Thiol-ene "Click" Synthesis and Pharmacological Evaluation of C-Glycoside sp2-Iminosugar Glycolipids
AbstractThe unique stereoelectronic properties of sp2-iminosugars enable their participation in glycosylation reactions, thereby behaving as true carbohydrate chemical mimics. Among sp2-iminosugar conjugates, the sp2-iminosugar glycolipids (sp2-IGLs) have shown a variety of interesting pharmacological properties ranging from glycosidase inhibition to antiproliferative, antiparasitic, and anti-inflammatory activities. Developing strategies compatible with molecular diversity-oriented strategies for structure–activity relationship studies was therefore highly wanted. Here we show that a reaction sequence consisting in stereoselective C-allylation followed by thiol-ene “click” coupling provides a very convenient access to α-C-glycoside sp2-IGLs. Both the glycone moiety and the aglycone tail can be modified by using sp2-iminosugar precursors with different configurational profiles (d-gluco or d-galacto in this work) and varied thiols, as well as by oxidation of the sulfide adducts (to the corresponding sulfones in this work). A series of derivatives was prepared in this manner and their glycosidase inhibitory, antiproliferative and antileishmanial activities were evaluated in different settings. The results confirm that the inhibition of glycosidases, particularly α-glucosidase, and the antitumor/leishmanicidal activities are unrelated. The data are also consistent with the two later activities arising from the ability of the sp2-IGLs to interfere in the immune system response in a cell line and cell context dependent manner. View Full-Text
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Sánchez-Fernández, E.M.; García-Moreno, M.I.; García-Hernández, R.; Padrón, J.M.; García Fernández, J.M.; Gamarro, F.; Ortiz Mellet, C. Thiol-ene "Click" Synthesis and Pharmacological Evaluation of C-Glycoside sp2-Iminosugar Glycolipids. Molecules 2019, 24, 2882.
Sánchez-Fernández EM, García-Moreno MI, García-Hernández R, Padrón JM, García Fernández JM, Gamarro F, Ortiz Mellet C. Thiol-ene "Click" Synthesis and Pharmacological Evaluation of C-Glycoside sp2-Iminosugar Glycolipids. Molecules. 2019; 24(16):2882.Chicago/Turabian Style
Sánchez-Fernández, Elena M.; García-Moreno, M. I.; García-Hernández, Raquel; Padrón, José M.; García Fernández, José M.; Gamarro, Francisco; Ortiz Mellet, Carmen. 2019. "Thiol-ene "Click" Synthesis and Pharmacological Evaluation of C-Glycoside sp2-Iminosugar Glycolipids." Molecules 24, no. 16: 2882.
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