Chemistry Reference
In-Depth Information
OH
O
O
O
O
OMe
MeO
OMe
D1
Podophyllotoxin
R
1
O
O
O
HN
NO
2
HO
O
OH
O
O
O
O
O
O
O
O
OMe
MeO
OMe
MeO
OR
2
OH
D2
Etoposide, R
1
=
Me, R
2
=
H
D5
GL331
,R
2
=
H
D3
Teniposide, R
1
=
S
D4
Etopophos, R
1
=
Me, R
2
=
PO
3
H
2
Figure 14.4
Structures of natural and synthetic podophyllotoxins.
14.1.5 Cephalotaxus species
The genus
Cephalotaxus
(Cephalotaxaceae family) contains coniferous evergreen
trees and shrubs that are indigenous to Asia. Historically, the bark has long been
used in TCM for various indications.
Powell et al. (59-61) originally isolated the antitumor alkaloids homoharring-
tonine (
E1
) and harringtonine (
E2
). Subsequently, Chinese investigators discov-
ered that alkaloids from
C. fortunei
Hook. F possess antitumor activity (62).
Consequently,
E1
was obtained from the Chinese evergreen tree
C. harringto-
nia
K. Koch var.
harringtonia
(63), and other active alkaloids were isolated
from various
Cephalotaxus
species (64, 65). Interestingly, the parent compound,
cephalotaxine (
E3
), is devoid of antitumor activity.
E1
has been investigated in anticancer clinical trials at the U.S. National Can-
cer Institute (NCI), particularly for the treatment of myeloid leukemia (66, 67).
However, its side effects still remain an issue. Thus, the authors have contin-
ued to study new natural constituents of
Cephalotaxus
species and to develop
