Chemistry Reference
In-Depth Information
available monosaccharides (
D
- Glc,
D
- Gal,
D
- Man,
D
- GlcA,
D
- GlcNAc,
D
- GalNAc,
L
-Fuc, and Neu5Ac, please see Chapter 1;
L
-IdoA, however, found in heparin and
heparan sulfate is not; for details of these proteoglycans, please see Chapter 11 ;
for biological relevance of IdoA, please see Chapter 1.3). Bacterial structures, in
contrast, often include rare monosaccharides (for example Kdo) that have to be
synthesized from commercially available precursors before being used in oligosac-
charide synthesis, which severely complicates these syntheses. When designing
the building blocks a decision has to be made about what type of donors should
be targeted. If a trichloroacetimidate donor is chosen, then the reducing end ano-
meric position has to be protected with a protecting group that eventually can be
removed selectively to free this anomeric position and allow the formation of the
trichloroacetamidate. If a thioglycoside or pentenyl donor block is chosen, then
this function is usually introduced at the anomeric position at the very beginning
of the block synthesis, since it is stable to most protecting group manipulations
as well as to many glycosylation conditions. Hence, a thioglycoside, containing a
free hydroxyl group, can function as an acceptor if proper donors and reaction
conditions are used. Since the thioglycoside itself is also a potential donor this is
often described as orthogonal coupling (only one of the two possible donors is
activated). Promoters used for the activation of halide donors (silver or mercury
salts) and trichloroacetimidate donors (TMS- trifl ate or BF
3
- etherate) normally do
not activate thioglycosides, and can therefore be used in the building up of thio-
glycoside blocks.
Protecting groups not only protect but confer different reactivity to the protected
derivative. Both in a donor and in an acceptor, electron- withdrawing protecting groups
(that is, acyl groups, acetates and benzoates) decrease the reactivity, whereas electron-
donating groups (that is, ether groups like benzyls) increase the reactivity. This intro-
duced reactivity difference can be large enough to facilitate glycosylation reactions
between the same type of glycoside donors, but differently protected (Figure 3.11 ).
Hence, a benzylated thioglycoside can be activated using a rather weak promoter
and used as a donor, whereas a benzoylated thioglycoside can be inert under these
conditions and used as an acceptor, allowing the construction of a thioglycoside
disaccharide, which in turn subsequently can be activated by a stronger promoter
and used as a donor. This is quite elegant, but it also puts a number of restrictions
Figure 3.11
Use of the ' armed - disarmed ' approach in orthogonal glycoside synthesis.
