Biomedical Engineering Reference
In-Depth Information
BnO
OH
CO
2
Me
HO
BnO
OH
BnO
OAcCl
1. NIS/TfOH, MS 3 Å
CH
2
Cl
2
(86%)
O
HN
CO
2
Me
SPh
O
O
+
HO
ClAcO
O
2. Thiourea, 2,6-lutidine
DMF, 70°C (85%)
BnO
O
OC
8
H
17
CO
2
Me
HN
O
HN
CO
2
Me
O
O
HO
O
O
OC
8
H
17
O
HN
only
α
O
HO
OH
BnO
OAcCl
O
CO
2
H
CO
2
Me
HO
ClAcO
O
O
Glycosylation and
deprotection sequence
AcHN
HN
O
O
HO
O
BnO
HO
HO
CO
2
Me
CO
2
H
O
HO
O
O
AcHN
HN
Full deprotection
O
O
HO
O
HO
BnO
O
CO
2
H
CO
2
Me
HO
HO
O
O
AcHN
HN
O
O
O
HO
HO
BnO
HO
CO
2
H
CO
2
Me
O
HO
O
O
OC
8
H
17
OC
8
H
17
AcHN
HN
HO
O
O
SCHEME 12.33
Synthesis of an oligo-
a
-(2
!
8)-sialoside by the oxazolidinone strategy.
OAc
OAc
OAc
OAc
CO
2
Me
SAda
BnO
OBn
NIS/TfOH, -78°C
MeCN/CH
2
Cl
2
(1/2)
OBn
OBn
AcO
O
O
AcO
O
CO
2
Me
OMe
AcN
+
HO
O
AcN
O
O
OMe
O
89%
OBn
O
OBn
O
(α/β
= 4:1)
SCHEME 12.34
Use of Crich and Li's highly reactive adamantanyl thiosialoside donor.
This system had the added advantage that the oxazolidinone group could be removed
selectively under very mild conditions, leaving the
N
-acetyl group of the target in
place. A cyclic 5-
N
,7-
O-
oxazine-protected sialyl donor has also been investigated, but
it was found to be predominantly
-directing [109]. Most recently, extending the
concept further, a tricyclic donor carrying a 4-
O
,5-
N
-oxazolidinone moiety and a
5-
N
,6-
O-
silylene “acetal” developed by the Ito group has shown considerable promise
as an
b
-sialoside donor.
As is apparent from Boons and Demchenko's approach to Neu5Ac
a
9)
Neu5Ac synthesis (Scheme 12.35),
N
,
N
-deprotection of sialyl acceptors also conveys
(2
!
a
OH
OH
CO
2
Me
AcO
O
OTE
AcHN
OAc
OAc
A
AcO
CO
2
Me
NIS/TfOH
MS 3 Å
CH
2
Cl
2
, -40°C
AcO
O
Ac
2
N
AcO
O
OH
CO
2
Me
67%
AcO
O
OTE
AcHN
AcO
OAc
OAc
CO
2
Me
(α/β
= 2.0:1)
AcO
O
SMe
Ac
2
N
AcO
NIS/TfOH
MS 3 Å
CH
2
Cl
2
, -40°C
OAc
OAc
CO
2
Me
AcO
O
(TE = CH
2
CH
2
TMS)
Ac
2
N
AcO
O
OH
OH
CO
2
Me
OH
CO
2
Me
AcO
AcO
O
OTE
O
OTE
Ac
2
N
AcO
Ac
2
N
B
AcO
98%
(
α/β =
2.5:1)
Application of Boons and Demchenko's
N
,
N
0
-diacetyl-protected method.
SCHEME 12.35
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