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In-Depth Information
qinghaosu research from the different disciplines of botany, chemistry, pharmacol-
ogy, and clinic medicine during the last two decades. Undoubtedly, the discovery of
qinghaosu is one of the most important achievements for the natural products chem-
istry during the last two decades of the twentieth century. It may be recognized as a
milestone in the progress of natural products chemistry in comparison with quinine
in the nineteenth century. Qinghaosu is also a star molecule just like Taxol in about
the same period. For the modernization of traditional Chinese medicine, qinghaosu
is also one of the most successful examples. This chapter intends to describe its
structure determination, reaction, and synthesis. The congeneric natural products
in qinghao are also mentioned. This chapter will review the progress in the search
for derivatives of qinghaosu, the chemical biology study, and the exploration on the
action mode. Because of the limitation of the volume and the massive publications
on this subject, this chapter will preferentially, rather than comprehensively, intro-
duce the progress achieved in China.
5.2 QINGHAOSU AND QINGHAO
(ARTEMISIA ANNUA L. COMPOSITES)
5.2.1
Discovery and Structure Determination of Qinghaosu
In the 1960s, drug-resistant malarial parasites developed and spread rapidly in
Southeast Asia and Africa; therefore, existing antimalarial drugs, such as quinine,
chloroquine, and pyrimethamine-sulphadoxine became less efficient. The introduc-
tion of a new generation of antimalarial drug was much anticipated by the
100,000,000 patients worldwide. Now malaria is no longer a serious infectious dis-
ease in China, but back then, Chinese people, especially those who lived in the
southern provinces, faced a critical situation. In 1967, a program involving several
hundred Chinese scientists nationwide was launched to take on this challenge. A
part of this program, called ''Program 523,'' endeavored to explore the traditional
Chinese medicine and herb. More than 1000 samples from different herbs have
been studied by the modern methods, and isolation of the active principles is mon-
itored with antimalarial screening in animal models. Several active principles, such
as yingzhaosu A (2, yingzhaosu) from yingzhao (Artabotrys hexapetalu (LF)
Bhand),
17
agrimols (3) from xianhecao (Agrimonia pilosa L.),
18,19
robustanol (4)
from dayean (Eucalyptus robusta Sm),
20
protopine (5) from nantianzhu (Nandina
domestica T.),
21
bruceine D and E (6 and 7) from yadanzi (Brucea javanica (L)
Merr),
22
and anluosu (8) from lingshuianluo [Polyalthia nemoralis A.(DC)],
23
have been identified. Total synthesis and structure modification of some principles,
such as yingzhaosu, agrimols, and febrifugine (9), which was isolated
24
from the
Chinese traditional antimalarial medicine changshan (Dichroa febrifuga Lour.) in
1948, were also identified thereafter (Structure 5-1). Unfortunately these natural
products and their synthetic derivatives were hardly available, insufficiently active,
or too toxic. However, just as the Chinese old proverb says, ''Heavens never fail the
people working with heart and soul,'' the great promise for the new generation of
antimalarial medicine did rise from an obscure weed, the old Chinese traditional
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