Biology Reference
In-Depth Information
5.2.4 2,4-HHDP-containing ellagitannins
5.2.4.1
Construction of a 2,4-bridged species
From the synthetic point of view, the 2,4- and 3,6-HHDP-containing
ellagitannins are much more challenging compounds than the 2,3- and
4,6-HHDP-containing ellagitannins, because their
D
-glucopyranose ring
adopts the thermodynamically less stable
1
C
4
-conformation and their
HHDP unit(s) the (
R
)-configuration. Up to now, there is no total
synthesis of any ellagitannin of this type. However, the Feldman group
recently reported the construction of the 2,4-HHDP-containing
glucopyranose derivative
97
, starting from
91
, which possesses a 1,6-
anhydro bridge that “freezes” the glucopyranose ring in the
1
C
4
-
conformation (Feldman
et al.
, 2003). A two-fold acylation of
91
with
the acid
8
, followed by desilylation gave the galloyl-derived bisester
92
(Fig. 5.19).
This material was then ready to be engaged in an oxidative
intramolecular coupling reaction to form the key biaryl bond between the
galloyl units linked to the 2- and 4-positions of the sugar core. As
previously described in this Chapter, Feldman
et al.
had already
demonstrated that such oxidative coupling reactions mediated by
Pb(OAc)
4
(
i.e.
, Wessely oxidation) and performed on galloylated
glucopyranose rings in their
4
C
1
-conformation are diastereoselective and
give only the corresponding biaryl (
S
)-atropoisomers. Here, two
questions then arose as to whether the coupling of 2,4-positioned galloyl
moieties would be at all possible under Wessely conditions and whether
the stereochemistry of the biaryl product will also be controlled in this
case.
Feldman
et al.
observed that the Pb(OAc)
4
-mediated oxidative
coupling of
92
gave at least six distinct isomers consisting of the
expected biaryl diphenylketal regioisomers and their corresponding
atropisomers (see
93
in Fig. 5.19). Unexpectedly, the hydrogenolysis of
this mixture gave the uncoupled bisgalloyl ester (not shown). Thus, it
was assumed that the biaryl bond had been broken by the
hydrogenolysis, maybe because of the relatively high strain energy of the
HHDP-containing species
93
.
