Stereoselective innovative synthesis and biological evaluation of new real carba analogues of minimal epitope Manα(1,2)Man as DC-SIGN inhibitors

Bordoni, Vittorio; Porkolab, Vanessa; Sattin, Sara; Thépaut, Michel; Frau, Ileana; Favero, Lucilla; Crotti, Paolo; Bernardi, Anna; Fieschi, Franck; Bussolo, Valeria Di

doi:10.1039/c6ra20401e

Cited by 15 publications

(8 citation statements)

References 32 publications

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“…As has been extensively reported [43,44,45], carbapyranose 1,2-epoxides with a β-manno configuration can be opened successfully by O - and N -nucleophiles with excellent regio- and stereoselectivity through a sterically and electronically favored 1,2-trans-diaxial process. Conversely, carbapyranose 1,2-epoxides with an α-gluco configuration do not give such a good result both in terms of regioselectivity and yields.…”

Section: Resultsmentioning

confidence: 76%

Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides

et al. 2019

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Carba analogues of biologically relevant natural carbohydrates are promising structures for the development of future drugs endowed with enhanced hydrolytic stability. An open synthetic challenge in this field is the optimization of new methodologies for the stereo- and regioselective opening of α-gluco carbasugar 1,2-epoxides that allow for the preparation of pseudo mono- and disaccharides of great interest. Therefore, we investigated the effect of Lewis acids and solvate ionic liquids (SILs) on the epoxide ring opening of a model substrate. Of particular interest was the complete stereo- and regioselectivity, albeit limited to simple nucleophiles, toward the desired C(1) isomer that was observed using LiClO4. The results obtained with SILs were also remarkable. In particular, Li[NTf2]/tetraglyme ([Li(G4)]TFSI) was able to function as a Lewis acid and to direct the attack of the nucleophile preferentially at the pseudo anomeric position, even with a more complex and synthetically interesting nucleophile. The regioselectivity observed for LiClO4 and [Li(G4)]TFSI was tentatively ascribed to the formation of a bidentate chelating system, which changed the conformational equilibrium and ultimately permitted a trans-diaxial attack on C(1). To the best of our knowledge, we report here the first case in which SILs were successfully employed in a ring-opening process of epoxides.

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Section: Resultsmentioning

confidence: 76%

Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides

et al. 2019

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“…The conformational behavior of different glycomimetics, including carbasugars,, C‐glycosyl compounds and other mimetics, have been largely discussed. Their ability to mimic the binding features of the natural saccharides has also been subject of detailed investigations , .…”

Section: Resultsmentioning

confidence: 99%

The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic

Calloni

Unione²,

Jiménez‐Osés

et al. 2018

Eur J Org Chem

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Neisseria meningitidis serogroup A (MenA) is an aerobic diplococcal Gram‐negative bacterium responsible for epidemic meningitis disease. Its capsular polysaccharide (CPS) has been identified as the primary virulence factor of MenA. This polysaccharide suffers from chemical lability in water. Thus, the design and synthesis of novel and hydrolytically stable structural analogues of MenA CPS may provide additional tools for the development of therapies against this disease. In this context, the structural features of the natural phosphorylated monomer have been analyzed and compared to those of its carba‐analogue, where the endocyclic oxygen has been replaced by a methylene moiety. The lowest energy geometries of the different molecules have been calculated using a combination of quantum mechanical techniques and molecular dynamics simulations. The predicted results have been compared and validated using NMR experiments. The results indicate that the more stable designed glycomimetics may adopt the conformation adopted by the natural monomer, although they display a wider flexibility around the torsional degrees of freedom.

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“…The Claisen rearrangement was also a key step in the construction of the carbocyclic system of pseudodisaccharides designed to mimic the minimal natural epitope Manα(1,2)Man 27 of dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin (DC‐SIGN; Figure ) . DC‐SIGN is a tetrameric transmembrane protein expressed by immature dendritic cells that binds to pathogens (human immunodeficiency virus [HIV], Ebola, and Dengue viruses) by specifically recognizing highly glycosylated structures displayed at their surface .…”

Section: Endocyclic Oxygen Replacementmentioning

confidence: 99%

Design and synthesis of glycomimetics: Recent advances

Tamburrini

Colombo

Bernardi

2019

Medicinal Research Reviews

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In the past few decades, our understanding of glycan information‐encoding power has notably increased, thus leading to a significant growth also in the design and synthesis of glycomimetic probes. Combining data from multiple analytical sources, such as crystallography, nuclear magnetic resonance spectroscopy, and other biophysical methods (eg, surface plasmon resonance and carbohydrate microarrays) has allowed to shed light on the key interaction events between carbohydrates and their protein‐targets. However, the low metabolic stability of carbohydrates and their high hydrophilicity, which translates in low bioavailability, undermine their development as drugs. In this framework, the design of chemically modified analogues (called carbohydrate mimics or glycomimetics) appears as a valid alternative for the development of therapeutic agents. Glycomimetics, as structural and functional mimics of carbohydrates, can replace the native ligands in the interaction with target proteins, but are designed to show enhanced enzymatic stability and bioavailability and, possibly, an improved affinity and selectivity toward the target. In the present account, we specifically focus on the most recent advances in the design and synthesis of glycomimetics. In particular, we highlight the efforts of the scientific community in the development of straightforward synthetic procedures for the preparation of sugar mimics and in their preliminary biological evaluation.

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Stereoselective innovative synthesis and biological evaluation of new real carba analogues of minimal epitope Manα(1,2)Man as DC-SIGN inhibitors

Cited by 15 publications

References 32 publications

Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides

Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides

The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba‐Mimetic

Design and synthesis of glycomimetics: Recent advances

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