Chemistry Reference
In-Depth Information
OH
O
O
N
MeO
N
O
N
Galanthamine
Rivastigmine
4.2
PROFILES OF HA
4.2.1
Discovery of HA
H. serrata and its related genera have been used as folk herbs for the treatment
of memory disorder and schizophrenia in the east of China. Phytochemical studies
disclosed that these plants contained mainly serratene-type triterpenes
15,16
and
Lycopodium alkaloids.
17-24
In the early 1970s, Chinese scientists reported that
the total alkaloids of H. serrata could relax the striated muscle and alleviate the
symptom of myasthenia gravis on the animal model. Biodirected assay caused
the phenolic alkaloids fraction to be spotlighted
25
and the following chemical com-
ponent isolation resulted in the finding of HA.
1
4.2.2
Physical Appearance of HA
HA is a rigid three-ring system molecule that consisted of a tetrahydroquinolinone,
three-carbon bridge ring, exocyclic ethylidene, and primary amino group. Its
empirical formula is C
15
H
18
N
2
O, and its molecular weight is 242. The compound
is optically active and in the plant is present only in its (
)-enantiomer. Its structure
and stereochemistry were elucidated as (5R,9R,11E)-5-amino-11-ethylidene-
5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta [b]pyridin-2[1H]-one on the
basis of nuclear magnetic resonance (NMR), infrared (IR), ultraviolet (UV), and
circular dichroism (CD) data and chemical transformations by Liu et al.,
1
which
was confirmed by x-ray crystallographic analysis.
26
Two similar reported mole-
cules, selagine
27
and isoselagine,
28
were reexamined to be the same with HA by
Sun et al.
29
and Ayer and Trifonov,
23
respectively.
From the viewpoint of biogenesis, HA belonged to the lycodine type of
Lycopodium alkaloids with the opening of ring-C and a carbon atom lost.
Lycopodium alkaloid is a class of alkaloids that possesses a unique ring system iso-
lated from the family of Huperziaceae and Lycopodiaceae of Lycopodiales order.
They have a common formula C
16
NorC
16
N
2
with three or four rings, which may
be subclassed into four types, namely, lycopodine, lycodine, fawcettimine, and mis-
cellaneous, on the basis of carbon skeleton and probable biogenetic pathway.
23
More than 200 Lycopodium alkaloids have been isolated and identified so far. Sur-
prisingly, they had no anti-ChE effect or far less than HA.
24
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