A Double Diastereoselective Michael-Type Addition as an Entry to Conformationally Restricted Tn Antigen Mimics

A totally stereocontrolled C-Michael addition
of serine-equivalent C-nucleophiles to tri-O-benzyl-2-nitro-d-galactal was used as the key
step to synthesize several pyrano­[3,2-b]­pyrrole structures.
These scaffolds could be regarded as conformationally restricted Tn
antigen mimics, as we have demonstrated by biological assays. The
pyranose rings retain their 4C1 chair conformation,
as shown by molecular modeling and NMR spectroscopy. The expected
bioactivity was established by a competition-tailored enzyme-linked
lectin assay using both soybean and Vicia villosa agglutinins as model lectins. The facile described synthetic route
and the strategic combination of computational and experimental techniques
to reveal conformational features and bioactivity demonstrate the
prepared glycomimics to be promising candidates for further exploitation
of this scaffold to give glycans for lectin blocking and vaccination.