Welcome to SINTCARB! 

Our group aim to provide new answers to some classical problems in connection with the synthesis of oligosaccharides and glycosides and intend also to provide efficient methods for the synthesis of sphingosines, glycosphingolipids and glycoclusters, and tackle a biologically oriented research. In this sense the SINTCARB group has a broad experience in carbohydrate chemistry and also in transition metal catalyzed reactions and asymmetric catalysis.

 

Structure-Based Design of Potent Tumor-Associated Antigens:

Modulation of Peptide Presentation by Single-Atom O/S or O/Se Substitutions at the Glycosidic Linkage.

Ismael Compan, Ana Guerreiro, Vincenzo Mangini, Jorge Castro-Lopez, Margarita Escudero-Casao, Alberto Avenoza, Jesus H. Busto, Sergio Castillón, Jesús Jiménez-Barbero, Juan L. Asensio, Gonzalo Jimenerz- Oses, Omar Boutureira, Jesus M. Peregrina, Ramón Hurtado-Guerrero, Roberto Fiammengo, Gonçalo J. L. Bernardes, Francisco Corzana.
J. Am. Chem. Soc.
2019, 141, 4063−4072

 

 Herein, we propose a new strategy for designing potent antigen mimics by means of O → S/Se replacement at the glycosidic linkage. These minimal chemical modifications increase the carbohydrate–peptide distance and change the orientation and dynamics of the glycosidic linkage. As a result, the peptide acquires a preorganized and optimal structure suited for antibody binding. Accordingly, these new glycopeptides display improved binding toward a representative anti-MUC1 antibody relative to the native antigens. The derivative bearing the S-glycosidic linkage was conjugated to gold nanoparticles and tested as an immunogenic formulation in mice without any adjuvant, which resulted in a significant humoral immune response. Importantly, the mice antisera recognize cancer cells in biopsies of breast cancer patients with high selectivity. This finding demonstrates that the antibodies elicited against the mimetic antigen indeed recognize the naturally occurring antigen in its physiological context.

 

   

Trifluoromethylation of Electron-Rich Alkenyl Iodides with Fluoroform-Derived "Ligandless" CuCF3

J. Mestre, A. Lishchynsky, S. Castillón, O. Boutureira
J. Org. Chem. 2018, 83, 8150-8160.

We herein present a flexible approach for the incorporation of CF3 units into a predefined site of electron-rich alkenes that exploits the regiocontrolled introduction of an iodine handle and subsequent trifluoromethylation of the C(sp2)–I bond using fluoroform-derived “ligandless” CuCF3. The broad substrate scope and functional group tolerance together with the scalability and purity of the resulting products enabled the controlled, late-stage synthesis of single regioisomers of complex CF3-scaffolds, such as sugars, nucleosides (antivirals), and heterocycles (indoles and chromones), with potential for academic and industrial applications.

   

Fluorinated triazole-containing sphingosine analogues.

Syntheses and in vitro evaluation as SPHK inhibitors

M. Escudero-Casao, A. Cardona, R. Beltrán-Debón, Y. Díaz, M. Isabel Matheu, S. Castillón
Org. Biomol. Chem. 2018, 16, 7230-7235.

Sphingosine analogues with a rigid triazole moiety in the aliphatic chain and systematic modifications in the polar head and different degrees of fluorination at the terminus of the alkylic chain were synthesized from a common alkynyl aziridine key synthon. This key synthon was obtained by enantioselective organocatalyzed aziridination and it was subsequently ring opened in a regioselective manner in acidic medium. Up to 16 sphingosine analogues were prepared in a straightforward manner. The in vitro activity of the obtained products as SPHK1 and SPHK2 inhibitors was evaluated, displaying comparable activity to that of DMS.

   

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