Biomedical Engineering Reference
In-Depth Information
AcO
AcO
O
O
AcO
OH
NPhth
BnO
BnO
O
O
Ph
O
AcO
AcO
AcO
O
O
O
O
N
3
HO
+
O
O
BnO
BnO
O
NPhth
AcO
NPhth
AcO
NPhth
O
CCl
3
AcO
AcO
1. BF
3
.OEt
2
, CH
2
Cl
2
, -25°C
(93%)
NH
O
O
AcO
2. Acetylation/Deprotection
(81%)
NPhth
AcO
AcO
AcO
AcO
AcO
OAc
O
O
O
O
O
PhthN
OAc
HO
OAc
AcO
AcO
O
AcO
BnO
BnO
O
O
PhthN
NPhth
O
HO
OAc
O
O
O
O
O
+
AcO
N
3
BnO
BnO
AcO
NPhth
NPhth
O
CCl
3
NH
AcO
AcO
88%
BF
3
.OEt
2
, CH
2
Cl
2
, -45°C
O
O
AcO
AcO
AcO
O
PhthN
OAc
O
AcO
OAc
O
OAc
PhthN
O
PhthN
AcO
AcO
OAc
OAc
AcO
O
O
O
O
O
OAc
AcO
AcO
BnO
BnO
O
O
NPhth
HO
O
O
O
O
N
3
BnO
BnO
NPhth
NPhth
SCHEME 12.12
Unverzagt's approach to multiantennary polysaccharides.
Martin-Lomas and coworkers [44] introduced
b
-mannose via indirect methods,
whereas Huang and coworkers used a direct
-mannosylation method [45]. Most
notably, Wang and coworkers [46] and Fairbanks and coworkers [47] described highly
efficient chemoenzymatic approaches to homogeneous synthetic glycoproteins pre-
senting the pentasaccharide motif.
b
12.2.2.
-Rhamnopyranosides
b
The
b
-rhamnopyranosides present
the same stereochemical challenges as the
b
-mannopyranosides, from which they differ only by the absence of the 6-OH
functionality. The absence of one C-O bond, however, completely changes the
problem insofar as it necessitates either the development of new stereocontrolled
methods avoiding the use of 4,6-
O-
acetal, which are generally inadequate for the
same reasons as in the mannose series, or a method for the efficient reductive cleavage
of the C6-O6 bond postglycosylation. The classical Hanessian-Hullar reaction for
the transformation of 4,6-
O-
benzylidene acetals to 4-
O-
benzoyl-6-bromo-6-deoxy
pyranosides with
N
-bromosuccinimide [48], or the more recent Roberts variant [49]
in which the acetal is converted directly to the 6-deoxy sugar by treatment with a
catalytic amount of thiol and a radical initiator, provided essential clues to the
development of a viable sequence but are not themselves generally applicable to
oligosaccharide synthesis because of their incompatibility with benzyl ethers. A first-
generation solution to this problem relied on the use of a modified benzylidene acetal
to control anomeric stereoselectivity in the glycosylation reaction, followed by a
radical fragmentation sequence of a specially installed thioester to provide the key
benzylidene radical susceptible to the fragmentation of the C6-O6 bond [50].
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