Synthetic transformations of higher terpenoids: XX.* synthesis and transformations of diterpene ureido Esters

Article abstract of DOI:10.1134/S1070428010080051

Lossen rearrangement of N-hydroxymaleopimaric acid amide p-toluenesulfonate in the presence of amines in methanol led to the formation of the corresponding diterpene ureido esters with high regio- and stereoselectivity. Treatment of the resulting ureides

Full text of DOI:10.1134/S1070428010080051

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 8, pp. 1140–1150. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © S.V. Chernov, E.E. Shul’ts, M.M. Shakirov, Yu.V. Gatilov, G.A. Tolstikov, 2010, published in Zhurnal Organicheskoi Khimii, 2010,
Vol. 46, No. 8, pp. 1142–1151.
Synthetic Transformations of Higher Terpenoids: XX.* Synthesis
and Transformations of Diterpene Ureido Esters
S. V. Chernov, E. E. Shul’ts, M. M. Shakirov, Yu. V. Gatilov, 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 July 1, 2009
Abstract—Lossen rearrangement of N-hydroxymaleopimaric acid amide p-toluenesulfonate in the presence of
amines in methanol led to the formation of the corresponding diterpene ureido esters with high regio- and
stereoselectivity. Treatment of the resulting ureides with phosphoryl chloride gave cyclic amidines via intra-
molecular ring closure. Substituted hydantoins were obtained by reactions of the ureido esters with glyoxal in
acid medium, and their treatment with sodium ethoxide in ethanol afforded compounds of the naphtho[1,2-h]-
quinazoline series.
DOI: 10.1134/S1070428010080051
Levopimaric acid adduct with maleic anhydride,
maleopimaric acid, and its methyl ester (I) have
found wide application in the technology of paints and
varnishes, as well as of other polymeric materials
[2, 3]. These compounds attract interest as synthons for
the design of pharmacologically important agents, such
as immune regulators [4], hepatoprotectors [5], and
fungicidal [6] and antinematoid agents [7]. Maleo-
pimaric acid methyl ester (I) was used as starting
compound to synthesize a series of chiral ligands [8].
In the present communication we describe a procedure
for the preparation of nitrogen-containing diterpenoids
via the Lossen rearrangement (Scheme 1). Lossen
rearrangements of N-acyloxy imides by the action of
amines have been reported [9–11]. Maleopimaric acid
methyl ester (I) was treated with hydroxylamine in
alcohol to obtain N-hydroxy imide II which was
readily converted into p-toluenesulfonate III. Lossen
rearrangement of p-toluenesulfonate III in the pres-
ence of amines (ammonia, methylamine, benzylamine,
aniline, allylamine, p-toluidine, glycine ester, and
phenylhydrazine) in methanol afforded 31–65% of
ureido esters IV–XI. By treatment of p-toluenesul-
fonate III with triethylamine in methanol we obtained
carbamate XII. In all case, initial N-hydroxy imide II
was also formed; it can be separated by treatment with
aqueous alkali.
The reaction occurred in anhydrous medium; in the
presence of water, N-hydroxy imide II was the only
product. In the reactions with weakly basic aromatic
amines addition of triethylamine was necessary. The
C16OOMe ester group (as well as C18OOMe) is stable
toward amines and hydrazine under usual conditions.
Attempts to introduce an amide group in the course of
the rearrangement were unsuccessful: p-toluenesulfo-
nate III remained unchanged upon treatment with ben-
zylamine in acetone for 4 h under reflux. No corre-
sponding ureides were formed in the reactions of III
with ortho-substituted anilines such as 2-iodoaniline
and 2-bromo-4-methylaniline; in these cases, only car-
bamate XII was obtained. Nevertheless, ureide VIII
readily underwent bromination with molecular bro-
mine at the aromatic ring to give N-(2-bromo-4-meth-
ylphenyl) ureide XIII (Scheme 2).
The structure of the obtained compounds was
favorable for some their intramolecular transforma-
tions. For example, treatment of ureides V–VII, IX,
XIII with phosphoryl chloride in toluene resulted in
their cyclization according to Vilsmeier with formation
of cyclic amidines XIV–XVIII (yield 55–73%).
N-Phenylamidine XV reacted with p-toluenesulfonyl
chloride to give the corresponding N-phenyl-N-p-tolyl-
sulfonyl derivative XIX, whereas the reaction of XV
with bromoacetophenone afforded N-phenacyl deriva-
tive XX whose structure was proved by X-ray analysis
* For communication XIX, see [1].
1140

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XX.
1141
Scheme 1.
16
Me
Me
15
Me
14
Me
12
O
O
H
H
H
H
10
11
13
20
1
3
NH2OH
2
Me
O
Me
N
OH
9
6
8
7
4
O
O
5
19
Me
18
17
Me
COOMe
COOMe
I
II
15
14
Me
Me
13
5
11
H
16
COOMe
6
20
7
RNH2, MeOH
Me
12
8
NH1C7ONHR
II
+
4
1
3
2
Me
H
9
Me
10
19
Me
18
O
H
H
COOMe
IV–XI
TsCl, Et3N
Me
N
OTs
Me
Me
O
H
H
Me
COOMe
COOMe
Et3N, MeOH
III
Me
II
+
NHCOOMe
Me
COOMe
XII
Ia, IV, R = H; Ib, V, R = Me; VI, R = Ph; VII, R = PhCH2; VIII, R = 4-MeC6H4; IX, R = CH2=CHCH2,
X, R = MeOC(O)CH2;
[12]. The structure of compound XX confirms com-
plete regio- and stereoselectivity of the Lossen rear-
rangement. Trisubstituted amidines XIX and XX are
characterized by considerable optical activity.
Scheme 3 illustrates other possible transformations
of terpenoid ureides IV, V, and VII, which lead to the
formation of heterocyclic derivatives. Ureides V and
VII reacted with glyoxal to afford hydantoins XXI and
XXII, respectively, in 69–78% yield. Treatment of
compounds IV, V, and VII with sodium ethoxide
produced compounds XXIII–XXV of the perhydro-
naphtho[1,2-h]quinazoline series (yield 55–68%).
We have found no analogous pentacyclic compounds
in the Cambridge Structural Database [13], but there
are data on the structures of 4-methyl-4-azatricyclo-
[5.2.2.02,6]undeca-3,5-dione monohydrate [14] and
hexahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]-
butyl}-4,7-ethano-1H-isoindole-1,3(2H)-dione hydro-
chloride [15] in which the tricyclic fragment is analo-
gous to that present in molecule III. The pyrrolidine
ring in III is planar within ±0.018 Å, and the bond
lengths therein are similar to those given in [13, 14].
The crystal packing of compound III consists of layers
parallel to the a0b plane. Among interlayer interac-
tions, shortened C5′–H · · · O2 (H · · · O 2.61 Å) and
C17=O4 ···C1 contacts [O···C 3.056(4) Å] should be
noted. The structure of ureido esters IV–XI was deter-
The structure of the isolated compounds was deter-
mined on the basis of their spectral data. The structure
of p-toluenesulfonate III in crystal is shown in Fig. 1.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

CHERNOV et al.
1142
Scheme 2.
17Me
18
Me
Me
Me
16
13
14
H
H
COOMe
3
COOMe
NH
NHR
2
6
5
Me
20
1
Br2
POCl3
Me
Me
V–VII
H
II
IX, XIII
12
9
N4
6a
7
H
8
N
H
O
19
Me
Br
15
Me
COOMe
COOMe
XIII
XIV–XVIII
Me
Me
Me
Me
Ph
Ph
COOMe
COOMe
N
N
PhCOCH2Br
TsCl
Me
Me
H
N
Ts
H
N
XV
O
H
H
Ph
Me
Me
COOMe
COOMe
XIX
XX
XIV, R = Me; XV, R = Ph; XVI, R = PhCH2; XVII, R = CH2=CHCH2; XVIII, R = 2-Br-4-MeC6H3.
Scheme 3.
15
17
14
Me
Me
16
Me
Me
13
5
15
11
O
13
16
H
H
COOMe
2
R
O
(CHO)2
EtOH, HCl
11
6
12
14
1
N
3
20
20
7
8
7
8
O
EtONa, EtOH
Me
Me
12
V, VII
IV, V, VII
4
2'
1'
N
4
1
10
7
N
3
2
9
8
R
N3'
H
H
H
9
5
10
18
6
5'
4'
19Me
19
Me
17
18
O
COOMe
COOMe
XXI, XXII
XXIII–XXV
XXIII, R = H; XXI, XXIV, R = Me; XXII, XXV, R = PhCH2.
1
mined by H and 13C NMR spectroscopy. In the
1H NMR spectra of these compounds, a signal at
δ 3.38–3.53 ppm was observed due to protons in the
ester methoxy group; also, signals from two NH pro-
tons appeared in the spectra. In the 13C NMR spectra
of IV–XI, the ester C16 signal was located at
δC 171.33–173.68 ppm, and the signal from the C17
carbonyl carbon atom was displaced upfield
(δC 155.66–158.58 ppm). cis Orientation of the 7-H
and 8-H protons is confirmed by the corresponding
spin–spin coupling constants (3J = 7.0–7.2 Hz).
pound XX given in [12]. Compounds XIV–XX dis-
1
played in the H NMR spectra a downfield shift of
signals from the C17H3 and C18H3 methyl groups to
δ 1.52–1.73 ppm, and a singlet at δ 2.91–3.09 ppm was
present due to 6-H. The NMR spectra of hydantoins
XXI and XXII contained signals from 5′-H and C2′,
C4′, and C5′ in the imidazole ring, and the 8-H signal
appeared in a weaker field as compared to initial
ureides, δ, ppm: 4.42 d (J = 6.8 Hz) and 3.84 d.d
(J = 7.2, 7.0 Hz) for compounds XXII and VII,
respectively.
The structure of amidines XIV–XX unambiguous-
ly follows from the X-ray diffraction data for com-
Perhydronaphtho[1,2-h]quinazoline derivatives
XXIII–XXV displayed in the 13C NMR spectra signals
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XX.
1143
C15
C16
C3′
C14
C4′
C5′
C2′
O8
C12
C20
C9a
C1′
C11
C10
C9b
O1
C8
C13
C9
C6′
C1
C11a
C19
C3b
C4
C2
C3
S1
O7
C3a
C7
O3
N2
C5a
C6
C17
C5
O2
O4
C18
Structure of the molecule of methyl (3aR,6R,9aR,11aR)-3b,11-(12-isopropyletheno)-6,9a-dimethyl-2-(4-methylphenylsulfonyloxy)-
1,3-dioxohexadecahydro-1H-naphtho[2,1-e]isoindole-6-carboxylate (III) according to the X-ray diffraction data. Selected bond
lengths, Å: O1–C1 1.200(4), C1–N2 1.387(5), N2–C3 1.396(4), O2–C3 1.192(4), N2–O5 1.388(4), C12–C13 1.324(4).
at δC 170 and 150 ppm from the carbonyl carbon atoms
in the fused uracil fragment. In the IR spectra of
XXIII–XXV we observed strong absorption bands at
1670 (C=O) and 3112, 3248 cm–1 (NH). cis-Junction
of the heterocyclic fragment follows from the spin–
spin coupling constant for the 12a-H and 4a-H protons
(3J = 6.8 Hz).
chloroform at 20–25°C. The progress of reactions was
monitored by TLC on Silufol UV-254 plates. The
products were isolated by column chromatography on
aluminum oxide.
Maleopimaric acid methyl ester (I) was synthe-
sized according to the procedure reported in [16].
Compounds III, V, VI, XIV, XV, and XX were
described by us previously [12].
EXPERIMENTAL
Methyl (3aR,6R,9aR,11aR)-2-hydroxy-3b,11-(12-
isopropyletheno)-6,9a-dimethyl-1,3-dioxohexadeca-
hydro-1H-naphtho[2,1-e]isoindole-6-carboxylate
(II). Hydroxylamine hydrochloride, 4.0 g (58 mmol),
was dissolved in 15 ml of water, 70 ml of ethanol was
added, and concentrated aqueous ammonia was then
added dropwise to pH ~9. Maleopimaric acid methyl
ester (I), 22.0 g (53 mmol), was added to the
resulting solution, the mixture was heated on a water
bath until it became homogeneous, 10 ml of water was
added, the mixture was cooled to room temperature,
and the precipitate was filtered off and washed with
50% ethanol. Yield 18.6 g (82%), mp 277°C (from
1
The H and 13C NMR spectra were measured on
1
Bruker AV-300 (300.13 MHz for H and 75.47 MHz
for 13C), AM-400 (400.13 MHz for 1H and
100.78 MHz for 13C) and Bruker DRX-500 instru-
1
ments (500.13 MHz for H and 125.76 MHz for 13C).
Signals in the NMR spectra were assigned using dif-
ferent proton–proton and carbon–proton shift correla-
tion techniques (COSY, COLOC), as well as two-
dimensional NOESY spectra (II, VII, XIX). The
molecular weights and elemental compositions were
determined from the high-resolution mass spectra
(electron impact, 70 eV) which were obtained on
a Finnigan MAT-8200 mass spectrometer (vaporizer
temperature 270–300°C). The IR spectra were re-
corded in KBr on a Bruker Vector-22 spectrometer.
The melting points were determined on a Kofler hot
stage apparatus. The optical rotations [α]D20 were meas-
ured on a PolAAr3005 polarimeter from solutions in
1
MeOH), [α]580 = –17° (c = 2.56). H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 0.50 s (3H, C20H3), 0.83 d
and 0.85 d (3H each, C15H3, C16H3, J = 7.0), 0.87 m
(1H, 9-H), 1.04 s (3H, C19H3), 1.06 m (1H, 5-H),
2
1.13 m (1H, 10-H, J = 13.3), 1.28–1.47 m (6H, 5-H,
7-H, 8-H, 9-H, 9b-H), 1.51–1.68 m (4H, 4-H, 5a-H,
7-H, 10-H), 2.09 m (1H, 14-H), 2.35 m (2H, 4-H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

CHERNOV et al.
1144
11a-H), 2.71 d.d (1H, 3a-H, J = 6.8, 2.0), 2.93 br.d
(1H, 11-H, J = 2.0), 3.57 s (3H, OCH3), 5.30 s (1H,
13-H), 9.0 br.s (1H, OH). 13C NMR spectrum (CDCl3),
δC, ppm: 15.28 q (C20), 16.40 q (C19), 16.70 t (C8),
19.79 q and 20.40 q (C15, C16), 21.40 t (C5), 27.25 t
(C10), 32.37 d (C14), 34.78 t (C4), 34.99 d (C11), 36.39 t
(C7), 37.37 s (C9a), 37.75 t (C9), 40.40 s (C3b), 41.97 d
(C3a), 46.82 s (C6), 49.12 d (C5a), 49.35 d (C11a),
51.73 q (C18), 53.60 d (C9b), 124.09 d (C13), 146.77 s
(C12), 172.58 s (C3), 173.40 s (C1), 179.06 s (C17).
Mass spectrum, m/z (Irel, %): 429 (8) [M]+, 412 (6), 352
(9), 316 (58), 315 (100). Found: m/z 429.2505 [M]+.
C25H35NO5. Calculated: M 429.25097.
Dimethyl (1R,4aR,7R,8R)-8-(3-benzylureido)-
6,8a-(11-isopropyletheno)-1,4a-dimethyltetradeca-
hydrophenanthrene-1,7-dicarboxylate (VII). A mix-
ture of 2.0 g (3.43 mmol) of compound III, 2 ml of
benzylamine, 2 ml of methylene chloride, and 15 ml of
methanol was kept for 2 days until it became homo-
geneous. The solvent was evaporated, the residue was
treated with ethyl acetate, the solution was washed
with 3% hydrochloric acid (2×15 ml), a 3% solution
of sodium hydroxide (2×15 ml), and water and evap-
orated, and the residue was recrystallized from metha-
nol. Yield 0.92 g (49%), mp 196–198°C, [α]D20 = +8.6°
1
(c = 9.1). H NMR spectrum (CCl4–CDCl3), δ, ppm
(J, Hz): 0.47 s (3H, C20H3), 0.79 d.t (1H, 4-H, J = 12.8,
2.8), 0.89–1.05 m (2H, 5-H, 10-H), 0.92 d and 0.96 d
(3H each, C14H3, C15H3, J = 7.0), 1.04 s (3H, C19H3),
1.16–1.46 m (8H, 2-H, 3-H, 4-H, 4b-H, 5-H, 9-H,
10-H), 1.56–1.70 m (3H, 2-H, 9-H, 10a-H), 2.40 m
(1H, 13-H), 2.52 br.s (1H, 6-H), 2.87 d (1H, 7-H, J =
7.2), 3.37 s (3H, OCH3), 3.53 s (3H, OCH3), 3.84 d.d
(1H, 8-H, J = 7.2, 7.0), 4.10 d.d (1H, PhCH2, J = 8.2,
2.2), 4.18 d.d (1H, PhCH2, J = 8.2, 1.8), 4.56 d (1H,
NH, J = 7.0), 5.10 s (1H, 12-H), 5.40 t (1H, NH, J =
2.2), 7.11–7.23 m (5H, Harom). 13C NMR spectrum
(CCl4–CDCl3), δC, ppm: 15.41 q (C20), 16.65 q (C19),
16.86 t (C3), 19.57 q and 20.78 q (C14, C15), 21.40 t
(C10), 28.56 t (C5), 32.56 d (C13), 33.51 t (C9), 36.64 d
(C6), 36.74 t (C2), 37.04 t (CH2), 37.94 t (C4), 41.95 s
(C4a), 44.06 s (C8a), 46.94 s (C1), 48.87 d (C10a),
50.85 q (CH3), 50.98 d (C4b), 51.58 d (C7), 51.64 q
(CH3), 57.59 d (C8), 122.18 d (C12), 126.86 d (Cp),
127.05 d (Cm), 128.22 d (Co), 139.28 s (Ci), 150.28 s
(C11), 157.54 s (C17), 173.37 s (C16), 178.79 s (C18).
Mass spectrum, m/z (Irel, %): 550 (0.4) [M]+, 520 (1),
519 (4), 368 (1), 318 (3), 317 (23), 316 (100), 187
(24), 146 (46). Found: m/z 550.3399 [M]+. C33H46N2O5.
Calculated: M 550.3401.
Dimethyl (1R,4aR,7R,8R)-6,8a-(11-isopropyl-
etheno)-1,4a-dimethyl-8-ureidotetradecahydro-
phenanthrene-1,7-dicarboxylate (IV). A mixture of
5 g (8.6 mmol) of p-toluenesulfonate III, 10 ml of
a 10% solution of ammonia in methanol, and 15 ml
of methanol was stirred until it became homogeneous
(~1 h). The solvent was distilled off, the residue was
treated with 50 ml of diethyl ether, the solution was
washed with a 3% solution of sodium hydroxide
(2×15 ml) and water and evaporated, and the residue
was recrystallized from ethyl acetate–petroleum ether.
Yield 1.1 g (36%), mp 172–175°C, [α]D20 = +7.7° (c =
2.9). 1H NMR spectrum (CCl4–CDCl3), δ, ppm (J, Hz):
0.47 s (3H, C20H3), 0.79 m (1H, 4-H), 0.88 d and
0.96 d (3H each, C14H3, C15H3, J = 7.0), 0.92–0.98 m
(2H, 5-H, 10-H), 1.03 s (3H, C19H3), 1.20–1.50 m (8H,
2-H, 3-H, 4-H, 4b-H, 5-H, 9-H, 10-H), 1.56–1.65 m
(2H, 2-H, 10a-H), 1.85 m (1H, 9-H, 2J = 13.0), 2.42 m
(1H, 13-H), 2.53 br.s (1H, 6-H), 2.91 d (1H, 7-H, J =
7.0), 3.48 s (3H, OCH3), 3.53 s (3H, OCH3), 3.98 d.d
(1H, 8-H, J = 7.0, 6.2), 4.73 m (2H, NH2), 4.82 t (1H,
NH, J = 6.2), 5.27 br.s (1H, 12-H). 13C NMR spectrum
(CCl4–CDCl3), δC, ppm: 15.37 q (C20), 16.58 q (C19),
16.80 t (C3), 19.46 q and 20.72 q (C14, C15), 21.42 t
(C10), 28.49 t (C5), 32.48 d (C13), 33.52 t (C9), 36.06 d
(C6), 36.26 t (C2), 36.99 s (C4a), 37.96 t (C4), 41.35 s
(C8a), 46.87 s (C1), 48.87 d (C10a), 50.82 d (C7),
51.17 q (CH3), 51.93 d (C4b), 52.12 q (CH3), 57.28 d
(C8), 122.10 d (C12), 149.88 s (C11), 158.46 s (C17),
173.03 s (C16), 178.81 s (C18). Mass spectrum, m/z
(Irel, %): 460 (0.1) [M]+, 445 (0.1), 443 (0.8), 430 (0.4),
429 (1.6), 318 (2.1), 317 (17), 316 (88), 187 (40), 146
(100). Found: m/z 460.2832 [M]+. C26H40N2O5. Cal-
culated: M 460.3007.
The aqueous solution was acidified to isolate 0.61 g
(41%) of N-hydroxy imide II.
Dimethyl (1R,4aR,7R,8R)-6,8a-(11-isopropyl-
etheno)-1,4a-dimethyl-8-(3-p-tolylureido)tetradeca-
hydrophenanthrene-1,7-dicarboxylate (VIII).
A mixture of 5.83 g (10 mmol) of compound III,
2.14 g (20 mmol) of p-toluidine, 3 ml of triethylamine,
and 20 ml of methanol was heated for 2 h under reflux.
The resulting solution was evaporated by half, 50 ml of
ethyl acetate was added, and the solution was washed
with 3% hydrochloric acid (3×15 ml), 3% sodium
hydroxide (2×15 ml), and water and evaporated. The
residue was recrystallized from ethyl acetate–petro-
The alkaline solution was acidified, the precipitate
was extracted into methylene chloride, and the extract
was washed with water and evaporated to isolate
0.65 g (44%) of N-hydroxy imide II.
leum ether. Yield 2.92 g (62%), oily substance, [α]D20
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XX.
1145
1
+5.5° (c = 5.6). H NMR spectrum (CDCl3), δ, ppm
28.01 t (C5), 32.61 d (C13), 33.76 t (C9), 36.18 t (C2),
36.32 d (C6), 37.18 s (C4a), 37.92 t (C4), 41.58 s (C8a),
42.92 t (CH2), 47.05 s (C1), 48.86 d (C10a), 50.92 d
(C7), 51.09 q (CH3), 51.36 d (C4b), 51.83 q (CH3),
57.52 d (C8), 115.03 t (CH2), 122.02 d (C12), 135.22 d
(CH), 150.48 s (C11), 156.48 s (C17), 173.68 s (C16),
179.03 s (C18). Mass spectrum, m/z (Irel, %): 500 (0.4)
[M]+, 469 (4), 317 (23), 316 (100), 187 (20), 146 (45).
Found: m/z 500.3247 [M]+. C29H44N2O5. Calculated:
M 500.3245.
(J, Hz): 0.49 s (3H, C20H3), 0.73 d.t (1H, 4-H, J = 12.6,
2.8), 0.89–1.05 m (2H, 5-H, 10-H), 0.96 d and 1.02 d
(3H each, C14H3, C15H3, J = 7.0), 1.06 s (3H, C19H3),
1.18–1.50 m (8H, 2-H, 3-H, 4-H, 4b-H, 5-H, 9-H,
10-H), 1.58–1.70 m (2H, 2-H, 10a-H), 1.88 m (1H,
9-H), 2.30 s (3H, CH3), 2.42 m (1H, 13-H), 2.58 br.s
(1H, 6-H), 3.00 d (1H, 7-H, J = 7.2), 3.42 s (3H,
OCH3), 3.56 s (3H, OCH3), 4.10 t (1H, NH, J = 7.0),
4.12 d (1H, 8-H, J = 7.2), 5.08 t (1H, NH), 5.18 s (1H,
12-H), 7.02 d (2H, o-H, J = 7.8), 7.10 d (2H, m-H, J =
7.8). 13C NMR spectrum (CDCl3), δC, ppm: 15.43 q
(C20), 16.93 q (C19), 16.86 t (C3), 19.43 q (CH3), 20.52 q
and 20.86 q (C14, C15), 21.42 t (C10), 28.51 t (C5),
32.61 d (C13), 33.64 t (C9), 36.18 t (C2), 36.32 d (C6),
37.05 s (C4a), 37.90 t (C4), 41.36 s (C8a), 46.92 s (C1),
48.80 d (C10a), 50.91 q (CH3), 51.07 d (C4b), 51.45 d
(C7), 51.70 q (CH3), 57.52 d (C8), 120.83 d (Co),
121.93 d (C12), 129.47 d (Cm), 132.62 s (Cp), 135.97 s
(Ci), 150.65 s (C11), 155.56 s (C17), 173.47 s (C16),
178.88 s (C18). Mass spectrum, m/z (Irel, %): 550 (0.7),
520 (2), 519 (4), 318 (3), 317 (22), 316 (100), 187
(15), 146 (31). Found: m/z 550.3381 [M]+. C33H46N2O5.
Calculated: M 550.3401.
The aqueous solution was acidified to isolate 1.4 g
(38%) of N-hydroxy imide II.
Dimethyl (1R,4aR,7R,8R)-6,8a-(11-isopropyl-
etheno)-8-[3-(methoxycarbonylmethyl)ureido]-1,4a-
dimethyltetradecahydrophenanthrene-1,7-dicar-
boxylate (X). A mixture of 2 g (3.43 mmol) of com-
pound III, 1 g (8 mmol) of glycine methyl ester hydro-
chloride, 2 ml of triethylamine, and 20 ml of methanol
was heated for 2 h under reflux. The solution was
concentrated, the residue was diluted with ethyl
acetate, the resulting solution was washed with 3%
sodium hydroxide (2×15 ml) and water and evaporat-
ed, and the residue was recrystallized from methanol.
Yield 0.75 g (41%), mp 206–208°C, [α]D20 = +14.5°
The aqueous solution was acidified to isolate 0.47 g
(32%) of N-hydroxy imide II.
1
(c = 4.11). H NMR spectrum (CCl4–CDCl3), δ, ppm
(J, Hz): 0.49 s (3H, C20H3), 0.78 d.t (1H, 4-H, J = 12.6,
2.8), 0.82–1.05 m (2H, 5-H, 10-H), 0.92 d and 0.96 d
(3H each, C14H3, C15H3, J = 7.0), 1.02 s (3H, C19H3),
1.22–1.44 m (8H, 2-H, 3-H, 4-H, 4b-H, 5-H, 9-H,
10-H), 1.56–1.65 m (2H, 2-H, 10-H), 1.87 m (1H,
9-H), 2.39 m (1H, 13-H), 2.54 br.s (1H, 6-H), 2.90 d
(1H, 7-H, J = 7.2), 3.46 s (3H, OCH3), 3.53 s (3H,
OCH3), 3.59 s (3H, OCH3), 3.67 d and 3.82 d (1H
each, CH2, J = 8.2), 3.94 d.d (1H, 8-H, J = 7.2, 7.0),
4.71 d (1H, NH, J = 7.0), 5.24 s (1H, 12-H), 5.29 t
(1H, NH). 13C NMR spectrum (CCl4–CDCl3), δC, ppm:
15.38 q (C20), 16.40 q (C19), 16.80 t (C3), 19.45 q and
20.75 q (C14, C15), 21.39 t (C10), 28.52 t (C5), 32.29 d
(C13), 32.49 t (C9), 36.10 d (C6), 36.21 t (C2), 37.03 t
(C4), 37.91 s (C4a), 41.33 t (CH2), 41.60 s (C8a), 46.92 s
(C1), 48.86 d (C10a), 50.75 q (CH3), 51.03 d (C4b),
51.56 d (C7), 51.64 q (2C, CH3), 57.65 d (C8), 122.03 d
(C12), 150.44 s (C11), 157.54 s (C17), 171.33 s (C=O),
173.42 s (C16), 178.91 s (C18). Mass spectrum, m/z (Irel,
%): 532 (10) [M]+, 515 (4), 501 (22), 457 (3.6), 444
(40), 316 (100), 284 (15), 257 (32), 187 (37), 146 (82).
Found: m/z 532.7209 [M]+. C29H44N2O7. Calculated:
M 532.6932.
Dimethyl (1R,4aR,7R,8R)-8-(3-allylureido)-6,8a-
(11-isopropyletheno)-1,4a-dimethyltetradecahydro-
phenanthrene-1,7-dicarboxylate (IX). A mixture of
5.0 g (8.6 mmol) of compound III, 2.5 ml of allyl-
amine, 2 ml of methylene chloride, and 20 ml of
methanol was left to stand for 2 days until it became
homogeneous. The solvent was evaporated, the residue
was treated with ethyl acetate, and the solution was
washed with 3% hydrochloric acid (2×15 ml), a solu-
tion of sodium hydroxide, and water and evaporated.
Yield 2.1 g (49%), viscous oily substance, [α]D20
=
+10.5° (c = 4.4). 1H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 0.57 s (3H, C20H3), 0.77 m (1H, 4-H), 0.82 m
(1H, 10-H), 1.00 m (1H, 5-H), 0.99 d and 1.04 d (3H
each, C14H3, C15H3, J = 7.0), 1.10 s (3H, C19H3), 1.20–
1.53 m (8H, 2-H, 3-H, 4-H, 4b-H, 5-H, 9-H, 10-H),
1.69 m (2H, 2-H, 10a-H), 1.88 m (1H, 9-H), 2.49 m
(1H, 13-H), 2.60 br.s (1H, 6-H), 2.97 d (1H, 7-H, J =
7.2), 3.49 s (3H, OCH3), 3.61 s (3H, OCH3), 3.63 d.d
(1H, CH2, J = 8.9, 5.8), 4.05 d.d (1H, 8-H, J = 7.2,
7.0), 4.54 d (1H, NH, J = 7.0), 4.80 m (1H, NH),
5.09 m and 5.15 m (1H each, =CH2), 5.32 d (1H, 12-H,
J = 1.6), 5.66–5.80 m (1H, CH=). 13C NMR spectrum
(CDCl3), δC, ppm: 15.81 q (C20), 16.93 q (C19), 17.12 t
(C3), 19.89 q and 20.86 q (C14, C15), 21.92 t (C10),
The aqueous solution was acidified to isolate 0.53 g
(36%) of N-hydroxy imide II.
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CHERNOV et al.
1146
Dimethyl (1R,4aR,7R,8R)-6,8a-(11-isopropyl-
8-H, J = 7.0, 6.8), 4.42 d (1H, NH, J = 6.8), 5.30 br.s
(1H, 12-H). 13C NMR spectrum (CCl4–CDCl3), δC,
ppm: 15.71 q (C20), 16.82 q (C19), 16.89 t (C3), 19.93 q
and 21.08 q (C14, C15), 21.81 t (C10), 27.82 t (C5),
32.77 d (C13), 33.09 t (C9), 36.48 d (C6), 36.52 t (C2),
36.91 s (C4a), 37.87 t (C4), 41.58 s (C8a), 47.11 s (C1),
49.15 d (C10a), 50.98 d (C7), 51.70 q (CH3), 50.98 d
(C4b), 51.77 q (2C, CH3), 58.84 d (C8), 122.05 d (C12),
148.65 s (C11), 157.96 s (C17), 172.45 s (C16), 179.11 s
(C18). Mass spectrum, m/z (Irel, %): 475 (11) [M]+, 317
(17), 316 (100). Found: m/z 475.3342[M]+. C27H41NO6.
Calculated: M 475.33503.
etheno)-1,4a-dimethyl-8-(3-phenylaminoureido)-
tetradecahydrophenanthrene-1,7-dicarboxylate
(XI). A mixture of 3 g (5.14 mmol) of compound III,
1 g (6.9 mmol) of phenylhydrazine hydrochloride,
1.5 ml of triethylamine, and 20 ml of methanol was
heated for 2 h under reflux. When the reaction was
complete, the mixture was treated as described above
in the synthesis of compound X. Yield of XI 0.88 g
(31%), mp 256–258°C, [α]D20 = +3.2° (c = 1.7). Also,
1.06 g (48%) of N-hydroxy imide II was isolated.
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 0.51 s
(3H, C20H3), 0.76 d.t (1H, 4-H, J = 12.4, 2.6), 0.88 d
and 0.96 d (3H each, C14H3, C15H3, J = 7.0), 0.90–
1.05 m (2H, 5-H, 10-H), 1.08 s (3H, C19H3), 1.21–
1.49 m (8H, 2-H, 3-H, 4-H, 4b-H, 5-H, 9-H, 10-H),
Dimethyl (1R,4aR,7R,8R)-8-[3-(2-bromo-4-
methylphenyl)ureido]-6,8a-(11-isopropyletheno)-
1,4a-dimethyltetradecahydrophenanthrene-1,7-di-
carboxylate (XIII). Molecular bromine was added
dropwise to a solution of 1.3 g (2.36 mmol) of com-
pound VIII and 0.5 g of potassium acetate in 10 ml of
acetic acid until persistent color. The mixture was
stirred for 10 min, and a 10% solution of Na2SO3 was
added to remove excess bromine. The mixture was
diluted with water, and the precipitate was filtered off,
washed with water, and recrystallized from aqueous
2
1.60–1.73 m (2H, 2-H, 10a-H), 1.79 m (1H, 9-H, J =
13.0), 2.39 m (1H, 13-H), 2.57 br.s (1H, 6-H), 2.95 d
(1H, 7-H, J = 7.0), 3.38 s (3H, OCH3), 3.62 s (3H,
OCH3), 4.02 d.d (1H, 8-H, J = 7.0, 7.1), 5.17 s (1H,
12-H), 5.74 d (1H, NH, J = 7.1), 6.22 m (1H, NH),
6.74 d (2H, o-H, J = 7.6), 6.87 t (1H, p-H, J = 7.6),
7.19 t (2H, m-H, J = 7.6). 13C NMR spectrum (CDCl3),
δC, ppm: 15.47 q (C20), 16.72 q (C19), 16.94 t (C3),
19.74 q and 20.93 q (C14, C15), 21.48 t (C10), 28.71 t
(C5), 32.70 d (C13), 33.61 t (C9), 36.38 t (C2), 36.53 d
(C6), 37.10 t (C4), 38.03 s (C4a), 41.65 s (C8a), 47.03 s
(C1), 48.91 d (C10a), 50.72 d (C7), 51.04 q (CH3),
51.47 d (C4b), 51.82 q (CH3), 57.18 d (C8), 112.93 d
(Co), 121.25 d (Cp), 122.24 d (C12), 129.13 d (Cm),
147.31 s (Ci), 150.60 s (C11), 158.58 s (C17), 172.96 s
(C16), 178.99 s (C18). Mass spectrum, m/z (Irel, %): 536
(16) [M]+, 457 (9), 441 (42), 316 (100). Found: m/z
536.70245 [M]+. C32H44N2O5. Calculated: M 536.7007.
methanol. Yield 1.3 g (88%), mp 204–206°C, [α]D20
=
+19.5° (c = 4.1). 1H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 0.48 s (3H, C20H3), 0.75 d.t (1H, 4-H, J = 12.6,
2.8), 0.92–1.12 m (2H, 5-H, 10-H), 0.98 d and 1.04 d
(3H each, C14H3, C15H3, J = 7.0), 1.08 s (3H, C19H3),
1.18–1.50 m (8H, 2-H, 3-H, 4-H, 4b-H, 5-H, 9-H,
10-H), 1.58–1.72 m (2H, 2-H, 10a-H), 1.86 m (1H,
9-H), 2.23 s (3H, CH3), 2.42 m (1H, 13-H), 2.62 br.s
(1H, 6-H), 3.00 d (1H, 7-H, J = 7.2), 3.50 s (3H,
OCH3), 3.59 s (3H, OCH3), 4.08 d.d (1H, 8-H, J = 7.2,
7.0), 4.80 d (1H, NH, J = 7.0), 5.25 s (1H, 12-H),
6.48 br.s (1H, NH), 7.00 d.d (1H, 5′-H, J = 7.8, 1.8),
7.22 d (1H, 3′-H, J = 1.8), 7.52 d (1H, 6′-H, J = 7.8).
13C NMR spectrum (CDCl3), δC, ppm: 15.44 q (C20),
16.68 q (C19), 16.86 t (C3), 19.60 q (CH3), 20.19 q and
20.82 q (C14, C15), 21.44 t (C10), 28.53 t (C5), 32.59 d
(C13), 33.61 t (C9), 36.23 t (C2), 36.30 d (C6), 37.06 s
(C4a), 37.90 t (C4), 41.43 s (C8a), 46.94 s (C1), 48.87 d
(C10a), 50.58 d (C7), 51.24 q (CH3), 51.55 d (C4b),
51.78 q (CH3), 57.12 d (C8), 115.37 s (C2′), 121.99 d
(C12), 123.21 d (C6′), 128.65 d (C5′), 132.51 d (C3′),
133.67 s (C4′), 134.62 s (C1′), 150.68 s (C11), 154.53 s
(C17), 173.29 s (C16), 178.90 s (C18). Mass spectrum,
m/z (Irel, %): 597 (2) [M – OCH3]+, 399 (1), 398 (2),
318 (3), 317 (26), 316 (100), 187 (16), 146 (32).
Found: m/z 597.2316 [M – OCH3]+. C33H45BrN2O5.
Calculated: 597.2322 [M – OCH3]+; M 628.4042.
Dimethyl (1R,4aR,7R,8R)-6,8a-(11-isopropyl-
etheno)-8-(methoxycarbonylamino)-1,4a-dimethyl-
tetradecahydrophenanthrene-1,7-dicarboxylate
(XII). A mixture of 5.0 g of compound III, 2.0 ml of
triethylamine, and 20 ml of methanol was heated under
reflux until it became homogeneous (1 h). After ap-
propriate treatment, we isolated 2.3 g (55%) of oily
carbamate XII and 0.95 g (26%) of N-hydroxy imide
II. [α]D20 = –6.8° (c = 4.0). H NMR spectrum (CCl4–
1
CDCl3), δ, ppm (J, Hz): 0.54 s (3H, C20H3), 0.93 m
(1H, 4-H), 0.97 d and 1.04 d (3H each, C14H3, C15H3,
J = 7.0), 0.89–0.98 m (2H, 5-H, 10-H), 1.07 s (3H,
C19H3), 1.28–1.50 m (7H, 2-H, 3-H, 4-H, 4b-H, 5-H,
9-H, 1-H), 1.52–1.69 m (3H, 2-H, 3-H, 10a-H), 1.89 m
(1H, 9-H, 2J = 13.0), 2.46 m (1H, 13-H), 2.59 br.s (1H,
6-H), 2.94 d (1H, 7-H, J = 7.0), 3.48 s (3H, OCH3),
3.53 s (3H, OCH3), 3.59 s (3H, OCH3), 3.84 d.d (1H,
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SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XX.
1147
Dimethyl (3R,3aR,9R,12aR)-5-benzylamino-2,6-
(isopropylidenemethano)-9,12a-dimethyl-1,2,3,3a,-
6,7,8,8a,9,10,11,12,12a,12b-tetradecahydronaphtho-
[2,1-d]indole-3,9-dicarboxylate (XVI). A mixture of
0.35 g of compound VII, 0.5 ml of phosphoryl
chloride, and 10 ml of toluene was heated for 20 min
under reflux until hydrogen chloride no longer
evolved. The mixture was washed with a solution of
ammonia and water and evaporated, and the residue
was recrystallized from aqueous methanol. Yield
0.19 g (55%), mp 128–130°C, [α]D20 = –106° (c = 5.2).
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 0.72 s
(3H, C20H3), 0.81 d.t (1H, H12, J = 13.2, 2.8), 0.89 m
(1H, 8-H), 1.02 m (1H, 11-H), 1.08 s (3H, C19H3),
1.30–1.60 m (5H, 1-H, 7-H, 8-H, 10-H, 11-H), 1.62–
1.72 m (5H, 1-H, 8a-H, 10-H, 12-H, 12b-H), 1.73 s
(6H, C17H3, C18H3), 1.82 m (1H, 7-H), 2.64 d (1H,
3-H, J = 5.4), 3.09 s (1H, 6-H), 3.06 br.s (1H, 2-H),
3.43 s (3H, OCH3), 3.56 d (1H, 3a-H, J = 5.4), 3.58 s
(3H, OCH3), 4.16 d and 4.32 d (1H each, PhCH2, J =
8.4), 4.24 m (1H, NH), 7.15 m (3H, Harom), 7.23 m
(2H, Harom). 13C NMR spectrum (CDCl3), δC, ppm:
13.39 q (C20), 16.27 q (C19), 17.04 t (C11), 19.82 q and
20.70 q (C17, C18), 21.61 t (C8), 30.10 t (C1), 32.12 d
(C2), 34.51 t (C7), 36.57 t (C10), 37.28 s (C12a), 37.52 t
(C12), 46.30 d (C12b), 46.96 s (C9), 47.12 s (C6a),
49.80 d (C3), 49.89 d (C8a), 50.08 d (C6), 50.79 q
(CH3), 51.62 q (CH3), 71.12 d (C3a), 126.63 s (C13),
127.14 d and 127.25 d (Co), 128.16 s (C16), 128.33 d
(Cp), 128.83 d (Cm), 139.58 s (Ci), 162.77 s (C5),
172.82 s (C14), 178.87 s (C15). Mass spectrum, m/z
(Irel, %): 533 (27) [M + H]+, 532 (86), 531 (25), 517
(19), 473 (19), 358 (10), 336 (21), 335 (100), 91 (39).
Found: m/z 532.3293 [M]+. C33H44N2O4. Calculated:
M 532.3296.
1.59 s (6H, C17H3, C18H3), 1.63 m (1H, 7-H), 2.47 d
(1H, 3-H, J = 5.4), 2.89 br.s (1H, 2-H), 2.91 br.s (1H,
6-H), 3.41 s (3H, OCH3), 3.42 d (1H, 3a-H, J = 5.4),
3.46 s (3H, OCH3), 3.52 m (2H, CH2), 4.88 m (3H,
NH, CH2=), 5.65 m (1H, CH=). 13C NMR spectrum
(CDCl3), δC, ppm: 12.98 q (C20), 15.91 q (C19), 16.65 t
(C11), 19.22 q and 20.34 q (C17, C18), 21.16 t (C8),
29.68 t (C1), 31.49 d (C2), 34.08 t (C7), 36.18 t (C10),
36.90 s (C12a), 37.13 t (C12), 44.87 t (CH2), 45.85 d
(C12b), 46.66 s (C9), 46.93 d (C3), 47.64 s (C6a), 49.11 d
(C8a), 49.45 d (C6), 50.53 q (CH3), 51.22 q (CH3),
71.22 d (C3a), 114.48 t (CH2=), 126.54 s (C13), 128.82 s
(C16), 134.21 d (CH=), 168.25 s (C5), 172.25 s (C14),
178.37 s (C15). Found: m/z 482.3122 [M]+. C29H42N2O4.
Calculated: M 482.3139.
Dimethyl (2S,3R,3aR,6aS,9R,12aR)-5-(2-bromo-
4-methylphenylamino)-2,6-(isopropylidenemeth-
ano)-9,12a-dimethyl-1,2,3,3a,6,7,8,8a,9,10,11,12,-
12a,12b-tetradecahydronaphtho[2,1-d]indole-3,9-
dicarboxylate (XVIII) was synthesized from 0.3 g of
compound XIII under similar conditions. Chromato-
graphic purification gave 0.21 g (73%) of amidine
XVIII with mp 161–163°C, [α]D20 = –121° (c = 5.4).
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 0.73 s
(3H, C20H3), 0.80 d.t (1H, 12-H, J = 13.0, 2.8), 1.16 s
(3H, C19H3), 1.18–1.25 m (2H, 8-H, 11-H), 1.38–
1.48 m (3H, 1-H, 7-H, 11-H), 1.50–1.72 m (7H, 1-H,
8-H, 8a-H, 10-H, 12-H, 12b-H), 1.76 s and 1.83 s (3H
each, C17H3, C18H3), 2.04 m (1H, 7-H), 2.22 s (3H,
C19H3), 2.61 d (1H, 3-H, J = 6.4), 3.13 br.s (1H, 2-H),
3.22 d.d (1H, 3a-H, J = 6.4, 1.8), 3.38 s (1H, 6-H),
3.57 s (3H, OCH3), 3.54 s (3H, OCH3), 4.65 br.s (1H,
NH), 6.61 d (1H, 6′-H, J = 8.2), 6.92 d.d (1H, 5′-H, J =
8.2, 2.0), 7.28 d (1H, 3′-H, J = 2.0). 13C NMR spec-
trum (CDCl3), δC, ppm: 13.80 q (C20), 16.36 q (C19),
17.13 t (C11), 20.22 q (CH3), 20.16 q and 21.68 q (C17,
C18), 22.53 t (C8), 30.05 t (C1), 30.82 d (C2), 34.53 t
(C7), 36.82 t (C10), 37.52 s (C12a), 37.76 t (C12), 45.38 s
(C9), 46.34 d (C12b), 47.13 s (C6a), 48.08 d (C6),
48.86 d (C3), 50.07 d (C8a), 51.54 q (CH3), 51.78 q
(CH3), 62.50 d (C3a), 115.96 s (C2′), 122.62 d (C6′),
126.09 s (C13), 128.74 d (C5'), 128.98 s (C16), 133.19 d
(C3′), 133.37 s (C4′), 146.25 s (C1′), 162.99 s (C5),
172.25 s (C14), 179.09 s (C15). Found: m/z 610.32 [M]+.
C33H43BrN2O4. Calculated: M 610.29.
Dimethyl (3R,3aR,9R,12aR)-5-allylamino-2,6-
(isopropylidenemethano)-9,12a-dimethyl-1,2,3,3a,-
6,7,8,8a,9,10,11,12,12a,12b-tetradecahydronaphtho-
[2,1-d]indole-3,9-dicarboxylate (XVII). A solution of
0.9 g of compound IX and 0.5 ml of phosphoryl
chloride in 10 ml of toluene was heated under reflux
until hydrogen chloride no longer evolved (20–
30 min). When the reaction was complete, the mixture
was washed with a 3% solution of ammonia and water
and evaporated. The residue was subjected to chroma-
tography using ethanol–diethyl ether (1:1) as eluent.
Yield 0.59 g (68%), oily substance, [α]D20 = –87.5° (c =
Dimethyl (2S,3R,3aR,6aS,9R,12aR)-2,6-(iso-
propylidenemethano)-9,12a-dimethyl-5-[(4-methyl-
phenylsulfonyl)(phenyl)amino]-1,2,3,3a,6,7,8,8a,-
9,10,11,12,12a,12b-tetradecahydronaphtho[2,1-d]-
indole-3,9-dicarboxylate (XIX). A solution of 0.3 g of
compound XV, 0.2 g of p-toluenesulfonyl chloride,
1
7.9). H NMR spectrum (CDCl3), δ, ppm (J, Hz):
0.60 s (3H, C20H3), 0.80 d.t (1H, 12-H, J = 13.0, 2.8),
0.89 m (1H, 8-H), 0.99 s (3H, C19H3), 1.08 m (1H,
11-H), 1.15–1.22 m (3H, 1-H, 7-H, 8-H), 1.42–
1.526 m (7H, 1-H, 8a-H, 10-H, 11-H, 12-H, 12b-H),
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CHERNOV et al.
1148
and 0.2 ml of triethylamine in 10 ml of chloroform was
kept for 18 h. When the reaction was complete, the
mixture was washed with water and evaporated, and
the residue was subjected to chromatography using
diethyl ether–petroleum ether (1:2) as eluent. Yield
0.22 g (57%), mp 145–147°C (from aqueous metha-
OCH3), 3.32 d and 3.50 d (1H each, 5′-H, J = 8.5),
3.52 s (3H, OCH3), 4.32 d (1H, 8-H, J = 7.0), 5.28 s
(1H, 12-H). 13C NMR spectrum (CDCl3), δC, ppm:
15.16 q (C20), 16.46 q (C19), 16.65 t (C3), 19.27 q and
20.77 q (C14, C15), 24.32 q (CH3), 21.40 t (C10), 28.23 t
(C5), 32.27 d (C13), 33.85 t (C9), 35.30 d (C6), 36.20 t
(C2), 37.03 s (C4a), 37.71 t (C4), 40.32 s (C8a), 46.63 s
(C1), 48.19 d (C7), 48.70 d (C10a), 49.12 t (C5′), 51.49 q
(CH3), 51.64 q (CH3), 52.53 d (C4b), 59.73 d (C8),
122.80 d (C12), 148.25 s (C11), 157.13 s (C2′), 169.45 s
(C4′), 172.31 s (C16), 178.22 s (C18). Mass spectrum,
m/z (Irel, %): 515 (0.3) [M + H]+, 514 (0.5), 484 (1),
483 (2), 423 (0.5), 341 (0.5), 340 (0.4), 317 (21), 316
(100). Found: m/z 515.3117 [M + H]+. C29H43N2O6.
Calculated: M + H 515.3115.
nol), [α]D20 = –239° (c = 2.4). H NMR spectrum
1
(CDCl3), δ, ppm (J, Hz): 0.78 s (3H, C20H3), 0.91 m
(1H, 12-H), 1.15 s (3H, C19H3), 1.38 m (3H, 1-H, 7-H,
8-H), 1.50–1.68 m (9H, 1-H, 8-H, 8a-H, 10-H, 11-H,
12-H, 12b-H), 1.74 s and 1.93 s (3H each, C17H3,
2
C18H3), 1.82 m (1H, 7-H, J = 8.4), 2.38 s (3H, CH3),
2.41 d (1H, 3-H, J = 5.6), 2.99 s (1H, 6-H), 3.06 br.s
(1H, 2-H), 3.67 s (3H, OCH3), 3.81 d (1H, 3a-H, J =
5.8), 3.82 s (3H, OCH3), 6.92 m (2H, m-H, J = 8.4),
7.12–7.28 m (5H, Ph), 7.43 d (2H, o-H, J = 8.4).
13C NMR spectrum (CDCl3), δC, ppm: 13.45 q (C20),
16.47 q (C19), 17.18 t (C11), 19.80 q and 21.42 q (C17,
C18), 21.46 q (CH3), 21.59 t (C8), 30.45 t (C1), 33.10 d
(C2), 34.72 t (C7), 36.81 t (C10), 37.54 s (C12a), 37.64 t
(C12), 44.17 d (C3), 46.11 d (C12b), 47.15 s (C9), 48.42 s
(C6a), 50.27 d (C8a), 50.62 d (C6), 51.74 q (OCH3),
53.30 q (OCH3), 72.43 d (C3a), 123.81 s (C13), 126.52 s
(C16), 128.02 d (Co), 128.25 d (Cp), 128.44 d (Co′),
129.07 d (Cm), 130.39 d (Cm′), 135.40 s (Ci′), 138.23 s
(Ci), 143.83 s (Cp′), 171.50 s (C5), 172.04 s (C14),
179.08 s (C15). Mass spectrum, m/z (Irel, %): 672 (2)
[M]+, 671 (2), 608 (76), 518 (61), 517 (100), 411 (12),
321 (38). Found: m/z 672.3213 [M]+. C39H48N2O6S.
Calculated: M 672.3237.
Dimethyl (1R,4aR,7R,8R)-8-(3-benzyl-2,4-dioxo-
imidazolidin-1-yl)-6,8a-(11-isopropyletheno)-1,4a-
dimethyltetradecahydrophenanthrene-1,7-dicar-
boxylate (XXII). A solution of 0.5 g of compound
VII, 0.3 ml of a glyoxal solution, and 0.3 ml of con-
centrated hydrochloric acid in 10 ml of ethanol was
heated for 1 h under reflux. After appropriate treat-
ment, followed by chromatographic purification, we
isolated 0.41 g (78%) of compound XXII as an oily
substance, [α]D20 = –50.6° (c = 3.7). H NMR spectrum
1
(CDCl3), δ, ppm (J, Hz): 0.52 s (3H, C20H3), 0.79 d.t
(1H, 4-H, J = 12.6, 2.6), 1.01 d and 1.07 d (3H each,
C14H3, C15H3, J = 7.0), 0.91–1.07 m (2H, 5-H, 10-H),
1.11 s (3H, C19H3), 1.20–1.53 m (8H, 2-H, 3-H, 4-H,
4b-H, 5-H, 9-H, 10-H), 1.59–1.71 m (3H, 2-H, 9-H,
10a-H), 2.52 m (1H, 13-H), 2.73 br.s (1H, 6-H),
2.89 d.d (1H, 7-H, J = 6.8, 1.2), 3.42 d and 3.50 d (1H
each, 5′-H, J = 8.6), 3.61 s (3H, OCH3), 4.42 d (1H,
8-H, J = 6.8), 4.49 d and 4.62 d (1H each, PhCH2,
J = 8.6), 5.34 s (1H, 12-H), 7.20–7.26 m (3H, Harom),
7.37 m (2H, Harom). 13C NMR spectrum (CDCl3), δC,
ppm: 15.31 q (C20), 16.64 q (C19), 16.83 t (C3), 19.39 q
and 20.90 q (C14, C15), 21.36 t (C10), 28.38 t (C5),
32.48 d (C13), 34.05 t (C9), 35.42 d (C6), 36.41 t (C2),
37.22 s (C4a), 37.89 t (C4), 40.45 s (C8a), 42.20 t (CH2),
46.91 s (C1), 48.59 d (C7), 48.92 d (C10a), 49.44 t (C5′),
51.14 q (CH3), 51.78 q (CH3), 52.79 d (C4b), 59.94 d
(C8), 122.88 d (C12), 126.98 d (C4″); 127.66 d,
127.70 d, 128.43 d, and 128.76 d (C2″, C3″, C5″, C6″),
136.09 s (C1″), 148.59 s (C11), 157.22 s (C2′), 169.43 s
(C4′), 172.71 s (C16), 178.83 s (C18).
Dimethyl (1R,4aR,7R,8R)-6,8a-(11-isopropyl-
etheno)-1,4a-dimethyl-8-(3-methyl-2,4-dioxoimid-
azolidin-1-yl)tetradecahydrophenanthrene-1,7-di-
carboxylate (XXI). Compound V, 0.3 g (0.7 mmol),
was dissolved in 10 ml of ethanol, 0.2 ml of 40%
aqueous glyoxal and 0.2 ml of concentrated hydro-
chloric acid were added, and the mixture was heated
for 5 min under reflux, diluted with water, and ex-
tracted with diethyl ether. The extract was washed with
water and evaporated, and the residue was purified by
chromatography using diethyl ether–petroleum ether
(1:1) as eluent. Yield 0.22 g (69%), mp 208–210°C
(from aqueous methanol), [α]D20 = –41° (c = 6.1).
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 0.47 s
(3H, C20H3), 0.80 d.t (1H, 4-H, J = 12.8, 2.8), 0.90 d
and 0.98 d (3H each, C14H3, C15H3, J = 7.0), 0.89–
1.05 m (2H, 5-H, 10-H), 0.99 s (3H, C19H3), 1.16–
1.40 m (7H, 2-H, 3-H, 4-H, 4b-H, 9-H, 10-H), 1.48 m
(1H, 5-H), 1.56–1.68 m (3H, 2-H, 9-H, 10a-H), 2.40 m
(1H, 13-H), 2.55 d (1H, 6-H, J = 1.2, 1.6), 2.80 s (3H,
CH3), 2.87 d.d (1H, 7-H, J = 7.0, 1.6), 3.27 s (3H,
Methyl (4aS,7R,10aR,12aR)-4b,12-(13-isopropyl-
etheno)-7,10a-dimethyl-1,3-dioxooctadecahydro-
naphtho[1,2-h]quinazoline-7-carboxylate (XXIII).
Compound IV, 0.3 g, was added to a solution of so-
dium ethoxide prepared from 0.2 g of metallic sodium
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

SYNTHETIC TRANSFORMATIONS OF HIGHER TERPENOIDS: XX.
1149
and 10 ml of anhydrous ethanol, and the mixture was
heated for 30 min at 60°C. When the reaction was
complete, the mixture was diluted with water and
extracted with diethyl ether. The extract was washed
with water and evaporated, and the residue was puri-
fied by chromatography using diethyl ether–petroleum
ether (1:1) as eluent. Yield 0.18 g (62%), oily sub-
(C5), 36.50 t (C8), 36.88 s (C10a), 37.69 t (C10), 38.42 d
(C12), 42.54 s (C4b), 43.45 d (C12a), 46.67 s (C7),
49.12 d (C6a), 50.96 d (C10b), 51.42 q (C19), 57.79 d
(C4a), 124.33 d (C14), 148.07 s (C13), 152.76 s (C3),
170.21 s (C1), 178.22 s (C18). Mass spectrum, m/z
(Irel, %): 443 (0.3) [M + H]+, 442 (0.1), 427 (0.2), 381
(0.1), 332 (0.3), 330 (7), 329 (0.2), 317 (24), 316 (96),
257 (15), 187 (44), 146 (100). Found: m/z 443.2907
[M + H]+. C26H38N2O4. Calculated: M + H 443.2905.
stance, [α]D20 = –68.5° (c = 2.3). H NMR spectrum
1
(CDCl3), δ, ppm (J, Hz): 0.55 s (3H, C20H3), 0.92 d
and 0.94 d (3H each, C15H3, C16H3, J = 6.9), 0.94 m
(1H, 10-H), 1.08–1.20 m (3H, 6-H, 10b-H, 11-H),
1.22 m (1H, 5-H, 2J = 13.0), 1.14 s (3H, C19H3), 1.28–
1.55 m (5H, 6-H, 8-H, 9-H, 10-H), 1.57–1.67 m (3H,
6a-H, 8-H, 11-H), 2.15 d.d.d (1H, 5-H, J = 13.0, 4.6,
2.0), 2.20 m (1H, 15-H), 2.87 d.d (1H, 12a-H, J = 6.8,
1.8), 3.07 br.d (1H, 12-H, J = 1.8), 3.33 d (1H, 4a-H,
J = 6.8), 3.53 s (3H, OCH3), 5.36 s (1H, 14-H), 6.98 s
(1H, NH), 8.88 s (1H, NH). 13C NMR spectrum
(CDCl3), δC, ppm: 15.39 q (C20), 16.37 q (C19), 16.57 t
(C8), 19.76 q and 20.26 q (C16, C17), 21.05 t (C6), 27.98
t (C11), 32.42 d (C15), 33.40 t (C5), 36.56 t (C8), 36.87 s
(C10a), 37.52 t (C10), 37.71 d (C12), 42.44 s (C4b),
42.67 d (C12a), 46.71 s (C7), 49.14 d (C6a), 51.01 d
(C10b), 51.63 q (C19), 59.65 d (C4a), 124.19 d (C14),
147.98 s (C13), 152.81 s (C3), 171.75 s (C1), 178.80 s
(C18). Mass spectrum, m/z (Irel, %): 429 (8) [M + H]+,
428 (2), 413 (2), 412 (6), 352 (9), 317 (58), 316 (100).
Found: m/z 429.2505 [M + H]+. C25H36N2O4. Calculat-
ed: M + H 429.25097.
Methyl (4aS,7R,10aR,12aR)-2-benzyl-4b,12-(13-
isopropyletheno)-7,10a-dimethyl-1,3-dioxooctadeca-
hydronaphtho[1,2-h]quinazoline-7-carboxylate
(XXV) was synthesized in a similar way from 0.28 g
of compound VII. Yield 0.15 g (55%), oily substance,
[α]D20 = –75° (c = 4.3). H NMR spectrum (CDCl3), δ,
1
ppm (J, Hz): 0.62 s (3H, C20H3), 0.69 d and 0.81 d (3H
each, C17H3, C16H3, J = 6.9), 0.92 m (1H, 10-H, J =
13.2, 8.6, 3.2), 1.14 s (3H, C19H3), 1.11–1.22 m (3H,
6-H, 10b-H, 11-H), 1.25 m (1H, 5-H, 2J = 13.0), 1.28–
1.52 m (5H, 6-H, 8-H, 9-H, 10-H), 1.57–1.65 m (3H,
6a-H, 8-H, 11-H), 1.88 m (1H, 15-H), 2.15 d.d.d (1H,
5-H, J = 13.0, 4.8, 2.2), 2.79 d.d (1H, 12a-H, J = 6.8,
1.8), 3.04 br.d (1H, 12-H, J = 1.8), 3.11 d (1H, 4a-H,
J = 6.8), 3.48 s (3H, OCH3), 4.68 d and 4.76 d (1H
each, PhCH2, J = 8.6), 5.29 s (1H, 14-H), 6.81 br.s
(1H, NH), 7.11–7.23 m (3H, Harom), 7.32 m (2H,
H
arom). 13C NMR spectrum (CDCl3), δC, ppm: 16.62 q
(C20), 17.38 q (C19), 17.87 t (C8), 20.53 q and 21.52 q
(C16, C17), 22.43 t (C6), 28.93 t (C11), 33.43 d (C15),
34.44 t (C5), 37.62 t (C8), 38.02 s (C10a), 38.11 t (C10),
38.79 d (C12), 43.63 s (C4b), 43.82 t (CH2), 44.30 d
(C12a), 47.59 s (C7), 50.30 d (C6a), 52.25 d (C10b),
52.59 q (C19), 59.06 d (C4a), 125.10 d (C14), 127.92 d
(Cp), 128.88 d and 129.17 d (Co, Cm), 138.49 s (Ci),
148.97 s (C13), 153.74 s (C3), 170.81 s (C1), 179.36 s
(C18). Mass spectrum, m/z (Irel, %): 519 (0.16) [M + H]+,
518 (0.11), 516 (0.2), 473 (0.2), 457 (0.1), 443 (0.4),
330 (9), 317 (18), 316 (100). Found: m/z 519.3198
[M + H]+. C32H42N2O4. Calculated: M + H 519.3195.
Methyl (4aS,7R,10aR,12aR)-4b,12-(13-isopropyl-
etheno)-2,7,10a-trimethyl-1,3-dioxooctadecahydro-
naphtho[1,2-h]quinazoline-7-carboxylate (XXIV)
was synthesized in a similar way from 0.3 g of com-
pound V. Chromatographic purification gave 0.23 g
(68%) of quinazoline XXIV with mp 185–187°C,
[α]D20 = –82° (c = 6.3). IR spectrum, ν, cm–1: 3330,
3248, 3112 (NH); 1714, 1670 (C=O); 1550, 698, 673
1
(C=C). H NMR spectrum (CDCl3), δ, ppm (J, Hz):
0.58 s (3H, C20H3), 0.92 d and 0.94 d (3H each, C15H3,
C16H3, J = 6.9), 0.92 m (1H, 10-H), 0.98–1.14 m (3H,
6-H, 10b-H, 11-H), 1.13 s (3H, C19H3), 1.22 m (1H,
X-Ray analysis of compound III. The X-ray dif-
fraction data for compound III were acquired on
a Bruker P4 diffractometer (MoKα irradiation, graphite
monochromator, 296 K, θ/2θ scanning, 2θ < 52°) from
a 0.60×0.55×0.45-mm single crystal. Colorless rhom-
bic crystals; C32H41NO7S; M 583.72. Unit cell param-
eters: a = 9.8877(7), b = 13.861(1), c = 22.496(1) Å;
2
5-H, J = 13.0), 1.30 d.d.d (1H, 10-H, J = 13.2, 9.2,
4.0), 1.34–1.55 m (5H, 6-H, 8-H, 9-H, 12-H), 1.57–
1.67 m (3H, 6a-H, 8-H, 11-H), 2.12 d.d.d (1H, 5-H, J =
13.0, 4.2, 2.0), 2.19 m (1H, 15-H), 2.87 d.d (1H,
12a-H, J = 6.8, 1.8), 3.07 br.d (1H, 12-H, J = 1.8),
3.22 d (1H, 4a-H, J = 6.8), 3.62 s (3H, OCH3), 5.38 s
(1H, 14-H), 6.71 s (1H, NH). 13C NMR spectrum
(CDCl3), δC, ppm: 15.44 q (C20), 16.45 q (C19), 16.75 t
(C8), 19.93 q and 20.37 q (C16, C17), 21.34 t (C6),
26.22 q (CH3), 28.04 t (C11), 32.56 d (C15), 33.25 t
V = 3083.2(3) Å3; space group P212121; Z = 4; dcalc
=
1.258 g/cm3; μ = 0.152 mm–1. Number of independent
reflections 3408 (Rint = 0.0055). The structure was
solved by the direct method using SIR2002 program
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

CHERNOV et al.
1150
Takigawa, M., Tsutsumi, T., and Kine, M., JPN Patent
Appl. no. 35058, 1984; Chem. Abstr., 1986, vol. 104,
no. 88884.
and was refined by the least-squares procedure in
anisotropic approximation (isotropic for hydrogen
atoms) using SHELXL-97 software package. A correc-
tion for absorption was introduced empirically (trans-
mission 0.96–0.98). The positions of hydrogen atoms
were set on the basis of geometry considerations and
were refined according to the riding model. The final
divergence factors were wR2 = 0.1249, S = 1.015 (all
reflections), and R = 0.0437 [2797 reflections with I >
2σ(I)]; absolute structure parameter –0.06(14). The
complete set of crystallographic data for compound III
(coordinates of atoms and their thermal vibration
factors and geometric parameters of the molecule) was
deposited to the Cambridge Crystallographic Data
Centre (entry no. CCDC 682305; http://www.ccdc.-
cam.uk/conts/retrieving.html)
6. Svikle, D.Ya., Kalnynsh, A.Ya., Karklin, R.Ya.,
Pruze, B.A., Prikule, A.Ya., Rumba, A.Ya., Razi-
nya, R.A., Baumane, G.K., and Kul’kevich, A.Ya.,
USSR Patent no. 584722, 1994; Byull. Izobret., 1994,
no. 13, p. 195; Chem. Abstr., 1995, vol. 123,
no. 314216; Aleksandrov, Yu.V., Kul’kevich, A.Ya.,
Svikle, D.Ya., and Prikule, A.Ya., Available from
VINITI, Riga, 1981, p. 8; Chem. Abstr., 1983, vol. 98,
no. 40529.
7. Schuller, W.H., Minor, J.C., Block, S.S., and Law-
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8. Tolstikov, A.G., Tolstikova, O.V., Khlebnikova, T.V.,
and Karpishev, N.I., Mendeleev Commun., 1996, no. 6,
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va, O.V., Khlebnikova, T.B., Sal’nikov, G.E., Mama-
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This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 09-03-00183, 08-03-00340).
9. Tuman, W.J. and Bauer, L., J. Org. Chem., 1972,
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