A facile synthesis of C-glycosylbarbiturates

Pérez, Juan Manuel Sánchez; Gonzalez, Martin Avalos; Requejo, Jose L. Jimenez; Albarran, Juan C. Palacios

doi:10.1016/0008-6215(83)88372-4

Cited by 9 publications

(4 citation statements)

References 3 publications

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“…Prior to the work reported with urazole, the aqueous glycosylation of another divalent noncanonical nucleobase, barbituric acid, was explored by Perez and co-workers starting in 1983 . Barbituric acid, formally 6-oxo(5 H )-uracil, is a pyrimidine and a carbon acid (at position 5) with a relatively low p K a of 4 in water (attributable to the aromaticity of the barbiturate anion).…”

Section: Synthesis Of Noncanonical Nucleosides By Divalent Nucleophil...mentioning

confidence: 99%

“…Upon deprotonation, barbituric acid acts as a strong nucleophile in Knoevenagel condensation reactions, even in water (unlike its close chemical relative, uracil). Perez and co-workers found that, under neutral to basic conditions, and at room temperature or with mild heating, barbituric acid (or its 1,3-dimethyl derivative) readily reacts with various sugars (both pentoses and hexoses) to form barbiturate glycosides. − For the reactions of hexoses and xylose, the β- C -pyranoside was produced exclusively. Arabinose produced the α- C -pyranoside exclusively.…”

Section: Synthesis Of Noncanonical Nucleosides By Divalent Nucleophil...mentioning

confidence: 99%

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Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

2020

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The origin of nucleotides is a major question in origins-of-life research. Given the central importance of RNA in biology and the influential RNA World hypothesis, a great deal of this research has focused on finding possible prebiotic syntheses of the four canonical nucleotides of coding RNA. However, the use of nucleotides in other roles across the tree of life might be evidence that nucleotides have been used in noncoding roles for even longer than RNA has been used as a genetic polymer. Likewise, it is possible that early life utilized nucleotides other than the extant nucleotides as the monomers of informational polymers. Therefore, finding plausible prebiotic syntheses of potentially ancestral noncanonical nucleotides may be of great importance for understanding the origins and early evolution of life. Experimental investigations into abiotic noncanonical nucleotide synthesis reveal that many noncanonical nucleotides and related glycosides are formed much more easily than the canonical nucleotides. An analysis of the mechanisms by which nucleosides and nucleotides form in the solution phase or in drying−heating reactions from pre-existing sugars and heterocycles suggests that a wide variety of noncanonical nucleotides and related glycosides would have been present on the prebiotic Earth, if any such molecules were present. CONTENTS 1. Introduction 4806 1.1. General Nomenclature and Definitions 4806 1.2. Challenges, Motivations, Opportunities, and Scope 4807 1.3. Defining Two Distinct Non-Enzymatic Glycosylation Reactions 4811 2. Synthesis of Noncanonical Nucleosides by Monovalent Nucleophilic Heterocycles 4812 3. Synthesis of Noncanonical Nucleosides by Divalent Nucleophilic Heterocycles 4813 4. Synthesis of Noncanonical Nucleosides by Concomitant Sugar-Nucleobase Formation 4818 5. Challenges Associated with Phosphate and the Possibility of Earlier Alternatives 4821 6. Discussion 4824 Author Information 4827 Corresponding Author 4827 Authors 4827 Notes 4827 Biographies 4827 Acknowledgments 4828 References 4828

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Section: Synthesis Of Noncanonical Nucleosides By Divalent Nucleophil...mentioning

confidence: 99%

Section: Synthesis Of Noncanonical Nucleosides By Divalent Nucleophil...mentioning

confidence: 99%

Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

2020

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“…Moreover, compare to oxyamine or hydrazine that are highly reactive and thus quite hardly handled, β‐diketone is a latent C ‐nucleophile activatable upon deprotonation. Surprisingly, since the first report of Knoevenagel condensation on unprotected sugars using barbituric acid (a cyclic β‐diketone) or N , N′ ‐dimethylbarbituric acid in 1983 by Galbis Perez et al, only few published works have benefited from this chemo‐ and β‐stereoselective reaction . Advantageously, the Knoevenagel condensation was performed in water at neutral pH and led to sodium salt of β‐ C ‐glycosylbarbiturates in excellent yields.…”

Section: Introductionmentioning

confidence: 99%

N,N′‐Disubstituted Barbituric Acid: A Versatile and Modular Multifunctional Platform for Obtaining β‐C‐Glycoconjugates from Unprotected Carbohydrates in Water

2019

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Direct access to non‐hydrolyzable glycoconjugates is highly mandatory for stabilizing their intrinsic biological or physical‐chemistry properties in the surrounding environment. Here, a simple and versatile approach for the preparation of multifunctional clickable β‐C‐glycoconjugates has been developed. Readily accessible N,N′‐disubstituted barbituric acids have been synthesized and ligated in water to the reducing end of unprotected carbohydrates via Knoevenagel condensation. Additionally, divalent glycoclusters have been built from bis‐urea backbones and showed ability to interact with a model lectin, the peanut agglutinin. This concept can be readily adapted for the preparation of other C‐glycoconjugates applicable in diverse area of glycosciences.

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“…Interestingly, the Knoevenagel condensation using β-diketones is another very convenient method that leads to β- C -glycosides in one step directly from unprotected sugar . However, it has been less developed in spite of its chemical and enzymatic stability and ring integrity of the terminal reducing sugar. , The major breakthrough in Knoevenagel condensation with unprotected carbohydrates has been achieved first when Galbis-Perez et al reported, in the mid-1980s, the direct reaction in neutral aqueous media with barbituric acids, a cyclic β-diketone, resulting in β- C -glycosyl barbiturates. Later, Lubineau et al demonstrated the efficient use of acetylacetone, a noncyclic β-diketone, for obtaining almost exclusively β- C -glycosidic ketones .…”

Section: Introductionmentioning

confidence: 99%

Expeditious Synthesis of C-Glycosyl Barbiturate Ligands of Bacterial Lectins: From Monomer Design to Glycoclusters and Glycopolymers

Portier

Halila

2018

Bioconjugate Chem.

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The approach developed here offers a straightforward and efficient access to -C-glycosyl barbiturates ligands, spanning from glycomimetics to multivalent C-neoglycoconjugates, with the aim of deciphering structural parameters impacting the binding to pathogenic lectins. We reinvestigated the Knoevenagel condensation of barbituratic acid on protecting-group free carbohydrates and successfully designed sodium and 5,5-disubstituted N,N-dimethyl barbiturate forms of D-galactose, Lfucose, melibiose, 2'-fucosyllactose, maltose and evaluated their binding affinity by isothermal titration calorimetry with LecA (galactose-binding lectin) and LecB (fucose-binding lectin) from Pseudomonas aeruginosa and RSL (fucose-binding lectin) from Ralstonia solanacearum. The barbiturate ring was shown detrimental for binding to LecA (K D in mM range) and even more to LecB (non-interaction) while RSL is much more tolerant especially in presence of an aromatic group (K D in M range). However, distancing the barbiturate ring from the recognition carbohydrate residue by using oligosaccharides increased affinity up to low micromolar range. Extension of our convenient synthetic approach led in two-steps to melibiose-based C-glycosyl barbiturates clusters and C-glycosyl barbiturate glycopolymers exhibiting a dramatic enhancement of binding avidity for LecA.

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A facile synthesis of C-glycosylbarbiturates

Cited by 9 publications

References 3 publications

Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

N,N′‐Disubstituted Barbituric Acid: A Versatile and Modular Multifunctional Platform for Obtaining β‐C‐Glycoconjugates from Unprotected Carbohydrates in Water

Expeditious Synthesis of C-Glycosyl Barbiturate Ligands of Bacterial Lectins: From Monomer Design to Glycoclusters and Glycopolymers

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