Biology Reference
In-Depth Information
5.20). Treatment of
98
with methoxymethyl chloride (
i.e.
, MOMCl) led
to the regioselective protection of the 3,6-hydroxyl groups and gave
99
in 64% yield. The free 2,4-hydroxyl groups of
99
were benzylated, and
the resulted product (not shown) was converted to the α,β-anomeric
mixture
100
by hydrolysis of the phenylthio group at the anomeric center
of the
D
-glucopyranose ring. The challenging conversion of the
stereochemistry of the
D
-glucopyranose ring from a
4
C
1
-conformation to
a
1
C
4
-conformation and the establishment of the HHDP moiety in a
correct absolute (
R
)-configuration were the main issues to be addressed
in this synthesis work. To this aim, the authors used the following and
quite elegant sequence: opening of the
4
C
1
-glucopyranose ring,
installation of the methyl ether-protected galloyl residues,
diastereoselective reductive Ullmann coupling of the galloyl residues to
build the (
R
)-HHDP moiety (
i.e.
, method
B
, see Fig. 5.1), followed by
closing of the sugar core into a glucopyranose ring having the
1
C
4
-
conformation, and this key transformation was achieved by exploiting
the template effect brought about by the (
R
)-HHDP moiety (Fig. 5.20).
Thus, the initial glucopyranose ring opening was accomplished
via
a
Wittig olefination of
100
to generate
101
. Its free hydroxyl group at C-5
was protected as a
p
-methoxybenzyl (PMB) ether, and the MOM groups
were then cleaved to afford the open-chain 3,6-diol
102
. Installation of
two 2-iodo-3,4,5-trimethoxybenzoyl units onto
102
could be achieved
by using 2-iodo-3,4,5-trimethoxybenzoic acid
103
, thus leading to the
Ullmann coupling substrate
104
. The copper-mediated Ullmann coupling
of
104
into the axially chiral biaryl intermediate
105
was examined at
different concentrations, the highest yield of 48% for (
R
)-
105
being
obtained when the final concentration of the product was 3 mM. The
PMB protective group, as well as the double bond, were then cleaved
under oxidative conditions. Remarkably, these conditions also allowed
for the reconstruction of the glucopyranose ring, which adopted the
desired
1
C
4
-conformation to furnish the advanced intermediate
106
in a
good yield. Anomeric acylation of the intermediate
106
with the
trimethylated galloyl chloride
62
under basic conditions led to the
formation of a 4:6 mixture of the corresponding α- and β-isomers of
107
.
These anomers were separated by chromatography, and hydrogenolytic
debenzylation of the β-isomer
107
furnished nonamethylcorilagin (
108
).
