Biomedical Engineering Reference
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a particularly important member of this family, which is known to play a crucial role in
cell-to-cell recognition process. It is one of the most important blood group antigens
and mediates inflammatory response via activation of E-selectin, and it has been the
leading structure for the development of new anti-inflammatory agents [96]. The sLe
X
is also a tumor-associated antigen and thus has been a key compound in the devel-
opment of potential synthetic carbohydrate-based cancer vaccines [97]. The main
challenge for the synthesis of most of gangliosides is the introduction of the sialyl
residue at the C3-position of the galactose [98].
12.5.1.1. Participating Groups at C3
Classically,
-sialic acid glycosides
were accessed by the introduction of a participating group at C3, such as a halogen
or chalcogen group, with removal after glycosylation, as in the example taken from
thework of Nicolaou and coworkers andWong and coworkers (Scheme 12.30). These
authors described a direct sialylation between a sialyl anomeric chloride bearing an
adjacent thiophenyl group and a trisaccharide terminating in the key galactopyranose
unit [99]. In this synthesis, the galactose unit was employed as a 2,3,4-triol in order to
reduce the effect of steric hindrance from the protecting group, ultimately yielding the
tetrasaccharide in 63% yield. The stereodirecting phenyl thioether was removed by
action of triphenyltin hydride and a radical initiator.
This direct
a
-sialylation has also been conductedwith auxiliary 3-seleno groups
(Scheme 12.31), which are removed more easily than the phenylthio auxiliary [100],
a
OBn
OH
OBn
O
OH
O
O
HO
O
OH
CO
2
H
AcHN
OH
OH
OBn
HO
OH
OH
O
O
1. Hg(CN)
2
, HgBr
2
CCl
4
, 40°C, 48 h (63%)
OBn
AcHN
O
OH
O
O
O
BnO
OBn
HO
OH
O
+
NHAc
2. Ph
3
SnH, AIBN, PhMe, 130°C (77%)
3. Deprotection steps
BnO
O
Cl
OBn
sLe
X
OH
BnO
CO
2
Me
O
HO
OH
AcHN
SPh
BnO
P
S
BnO
Promotor
OBn
O
BnO
CO
2
Me
AcHN
BnO
ROH
SCHEME 12.30
Use of a participating group at C3.
BnO
AcO
F
Cl
OBn
OAc
BnO
AcO
O
CO
2
Me
O
CO
2
Me
AcHN
AcHN
SePh
O
BnO
AcO
S
R
Promotor
Promotor
(R = Ph or OPh)
R
P
Se
BnO
AcO
S
OBn
OAc
O
O
BnO
AcO
CO
2
Me
CO
2
Me
O
AcHN
AcHN
BnO
AcO
ROH
ROH
SCHEME 12.31
Alternative participating groups at C3.
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