Chemistry Reference
In-Depth Information
Info Box 2
Sucrose, normal table sugar, which plants can make tons of, is very diffi cult to synthesize
chemically. When looking at the structure (below) one can realize why - sucrose is a nonre-
ducing sugar where the anomeric positions of an
- fructofuranosyl
are linked together. Thus, when performing the glycosylation the stereoconfi gurations in
both the anomeric positions have to be controlled and they are both 1,2-
cis
- linkages! The fi rst
chemical synthesis of sucrose was reported by R.U. Lemieux and G. Huber in 1953. Their
synthesis gave a mixture of all anomers and the yield of sucrose in the coupling was only
5%. The solution to a stereoselective synthesis of sucrose came almost 50 years later, when
a
α
- glucopyranosyl and a
β
-directing fructofuranosyl donor was developed by Oscarson and Seghelmeble. This thio-
glycoside donor contained a bridge, a silyl acetal, between the 1- and 4 - OH group. Since
the 4-OH group is on the
β
α
-side, this locked the anomeric CH
2
OH group in the
α
- position
allowing incoming acceptors to attack only from the
β
- side. As acceptor tetra -
O
- benzyl -
α
-
D
-
glycopyranose was selected, the pure
-anomer obtainable by crystallization. The DMTST-
promoted glycosylation afforded protected sucrose in 80% yield, which could be deprotected
to give sucrose.
α
.
The general way to synthesize these types of glycosides is the same as discussed
for
-
D
- glucopyranosides and galactopyranosides - an optimization of the glycosyl-
ation conditions to obtain as high a
α
ratio as possible and then separate the
anomers (Figure 3.9). The type of donors is also the same, halide sugars and
thioglycosides being most frequently used. For NeuAc glycosides conditions often
can be found which afford high yields and stereoselectivity [4], but with Kdo this
is often still a problem [5]. Therefore, methods have been developed to try to deal
with this problem.
These methodologies involve the use of a temporary participating group to
control the stereoselectivity in the glycosylation - a group which is then removed
to give the natural deoxy function. This temporary participating group is generally
a halide (bromine or iodine) or a selenium or thio ether and can be introduced
in situ
if the glycal is used as donor (Figure 3.10). The participating group is
preferably introduced on the
α
/
β
β
-side, allowing acceptor attack only from the
α
- side,
