Biology Reference
In-Depth Information
than in β-anomers (Garegg
et al.
, 1976, Iversen
et al.
, 1977). This
phenomenon was to be exploited in our synthetic strategy.
The key starting material for the synthesis of both gemin D (
37
) and
hippomanin A (
38
) is 1-
O
-benzyl-4,6-
O
-benzylidene-β-
D
-glucopyranose
(
28
), which can be prepared by acetalisation of the commercially
available 1-
O
-benzyl-β-
D
-glucopyranose using benzaldehyde and
anhydrous ZnCl
2
(Petit and Sinay, 1978, Sen and Banerji, 1989).
Various alternative strategies exist for the selective monoalkylation
of the hydroxyl group at C-2 of
D
-glucopyranose derivatives. For
example, limiting the quantity of base or alkylating agent, as well as
shortening the reaction time, can give the required selectivity (Ogawa
et al.
, 1978). Another method has been developed for the selective
monobenzylation of the 2-OH group of 2,3-diol derivatives of
D
-
glucopyranose protected at the 1,4,6-positions (Garegg
et al.
, 1976) by
using tetra-
n
-butylammonium hydrogenosulfate (
n
-Bu
4
NHSO
4
) as a
phase transfer catalyst. On the basis of these literature precedents, we
performed the reaction of diol
28
with benzyl bromide (BnBr) in the
presence of tetra-
n
-butylammonium iodide
(
n
-Bu
4
NI) as a phase transfer
catalyst and obtained an inseparable mixture of both regioisomers
29
and
30
in 74% overall yield (Fig. 5.7).
The ratio of 2-
O
-benzylated product
29
to its 3-
O
-benzyl ether
variant
30
was 3:1, as determined by NMR analysis. Due to the low
selectivity of the monobenzylation reaction, the 1-
O
-benzylated 4,6-
O
-
benzylidene-β-
D
-glucopyranose
28
thus provided access to both natural
products
37
and
38
. The regioisomeric mixture
29
/
30
was then acylated
with 3,4,5-tri-
O
-benzylgallic acid (
22
), under standard Steglich
conditions, to afford the glucopyranose derivatives
31
and
32
, which
were easily separated by silica gel chromatography. Both natural
ellagitannins gemin D (
37
) and hippomanin A (
38
) were then
synthesized in parallel. First, the benzylidene acetals were cleaved from
31
and
32
by acidic hydrolysis using 2 N HCl to yield the corresponding
4,6-diols
33
and
35
. This was followed by acylation with racemic
hexabenzyloxydiphenic acid
rac
-
16
. These acylation reactions of the 4,6-
positions of sugars
33
and
35
were both fully diastereoselective, as
observed in the strictinin total synthesis (Khanbabaee
et al.
, 1997) and
led to the perbenzylated precursors
34
and
36
in 68% and 66% yield,
