Biomedical Engineering Reference
In-Depth Information
t
-Bu
O
Si
t
-Bu
OBn
O
BnO
O
O
Si
O
O
OH
O
O
t
-Bu
t
-Bu
O
O
STol
O
t
-Bu
t
-Bu
t
-Bu
t
-Bu
Si
Si
OBz
NIS, AgOTf
CH
2
Cl
2
, -30°C
OBz
O
O
O
O
O
O
Ara
f
22
domain of
microbacterial AG
70%
t
-Bu
O
t
-Bu
O
OPMP
O
OPMP
O
Si
Si
t
-Bu
t
-Bu
O
O
O
O
OH
O
BnO
O
O
t
-Bu
t
-Bu
Si
O
SCHEME 12.47
Application to the synthesis of the Araf
22
domain of
M. tuberculosis
.
The
E
3
conformer of the oxcarbenium ion places C5 and
O-
3 in pseudoequa-
torial orientations, resulting in a perfect chair conformation of 3,5-
O-
di-
tert
-butyl-
silane protecting group. In contrast, in the alternative
3
E
conformation, the fused ring
is distorted from the chair conformation, inducing considerable ring strain. Overall,
the
-approach on the
E
3
conformer is more favorable because it encounters only
staggered substituents.
In a demonstration of progress in the area, Lowary and coworkers synthesized
the docosanasaccharide arabinan domain chain, containing 22
D
-arabinofuranose
residues [131], which was identified in the cell wall of
M. tuberculosis
(Scheme 12.47).
The arabinan domain contains four
b
-linked bonds created efficiently using 3,5-
O-
di-
tert
-butylsilane protecting group as stereodirecting agent. The reaction of a
thioglycosyl donor with a trisaccharide acceptor presenting two free alcohols gave
a pentasaccharide in 70% yield with complete
b
-selectivity. The latter was further
engaged in the total synthesis of the full Araf
22
domain of the arabinan.
b
12.7.2.
-Selective Donors with Acyclic Protecting Groups
Standing out from the various approaches with cyclic protecting groups, and in con-
trast to earlier reports in the literature, Lowary and coworkers and Kim and coworkers
described a series of highly
b
-selective arabinofuranosylations (Scheme 12.48)
by employing a simple perbenzylated donor that enabled them to prepare the key
b
OBn
OBn
OH
NIS, AgOTf
CH
2
Cl
2
, -78°C
BnO
BnO
O
BnO
BnO
O
O
O
BnO
OMe
STol
O
73%
OBn
OBn
OMe
Lowary and coworkers
OBn
OBn
OBn
OH
Tf
2
O, DTBMP
CH
2
Cl
2
, -78°C
BnO
BzO
O
O
O
BnO
BnO
O
O
BzO
OMe
90%
O
OBn
OBz
CO
2
H
OMe
Kim and coworkers
OBz
= 1:20
SCHEME 12.48
b
-Selective arabinofuranosylations using donors without cyclic protection.
α/β
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