First examples of hydroxycyclopropanation in the series of lupane triterpenoids

Article abstract of DOI:10.1134/S1070428009100078

Hydroxycyclopropanation at the ester group in the series of lupane triterpenoids was performed for the first time using 3,3-ethylenedioxybetulonic acid methyl ester and its 20,29-dihydro analog as substrates.

Full text of DOI:10.1134/S1070428009100078

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 10, pp. 1464–1467. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.N. Odinokov, E.R. Shakurova, L.M. Khalilov, U.M. Dzhemilev, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45,
No. 10, pp. 1479–1482.
First Examples of Hydroxycyclopropanation
in the Series of Lupane Triterpenoids
V. N. Odinokov, E. R. Shakurova, L. M. Khalilov, and U. M. Dzhemilev
Institute of Petroleum Chemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: ink@anrb.ru
Received October 23, 2008
Abstract—Hydroxycyclopropanation at the ester group in the series of lupane triterpenoids was performed for
the first time using 3,3-ethylenedioxybetulonic acid methyl ester and its 20,29-dihydro analog as substrates.
DOI: 10.1134/S1070428009100078
3
1
32
3
Hydroxycyclopropanation of carboxylic acid esters
by the action of ethylmagnesium bromide in the pres-
ence of titanium(IV) isopropoxide as catalyst (Kulin-
kovich reaction) opened a way of introducing a phar-
macologically important cyclopropane fragment into
biologically active molecules [1] and determined new
synthetic approaches to complex natural compounds
and their analogs [2]. In the recent years, modification
of betulin and its derivatives has attracted increased
interest [3], and specific attention has been given to
transformations of carboxy group with a view to obtain
compounds possessing versatile biological activity [4].
(C , C ) instead of signal typical of the C =O
carbonyl carbon atom in I and II (δ 217.83 and
217.96 ppm, respectively). Compounds III and IV
displayed in the H NMR spectra additional multiplet
signals in the region δ 3.81–3.93 ppm due to protons in
C
1
the ethylenedioxy group.
While studying Kulinkovich hydroxycyclopropana-
tion of esters III and IV we found that target com-
pounds V and VI were formed only when a solution of
ester III or IV and Ti(OPr-i) in diethyl ether was
4
added to a freshly prepared suspension of ethylmagne-
sium bromide. If the reactants were mixed in a dif-
ferent order, e.g., when a solution of EtMgBr and
We were the first to effect hydroxycyclopropana-
tion in the series of lupane triterpenoids using 3,3-eth-
ylenedioxybetulonic acid methyl ester (III) and its
Ti(OPr-i) in diethyl ether was added to a solution of
4
the substrate, no hydroxycyclopropanation occurred.
Presumably, the presence of the initial reactants at the
moment of formation of the true hydroxycyclo-
propanating agent, diisopropoxytitanacyclopropane, is
necessary for successful reaction [1].
The yields of 3,3-ethylenedioxy-28,28-ethanolup-
20(29)-en-28-ol (V) and its 20,29-dihydro analog VI
were 84 and 75%, respectively. Their structure was
confirmed by the NMR data ( H, C, DEPT-135°),
including two-dimensional experiments (COSY,
HSQC). In the C NMR spectrum of V, we observed
a signal at δ 60.17 ppm (C OH) and two new triplets
from the cyclopropane fragment (δ 15.80 and
2
0,29-dihydro analog IV as substrates. Ethylene
acetals III and IV were obtained by reactions of
betulonic acid methyl ester I and its 20,29-dihydro
derivative II, respectively, with ethylene glycol in the
presence of p-toluenesulfonic acid. 20,29-Dihydro
analog II was synthesized by hydrogenation of ester I
over platinum oxide. The formation of II was con-
1
13
1
1
13
firmed by the H and C NMR data. The H NMR
spectrum of II contained two doublets at δ 0.73 and
1
3
0
.84 ppm (J = 6.4, 6.8 Hz) from protons in diastereo-
2
8
topic methyl groups in the isopropyl substituent
instead of signals typical of isopropylidene group
C
C
(
δC 150.25, 109.51, 19.49 ppm). The structure of
15.63 ppm, DEPT-135°) instead of signals from the
2
8
ethylene acetals III and IV follows from the presence
in their C NMR spectra of signals from carbon atoms
in the dioxolane ring [δ , ppm: III: 113.21 (C ), 64.75,
6
C (O)OMe ester group (δ 176.53, 51.14 ppm),
C
1
3
17
18
while signals from C (δ 41.37 ppm) and C
C
3
(δ
C
38.98 ppm) were displaced upfield relative to the
C
3
1
32
3
4.64 (C , C ); IV: 113.33 (C ), 64.86, 64.73 ppm
corresponding signals of its precursor III (∆δ 15.09
C
1
464

FIRST EXAMPLES OF HYDROXYCYCLOPROPANATION
1465
Scheme 1.
2
9
CH2
Me
30Me
20
1
Me
Me
9
21
H
2
H
1
1
8
22
O
O
1
1
25
26
1
3
17
i
2
8
Me
Me
H
14 16
Me
Me
H
9
1
5
1
4
OMe
OMe
2
3
10
8
Me27
H
6
H
Me
5
7
O
2
O
2
3
4
Me
Me
Me
I
II
R
R
H
H
33
O
ii
iii
34
Me
H
Me
H
Me
Me
Me
H
I, II
OMe
OH
O
O
O
3
1
Me
H
Me
3
2
O
Me
Me
Me
III, IV
V, VI
2
III, V, R = CH =C(Me); IV, VI, R = Me
2
CH; i: H
2
/PtO
2
, MeOH–CHCl
3 2 2
, 2:1; ii: HOCH CH OH, TsOH, benzene, 80°C;
iii: (1) Ti(OPr-i)
4
/EtMgBr, Et
2
O; (2) 5% NaOH.
and 3.05 ppm, respectively). Signals from the other
were determined on a Boetius melting point apparatus.
Column chromatography was performed on KSKG
silica gel, and Silufol UV-254 plates were used for
TLC; spots were detected by treatment with a 20% so-
lution of phosphotungstic acid in ethanol, followed by
heating at 100–120°C for 2–3 min.
1
3
carbon atoms in the C NMR spectra of compounds V
1
and III coincided within 1 ppm. The H NMR spec-
trum of V contained two new strongly coupled two-
proton signals (δ 0.83 and 0.67 ppm; COSY), which
3
3
34
gave rise to cross peaks with C and C in the HSQC
spectrum. Analogous differences were observed in the
Betulonic acid methyl ester (I) was synthesized
according to the procedures described in [5, 6] from
betulin isolated from Betula pendula bark [7].
1
13
H and C NMR spectra of compound VI and its
precursor IV. The above data indicated that the
2
8
C (O)OMe group in III and IV was converted into
hydroxycyclopropane fragment, the configuration of
the other chiral centers remaining unchanged.
Methyl 3-oxolupan-28-oate (II, 20,29-dihydro-
betulonic acid methyl ester). Platinum(IV) oxide,
0
.005 g, was added to a solution of 0.50 g (1.06 mmol)
of compound I in 30 ml of a 2:1 methanol–chloroform
mixture, and the mixture was stirred for 8 h under
nitrogen. The mixture was filtered, the filtrate was
evaporated, and the residue was subjected to chroma-
tography in a column charged with 5 g of silica gel
using chloroform–methanol (50 : 1) as eluent. Yield
0.47 g (94%), colorless crystals, mp 182–184°C (from
EXPERIMENTAL
The IR spectra were recorded on a Specord 75IR
1
13
instrument. The H and C NMR spectra were meas-
1
ured on Bruker AM-300 (300.13 MHz for H and
1
3
7
5.48 MHz for C) and Bruker Avance-400 spectrom-
1
13
eters (400.13 MHz for H and 100.62 MHz for C)
2
0
using CDCl as solvent and tetramethylsilane as in-
methanol), [α]
trum (KBr), ν, cm : 2950, 1725, 1470. H NMR spec-
trum (400.13 MHz), δ, ppm: 0.73 d (3H, C H
6.4 Hz), 0.81 s (3H, C H
D
= +5.059° (c = 1.64, CHCl ). IR spec-
3
3
–
1
1
ternal reference. Homo- and heteronuclear correlations
experiments (DEPT-135°, COSY, HSQC) were per-
formed on a Bruker Avance-400 instrument (400.13
2
9
, J =
, J =
3
2
3
30
), 0.84 d (3H, C H
3
3
1
13
24
26
and 100.62 MHz for H for C, respectively). The
optical rotations were determined on a Perkin–Elmer-
6.8 Hz), 0.85 s (3H, C H
3
), 0.89 s (3H, C H
3
), 0.93 s
2
5
(3H, C H
(1H, 5-H), 1.05 s (3H, C H
(2H, 7-H), 1.13 m and 1.44 m (2H, 1-H), 1.19 m (1H,
), 1.01 m and 1.92 m (2H, 16-H), 1.04 m
3
2
7
1
41 polarimeter. Elemental analysis was performed
using a Carlo Erba 1106 analyzer. The melting points
3
), 1.05 m and 1.32 m
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009

1
466
ODINOKOV et al.
36.99 (C ), 37.06 (C ), 38.18 (C ), 40.63 (C ), 42.03
1
0
1
13
8
1
1
1
1
(
(
8-H), 1.21 m and 1.40 m (2H, 6-H), 1.29 m and
.48 m (2H, 2-H), 1.32 m and 1.48 m (2H, 21-H),
.37 m (1H, 9-H), 1.39 m and 1.89 m (2H, 22-H),
.41 m and 1.48 m (2H, 11-H), 1.44 br.s and 1.76 br.s
1
8
14
4
19
9
(C ), 42.34 (C ), 46.90 (C ), 49.36 (C ), 50.19 (C ),
5
17
32
51.14 (OCH ), 53.30 (C ), 56.46 (C ), 64.64 (C ),
3
3
1
29
3
20
64.75 (C ), 109.49 (C ), 113.21 (C ), 150.47 (C ),
176.53 (C ). Found, %: C 77.60; H 10.07. C H O .
28
2H, 15-H), 1.66 m (1H, 20-H), 1.76 m and 1.05 m
2H, 12-H), 1.90 m (1H, 19-H), 2.23 d.d (1H, 13-H,
33 52 4
Calculated, %: C 77.30; H 10.22.
1
3
J = 11.2, 9.6 Hz), 3.64 s (3H, OCH ). C NMR spec-
trum (100.62 MHz), δ , ppm: 14.53 (C ), 14.67 (C ),
3
Methyl 3,3-ethylenedioxylupan-28-oate (IV).
Compound II, 0.20 g (0.42 mmol), was dissolved in
0 ml of anhydrous benzene, 0.33 g (5.25 mmol) of
anhydrous ethylene glycol and 0.02 g (0.10 mmol) of
p-toluenesulfonic acid were added, and the mixture
was heated for 3 h under reflux in a flask equipped
with a Dean–Stark trap and was then treated as de-
scribed above in the synthesis of III. Yield 0.22 g
2
7
29
C
2
4
25
30
6
1
(
2
(
4
(
(
5.77 (C ), 15.88 (C ), 19.63 (C ), 21.03 (C ), 21.42
5
2
6
11
23
12
15
C ), 22.75 (C ), 22.96 (C ), 26.59 (C ), 26.90 (C ),
2
0
16
22
2
9.64 (C ), 29.72 (C ), 31.99 (C ), 33.68 (C ), 34.11
2
1
7
10
1
13
C ), 36.86 (C ), 37.26 (C ), 38.17 (C ), 39.58 (C ),
8
18
14
4
0.61 (C ), 42.57 (C ), 44.14 (C ), 47.30 (C ), 48.86
C ), 49.65 (C ), 51.15 (OCH ), 54.94 (C ), 56.96
C ), 176.77 (C ), 217.96 (C ). Found, %: C 79.36;
H 9.98. C H O . Calculated, %: C 79.10; H 10.71.
1
9
9
5
3
1
7
28
3
(
99%), colorless crystals, mp 206–208°C (from
3
1
50
3
20
MeOH), [α] = –31.6° (c = 0.75, CHCl ). IR spectrum
D
3
–
1
1
Methyl 3,3-ethylenedioxylup-20(29)-en-28-oate
III). Compound I, 0.30 g (0.64 mmol), was dissolved
(
(
0
0
KBr), ν, cm : 2935, 1720, 1450. H NMR spectrum
29
(
400.13 MHz), δ, ppm: 0.74 d (3H, C H , J = 6.8 Hz),
.84 d (3H, C H , J = 5.6 Hz), 0.86 s (3H, C H ),
3 3
.87 s (3H, C H ), 0.87 s (3H, C H ), 0.95 s (3H,
C H ), 1.01 m and 1.82 m (2H, 16-H), 1.02 s (3H,
3
3
0
23
in 50 ml of anhydrous benzene, 0.49 g (8 mmol) of
anhydrous ethylene glycol and 0.02 g (0.10 mmol) of
p-toluenesulfonic acid were added, and the mixture
was heated for 3 h under reflux in a flask equipped
with a Dean–Stark trap. The mixture was evaporated to
/4 of the initial volume and extracted with diethyl
ether (2 × 15 ml), the extract was washed with a satu-
rated solution of sodium hydrogen carbonate (2×
2
4
26
3
3
25
3
27
C H ), 1.05 m (1H, 5-H), 1.07 m and 1.32 m (2H,
3
7
1
2
1
1
1
1
-H), 1.12 m and 1.54 m (2H, 1-H), 1.17 m (1H, 18-H),
.22 m and 1.40 m (2H, 6-H), 1.30 m and 1.57 m (2H,
-H), 1.32 m and 1.57 m (2H, 21-H), 1.37 m and
.82 m (2H, 22-H), 1.37 m (1H, 9-H), 1.41 m and
.57 m (2H, 11-H), 1.46 br.s and 1.76 br.s (2H, 15-H),
.67 m (1H, 20-H), 1.76 m and 1.07 m (2H, 12-H),
.79 m (1H, 19-H), 2.19 d.d (1H, 13-H, J = 12.0,
.0 Hz), 3.65 s (3H, OCH ), 3.89–3.98 m (4H, CH ).
1
1
5 ml), water, and a saturated solution of sodium
chloride and dried over magnesium sulfate, the solvent
was distilled off, and the residue was subjected to
column chromatography on silica gel (5 g) using
chloroform–methanol (50:1) as eluent. Yield 0.31 g
99%), colorless crystals, mp 156–158°C (from
MeOH), [α] = –6.6° (c = 0.62, EtOAc). IR spectrum
KBr), ν, cm : 2547, 1730, 1475. H NMR spectrum
300.13 MHz), δ, ppm: 0.81 s (3H, C H ), 0.85 s (3H,
C H ), 0.94 s (3H, C H ), 0.96 s (3H, C H ), 1.01 m
and 1.92 m (2H, 16-H), 1.02 s (3H, C H ), 1.04 m
4
3
2
13
C NMR spectrum (100.62 MHz), δ , ppm: 14.69
C
(
2
7
29
24
25
2
0
(C ), 14.72 (C ), 15.93 (C ), 14.55 (C ), 18.45
D
–
30
6
26
11
23
1
1
(C ), 19.99 (C ), 20.94 (C ), 22.77 (C ), 22.92 (C ),
(
(
1
2
15
20
16
2
3
22.98 (C ), 26.91 (C ), 26.93 (C ), 29.66 (C ),
3
22
2
21
7
2
4
26
25
29.74 (C ), 32.07 (C ), 34.25 (C ), 37.05 (C ), 37.15
3
3
3
10
1
13
8
18
2
7
(C ), 37.31 (C ), 38.12 (C ), 40.72 (C ), 42.14 (C ),
3
14
4
19
9
4
(
(
2.58 (C ), 44.21 (C ), 48.93 (C ), 50.03 (C ), 51.13
OCH ), 53.37 (C ), 57.01 (C ), 64.73 (C ), 64.86
C ), 113.33 (C ), 176.89 (C ). Found, %: C 76.60;
(
1H, 5-H), 1.06 m and 1.32 m (2H, 7-H), 1.12 m and
5
17
32
3
1
1
1
1
(
(
(
.53 m (2H, 1-H), 1.18 m (1H, 18-H), 1.22 m and
.40 m (2H, 6-H), 1.31 m and 1.57 m (2H, 2-H),
.32 m and 1.57 m (2H, 21-H), 1.36 m (1H, 9-H),
.39 m and 1.89 m (2H, 22-H), 1.41 m and 1.57 m
2H, 11-H), 1.45 br.s and 1.76 br.s (2H, 15-H), 1.67 s
3H, C H ), 1.72 m and 1.06 m (2H, 12-H), 2.19 d.d
3
1
3
28
H 10.32. C H O . Calculated, %: C 76.99; H 10.57.
3
3
54
4
28,28-Ethano-3,3-ethylenedioxylup-20(29)-en-
28-ol (V). A solution of 0.75 g (1.46 mmol) of com-
pound III and 0.04 g (0.15 mmol) of titanium(IV)
isopropoxide in 40 ml of anhydrous diethyl ether was
added with stirring under argon at ~25°C to a solution
of ethylmagnesium bromide prepared from 0.17 g
(7.3 mmol) of metallic magnesium and 0.79 g
(7.3 mmol) of ethyl bromide in 10 ml of anhydrous
diethyl ether. The mixture was stirred for 0.5 h, treated
with 50 ml of 5% aqueous sodium hydroxide, and ex-
3
0
3
1H, 13-H, J = 12.0, 8.0 Hz), 2.98 d.t (1H, 19-H, J =
2.0, 4.0 Hz), 3.65 s (3H, OCH ), 3.81–3.93 m (4H,
1
3
1
3
CH ), 4.58 s and 4.72 s (2H, 29-H). C NMR spec-
2
27
24
trum (75.48 MHz), δ , ppm: 14.73 (C ), 15.86 (C ),
C
2
5
23
30
26
1
2
(
8.36 (C ), 19.28 (C ), 19.89 (C ), 20.82 (C ),
11
6
12
15
2.71 (C ), 22.84 (C ), 25.38 (C ), 26.82 (C ), 29.58
1
6
22
2
21
7
C ), 30.52 (C ), 32.07 (C ), 34.11 (C ), 36.87 (C ),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009

FIRST EXAMPLES OF HYDROXYCYCLOPROPANATION
1467
2
6
27
25
tracted with diethyl ether (3×40 ml). The extract was
washed with water and a saturated solution of sodium
chloride, dried over sodium sulfate, and evaporated,
and the residue was subjected to column chromatog-
raphy on silica gel (5 g) using chloroform–methanol
(3H, C H ), 0.96 s (3H, C H ), 0.99 s (3H, C H ),
3 3 3
1.01 m and 1.91 m (2H, 16-H), 1.05 m (1H, 5-H),
1.05 m and 1.31 m (2H, 7-H), 1.18 m and 1.53 m (2H,
1-H), 1.18 m (1H, 18-H), 1.23 m and 1.41 m (2H,
6-H), 1.34 m and 1.57 m (2H, 2-H), 1.34 m and 1.57 m
(2H, 21-H), 1.37 m (1H, 9-H), 1.37 m and 1.87 m (2H,
22-H), 1.41 m and 1.55 m (2H, 11-H), 1.65 m (1H,
20-H), 1.71 m and 1.05 m (2H, 12-H), 1.75 br.s and
1.45 br.s (2H, 15-H), 1.89 m (1H, 19-H), 2.19 d.d (1H,
13-H, J = 12.0, 6.0 Hz), 3.88–3.95 m (4H, CH ),
C NMR spectrum (100.62 MHz), δ , ppm: 14.07
(C ), 14.57 (C ), 14.81 (C ), 15.94 (C ), 16.22
(C ), 17.45 (C ), 18.43 (C ), 20.00 (C ), 21.05 (C ),
22.93 (C ), 23.09 (C ), 23.89 (C ), 26.92 (C ), 28.72
(C ), 29.69 (C ), 29.91 (C ), 33.62 (C ), 34.30 (C ),
37.00 (C ), 37.13 (C ), 37.82 (C ), 40.28 (C ), 41.24
(C ), 42.13 (C ), 43.00 (C ), 45.31 (C ), 48.62 (C ),
49.52 (C ), 49.97 (C ), 53.31 (C ), 59.83 (C ), 64.72
(C ), 64.83 (C ), 113.32 (C ). Found, %: C 79.94;
H 11.06. C H O . Calculated, %: C 79.63; H 11.01.
(
50:1) as eluent. Yield 0.63 g (84%), colorless crystals,
2
0
mp 112–114°C (from MeOH), [α] = –5.7° (c = 2.54,
EtOAc). IR spectrum (KBr), ν, cm : 3445, 2595,
1
0
C H ), 0.83 m (2H, 33-H), 0.88 s (3H, C H ), 0.98 s
(
(
D
–
1
1
225. H NMR spectrum (400.13 MHz), δ, ppm:
2
3
.67 m (2H, 34-H), 0.80 s (3H, C H ), 0.83 s (3H,
3
2
2
4
26
13
3
3
C
2
7
25
27
29
34
33
3H, C H ), 0.99 s (3H, C H ), 1.01 m and 1.93 m
3
3
2
4
25
30
6
26
2H, 16-H), 1.04 m (1H, 5-H), 1.06 m and 1.72 m (2H,
1
1
23
12
15
1
1
1
1
1
2-H), 1.11 m and 1.53 m (2H, 1-H), 1.18 m (1H,
8-H), 1.23 m and 1.40 m (2H, 6-H), 1.31 m and
.06 m (2H, 7-H), 1.32 m and 1.57 m (2H, 2-H),
.37 m (1H, 9-H), 1.38 m and 1.90 m (2H, 22-H),
.42 m and 1.55 m (2H, 11-H), 1.57 m and 1.32 m
2
0
16
22
2
21
7
10
1
13
8
18
17
14
4
1
9
9
5
28
30
32
31
3
(
(
2H, 21-H), 1.67 s (3H, C H ), 1.75 br.s and 1.42 br.s
2H, 15-H), 2.31 d.d (1H, 13-H, J = 12.0, 3.0 Hz),
3
3
4
56
3
2
.75 d.t (1H, 19-H, J = 11.0, 6.0 Hz), 3.86–3.92 m
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 07-03-00438) and by the Presidium of the Russian
Academy of Sciences (Program P-08 “Development of
Methods of Organic Synthesis and Design of Com-
pounds with Practically Important Properties” and
1
3
(
4H, CH ), 4.56 s and 4.71 s (2H, 29-H). C NMR
2
27
spectrum (100.62 MHz), δ , ppm: 14.96 q (C ), 15.63 t
C
3
4
33
24
25
(
C ), 15.80 t (C ), 16.20 q (C ), 16.27 q (C ),
6
30
26
11
1
2
2
3
3
4
6
8.65 t (C ), 18.88 q (C ), 20.18 q (C ), 21.21 t (C ),
2
3
12
15
16
3.12 q (C ), 25.57 t (C ), 27.13 t (C ), 29.21 t (C ),
2
2
2
21
7
9.89 t (C ), 31.67 t (C ), 34.41 t (C ), 34.67 t (C ),
“
Fundamental Sciences for Medicine”).
1
0
1
13
8
7.24 s (C ), 37.37 t (C ), 38.13 d (C ), 38.41 s (C ),
1
8
17
14
4
8.98 d (C ), 41.37 s (C ), 42.34 s (C ), 42.94 s (C ),
REFERENCES
1
9
9
5
28
8.52 d (C ), 50.43 d (C ), 53.57 d (C ), 60.17 s (C ),
3
2
31
29
4.92 t (C ), 65.03 t (C ), 110.03 t (C ), 113.54 s
1. Kulinkovich, O.G., Chem. Rev., 2003, vol. 103, p. 2597.
3
20
(
C ), 151.26 s (C ). Found, %: C 79.86; H 10.71.
2
. Bekish, A.V., Isakov, V.E., and Kulinkovich, O.G., Tetra-
hedron Lett., 2005, vol. 46, p. 6979.
C H O . Calculated, %: C 79.95; H 10.66.
3
4
54
3
3
. Hiroya, K., Takahashi, T., Miura, N., Naganuma, A., and
Sakamoto, T., Bioorg. Med. Chem. Lett., 2002, vol. 10,
p. 3229.
. Flekhter, O.B., Medvedeva, N.I., Karachurina, L.T., Bal-
tina, L.A., Zarudii, F.S., Galin, F.Z., and Tolstikov, G.A.,
Khim.-Farm. Zh., 2002, vol. 36, p. 29.
2
8,28-Ethano-3,3-ethylenedioxylupan-28-ol (VI).
A solution of 0.70 g (1.42 mmol) of compound IV and
.04 g (0.15 mmol) of titanium(IV) isopropoxide in
0 ml of anhydrous diethyl ether was added with stir-
ring under argon at ~25°C to a solution of ethylmagne-
sium bromide prepared from 0.17 g (7.3 mmol) of
metallic magnesium and 0.79 g (7.3 mmol) of ethyl
bromide in 10 ml of anhydrous diethyl ether. The mix-
ture was stirred for 0.5 h and treated as described
above in the synthesis of V. Yield 0.52 g (75%), color-
less crystals, mp 176–177°C (from methanol), [α] =
32.36° (c = 1.26, CHCl ). IR spectrum (KBr), ν, cm :
227, 2590, 3435. H NMR spectrum (400.13 MHz),
δ, ppm: 0.67 m (2H, 34-H), 0.77 d (3H, C H , J =
0
4
4
5
6
. Tolstikov, G.A., Goryaev, M.I., Kim, Kh.O., and Khe-
gai, R.A., Zh. Prikl. Khim., 1967, vol. 40, p. 920.
. Flekhter, O.B., Nigmatullina, L.R., Baltina, L.A., Kara-
churina, L.T., Galin, F.Z., Zarudii, F.S., Tolstikov, G.A.,
Boreko, E.I., Pavlova, N.I., Nikolaeva, S.N., and Savino-
va, O.V., Khim.-Farm. Zh., 2002, vol. 36, p. 26.
. Weygand–Hilgetag Organisch-chemische Experimen-
tierkunst, Hilgetag, G. and Martini, A., Eds., Leipzig:
Johann Ambrosius Barth, 1964, 3rd ed. Translated under
the title Metody eksperimenta v organicheskoi khimii,
Moscow: Khimiya, 1968, p. 548.
2
0
D
–
1
–
1
3
7
1
2
9
3
2
3
30
6
8
.8 Hz), 0.81 s (3H, C H ), 0.82 d (3H, C H , J =
.8 Hz), 0.83 s (3H, C H ), 0.85 m (2H, 33-H), 0.88 s
3 3
2
4
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009