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Open AccessArticle

Thiol-ene "Click" Synthesis and Pharmacological Evaluation of C-Glycoside sp2-Iminosugar Glycolipids

Department of Organic Chemistry, Faculty of Chemistry, University of Seville, C/Profesor García González 1, 41012 Seville, Spain
Instituto de Parasitología y Biomedicina “López-Neyra”, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, 18016 Granada, Spain
BioLab, Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Centro de Investigaciones Biomédicas de Canarias (CIBCAN), Universidad de La Laguna, 38206 La Laguna, Spain
Instituto de Investigaciones Químicas (IIQ), CSIC - University of Sevilla, Avda. Américo Vespucio 49, 41092 Sevilla, Spain
Authors to whom correspondence should be addressed.
Academic Editors: David Díez and María Ángeles Castro
Molecules 2019, 24(16), 2882;
Received: 22 July 2019 / Revised: 5 August 2019 / Accepted: 7 August 2019 / Published: 8 August 2019
(This article belongs to the Special Issue Application of Organic Synthesis to Bioactive Compounds)
PDF [1434 KB, uploaded 12 August 2019]


The 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
Keywords: sp2-Iminosugars; C-glycosides; glycolipids; glycomimetics; glycosidase inhibitors; Leishmaniasis; cancer sp2-Iminosugars; C-glycosides; glycolipids; glycomimetics; glycosidase inhibitors; Leishmaniasis; cancer

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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.

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