Biomedical Engineering Reference
In-Depth Information
in this final coupling was disappointing, probably due to the bulky substituent at the
C3 position of the glycosyl donor, the coupling was conducted with almost stoi-
chiometric quantities of the two coupling partners and despite the poor selectivity
afforded the desired hexasaccharide in a single reaction. Finally, hydrogenolysis over
palladium on carbon afforded the alternating mannan in 93% yield.
Comparison of the two strategies reveals that the linear synthesis, with 1.9%
overall yield for 11 steps, is less efficient than the block synthesis, achieved in 4.4%
global yield for eight steps despite the modest yields and selectivity for the final
coupling step [37].
12.2.1.4. Biantennary Compounds
A more important example of the appli-
cation of the benzylidene-directed
-mannosylation method is its application to the
synthesis of the core pentasaccharide fragment common to
N
-linked glycopro-
teins [18]. These almost ubiquitous glycans decorate the gp120 proteins on the cell
surfaces of the HIV virus and are overexposed on cancer cell surfaces. Accordingly,
they are considered as possible targets for the development of synthetic vaccines.
Such glycans also serve in the synthesis and study of artificial
N
-glycan-containing
glycoproteins [38].
In an example of the general strategy adapted by Danishefsky and coworkers
toward this type of linkage (Scheme 12.10), a protected chitobiosyl acceptor,
assembled by a variation on the theme of the glycal assembly method (see below),
b
1. Tf
2
O, DTBMP
CH
2
Cl
2
, -78°C
(78%,
OBn
BnO
HO
BnO
OBn
BnO
O
BnO
BnO
O
BnO
O
O
O
Ph
Ph
O
O
O
α/β
= 1:8)
O
O
O
O
O
+
HO
PMBO
BnO
2. CAN, MeCN/H
2
O (74%)
BnO
PhSO
2
HN
PhSO
2
HN
PhSO
2
HN
PhSO
2
HN
SOPh
OTBS
OTBS
BnO
BnO
OBz
OBn
BnO
BnO
O
O
O
O
1.
(BrC
6
H
4
)
3
NSbCl
6
MeCN (80%)
BnO
SEt
BnO
BnO
SPh
OBn
OBn
NPhth
BnO
O
BnO
BnO
O
O
Ph
O
O
O
O
1. (BrC
6
H
4
)
3
NSbCl
6
, MeCN (60%)
O
BnO
BnO
PhSO
2
HN
PhSO
2
HN
2. NaOMe, MeOH (89%)
2. Functional group adjustment (38%)
BnO
OTBS
O
BnO
OH
BnO
HO
OBn
BnO
O
BnO
BnO
BnO
BnO
O
OAcCl
O
O
O
O
O
BnO
BnO
BnO
PhSO
2
HN
PhSO
2
HN
O
OBn
BnO
OTBS
1. (BrC
6
H
4
)
3
NSbCl
6
, MeCN (78%
)
O
+
O
OBn
BnO
BnO
BnO
BnO
O
2. Full deprotection and
2.
functional group ajustment
O
O
O
O
BnO
SPh
BnO
BnO
BnO
OBn
NPhth
O
OAcCl
BnO
HO
HO
OH
O
HO
O
OH
O
HO
OH
O
OH
HO
O
HO
O
steps
HO
O
O
O
O
Glycopeptide
HO
O
O
HO
NH
2
HO
OH
HO
HO
NHAc
NHAc
HO
O
OH
HO
HO
HO
O
O
O
O
HO
HO
OH
NHAc
SCHEME 12.10
Danishefsky's approach to multiantennary polysaccharides.
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