Biomedical Engineering Reference
In-Depth Information
12.3.
1,2-trans-EQUATORIAL LINKAGES
While
-glucopyranoside and other 1,2-
trans
-equatorial glycopyranosides can be
routinely accessed through the use of neighboring group participation, the dual
imperatives of greater efficiency and maneuverability necessitate the development
of alternative routes. One of themost reliable of thesemethods involves the use of ether
protecting groups for
O-
2 of the donor and acetonitrile as solvent or at least
as a component thereof [56]. This method, which also functions in the synthesis of
2-azido-2-deoxy-
b
-glycopyranosides [57], is considered on the basis of trapping
experiments to involve solvent participation in the form of an
b
-nitrilium ion even
if such a species has yet to be detected spectroscopically [56d,57,58]. When tem-
peratures lower than
a
40
C accessible with acetonitrile are required, propionitrile
rises to the occasion [14a,56b]. Intriguingly, however, the method is not applicable to
the synthesis of
-nitri-
lium ion shows an increased propensity to take part in Ritter-type reactions with the
glycosyl acceptor [59].
-manno- and
-rhamnopyranosides when the intermediate
b
b
a
12.3.1. The Globo-H Polysaccharide
Globo-H (Scheme 12.16) is a hexasaccharide of the GSL family, a series of antigenic
carbohydrates that are highly expressed as glycolipids and possibly as glycoprotein on
the cell surfaces of various types of cancers, especially those of the breast, prostate,
and lung [60]. Consequently, it is an attractive target for synthesis that has received
considerable attention from many groups. Here, it serves to illustrate the different
strategies for the construction of
-gluco- and galactopyranosyl linkages.
b
12.3.2. Nitrile Effect
The nitrile-directing effect is illustrated by the Boons approach to globo-H [61],
in which the application of one donor preglycosylated at the 2-position obviated
the use of neighboring group participation and a further disaccharide donor carried a
2-
O-
benzyl ether, enabling the avoidance of a saponification step later in the synthesis
(Scheme 12.17). Boons' synthesis also takes advantage of the othogonality of the
glycosyl fluorides with conditions for the activation and coupling of thioglycosides.
In this manner, as expounded by Nicolaou and Ueno [62] and others [63], a
hydroxyglycosyl fluoride serves as an acceptor alcohol in the first glycoside bond
forming step, giving directly a trisaccharyl donor ready for use in a subsequent
coupling reaction without the need for intermediate adjustment of functionality.
OH
OH
HO
HO
OH
HO
O
O
O
O
O
HO
O
NHAc
O
HO
O
OH
OH
HN
C
18
H
37
O
HO
OH
O
OH
OH
O
O
O
C
13
H
27
HO
HO
OH
OH
SCHEME 12.16
Globo-H antigenic glycosphingolipid.
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