Chemistry Reference
In-Depth Information
30
20
R
29
21
22
H
H
19
H
E
12
18
O
11
O
H
28
25
26
13
14
17
H
H
COOH
1
9
NH(CH
2
)
10
COOH
R
1
2
16
R
2
R
2
H
10
8
H
15
H
3
5
27
7
4
R
1
HO
HO
H
H
6
H
23
24
O
187
R
1
=OH, R
2
=H
188
R
1
=H, R
2
=OH
189
R
1
+R
2
=O
190
R
1
=R
2
=H
182
betulinic acid, R
1
= H, R
2
= OH
183
alphitolic acid, R
1
= R
2
= OH
184
betulinylglycine
R
1
=H, R
2
=NHCH
2
COOH
185
platonic acid, R =
186
dihydrobetulinic acid, R =
H
H
O
O
H
H
HO
HO
NH(CH
2
)
10
COOH
H
H
NH(CH
2
)
10
COOH
HO
O
H
H
191
192
R
H
19
O
H
H
O
H
NH(CH
2
)
10
COOH
H
NH(CH
2
)
10
COOH
HO
H
H
H
O
O
193
194
R =
195
R =
196
R =
OH
Figure 9-10. Structures of lupane triterpenes and betulinic acid derivatives (182-196).
found to inhibit the cytopathogenicity of HIV-1 in CEM-4 cells, including betuli-
nylaminoundecanoic acid (187) with IC
50
values of 0.23 and 0.44 mM in CEM and
MT-4 cells, respectively. Changing the 3-hydroxy position from 3b (187)to3a
(188) led to a ten-fold decrease in activity (IC
50
ΒΌ
3.0 and 2.52 mM). The 3-keto
compound (189) exhibited intermediate activity. Interestingly, both the 3-deoxy
analog (190) and the 3,4-dihydroxy derivative (191) lost activity. Furthermore,
the antiviral activities of the 3,4-diketone (192) and 2,3-dehydro (193) derivatives
were low. Therefore, chemical modification in ring A led to considerable loss of
activity
77
(Figure 9-10).
9.4.1.2 Modification of the C-19 Side Chain
Hydrogenation of the isopropylidene double bond (194) reduced the activity of 187
by about five-fold. The replacement of the isopropylidene by an acetyl (195)ora
carboxylic
acid
(196)
led
to
virtually
inactive
molecules.
However,
various
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