Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist







Alice Tamburrini, Silvia Achilli, Francesca Vasile, Sara Sattin, Corinne Vivès, Cinzia Colombo,
Franck Fieschi, Anna Bernardi

Bioorganic & Medicinal Chemistry 25 (2017) 5142–5147


The synthesis and conformational analysis of pseudo-thio-1,2-dimannoside are described. This molecule
mimics mannobioside (Mana(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected
increased stability to enzymatic hydrolysis. A short and efficient synthesis was developed based on an
epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate.
NMR-NOESY studies supported by MM3⁄ calculations showed that the pseudo-thio-1,2-dimannoside
shares the conformational behavior of the pseudo-1,2-dimannoside and is a structural mimic of
the natural disaccharide. Its affinity for DC-SIGN was measured by SPR and found to be comparable to
the corresponding O-linked analog, offering good opportunities for further developments.