Chemistry Reference
In-Depth Information
on the protecting group pattern allowed, so most often it is easier to use different
types of donors in these orthogonal glycosylations and in the build-up of the dif-
ferent blocks. Still, thioglycosides can be used as the sole precursors since they
are easily transformed into halide donors or trichloroacetimidate donors under
mild conditions.
3.8
Protecting Group Manipulations
Without the help of the glycosyltransferases, apart from the problem with stereo-
selectivity we also have to address the problem of regioselectivity. How do we allow
only one of the many hydroxyl groups present in the acceptor and in the donor
saccharides to react with the anomeric position of the donor to form the new gly-
cosidic bond? This problem is solved by protecting all the other hydroxyl groups.
A major part of carbohydrate chemistry is therefore involved with protective group
manipulations - both the introduction of protective groups as well as their removal
[6] .
In spite of the fact that it is more or less only hydroxyl protecting groups that have
to be considered, often several different types of protecting groups have to be uti-
lized. This is partly due to the fact that we want different protecting group patterns
to get different reactivities, as discussed above, but also because if larger structures
than a disaccharide are to be synthesized, two types of protecting groups are
required - persistent (permanent) ones that will remain until the very last deprotec-
tion step(s) and temporary ones that will be removed somewhere along the synthetic
pathway to expose a new hydroxyl group allowing another glycosylation reaction
(please compare Figure 3.1). Obviously, these types of protecting groups have to be
what is called orthogonal, that is, that they can be removed in the presence of each
other (compare defi nition of orthogonal glycosylations in Section 3.7).
By far the most used hydroxyl protecting groups, which can be used both as
temporary and permanent ones, are acetyl, benzoyl and benzyl groups, all of which
are easy to introduce and also to remove even at multiple positions. In addition,
there are various other groups that can be used as temporary protecting groups,
being effi ciently introduced at one or a few positions and also selectively cleaved
when desired (examples are silyl, chloroacetyl,
p
- methoxybenzyl and various acetal
groups).
3.9
An Example
With all this knowledge in hand, let us now apply them to a real case - the synthesis
of the Le
b
hexasaccharide (Figure 3.12; please see Chapter 17.1.2.1 for information
on its role as docking points for infections with
Helicobacter pylori
causing gastric
ulcers; its availability has a therapeutic perspective, especially when presented as
clusters: please see next chapter for design of glycoclusters) [7]. Of the six glyco-
