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

Publication date: Available online 22 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Alice Tamburrini, Silvia Achilli, Francesca Vasile, Sara Sattin, Corinne Vivès, Cinzia Colombo, Franck Fieschi, Anna Bernardi
The synthesis and conformational analysis of pseudo-thio-1,2-dimannoside are described. This molecule mimics mannobioside (Manα(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 analogue, offering good opportunities for further developments.

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