Biomedical Engineering Reference
In-Depth Information
t
-Bu
Si
O
t
-Bu
O
O
BzO
t
-Bu
BzO
Si
O
1. TBAF
2. Bz
2
O, DMAP, pyridin e
3. MeONa, MeOH
t
-Bu
O
CCl
3
NH
OH
O
HO
TMSOTf
AW-300
O
O
O
BzO
O
HO
BzO
HO
HN
C
17
H
35
HN
C
17
H
35
82%
CH
2
Cl
2
, 0°C
60%
O
O
C
13
H
27
O
C
13
H
27
HN
C
17
H
35
OBz
OH
HO
C
13
H
27
α
-GalCer
OBz
SCHEME 12.26
Synthesis of an
a
-galactosyl ceramide by Kiso and coworkers.
Ph
O
O
O
RO
RO
OR'
SCHEME 12.27
Stereoelectronic effects in 4,6-
O-
benzylidene-protected galactosides.
A 4,6-
O-
bis(
tert
-butylsilylene) acetal, as described by Kiso and coworkers [88],
is also highly directing in the galactopyranose series, even to the extent that its
influence overcomes that of a normally participating group at the 2-position [88b].
Among other targets, Kiso and coworkers described the synthesis of
a
-galactosyl
ceramides (
-GalCer) that are recognized by a T-cell antigen receptor on the surface of
an NKT [88b]. Such recognition results in the stimulation of NKT cells, which are
essential not only for the defense against pathogens, but also for the initiation and
regulation of immune responses [89]. InKiso's synthesis, glycosylationwas performed
on the silylene-protected donor (Scheme 12.26) and furnished the protected target as a
single
a
-isomer in 60% yield.
Although the effect of 4,6-
O-
acetals in the galactopyranose series, whether of
the benzylidene or of the silylene class, has been ascribed to steric shielding of the
b
a
-face of the galactopyranosyl cation by the acetal [88b,90], it would appear that a
significant contributing factor must simply be the locking of the C5-C6 bond in the
gauche-gauche (gg) conformation. In effect, because of the presence of the acetal, the
stereoelectronic relationship of the C6-O6 bond to the pyranose ring oxygen is
identical to the relationship of the latter with the C4-O4 bond in the galactose effect
(see above); therefore, it must facilitate formation of the galactopyranosyl cation and
result in looser ion pairs (Scheme 12.27).
12.4.3. Boons' Participation Method
Boons and coworkers developed an elegant method [91] that relies on the participa-
tion of a phenyl-2-(phenylsulfanyl)ethyl moiety at C2 of the glycosyl donor
(Scheme 12.28). Upon formation of the oxocarbenium ion, the nucleophilic sulfur
intervenes so as to form a
trans
-or
cis
-decalin-like system. The
trans
system is
favored due to the equatorial position of the phenyl group. The acceptor then displaces
the sulfonium ion to give 1,2-
cis
-axial glycoside. The so-formed disaccharyl
thioglycoside was engaged in a further glycosylation step to afford a protected
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