Biology Reference
In-Depth Information
5.2.2.5.2 Synthesis of
O
-permethyltellimagrandin II
Also in 1994, Lipshutz
et al.
published the synthesis of
O
-
permethyltellimagrandin II (
61
), the key step being this time a
cyanocuprate-catalyzed diastereoselective biaryl coupling. Nucleophilic
substitution of the benzylic bromide function of the starting dibromide
55
with enantiopure (
S
)-1,2-diphenylethane-1,2-diol (
56
) furnished the
diether
57
. Reaction of
57
with
tert
-BuLi and CuCN formed a
cyanocuprate intermediate, which was converted to the cyclic product
58
in 77% yield. Hydrogenolytic cleavage of the bisbenzylic ether bridge,
followed by oxidation of the resulting benzylic alcohols, yielded the
enantiomerically pure (
S
)-hexamethoxydiphenic acid (
S
)-
50
(Fig. 5.11).
The second building block used was the 4,6-diol derivative of
D
-glucopyranose
60
, which was prepared in three steps from
D
-
glucopyranose
59
,
i.e.
, selective protection of its 4,6-hydroxyl groups,
acylation with TMGCl
62
(Keck and Boden, 1985) and deprotection of
the dimethoxyketal unit. The final step entails the esterification of (
S
)-
50
with
60
to furnish the permethylated tellimagrandin II (
61
, Fig. 5.11).
5.2.2.5.3 Total synthesis of tellimagrandin I
With the successful accomplishment of the total synthesis of
tellimagrandin I (
67
, see Fig. 5.12), the Feldman group was the first to
report a synthesis of a representative member of the ellagitannin class of
natural products (Feldman
et al.
, 1994). As alluded to above (see method
B
in Fig. 5.1), their strategy for the stereoselective construction of an
(
S
)-HHDP unit was based on a biomimetic oxidative biaryl coupling of
neighbouring galloyl groups using lead tetraacetate (Quideau and
Feldman, 1996).
In tellimagrandin I (
67
), the biaryl unit is linked to the 4,6-positions
of its
D
-glucopyranosyl core; the galloyl residues at the 2- and 3-
positions are not coupled to each other. In the first synthesis route, this
regioselectivity was controlled as follows: starting from the
D
-
glucopyranose derivative
28
, the anomeric center of which being
protected as a benzyl ether and its O-4 and O-6 centers as a benzylidene
acetal unit, the free hydroxyl functions at C-2 and C-3 were acylated
with the tribenzylated gallic acid
22
to form the diester
63
. Hydrolysis of
