Antibacterial and antifungal vaccines based on synthetic oligosaccharides - Carbohydrate Chemistry: Chemical and Biological Approaches - page 584

Scheme 15

layers of B. anthracis spores is a glycoprotein exposing multiple copies of
a tetrasaccharide that includes an unusual monosaccharide termed
anthrose at its nonreducing end bearing a hydroxy-methyl-butyric acid
side chain. 157 This tetrasaccharide is unique to B. anthracis, as it is not
found even in closely related species, and therefore has become a target
for vaccine development (Scheme 15).
Two syntheses have been reported in studies of this tetrasaccharide.
The first complete syntheses were published in 2005 158 followed by sec-
ond, stepwise elongation strategy to the B. anthracis spacer-arm tetra-
saccharide 44. 159 An improved and shorter route to the target
tetrasaccharide was based on a convergent [2 þ 2] assembly. 160 44-KLH
conjugates elicited specific antibodies that recognize B. anthracis endo-
spores. 161 A panel of anthrose N-acyl-substituted trisaccharides was
synthesized and conjugated to proteins for study recognition of antisera
raised against live or irradiated spores of B. anthracis. As a result, critical
structural elements for the antigenicity of the oligosaccharide epitope
were defined within the anthrose moiety. 162
In addition to the anthrax carbohydrate present on the surface of
spores described above, the structure of the secondary cell wall poly-
saccharide of B. anthracis vegetative cells consists of hexasaccharide
repeating units having unusual b-linked N-acetylmannosamine 45. 163
The two corresponding synthetic trisaccharides were recognized by the
sera from rabbits exposed to spores of B. anthracis. 164 The first total
synthesis of the hexasaccharide repeating unit was accomplished

recently. 165