Chemistry Reference
In-Depth Information
Assembly of the hexasaccharide
With the building blocks available, their connection can now be accomplished.
Two ways are possible:
(i)
The fucosyl linkages are formed fi rst (possible since halide-assisted glycosyl-
ation conditions are orthogonal to thioglycosides) to give a tetrasaccharide
donor, which is then coupled to the lactose acceptor
(ii) The LacNAc donor is fi rst coupled to the lactose acceptor to create a tetrasac-
charide acceptor into which the fucosyl moieties are then introduced.
Since neither of theses glycosylations would be considered as 'diffi cult ' , both
these potential approaches to the hexasaccharide are similar, but practically it was
found that the latter approach is the preferred one. Hence, activation of the LacNAc
thioglycoside with NIS/TfOH in the presence of the lactose acceptor afforded the
(1 - 3) -
-linked tetrasaccharide in high yield (Figure 3.15). Protecting group manipu-
lations then changed the
N
-phtalimido group into the target
N
- acetamido group.
Concomitant removal of the temporary acetyl protecting groups gave the trihy-
droxyl acceptor, which was
β
-difucosylated using the fucosyl donor and halide-
assisted conditions to yield the target hexasaccharide (Figure 3.16), again taking
advantage of the low reactivity of the axial 4
α
-hydroxyl group to perform a regiose-
lective glycosylation. Final deprotection, consisting of only one step (hydrogenoly-
sis), removed the benzyl protecting groups as well as reduced the azido group of
the spacer to yield an amino group ready for conjugation, afforded the target
hexasaccharide.
′
Figure 3.15
Synthesis of
N
- lactotetraose acceptor.
3.10
Conclusions
Regio - (polyhydroxy compounds) and stereo - (
- confi guration) selective issues
are encountered in oligosaccharide synthesis. The regioselectivity problem is
addressed by protecting all hydroxyl groups except the one in the acceptor used to
α
/
β
