Chemistry Reference
In-Depth Information
It is not understood which components of EGb 761 are efficacious, but it is
assumed that the major components flavonoids and terpene trilactones play important
roles. However, when dealing with effects in the CNS, it is assumed that the
flavonoids do not penetrate the blood-brain barrier (BBB),
10
whereas it has been
suggested that terpene trilactones do penetrate the BBB.
23-25
However, in contrast
to the wealth of studies that have been performed with EGb 761, far fewer studies
have looked at the effect of the individual components of these extracts, in particu-
lar flavonoids and terpene trilactones.
7.1.2 Isolation and Structure Elucidation of Ginkgolides
The terpene trilactones, ginkgolides and bilobalide,
26
are the unique constituents of
G. biloba, which are found exclusively in the G. biloba tree. The ginkgolides are
diterpenes with a cage skeleton consisting of six five-membered rings, including
three lactones, a tetrahydrofuran ring, and a spiro[4.4]nonane skeleton, and a
characteristic tert-butyl group. The ginkgolides vary only in the number and
positions of their hydroxyl groups. Bilobalide is also a terpene trilactones with a
structure similar to the ginkgolides and is the major single component in EGb
761, comprising about 3% of the total extract, whereas the five ginkgolides take
up another 3%.
O
O
HO
HO
O
O
10
R
1
C
O
O
1
D
F
O
3
A
B
O
O
OH
7
O
Me
E
R
3
O
O
R
2
O
bilobalide (BB)
R
1
R
2
R
3
H
OH
OH
H
OH
H
H
OH
OH
OH
OH
OH
OH
OH
H
ginkgolide A (GA)
ginkgolide B (GB)
ginkgolide C (GC)
ginkgolide J (GJ)
ginkgolide M (GM)
The complex structures of ginkgolides were discovered in 1967 by pioneering
work of Nakanishi et al. Since then, a wealth of studies involving ginkgolides
have been published, including intriguing total syntheses pioneered by Corey, stu-
dies of their biosynthesis revealing a novel, general biosynthetic pathway, and pre-
paration of several derivatives for SAR studies at the PAF receptor and, more
recently, at the glycine (Gly) receptors.
The structural studies by Nakanishi et al. that led to the discovery of the struc-
tures of ginkgolides rank among the greatest achievements in natural products
research, and the fascinating account of these studies has been given elsewhere.
27,28
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