Biomedical Engineering Reference
In-Depth Information
C
8
H
17
1. BSP, TTBP, Tf
2
O
CH
2
Cl
2
, -60°C
B
OBn
O
B
OBn
O
O
O
O
O
BnO
O
2. 3
β
-Cholestanol
BnO
SPh
C
8
H
17
Acetone/H
2
O
78%
O
S
B
OBn
BSP =
N
O
O
O
O
BnO
β/α
> 9/1
SCHEME 12.7
Polymer-supported synthesis of
b
-mannosides by Crich and Smith.
-mannosides was first achieved by Crich and
Smith, who investigated 4,6-
O-
polystyrylboronate group as a combined surrogate for
the benzylidene acetal and linker to the resin [35] (Scheme 12.7). Activation of the
bound thioglycoside was achieved with their BSP/Tf
2
O/TTBP mixture, followed
by the addition of the acceptor alcohol [23b]. The final product was released from
the resin by heating in aqueous acetone to give high selectivity on
Polymer-supported synthesis of
b
b
-mannosides with
good yields.
12.2.1.3.
Linear Versus Block Synthesis of an Alternating
-(1
!
4)-
b
3)-Mannan
The synthesis of complex oligosaccharides typically imposes
a strategic choice between linear and block routes [36]. In a rare effort at comparison,
Crich and coworkers described both linear and block syntheses of a complex antigenic
mannan from
Rhodotorula glutinis
,
Rhodotorula mucilaginosa
, and
Leptospira
biflexa
[37], in which synthetic challenge was a consequence of the
-(1
!
b
-mannoside
linkages and the need for alternating glycosyl donors with necessarily orthogonal
protection at positions 3 and 4. In the linear synthesis (Scheme 12.8), the first glycosyl
donor, protected in the form of a standard 4,6-
O-
benzylidene acetal, carried a
3-
O-p-
methoxybenzyl ether selectively cleavable with DDQ, while the second donor
bore a 4,6-
O-p-
methoxyphenylene acetal that could be transformed in a second step
to the corresponding 6-
O-
benzyl ether with a free OH at the 4-position. Iterative
deprotection/glycosylations with the same two glycosyl donors eventually led to
the targeted fully protected hexasaccharide. Selectivities and yields remained good
throughout the sequence.
For the convergent approach (Scheme 12.9), the target was dissected into two
trisaccharides, each of which could potentially be assembled from a common
disaccharide, thereby reducing the overall number of steps significantly. The success
of this pivotal disaccharide, in which the acceptor itself is a thioglycoside, is a func-
tion of the prior activation of the donor before addition of the acceptor, a standard
feature of the direct
b
-mannosylation protocol. Following a series of selective
deprotection/reprotection sequences, the so-assembled disaccharide was converted
to both a trisaccharide donor and an acceptor, ready for assembly into the target
hexasaccharide. In the final step of this convergent synthesis, the two trisaccharides
were combined by the BSP protocol to give a
b
-hexasaccharide and its
-anomer, in
b
a
35% and 53% yields, respectively, with a
/
ratio of 1:1.5. Although the selectivity
b
a
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