Biomedical Engineering Reference
In-Depth Information
The counter-thermodynamic nature of this radical fragmentation, as explained by
Roberts and coworkers, derives from the strain induced in the transition state for the
competing fragmentation of C4-O4 bond due to the recoil of C4 and its rehybridiza-
tion from sp
3
to sp
2
as the bond cleaves [49].
This sequence of reactions was employed in the synthesis of the tetrasaccha-
ride repeating unit from the lipopolysaccharide from
Escherichia hermanii
ATCC
33650, which contains a novel sequence of a
-
D
-rhamnopyranoside linked to a
b
-linkage was
installed in the now classical manner of the acetal-directed mannosylation, while that
of the
-
D
-rhamnopyranoside [51]. In this synthesis (Scheme 12.13), the
a
b
-directing effect of a carboxylate ester at the 3-
O-
position to overcome the influence of the acetal. This latter effect, for which
arguments have been advanced both in favor of [6a] and against neighboring group
participation [8a], is a powerful one and brings about a complete change of selectivity
in the mannopyranose series.
After removal of the chloroacetate group from the trisaccharides, double
application of the radical fragmentation sequence in a one-pot fashion provided the
two rhamnopyranosyl moieties. The final galactopyranoside unit was installed with a
4,6-
O-
benzylidene-protected galactosyl donor with excellent
-linkage relied on the
a
a
a
-selectivity (see below).
I
I
I
O
S
O
S
O
S
1. BSP, Tf
2
O, TTBP
CH
2
Cl
2
, -78°C
OBn
OBn
OBn
O
Ph
O
OBn
O
Ph
OBn
O
O
DDQ
83%
O
O
O
Ph
O
O
NAPO
OMe
O
O
NAPO
O
2.
OBn
BnO
OMe
HO
SPh
BnO
OBn
O
HO
OMe
OBn
I
BnO
OBn
Acceptor
92% (
α/β
= 7:85)
O
S
I
OBn
OBn
O
Ph
O
O
O
O
OMe
O
BnO
O
S
OBn
ClAcO
OBn
OBn
1. Ph
2
SO, Tf
2
O
TTBP, CH
2
Cl
2
, -78°C
O
OBn
O
O
Ph
BzO
O
O
O
Ph
1. H
2
NCH
2
CH
2
NH
2
(80%)
O
O
OBn
OMe
O
O
BnO
ClAcO
2.
Acceptor
75% (only
2. Bu
3
SnH, AIBN
PhMe, reflux (54%)
OBn
O
S
HO
SPh
α)
BzO
O
Acceptor 2
OBn
I
Ph
Ph
O
O
O
OBn
1. Tf
2
O, BSP, TTBP
CH
2
Cl
2
, -78°C
OBn
O
O
O
BnO
BzO
O
O
OBn
O
NAP =
BnO
OMe
SPh
O
BnO
BnO
2. Acceptor 2
64%
OBn
O
BzO
O
OBn
1. MeONa (66%)
2. H
2
, Pd(OH)
2
(88%)
OH
OH
OH
OH
O
HO
O
HO
O
HO
O
OMe
O
HO
OH
O
HO
O
OH
SCHEME 12.13
Synthesis of a tetrasaccharide from
E. hermanii
ATCC 33650 by Crich and
coworkers.
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