Chemistry Reference
In-Depth Information
As always, there are both advantages and disadvantages with either approach
(Table 3.1 ).
At fi rst, the linear strategy was almost the only possible choice, since there were
few stable block donors available. However, with the development of new types of
stable building block donors, convergent syntheses could be considered and they
nowadays are often the strategy of choice. The convergent approach is especially
attractive if there are repeated motifs in the target structure, which could then be
introduced simultaneously using the same donor block.
To be able to design a proper strategy, knowledge about various methodologies
to prepare the glycosidic bonds and also the ability to identify different types of
glycosidic linkages and their inherent diffi culty of formation are essential. The
next section will address these issues.
Table 3.1
Advantages and disadvantages of linear and convergent (block) synthesis.
Advantages
Disadvantages
Linear synthesis
Only (most often easily
available) monosaccharide
donors are used
Many manipulations on large
structures
No
orthogonal
glycosyla-
No choice in the formation se-
quence of the glycosidic link-
ages
a
necessary
tions
Orthogonal glycosylations
a
of-
ten needed
Convergent (block) synthesis
Most of the manipulations
are performed on smaller
structures
' Diffi cult ' glycosylations can
be performed early
Block donors not always stable
a
For information on orthogonal glycosylations please see Chapter 3.7 .
3.2
Glycosidic Bond Formation
Fundamentally, the chemist's way to synthesize a glycoside is not that different
from Nature's own way. In Nature, a glycosyl donor (so called because it donates
a glycosyl moiety), a nucleotide sugar such as UDP-Glc, with a good leaving group
(a pyrophosphate) in the anomeric position, reacts, in the presence of a glycosyl-
transferase, to exchange the leaving group with the free hydroxyl group of an
acceptor to form the product glycosidic linkage. In the chemical laboratory we also
follow this strategy and use glycosyl donors containing an anomeric leaving group
and acceptors with a free hydroxyl group to create the glycosidic linkage in a
manner similar to Nature's own way (Figure 3.2). However, since we do not have
