Synthesis of 30-Bromo- and 30-Azido-20-oxo-29-nor-3β,28-diacylbetulin Derivatives

Article abstract of DOI:10.1134/S1070428019110150

Ozonolysis of 3β,28-diacyloxylup-20,29-enes gave 20-oxo-29-nor-3β,28-diacyloxylup-20,29-enes, which were brominated with molecular bromine in AcOH to obtain a mixture of 30-bromo- and 30-dibromo derivatives. Ozonolysis of 30-bromo-3β,28-diacylbetulin prod

Full text of DOI:10.1134/S1070428019110150

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 11, pp. 1735–1741. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55, No. 11, pp. 1773–1780.
Synthesis of 30-Bromo-
and 30-Azido-20-oxo-29-nor-3β,28-diacylbetulin Derivatives
a,
a
a
V. A. Glushkov *, D. A. Schemyakina , and N. K. Zhukova
a
Institute of Technical Chemistry, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences,
ul. Akademika Koroleva 3, Perm, 614013 Russia
*
e-mail: glusha55@gmail.com
Received May 8, 2019; revised September 19, 2019; accepted September 20, 2019
Abstract—Ozonolysis of 3β,28-diacyloxylup-20,29-enes gave 20-oxo-29-nor-3β,28-diacyloxylup-20,29-enes,
which were brominated with molecular bromine in AcOH to obtain a mixture of 30-bromo- and 30-dibromo
derivatives. Ozonolysis of 30-bromo-3β,28-diacylbetulin produced 29-nor-30-bromoketones, whose reaction
with sodium azide afforded 29-nor-30-azidoketones of the lupane series.
Keywords: betulin, ozonolysis, α-azidoketones
DOI: 10.1134/S1070428019110150
The recent discovery of the anticancer and
cytotoxic activity of pentacyclic triterpenoids of the
lupane series [1–3] gave new impetus to research into
chemical modification of betulin and synthesis of its
previously unknown derivatives [4–12]. We earlier syn-
thesized conjugates of lupane triterpenoids and oleanan
with ferrocene by aldol condensation and click che-
mistry [13–15]. The aim of the present work was to syn-
thesize 30-bromo- and 30-azido-20-oxo-29-nor-3β,28-
diacyl derivatives of betulin.
[24, 25] we obtained 20-oxo-29-nor derivatives 2a–2c
(Scheme 1).
Evidence for the formation of compounds 2a–2c is
provided by the appearance of an additional acetyl
1
proton signal (δ 2.14–2.16 ppm) in the Н NMR
spectra and the third, downfield (δ 210.8–211.5 ppm)
13
carbonyl carbon signal in the С NMR spectra.
The bromination of ketones 2a–2c with molecular
bromine in acetic acid at 10–15°С (Scheme 2, method a)
gave a mixture of 30-bromo- (3a, 3b) and 30,30-
dibromo derivatives 4a–4c, which was separated by
column chromatography. With pyridinium perbromide
in AcOH, the same result was obtained. It is interesting
to note that the reaction with dibenzoyl derivative 2c
Ozonolysis is widely used for oxidative functiona-
lization of pentacyclic triterpenoids [16–18]. By ozono-
lysis of 3β,28-diacetylbetulin 1a [19–21], as well as
dipropanoylbetulin 1b [22, 23] and dibenzoylbetulin 1с
Scheme 1.
O
R1
R1
O
O
1
) O3, CH Cl ,
2
2
O
_85°C, 2 h
O
O
O
2
) Zn, AcOH,
20°C, 12 h
R1
O
R1
O
a_1c
2a 2c, 34 45%
_
_
1
1
, 2, R = Me (a), R = Et (b), R = Ph (c).
735
1

1
736
GLUSHKOV et al.
Scheme 2.
Br
Br
Br
O
O
R1
R1
O
O
Br /AcOH
2
2
a_2c
+
1
5_20°C, 12 h
O
O
O
O
R1
O
R1
O
_
_
_
3
a, 3b, 53 60%
4a 4c, 10 63%
under these conditions resulted in the exclusive
formation of dibromide 4c (yield 63%).
quite difficult to separate by column chromatography.
To obtain pure bromoketones 3a–3c, we developed a
synthetic approach involving ozonolysis of allyl
bromides 5a–5c (Scheme 3, method b) [26]. The
reaction of bromoketones 3a–3c with sodium azide in
MeCN under reflux gave azides 6a–6c in yields of 31–
The formation of bromides 3a and 3b is
accompanied by the disappearance of the acetyl singlet
at δ 2.14–2.16 ppm and appearance of two doublets of
3
0
the diastereotopic С Н protons at δ 3.80–3.81 and
3
2
3
1
45%. The R values of azidoketones 6a–6c are slightly
f
.89–3.94 ppm ( J 12.0–12.8 Hz). The Н NMR
larger than those of bromides 3a–3c. The IR spectra of
compounds 6a–6c contain a very strong absorption
spectra of dibromoketones 4a–4c contain a characteris-
3
0
tic С НBr singlet at δ 5.93–5.95 ppm
–1
1
2
band of the azido group at 2105–2106 cm . The Н
NMR spectra of bromoketones 3a–3c and azidoke-
tones 6a–6c are quite similar to each other; as a
difference criterion, we can consider the upfield shift
The R values of dibromides 4a–4c are slightly
f
larger compared to bromides 3a–3c, but still very close
to them, and, therefore, these groups of compounds are
Scheme 3.
Br
Br
O
19
R
R
O
O
1
) O3, _90°C, 2 h;
O
2) Me S, 20°C, 12 h
2
O
O
O
R
O
R
O
a_5c
3a 3c, 42 58%
_
_
5
N3
19
O
R
O
NaN3
a_3c
3
MeCN,
O
O
8
0°C, 5 h
R
O
_
_
6
a 6c, 31 45%
1
, 2, R = Me (a), R = Et (b), R = Ph (c).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

SYNTHESIS OF 30-BROMO- AND 30-AZIDO-20-OXO-29-NOR-3β,28-DIACYLBETULIN
1737
1
9
of the НС proton signal from δ 2.95–3.05 ppm in
bromides 3a–3c to δ 2.67–2.69 ppm in azides 6a–6c.
20-Oxo-29-norlupane-3β,28-diyl diacetate (2a)
was obtained by the ozonolysis of 4.0 g (7.5 mmol) of
betulin 3β,28-diacetate (1a) [19–21] in 150 mL of
anhydrous dichloromethane at ~ –90°С (a mixture of
Further on we undertook an attempt to involve
azidoketones in a click reaction with ethynylferrocene,
catalyzed by CuI/TMEDA [14, 15, 26]. However,
under these conditions azidoketones 6a–6c fail to react
with ethynylferrocene. Attempts to perform the click
reaction in “classical” conditions, specifically in
aqueous tert-butanol at 40–50°С in the presence of a
CuSO /sodium ascorbate catalytic system [27], too,
have not met with success. Click reactions of
α-azidoketones have been reported in the literature
28–30], though few in number. Obviously, the
5
0% aqueous ethanol and liquid nitrogen) for 2 h by
the procedure in [31, 32]. After ozonolysis was
complete, 4 mL of AсOН, 2 mL of conc. HCl, and 2 g
of Zn dust were added to the reaction mixture, and it
was stirred and left to stand for 12 h at room
temperature to decompose ozonide. The solution was
then decanted from residual zinc, washed with water
and NaHCO solution, and dried over MgSO . The
4
3
4
solvent was removed by distillation, and the residue
was subjected to column chromatography. Yield 1.90 g
[
carbonyl group in our triterpenoid substrate so strongly
deactivates the azide function that a copper-catalyzed
click reaction becomes impossible.
(
[
48%), colorless crystals, mp 183–185°С (190–191°С
1
32]; 188–189°С [33]), R 0.38. The Н NMR spectrum
f
13
coincides with that in [33]. С NMR spectrum, δ,
ppm: 14.57, 15.87, 16.02, 16.39, 18.03, 20.70, 20.90,
21.19, 23.55, 26.88, 27.12, 27.40, 27.83, 29.26, 29.56,
33.93, 34.33, 36.33, 36.95, 37.68, 38.22, 40.68, 42.44,
46.24, 49.26, 50.01, 51.56, 55.21, 62.39, 80.70, 170.79
(С=Oester), 171.35, (С=Oester), 211.49 (С=Oketone).
Thus, our developed method of synthesis of pure
bromoketones 3a–3c allows further functionalization
of such 29-nor-triterpenoids by С and С (azidoketo-
nes 6a–6c, aminoketones, etc.) with the aim of
preparing novel heterocyclic derivatives of the lupane
series.
20
30
2
0-Oxo-29-norlupane-3β,28-diyl dipropanoate
2b) was obtained by the ozonolysis of 2.2 g (3.9
mmol) of betulin 3β,28-dipropanoate 1b [22, 23] in
50 mL of anhydrous dichloromethane. Further work-
(
EXPERIMENTAL
1
The IR spectra were recorded on a Bruker
VERTEX 80v spectrometer in thin films obtained by
evaporation of chloroform solutions. The Н and
NMR spectra in CDCl were obtained on a Bruker
Avance III HD 400 spectrometer at 400 and 100 МHz,
respectively, using HMDS as internal references for Н
NMR and the CDCl signal (δ 77.0 ppm) as internal
references for С NMR. Elemental analysis was
performed on an Elementar Vario EL cube analyzer.
The melting points were determined on a PTP device.
The specific rotation was measured on a Perkin–Elmer
up was performed as described for compound 2a. Yield
505 mg (23%), colorless crystals, mp 125–127°С.
1
13
С
2
5
–1
[
α]D –11.5 (c 1, CHCl ), R 0.50. IR spectrum, ν, cm
3 f
3
(
thin film): 2945, 2874, 1733 (С=O), 1462, 1423,
1
1390, 1378, 1365, 1277, 1216, 1187, 1083, 1017, 970,
1
7
35. Н NMR spectrum, δ, ppm: 0.81 s (6H, 2Me),
3
C
1
3
0.83 s (3H, Me), 0.97 s (3H, Me), 1.00 s (3H, Me),
1
2
.09–1.14 m (6Н, 2Мe), 2.12 s [3H, CH C(O)], 2.27–
3
1
9
28
.35 m (4Н, OСН ), 2.63 m (1Н, Н ), 3.77 d (1H, Н ,
2
2
28 2
J 12.0 Hz), 4.21 d (1H, Н , J 12.0 Hz), 4.44 m (1Н,
3
13
Н ). С NMR spectrum, δ, ppm: 8.63, 8.80, 14.16,
3
41 polarimeter in chemical grade chloroform contai-
–
1
–1
2
15.45, 15.84, 17.62, 20.30, 23.15, 26.51, 26.68, 26.99,
ning 0.5% of ethanol and reported in 10 ·deg·g ·cm .
Column chromatography was performed on an Alfa
Aesar Silicagel 60 (0.060–0.2 mm, 70–230 mesh),
eluent petroleum ether–ethyl acetate. The reaction
2
3
5
7.11, 27.40, 27.49, 28.95, 33.55, 33.93, 35.96, 36.57,
7.34, 37.83, 40.31, 42.05, 45.96, 48.88, 49.64, 51.23,
4.84, 61.73, 79.94, 173.49 (С=Oester), 174.08
(С=Oester), 210.76 (С=Oketone). Found, %: C 75.90; Н
progress was monitored, and the R values were
f
1
0.23. C H O . Calculated, %: C 75.50; Н 10.14.
3
5
56
5
measured by TLC on Sorbfil plates, eluent petroleum
ether–ethyl acetate, 7 : 3; the spots were visualized by
spraying 20% H SO followed by heating. Dimethyl
disulfide was purchased from Merck and pure grade
petroleum ether and chemical grade ethyl acetate,
dichloromethane, and glacial acetic acid were
purchased from Russian producers.
20-Oxo-29-norlupane-3β,28-diyl dibenzoate (2c)
2
4
was obtained by the ozonolysis of 3.03 g (4.65 mmol)
betulin 3β,28-dibenzoate 1c [24, 25] in 170 mL of
anhydrous dichloromethane. Further workup was per-
formed as described for compound 2a. Yield 1.31 g
(43%), colorless crystals, mp 143–147°С, R 0.60,
f
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

1
738
GLUSHKOV et al.
2
4
–1
[
α]D +21.3 (c 1, CHCl ). IR spectrum, ν, cm : 2947,
27.92, 29.03, 29.45, 34.06, 34.64, 34.67, 36.39, 37.09,
37.79, 38.36, 40.82, 42.66, 46.35, 48.13, 49.98, 50.09,
55.33, 62.55, 80.79, 170.73 (O–C=O), 171.37 (O–
C=O), 204.89 (C=Oketone). Found, %: C 65.78; H 9.03.
С H BrO . Calculated, %: C 65.23; H 8.46.
3
2
1
0
873, 1716, 1635, 1451, 1391, 1315, 1275, 1176, 1114,
070, 1026, 972, 757, 712. Н NMR spectrum, δ, ppm:
.89 s (3H, Me), 0.90 s (3H, Me), 0.99 s (3H, Me), 1.04
s (3H, Me), 1.07 s (3H, Me), 2.16 s [3H, CH C(O)],
.73 m (1Н, Н ), 4.03 d (1Н, Н , J 12.0 Hz), 4.48 d
1Н, Н , J 12.0 Hz), 4.71 m (1Н, Н ), 7.40–7.44 m
4Нarom), 7.50–7.56 m (2Нarom), 8.02 m (4Нarom).
NMR spectrum, δ, ppm: 14.77, 16.05, 16.13, 16.77,
8.19, 20.88, 23.74, 27.11, 27.28, 27.57, 28.11, 29.59,
9.63, 34.09, 34.60, 36.61, 37.16, 38.22, 38.40, 40.89,
2.68, 46.78, 49.48, 50.20, 51.79, 55.45, 62.97,
0.79, 166.21 (O–C=O), 166.83 (O–C=O), 211.42
C=Oketone). Found, %: C 78.87; H 8.60. C H O .
Calculated, %: C 79.10; H 8.65.
1
3
33 51
5
1
9
28 2
2
(
(
30-Bromo-20-oxo-29-norlupane-3β,28-diyl dipro-
2
8
2
3
panoate (3b). a. A solution of 139 mg (0.87 mmol) of
bromine in 10 mL of glacial AсOН was added over the
course of 2 h at 10–15°С to a solution of 440 mg
1
3
С
1
2
4
8
(
0.79 mmol) of compound 2b [26], in 40 mL of glacial
AсOН. The mixture was left to stand for 12 h at room
temperature and then poured into water and extracted
with dichloromethane. The organic extract was washed
with aqueous NaHCO , dried over MgSO , and sub-
(
43 56 5
3
4
jected to column chromatography. The first fraction
contained dibromide 4b (R 0.62), and the second
3
0-Bromo-20-oxo-29-norlupane-3β,28-diyl
f
fraction contained bromide 3b (R 0.57). Yield 266 mg
diacetate (3a). a. A solution of 113 mg (0.71 mmol) of
bromine in 8 mL of AсOН was added to a solution of
50 mg (0.65 mmol) of compound 2a in 30 mL of
glacial AсOН at 10–15°С. The mixture was stirred for
2 h at room temperature and then poured into water
and extracted with dichloromethane. The organic
extract was washed with aqueous NaHCO , dried over
MgSO , and subjected to column chromatography. The
first fraction contained dibromide 4a, and the second
fraction contained bromide 3a.
f
2
D
4
(
53%). Colorless crystals, mp 70–73°С, [α] –13.3 (c
–
1
1
1
7
0
1
, CHCl ). IR spectrum, ν, cm : 2944, 2874, 1732,
3
3
462, 1390, 1357, 1276, 1216, 1188, 1083, 1017, 972,
56. Н NMR spectrum, δ, ppm: 0.83 s (6H, 2Me),
.84 s (3H, Me), 0.99 s (3H, Me), 1.02 s (3H, Me),
.13–1.15 m (6Н, 2Мe), 2.27–2.37 m [4Н, 2С(O)
СН ], 2.95 m (1Н, Н ), 3.81 d (1H, Н , J 12.0 Hz),
.89 d (NCH, J 12.8 Hz), 3.94 d (NCH, J 12.8 Hz),
.22 m (1H, Н , J 12.0 Hz), 4.46 m (1Н, Н ).
1
1
3
19
28 2
2
4
2
2
3
4
2
8
2
3
13
С
NMR spectrum, δ, ppm: 9.14, 9.27, 14.49, 15.95,
b. Compound 3a was prepared by the ozonolysis of
1
2
3
4
1
6
8
6.05, 16.48, 18.11, 20.80, 23.36, 23.65, 25.11, 26.99,
7.52, 27.63, 27.91, 28.01, 29.02, 29.46, 34.02, 34.66,
6.35, 37.07, 37.85, 38.32, 40.79, 42.61, 46.43, 48.14,
9.99, 50.06, 55.31, 62.27, 80.43, 174.08 (С=Oester),
74.58 (С=Oester), 204.68(С=Oketone). Found, %: C
5.84; H 9.02. С H BrO . Calculated, %: C 66.13; H
5
.509 g (9 mmol) of compound 5a [34] in 180 mL of
anhydrous dichloromethane at ~ −90°С (a mixture of
0% aqueous ethanol and liquid nitrogen) for 2 h, the
flow rate of air through the ozone generator was 1.3–
.4 L/min. The reaction progress was monitored by
TLC. After the reaction had been complete, 0.88 mL
745 mg, 11.9 mmol) of dimethyl sulfide was added,
and the mixture was left to stand for 12 h at room
temperature. The solvent was then removed by
distillation, and the residue was purified on a silica gel
column (eluent petroleum ether–ethyl acetate, 20 : 1)
to obtain 2.46 g (45%) of bromoketone 3a, colorless
crystals, mp 163–167°С (from МeOН), R 0.54, [α]
13.7 (c 1, CHCl ). IR spectrum, ν, cm : 2947, 2873,
732 (С=O), 1458, 1390, 1367, 1246, 1031, 980, 757.
Н NMR spectrum, δ, ppm: 0.83 s (3H, Me), 0.84 s
6H, 2Me), 0.98 s (3H, Me), 1.01 s (3H, Me), 2.02 s
3H, CH C(O)], 2.06 s [3H, CH C(O)], 2.95 m (1Н,
Н ), 3.80 d (1Н, Н , J 12.0 Hz), 3.94 d (1Н, Н , J
2.0 Hz), 4.21 d (1Н, Н , J 12.0 Hz), 4.45 m (1Н,
5
1
35
55
5
.72.
(
b. The ozonolysis of 2.13 g (3.84 mmol) of
compound 5b in dichloromethane at –90°С by the
procedure described for compound 3a, followed by
decomposition with 1.1 mL (0.93 g, 14.9 mmol) of
dimethyl sulfide gave 1.415 g (58%) of compound 3b.
2
D
4
f
30-Bromo-20-oxo-29-norlupane-3β,28-diyl diben-
zoate (3c) was prepared by method b similarly to
compound 3a by the ozonolysis of 1.028 g (1.4 mmol)
of compound 5с [26] in dichloromethane at –90°С
followed by decomposition with 0.4 mL (5.5 mmol) of
dimethyl sulfide. The solvent was then removed by
distillation, and the residue was subjected to column
chromatography, eluent petroleum ether–ethyl acetate
(the fraction of ethyl acetate was gradually increased
from 0 to 10%). Yield 0.90 g (42%), white powder, mp
–
1
–
3
1
1
(
[
3
3
1
9
30
2
30 2
2
8 2
1
3
13
Н ). С NMR spectrum, δ, ppm: 14.61, 15.98, 16.08,
6.46, 18.14, 20.83, 20.92, 21.22, 23.65, 26.96, 27.55,
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

SYNTHESIS OF 30-BROMO- AND 30-AZIDO-20-OXO-29-NOR-3β,28-DIACYLBETULIN
1739
2
4
–1
1
48–152°С (from МeOН), R 0.60, [α] –14.7 (c 1,
CHCl ). IR spectrum, ν, cm : 2947, 2873, 1715, 1602,
f
D
3
–
1
CHCl ). IR spectrum, ν, cm : 2947, 2873, 1732, 1458,
390, 1367, 1246, 1031, 980, 757. Н NMR spectrum,
1584, 1451, 1390, 1316, 1275, 1176, 1115, 1070, 1026,
973, 757, 712. Н NMR spectrum, δ, ppm: 0.90 s (3H,
3
1
1
1
δ, ppm: 0.90 s (3H, Me), 0.92 s (3H, Me), 0.99 s (3H,
Me), 1.04 s (3H, Me), 1.07 s (3Н, Мe), 3.05 m (1Н,
Me), 0.92 s (3H, Me), 0.99 s (3H, Me), 1.04 s (3H,
1
9
Me), 1.07 s (3H, Me), 3.19 m (1Н, Н ), 4.08 d (1Н,
1
9
2
28
2
28 2
HС ), 3.92 d (1Н, BrССН , J 12.0 Hz), 3.97 d (1Н,
Н , J 12.0 Hz), 4.49 d (1Н, Н , J 12.0 Hz), 4.71 m
2
2
28
2
3
30
BrССН , J 12.0 Hz), 4.06 d (1Н, Н , J 12.0 Hz),
.48 d (1Н, Н , J 12.0 Hz), 4.71 m (1Н, Н ), 7.43 m
4Нarom), 7.55 m (2Нarom), 8.03 m (4Нarom). С NMR
(1Н, Н ), 5.95 s (1Н, Н ), 7.40–7.45 m (4Нarom), 7.50–
7.57 m (2Нarom), 8.01–8.05 m (4Нarom). С NMR spec-
2
2
8
2
3
13
4
(
1
3
trum, δ, ppm: 14.68, 16.02, 16.10, 16.75, 18.16, 20.86,
23.70, 27.04, 27.39, 28.11, 29.76, 31.62, 34.08, 35.11,
36.60, 37.17, 38.22, 38.42, 40.90, 42.88, 43.30, 46.04,
46.62, 540.11, 50.90, 55.42, 63.20, 81.45, 128.28,
128.45, 129.51, 129.56, 130.21, 131.06, 132.64, 133.06,
166.22, 166.84, 199.25. Found, %: C 64.16; H 7.16.
C H Br O . Calculated, %: C 63.71; H 6.71; Br 19.71.
spectrum, δ, ppm: 14.68, 16.02, 16.10, 16.75, 18.16,
2
3
4
1
1
0.86, 23.70, 27.04, 27.57, 28.06, 29.10, 29.65, 34.06,
4.66, 34.79, 36.48, 37.14, 38.19, 38.37, 40.86, 42.74,
6.71, 48.20, 50.07, 50.11, 55.40, 63.01, 81.38,
28.25, 128.40, 129.49, 129.53, 130.23, 131.03,
32.61, 132.99, 166.21 (С=O), 166.81 (С=O), 204.70
43
54
2
5
(
С=O). Found, %: C 70.32; H 7.60; Br 10.78.
3
0-Azido-20-oxo-29-norlupane-3β,28-diyl diace-
tate (6a). A mixture of bromoketone 3a, 725 mg
1.23 mmol) and 240 mg (3.69 mmol, three-fold
excess) of sodium azide was heated under reflux in
50 mL of acetonitrile for 5 h. The solvent was
C H BrO . Calculated, %: C 70.57; H 7.58; Br 10.92.
4
3
55
5
(
3
0,30-Dibromo-20-oxo-29-norlupane-3β,28-diyl
diacetate (4a) formed as an admixture (~10–15%) to
bromide 6a in the experiment on the bromination of
ketone 2a with bromine or pyridinium perbromide in
1
removed in a vacuum, and the residue was subjected to
column chromatography, eluent petroleum ether–ethyl
acetate (the fraction of ethyl acetate was gradually
increased from 0 to 10%). Yield 306 mg (45%), white
foam, decomp. point 120–123°С, [α]D –17.0 (c 0.5,
CHCl ), R 0.61. IR spectrum, ν, cm : 2947, 2873,
1
AcOH. Colorless oil, R 0.56 (bromide 3a: R 0.54). Н
f
f
NMR spectrum, δ, ppm: 0.82 s (3H, Me), 0.84 s (6H,
Me), 0.98 s (3H, Me), 1.01 s (3H, Me), 2.02 s [3H,
2
2
2
1
9
CH C(O)], 2.07 s [3H, CH C(O)], 3.10 m (1Н, Н ),
3
1
3
3
–
1
2
8
2
28
2
3 f
.81 d (1Н, Н , J 12.0 Hz), 4.21 d (1Н, Н , J
2.0 Hz), 4.45 m (1Н, Н ), 5.93 s (1Н, Н ). С NMR
3
30 13
2106 (N ), 1732 (С=O), 1458, 1390, 1367, 1246, 1031,
3
1
9
0
2
79, 756. Н NMR spectrum, δ, ppm: 0.86 s (6H, 2Me),
.87 s (3H, Me), 1.02 s (3H, Me), 1.05 s (3H, Me),
.05 s [3Н, С(O)Мe], 2.09 s [3Н, С(O)Мe], 2.69 m
1Н, Н ), 3.81 d (1H, Н , J 12.0 Hz), 3.94 d (NCH,
J 16.0 Hz), 4.00 d (NCH, J 16.0 Hz), 4.22 d (1H, Н ,
J 12.0 Hz), 4.49 m (1Н, Н ). С NMR spectrum, δ, ppm:
3.78, 15.19, 15.40, 15.96, 17.90, 20.40, 20.70, 23.16,
6.48, 27.44, 28.67, 33.53, 35.85, 36.61, 37.23, 37.66,
spectrum, δ, ppm: 14.60, 15.98, 16.08, 16.46, 18.15,
2
3
4
8
0.81, 20.93, 21.22, 23.65, 26.92, 27.34, 27.93, 29.46,
1.47, 34.06, 34.90, 36.48, 37.09, 37.80, 38.39, 40.83,
2.77, 43.25, 45.93, 46.24, 50.08, 50.78, 55.33, 62.61,
0.79, 170.86 (O–C=O), 171.39 (O–C=O), 199.23
1
9
28 2
(
2
2
28
2
3
13
(C=Oketone). С H Br O . Satisfactory elemental ana-
33 50 2 5
1
2
lysis could not be obtained.
3
0,30-Dibromo-20-oxo-29-norlupane-3β,28-diyl
40.35, 42.13, 42.77, 45.91, 47.54, 48.93, 49.60, 50.28,
54.86, 56.86, 61.90, 80.22, 170.29 (С=Oester), 170.81
(С=Oester), 206.51 (С=Oketone). Found, %: C 69.49; H
dipropanoate (4b) could not be isolated pure and
characterized; it formed as a hardly separable
admixture (~20%) to bromide 3b in the bromination of
ketone 2b with bromine un AcOH.
8.92; N 7.35. C33
9.02; N 7.37.
H N O . Calculated, %: C 69.56; H
51 3 5
3
0,30-Dibromo-20-oxo-29-norlupane-3β,28-diyl
30-Azido-20-oxo-29-norlupane-3β,28-diyl dipro-
panoate (6b) was prepared similarly to azide 6a from
1.00 g (1.57 mmol) of bromoketone 3b and 0.307 g
(4.7 mmol) of sodium azide in 250 mL of acetonitrile.
Yield 310 mg (33%), colorless crystals, mp 78–80°С.
dibenzoate (4c). A solution of compound 2с, dissolved
in 50 mL of glacial AсOН, was brominated at 10–15°С
in a solution of 0.79 mL (1.53 mmol) of bromine in
1
0 mL of glacial AсOН for 12 h. The reaction mixture
2
5
was poured into water and extracted with dichloro-
methane. The organic extract was washed with
aqueous NaHCO , dried over MgSO , and subjected to
column chromatography. Yield 0.71 g (73%), colorless
crystals, mp 220–222°С, R 0.52, [α] –1.4 (c 1,
[α]
D
–18.8 (c 0.25, CHCl
3
), R
), 1731 (С=O), 1462, 1390,
3
f
0.63. IR spectrum, ν,
–
1
cm : 2945, 2874, 2105 (N
1
1357, 1277, 1188, 1083, 1017, 969, 757. Н NMR
spectrum, δ, ppm: 0.83 s (6H, 2Me), 0.84 s (3H, Me),
0.99 s (3H, Me), 1.01 s (3H, Me), 1.13 t (3Н, Мe),
3
4
2
D
4
f
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

1
1
740
GLUSHKOV et al.
.14 t (3Н, Мe), 2.27–2.37 m [4Н, 2С(O)СН ], 2.67 m
1Н, Н ), 3.78 d (1H, Н , J 12.0 Hz), 3.92 d (NCH,
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28 2
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8
. Pettit, G.R., Melody, N., Hempenstall, F., Chapuis, J.-C.,
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3
4
1
1
7.07, 27.79, 28.04, 28.12, 29.42, 29.60, 30.83, 34.08,
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55
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ACKNOWLEDGMENTS
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The authors are grateful to Engineer I.A. Borisova for
recording the IR spectra, Leading Engineer O.A. Maiorova
for recording the Н and С spectra, and Scientific
1
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1
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Haley, M., Benkovics, T., Nye, J., Xu, Z., Tan, Y.,
Ayers, S., Gao, Q., and Kiau, S., J. Org. Chem., 2017,
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The work was performed by State order (contract
no. AAA-A18-118030790037-7).
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CONFLICT OF INTEREST
1
2. Kahnt, M., Heller, L., Grabandt, P., Al-Harrasi, A., and
The authors declare no conflict of interest.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

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