Biomedical Engineering Reference
In-Depth Information
O
O
OH
ROH (1.9-2.6 equiv)
DDQ, CH
2
Cl
2
, rt
MeOTf, DTBMP
O
Ph
O
O
OR
DCE, rt
TBDMSO
O
OR
O
O
O
Ph
Ph
O
O
O
O
TBDMSO
TBDMSO
ROH
Yield
SMe
SMe
HO
BnO
O
OBn
43%
TBDMSO
O
OBn
BnO
HO
O
OBn
48-50%
TBDMSO
OBn
O
O
Ph
O
O
BnO
HO
O
TBDMSO
F
NPhth
37%
TBDMSO
SMe
SCHEME 12.5
Supported intramolecular aglycon delivery by Ito and coworkers.
retained on the polymeric support. Intramolecular aglycon transfer and concomitant
release of the saccharide from the support were achieved upon activation of the
glycosyl donor.
Seeberger and coworkers demonstrated that the
-mannoside linkage can be
accessed by automated solid-phase synthesis [33]. In such an automated supported
sequence, an excess of reagents can be used to ensure complete reaction on each
coupling, and resin washes can remove any soluble impurities. Only a single
purification step is necessary after the liberation of the polysaccharide from the
solid support [34]. Seeberger's synthesis of
b
-mannosides relies on Kim's modifi-
cation [25c] of the Crich method and employs carboxybenzyl glycosides, which can
be activated using Tf
2
O/DTBMP with only phthalide as an inert by-product.
The trisaccharide synthesized in this manner (Scheme 12.6), containing one
b
- and
a
two
-linkages, was obtained in 50%overall yield as a mixture of anomers (8:1:1.3, in
favor of the desired products). This synthesis also featured the use of the novel
triisopropylsilyloxymethyl (Tom) group for the
O-
3 position of the donor, and release
from the polymeric support by cross-metathesis with ethylene [33].
b
BnO
OPiv
O
OBn
AcO
O
Ph
BnO
O
O
TomO
O
CCl
3
NH
OCB
O
OPiv
BnO
1. TMSOTf
PhMe/CH
2
Cl
2
1. Tf
2
O, DTBMP
CH
2
Cl
2
, -30°C
OBn
O
O
Ph
O
O
O
O
HO
BnO
HO
2. MeONa, 0°C
MeOH/CH
2
Cl
2
2. TBAF, THF
O
OBn
O
Ph
O
CO
2
H
O
BnO
CB =
Tom =
OCB
OTIPS
1. Tf
2
O, DTBMP
CH
2
Cl
2
, -30°C
2. Grubb
s catalyst
Ethylene, CH
2
Cl
2
′
BnO
OPiv
OBn
OBn
O
O
Ph
Ph
O
O
O
O
O
O
O
BnO
BnO
O
SCHEME 12.6
Polymer-supported synthesis of
b
- mannosides by Seeberger and coworkers.
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