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

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posted on 2013-11-01, 00:00 authored by Carlos Aydillo, Claudio D. Navo, Jesús H. Busto, Francisco Corzana, María M. Zurbano, Alberto Avenoza, Jesús M. Peregrina
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.