Chemistry Reference
In-Depth Information
been reviewed elsewhere.
2
Additionally, as phosphate linkages are not
present in GAG, we do not include oligosaccharides containing this
glycosidic bond in this review. GAG containing phosphated positions are
also not described along these lines due to their particular behaviours
and unusual synthetic strategies.
2 Synthesis
2.1 Carboxylic acid-containing oligosaccharides
The synthesis of uronic acid containing oligosaccharides requires the
preparation of uronic acids precursors to be used as donors and/or
acceptors in glycosylation reactions or alternatively follows a post-
glycosylation oxidation strategy, from oligosaccharides containing glycosyl
units with a free primary hydroxyl group which can be oxidized selectively.
Uronates donors are particularly challenging because the reactivity at
the anomeric position is decreased by the presence of the C-5 carboxylic
group. Different methodologies have been investigated in order to over-
come this drawback and to develop general strategies allowing the syn-
thesis of oligosaccharides of biological importance in a regio- and
stereoselective manner.
3,4
To overcome the poor reactivity or the lack of
selectivity of some uronic acids, these latters have been used as acceptors
rather than donors in the synthesis of oligosaccharides. Usual conditions
used for glycosylations will not be reported here.
5-8
Uronic acids esters can be activated as imidates, bromides or thio-
phenyl glycosides among others. Imidate donors are the most common
activating groups for the synthesis of di- and oligosaccharides. As an
example the synthesis of the putative prion-associated HS tetrasaccharide
containing two
D
-glucuronic acid units with b-
D
-GlcA-(1
4)-
D
-GlcNAc
sequences was reported
9
for the preparation of libraries of GAG. The
synthesis of a disaccharide intermediate 3 was realized from 2-O-benzoyl-
protected
D
-glucuronate imidate 1 and 2-azido-1-thiophenyl acceptor 2,
using TMSOTf as promotor for glycosylation in 89% yield, see Scheme 1.
The disaccharide thioglycoside 3 was then coupled to a disaccharide
acceptor 4 and the corresponding tetrasaccharide 5 was isolated in 56%
yield.
-
OBn
OBn
CO
2
tBu
CO
2
tBu
TMSOTf
O
O
O
Bn
BnO
HO
BnO
BnO
BnO
SPh
O
+
BnO
SPh
Tolu ene, -30 °C
89%
BzO
N
3
BzO
N
3
O
CCl
3
1
2
3
NH
OBn
CO
2
tBu
DMTST
Et
2
O, CH
2
Cl
2
56%
O
H
BnO
O
BnO
BzO
AcHN
4
OMe
OBn
CO
2
tBu
CO
2
tBu
OBn
O
Bn
BnO
O
O
BnO
O
BnO
O
O
BnO
BzO
N
3
BzO
AcHN
OMe
5
Scheme 1
Search WWH ::
Custom Search