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Br
O
O
O
O
Ni Raney
O
O
R
1
R
1
H
2
(10 bars)
O
O
O
O
24 h, AcOEt
6
21
OMe
COOMe
R
1
=
NH
2
88%
77%
46%
69%
Scheme 7 Reduction of monobromo exo-glycals.
H
2
,50bars
R
1
O
H
O
O
O
S
PtO
2
R
1
COOMe
O
O
COOMe
AcOEt, 24 h
O
O
O
O
17
22
OMe
R
1
=
a
b
c
d
NH
2
40%
42%
0%
54%
Scheme 8 Reduction of substituted activated exo-glycals.
freshly prepared Raney nickel without the need of hydrogen atmos-
phere,
2,6,7
simple hydrogenation using palladium catalysts was ecient
to reduce activated exo-glycals 3 and 4.
1,23,26
The C-glycosyl compounds
obtained this way have found applications as template for the con-
struction of peptidomimetics which are recognized by the neuropilin-1
receptor,
27
a co receptor of the vascular endothelium growth factor
(VEGF) implicated in angiogenesis and cancer.
28
Having access to new tetrasubstituted exo-glycals, the reduction of the
double bond was attempted. Monobromo exo-glycal like 6 was reduced
cleanly using Raney nickel catalyst, needed to cleave the C-Br bond, but
the reaction needed high pressure (10 bars) of hydrogen to obtain the
C-glycosyl derivative 21 in 46-88% yield (Scheme 7).
The reduction of tetrasubstituted double bond which would lead in
principle to C-glycosyl compounds with formation of a new chiral centre
has been also investigated. This reduction required rather harsh con-
ditions. Thus, compounds 17 were reduced under 50 bars of hydrogen
atmosphere in the presence of platinum oxide for 24 h in fair yield. If the
reaction worked well with 17a, 17c and 17d, poor results were obtained
with 17b (Scheme 8). A single diastereoisomer 22 was obtained in all
cases, the reduction occurring stereospecifically from the less hindered b
face of the glycal.
23
The S configuration of the newly formed chiral centre
of 22 was deduced from the E configuration of 17.
3.2 Formation of C-O bond at the anomeric centre
The formation of a C-O bond at the anomeric centre of exo-glycals has
been investigated as an easy way to make ketoses which could not be
attained by direct nucleophilic addition on lactones.
4a,29
Water addition
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