Chemistry Reference
In-Depth Information
O
O
CH
3
(CH
2
)
10
CH
3
(CH
2
)
10
O
O
O
O
H
H
H
H
O
O
O
O
HO
HO
HO
HO
O
O
OR
O
(CH
2
)
14
CH
3
K1
Kansuiphorin A, R
=
CO(CH
2
)
14
CH
3
K5
DBDI, R
=
H
K2
Kansuiphorin B
H
H
O
O
H
H
H
H
O
HO
HO
C
6
H
5
O
AcO
O
AcO
C
6
H
5
O
K3
Kansuiphorin C
K4
Kansuiphorin D
OH
H
H
H
H
HO
O
O
HO
H
R
2
R
1
K8
Yuexiandajisu F
K6
Yuexiandajisu D, R
1
=
β
-OH, R
2
=
α
-OH
K7
Yuexiandajisu E, R
1
=
α
-OH, R
2
=
β
-OH
Figure 14.11
Structures of Kansui natural products.
After additional synthetic modification to improve potency, 4-methyl DCK
(
L3
) and then 3-hydroxymethyl-4-methyl DCK (
L4
) were found. The latter com-
pound was selected as a clinical trial candidate (114).
Furthermore, a positional isomer of DCK, 3
R
,4
R
-di-
O
-(
−
)-camphanoyl-
2
,2
dimethyldihydropyrano(2,3-f)chromone (DCP) (
L5
) is even more promising
because most DCP analogs are active against drug-resistant HIV strains,
although DCK analogs are not. Adding an ethyl group at the 2-position of DCP
decreased toxicity to cells compared with DCP, so, to date, the most likely
clinical trials candidate in the DCP series is 2-ethyl DCP (
L6
) (114, 115).
The DCK and DCP compounds exert their antiviral activity by blocking the
HIV reverse transcriptase (RT), however, at a later step than that affected by
