Synthetic transformations of higher terpenoids: XV. Transformations of azlactone derived from 16-formyllambertianic acid methyl ester

Article abstract of DOI:10.1134/S1070428007060073

Condensation of 16-formyllambertianic acid methyl ester with hippuric acid gave methyl 15,16-epoxy-16-[(4Z)-5-oxo-2-phenyl-4,5-dihydrooxazol-4- ylidenemethyl]labda-8(20),13(16),14-trien-19-oate which underwent ready transformation into 2-benzoylamino-3-(2

Full text of DOI:10.1134/S1070428007060073

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 6, pp. 839–851. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © Yu.V. Kharitonov, E.E. Shul’ts, M.M. Shakirov, G. A. Tolstikov, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43,
No. 6, pp. 843–854.
Synthetic Transformations of Higher Terpenoids:
XV.* Transformations of Azlactone Derived
from 16-Formyllambertianic Acid Methyl Ester
Yu. V. Kharitonov, E. E. Shul’ts, M. M. Shakirov, and G. A. Tolstikov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: schultz@nioch.nsc.ru
Received June 1, 2006
Abstract—Condensation of 16-formyllambertianic acid methyl ester with hippuric acid gave methyl 15,16-ep-
oxy-16-[(4Z)-5-oxo-2-phenyl-4,5-dihydrooxazol-4-ylidenemethyl]labda-8(20),13(16),14-trien-19-oate which
underwent ready transformation into 2-benzoylamino-3-(2-furyl)acrylic acid of the labdanoid series. Reactions
of the diterpenoid azlactone with amines and α-amino acid esters led to the formation of the corresponding
carbamoylvinylbenzamides and N-(2-benzoylaminoacryloyl) amino acid esters, and furylacrylic acid hydra-
zides were formed in reactions with hydrazines. Cyclization of the N′-phenylhydrazide by the action of 1 M
aqueous sodium hydroxide gave the corresponding 1,2,4-triazin-6-one. By treatment of the azlactone with
aqueous ammonia on heating, 4-substituted 2-phenyl-4,5-dihydroimidazol-5-one was obtained.
DOI: 10.1134/S1070428007060073
Reactions of aldehydes with acylaminoacetic acids
(Erlenmeyer reaction) lead to the formation of oxazol-
5(4H)-ones [2–4]. From the synthetic viewpoint, these
reactions ensure preparation of amino acid derivatives
under mild conditions. Aldehyde nature considerably
affects the reaction course. Aromatic aldehydes and
most heterocyclic aldehydes readily react with hippuric
acid to give the corresponding oxazolones in good
yields. However, the yields of condensation products
from substituted aldehydes are not always satisfactory.
Fatty aldehydes difficultly react with hippuric acid,
while analogous reactions of terpenoid aldehydes were
not studied.
a result of strong tarring. On the other hand, the yield
of azlactone III increased to 76% when potassium car-
bonate was used instead of sodium acetate [7]. Com-
pound III was formed as a single isomer having Z con-
figuration of the double bond.
Azlactone III smoothly reacted with primary
amines [such as aniline, benzylamines, and phenyl-
ethyl(propyl)amines] and 7-aminoheptanoic acid on
heating in benzene to give 59–91% of N-(1-carbamoyl-
vinyl)benzamides IV–X (Scheme 1). The lowest yield
was observed in the reaction with 3,5,6-trimethoxy-
benzylamine; extension of the alkyl chain between the
benzene ring and amino group increases the product
yield. Reactions of compound III with secondary
amines (piperidine and N-methylphenylmethanamine
required prolonged heating, and the corresponding
terpenoid N-(carbamoylvinyl)benzamides XI and XII
were isolated in 73–80% yield. Treatment of III with
L-proline tert-butyl ester smoothly afforded 83% of
pyrrolidine-containing labdanoid XIII. The NMR
spectra of compounds XI and XIII in CDCl3 revealed
conformational isomerism arising from restricted
rotation about the amide C–N bond; no such isomerism
was observed in DMSO-d6 [8]. Azlactone III readily
reacted with α-amino acid (leucine and isoleucine)
The goal of the present work was to synthesize
diterpenoid azlactone from 16-formyllambertianic acid
methyl ester (I) [5] and study its reactions with nucleo-
philes. We have found that aldehyde I reacts with
hippuric acid (II) under standard conditions (heating in
boiling acetic anhydride in the presence of sodium
acetate) [6] to give labdanoid oxazol-5(4H)-one III in
44% yield (conversion 56%) (Scheme 1). We failed to
raise the product yield by increasing the reaction time
to 90 min; by contrast, the yield was as poor as 25% as
* For communication XIV, see [1].
839

KHARITONOV et al.
840
Scheme 1.
O
O
1
5
4
Ph
3
2
4a
N
CHO
O
16'
12
13'
11
O
17
14'
PhCONHCH2COOH (II)
Ac2O, K2CO3
Me
Me
15'
CH2
CH2
1
4
9
6
20
2
3
10
5
8
7
19
18
Me
COOMe
Me
COOMe
I
III
H2NCHRCOOR'
PhH, 75°C
NHRR'
PhH, 75°C
H+
H
O
N 2''
COOR'
CONRR'
2'
COOH
2'
1''
2'
3''
R
1'
1'
1'
NHCOPh
NHCOPh
NHCOPh
3' 4'
O
O
O
Me
Me
Me
CH2
CH2
CH2
Me
COOMe
Me
COOMe
Me
COOMe
IV–XIII
XIV, XV
XVI
IV–X, R′ = H; IV, R = Ph; V, R = PhCH2; VI, R = 4-HOC6H4(CH2)2; VII, R = 3,4,5-(MeO)3C6H2CH2; VIII, R = 3,5-(t-Bu)2-
4-HOC6H2(CH2)2; IX, R = 3,5-(t-Bu)2-4-HOC6H2(CH2)3; X, R = HOCO(CH2)6; XI, R = PhCH2, R′ = Me; XII, RR′ = (CH2)5;
XIII, RR′N = 2-(tert-butoxycarbonyl)pyrrolidin-1-yl; XIV, R = MeCH2CH(Me), R′ = Me; XV, R = Me2CHCH2, R′ = t-Bu.
esters, yielding 62–78% of terpenoid N-(2-benzoyl-
aminoacryloyl) amino acid esters XIV and XV. Ter-
penoid oxazol-5(4H)-one III undergoes hydrolysis on
treatment with a solution of hydrogen chloride in di-
ethyl ether or with 10% alcoholic alkali; the hydrolysis
product is individual α-acylamino acid XVI with Z
configuration of the double bond.
tuted 1,2,4-triazin-6-one XIX in 80% yield by heating
in 1 M aqueous sodium hydroxide for a short time.
4,5-Dihydroimidazol-5-one XX of the labdane series
was synthesized in 56% yield by heating azlactone III
with aqueous ammonia in the presence of a base in
a sealed ampule. Compounds XIX and XX were isolat-
ed as individual isomers having Z configuration of the
double bond.
Some naturally occurring heterocyclic diterpenoids
(e.g., lissoclimides and echinophyllins) exhibit pro-
nounced pharmacological activity [9, 10]. Taking this
into account, we made an attempt to obtain nitrogen-
containing heterocyclic derivatives via transformations
of azlactone III. Reactions of III with hydrazines on
heating in methanol gave the corresponding acrylic
acid hydrazides XVII and XVIII in 77–90% yield
(Scheme 2). It is known that hydrazides derived from
α,β-unsaturated acids undergo cyclization to 1,2,4-tri-
azin-6-ones [11] or pyrazole derivatives [12]. N′-Phen-
ylhydrazide XVIII was converted into 3,5-disubsti-
The structure of labdanoids III–XX was proved by
the analytical and spectral data. The 1H NMR spectrum
of azlactone III contained signals from protons in the
diterpene fragment, a signal from the 4a-H olefinic
proton, and signals from protons in the phenyl group at
δ 7.41 (2H), 7.48 (1H), and 8.07 ppm (2H). The Z con-
figuration of the exocyclic double bond was determin-
ed on the basis of the 3JCH coupling constant in the 13C
NMR spectrum. According to published data [13], the
vicinal coupling constant between the carbonyl carbon
atom in the oxazolone ring and olefinic Hβ proton
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XV.
841
Scheme 2.
O
NH
CONHNHR
NHCOPh
1
5
4
Ph
3
N
2
4a
Aqueous NH3
RNHNH2
Na2CO3, 110°C
MeOH, 25°C
O
O
III
Me
Me
CH2
CH2
Me
COOMe
Me
COOMe
XX
XVII, XVIII
H
N
1
O
N2
3
6
5
5a
N4
H
Ph
1 M NaOH, 100°C
O
XVIII
Me
CH2
Me
COOMe
XIX
XVII, R = H; XVIII, R = Ph.
1
[3J(C5,4a-H)] is 5.5 Hz for Z isomers XXIa and 12.5 Hz
for E isomers XXIb (Scheme 3). In our case, the JCH
signal in the H NMR spectra of IV–X appears in
a stronger field (Δδ = 0.28–0.48 ppm) relative to the
corresponding signal of azlactone III. Analogous up-
field shift of the C1′ signal is observed in the 13C NMR
spectra (δC 110–112 ppm). N,N-Disubstituted amides
3
coupling constant was equal to 5.1 Hz. The oxazolone
C=O signal appears as a doublet at δC 167.53 ppm
due to coupling with 4a-H; therefore, this signal can
be readily distinguished from the nearby signals
belonging to the C=N carbon atom (a multiplet at
δC 162.14 ppm due to coupling with ortho protons of
the phenyl group) and ester carbonyl carbon atom in
the terpenoid moiety (δC 177.27 ppm). Likewise, we
have assigned signals from the carbonyl groups and
determined Z configuration of the olefinic bond in
1
XI–XIII characteristically showed in the H NMR
spectra an upfield shift of the 1′-H signal (Δδ = 1.06–
1.25 ppm) as compared to azlactone III. Restricted
rotation about the amide C–N bond in molecule XI
(E/Z-conformer ratio 1: 1) leads to doubling of signals
from the benzylic CH2 protons (δ 4.71, 4.78 ppm),
olefinic 1′-H proton (δ 5.74 s, 5.81 s), and protons in
the terpene fragment [δ 6.32, 6.38 (14-H), 7.57, 7.58
(15-H), 4.90, 4.92 and 4.55, 4.57 ppm (17-H)] in the
1H NMR spectrum recorded from a solution in CDCl3.
In the 13C NMR spectrum of XI, signals from two
carbonyl carbon atoms, C1′, C2′, C8, C16, and CH2
(δC 32.93, 36.44 ppm) and CH3 groups (δC 50.56,
55.16 ppm) are doubled. In going to DMSO-d6, no
signal doubling is observed, for the conformational
equilibrium is completely displaced toward one of the
conformers (XIa or XIb; Scheme 3).
3
hydrolysis product XVI: J(2′-C, 1′-H) = 5.1 Hz;
δC 167.60 (COOH), 166.40 ppm (NHCOPh).
Introduction of acylaminoacrylic acid fragments
into the molecule of lambertianic acid methyl ester
(XXII) gives rise to additional signals in the 1H NMR
spectra of compounds IV–X, which belong to protons
in the amine moiety. The amide proton (CONHR)
resonates as a broadened singlet in the region δ 6.7–
6.5 ppm, and the NH proton in the benzoylamino
group gives a singlet at δ 8.7–8.5 ppm. Signals from
the carbonyl carbon nuclei (δC 163–170 ppm and 166–
167 ppm for CONHR and NHCOPh, respectively) are
readily distinguished in the 13C NMR spectra. The 1′-H
In the IR spectra of hydrazides XVII and XVIII we
observed absorption bands typical of hydrazide and
amide groups at 1640–1675, 3059, 3239, and 3431 cm–1.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

KHARITONOV et al.
842
Scheme 3.
O
H
H
Me
O
CH2
N
R
O
X
X
N
O
O
Me
COOMe
R
Z-XXIa
E-XXIa
XXII
Ph
HN
Ph
HN
O
O
Me
CH2Ph
15
O
O
2'
N
N
16
14
CH2Ph
Me
1'
13
13
O
O
17
CH2
OMe
Me
OMe
Me
CH2
O
O
9
H
H
Me
Me
XIa
XIb
1
Three NH proton signals in the H NMR spectrum of
hydrazide XVIII are readily distinguished: the hydra-
zide CONHaNHbPh protons resonate as broadened
singlets at δ 8.33 (Ha, halfwidth 5 Hz) and 6.26 ppm
(Hb, halfwidth 12 Hz), and the NHCOPh signal is
a singlet at δ 8.64 ppm. Singlets at δ 9.07 and 9.09 ppm
exocyclic double C=C bond. The 4a-H signal is locat-
ed at δ 7.03 ppm (br.s) in the 1H NMR spectrum, i.e., it
appears in a weaker field relative to the corresponding
signal in the spectrum of III; the NH proton resonates
as a singlet at δ 11.79 ppm.
Thus, the condensation of 16-formyllambertianic
acid methyl ester with hippuric acid gives the corre-
sponding 4,5-dihydrooxazol-5-one derivatives whose
subsequent transformations open synthetic routes to
new nitrogen-containing derivatives of the labdane
series.
1
in the H NMR spectra of XIX were assigned to
protons on N1 and N4, respectively, of the 1,2,4-triazin-
6-one fragment. Compound XIX was identified as
3,5-disubstituted 1,2,4-triazine derivative on the basis
of the following data. Its 13C NMR spectrum contained
three singlets at δC 161.38, 123.96, and 159.49 ppm,
which belong to C6, C5, and C3, respectively; they were
assigned using two-dimensional 13C–1H correlation
technique (COLOC). The C3 nucleus showed coupling
with ortho protons in the phenyl substituent, and the C5
and C6 nuclei were coupled with 5a-H. The coupling
EXPERIMENTAL
The IR spectra were recorded in KBr on a Vector-
22 spectrometer. The UV spectra were measured on
an HP 8453 UV-Vis spectrophotometer from solutions
in ethanol with a concentration of about 10–4 M. The
NMR spectra were obtained from solutions in CDCl3
on Bruker AV-300 (300.13 MHz for 1H and 75.47 MHz
constant J between C6 and 5a-H is 5.3 Hz, indicating
3
Z configuration of the exocyclic double bond. The
presence of a triazinone ring in molecule XIX is also
confirmed by the mass spectrum of this compound,
which contains a fragment ion peak with m/z 187
(Irel 83.5%; phenylmethyldihydrotriazol-1-one).
1
for 13C), Bruker AM-400 (400.13 MHz for H and
100.78 MHz for 13C), and Bruker DRX-500 instru-
1
ments (500.13 for H and 125.76 MHz for 13C).
Signals were assigned using various proton–proton and
carbon–proton shift correlation techniques (COSY,
COLOC, CORRD). The high-resolution mass spectra
(electron impact, 70 eV) were run on a Finnigan MAT-
8200 mass spectrometer (vaporizer temperature 200–
270°C). The melting points were determined using
a Kofler hot stage. The optical rotations were meas-
ured on a Polamat A polarimeter from solutions in
The structure of imidazolone XX follows from the
NMR data. Three singlets in the 13C NMR spectrum of
XX at δC 148.01, 158.04, and 174.05 ppm belong,
respectively, to the C4, C2, and C5 atoms of the imida-
zole ring. The C5 signal in the spectrum recorded
without decoupling from protons appears as a doublet
(3JCH = 5.1 Hz) due to coupling with 4a-H; this cou-
pling constant corresponds to Z configuration of the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XV.
843
3.51 s (3H, OCH3), 4.53 s, 4.92 s (2H, 20′-H), 6.40 d
(1H, 14′-H, J = 1.8 Hz), 6.92 s (1H, 4a-H), 7.41 m
(2H, 3″-H, 5″-H), 7.48 m (1H, 4″-H), 7.68 d (1H,
15′-H, J = 1.8 Hz), 8.07 m (2H, 2″-H, 6″-H). 13C NMR
spectrum, δC, ppm: 12.36 q (C17′), 19.54 t (C2′), 23.49 t
(C12′), 23.89 t (C11′), 25.90 t (C6′), 28.39 q (C18′),
37.74 t (C3′), 38.19 t (C7′), 38.65 t (C1′), 39.78 s (C4′),
43.87 s (C10′), 50.81 q (OCH3), 54.17 d (C9′), 55.77 d
(C5′), 106.58 t (C20′), 113.67 d (C14′), 115.00 d (C4a),
125.32 s (C1″), 127.86 d (C2″, C6″), 128.18 s (C4),
128.49 d (C3″, C5″), 132.64 d (C4″), 137.80 s (C13′),
146.80 s (C16′), 147.14 s (C8′), 147.71 d (C15′), 162.14 s
(C2), 167.53 s (C5), 177.27 s (C19′). Found, %: C 74.03;
H 7.11; N 2.7. C31H35NO5. Calculated, %: C 74.25;
H 6.99; N 2.79.
chloroform or ethanol at room temperature (20–23°C).
The progress of reactions was monitored by TLC on
Silufol UV-254 plates; spots were visualized by spray-
ing with a 10% aqueous solution of sulfuric acid. Col-
umn chromatography was performed on KSK silica gel
(grain size 0–70 μm).
16-Formyllambertianic acid methyl ester (I) was
synthesized from ester XXII according to the proce-
dure reported in [5], and compound XXII was pre-
pared as described in [14].
Methyl (Z)-(1S,4aR,5S)-1,4a-dimethyl-6-methyli-
dene-5-{2-[2-(5-oxo-2-phenyl-4,5-dihydro-1,3-oxa-
zol-4-ylidenemethyl)furan-3-yl]ethyl}decahydro-
naphthalene-1-carboxylate {III, methyl 15,16-ep-
oxy-16-[(4Z)-5-oxo-2-phenyl-4,5-dihydro-1,3-oxa-
zol-4-ylidenemethyl]labda-8(20),13(16),14-trien-19-
oate}. a. Hippuric acid (II), 0.50 g (2.79 mmol), and
potassium carbonate, 0.38 g (2.8 mmol), were added
under stirring to a solution of 1.00 g (2.8 mmol) of
aldehyde I in 15 ml of acetic anhydride. The mixture
was stirred for 5 h and left overnight, and the precip-
itate was filtered off, washed with water, dried under
reduced pressure, and recrystallized from petroleum
ether–diethyl ether (2:1). Yield 1.06 g (76%).
Methyl (1S,4aR,5S)-5-{2-[2-(2-benzoylamino-3-
oxo-3-phenylaminoprop-1-en-1-yl)furan-3-yl]-
ethyl}-1,4a-dimethyl-6-methylidenedecahydronaph-
thalene-1-carboxylate [IV, methyl 16-(2-benzoyl-
amino-3-oxo-3-phenylaminoprop-1-en-1-yl)-15,16-
epoxylabda-8(20),13(16),14-trien-19-oate]. Aniline,
0.11 g (1.2 mmol), was added to a solution of 0.50 g
(1.0 mmol) of azlactone III in 7 ml of benzene, and the
mixture was heated for 2 h at 70°C. After cooling, the
precipitate was filtered off, washed with diethyl ether,
and dried under reduced pressure. Yield 0.49 g (82%),
mp 156–159°C, [α]D20 = 14.8° (c = 3.1, CHCl3). IR
spectrum, ν, cm–1: 700, 754, 891, 1500, 1600, 3075
(C=C); 1722 (C=O); 1638, 1657, 3420 [C(O)NH].
UV spectrum, λmax, nm (logε): 226 (3.89), 326 (4.05).
1H NMR spectrum (CDCl3), δ, ppm: 0.45 s (3H,
C17H3), 0.91 t.d (1H, 1-H, J = 13.5, 3.3 Hz), 0.98 t.d
(1H, 3-H, J = 13.6, 3.0 Hz), 1.14 s (3H, C18H3),
1.22 d.d (1H, 5-H, J = 12.8, 2.6 Hz), 1.45 d.m (1H,
b. Hippuric acid (II), 0.50 g (2.8 mmol), and so-
dium acetate, 0.23 g (2.8 mmol), were added to a solu-
tion of 1.00 g (2.8 mmol) of compound I in 15 ml of
acetic anhydride. The mixture was heated for 1 h under
reflux, cooled to room temperature, and passed
through 25 g of aluminum oxide. The solvent was
removed under reduced pressure, and the residue was
subjected to chromatography on silica gel using pe-
troleum ether–diethyl ether (4:1) as eluent to isolate
1.00 g of a mixture of initial compound I and product
III. Recrystallization from petroleum ether–diethyl
ether (6 : 1) gave 0.61 g (44%) of compound III.
mp 112–115°C, [α]D20 = 1.2° (c = 7.7, CHCl3). IR spec-
trum, ν, cm–1: 702, 780, 883, 983, 1551 (C=C); 1645,
1720, 1759, 1789 (C=O). UV spectrum, λmax, nm
(logε): 232 (3.41), 266 (3.75), 392 (4.18), 409 (4.17).
1H NMR spectrum (CDCl3), δ, ppm: 0.43 s (3H,
C17′H3), 0.82 d.d.d (1H, 1′-H, J = 13.5, 13.2, 4.2 Hz),
0.90 t.d (1H, 3′-H, J = 13.2, 4.0 Hz), 1.06 s (3H,
C18′H3), 1.13 d.d (1H, 5′-H, J = 12.4, 3.1 Hz), 1.38 d.m
2
2-H, J = 12.8 Hz), 1.48–1.53 m (2H, 9-H, 11-H),
1.61 m (1H, 11-H), 1.67–1.79 m (3H, 1-H, 6-H, 2-H),
1.85 t.d (1H, 7-H, J = 12.8, 3.2 Hz), 1.95 d.m (1H,
2
2
6-H, J = 13.2 Hz), 2.11 d.m (1H, 3-H, J = 13.6 Hz),
2.26 m (1H, 12-H, 2J = 15.5 Hz), 2.38 d.t (1H, 7-H, J =
12.8, 2.6 Hz), 2.46 d.d.d (1H, 12-H, J = 15.5, 6.6,
4.2 Hz), 3.57 s (3H, OCH3), 4.52 s and 4.90 s (1H
each, 20-H), 6.40 d (1H, 14-H, J = 1.8 Hz), 6.85 s (1H,
1′-H), 7.04 t (1H, 4″-H, J = 7.6 Hz), 7.24 m (2H, 3″-H,
5″-H), 7.34 d (1H, 15-H, J = 1.8 Hz), 7.46 m (2H,
7′-H, 9′-H), 7.55 t (1H, 8′-H, J = 8.0 Hz), 7.57 m (2H,
2″-H, 6″-H), 7.95 d (2H, 6′-H, 10′-H, J = 7.6 Hz),
2
(1H, 2′-H, J = 14.2 Hz), 1.48 d (1H, 9′-H, J =
13
10.8 Hz), 1.60–1.80 m (6H, 7′-H, 2′-H, 6′-H, 11′-H,
8.71 s (1H, 3′-H), 8.80 s (1H, NHPh). C NMR spec-
2
1′-H), 1.89 d.m (1H, 6′-H, J = 13.2 Hz), 2.05 d.d.d
trum, δC, ppm: 12.47 q (C17), 19.73 t (C2), 23.20 t
(C12), 24.14 t (C11), 26.10 t (C6), 28.60 q (C18), 37.96 t
(C3), 38.46 t (C7), 38.88 t (C1), 40.00 s (C4), 44.11 s
(C10), 51.01 q (OCH3), 54.75 d (C9), 55.92 d (C5),
(1H, 3′-H, J = 13.2, 3.3, 1.3 Hz), 2.36 m (1H, 7′-H,
2J = 12.6 Hz), 2.51 d.d.d (1H, 12′-H, J = 14.4, 9.0,
7.7 Hz), 2.66 d.d.d (1H, 12′-H, J = 14.4, 7.8, 4.5 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

KHARITONOV et al.
844
106.53 t (C20), 111.52 d (C1′), 112.86 d (C14), 120.07 d
(C2″, C6″), 123.99 d (C4″), 126.40 s (C2′), 127.44 d (C6′,
C10′), 128.63 d and 128.66 d (C3″, C5″, C7′, C9′),
130.52 s (C13), 132.23 d (C8′), 132.94 s (C1″), 137.98 s
(C5′), 143.52 d (C15), 146.16 s (C16), 147.49 s (C8),
163.00 s (CONH), 166.00 s (C4′), 177.62 s (C19).
Found, %: C 74.52; H 7.79; N 4.59. C37H42N2O5. Cal-
culated, %: C 74.75; H 7.71; N 4.71.
Methyl (1S,4aR,5S)-5-[2-(2-{2-benzoylamino-3-
[2-(4-hydroxyphenyl)ethylamino]-3-oxoprop-1-en-
1-yl}furan-3-yl)ethyl]-1,4a-dimethyl-6-methylidene-
decahydronaphthalene-1-carboxylate (VI, methyl
16-{2-benzoylamino-3-[2-(4-hydroxyphenyl)ethyl-
amino]-3-oxoprop-1-en-1-yl}-15,16-epoxylabda-
8(20),13(16),14-trien-19-oate). A mixture of 0.50 g
(1.0 mmol) of azlactone III and 0.14 g (1.0 mmol) of
2-(4-hydroxyphenyl)ethanamine in 7 ml of benzene
was heated for 4 h at 70°C on an oil bath. The solvent
was removed under reduced pressure, and the residue
was subjected to chromatography on silica gel using
chloroform–methanol (100:1) as eluent. The subse-
quent recrystallization from diethyl ether gave 0.53 g
(84%) of compound VI, mp 125–128°C, [α]D20 = 13.7°
(c = 6.5, CHCl3). IR spectrum, ν, cm–1: 712, 828, 893,
1515 (C=C); 1723 (C=O); 1648, 1650, 3423 (CONH);
3347 (OH). UV spectrum, λmax, nm (logε): 225 (3.33),
316 (3.38). 1H NMR spectrum (CDCl3), δ, ppm: 0.43 s
(3H, C17H3), 0.89 t.d (1H, 1-H, J = 13.2, 3.1 Hz),
0.95 t.d (1H, 3-H, J = 13.3, 2.6 Hz), 1.10 s (3H,
C18H3), 1.21 d (1H, 5-H, J = 12.4, 2.2 Hz), 1.42 m (1H,
Methyl (1S,4aR,5S)-5-{2-[2-(2-benzoylamino-3-
benzylamino-3-oxoprop-1-en-1-yl)furan-3-yl]ethyl}-
1,4a-dimethyl-6-methylidenedecahydronaphtha-
lene-1-carboxylate [V, methyl 16-(2-benzoylamino-
3-benzylamino-3-oxoprop-1-en-1-yl)-15,16-epoxy-
labda-8(20),13(16),14-trien-19-oate]. A solution of
0.50 g (1.0 mmol) of azlactone III and 0.14 g
(1.2 mmol) of benzylamine in 7 ml of benzene was
heated for 2 h at 70°C on an oil bath. The solvent was
removed under reduced pressure, the residue was
treated with 7 ml of diethyl ether, and the precipitate
was filtered off, washed with diethyl ether (3×10 ml),
and dried under reduced pressure. Yield 0.38 g (62%).
Column chromatography of the mother liquor on silica
gel (using chloroform as eluent) gave an additional
portion, 0.15 g (24%), of compound V. mp 98–100°C,
[α]D20 = 12.3° (c = 5.4, CHCl3). IR spectrum, ν, cm–1:
698, 715, 750, 893, 1516, 1575 (C=C); 1721 (C=O);
1645, 3424 [C(O)NH]. UV spectrum, λmax, nm (logε):
2
2-H, J = 12.6 Hz), 1.50 m (2H, 9-H, 11-H), 1.61 m
(1H, 11-H), 1.66–1.75 m (3H, 1-H, 6-H, 2-H), 1.84 t.d
(1H, 7-H, J = 13.2, 3.0 Hz), 1.92 m (1H, 6-H),
2
2.07 d.m (1H, 3-H, J = 13.3 Hz), 2.27 m (1H, 12-H),
2
2.35 m (1H, 7-H, J = 12.6 Hz), 2.49 m (1H, 12-H),
2.66 t (2H, CH2, J = 6.3 Hz), 3.45 d.d (2H, CH2NH,
J = 14.1, 6.3 Hz), 3.54 s (3H, OCH3), 4.51 s and 4.87 s
(1H each, 20-H), 6.27 d (1H, 14-H, J = 1.8 Hz),
6.63 br.s (1H, CONH), 6.67 m (2H, 3″-H, 5″-H), 6.74 s
(1H, 1′-H), 6.86 d (2H, 2″-H, 6″-H, J = 7.2 Hz), 7.29 d
(1H, 15-H, J = 1.8 Hz), 7.38 m (2H, 7′-H, 9′-H), 7.46 t
(1H, 8′-H, J = 7.1 Hz), 7.83 m (2H, 6′-H, 10′-H),
8.00 br.s (1H, OH), 8.56 s (1H, 3′-H). 13C NMR spec-
trum, δC, ppm: 12.37 q (C17), 19.62 t (C2), 23.08 t
(C12), 24.02 t (C11), 25.99 t (C6), 28.47 q (C18), 34.34 t
(CH2), 37.79 t (C3), 38.34 t (C7), 38.68 t (C1), 39.89 s
(C4), 41.31 t (CH2N), 44.00 s (C10), 50.96 q (OCH3),
54.56 d (C9), 55.74 d (C5), 106.44 t (C20), 111.44 d
(C1′), 112.67 d (C14), 115.41 d (C3″, C5″), 125.52 s (C2′),
127.31 d (C6′, C10′), 128.48 d (C2″, C6″), 129.33 s (C1″),
129.40 d (C7′, C9′), 130.19 s (C13), 132.03 d (C8′),
132.87 s (C5′), 143.38 d (C15), 145.90 s (C16), 147.40 s
(C8), 155.14 s (C4″), 165.25 s (CONH), 166.53 s (C4′),
177.72 s (C19). Found, %: C 73.15; H 7.36; N 4.45.
C39H46N2O6. Calculated, %: C 73.35; H 7.21; N 4.39.
1
226 (4.08), 317 (4.36). H NMR spectrum (CDCl3), δ,
ppm: 0.45 s (3H, C17H3), 0.93 m (2H, 1-H, 3-H), 1.13 s
(3H, C18H3), 1.22 m (1H, 5-H), 1.44 m (1H, 2-H),
1.58 m (2H, 9-H, 11-H), 1.70–1.88 m (5H, 11-H, 1-H,
2-H, 7-H, 6-H), 1.94 m (1H, 6-H), 2.09 m (1H, 3-H),
2.32 m (2H, 7-H, 12-H), 2.53 m (1H, 12-H), 3.57 s
(3H, OCH3), 4.86 s (2H, CH2), 4.55 s and 4.86 s (1H
each, 20-H), 6.32 d (1H, 14-H, J = 1.8 Hz), 6.67 s (1H,
1′-H), 7.05 m (4H, 15-H, 4″-H, 3″-H, 5″-H), 7.30 m
(5H, NH, 2′-H, 6″-H, 7′-H, 9′-H), 7.41 t (1H, 8′-H, J =
7 Hz), 7.75 d (2H, 6′-H, 10′-H), 8.64 s (1H, 3′-H).
13C NMR spectrum, δC, ppm: 12.48 q (C17), 19.78 t
(C2), 23.50 t (C12), 24.26 t (C11), 26.15 t (C6), 28.64 q
(C18), 38.03 t (C3), 38.54 t (C7), 38.92 t (C1), 40.07 s
(C4), 43.40 t (CH2), 44.16 s (C10), 50.94 q (OCH3),
55.16 d (C9), 56.04 d (C5), 106.48 t (C20), 109.00 d
(C1′), 112.50 d (C14), 127.44 d (C6′, C10′), 127.47 s
(C2′), 127.75 d (C2″, C6″), 128.36 d (C3″, C5″), 128.36 s
(C4″), 128.47 d (C7′, C9′), 130.52 s (C13), 131.39 d (C8′),
134.32 s (C5′), 134.43 s (C1″), 143.30 d (C15), 147.06 s
(C16), 147.62 s (C8), 165.29 s (C4′), 170.53 s (CONH),
177.61 s (C19). Found, %: C 75.35; H 7.23; N 4.64.
C38H44N2O5. Calculated, %: C 75.00; H 7.24; N 4.64.
Methyl (1S,4aR,5S)-5-(2-{2-[2-benzoylamino-3-
oxo-3-(3,4,5-trimethoxybenzylamino)prop-1-en-1-
yl]furan-3-yl}ethyl)-1,4a-dimethyl-6-methylidene-
decahydronaphthalene-1-carboxylate {VII, methyl
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XV.
845
hydroxyphenyl)ethylamine in 7 ml of benzene was
heated for 6 h at 70°C. The solvent was removed under
reduced pressure, and the residue was subjected to
chromatography on silica gel using chloroform as
eluent, followed by recrystallization from diethyl ether.
Yield 0.57 g (76%), mp 91–93°C, [α]D20 = 9.4° (c = 1.9,
CHCl3). IR spectrum, ν, cm–1: 713, 750, 769, 890,
1515 (C=C); 1722 (C=O); 1578, 1640, 1665 (CONH);
3300, 3426 (OH, NH). UV spectrum, λmax, nm (logε):
16-[2-benzoylamino-3-oxo-3-(3,4,5-trimethoxy-
benzylamino)prop-1-en-1-yl]-15,16-epoxylabda-
8(20),13(16),14-trien-19-oate}. A mixture of 0.50 g
(1.0 mmol) of azlactone III and 0.22 g (1.1 mmol)
of 3,4,5-trimethoxybenzylamine in 7 ml of benzene
was heated for 4 h at 70°C on an oil bath. The solvent
was removed under reduced pressure, and the residue
was subjected to chromatography on silica gel using
chloroform as eluent. A fraction containing compound
VII was evaporated, and the residue was ground
with hexane. Yield 41.0 g (59%), mp 78–80°C, [α]D20 =
12.9° (c = 3.4, CHCl3). IR spectrum, ν, cm–1: 714, 775,
892, 1508 (C=C); 1721 (C=O); 1638, 1670, 3368,
3410 (CONH). UV spectrum, λmax, nm (logε): 230
1
226 (2.89), 316 (3.26). H NMR spectrum (CDCl3), δ,
ppm: 0.48 s (3H, C17H3), 0.94 t.d (1H, 1-H, J = 13.3,
3.8 Hz), 0.99 t.d (1H, 3-H, J = 13.5, 3.5 Hz), 1.14 s (3H,
C18H3), 1.25 d.d (1H, 5-H, J = 12.4, 3.0 Hz), 1.37 s
(18H, t-Bu), 1.48 m (1H, 2-H), 1.56 m (2H, 9-H,
11-H), 1.68–1.80 m (4H, 1-H, 6-H, 2-H, 11-H), 1.87 m
1
(2.94), 316 (3.28). H NMR spectrum (CDCl3), δ,
2
ppm: 0.47 s (3H, C17H3), 0.94 m (1H, 1-H), 0.99 m
(1H, 3-H), 1.15 s (3H, C18H3), 1.24 d.d (1H, 5-H, J =
12.5, 2.8 Hz), 1.46 m (1H, 2-H), 1.56 m (2H, 9-H,
11-H), 1.68–1.81 m (4H, 1-H, 6-H, 2-H, 11-H), 1.86 m
(1H, 7-H, J = 12.6 Hz), 1.96 m (1H, 6-H), 2.12 d.m
2
(1H, 3-H, J = 12.6 Hz), 2.33 m (2H, 12-H, 7-H),
2.58 m (1H, 12-H, J = 14.2, 6.8, 4.2 Hz), 2.79 t (2H,
CH2C6H2, J = 6.2 Hz), 3.58 s (3H, OCH3), 3.61 m (2H,
NHCH2), 4.56 s and 4.91 s (1H each, 20-H), 5.07 s
(1H, OH), 6.32 d (1H, 14-H, J = 1.8 Hz), 6.54 t (1H,
CONH, J = 5.6 Hz), 6.83 s (1H, 1′-H), 7.00 s (2H,
2″-H, 6″-H), 7.34 d (1H, 15-H, J = 1.8 Hz), 7.46 t (2H,
7′-H, 9′-H, J = 7.0 Hz), 7.54 t (1H, 8′-H, J = 7.0 Hz),
7.91 d (2H, 6′-H, 10′-H, J = 7.8 Hz), 8.55 br.s (1H,
3′-H, halfwidth 5.5 Hz). 13C NMR spectrum, δC, ppm:
12.44 q (C17), 19.69 t (C2), 23.21 t (C12), 24.12 t (C11),
26.07 t (C6), 28.56 q (C18), 30.09 q (CH3)3, 34.06 s
[C(CH3)3], 35.58 t (CH2C6H2), 37.93 t (C3), 38.43 t
(C7), 38.86 t (C1), 39.98 t (CH2N), 41.56 s (C4), 44.07 s
(C10), 50.96 q (OCH3), 54.70 d (C9), 55.90 d (C5),
106.48 t (C20), 110.72 d (C1′), 112.78 d (C14), 125.11 d
(C2″, C6″), 126.31 s (C2′), 127.32 d (C6′, C10′), 128.58 d
(C7′, C9′), 129.33 s and 129.81 s (C5′, C13), 132.05 d
(C8′), 133.19 s (C1″), 135.76 s (C3″, C5″), 143.14 d
(C15), 146.24 s (C16), 147.50 s (C8), 152.10 s (C4″),
164.80 s (CONH), 166.22 s (C4′), 177.58 s (C19).
Found, %: C 74.61; H 8.73; N 3.70. C47H62N2O6. Cal-
culated, %: C 75.20; H 8.28; N 3.73.
2
(1H, 7-H), 1.96 m (1H, 6-H), 2.13 d.m (1H, 3-H, J =
13.1 Hz), 2.38 m (2H, 12-H, 7-H), 2.60 m (1H, 12-H),
3.58 s (3H, OCH3), 3.79 s (3H, 4″-OCH3), 3.84 s (6H,
3″-OCH3, 5″-OCH3), 4.51 d (2H, CH2C6H2, J =
6.2 Hz), 4.55 s and 4.89 s (1H each, 20-H), 6.34 d (1H,
14-H, J = 1.8 Hz), 6.61 s (2H, 2″-H, 6″-H), 6.70 t (1H,
CONH, J = 6.1 Hz), 6.88 s (1H, 1′-H), 7.37 d (1H,
15-H, J = 1.8 Hz), 7.46 m (2H, 7′-H, 9′-H), 7.54 t (1H,
8′-H, J = 7.4 Hz), 7.90 d (2H, 6′-H, 10′-H, J = 7.8 Hz),
8.60 br.s (1H, 3'-H). 13C NMR spectrum, δC, ppm:
12.49 q (C17), 19.78 t (C2), 23.37 t (C12), 24.23 t (C11),
26.14 t (C6), 28.59 q (C18), 38.03 t (C3), 38.52 t (C7),
38.98 t (C1), 40.06 s (C4), 43.94 t (CH2), 44.17 s (C10),
50.93 q (OCH3), 54.94 d (C9), 56.04 q (3″-OCH3,
5″-OCH3), 56.04 d (C5), 65.64 q (4″-OCH3), 104.57 d
(C2″, C6″), 106.47 t (C20), 111.03 d (C1′), 112.92 d (C14),
126.29 s (C2′), 127.31 d (C6′, C10′), 128.65 d (C7′, C9′),
130.11 s (C13), 132.16 d (C8′), 133.22 s, 133.90 s (C4″,
C5′), 137.08 s (C1″), 143.38 d (C15), 146.31 s (C16),
147.60 s (C8), 153.28 s (C3″, C5″), 164.83 s (CONH),
166.22 s (C4′), 177.52 s (C19). Found, %: C 70.17;
H 7.25; N 3.97. C41H50N2O8. Calculated, %: C 70.49;
H 7.16; N 4.01.
Methyl (1S,4aR,5S)-5-[2-(2-{2-benzoylamino-3-
[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl-
amino]-3-oxoprop-1-en-1-yl}furan-3-yl)ethyl]-1,4a-
dimethyl-6-methylidenedecahydronaphthalene-1-
carboxylate (IX, methyl 16-{2-benzoylamino-3-[3-
(3,5-di-tert-butyl-4-hydroxyphenyl)propylamino]-3-
oxoprop-1-en-1-yl}-15,16-epoxylabda-8(20),13(16),-
14-trien-19-oate). A mixture of 0.50 g (1.0 mmol) of
azlactone III and 0.27 g (1.1 mmol) of 3-(3,5-di-tert-
butyl-4-hydroxyphenyl)propylamine in 7 ml of ben-
zene was heated for 6 h at 70°C. The solvent was
removed under reduced pressure, and the residue was
Methyl (1S,4aR,5S)-5-[2-(2-{2-benzoylamino-3-
[2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethylamino]-
3-oxoprop-1-en-1-yl}furan-3-yl)ethyl]-1,4a-dimeth-
yl-6-methylidenedecahydronaphthalene-1-carbox-
ylate (VIII, methyl 16-{2-benzoylamino-3-[2-(3,5-di-
tert-butyl-4-hydroxyphenyl)ethylamino]-3-oxoprop-
1-en-1-yl}-15,16-epoxylabda-8(20),13(16),14-trien-
19-oate). A mixture of 0.50 g (1.0 mmol) of azlactone
III and 0.27 g (1.1 mmol) of 2-(3,5-di-tert-butyl-4-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

KHARITONOV et al.
846
subjected to chromatography on silica gel using
chloroform as eluent, followed by recrystallization
from diethyl ether. Yield 0.69 g (91%), mp 85–87°C,
[α]D20 = 11.1° (c = 3.2, CHCl3). IR spectrum, ν, cm–1:
713, 747, 769, 890, 1513 (C=C); 1546, 1580, 1641,
1665 (CONH); 1723 (C=O); 3325, 3400 (OH, NH).
UV spectrum, λmax, nm (logε): 226 (2.89), 315 (3.24).
1H NMR spectrum (CDCl3), δ, ppm: 0.48 s (3H,
C17H3), 0.93 t.d (1H, 1-H, J = 13.5, 3.2 Hz), 0.98 t.d
(1H, 3-H, J = 13.2, 3.0 Hz), 1.14 s (3H, C18H3),
1.25 d.d (1H, 5-H, J = 12.8, 2.6 Hz), 1.40 s (18H,
t-Bu), 1.45 m (1H, 2-H), 1.55 m (2H, 9-H, 11-H),
1.66–1.80 m (4H, 1-H, 7-H, 2-H, 11-H), 1.86 m (3H,
907, 1522 (C=C); 1572, 1650, 1661 (CONH); 1717
(CO2Me); 3274, 3300 (OH, NH). UV spectrum, λmax
,
1
nm (logε): 227 (3.05), 315 (3.25). H NMR spectrum
(CDCl3), δ, ppm: 0.48 s (3H, C17H3), 0.92 t.d (1H, 1-H,
J = 13.3, 3.4 Hz), 0.98 t.d (1H, 3-H, J = 13.1, 2.9 Hz),
1.14 s (3H, C18H3), 1.24 d.d (1H, 5-H, J = 12.6,
2.8 Hz), 1.34 m (4H, 5″-H, 4″-H), 1.45 m (1H, 2-H,
2J = 12.8 Hz), 1.50–1.62 m (5H, 9-H, 6″-H, 3″-H),
1.66 m (1H, 2-H), 1.70–1.79 m (4H, 1-H, 6-H, 11-H),
1.86 t.d (1H, 7-H, J = 12.8, 3.6 Hz), 1.95 d.m (1H,
2
2
6-H, J = 12.8 Hz), 2.11 d.m (1H, 3-H, J = 13.1 Hz),
2.28 t (2H, 2″-H, J = 7.2 Hz), 2.34 m and 2.37 m (1H
each, 12-H, 7-H), 2.56 m (1H, 12-H, J = 14.8, 6.6,
4.0 Hz), 3.32 m (2H, 7″-H), 3.57 s (3H, OCH3), 4.55 s
and 4.91 s (1H each, 20-H), 6.30 d (1H, 14-H, J =
1.8 Hz), 6.57 t (1H, CONH, J = 6.0 Hz), 6.81 s (1H,
1′-H), 7.33 d (1H, 15-H, J = 1.8 Hz), 7.46 m (2H, 7′-H,
9′-H), 7.52 t (1H, 8′-H, J = 7 Hz), 7.91 m (2H, 6′-H,
10′-H), 8.56 br.s (1H, 3′-H, halfwidth 4.8 Hz).
13C NMR spectrum, δC, ppm: 12.47 q (C17), 19.74 t
(C2), 23.26 t (C12), 24.18 t (C11), 24.33 t (C6″), 26.11 t
(C6), 26.24 t and 28.44 t (C5″, C4″), 28.59 q (C18), 29.01
t (C3″), 33.72 t (C2″), 37.97 t (C3), 38.50 t (C7), 38.89 t
(C1), 39.79 t (C7″), 40.01 s (C4), 44.12 s (C10), 51.01 q
(OCH3), 54.74 d (C9), 55.94 d (C5), 106.50 t (C20),
110.60 d (C1′), 112.82 d (C14), 126.12 s (C2′), 127.39 d
(C6′, C10′), 128.61 d (C7′, C9′), 130.04 s (C13), 132.10 d
(C8′), 133.21 s (C5′), 143.24 d (C15), 146.24 s (C16),
147.56 s (C8), 164.88 s (CONH), 165.05 s (C4′), 177.64
(C19), 178.30 s (C7″). Found, %: C 71.02; H 7.59;
N 4.29. C38H50N2O7. Calculated, %: C 70.59; H 7.74;
N 4.33.
2
NCH2CH2, 6-H), 1.96 d.m (1H, 6-H, J = 12.8 Hz),
2
2.12 d.m (1H, 3-H, J = 13.2 Hz), 2.38 m (2H, 12-H,
7-H), 2.58 m (3H, CH2C6H2, 12-H), 3.41 m (2H,
NCH2), 3.58 s (3H, OCH3), 4.56 s and 4.92 s (1H each,
20-H), 5.03 s (1H, OH), 6.33 d (1H, 14-H, J = 1.8 Hz),
6.52 t (1H, NH, J = 6.2 Hz), 6.81 s (1H, 1′-H), 6.97 s
(2H, 2″-H, 6″-H), 7.35 d (1H, 15-H, J = 1.8 Hz), 7.47 t
(2H, 7′-H, 9′-H, J = 7.2 Hz), 7.55 t (1H, 8′-H, J =
7.2 Hz), 7.93 d (2H, 6′-H, 10′-H, J = 7.2 Hz), 8.59 br.s
(1H, 3′-H, halfwidth 5.6 Hz). 13C NMR spectrum, δC,
ppm: 12.50 q (C17), 19.76 t (C2), 23.27 t (C12), 24.21 t
(C11), 26.13 t (C6), 28.61 q (C18), 30.21 q [C(CH3)3],
31.59 t (CH2), 35.09 t (CH2C6H2), 34.14 s [C(CH3)3],
37.99 t (C3), 38.51 t (C7), 38.92 t (C1), 39.69 t (CH2N),
40.04 s (C4), 44.13 s (C10), 51.03 q (OCH3), 54.74 d
(C9), 55.95 d (C5), 106.55 t (C20), 110.60 d (C1′),
112.87 d (C14), 124.76 d (C2″, C6″), 126.53 s (C2′),
127.38 d (C6′, C10′), 128.65 d (C7′, C9′), 129.79 s (C13),
132.03 s (C5′), 132.14 d (C8′), 133.25 s (C1″), 135.62 s
(C3″, C5″), 143.17 d (C15), 146.36 s (C16), 147.57 s (C8),
151.74 s (C4″), 164.88 s (CONH), 166.22 s (C4′),
177.65 s (C19). Found, %: C 75.32; H 8.63; N 3.62.
C48H2O6N64. Calculated, %: C 75.39; H 8.38, N 3.66.
Methyl (1S,4aR,5S)-5-(2-{2-[2-benzoylamino-3-
benzyl(methyl)amino-3-oxoprop-1-en-1-yl]furan-3-
yl}ethyl)-1,4a-dimethyl-6-methylidenedecahydro-
naphthalene-1-carboxylate {XI, methyl 16-[2-ben-
zoylamino-3-benzyl(methyl)amino-3-oxoprop-1-en-
1-yl]-15,16-epoxylabda-8(20),13(16),14-trien-19-
oate}. A mixture of 0.50 g (1.0 mmol) of azlactone III
and 0.15 g (1.2 mmol) of N-benzylmethanamine in
7 ml of benzene was heated for 6 h at 70°C. The
solvent was removed under reduced pressure, and the
residue was subjected to chromatography on silica gel
using petroleum ether–diethyl ether (1:1) as eluent.
The subsequent recrystallization from petroleum ether
gave 0.49 g (80%) of compound XI. mp 69–72°C,
[α]D20 = 9.9° (c = 3.1, CHCl3). IR spectrum, ν, cm–1:
706, 732, 890, 912, 1515 (C=C); 1720 (CO2Me); 1581,
1646, 1680, 3419 (CONH). UV spectrum, λmax, nm
7-[2-Benzoylamino-3-(3-{2-[(1S,4aR,5S)-5-meth-
oxycarbonyl-5,8a-dimethyl-2-methylidedecahydro-
naphthalen-1-yl]ethyl}furan-2-yl)prop-2-enoyl-
amino]heptanoic acid (X, methyl 16-[2-benzoyl-
amino-3-(6-carboxyhexylamino)-3-oxoprop-1-en-1-
yl]-15,16-epoxylabda-8(20),13(16),14-trien-19-oate
(X). 7-Aminoheptanoic acid, 0.17 g (1.1 mmol), was
added to a solution of 0.50 g (1.0 mmol) of azlactone
III in 7 ml of benzene, and the mixture was heated for
6 h at 70°C. The solvent was removed under reduced
pressure, and the residue was subjected to chromatog-
raphy on silica gel using chloroform as eluent. The
subsequent recrystallization from diethyl ether gave
0.47 g (73%) of compound X. mp 106–109°C, [α]2D0 =
17.3° (c = 2.5, CHCl3). IR spectrum, ν, cm–1: 712, 889,
1
(logε): 226 (3.11), 319 (3.12). H NMR spectrum, δ,
ppm: in CDCl3: 0.48 s and 0.50 s (3H, C17H3), 0.87 m
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XV.
847
(1H, 1-H), 1.02 t.d (1H, 3-H), 1.17 s (3H, C18H3),
1.26 m (1H, 5-H), 1.51 m (3H, 9-H, 11-H, 2-H), 1.71–
1.98 m (6H, 1-H, 6-H, 2-H, 11-H, 7-H), 2.14 m (1H,
3-H), 2.37 m (2H, 12-H, 7-H), 2.56 m (1H, 12-H),
3.03 s (3H, NCH3), 3.62 s (3H, OCH3), 4.55 s and
4.57 s (1H, 20-H), 4.71 s and 4.78 s (2H, CH2), 4.90 s
and 4.94 s (1H, 20-H), 5.74 s and 5.81 s (1H, 1′-H),
6.32 s and 6.38 s (1H, 14-H), 7.32–7.45 m (4H, 15-H,
3″-H, 4″-H, 5″-H), 7.49 m (2H, 7′-H, 9′-H), 7.53 m
(3H, 2″-H, 6″-H, 8′-H), 7.96 d (2H, 6′-H, 10′-H),
9.51 br.s (1H, 3′-H); in DMSO-d6: 0.30 s (3H, C17H3);
0.79 m (1H, 1-H); 0.89 t.d (1H, 3-H, J = 13.2, 3.0 Hz);
0.99 s (3H, C18H3); 1.16 d.d (1H, 5-H, J = 12.6,
2.8 Hz); 1.28 m and 144 m (3H, 9-H, 11-H, 2-H);
1.56 m, 1.74 t, and 1.80 m (6H, 1-H, 6-H, 2-H, 11-H,
7-H, J = 13 Hz); 1.91 d (1H, 3-H, J = 14 Hz); 2.22 m
(2H, 12-H, 7-H); 2.72 m (1H, 12-H); 3.22 s (3H,
NCH3); 3.42 s (3H, OCH3); 4.45 s (1H, 20-H); 4.51 m
(2H, CH2, J = 7.0 Hz); 4.78 s (1H, 20-H); 5.92 s (1H,
1′-H); 6.39 s (1H, 14-H); 7.16 m and 7.24 m (5H, Ph);
7.42 t (2H, 7′-H, 9′-H, J = 7.2 Hz); 7.49 t (1H, 8′-H,
J = 7.2 Hz); 7.62 d (1H, 15-H, J = 1.8 Hz); 7.90 d (2H,
6′-H, 10′-H, J = 7.2 Hz); 9.87 s (1H, 3′-H). 13C NMR
spectrum (CDCl3), δC, ppm: 12.62 q (C17), 19.90 t (C2),
23.01 t and 23.22 t (C12), 24.14 t and 24.31 t (C11),
26.26 t (C6), 28.74 q (C18), 32.93 t and 36.44 t
(NCH2Ph), 38.14 t (C3), 38.65 t (C7), 39.04 t (C1),
40.14 s (C4), 44.28 s (C10), 51.13 q (OCH3), 50.56 q
(NCH3), 54.62 d and 54.71 d (C9), 55.16 q (NCH3),
56.11 d (C5), 100.77 d and 101.04 d (C1′), 106.50 t
(C20), 112.94 d (C14), 126.02 s and 126.19 s (C2′),
127.02 d (C4″), 127.43 d (C6′, C10′), 127.75 s (C13),
128.26 d (C2″, C6″), 128.62 d (C3″, C5″), 128.79 d (C7′,
C9′), 132.21 d (C8′), 133.20 s (C5′), 136.92 s and
137.12 s (C1″), 141.94 d (C15), 146.71 s and 147.10 s
(C16), 147.82 s and 147.81 s (C8), 163.95 s and
164.13 s [CON(CH3)CH2Ph], 167.86 s and 168.44 s
(C4′), 177.69 s (C19). Found, %: C 75.23; H 7.36;
N 4.10. C39H46N2O5. Calculated, %: C 75.24; H 7.36;
N 4.50.
chloroform as eluent. A fraction containing compound
XII was evaporated, and the residue was ground with
hexane. Yield 0.43 g (73%), mp 89–90°C, [α]D20 = 13.7°
(c = 3.3, CHCl3). IR spectrum, ν, cm–1: 707, 853, 889,
1514 (C=C); 1723 (C=O); 1581, 1644, 1683, 3423
(CONH). UV spectrum, λmax, nm (logε): 227 (4.16),
320 (4.23). 1H NMR spectrum (CDCl3), δ, ppm: 0.49 s
(3H, C17H3), 0.94 m (1H, 1-H), 1.00 t.d (1H, 3-H, J =
13.3, 3.1 Hz), 1.16 s (3H, C18H3), 1.26 d.d (1H, 5-H,
J = 12.6, 2.8 Hz), 1.50 m (1H, 2-H), 1.57–1.82 m
(12H, 9-H, 11-H, 1-H, 6-H, 2-H, 3″-H, 4″-H, 4′-H,
5″-H), 1.83 t.d (1H, 7-H, J = 12.6, 3.4 Hz), 1.96 m
2
(1H, 6-H), 2.14 d.m (1H, 3-H, J = 13.3 Hz), 2.31 m
2
(1H, 12-H), 2.11 m (1H, 7-H, J = 12.6 Hz), 2.55 m
(1H, 12-H), 3.60 s (3H, OCH3), 3.60 m (4H, 2″-H,
6″-H), 4.58 s and 4.92 s (1H each, 20-H), 5.67 s (1H,
1′-H), 6.35 d (1H, 14-H, J = 1.8 Hz), 7.47 m (3H,
15-H, 7′-H, 9′-H), 7.52 t (1H, 8′-H, J = 7 Hz), 7.91 d
(2H, 6′-H, 10′-H, J = 8 Hz), 9.47 br.s (1H, 3′-H).
13C NMR spectrum, δC, ppm: 12.50 q (C17), 19.78 t
(C2), 23.15 t (C12), 24.23 t (C11), 24.60 t (C4″), 25.18 t
and 25.38 t (C3″, C5″), 26.12 t (C6), 28.61 q (C18), 38.01 t
(C3), 38.52 t (C7), 38.97 t (C1), 40.05 s (C4), 42.78 t
and 48.45 t (C2″, C6″), 44.16 s (C10), 51.02 q (OCH3),
54.58 d (C9), 55.96 d (C5), 100.12 d (C1′), 106.35 t
(C20), 112.80 d (C14), 125.55 s (C2′), 127.26 d (C6′,
C10′), 127.71 s (C13), 128.62 d (C7′, C9′), 132.97 d (C8′),
133.23 s (C5′), 141.68 d (C15), 146.99 s (C16), 147.80 s
(C8), 163.67 s (CONH), 166.21 s (C4′), 177.58 s (C19).
Found, %: C 73.72; H 7.85; N 4.78. C36H46N2O5. Cal-
culated, %: C 73.72; H 7.85; N 4.78.
tret-Butyl 1-[(2Z)-2-benzoylamino-3-(3-{2-
[(1S,4aR,5S)-5-methoxycarbonyl-5,8a-dimethyl-2-
methylidenedecahydronaphthalen-1-yl]ethyl}furan-
2-yl)prop-2-enoyl]pyrrolidine-2-carboxylate (XIII).
A mixture of 0.50 g (1.0 mmol) of azlactone III and
0.20 g (1.2 mmol) of L-proline tert-butyl ester in 7 ml
of benzene was heated for 5 h at 70°C. The solvent
was removed under reduced pressure, and the residue
was recrystallized from diethyl ether. Yield 0.56 g
(83%), mp 173–175°C, [α]2D0 = 17.9° (c = 3.3, CHCl3).
IR spectrum, ν, cm–1: 720, 760, 886, 909, 1510 (C=C);
1727 (C=O); 1580, 1638, 1661, 3422, 3510 (CONH).
UV spectrum, λmax, nm (logε): 228 (3.13), 319 (3.22).
1H NMR spectrum, δ, ppm: in CDCl3: 0.48 s (3H,
C17H3), 1.00 m (2H, 1-H, 3-H), 1.15 s (3H, C18H3),
1.26 d.d (1H, 5-H), 1.47 s (12H, t-Bu, 2-H, 4″-H),
1.57 s (2H, 9-H, 11-H), 1.68–1.90 m (5H, 1-H, 7-H,
2-H, 11-H, 6-H), 1.96 m (3H, 6-H, 3″-H), 2.12 m (1H,
3-H), 2.31 m (1H, 12-H), 2.40 m (1H, 7-H), 2.56 m
(1H, 12-H), 3.58 s (3H, OCH3), 3.79 m (2H, 5″-H),
Methyl (1S,4aR,5S)-5-{2-[2-(2-benzoylamino-3-
oxo-3-piperidinoprop-1-en-1-yl)furan-3-yl]ethyl}-
1,4a-dimethyl-6-methylidenedecahydronaphtha-
lene-1-carboxylate [XII, methyl 16-(2-benzoyl-
amino-3-oxo-3-piperidinoprop-1-en-1-yl)-15,16-ep-
oxylabda-8(20),13(16),14-trien-19-oate]. Piperidine,
0.10 g (1.2 mmol), was added to a solution of 0.50 g
(1.0 mmol) of azlactone III in 7 ml of benzene, and the
mixture was heated for 5 h at 70°C. The solvent was
removed under reduced pressure, and the residue was
subjected to chromatography on silica gel using
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

KHARITONOV et al.
848
4.53 s (1H, 20-H), 4.55 m (1H, 2′-H), 4.91 s (1H,
20-H), 5.86 s and 5.94 s (1H, 1′-H), 6.34 d and 6.35 d
(1H, 14-H, J = 1.8 Hz), 7.45 m (3H, 15-H, 7′-H, 9′-H),
7.53 m (1H, 8′-H), 7.88 d (2H, 6′-H, 10′-H, J = 7.8 Hz),
9.24 br.s and 9.30 br.s (1H, 3′-H); in DMSO-d6: 0.31 s
(3H, C17H3), 0.87 m (2H, 1-H, 3-H), 0.99 s (3H,
C18H3), 1.16 m (1H, 5-H), 1.29 s (9H, t-Bu), 1.43 m
and 1.49 m (3H, 2-H, 4″-H), 1.58–1.79 m (10H, 1-H,
2-H, 6-H, 7-H, 9-H, 11-H, 3′-H, 3″-H), 1.91 d.m (1H,
0.93 d (3H, CH3, J = 7.2 Hz), 0.98 m (2H, 1-H, 3-H),
1.13 s (3H, C18H3), 1.17 m (1H, 5″-H), 1.28 d.d (1H,
5-H, J = 12.6, 2.6 Hz), 1.44 m (2H, 2-H, 5″-H), 1.56 m
(1H, 9-H), 1.58 m (1H, 11-H), 1.67–1.81 m (4H, 11-H,
2-H, 1-H, 7-H), 1.86 m (1H, 6-H, J = 12, 4 Hz),
1.94 m (2H, 6-H, 4″-H), 2.10 m (1H, 3-H), 2.38 m
(2H, 7-H, 12-H), 2.57 m (1H, 12-H), 3.56 s (3H,
OCH3), 3.68 s (3H, OCH3), 4.54 s (1H, 20-H), 4.70 d.d
(1H, 3″-H, J = 8.2, 4.5 Hz), 4.91 s (1H, 20-H), 6.32 d
(1H, 14-H, J = 1.8 Hz), 6.85 s (1H, 1′-H), 6.91 d (1H,
2″-H, J = 5.8 Hz), 7.36 d (1H, 15-H, J = 1.8 Hz), 7.46 t
(2H, 7′-H, 9′-H, J = 7.8 Hz), 7.53 t (1H, 8′-H, J =
7.8 Hz), 7.91 d (2H, 10′-H, 6′-H, J = 8 Hz), 8.54 s (1H,
3′-H). 13C NMR spectrum, δC, ppm: 11.46 q (C6″),
12.43 q (C17), 15.25 q (CH3), 19.69 t (C2), 23.29 t
(C12), 24.16 t (C11), 25.03 t (C5″), 26.07 t (C6), 28.55 q
(C18), 37.93 t (C3), 37.99 d (C4″), 38.40 t (C7), 38.85 t
(C1), 39.97 s (C4), 44.07 s (C10), 50.95 q (OCH3),
51.86 q (OCH3), 54.75 d (C9), 55.89 d (C5), 56.67 d
(C3″), 106.45 t (C20), 111.22 d (C1′), 112.85 d (C14),
125.86 s (C2′), 127.28 d (C10′, C6′), 128.58 d (C7′, C9′),
130.18 s (C13), 131.98 d (C8′), 133.37 s (C5′), 143.30 d
(C15), 146.19 s (C16), 147.50 s (C8), 164.33 s (C1″),
166.33 s (C4′), 172.20 (C=O), 177.57 s (C19). Found,
%: C 70.44; H 7.73; N 4.15. C38H50N2O7. Calculated,
%: C 70.59; H 7.73; N 4.33.
2
3-H, J = 13.2 Hz), 2.05 m (1H, 12-H), 2.19 m and
2.24 m (2H, 7-H, 12-H), 3.22 s (3H, OCH3), 3.50 m
(2H, 5″-H), 4.10 d.d (1H, 2″-H, J = 7, 5 Hz), 4.46 s
(1H, 20-H), 4.78 s (1H, 20-H), 6.06 s (1H, 1′-H),
6.40 d (1H, 14-H, J = 1.8 Hz), 7.40 t (2H, 7′-H, 9′-H,
J = 7.2 Hz), 7.48 t (1H, 8′-H, J = 7.2 Hz), 7.60 d (1H,
15-H, J = 1.8 Hz), 7.87 d (2H, 6′-H, 10′-H, J =
7.2 Hz), 9.82 s (1H, 3′-H). 13C NMR spectrum
(DMSO-d6), δ, ppm: 12.63 q (C17), 19.76 t (C2), 23.36 t
(C12), 24.42 t (C11), 25.06 t (C4″), 26.12 t (C6), 27.87 q
(C18), 28.03 q [C(CH3)3], 29.00 t (C3″), 37.79 t (C3),
38.26 t (C7), 38.63 t (C1), 40.18 s (C4), 43.94 s (C10),
49.10 t (C5″), 51.31 q (OCH3), 54.59 d (C9), 55.39 d
(C5), 59.98 t (C2″), 80.40 s [C(CH3)3], 106.63 t (C20),
109.27 d (C1′), 113.08 d (C14), 126.58 s (C2′), 127.41 d
(C13), 127.96 s (C2, C6′, C10′), 128.81 d (C7′, C9′),
132.17 d (C8′), 133.35 s (C5′), 145.82 d (C15), 146.56 s
(C16), 147.96 s (C8), 164.31 s (CONH), 165.87 s (C4′),
171.48 s (C=O), 177.71 s (C19). Found, %: C 71.21;
H 7.86; N 3.91. C40H52N2O7. Calculated, %: C 71.42;
H 7.73; N 4.17.
Methyl (1S,4aR,5S)-5-(2-{2-[(Z)-2-benzoylamino-
3-(1-tert-butoxycarbonyl-3-methylbutylamino)-3-
oxoprop-1-en-1-yl]furan-3-yl}ethyl)-1,4a-dimethyl-
6-methylidenedecahydronaphthalene-1-carboxylate
{XV, methyl 16-[(Z)-2-benzoylamino-3-(1-tert-but-
oxycarbonyl-3-methylbutylamino)-3-oxoprop-1-en-
1-yl]-15,16-epoxylabda-8(20),13(16),14-trien-19-
oate (XV). A mixture of 0.50 g (1.0 mmol) of azlac-
tone III and 0.17 g (1.2 mmol) of L-leucine tert-butyl
ester in 7 ml of benzene was heated for 6 h at 70°C.
The solvent was removed under reduced pressure, and
the residue was subjected to chromatography on silica
gel using petroleum ether–diethyl ether (2:1) as eluent.
A fraction containing compound XV was evaporated,
and the residue was recrystallized from petroleum
Methyl (1S,4aR,5S)-5-(2-{2-[(Z)-2-benzoylamino-
3-(1-methoxycarbonyl-2-methylbutylamino)-3-oxo-
prop-1-en-1-yl]furan-3-yl}ethyl)-1,4a-dimethyl-6-
methylidenedecahydronaphthalene-1-carboxylate
{XIV, methyl 16-[(Z)-2-benzoylamino-3-(1-meth-
oxycarbonyl-2-methylbutylamino)-3-oxoprop-1-en-
1-yl]-15,16-epoxylabda-8(20),13(16),14-trien-19-
oate}. A mixture of 0.35 g (0.64 mmol) of azlactone
III and 0.12 g (0.77 mmol) of L-isoleucine methyl
ester in 7 ml of benzene was heated for 6 h at 70°C.
The solvent was removed under reduced pressure, and
the residue was subjected to chromatography on silica
gel using chloroform–methanol (200:1) as eluent.
A fraction containing compound XIV was evaporated,
and the residue was crystallized from petroleum ether.
Yield 0.35 g (78%), mp 57–60°C, [α]D20 = 15.8° (c =
3.2, CHCl3). IR spectrum, ν, cm–1: 712, 748, 891, 1511
(C=C); 1273, 1724 (C=O); 1578, 1652, 1673, 3369,
3431 (CONH). UV spectrum, λmax, nm (logε): 227
ether. Yield 0.41 g (62%), mp 122–124°C, [α]D20
=
17.8° (c = 3.4, CHCl3). IR spectrum, ν, cm–1: 694, 728,
848, 889, 1518 (C=C); 1725 (C=O); 1553, 1581, 1631–
1651, 3262, 3440 (CONH). UV spectrum, λmax, nm
1
(logε): 226 (4.06), 317 (4.26). H NMR spectrum
(CDCl3), δ, ppm: 0.46 s (3H, C17H3), 0.91 d and 0.96 d
(6H, CH3, J = 7.0 Hz), 0.98 m (2H, 1-H, 3-H), 1.13 s
(3H, C18H3), 1.24 d.d (1H, 5-H, J = 12.8, 2.8 Hz),
1.42 s [9H, C(CH3)3], 1.49 m (1H, 2-H), 1.55 m (2H,
9-H, 11-H), 1.57–1.78 m (6H, 11-H, 1-H, 2-H, 6-H,
1
(3.18), 317 (3.06). H NMR spectrum (CDCl3), δ,
ppm: 0.45 s (3H, C17H3), 0.89 t (3H, 6″-H, J = 7 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XV.
849
2
4″-H), 1.87 m (1H, 7-H), 1.94 d.m (1H, 6-H, J =
13.8 Hz), 2.10 d.m (1H, 3-H, J = 13.6 Hz), 2.38 m
(2H, 7-H, 12-H), 2.58 m (1H, 12-H), 3.57 s (3H,
OCH3), 4.57 s (1H, 20-H), 4.62 m (1H, 3″-H), 4.91 s
(1H, 20-H), 6.31 d (1H, 14-H, J = 1.8 Hz), 6.76 m (1H,
2″-H), 6.86 s (1H, 1′-H), 7.35 d (1H, 15-H, J =
1.8 Hz), 7.46 t (2H, 7′-H, 9′-H, J = 7.8 Hz), 7.53 t (1H,
8′-H, J = 7.8 Hz), 7.92 d (2H, 6′-H, 10′-H, J = 7.8 Hz),
8.47 s (1H, 3′-H). 13C NMR spectrum, δC, ppm: 12.46 q
(C17), 19.71 t (C2), 22.16 q and 22.63 q (5″-CH3),
23.31 t (C12), 24.16 t (C11), 24.72 q (C5″), 26.09 t (C6),
27.82 q [C(CH3)3], 28.59 q (C18), 37.95 t (C3), 38.44 t
(C7), 38.88 t (C1), 39.98 s (C4), 42.07 t (C4″), 44.10 s
(C10), 50.98 q (OCH3), 51.67 d (C3″), 54.70 d (C9),
55.92 d (C5), 81.61 d [C(CH3)3], 106.48 t (C20),
111.51 d (C1′), 112.82 d (C14), 125.90 s (C2′), 127.34 d
(C10′, C6′), 128.57 d (C7′, C9′), 130.28 s (C13), 131.97 d
(C8′), 133.42 s (C5′), 143.27 d (C15), 146.22 s (C16),
147.52 s (C8), 164.16 s (C1″), 166.24 s (C4′), 171.99 s
(C=O), 177.62 s (C19). Found, %: C 71.55; H 8.23;
N 4.20. C41H56N2O7. Calculated, %: C 71.51; H 8.14;
N 4.07.
(Z)-2-Benzoylamino-3-(3-{2-[(1S,4aR,5S)-5-
methoxycarbonyl-5,8a-dimethyl-2-methylidedeca-
hydronaphthalen-1-yl]ethyl}furan-2-yl)prop-2-en-
oic acid {XVI, (Z)-2-benzoylamino-3-[15,16-epoxy-
19-methoxy-19-oxolabda-8(20),13(16),14-trien-16-
yl]prop-2-enoic acid}. a. A saturated solution of hy-
drogen chloride in 10 ml of diethyl ether was added to
a solution of 0.50 g (1.0 mmol) of compound III in
5 ml of diethyl ether, and the mixture was left over-
night. The precipitate was filtered off and dried under
reduced pressure. Yield 0.45 g (87%).
(1H, 7-H), 1.97 d.m (1H, 6-H, 2J = 13.1 Hz), 2.12 d.m
(1H, 3-H, J = 13.3 Hz), 2.40 m (2H, 12-H, 7-H),
2
2.64 m (1H, 12-H, J = 14.5, 6.8, 4.2 Hz), 3.58 s (3H,
OCH3), 4.57 s and 4.94 s (2H, 20-H), 6.39 d (1H,
14-H, J = 1.8 Hz), 7.15 s (1H, 1′-H), 7.46 d (1H, 15-H,
J = 1.8 Hz), 7.49 t (2H, 7′-H, 9′-H, J = 7.4 Hz), 7.57 t
(1H, 8′-H, J = 7.4 Hz), 7.93 d (2H, 6′-H, 10′-H, J =
7.4 Hz), 8.65 br.s (1H, 3′-H). 13C NMR spectrum, δC,
ppm: 12.51 q (C17), 19.76 t (C2), 23.50 t (C12), 24.24 t
(C11), 26.14 t (C6), 28.63 q (C18), 38.00 t (C3), 38.48 t
(C7), 38.92 t (C1), 40.05 s (C4), 44.15 s (C10), 51.04 q
(OCH3), 54.82 d (C9), 56.00 d (C5), 106.61 t (C20),
113.29 d (C14), 115.31 d (C1′), 121.78 s (C2′), 127.46 d
(C6′, C10′), 128.71 d (C7′, C9′), 132.31 d (C8′), 132.67 s
(C13), 133.11 s (C5′), 144.34 d (C15), 145.99 s (C16),
147.43 s (C8), 166.40 s (C4′), 167.60 s (C=O), 177.70 s
(C19). Mass spectrum, m/z (Irel, %): 501 [M – 18] (3),
275 (6), 315 (6), 252 (6), 239 (10), 121 (12), 105
(100), 77 (23). Found, %: C 75.32; H 8.63; N 3.62.
C31H37NO6. Calculated, %: C 75.39; H 8.38; N 3.66.
Methyl (1S,4aR,5S)-5-(2-{2-[(Z)-2-benzoylamino-
3-hydrazino-3-oxoprop-1-en-1-yl]furan-3-yl}ethyl)-
1,4a-dimethyl-6-methylidenedecahydronaphtha-
lene-1-carboxylate {XVII, methyl 16-[(Z)-2-benzoyl-
amino-3-hydrazino-3-oxoprop-1-en-1-yl]-15,16-ep-
oxylabda-8(20),13(16),14-trien-19-oate}. Hydrazine
hydrate, 0.2 ml, was added dropwise under stirring to
a solution of 1.00 g (2.0 mmol) of azlactone III in
10 ml of methanol. The mixture was stirred for 5 h and
left overnight, the solvent was removed under reduced
pressure, and the residue was ground with hexane.
Yield 0.96 g (90%), mp 72–75°C, [α]D20 = 2.76° (c =
3.2, CHCl3). IR spectrum, ν, cm–1: 713, 750, 888, 1467
(C=C); 1722 (C=O); 1665, 1664, 3309 (CONH, NH2).
UV spectrum, λmax, nm (logε): 225 (2.99), 318 (3.11),
405 (2.02). 1H NMR spectrum (CDCl3), δ, ppm: 0.47 s
(3H, C17H3), 0.94 m (2H, 1-H, 3-H), 1.14 s (3H,
C18H3), 1.25 d.d (1H, 5-H, J = 12.6, 2.8 Hz), 1.46 m
(1H, 2-H), 1.55 m (1H, 9-H), 1.66–1.80 m (5H, 1-H,
6-H, 2-H, 11-H), 1.87 t.d (1H, 7-H, J = 13.0, 3.3 Hz),
b. Potassium hydroxide, 0.07 g (1.2 mmol), was
added to a solution of 0.50 g (1.0 mmol) of compound
III in 5 ml of ethanol. The mixture was stirred for 6 h,
left to stand overnight, poured onto ice, and extracted
with chloroform (3×20 ml). The extracts were com-
bined, washed with cold water (3×20 ml), dried over
MgSO4, and evaporated under reduced pressure. The
residue was recrystallized from diethyl ether. Yield
0.43 g (82%), mp 211–213°C, [α]D20 = 15.5° (c = 3.2,
CHCl3). IR spectrum, ν, cm–1: 724, 752, 891, 1510
(C=C); 1572, 1603, 1642, 1665 (CONH); 1693, 1725
(C=O); 3360 (NH, OH). UV spectrum, λmax, nm (logε):
2
1.96 d.m (1H, 6-H, J = 12.6 Hz), 2.12 d.m (1H, 3-H,
2J = 13.3 Hz), 2.34 m (1H, 12-H), 2.38 m (1H, 7-H),
2.57 m (1H, 12-H), 3.57 s (3H, OCH3), 3.60 br.s (2H,
NH2), 4.55 s and 4.92 s (1H each, 20-H), 6.33 d (1H,
14-H, J = 1.8 Hz), 6.75 s (1H, 1′-H), 7.32 s (1H,
CONH), 7.36 d (1H, 15-H, J = 1.8 Hz), 7.44 t (2H,
7′-H, 9′-H, J = 7.2 Hz), 7.52 t (1H, 8′-H, J = 7.2 Hz),
7.89 d (2H, 6′-H, 10′-H, J = 7.2 Hz), 8.60 br.s (1H,
3′-H). 13C NMR spectrum, δC, ppm: 12.51 q (C17),
19.74 t (C2), 23.30 t (C12), 24.16 t (C11), 26.10 t (C6),
28.66 q (C18), 37.98 t (C3), 38.38 t (C7), 38.92 t (C1),
1
224 (3.02), 319 (3.22). H NMR spectrum (CDCl3), δ,
ppm: 0.48 s (3H, C17H3), 0.95 t.d (1H, 1-H, J = 13.2,
3.2 Hz), 1.00 t.d (1H, 3-H, J = 13.3, 3.2 Hz), 1.15 s
(3H, C18H3), 1.26 d.d (1H, 5-H, J = 12.6, 2.6 Hz),
1.47 d.m (1H, 2-H, J = 13.2 Hz), 1.60 m (2H, 9-H,
11-H), 1.69–1.80 m (4H, 1-H, 6-H, 2-H, 11-H), 1.88 m
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

KHARITONOV et al.
850
40.03 s (C4), 44.12 s (C10), 51.05 q (OCH3), 54.92 d
(C9), 56.00 d (C5), 106.06 t (C20), 111.11 d (C1′),
113.04 d (C14), 124.43 s (C2′), 127.47 d (C6′, C10′),
129.19 d (C7′, C9′), 130.48 s (C13), 132.20 s (C5′),
133.10 d (C8′), 142.78 d (C15), 146.09 s (C16), 147.40 s
(C8), 165.53 s (C4′, CONH), 177.56 s (C19). Found, %:
C 69.23; H 7.39; N 7.46. C31H39N3O5. Calculated, %:
C 69.79; H 7.31; N 7.88.
146.19 s (C16), 147.55 s (C8), 147.55 s (C1″), 165.57 s
(C4′), 166.65 s (CONH), 177.57 s (C19).
Methyl (1S,4aR,5S)-1,4a-dimethyl-6-methylidene-
5-(2-{2-[(Z)-6-oxo-3-phenyl-1,4,5,6-tetrahydro-
1,2,4-triazin-5-ylidenemethyl]furan-3-yl}ethyl)-
decahydronaphthalene-1-carboxylate {XIX, methyl
15,16-epoxy-16-[(Z)-6-oxo-3-phenyl-1,4,5,6-tetra-
hydro-1,2,4-triazin-5-ylidenemethyl]labda-8(20),-
13(16),14-trien-19-oate}. A mixture of 0.50 g
(0.9 mmol) of hydrazide XVIII and 10 ml of 1 M
aqueous sodium hydroxide was heated for 10 min at
100°C. The mixture was cooled, acidified to pH 1 by
adding 1 ml of 6 M hydrochloric acid, and extracted
with chloroform (3×25 ml). The extracts were com-
bined, washed with water (3×20 ml), and dried over
MgSO4. The solvent was removed under reduced pres-
sure, and the residue was subjected to chromatography
on silica gel using petroleum ether–chloroform (1:1)
as eluent. The product was additionally recrystallized
from diethyl ether. Yield 0.19 g (80%), mp 165–168°C,
[α]D20 = 17.5° (c = 2.8, CHCl3). IR spectrum, ν, cm–1:
692, 770, 892, 1519 (C=C); 1640, 1670 (C=O, C=N);
1724 (C=O); 3202, 3409 (NH). UV spectrum, λmax, nm
(logε): 254 (3.16), 327 (3.22), 340 (3.22); in 1 M
NaOH: 285, 320, 405; in 1 M HCl: 251, 326, 340.
1H NMR spectrum (CDCl3), δ, ppm: 0.48 s (3H,
C17′H3), 1.02 m (1H, 1′-H), 1.06 m (1H, 3′-H), 1.15 s
(3H, C18′H3), 1.31 d.d (1H, 5′-H, J = 12.0, 2.8 Hz),
Methyl (1S,4aR,5S)-5-(2-{2-[(Z)-2-benzoylamino-
3-(N′-phenylhydrazino)-3-oxoprop-1-en-1-yl]furan-
3-yl}ethyl)-1,4a-dimethyl-6-methylidenedecahydro-
naphthalene-1-carboxylate {XVIII, methyl 16-[(Z)-
2-benzoylamino-3-(N′-phenylhydrazino)-3-oxoprop-
1-en-1-yl]-15,16-epoxylabda-8(20),13(16),14-trien-
19-oate} (XVIII). Phenylhydrazine, 0.13 g (2.0 mmol),
was added dropwise under stirring to a solution of
0.50 g (1.0 mmol) of azlactone III in 10 ml of metha-
nol, and the mixture was stirred for 5 h and left over-
night. The solvent was removed under reduced pres-
sure, the residue was subjected to chromatography on
silica gel using chloroform as eluent, and the product
was additionally purified by recrystallization from di-
ethyl ether. Yield 0.47 g (77%), mp 141–144°C, [α]D20 =
5.9° (c = 2.2, CHCl3). IR spectrum, ν, cm–1: 692, 760,
899, 1496 (C=C); 1723 (C=O); 1624, 1644, 1664,
3239, 3325, 3431 (CONH, NH). UV spectrum, λmax
,
1
nm (logε): 233 (3.96), 318 (3.96). H NMR spectrum
(CDCl3), δ, ppm: 0.46 s (3H, C17H3), 0.92 t.d (1H, 1-H,
J = 13.0, 3.0 Hz), 0.97 t.d (1H, 3-H, J = 13.1, 3.2 Hz),
1.13 s (3H, C18H3), 1.24 d.d (1H, 5-H, J = 12.8,
2
1.52 d.m (1H, 2′-H, J = 14 Hz), 1.65 m (2H, 9′-H,
11′-H), 1.73–1.88 m (4H, 1′-H, 6′-H, 2′-H, 11′-H),
1.93 m (1H, 7′-H), 2.02 m (1H, 6′-H), 2.18 d.m (1H,
3′-H, J = 13.0 Hz), 2.42 m (1H, 12′-H), 2.47 m (1H,
7′-H), 2.65 m (1H, 12′-H), 3.58 s (3H, OCH3), 4.59 s
and 4.94 s (1H each, 20′-H), 6.33 s (1H, 5a-H), 6.38 d
(1H, 14′-H, J = 1.8 Hz), 7.46 d (1H, 15′-H, J = 1.8 Hz),
7.47 m (3H, 3″-H, 4″-H, 5″-H), 7.73 m (2H, 2″-H,
6″-H), 9.07 s (1H, 1-H), 9.09 s (1H, 4-H). 13C NMR
spectrum, δC, ppm: 12.38 q (C17′), 19.67 t (C2′), 23.19 t
(C12′), 24.19 t (C11′), 26.03 t (C6′), 28.52 q (C18′), 37.96 t
(C3′), 38.43 t (C7′), 38.88 t (C1′), 39.93 s (C4′), 44.05 s
(C10′), 50.87 q (OCH3), 54.89 d (C9′), 55.98 d (C5′),
91.36 d (C5a), 106.45 t (C20′), 112.96 d (C14′), 123.96 s
(C5), 125.11 d (C2″, C6″), 131.03 d (C3″, C5″), 130.40 d
(C4″), 131.03 s (C13′), 141.04 d (C15′), 141.42 s (C16′),
147.40 s (C1″), 148.11 s (C8′), 159.49 s (C3), 161.38 s
(C6), 177.53 s (C19′). Mass spectrum, m/z (Irel, %): 515
[M]+ (26), 279 (21), 266 (33), 187 (83), 130 (18), 121
(100), 118 (55), 109 (39), 105 (34), 93 (30), 77 (47),
55 (57), 43 (60). Found: [M]+ 515.27657. C31H37N3O4.
Calculated: M 515.27839.
2
3.0 Hz), 1.45 d.m (1H, 2-H, J = 13 Hz), 1.55 s (1H,
9-H), 1.60 m (1H, 11-H), 1.67–1.76 m (4H, 1-H, 7-H,
2-H, 11-H), 1.84 m (1H, 7-H), 1.93 m (1H, 6-H),
2
2.12 d.m (1H, 3-H, J = 13.1 Hz), 2.39 m (2H, 12-H,
7-H), 2.59 m (1H, 12-H), 3.57 s (3H, OCH3), 4.57 s
and 4.93 s (1H each, 20-H), 6.26 br.s (1H, NHPh,
halfwidth 12 Hz), 6.35 d (1H, 14-H, J = 1.8 Hz), 6.73 t
(1H, 4″-H, J = 8 Hz), 6.90 m (3H, 1′-H, 2″-H, 6″-H,
J = 8 Hz), 7.20 t (2H, 3″-H, 5″-H, J = 8 Hz), 7.40 d
(1H, 15-H, J = 1.8 Hz), 7.47 t (2H, 7′-H, 9′-H, J =
7.2 Hz), 7.56 t (1H, 8′-H, J = 7.2 Hz), 7.93 d (2H,
6′-H, 10′-H, J = 7 Hz), 8.33 br.s (1H, CONH, half-
width 5 Hz), 8.64 s (1H, 3′-H). 13C NMR spectrum, δC,
ppm: 12.48 q (C17), 19.74 t (C2), 23.34 t (C12), 24.18 t
(C11), 26.11 t (C6), 28.58 q (C18), 37.98 t (C3), 38.49 t
(C7), 38.92 t (C1), 40.03 s (C4), 44.13 s (C10), 50.97 q
(OCH3), 54.78 d (C9), 55.98 d (C5), 106.52 t (C20),
111.85 d (C1′), 113.04 d (C14), 113.69 d (C2″, C6″),
120.89 d (C4″), 124.45 s (C2′), 127.37 d (C6′, C10′),
128.69 d and 128.96 d (C7′, C9′ or C3″, C5″), 132.34 s
(C13), 132.42 d (C8′), 133.04 s (C5′), 143.83 d (C15),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XV.
851
(C4″), 135.82 s (C13′), 137.02 s (C16′), 147.39 d (C15′),
147.64 s (C8′), 148.01 s (C4), 158.04 s (C2), 174.05 s
(C5), 177.59 s (C19′). Found, %: C 74.61; H 7.11;
N 5.41. C31H36N2O4. Calculated, %: C 74.40; H 7.20;
N 5.60.
Methyl (1S,4aR,5S)-1,4a-dimethyl-6-methylidene-
5-(2-{2-[(Z)-5-oxo-2-phenyl-4,5-dihydro-1H-imida-
zol-4-ylidenemethyl]furan-3-yl}ethyl)decahydro-
naphthalene-1-carboxylate {XX, methyl 15,16-ep-
oxy-16-[(Z)-5-oxo-2-phenyl-4,5-dihydro-1H-imida-
zol-4-ylidenemethyl]labda-8(20),13(16),14-trien-19-
oate}. A mixture of 0.25 g (0.5 mmol) of compound
III, 0.06 g (0.6 mmol) of sodium carbonate, and 10 ml
of aqueous ammonia was heated for 14 h at 110–115°C
in a sealed ampule. The ampule was cooled and
opened, and the mixture was poured into 30 ml of
water and extracted with methylene chloride (3×30 ml).
The extracts were combined, dried over MgSO4, and
evaporated under reduced pressure, and the residue
was subjected to chromatography on silica gel using
chloroform as eluent. Fractions containing compound
XX were evaporated, and the product was recrystal-
lized from diethyl ether. Yield 0.14 g (56%), mp 208–
209°C, [α]2D0 = 12.5° (c = 1.1, CHCl3). IR spectrum, ν,
cm–1: 694, 784, 899, 918, 1500, 1531, 1598, 1631,
3069 (C=C, C=N); 1700, 1722 (C=O); 3120, 3200,
3400, 3427 (NH). UV spectrum, λmax, nm (logε): 266
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 06-03-32150) and by the President of the Russian
Federation (program for support of young scientists,
project no. MK 2180.2005.3).
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2.68 m and 2.74 m (2H, 12′-H), 3.57 s (3H, OCH3),
4.65 s and 5.02 s (1H each, 20′-H), 6.43 d (1H, 14-H,
J = 1.7 Hz), 7.03 br.s (1H, 4a-H), 7.54 m (3H, 3″-H,
5″-H, 4″-H), 7.72 d (1H, 15-H, J = 1.7 Hz), 8.19 m
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(C12′), 24.16 t (C11′), 26.16 t (C6′), 28.52 q (C18′), 38.00 t
(C3′), 38.52 t (C7′), 38.90 t (C1′), 40.01 s (C4′), 44.16 s
(C10′), 51.00 q (OCH3), 54.26 d (C9′), 56.06 d (C5′),
106.71 t (C20′), 112.70 d (C4a), 113.70 d (C14′), 127.24 d
(C2″, C6″), 128.06 s (C1″), 128.82 d (C3″, C5″), 132.00 d
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007