Chemistry Reference
In-Depth Information
requirements of a glycosyl donor, and especially of its anomeric leaving group, are
that it should be easy to prepare and be stable until it is intentionally activated by
a promoter.
The traditional donors are the halide sugars, especially the bromides and chlo-
rides, which have been used for more than a century.
Advantages
(i) They are easily prepared in large amounts.
(ii) They are effi ciently activated by a number of promoters, mainly heavy atom
(Hg
2+
, Ag
+
) salts.
Disadvantages
(i)
The conditions under which they are prepared are usually quite strongly
acidic (HBr/HOAc). This allows more or less only acyl protecting groups
(acetates and benzoates) and smaller donors, since glycosidic linkages might
be cleaved.
(ii) Stoichiometric amounts of promoter are needed, which might be expensive
(silver salts) and not environmentally friendly (mercury salts).
(iii) They are quite labile and have to be prepared just before the glycosylation
reaction is performed.
The trichloroacetimidate donors have some of the drawbacks of the halide
sugars, but also a number of advantages in comparison.
Advantages
(i)
The preparation of the trichloroacetimidates is performed under mild basic
conditions, allowing almost any type of protecting group pattern and glyco-
sidic linkages in the donor molecule.
(ii) The activation, using simple hard acids, typically BF
3
- etherate or TMS - trifl ate
(trimethylsilyl trifl uoromethylsulfonate), requires only catalytic amount of the
promoter - a quite unique feature among frequently used glycosyl donors.
(iii) They can, under optimized conditions, be activated to allow the glycosylation
to proceed via a direct displacement mechanism (Figure 3.2 , fi rst mecha-
nism). Since they can be prepared either as the
- imidate, by using
different basic conditions, this allows one way to control stereoselectivity.
α
- or the
β
Disadvantages
(i) They are still rather labile and have to be prepared more or less immediately
before the glycosylation reaction is performed, which, thus, require some
temporary protection of the anomeric position up until the introduction of the
trichloroacetimidate function.
