776
KAZAKOVA et al.
13C NMR spectrum: 14.7, 15.3, 16.0, 16.7, 18.3, 19.1,
20.8, 22.6, 23.6, 25.2, 27.1, 28.0, 29.2, 29.8, 34.0,
34.6, 36.9, 37.3, 38.2, 38.7, 40.9, 42.7, 46.7, 48.8,
50.3, 55.7, 63.0 (C28), 78.8 (C3), 109.9 (C29), 123.3
(C5'), 126.4 (C3'), 137.1 (C4'), 149.8 (C2'), 150.7
(C20), 153.3 (C6'), 165.5 (OC=O).
tone was added by drops to a solution containing
0.55 g (1 mmol) of compound (XII) in 30 ml of aceꢀ
tone at
mixed at
0
°
С
within 30 min. The reaction mass was
0 С for 4 h, followed by the addition of 1 ml
°
MeOH and was poured into ice (10 g). The residue was
filtered, washed by water, and dried; the residue was
dissolved in 20 ml СНСl3 and passed through a layer
(1 cm) of Al2O3; the solvent was evaporated in a vacꢀ
uum; and the residue was recrystallized from the ethaꢀ
3 ꢀHemisuccinylꢀ28ꢀorthoꢀnicotinoylꢀlupaꢀ20(29)ꢀene
β
(XIII). Succinic anhydride in an amount of 4 mmol
was added to a solution containing 0.55 g (1 mmol) of
compound (XII) in 10 ml pyridine and boiled for 4 h
with a backflow condenser and poured into 50 ml 5%
HCl; the residue was filtered, washed by water, dried,
and crystallized from the ethanol. Yield was 0.55 g
20
nol. Yield was 0.46 g (85%). Rf 0.30. Tm 128–130
°С.
Found, %: C 79.01; H 9.48; N 2.37. C36H51NO3
(Mr 545.80). Calculated, %: C 79.22; H 9.42; N 2.57.
1H NMR spectrum: 0.85, 0.93, 0.93, 0.98, 1.02 (15 Н,
5 s, 5 СН3), 1.63 (3 H, s, H30), 0.99–2.30 (24 H, m,
CH, СН2), 2.42 (1 H, m, H19), 4.06 and 4.50 (2 H,
(85%). Rf 0.20. Tm 130–132
°
С. [α]D + 13 (c 0.3,
°
both d,
7.31 (1 H, dd,
1.7, 1.3, H4'), 8.71 (1 H, dd,
J
11, H28), 4.53 and 4.63 (2 H, both s, H29),
8.0, 4.8, H5'), 8.21 (1 H, ddd, 8.0
4.8, 1.7, H6'), 9.18 (1 H,
J 1.3, H2'). C NMR spectrum: 14.7, 15.8, 15.9,
CHCl3). Found, %: C 74.25; H 8.77; N 2.05.
C40H57NO6 (Mr 647.89). Calculated, %: C 74.15; H
8.87; N 2.16. H NMR spectrum: 0.83, 0.88, 0.92,
J
J
,
J
1
13
d,
0.99, 1.01 (15 Н, 5 s, 5 СН3), 1.10–2.00 (25 H, m, CH,
19.1, 19.5, 21.0, 21.2, 25.1, 26.5, 27.0, 29.5, 29.8,
33.4, 34.1, 34.6, 36.8, 37.7, 39.5, 40.8, 42.7, 46.6,
47.3, 47.7, 48.7, 49.6, 54.9, 63.6 (C28), 110.0 (C29),
123.2 (C5'), 126.2 (C3'), 136.9 (C4'), 149.8 (C2'),
150.8 (C20), 153.3 (C6'), 165.5 (OC=O), 217.8 (C3).
СН2), 1.65 (3 H, s, H30), 2.50 (1 H, dt,
H19), 2.62–2.69 (4 H, m, H1'', H2''), 4.05 (1 H, d,
11, H28), 4.48–4.73 (3 H, m, H28, H29), 4.11–4.20
(1 H, m, H3), 7.45 (1 H, dd, 7.9, 4.8, H5'), 8.33 (1
H, ddd, 7.9, 1.2, 1.8, H4'), 8.81 (1 H, dd, 4.8, 1.8,
H6'), 9.21 (1 H, d, 1.2, H2'). C NMR spectrum:
J 5, 11, 11,
J
J
J
J
13
3
β
,28ꢀDiꢀorthoꢀnicotinoylꢀ20ꢀoxoꢀ29ꢀnorlupan
(XVII). Ozone was passed through 1 mmol betulin
XI) in 20 ml CH2Cl2 at –60 until the disappearance
J
14.8, 16.0, 16.1, 16.5, 18.1, 19.1, 20.8, 23.6, 25.2,
27.1, 27.9, 29.1, 29.5 (C1''), 29.9 (C2''), 34.1, 34.6,
(
°
С
37.1, 37.7, 37.8, 38.4, 40.9, 42.7, 46.7, 47.7, 48.8, of the primary substance (THF control). The temperꢀ
50.3, 55.4, 60.4, 63.9 (C28), 81.4 (C3), 110.0 (C29), ature was brought to room temperature; the solvent
123.5 (C5'), 126.0 (C3'), 137.5 (C4'), 149.9 (C2'), was evaporated in a vacuum. The residue consisting of
150.2 (C20), 152.8 (C6'), 165.0, 172.0 (OC=O), 176.6 20ꢀoxobetulin (XVI) was acylated by nicotinic chloraꢀ
(COOH).
nhydride according to the abovementioned technique.
The reaction product (XVII) was purified by the colꢀ
umn chromatography method; the eluents were benꢀ
3,20ꢀDioxoꢀ28ꢀorthoꢀnicotinoylꢀ29ꢀnorlupan
(XIV). CrO3 in an amount of 0.6 g was added to a soluꢀ
zene and chloroform. Yield was 0.50 g (76%). Rf 0.28
.
tion containing 0.55 g (1 mmol) of compound (XII) in
50 ml acetic acid and boiled for 4 h with a backflow
condenser and poured into 50 ml of water; the residue
was filtered, washed by water, dried, and purified by
column chromatography; the eluent was chloroform,
chloroform–methanol, 10 : 1. Yield was 0.35 g (65%).
20
20
T
m 138–140
°
С. [α]D + 7
°
(
c
0.5, CHCl3). Found, %:
r 654.89). Calꢀ
culated, %: C 75.20; H 8.31; N 4.28. H NMR specꢀ
C 75.10; H 8.22; N 4.08. C41H54N2O5 (
M
1
trum: 0.72, 0.81, 0.89, 0.99, 1.09 (15 Н, 5 s, 5 СН3),
1
.11–2.12 (24 H, m, CH, СН2), 2.11 (3 H, s, H30),
2.65 (1 H, dt, 11.1, 5.9, H19), 3.98 and 4.44 (2 H,
Found, %: C 76.60; H 8.89; N 2.36. C35H49NO4 (Mr both d,
11, H28), 4.65 (1 H, dd, 10.1, 5.7, H3), 7.29
and 7.35 (2 H, both dd, 8.0, 3.9, H5', H5''), 8.23 and
8.26 (2 H, both ddd, 8.0, 1.6, 1.3, H4', H4''), 8.72 and
8.74 (2 H, both dd, 3.9, 1.6, H6', H6''), 9.14 and 9.17
(2 H, both d, 1.3, H2', H2''). C NMR spectrum:
Rf 0.30. Tm 195–197
°
С. [α]D + 28 (c 0.3, CHCl3).
°
J
J
J
1
J
547.76). Calculated, %: C 76.74; H 9.02; N 2.56. H
NMR spectrum: 0.86, 0.98, 1.00, 1.02, 1.08 (15 Н, 5 s,
5 СН3), 1.10–2.10 (24 H, m, CH, СН2), 2.18 (3 H, s,
J
J
13
J
H30), 2.70 (1 H, dt,
H, both d, 11.0, H28), 7.31 (1 H, dd,
8.21 (1 H, ddd, 8.0, 1.7, 1.3, H4'), 8.70 (1 H, dd,
4.8, 1.7, H6'), 9.18 (1 H, d,
1.3, H2'). 13C NMR specꢀ
J
11.3, 5.2, H19), 4.06 and 4.50 (2
14.6, 15.9, 16.6, 18.0, 19.2, 20.1, 23.5, 26.9, 27.0,
27.3, 27.9, 29.3, 29.5, 33.8, 34.3, 36.4, 36.9, 37.9,
38.2, 40.7, 42.3, 46.5, 49.2, 49.9, 51.4, 55.2, 63.2
(C28), 82.0 (C3), 123.1 (C5'), 123.2 (C5''), 125.9
(C3'), 126.6 (C3''), 152.9 (C6'), 153.0 (C6''), 136.8
(C4'), 136.8 (C4''), 150.6 (C2'), 150.6 (C2''), 165.3
and 164.7 (OC=O), 211.1 (C20).
J
J
8.0, 4.8, H5'),
J
J
J
trum: 14.7, 15.8, 15.9, 19.6, 21.0, 21.4, 26.7, 27.1,
27.3, 27.5, 29.5, 29.7, 33.5, 34.0, 34.5, 36.7, 36.9,
39.5, 40.8, 42.7, 46.8, 47.3, 49.3, 49.6, 51.9, 54.9, 63.4
(C28), 123.4 (C5'), 126.9 (C3'), 137.0 (C4'), 150.9
(C2'), 153.5 (C6'), 165.3 (OC=O), 211.2 (C20), 217.8
(C3).
28ꢀorthoꢀnicotinoylꢀlupaꢀ2(3),20(29)ꢀdiene (XVIII).
SOCl2 in an amount of 1 ml was added to a solution
3ꢀOxoꢀ28ꢀorthoꢀnicotinoylꢀlupaꢀ20(29)ꢀene (XV). containing 0.55 g (1 mmol) of compound (XII) in
The Jones reagent in an amount of 1.6 ml in 5 ml aceꢀ 10 ml of pyridine and boiled for 2 h with a backflow
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 36
No. 6
2010