Biomedical Engineering Reference
In-Depth Information
OPMB
O
Ph
O
O
1. Tf
2
O, TTBP
CH
2
Cl
2
, -78°C
O
OPMB
OPMB
BnO
O
O
1. DDQ
Ph
Ph
O
O
O
O
O
Ph
OC
6
H
11
O
2. Cyclohexanol
77%
O
2. Donor
Tf
2
O, TTBP
CH
2
Cl
2
, -78°C
BnO
BnO
OC
6
H
11
BnO
S
O
Et
/ = 100:0
Donor
94%
PMB-deprotection/
Glycosylation steps
OPMB
OH
O
Ph
HO
HO
O
O
O
t-Bu
O
O
BnO
HO
N
O
TTBP =
HO
HO
HO
H
2
Pd/C
Ph
O
O
O
O
t-Bu
N
t-Bu
O
BnO
6
6
O
HO
HO
HO
Ph
O
O
O
OC
6
H
11
OC
6
H
11
BnO
SCHEME 12.4
Synthesis of immunogenic
b
-(1
!
2)-mannans by Crichand coworkers.
This chemistry has subsequently been widely adopted by many groups and
extended beyond the sulfoxide method to include the use of thioglycosides [23],
trichloroacetimidates [24], and so on [25] as donors. Its use is illustrated here through
the syntheses of various complex oligosaccharides.
12.2.1.1.
2)-Mannooctaose from Candida albicans
Oligomeric
b
-(1
!
2)-linked mannans are found in
C. albicans
bacterial cell wall and in
phosphopeptidomannans [26]. They are immunogenic and elicit specific antibodies
in both humans and animals. Furthermore, it has been shown that
-(1
!
b
2)-mannans
induce TNF1-R synthesis from cells of the macrophage lineage and bind to mac-
rophage cell membranes [27]. Adapting the sulfoxide method to the synthesis of
these oligomers, Crich and coworkers established a two-step iterative protocol for the
introduction of each successive linkage involving the formation of
-(1
!
b
-mannoside bond
and selective oxidative deprotection of 2-
O-p-
methoxybenzyl ether (Scheme 12.4).
Selectivities were high for the first three linkages but were somewhat reduced for
the subsequent ones, owing to the increased steric hindrance around the acceptor
alcohol [28].
b
12.2.1.2. Solid-Phase Synthesis of
-Mannosides
One of the most concep-
b
tually elegant solutions to
-mannopyranoside synthesis is that of intramolecular
aglycon delivery (IAD). In this approach, introduced first by Hindsgaul and
Barresi [29] and then by Stork and Kim [30], the acceptor alcohol is first tethered
to
O-
2 of the donor by a mixed acetal or mixed silylene acetal. Upon activation of the
donor, the acceptor is then delivered intramolecularly to give
b
-glycosidic bond
with perfect control of selectivity. The main drawback of this method is the need for
the synthesis of the mixed acetal or silylene acetal, particularly in the case of
complex acceptors, which often leaves scope for considerable improvement. The
method, which has been reviewed several times [31], was perfected by Ito and
coworkers (Scheme 12.5), who employed a polymer-supported
p-
methoxybenzyl
ether as the protecting group for
O-
2 of the donor and that was activated toward
mixed acetal formation by oxidation with DDQ [32]. Such a protocol enabled the
use of an excess of acceptor in this critical step, with only the mixed acetal being
b
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