Biomedical Engineering Reference
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was coupled with excellent yield and selectivity to a
-mannosyl donor selectively
protected with a PMB group on the 3-OH [39]. Oxidative removal of the latter was
followed by introduction of a
a
-mannosyl unit with activation of the thioglycoside
under oxidative conditions with a triarylamminium salt, as first applied in carbohy-
drate chemistry by Sina
b
y and coworkers [40]. Cleavage of the directing ester enabled
introduction of a further disaccharide, employing the same activation method, but this
time taking advantage of the bulky phthalimido group to access the
€
-stereochemistry.
Regioselective reductive cleavage of benzylidene acetal with BH
3
b
THF in the
presence of
n
-Bu
2
BOTf converted it to a 4-
O-
benzyl ether, leaving the primary
6-OH of the core
-mannoside vacant for the introduction of the second chain of the
biantennary system. A series of deprotecting steps then led to the target nonasacchar-
ide for conjugation to a peptide chain.
The advantages of this method are apparent from comparison, for example,
with the highly refined but more classical approach to the same structural motif
from Unverzagt and coworkers, who developed a convergent synthesis of a series
of multiantennary complex type
N
-glycans by use of modular building blocks
(Scheme 12.11) [41]. The key
b
-mannoside linkage to a preassembled chitobiosyl
acceptor was introduced by the Kunz method [42], in which a
b
-glucoside is formed
via neighboring group participation. A series of subsequent steps involving manip-
ulation at
O-
3 and
O-
2 eventually enable inversion of the latter and the formation of
b
b
-mannoside in the turn of its 2,3-
O-
carbonate. Hydrolysis of the latter furnished the
targeted
-mannose. This strategy, although providing the desired compound with
the correct stereochemistry, is long and inefficient when compared to the direct
b
-mannosylation methods.
A further series of glycosylations with a set of complex saccharide donors and
functional transformations delivered the target compound (Scheme 12.12). Most
notably, chemoselective
b
-mannosylation on 3-OH of 2,3-diol and subsequent
removal of benzylidene acetal provided stereo- and regioselectively a hexasaccharide.
Subsequent regioselective glycosylation of primary hydroxyl with further complex
donors then provided the target compound in good yields.
A number of other groups have developed different methods to access
such multiantennary oligosaccharides. Among these, Boons and Watt [43] and
a
BnO
HO
BnO
1. TMSOTf
CH
2
Cl
2
(62%)
BnO
O
O
BnO
BnO
O
Ph
O
O
O
Ph
O
O
O
O
O
N
3
O
O
O
+
O
PhHN
BnO
N
3
2. K
2
CO
3
MeOH/CH
2
Cl
2
(89%)
PhHN
ClAcO
BnO
NPhth
NPhth
OH
BnO
O
NPhth
NPhth
O
NH
O
Cl
3
C
NPh
O
BnO
Tf
2
O
Pyridine
BnO
O
O
O
Ph
O
BnO
BnO
O
O
O
Pyridine
O
O
O
Ph
O
O
N
3
O
O
PhHN
O
O
BnO
OTf
BnO
N
3
CH
2
Cl
2
DMF, 65°C
NPhth
NPhth
BnO
BnO
O
NPhth
NPhth
1. AcOH
H
2
O/dioxane
OH
BnO
BnO
O
O
Ph
O
O
O
O
O
N
3
HO
2. MeONa
MeOH/CH
2
Cl
2
BnO
BnO
NPhth
NPhth
70% (over 4 steps)
SCHEME 12.11
Synthesis of a pivotal
b
-mannoside trisaccharide by Unverzagt and coworkers.
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