Biology Reference
In-Depth Information
The different protecting groups on the galloyl units of the resulting
compound (not shown) permitted a stepwise deprotection sequence.
First, the
t
-butyldimethylsilyl ether groups were cleaved using
n
-Bu
4
NF
to furnish
77
, in which the galloyl moieties at the 4- and 6-positions of
both glucopyranosyl units were ready to be engaged in a double
oxidative coupling step. This was again performed using Pb(OAc)
4
, and
the resulting regioisomeric mixture
78
was then fully debenzylated to
furnish the dimer coriariin A (
79
, Fig. 5.15).
5.2.3 2,3,4,6-HHDP-containing ellagitannins
5.2.3.1
Synthesis of O-permethyl-
α
-pedunculagin
The chemical structure of pedunculagin (
87
) consists of two (
S
)-
configured HHDP moieties that are located at the 2,3- and 4,6-positions
of the
D
-glucopyranose core (Okuda
et al.
, 1983b). Pedunculagin (
87
)
has been shown to inhibit the promising anticancer target enzyme DNA
topoisomerase II
in vivo
, with an IC
100
of 500 nM (Kashiwada
et al.
,
1993).
Itoh's strategy for the construction of ellagitannins is based on the
concept of kinetic racemate resolution by esterification of racemic
hexamethoxydiphenic acid dichloride
rac
-
80
with suitable
D
-
glucopyranosyl derivatives (
i.e.
, see Fig. 5.1, method
A
). There is no
need for atropodiastereoselective formation of the chiral biaryl axis,
since the chiral axis is already present in the biaryl unit (Itoh and Chika,
1995, Itoh
et al.
, 1996). Their synthesis of trideca-
O
-methyl-α-
pedunculagin (
84
, see Fig. 5.16) relied on the application of this kinetic
resolution tactic (Itoh
et al.
, 1996). They also investigated the
stereoselectivity outcome of the esterification reactions under different
conditions, and found out that the diastereoisomeric ratio strongly varies
depending upon the base used, for example, sodium hydride or
dimethylaminopyridine (DMAP). The reaction of commercially available
1-
O
-methyl-4,6-
O
-benzylidene-α-
D
-glucopyranose (
51
) with
rac
-
80
in
the presence of DMAP resulted in the formation of the two
diastereomers
81
and
82
, which were then separated by silica gel. The
