Chemistry Reference
In-Depth Information
HO
H
H
OH
H
OH
3
OH
O
O
O
O
O
O
10
9
1
O
O
O
O
O
H
H
H
H
O
O
O
O
O
O
O
O
109
110
111
112
Structure 5-9
chrysogenum in low yield.
118
However, in 2002, Zhan et al. obtained the biotransfer
product 9b-hydroxy-qinghaosu (109), 3b-hydroxy-qinghaosu (110), 14 and 15 with
Mucor polymorphosporus, and 15 and 1a-hydroxyqinghaosu (111) with Aspergillus
niger.
119
In another report, 10b-hydroxyqinghaosu (112) was obtained with
Cunninghamella echinulata (Structure 5-9).
120
It is worth noticing that compound
15 might be the reaction product of qinghaosu with iron ion-reducing agents in the
incubating medium.
In the meantime, there were several reports about the microbial transformation
of artemether and arteether, from which several 1a,9a,9b, 14-hydroxy derivatives
and the products derived probably from the reaction with iron ion-reducing agents
in the incubating medium were identified.
121-124
5.4 CHEMICAL SYNTHESIS AND BIOSYNTHESIS
OF QINGHAOSU
5.4.1
Partial Synthesis and Total Synthesis of Qinghaosu
The outstanding antimalarial activity and the unique structure of qinghaosu have
attracted great attention in the research area of organic synthesis. Over nine syn-
thetic routes for qinghaosu have appeared in the literature. In general, the starting
materials for these synthetic routes are usually from optical monoterpene or sesqui-
terpene and the key step introducing peroxy group, except one, is based on the
photooxidation. The photooxidation can be performed with singlet oxygen proceed-
ing a [2
þ
2] addition with enol ether or a biomimetic manner. These syntheses are
outlined in Scheme 5-7. In the earliest two synthetic routes (A)
125-128
and (B),
129
enol methyl ether 117 is the common substrate of the key step photooxidation.
(
)-Isopulegol (115) is the starting material in route (B), whereas in the route
(A), artemisinic acid (20, arteannuinic acid, qinghao acid) is the starting material
to synthesize 117 through dihydro-artmisinic acid (23) to finish the partial synthesis
and then 23 and 20 are synthesized from the commercially available citronellal
(114) to finish the total synthesis. In route (C), a degradation product 105 serves
as
118.
130
the
relay
intermediate
to
conveniently
prepare
the
key
intermediate
Both route (D)
131
and route (E)
132,133
published in 1990 and 2003, respectively, use
Search WWH ::
Custom Search