alkenyl
substituents into the furan ring of labdanoids VI, XIII,
XXII–XXIV, XXVII, XXX results in the appearance in
the UV spectra of two absorption bands with the maxima
in the regions 236–285 and 307–334 nm.
Hence based on the oxidative coupling of methyl
phlomisoate with the activated alkenes we synthesized
diverse 16-(Е)-alkenyl-substituted furanolabdanoids.
Performing the reaction in the presence of the catalytic
system Pd(OAc)2/Cu(OAc)2/BQ and the application
of acetonitrile as the cosolvent results in the increased
regioselectivity of the reaction of methyl phlomisoate
with methyl acrylate or styrene The largest yields of
the oxidative coupling products were obtained in the
reactions of the furanolabdanoid with vinyl ketones and
acrylamides.
1Н and 13С NMR spectra of compounds V, VI, XIII,
XV, XXII–XXVII, XXIX, XXX, XXXII, XXXIV are
in complete agreement with their assumed structure and
contain a single set of the characteristic signals of the
furanolabdane scaffold and of the corresponding sub-
stituent. The position of substituents at the atom С16 in
the monosubstituted labdanoids V, VI, VIII, XIII–XV,
XXII–XXVII, XXIX, XXXII, XXXIV, XXXV is con-
The interest to the development of methods of
preparation furan derivatives containing alkenyl
fragments in the positions 2 and 5 is due to the valuable
biological properties of a number of inaccessible furan
metabolites [10].
1
firmed by the data of Н NMR spectra containing the
proton signals of the furan ring [δ 6.31–6.42 ppm (H14)
and 7.31–7.40 ppm (H15), J 1.6–1.9 Hz]. The presence
of the (1-phenyl)vinyl substituent in the position С16 of
compound V is indicated by the doublet signals of the
protons of the terminal vinyl group Н2'А,2'В (δ 5.44 and
5.51 ppm, J 1.1 Hz). These data unambiguously prove
the regioselectivity of the reaction.
EXPERIMENTAL
1Н and 13С NMR spectra were registered on spec-
trometers Bruker AV-300 [operating frequencies 300.13
(1Н) and 75.47 MHz (13С)], Bruker AV-400 [operating
frequencies 400.13 (1Н) and 100.78 MHz (13С)], Bruker
AV-600 [operating frequencies 600.30 (1Н) and 150.96
MHz (13С)] from solutions of compounds in CDCl3, refer-
ence TMS. In the description of 1Н and 13С NMR spectra
the numeration of the labdane scaffold corresponds to
that shown for structure I. The assignment of NMR
signals was performed using various 2D proton-proton
and proton-carbon correlation spectra (СOSY, COXH,
COLOC). The multiplicity of signals in the 13С NMR
spectra was established by registering spectra in the
J modulation mode.
The protons of the double bond H1',2' in the 1Н NMR
spectra of compounds XIII–XV, XXII–XXVII,
XXIX, XXXII, XXXIV, and also the protons H1'',2'' of
compound XXXV appear as doublets in the region δ
7.35–7.55 and 6.20–6.68 ppm respectively. The value
J(H1', Н2' ) [J(H1”,2”)] in the 16-substituted labdanoids
equals 14.8–15.8 Hz indicating the trans-position of
the protons. The protons of the double bond H1',2' in the
spectrum of compound VI are observed at δ 7.00 and
6.91 ppm respectively (J 16.1 Hz). The characteristic
features of the 1Н NMR spectrum of 13,15,16-substituted
furanolabdanoid XXX are a singlet signal of the proton
H14 (δ 6.39 ppm) and two pairs of doublet proton signals
from the double bonds of 3-oxobut-1-ene [δ 6.66 m (Н2'),
δ 7.30 ppm (Н1'), J 15.4 Hz] and styrene substituents
[δ 6.83 (Н2"), δ 7.17 ppm (Н1"), J 16.4 Hz]. The reported
data prove the (E)-configuration of the double bond
С1'=С2' in compounds VI–IX, XIII–XV, XXII–XXVII,
XXIX, XXXII, XXXIV and С1'=С2', С1"=С2" in
compounds XXX, XXXV. The relative simplicity of the
1Н and 13С NMR spectra of compound XXXV containing
a single set of proton and carbon signals of the labdane
scaffold and the trans-double bond of the acrylamide
substituent demonstrates the symmetry of the molecule.
The ratio of the integral intensities of the protons of the
Recording of mass spectra, the determination of the
molecular mass and elemental composition of compounds
was carried out using high-resolution mass spectrometer
DFS Thermo Scientific (EI 70 eV, vaporizer temperature
230–280°С). Elemental analysis was performed on a
СНN-analyzer Carlo Erba 1106.
The values of specific rotation [α]D20 were measured
on a polarimeter poLAAr 3005 at room temperature
(20–23°С). IR spectra were recorded on a spectropho-
tometer Vector-22 from pellets with KВr. UV absorption
spectra were taken on a spectrophotometer HР 8453 UV
Vis in ethanol (с 10–4 mol L−1).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

KHARITONOV et al.
1694
The monitoring of the reaction progress and checking
6.27 d.d (1Н, СН2=, J 17.1, 1.6 Hz).
the purity of compounds obtained was performed by TLC
on Silufol UV-254 plates, eluents: chloroform–ethanol,
3 : 1; petroleum ether–ethyl acetate, 10 : 1. The spots
visualization was carried out by spraying on the plates
10% aqueous H2SO4 followed by heating to 100°C or
by UV irradiation.
Reaction of methyl phlomisoate with styrene. а.
To a solution of 1.00 g (3.03 mmol) of methyl phlomiso-
ate (I) in a mixture of 4 mL of propionic acid and 4 mL
of acetonitrile while stirring was added in succession
0.35 mL(3.03 mmol) of styrene (II), 0.046 g (0.15 mmol)
of Pd(OAc)2, 0.275 g (1.51 mmol) of Cu(OAc)2, and
0.03 g (0.30 mmol) of 1,4-benzoquinone. The reaction
mixture was stirred in an oxygen flow at 35°С for 10 h,
then it was cooled and poured into 30 mL of water, the
reaction products were extracted with chloroform (3 ×
40mL). The combined organic solutions were washed
with water (3 × 50 mL) and dried with MgSO4. The
solvent was removed in a vacuum, the residue was
chromatographed on a column packed with silica gel
(eluent petroleum ether–ethyl ether, 10 : 1). The elution
provided in succession 0.29 g (22%) of a mixture of
methyl esters of 16-(1-phenylvinyl)- (V) and 16-[(Е)-
styryl]-15,16-epoxy-8(9),13(16),14-labdatrien-18-oic
Methyl phlomisoate (I) was obtained by procedure
[11], Pd(OAc)2, by method [12]. Commercially availably
reagents styrene (II), methyl acrylate (III), and methyl
vinyl ketone (XI) were used in the study without addi-
tional purification. Phenyl acrylate (X) [13], vinyl phenyl
ketone (XII) [14], N,N'-(hexane-1,6-diyl)bisacrylamide
(XXXIII) [15] were prepared by known procedures. The
physicochemical characteristics of N,N'-(hexane-1,6-
diyl)bisacrylamide (XXXIII) were consistent with the
published data [16].
Amides XVI–XXI, XXVIII and pentane-1,5-diyl
diacrylate (XXXI). General procedure. To a solution of
10.0 mmol of amine (pentane-1,5-diol) and 15.0 mmol
of acryloyl chloride in 20 mL of dichloromethane at
0°С under an argon atmosphere was added dropwise
while stirring 30.0 mmol of triethylamine in 10 mL of
dichloromethane. The reaction mixture was warmed to
room temperature and stirred for 6 h. The solvent was
removed in a vacuum, the residue was diluted with 20 mL
of ether, the precipitated salt Et3N·HCl was filtered off.
The mother liquor was evaporated in a vacuum, as the
residue were obtained the corresponding amides XVI–
XXI, XXVIII or pentane-1,5-diyl diacrylate (XXXI) in
60–90% yields. The physicochemical constants of anilide
of acrylic acid (XVI), N-(p-tolyl)acrylamide (XVII),
N-benzylacrylamide (XVIII), methyl 2-(acryloylami-
nopropanoate (XIX), 4-acryloylmorpholine (XXVIII),
and pentane-1,5-diyl diacrylate (XXXI) are published
in [16–21].
1
acids (VI) in a ratio 4.5 : 1 as showed Н NMR data
(fraction 1), and 0.065 g (4%) of methyl 15,16-bis[(Е)-
styryl]-15,16-epoxy-8(9),13(16),14-labdatrien-18-oate
(IV). The repeated chromatography of the fraction 1 on a
column with silica gel afforded methyl (1S,4aS,8aR)-5-
(2-{2-[(Е)-styryl]-furan-3-yl}ethyl)-1,4a,6-trimethyl-
1,2,3,4,4a,7,8,8a-octahydronaphthalene-1-carboxylate
{methyl 16-[(Е)-styryl)]-15,16-epoxy-8(9),13(16),14-
labdatriе-18-oate} (VI), oily substance. IR spectrum,
cm–1: 3433, 2955, 2932, 2873, 1723, 1602, 1459, 1381,
1235, 1153, 974, 956, 847, 753, 694. UV spectrum, λmax
,
1
nm (logε): 285 (3.95), 334 (3.78). Н NMR spectrum,
δ, ppm: 0.80 s (3H, С20Н3), 1.06 d.t (1Н, Н3, J 13.7,
4.2 Hz), 1.23 s (3Н, С19Н3), 1.28 m (1Н, Н1), 1.38 d.d
(1H, H5, J 12.7, 1.7 Hz), 1.59 m (1H, H2), 1.70 s (3H,
С17Н3), 1.75 d.d (1Н, Н6, J 12.7, 6.8 Hz), 1.80–1.92 m
(1Н, H2), 1.94–2.01 m (3H, H1,7,6), 2.04–2.14 m (2H,
H7,11), 2.22–2.29 m (2Н, Н3,11), 2.55 m (2H, H12,12), 3.64 s
(3Н, ОСН3), 6.35 d (1H, H14, J 1.7 Hz), 6.91 d (1Н, Н2',
J 16.1 Hz), 7.00 d (1Н, Н1', J 16.1 Hz), 7.23 t.m (1Н,
Н4'', J 7.6 Hz), 7.34 t (3Н, Н15, Н3'',5'', J 7.6 Hz), 7.49 d.d
(2Н, Н2",6”, J 7.6, 1.2 Hz). 13C NMR spectrum, δ, ppm:
17.69 q (C20), 19.55 t (C2), 19.82 q (C17), 20.75 t (C6),
25.58 t (C12), 28.36 q (C19), 29.27 t (C11), 34.21 t (C7),
37.23 t (C1), 37.64 t (C3), 39.54 s (C10), 43.82 s (C4),
51.03 q (ОСН3), 53.43 d (С5), 112.55 d (C14), 114.51 d
(С1'), 124.09 s (C13), 125.42 d (С2'), 125.99 d (С6",2”),
127.17 d (С4"), 127.49 s (C8), 127.31 d (С3"), 128.59 d
(С5"), 137.34 s (С1"), 138.51 s (C9), 141.47 d (С15),
Methyl 3-acryloylamino-3-phenylpropanoate (XX).
Oily substance. 1Н NMR spectrum, δ, ppm: 2.81 d.d (1Н,
СН2, J 15.9, 5.9 Hz), 2.92 d.d (1Н, СН2, J 15.9, 5.9 Hz),
3.55 s (3Н, ОСН3), 5.46 t (1Н, СН, J 5.9 Hz), 5.59 d.d
(1Н, СН2=, J 10.2, 1.6 Hz), 6.11 d.d (1Н, СН=, J 16.9,
10.2 Hz), 6.24 d.d (1Н, СН2=, J 16.9, 1.6 Hz), 7.22 m,
7.26 m (5Н, Ph).
Methyl 2-acryloylaminobutanoate (XХI). Oily
1
substance. Н NMR spectrum, δ, ppm: 0.88 t (3Н,
СН3, J 7.3 Hz), 1.72 m, 1.89 m (2Н, СН2), 3.71 s
(3Н, ОСН3), 4.61 m (1Н, СН), 5.63 d.d (1Н, СН2=,
J 10.0, 1.6 Hz), 6.14 d.d (1Н, СН=, J 17.1, 10.0 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XXXII.
1695
148.17 s (C16), 177.96 s (C18). Found, %: С 80.22; H 8.65.
C29H36O3. Calculated, %: С 80.52; H 8.39.
silica gel (eluent petroleum ether–ethyl ether, 4 : 1).
The successive elution afforded 1.08 g (54%) of methyl
esters of 16-(3-methoxy-3-oxoprop-1-yl)- (VIII) and
0.45 g (5%) of 15,16-bis(3-methoxy-3-oxoprop-1-en-
1-yl)-15,16-epoxy-8(9),13(16),14-labdatrien-18-oic
VII) acids.
Methyl (1S,4aS,8aR)-5-{2-[2-(1-phenylvinyl)
furan-3-yl]ethyl}-1,4a,6-trimethyl-1,2,3,4,4a,7,8,8a-
octahydronaphthalene-1-carboxylate (V) we failed to
isolate as individual substance due to its instability dur-
1
ing chromatographic separation. Н NMR spectrum of
b. To a solution of 2.00 g (6.06 mmol) of methyl
phlomisoate (I) in a mixture of 8 mL of propionic acid
and 8 mL of ethyl ether while stirring was added in suc-
cession 0.56 mL (6.06 mmol) of methyl acrylate (III),
0.09 g (0.30 mmol) of Pd(OAc)2, 2.20 g (12.1 mmol) of
Cu(OAc)2, and 0.07 g (0.60 mmol) of 1,4-benzoquinone.
The reaction mixture was intermittently stirred in an argon
flow at 40°С for 80 h, it was poured into 30 mL of water,
the reaction products were extracted with chloroform (3 ×
50 mL). The combined organic solutions were washed
with water (3 × 50 mL) and dried with MgSO4. The sol-
vent was removed in a vacuum, the residue consisted of a
mixture of compounds VII, VIII, and IX in a ratio 1 : 5 : 1.
compound V (extracted from the spectrum of the mixture
of compounds V and VI), δ, ppm: 0.80 s (3H, С20Н3),
1.06 d.t (1Н, Н3, J 13.7, 4.2 Hz), 1.23 s (3Н, С19Н3),
1.28 m (1Н, Н1), 1.38 d.d (1H, H5, J 12.7, 1.7 Hz), 1.59 m
(1H, H2), 1.69 s (3H, С17Н3), 1.75 d.d (1Н, Н6, J 12.7,
6.8 Hz), 1.80–1.92 m (1Н, H2), 1.94–2.01 m (3H, H1,7,6),
2.04–2.14 m (2H, H7,11), 2.22–2.29 m (2Н, Н3,11), 2.55 m
(2H, H12,12), 3.62 s (3Н, ОСН3), 5.44 d (1Н, Н2'А, J 1.1 Hz),
5.51 d (1Н, Н2'В, J 1.1 Hz), 6.38 d (1H, H14, J 1.6 Hz),
7.23 t.m (1Н, Н4", J 7.6 Hz), 7.34 m (3Н, Н15, Н3",5”
J 7.6 Hz), 7.49 d.d (2Н, Н2",6”, J 7.6, 1.2 Hz).
,
b. To a solution of 1.00 g (3.03 mmol) of methyl
phlomisoate (I) in a mixture of 4 mL of propionic acid
and 4 mL of DMF while stirring was added in succession
0.35 mL(3.03 mmol) of styrene (II), 0.046 g (0.15 mmol)
of Pd(OAc)2, 0.275 g (1.51 mmol) of Cu(OAc)2, and
0.03 g (0.30 mmol) of 1,4-benzoquinone. The reaction
mixture was stirred in an oxygen flow at 35°С for 10 h,
then it was cooled and poured into 30 mL of water, the
reaction products were extracted with chloroform (3 ×
40mL). The combined organic solutions were washed
with water (3 × 50 mL) and dried with MgSO4. The
solvent was removed in a vacuum, the residue was chro-
matographed on a column packed with silica gel (eluent
petroleum ether–ethyl ether, 10 : 1). The successive elu-
tion afforded 0.09 g (7%) of compound VI and 0.08 g
(5%) of compound IV.
c. To a solution of 2.00 g (6.06 mmol) methyl phlo-
misoate (I) in a mixture of 8 mL of propionic acid and
8 mL of acetonitrile while stirring was added in suc-
cession 0.56 mL (6.06 mmol) of methyl acrylate (III),
0.09 g (0.30 mmol) of Pd(OAc)2, 2.20 g (12.1 mmol) of
Cu(OAc)2, and 0.07 g (0.60 mmol) of 1,4-benzoquinone.
The reaction mixture was intermittently stirred in an
argon flow at 40°С for 80 h, it was poured into 30 mL of
water, the reaction products were extracted with chloro-
form (3 × 50 mL). The combined organic solutions were
washed with water (3 × 50 mL) and dried with MgSO4.
The solvent was removed in a vacuum, the residue was
chromatographed on a column packed with silica gel
(eluent petroleum ether–ethyl ether, 4 : 1). The successive
elution afforded 0.13 g (7%) of initial diterpenoid I and
0.68 g (34%) of compound VIII.
Reaction of methyl phlomisoate with methyl ac-
rylate. а. To a solution of 2.00 g (6.06 mmol) of methyl
phlomisoate (I) in a mixture of 8 mL of propionic acid
and 8 mL of acetonitrile while stirring was added in suc-
cession 0.56 mL (6.06 mmol) of methyl acrylate (III),
0.09 g (0.30 mmol) of Pd(OAc)2, 0.50 g (3.03 mmol) of
Cu(OAc)2, and 0.07 g (0.60 mmol) of 1,4-benzoquinone.
The reaction mixture was intermittently stirred in an
oxygen atmosphere at 40°С for 80 h, it was poured into
30 mL of water, the reaction products were extracted
with chloroform (3 × 50 mL). The combined organic
solutions were washed with water (3 × 50 mL) and dried
with MgSO4. The solvent was removed in a vacuum, the
residue was chromatographed on a column packed with
Methyl (1S,4aS,8aR)-1,4a,6-trimethyl-5-(2-{2-[(E)-
3-oxo-3-phenoxyprop-1-en-1-yl]furan-3-yl}-ethyl)-
1,2,3,4,4a,7,8,8a-octahydronaphthalene-1-carboxylate
[methyl 16-(3-oxo-3-phenoxyprop-1-en-1-yl)-15,16-
epoxy-8(9),13(16),14-labdatrien-18-oate] (XIII). To
a solution of 0.50 g (1.52 mmol) of methyl phlomisoate
(I) in a mixture of 2 mL of propionic acid and 2 mL of
acetonitrile while stirring was added in succession 0.22 g
(1.52 mmol) of phenyl acrylate (X), 0.02 g (0.08 mmol)
of Pd(OAc)2, 0.55 g (3.03 mmol) of Cu(OAc)2, and
0.016 g (0.15 mmol) of 1,4-benzoquinone. The reaction
mixture was intermittently stirred in an argon flow at
40°С for 80 h, on cooling it was poured into 30 mL of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

KHARITONOV et al.
1696
petroleum ether–ethyl ether, 4 : 1). Yield 0.68 g (54%).
Oily substance, [α]D20 +60.7° (c 0.34, CHCl3). Found %:
С 75.76; H 8.53. C25H34O4. Calculated %: С 75.34; H
8.60. The data of IR, UV, and NMR spectra were analo-
gous to the data published in [7].
water, the reaction products were extracted with chloro-
form (3 × 50 mL) The combined organic solutions were
.
washed with water (3 × 50 mL) and dried with MgSO4.
The solvent was removed in a vacuum, the residue was
chromatographed on a column packed with silica gel
(eluent petroleum ether–ethyl ether, 1 : 1). The successive
elution afforded 0.18 g (36%) of initial diterpenoid I and
Methyl (1S,4aS,8aR)-1,4a,6-trimethyl-5-(2-{2-
[(E)-3-oxo-3-phenylprop-1-en-1-yl]furan-3-yl}-ethyl)-
1,2,3,4,4a,7,8,8a-octahydronaphthalene-1-carboxylate
[methyl 16-(3-oxo-3-phenylprop-1-en-1-yl)-15,16-
epoxy-8(9),13(16),14-labdatriеn-18-oate] (XV). To a
solution of 0.50 g (1.52 mmol) of methyl phlomisoate
(I) in a mixture of 2 mL of propionic acid and 2 mL
of acetonitrile while stirring was added in succes-
sion 0.25 g (1.75 mmol) of vinyl phenyl ketone (XII),
0.03 g (0.09 mmol) of Pd(OAc)2, 0.83 g (3.5 mmol) of
Cu(OAc)2, and 0.035 g (0.3 mmol) of 1,4-benzoquinone.
The reaction mixture was intermittently stirred in an
argon flow at 40°С for 80 h, on cooling it was poured
into 30 mLof water, the reaction products were extracted
27
0.18 g (29%) of compound XIII. Oily substance, [α]D
+42.51° (c 0.89, СНCl3). IR spectrum, cm–1: 3525, 2947,
2862, 1705, 1633, 1459, 1434, 1351, 1256, 1194, 1152,
1117, 1102, 1087, 1063, 1011, 617. UV spectrum, λmax
,
1
nm (logε): 250 (3.83), 332 (3.88). Н NMR spectrum,
δ, ppm: 0.77 s (3H, С20Н3), 1.02 d.t (1Н, Н3, J 13.5,
4.3 Hz), 1.20 с (3Н, С19Н3), 1.25 m (1Н, Н1), 1.34 d.d
(1H, H5, J 12.4, 1.6 Hz), 1.55 m (1H, H2), 1.64 s (3H,
С17Н3), 1.74 d.t (1Н, Н6, J 12.4, 5.6 Hz), 1.87 m (1Н,
H2), 1.90 m, 1.94 m, 1.98 m (3H, H1,6,7), 2.05–2.14 m
(2H, H7,11), 2.22 m (2Н, Н3,11), 2.58 m (2H, H12,12), 3.62 s
(3Н, ОСН3), 6.42 d (1Н, Н14, J 1.8 Hz), 6.44 d (1Н, Н2',
J 15.6 Hz), 7.14 m (2Н, Н2",6"), 7.24 m (1Н, Н4"), 7.38 m
(4Н, Н3",5", Н15,1'). 13C NMR spectrum, δ, ppm: 17.19 q
(C20), 18.96 t (C2), 19.31 q (C17), 20.19 t (C6), 25.14 t
(C12), 27.81 q (C19), 28.48 t (C11), 33.70 t (C7), 36.70 t
(C1), 37.06 t (C3), 38.99 с (C10), 43.28 s (C4), 50.50 q
(ОСН3), 52.83 d (С5), 112.33 d (C14), 112.74 d (С2'),
120.92 d, 120.97 d (С2",6”),125.02 d (С1'), 125.25 d (С4"),
128.77 d, 128.86 d (С3",5”),127.48 s (C8), 131.48 s (C13),
137.63 s (C9), 144.20 d (С15), 145.82 s (C16), 150.14 s
(C1”), 170.54 s (СО), 177.44 s (C18). Found, %: С 76.51;
H 7.41. C30H36O5. Calculated, %: С 75.60; H 7.61.
with chloroform (3 × 50 mL). The combined organic
solutions were washed with water (3 × 50 mL) and dried
with MgSO4. The solvent was removed in a vacuum,
the residue was chromatographed on a column packed
with silica gel (eluent petroleum ether–ethyl ether, 1 :
20
1). Yield 0.22 g (44%). Oily substance, [α]D +23.67°
(c 0.54, СНCl3). IR spectrum, cm–1: 3300, 2953, 1724,
1663, 1460, 1370, 1236, 1138, 1021, 969, 889, 758,
656. 1Н NMR spectrum, δ, ppm: 0.77 s (3H, С20Н3), 1.04
d.t (1Н, Н3, J 13.2, 4.3 Hz), 1.21 s (3Н, С19Н3), 1.24 m
(1Н, Н1), 1.35 d.d (1H, H5, J 13.2, 1.7 Hz), 1.55 m (1H,
H2), 1.64 s (3H, С17Н3), 1.74 d.t (1Н, Н6, J 13.2, 5.6 Hz),
1.86 m, 1.92 m, 1.99 m (4H, H1,6,7,2), 2.03–2.15 m (2H,
H7,11), 2.21 m (2Н, Н3,11), 2.60 m (2H, H12,12), 3.62 s
(3Н, ОСН3), 6.34 d (1Н, Н14, J 1.7 Hz), 6.60 d (1Н, Н2',
J 15.2 Hz), 7.38 d (1Н, Н15, J 1.7 Hz), 7.44–7.50 m (2Н,
Н3",5"), 7.55 m (1Н, Н4"), 7.65 d (1Н, Н1', J 15.2 Hz), 7.95 m
(2Н, Н2",6"). 13C NMR spectrum, δ, ppm: 17.58 q (C20),
19.35 t (C2), 19.71 q (C17), 20.57 t (C6), 25.58 t (C12),
28.19 q (C19), 28.85 t (C11), 34.05 t (C7), 37.16 t (C1),
37.43 t (C3), 39.34 s (C10), 43.64 s (C4), 50.85 q (ОСН3),
53.17 d (С5), 113.36 d (C14), 117.42 d (С2'), 127.82 d,
128.10 d, 128.37 d, 128.42 d (С2",6”,3”,5”), 132.54 s (C8),
132.34 d (С1'), 133.13 d (С4"), 136.37 s (C13), 137.97 s
(С1"), 138.11 s (C9), 144.29 d (С15), 147.10 s (C16),
177.75 s (C18), 189.51 s (СО). Found, %: С 77.89; H 8.04.
C30H36O4. Calculated, %: С 78.23; H 7.88.
Methyl (1S,4aS,8аR)-1,4a,6-trimethyl-5-(2-{2-[(Е)-
3-oxobut-1-en-1-yl]furan-3-yl}ethyl)-1,2,3,4,4a,7,8,8a-
octahydronaphthalene-1-carboxylate [methyl
16-(3-oxobut-1-en-1-yl)-15,16-epoxy-8(9),13(16),14-
labdatrien-18-oate] (XIV). To a solution of 1.00 g
(3.03 mmol) of methyl phlomisoate (I) in a mixture of
4 mL of propionic acid and 4 mL of acetonitrile while
stirring was added in succession 0.6 mL (3.03 mmol)
of methyl vinyl ketone (XI), 0.05 g (0.15 mmol) of
Pd(OAc)2, 1.10 g (6.06 mmol) of Cu(OAc)2, and 0.033 g
(0.30 mmol) of 1,4-benzoquinone. The reaction mixture
was intermittently stirred in an oxygen atmosphere at
40°С for 80 h, it was poured into 30 mL of water, the
reaction products were extracted with chloroform (3 ×
50 mL). The combined organic solutions were washed
with water (3 × 50 mL) and dried with MgSO4. The
solvent was removed in a vacuum, the residue was chro-
matographed on a column packed with silica gel (eluent
Methyl (1S,4aS,8aR)-1,4a,6-trimethyl-5-(2-{2-
[(Е)-3-oxo-3-(phenylamino)prop-1-en-1-yl]furan-
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SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XXXII.
1697
3-yl}ethyl)-1,2,3,4,4a,7,8,8a-octahydronaph-
thalene-1-carboxylate [methyl (E)-16-[3-oxo-
3-(phenylamino)prop-1-en-1-yl]-15,16-epoxy-
8(9),13(16),14-labdatrien-18-oate] (XXII). To a solu-
tion of 1.00 g (3.03 mmol) of methyl phlomisoate (I) in a
mixture of 4 mLof propionic acid and 4 mLof acetonitrile
while stirring was added in succession 0.52 g (3.5 mmol)
of acrylic acid anilide (XVI), 0.05 g (0.18 mmol) of
Pd(OAc)2, 1.60 g (7.00 mmol) of Cu(OAc)2, and 0.004 g
(0.04 mmol) of 1,4-benzoquinone. The reaction mixture
was intermittently stirred in an argon flow at 40°С for
80 h, on cooling it was poured into 30 mL of water, the
reaction products were extracted with chloroform (3 ×
methyl phlomisoate (I) in a mixture of 2 mL of propionic
acid and 2 mL of acetonitrile while stirring was added
in succession 0.162 g (1.75 mmol) N-(p-tolyl)acryl-
amide (XVII), 0.03 g (0.09 mmol) of Pd(OAc)2, 0.83 g
(3.5 mmol) of Cu(OAc)2, and 0.018 g (0.15 mmol) of
1,4-benzoquinone. The reaction mixture was intermit-
tently stirred in an argon flow at 40°С for 80 h, on
cooling it was poured into 30 mL of water, the reaction
products were extracted with chloroform (3 × 50 mL)
.
The combined organic solutions were washed with water
(3 × 50 mL) and dried with MgSO4. The solvent was
removed in a vacuum, the residue was chromatographed
on a column packed with silica gel (eluent petroleum
ether–ethyl ether, 1:1). Yield 0.25 g (42%). Oily sub-
50 mL). The combined organic solutions were washed
20
with water (3 × 50 mL) and dried with MgSO4. The
solvent was removed in a vacuum, the residue was chro-
matographed on a column packed with silica gel (eluent
petroleum ether–ethyl ether, 1 : 1). Yield 0.59 g (59%).
Oily substance, [α]D20 +22.97° (c 0.93, СНCl3). IR spec-
trum, cm–1: 3379, 2922, 1725, 1657, 1626, 1537, 1460,
1436, 1380, 1330, 1235, 1188, 1142, 1031, 972, 691.
UV spectrum, λmax, nm (logε): 245 (4.07), 307 (4.53).
1Н NMR spectrum, δ, ppm: 0.75 s (3H, С20Н3), 1.03 d.t
(1Н, Н3, J 13.5, 4.4 Hz), 1.20 s (3Н, С19Н3), 1.25 m (1Н,
Н1), 1.34 d (1H, H5, J 11.4 Hz), 1.54 m (1H, H2), 1.62 s
(3H, С17Н3), 1.71 d.t (1Н, Н6, J 11.4, 5.0 Hz), 1.85 m
(1Н, H2), 1.88–1.97 m (3H, H1,6,7), 2.04 m, 2.10 m (2H,
H7,11), 2.18 m, 2.22 m (2Н, Н3,11), 2.53 m (2H, H12,12),
3.61 s (3Н, ОСН3), 6.37 d (1H, H14, J 1.8 Hz), 6.43 d (1Н,
Н2', J 15.2 Hz), 7.08 t (1Н, H4”, J 7.9 Hz), 7.30 t (2Н,
H3”,5”, J 7.9 Hz), 7.32 d (1H, H15, J 1.8 Hz), 7.55 d (1Н,
Н1', J 15.2 Hz), 7.61 d (2Н, H2”,6”, J 7.9 Hz). 13C NMR
spectrum, δ, ppm: 17.62 q (C20), 19.42 t (C2), 19.75 q
(C17), 20.65 t (C6), 25.41 t (C12), 28.26 q (C19), 28.82 t
(C11), 34.13 t (C7), 37.08 t (C1), 37.50 t (C3), 39.39 s (C10),
43.75 s (C4), 50.96 q (ОСН3), 53.28 d (С5), 112.91 d (C14),
119.80 d (С2'), 123.93 d (С1'), 126.63 s (C8), 127.74 d
(С6",2”), 128.75 d (С3",5”,4”), 130.15 s (С1"), 138.10* s
(C13), 138.24* s (C9), 143.49 d (С15), 146.68 s (C16),
165.29 s (СОNH), 178.04 s (C18). Found, %: С 76.07;
H 7.83; N 2.78. C30H37NO4. Calculated, %: С 75.76; H
7.84; N 2.94.
stance, [α]D +12.75° (c 0.53, СНCl3). UV spectrum,
λmax, nm (logε): 249 (3.97), 327 (4.41). IR spectrum, ν,
cm–1: 3401, 2944, 2837, 1771, 1728, 1663, 1605, 1541,
1439, 1405, 1375, 1325, 1245, 1037, 972, 815, 736.
1Н NMR spectrum, δ, ppm: 0.75 s (3H, С20Н3), 1.03 d.t
(1Н, Н3, J 13.0, 4.3 Hz), 1.20 s (3Н, С19Н3), 1.24 m (1Н,
Н1), 1.34 d.d (1H, H5, J 12.4, 1.6 Hz), 1.56 m (1H, H2),
1.63 s (3H, С17Н3), 1.71 m (1Н, Н6), 1.86 m (1Н, H2),
1.88 m, 1.93 m, 1.97 m (3H, H1,6,7), 1.99–2.11 m (2H,
H7,11), 2.20 d (1Н, Н3, J 13.0 Hz), 2.20 m (1Н, Н11),
2.30 s (3Н, СН3), 2.54 m (2H, H12,12), 3.62 s (3Н, ОСН3),
6.38 d (1Н, Н2', J 15.1 Hz), 6.38 d (1H, H14, J 1.6 Hz),
7.11 d (2Н, Н2",6”, J 8.3 Hz), 7.35 d (1H, H15, J 1.6 Hz),
7.48 d (2Н, Н3",5”, J 8.3 Hz), 7.54 d (1Н, Н1', J 15.1 Hz).
13C NMR spectrum, δ, ppm: 17.67 q (C20), 19.47 t (C2),
19.85 q (СН3), 20.70 t (C6), 20.78 q (C17), 25.50 t (C12),
28.33 q (C19), 28.89 t (C11), 34.19 t (C7), 37.14 t (C1),
37.56 t (C3), 39.46 s (C10), 43.78 s (C4), 51.01 q (ОСН3),
53.33 d (С5), 113.00 d (C14), 119.66 d (С2'), 126.61 d (С1'),
127.81 s (C8), 138.18 s (C13), 138.71 s (C9), 129.38 d
(С2",6”), 129.62 d (С3",5”), 130.16 s (С4"), 133.65 s (С1"),
143.54 d (С15), 146.69 s (C16), 163.94 s (СОNH), 178.00 s
(C18). Found, %: С 75.92; H 7.94; N 2.81. C31H39NO4.
Calculated, %: С 76.04; H 8.03; N 2.86.
Methyl (1S,4aS,8aR)-1,4a,6-trimethyl -5-(2-{2-[(Е)-
3-(benzylamino)-3-oxoprop-1-en-1-yl]-furan-3-yl}
ethyl)-1,2,3,4,4a,7,8,8a-octahydronaphthalene-1-
carboxylate {methyl 16-[3-(benzylamino)-3-oxoprop-
1-en-1-yl]-15,16-epoxy-8(9),13(16),14-labdatrien-18-
oate} (XXIV). To a solution of 1.00 g (3.03 mmol) of
methyl phlomisoate (I) in a mixture of 4 mL of propionic
acid and 4 mL of acetonitrile while stirring was added
in succession 0.48 g (3.5 mmol) of N-benzylacrylamide
(XVIII), 0.05 g (0.18 mmol) of Pd(OAc)2, 1.60 g
Methyl (1S,4aS,8aR)-1,4a,6-trimethyl -5-(2-{2-[(Е)-
3-oxo-3-(p-tolylamino)prop-1-en-1-yl]furan-3-yl}
ethyl)-1,2,3,4,4a,7,8,8a-octahydronaphthalene-1-car-
boxylate [methyl (E)-16-[3-(p-tolylamino)-3-oxoprop-
1-en-1-yl]-15,16-epoxy-8(9),13(16),14-labdatrien-18-
oate] (XXIII). To a solution of 0.50 g (1.52 mmol) of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

KHARITONOV et al.
1698
(7.00 mmol) Cu(OAc)2, and 0.035 g (0.3 mmol) of
1,4-benzoquinone. The reaction mixture was intermit-
tently stirred in an argon flow at 40°С for 80 h, on cooling
it was poured into 30 mL of water, the reaction products
vacuum, the residue was chromatographed on a column
packed with silica gel (eluent petroleum ether–ethyl ether,
1 : 1). The successive elution afforded 0.32 g (64%) of
initial diterpenoid I and 0.1 g (20%) of compound XXV.
Oily substance, [α]D20 +21.53° (c 0.89, СНCl3). IR spec-
trum, cm–1: 3435, 2986, 1765, 1632, 1455, 1368, 1228,
1043, 926, 809, 751. 1Н NMR spectrum, δ, ppm: 0.75 s
(3H, С20Н3), 1.02 d.t (1Н, Н3, J 13.2, 4.3 Hz), 1.20 s (3Н,
С19Н3), 1.25 m (1Н, Н1), 1.33 d.d (1H, H5, J 12.1, 1.4 Hz),
1.45 d (3Н, CH3, J 7.3 Hz), 1.52–1.58 m (1H, H2), 1.63 s
(3H, С17Н3), 1.73 d.t (1Н, Н6, J 12.1, 5.7 Hz), 1.85 m (1Н,
H2), 1.88 m, 1.89 m, 1.97 m (3H, H1,6,7), 2.00–2.10 m
(2H, H7,11), 2.18 m, 2.21 m (2Н, Н3,11), 2.52 m (2H,
H12,12), 3.61 s (3Н, ОСН3), 3.76 s (3Н, CO2CH3), 4.71 m
(1Н, СН), 6.13 d (1Н, NН, J 7.5 Hz), 6.21 d (1Н, Н2',
J 15.1 Hz), 6.37 d (1H, H14, J 1.9 Hz), 7.35 d (1Н, Н15,
J 1.9 Hz), 7.44 d (1Н, Н1', J 15.1 Hz). 13C NMR spectrum,
δ, ppm: 17.36 q (C20), 18.25 q (СН3), 19.14 t (C2), 19.49 q
(C17), 20.37 t (C6), 25.16 t (C12), 28.00 q (C19), 29.25 t
(C11), 33.88 t (C7), 36.86 t (C1), 37.25 t (C3), 39.15 s (C10),
43.47 s (C4), 47.65 d (СН), 50.65 q (ОСН3), 52.06 q
(СО2СН3), 53.03 d (С5), 112.59 d (C14), 115.62 d (С2'),
126.10 d (С1'), 127.45 s (C13), 129.62 s (C8), 137.93 s
(C9), 143.16 s (С16), 146.22 d (C15), 165.05 s (СОNH),
173.19 s (СО2СН3), 177.64 s (C18). Found, %: С 69.53;
H 7.91; N 2.74. C28H39NO6. Calculated, %: С 69.25; H
8.09; N 2.88.
were extracted with chloroform (3 × 50 mL). The com-
bined organic solutions were washed with water (3 ×
50 mL) and dried with MgSO4. The solvent was removed
in a vacuum, the residue was chromatographed on a col-
umn packed with silica gel (eluent petroleum ether–ethyl
20
ether, 1 : 1). Yield 0.30 g (30%). Oily substance, [α]D
+37.48° (c 0.95, СНCl3). IR spectrum, cm–1: 3379, 2926,
1728, 1602, 1537, 1447, 1377, 1330, 1241, 1194, 1161,
1041, 975, 767, 692. UV spectrum, λmax, nm (logε): 243
1
(4.33), 325 (4.36). Н NMR spectrum, δ, ppm: 0.83 s
(3H, С20Н3), 0.98 d.t (1Н, Н3, J 13.3, 4.4 Hz), 1.16 s (3Н,
С19Н3), 1.25 m (1Н, Н1), 1.35 m (1H, H5), 1.54 m (1H,
H2), 1.59 s (3H, С17Н3), 1.67 m (1Н, Н6), 1.81 m (1Н,
H2), 1.88 m, 1.92 m, 1.94 m (3H, H1,6,7), 1.97–2.08 m (2H,
H7,11), 2.14 m, 2.18 m (2Н, Н3,11), 2.49 m (2H, H12,12),
3.57 s (3Н, ОСН3), 4.49 d (2Н, СН2, J 5.9 Hz), 6.08 t
(1Н, NH, J 5.9 Hz), 6.23 d (1Н, Н2', J 15.2 Hz), 6.32 d
(1H, H14, J 1.8 Hz), 7.22–7.36 m (6Н, H15, Ph), 7.45 d
(1Н, Н1', J 15.2 Hz). 13C NMR spectrum, δ, ppm: 17.65 q
(C20), 19.43 t (C2), 19.80 q (C17), 20.68 t (C6), 25.44 t
(C12), 28.29 q (C19), 28.87 t (C11), 31.79 t (СН2), 34.18 t
(C7), 37.14 t (C1), 37.55 t (C3), 39.44 s (C10), 43.69 s (C4),
50.97 q (ОСН3), 53.33 d (С5), 112.87 d (C14), 116.31 d
(С2'), 126.18 d (С1'), 127.32 s (C8), 127.70 d (С6",2”),
128.53 d (С3",5”,4”), 129.69 s (C13), 138.20 s (C9,1”),
143.31 d (С15), 146.62 s (C16), 166.06 s (СОNH), 178.00 s
(C18). Found, %: С 76.25; H 7.89; N 2.97. C31H39NO4.
Calculated, %: С 76.04; H 8.03; N 2.86.
Methyl (1S,4aS,8aR)-1,4а,6-trimethyl -5-[2-(2-{(1E)-
3-[(3-methoxy-3-oxo-1-phenyl пропил)amino]-3-
oxoprop-1-ен-1-yl}furan)ethyl]-1,2,3,4,4а,7,8,8а-
octahydronaphthalene-1-carboxylate (XXVI). To a
solution of 0.50 g (1.52 mmol) of methyl phlomisoate
(I) in a mixture of 2 mL of propionic acid and 2 mL of
acetonitrile while stirring was added in succession 0.35 g
(1.75 mmol) of methyl 3-acryloylamino-3-phenyl pro-
panoate (XX), 0.03 g (0.09 mmol) of Pd(OAc)2, 0.83 g
(3.5 mmol) of Cu(OAc)2, and 0.018 g (0.15 mmol) of
1,4-benzoquinone. The reaction mixture was intermit-
tently stirred in an argon flow at 40°С for 80 h, on cooling
it was poured into 30 mL of water, the reaction products
Methyl (1S,4aS,8aR)-1,4а,6-trimethyl-5-[2-(2-
{(1E)-3-[(4-methoxy-4-oxobutan-2-yl)amino]-3-oxo-
prop-1-en-1-yl}furan-3-yl)ethyl]-1,2,3,4,4а,7,8,8а-
octahydronaphthalene-1-carboxylate (XXV). To a
solution of 0.50 g (1.52 mmol) of methyl phlomisoate
(I) in a mixture of 2 mL of propionic acid and 2 mL
of acetonitrile while stirring was added in succession
0.20 g (1.75 mmol) of methyl 2-acryloylaminopropano-
ate (XIX), 0.03 g (0.09 mmol) of Pd(OAc)2, 0.83 g
(3.5 mmol) of Cu(OAc)2, and 0.018 g (0.15 mmol) of
1,4-benzoquinone. The reaction mixture was intermit-
tently stirred in an argon flow at 40°С for 80 h, it was
poured into 30 mL of water, the reaction products were
were extracted with chloroform (3 × 50 mL). The com-
bined organic solutions were washed with water (3 ×
50 mL) and dried with MgSO4. The solvent was removed
in a vacuum, the residue was chromatographed on a col-
umn packed with silica gel (eluent petroleum ether–ethyl
ether, 1 : 1). The successive elution afforded 0.18 g (36%)
of initial diterpenoid I and 0.12 g (25%) of compound
XXVI. Oily substance, [α]D20 +24.67° (c 0.72, СНCl3).
extracted with chloroform (3 × 50 mL). The combined
organic solutions were washed with water (3 × 50 mL)
and dried with MgSO4. The solvent was removed in a
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XXXII.
1699
IR spectrum, cm–1: 3300, 2953, 1724, 1663, 1460, 1370,
1236, 1138, 1021, 969, 889, 758, 656. 1Н NMR spectrum,
δ, ppm: 0.75 s (3H, С20Н3), 1.02 d.t (1Н, Н3, J 13.4,
4.3 Hz), 1.20 s (3Н, С19Н3), 1.25 m (1Н, Н1), 1.33 d.d
(1H, H5, J 12.6, 1.3 Hz), 1.52–1.59 m (1H, H2), 1.62 s,
1.63 s (3H, С17Н3), 1.73 d.t (1Н, Н6, J 12.6, 5.6 Hz),
1.84 m (1Н, H2), 1.90 m, 1.96 m, 1.97 m (3H, H1,6,7),
2.01–2.11 m (2H, H7,11), 2.18 m, 2.22 m (2Н, Н3,11),
2.52 m (2H, H12,12), 2.88 d.d (1Н, СН2, J 15.9, 5.9 Hz),
2.99 d.d (1Н, СН2, J 15.9, 5.6 Hz), 3.62 s (6Н, ОСН3,
CO2CH3), 5.54 m (1Н, СН), 6.29 d (1Н, Н2', J 14.9 Hz),
6.37 d (1H, H14, J 1.7 Hz), 6.64 d (1Н, NН, J 8.3 Hz),
7.31 m, 7.32 m (5Н, Ph), 7.35 d (1Н, Н15, J 1.7 Hz), 7.45 d
(1Н, Н1', J 14.9 Hz). 13C NMR spectrum, δ, ppm: 17.66 q
(C20), 19.45 t (C2), 19.83 q (C17), 20.70 t (C6), 25.47 t
(C12), 28.31 q (C19), 28.91 t (C11), 34.19 t (C7), 37.13 t
(C1), 37.56 t (C3), 39.46* s (C10), 39.69* t (СН2), 43.78 s
(C4), 49.56 d (СН), 51.00 q (ОСН3), 51.74 q (СО2СН3),
53.34 d (С5), 112.91 d (C14), 116.35 d (С2'), 126.30 d
(С1'), 126.16 d (С6",2”), 127.47 d (С4"), 128.59 d (С3",5”),
127.75 s (C8), 129.79 s (С1"), 138.24 с (C13), 140.50 s
(C9), 143.41 d (С15), 146.60 s (C16), 165.29 s (СОNH),
171.59 s (СО2СН3), 177.99 s (C18). Found, %: С 71.89;
H 8.02; N 2.32. C34H43NO6. Calculated, %: С 72.70;
H 7.72; N 2.49.
756. UV spectrum, λmax, nm (logε): 236 (3.53), 309 (4.29).
1Н NMR spectrum, δ, ppm: 0.72 s (3H, С20Н3), 0.90 t
(3Н, СН2СН3, J 7.5 Hz), 1.00 d.t (1Н, Н3, J 13.4, 4.4 Hz),
1.17 s (3Н, С19Н3), 1.22 m (1Н, Н1), 1.31 d.d (1H, H5,
J 12.8, 1.8 Hz), 1.52 m (1H, H2), 1.60 s (3H, С17Н3),
1.70–1.77 m, 1.88 m, 1.90 m, 1.95 m (7H, H1,6,7,2,6
,
СН2СН3), 1.98–2.08 m (2H, H7,11), 2.15 m, 2.19 m (2Н,
Н3,11), 2.49 m (2H, H12,12), 3.59 s (3Н, ОСН3), 3.73 s (3Н,
CO2CH3), 4.68 m (1Н, СН), 6.29 br.s (1Н, NН), 6.30 d
(1Н, Н2', J 15.0 Hz), 6.34 d (1H, H14, J 1.8 Hz), 7.31 d
(1Н, Н15, J 1.8 Hz), 7.42 d (1Н, Н1', J 15.0 Hz). 13C NMR
spectrum, δ, ppm: 9.08 q (СН3), 17.34 q (C20), 19.12 t
(C2), 19.47 q (C17), 20.36 t (C6), 25.13 t (C12), 25.33 t
(СН2), 27.97 q (C19), 28.56 t (C11), 33.85 t (C7), 36.82 t
(C1), 37.22 t (C3), 39.12 s (C10), 43.45 s (C4), 50.64 q
(ОСН3), 51.88 q (СО2СН3), 52.94 d (СН), 52.99 d (С5),
112.58 d (C14), 115.75 d (С2'), 125.98 d (С1'), 127.41 s
(C13), 129.52 s (C8), 137.90 s (C9), 143.09 d (C15),
146.25 s (С16), 165.35 s (СОNH), 172.59 s (СО2СН3),
177.62 s (C18). Mass spectrum, m/z (Irel, %): 499 (2), 267
(12), 252 (11), 251 (70), 189 (15), 175 (10), 173 (15), 135
(18), 134 (100), 133 (10), 119 (14), 107 (11), 105 (10), 91
(10), 58 (23), 41 (11). Found [M]+ 499.2927. C29H41O6N.
Calculated m 499.2928.
Methyl (1S,4aS,8aR)-1,4a,6-trimethyl-5-(2-{2-
[(1Е)-3-(morpholin-4-yl)-3-oxoprop-1-ен-1-yl]-
furan-3-yl}ethyl)-1,2,3,4,4a,7,8,8a-octahydronaph-
thalene-1-carboxylate {methyl 16-[3-(morpholin-4-
yl)-3-oxoprop-1-ен-1-yl]-15,16-epoxy-8(9),13(16),14-
labdatrien-18-oate} (XXIX). To a solution of 0.50 g
Methyl (1S,4aS,8aR)-1,4а,6-trimethyl-5-[2-(2-
{(1E)-3-[(1-methoxy-1-oxobutan-2-yl)amino]-3-
oxo-prop-1-en-1-yl}furan)ethyl]-1,2,3,4,4а,7,8,8а-
octahydronaphthalene-1-carboxylate (XXVII). To a
solution of 0.50 g (1.52 mmol) of methyl phlomisoate
(I) in a mixture of 3 mL of propionic acid and 3 mL (1.52 mmol) of methyl phlomisoate (I) in a mixture of
of ethyl ether while stirring was added in succession
0.37 g (2.37 mmol) of methyl 2-acryloylaminobutano-
ate ы (XXI), 0.05 g (0.16 mmol) of Pd(OAc)2, 0.14 g
(0.79 mmol) of Cu(OAc)2, and 0.02 g (0.16 mmol) of
1,4-benzoquinone. The reaction mixture was intermit-
tently stirred in an oxygen flow at 40°С for 80 h, on
cooling it was poured into 30 mL of water, the reaction
2 mL of propionic acid and 2 mL of acetonitrile while
stirring was added in succession 0.13 g (1.75 mmol)
of 4-acryloylaminomorpholine (XXVIII), 0.03 g
(0.09 mmol) of Pd(OAc)2, 0.8 g (3.5 mmol) of Cu(OAc)2,
and 0.018 g (0.15 mmol) of 1,4-benzoquinone. The reac-
tion mixture was intermittently stirred in an argon flow
at 40°С for 80 h, on cooling it was poured into 30 mL of
water, the reaction products were extracted with chloro-
products were extracted with chloroform (3 × 50 mL)
.
The combined organic solutions were washed with water
(3 × 50 mL) and dried with MgSO4. The solvent was
removed in a vacuum, the residue was chromatographed
on a column packed with silica gel (eluent chloroform).
The successive elution afforded 0.10 g (20%) of initial
diterpenoid I and 0.15 g (16%) of compound XXVII. [α]
form (3 × 50 mL). The combined organic solutions were
washed with water (3 × 50 mL) and dried with MgSO4.
The solvent was removed in a vacuum, the residue was
chromatographed on a column packed with silica gel
(eluent petroleum ether–ethyl ether, 1 : 1). The succes-
sive elution afforded 0.14 g (28%) of initial diterpenoid
I and 0.04 g (8%) of compound XXIX. Oily substance,
+66.92° (c 1.07, СНCl3). IR spectrum, cm–1: 3364,
20
D
[α]D +34.79° (c 0.13, СНCl3). IR spectrum, cm–1:
20
3298, 2953, 2878, 2853, 1744, 1726, 1661, 1620, 1533,
1462, 1437, 1377, 1344, 1231, 1204, 1153, 1142, 972,
3303, 2948, 1724, 1667, 1463, 1369, 1235, 1134, 1022.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

KHARITONOV et al.
1700
1Н NMR spectrum, δ, ppm: 0.75 s (3H, С20Н3), 1.02 d.t
(1Н, Н3, J 13.7, 4.3 Hz), 1.19 s (3Н, С19Н3), 1.23 m
(1Н, Н1), 1.33 d (1H, H5, J 12.1 Hz), 1.55 m (1H, H2),
1.63 s (3H, С17Н3), 1.68–1.75 m (1Н, Н6), 1.85 m (1Н,
H2), 1.91–1.97 m (3H, H1,6,7), 1.99–2.10 m (2H, H7,11),
2.20 d (1Н, Н3, J 13.7 Hz), 2.20 m (1Н, Н11), 2.53 m (2H,
H12,12), 3.61 s (3Н, ОСН3), 3.70 br.s (8Н, СН2), 6.38 d
(1H, H14, J 1.6 Hz), 6.68 d (1Н, Н2', J 14.8 Hz), 7.35 d
(1H, H15, J 1.6 Hz), 7.52 d (1Н, Н1', J 14.8 Hz). 13C NMR
spectrum, δ, ppm: 17.67 q (C20), 19.47 t (C2), 19.85 q
(C17), 20.70 t (C6), 25.50 t (C12), 28.34 q (C19), 28.97 t
(C11), 34.20 t (C7), 37.16 t (C1), 37.58 t (C3), 39.46 s
(C10), 43.79 s (C4), 51.01 q (ОСН3), 53.35 d (С5), 66.78 t
(4СН2), 112.06 d (C14), 113.04 d (С2'), 127.78 s (C8),
127.90 d (С1'), 129.92 s (C13), 138.24 s (C9), 143.37 d
(С15), 146.95 s (C16), 165.59 s (СОN), 177.98 s (C18).
Found, %: С 71.47; H 8.22; N 2.57. C28H39NO5. Calcu-
lated, %: С 71.61; H 8.37; N 2.98.
1.84 m (1Н, H2), 1.89 m, 1.94 m, 1.99 m (3H, H1,7,6),
2.01–2.14 m (2H, H7,11), 2.22 d.m (1Н, Н3, J 13.6 Hz),
2.22 m (1Н, Н11), 2.33 s (3Н, СН3), 2.54 m (2H, H12,12),
3.62 s (3Н, ОСН3), 6.39 s (1H, H14), 6.66 d (1Н, Н2',
J 15.4 Hz), 6.83 d (1Н, Н2", J 16.4 Hz), 7.17 d (1Н, Н1",
J 16.4 Hz), 7.28 d.t (1Н, Ph, J 7.3, 2.2 Hz ), 7.30 d (1Н,
Н1', J 15.4 Hz), 7.35 t (2Н, Ph, J 7.3 Hz), 7.48 d.m (2Н,
Ph, J 7.3 Hz). 13C NMR spectrum, δ, ppm: 17.79 q (C20),
19.59 t (C2), 19.91 q (C17), 20.78 t (C6), 25.80 t (C12),
28.03* q (C19), 28.43* q (СН3), 29.02 t (C11), 34.28 t
(C7), 37.33 t (C1), 37.66 t (C3), 39.61 s (C10), 43.88 s (C4),
51.13 q (ОСН3), 53.44 d (С5), 112.39 d (C14), 115.49 d
(С1"), 122.14 d (С2'), 126.55 d (С2"), 128.63 d (2С, Ph),
128.22 d (Ph), 128.03 s (C8), 128.79 d (2С, Ph), 130.07 d
(С1'), 134.82 s (C13), 136.40 s (Ph), 138.17 s (C9), 146.18 s
(С15), 154.99 s (C16), 178.00 s (C18), 197.59 s (СОСН3).
Found, %: С 79.07; H 7.87. C33H40O4. Calculated, %:
С 79.16; H 8.05.
Methyl (1S,4aS,8aR)-5-(2-{2-[(Е)-3-{[5-
(acryloylaminooxy)pentyl]oxy}-3-oxoprop-1-en-1-yl]
furan-3-yl}ethyl)-1,4a,6-trimethy-1,2,3,4,4a,7,8,8a-
octahydronaphthalene-1-carboxylate (XXХII). To a
solution of 1.00 g (3.03 mmol) of methyl phlomisoate
(I) in a mixture of 4 mL of propionic acid and 4 mL
of ethyl ether while stirring was added in succession
0.77 mL(3.60 mmol) pentane-1,5-diyl diacrylate (XXXI),
0.09 g (0.30 mmol) of Pd(OAc)2, 0.28 g (1.51 mmol) of
Cu(OAc)2, and 0.03 g (0.30 mmol) of 1,4-benzoquinone.
The reaction mixture was intermittently stirred in an
oxygen flow at 40°С over 80 h, on cooling it was poured
into 30 mLof water, the reaction products were extracted
Methyl (1S,4aS,8aR)-5-(2-{2-[(1Е)-3-oxobut-1-en-
1-yl]-5-[(Е)-phenylethenyl)furan-3-yl}ethyl)-1,4a,6-
trimethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalene-1-
carboxylate {methyl 16-[(Е)-3-oxobut-1-ен-1-yl]-15-
[(Е)-styryl]-15,16-epoxy-8(9),13(16),14-labdatrien-
18-oate} (XXX). To a solution of 0.50 g (1.25 mmol)
of methyl ester VIII in a mixture of 4 mL of propionic
acid and 4 mL of ethyl ether while stirring was added
in succession 0.22 mL (1.88 mmol) of styrene (II),
0.038 g (0.13 mmol) of Pd(OAc)2, 0.11 g (0.63 mmol) of
Cu(OAc)2, and 0.014 g (0.13 mmol)of 1,4-benzoquinone.
The reaction mixture was intermittently stirred in an
oxygen atmosphere at 35°С over 80 h, on cooling it was
poured into 30 mL of water, the reaction products were
with chloroform (3 × 50 mL). The combined organic
solutions were washed with water (3 × 50 mL) and dried
with MgSO4. The solvent was removed in a vacuum, the
residue was chromatographed on a column packed with
silica gel (eluent petroleum ether–ethyl ether, 4:1). The
successive elution afforded 0.55 g (55%) of initial diterpe-
noid I and 0.16 g (10%) of compound XXХII. Oily sub-
stance, [α]D20 +38.46° (c 0.84, СНCl3). IR spectrum, cm–1:
3523, 2946, 2860, 1705, 1631, 1457, 1434, 1352, 1253,
1120, 1156, 1122, 1105, 1079, 1063, 1013, 617. 1Н NMR
spectrum, δ, ppm: 0.73 s (3H, С20Н3), 0.99 d.t (1Н, Н3,
J 13.5, 4.4 Hz), 1.17 s (3Н, С19Н3), 1.20 m (1Н, Н1),
1.31 d.d (1H, H5, J 10.2, 1.8 Hz), 1.42–1.50 m (3H, СН2,
H2), 1.60 s (3H, С17Н3), 1.64–1.71 m (6Н, 2СОСН2СН2,
Н2,6), 1.80–1.91 m (3H, H1,6,7), 1.94–2.09 m (2H, H7,11),
2.16 m, 2.19 m (2Н, Н3,11), 2.50 m (2H, H12,12), 3.58 s
(3Н, ОСН3), 4.14 d.d (4Н, 2СОСН2, J 12.4, 6.5 Hz),
extracted with chloroform (3 × 40mL). The combined
organic solutions were washed with water (3 × 50 mL)
and dried with MgSO4. The solvent was removed in a
vacuum, the residue was chromatographed on a column
packed with silica gel (eluent petroleum ether–ethyl
ether, 4 : 1). The successive elution afforded 0.27 g of
initial labdanoid VIII and 0.06 g (10%) of compound
XXX, [α]D20 +40.21° (c 1.00, СНCl3). IR spectrum, cm–1:
3435, 2953, 2876, 2853, 1769, 1722, 1684, 1665, 1620,
1609, 1566, 1468, 1449, 1433, 1379, 1360, 1345, 1232,
1192, 1161, 1142, 1099, 1038, 978, 947, 893, 756, 710.
UV spectrum, λmax, nm (logε): 281 (3.63), 329 (3.79).
1Н NMR spectrum, δ, ppm: 0.77 s (3H, С20Н3), 1.04 d.t
(1Н, Н3, J 13.6, 4.4 Hz), 1.21 s (3Н, С19Н3), 1.25 m (1Н,
Н1), 1.35 d.d (1H, H5, J 12.5, 1.7 Hz), 1.58 m (1H, H2),
1.65 s (3H, С17Н3), 1.73 d.d (1Н, Н6, J 12.5, 5.4 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XXXII.
1701
5.76 d.d (1Н, СН=, J 10.4, 1.7 Hz), 6.10 d (1Н, СН2=,
J 10.4 Hz), 6.20 d (1Н, Н2', J 15.8 Hz), 6.32 d (1Н, СН2=,
J 1.7 Hz), 6.34 d (1H, H14, J 1.8 Hz), 7.35 d (1H, H15,
J 1.8 Hz), 7.42 d (1Н, Н1', J 15.8 Hz). 13C NMR spec-
trum, δ, ppm: 17.34 q (C20), 19.15 t (C2), 19.43 q (C17),
20.35 t (C6), 22.07 t (СН2), 25.25 t (C12), 27.96 q (C19),
28.67 t (C11), 29.22 t (2СОСН2СН2), 33.85 t (C7), 36.88 t
(C1), 37.24 t (C3), 39.14 s (C10), 43.42 s (C4), 50.60 q
(ОСН3), 52.99 d (С5), 63.60 t (СОСН2), 63.83 t (СОСН2),
112.71 d (C14), 113.54 d (С2'), 127.45 t (СН2=), 128.10* d
(С1'), 128.55* d (СН=), 130.01 s (C8), 130.48 s (C13),
137.84 s (C9), 143.76 d (С15), 146.02 s (C16), 165.69 s
(СО), 166.87 s (СО), 177.45 s (C18). Found, %: С 70.87;
H 7.99. C32H44O7. Calculated, %: С 71.08; H 8.20.
(1Н, NH), 6.61 br.s (1Н, NH), 7.31 d (1H, H15, J 1.3 Hz),
7.37 d (1Н, Н1', J 15.2 Hz). 13C NMR spectrum, δ, ppm:
17.61 q (C20), 19.43 t (C2), 19.79 q (C17), 20.67 t (C6),
25.41 t (C12), 25.88 t (СН2СН2), 28.29 q (C19), 28.94 t
(C11), 29.13 t (СОNСН2СН2), 29.33 t (СОNСН2СН2),
34.13 t (C7), 37.08 t (C1), 37.52 t (C3), 38.96 t (СОNСН2),
39.08 t (СОNСН2), 39.41 s (C10), 43.74 s (C4), 51.01 q
(ОСН3), 53.28 d (С5), 112.82 d (C14), 117.05 d (С2'),
128.35 d (С1'), 125.92 t (СН2=), 127.69 s (C8), 129.26 s
(C13), 130.97 d (СН=), 138.16 s (C9), 143.19 d (С15),
146.63 s (C16), 165.81 s (СОN), 166.42 s (СОN), 178.04 s
(C18). Found, %: С 72.02; H 8.71; N 5.27. C33H48N2O5.
Calculated, %: С 71.71; H 8.75; N 5.07.
Dimethyl (1S,1'S,4aS,4a'S,8aR,8a'R)-5,5'-(2,2'-
{2,2'-[(1E,1'E)-3,3'-(hexane-1,6-diyldiimino)bis-
(3-oxoprop-1-en-1-yl)]bis(furan-3-yl)}bisethyl)-
bis(1,4a,6-trimethyl-1,2,3,4,4a,7,8,8a-octahydro-
naphthalene-1-carboxylate) (XXXV). Oily substance,
[α]D20 +7.39° (c 0.12, СНCl3). IR spectrum, cm–1: 3405,
2940, 2833, 1764, 1669, 1728, 1611, 1543, 1438, 1372,
1325, 1239, 1037, 976, 821. 1Н NMR spectrum, δ, ppm:
0.73 s (6H, С20Н3, С20'Н3), 0.97 m (2Н, Н3,3'), 1.14 s
(6Н, С19Н3, С19'Н3), 1.20 m (2Н, Н1,1'), 1.30 m, 1.36 m
(6H, СН2СН2, H5,5'), 1.53 m (6H, 2СОNСН2СН2,
H2,2'), 1.61 s (6H, С17Н3, С17'Н3), 1.65–1.79 m (4Н,
Н2,2',6,6'), 1.82–1.94 m (6H, H1,1',6,6',7,7'), 2.01–2.06 m
(4H, H7,7',11,11'), 2.13 m, 2.17 m (4Н, Н3,3',11,11'), 2.50 m
(4H, H12,12',12,12'), 3.33 m (4Н, 2СОNСН2), 3.60 s
Methyl (1S,4aS,8aR)-5-[2-(2-{(Е)-3-[6-
(acryloylamino)hexylamino]-3-oxoprop-1-en-1-yl}
furan-3-yl)ethyl]-1,4a,6-trimethyl -1,2,3,4,4a,7,8,8a-
octahydronaphthalene-1-carboxylate (XXXIV). To a
solution of 1.00 g (3.03 mmol) of methyl phlomisoate (I)
in a mixture of 4 mL of propionic acid and 4 mL of ethyl
ether while stirring was added in succession 0.68 mL
(3.03 mmol) of N,N'-(hexane-1,6-diyl)bisacrylamide
(XXXIII), 0.09 g (0.30 mmol) of Pd(OAc)2, 0.28 g
(1.51 mmol) of Cu(OAc)2, and 0.03 g (0.30 mmol) of
1,4-benzoquinone. The reaction mixture was intermit-
tently stirred in an oxygen flow at 40°С over 60 h, on
cooling it was poured into 30 mL of water, the reaction
products were extracted with chloroform (3 × 50 mL). The
(6Н, ОСН3), 6.01 br.s (2Н, 2NH), 6.25 d (2Н, Н2",2”
,
combined organic solutions were washed with water (3 ×
50 mL) and dried with MgSO4. The solvent was removed
in a vacuum, the residue was chromatographed on a col-
umn packed with silica gel (eluent petroleum ether–ethyl
ether, 4:1). The successive elution afforded 0.40 g (40%)
of initial diterpenoid I, 0.05 g (2%) of compound XXХV,
and 0.44 g (26%) of compound XXХIV.
J 15.1 Hz), 6.34 s (2H, H14,14'), 7.32 s (2H, H15,15'),
7.42 d (2Н, Н1",1”, J 15.1 Hz). 13C NMR spectrum, δ,
ppm: 17.61 q (C20,20'), 19.42 t (C2,2'), 19.75 q (C17,17'),
20.69 t (C6,6'), 25.41 t (C12,12'), 25.84 t (2СОNСН2СН2),
28.26 q (C19,19'), 29.01 t (C11,11'), 27.80 t (СН2), 34.15 t
(C7,7'), 37.11 t (C1,1'), 37.52 t (C3,3'), 38.54 t (СОNСН2),
39.42 s (C10,10'), 44.00 s (C4,4'), 51.06 q (ОСН3), 53.29 d
(С5,5'), 112.78 d (C14,14'), 116.58 d (С2",2”), 129.03 d
(С1",1”), 128.67 s (C8,8'), 129.25 s (C13,13'), 138.12 s (C9,9'),
143.21 d (С15,15'), 146.59 s (C16,16'), 166.85 s (2СОN),
178.02 s (C18,18'). Found, %: С 73.42; H 8.75; N 2.94.
C54H76N2O8. Calculated, %: С 73.60; H 8.69; N 3.18.
20
Compound XXXIV. Oily substance. [α]D +18.65°
(c 0.22, СНCl3). IR spectrum, cm–1: 3401, 2939, 2838,
1772, 1728, 1668, 1607, 1542, 1441, 1409, 1372, 1324,
1245, 1035, 971, 820, 738. 1Н NMR spectrum, δ, ppm:
0.70 s (3H, С20Н3), 0.97 d.t (1Н, Н3, J 13.0, 4.3 Hz), 1.15 s
(3Н, С19Н3), 1.20 m (1Н, Н1), 1.30 m (5H, СН2СН2, H5),
1.48 m (5H, 2СОNСН2СН2, H2), 1.58 s (3H, С17Н3),
1.63–1.79 m (2Н, Н2,6), 1.80–1.93 m (3H, H1,6,7),
1.97–2.05 m (2H, H7,11), 2.13 m, 2.17 m (2Н, Н3,11),
2.47 m (2H, H12,12), 3.27 m (4Н, 2СОNСН2), 3.57 s (3Н,
ОСН3), 5.55 d.d (1Н, СН=, J 9.4, 2.3 Hz), 6.17 d (1Н,
СН2=, J 9.4 Hz), 6.21 d (1Н, СН2=, J 2.3 Hz), 6.29 d
(1Н, Н2', J 15.2 Hz), 6.31 d (1H, H14, J 1.3 Hz), 6.49 br.s
The signals marked with an asterisk (*) are mutu-
ally exchangeable within the description of the same
compound.
ACKNOWLEDGMENTS
The study was carried out under the financial support
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

KHARITONOV et al.
1702
Oxygen and sulfurcontaining heterocycles, Kartsev, V.G.,
Ed., Moskow: IBS Oress, 2003, vol. 1, p. 94; Gonzalez-
Coloma, A., Guadano, A., Tonn, C.E., and Sosa, M.E.,
Zeitsch. Naturforsch. C: J. Biosci., 2005, vol. 60, p. 855;
Liu, Y., Zhang, S., andAbreu, P.J.M., Nat. Prod. Rep., 2006,
vol. 23, p. 630.
of the Russian Foundation for Basic Research (grant
no. 11-03-00242).
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