Chemistry Reference
In-Depth Information
H
2
N
NH
OH
O
O
HO
NH
NH
O
N
HN
OH
CH
3
HO
O
H
2
N
O
NH
N
O
OH
HO
H
O
OH
HO
Caspofungin (
40
)
HO
OH
HO OH
O
O
O
O
HO
NH
HO
NH
NH
O
NH
O
N
N
O
N
HN
OH
CH
3
HN
O
OH
CH
3
HO
O
H
2
N
O
O
HO
NH
N
NH
N
O
O
O
O
OH
OH
HO
N
H
HO
H
O
O
O
OH
OH
HO
3
SO
HO
HO
Micafungin (
41
)
Anidulafungin (
42
)
the most successful antimalarial agents, chloroquine and its successors. However,
the development of resistance by the malarial parasite
Plasmodium falciparum
for these drugs has rendered them ineffective. Artemisinin (
43
), a sesquiter-
pene peroxide originally isolated from a Chinese herb
Artemisia annua
in 1972
as an antimalarial agent, was chemically modified to a derivative, artemether
(
44
), which is a very effective and widely used antimalarial agent (18). Unfortu-
nately, limited supply of this plant-derived compound rendered it inaccessible for
wider use. Biosynthetic genes of artimisinin have been identified and successfully
transfected to an heterologous host,
Escherichia coli
. This method has allowed
the production of an intermediate, amorphadiene (
45
) and artemisinic acid (
46
),
which could be transformed chemically to artmether and potentially could relieve
the strain of supply and could provide wider availability (19-21).
12.5 ANTIVIRALS
Most antiviral agents are based on nucleoside structures and have their origin from
spongouridine (
47
) and spongothymidine (
48
) that were isolated from marine
sponges in the 1950s by Bergmann and his coworkers (22-24). These natural
