Jean-Marc Escudier

Synthesis of Bicyclonucleosides Having a C−C Bridge†

Université de Nantes, CNRS, Laboratoire CEISAM-UMR-CNRS 6230, Faculté des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France, Université Paul Sabatier Laboratoire de Synthèse et Physicochimie des Molécules d’Intérêt Biologique UMR-CNRS 5068, 31062 Toulouse Cedex, France, and Université de Technologie de Compiègne, Ecole Supérieure de Chimie Organique Minérale, EA 4297, Transformations Intégrées de la Matière Renouvelable, 1 allée du Réseau Jean-Marie Buckmaster, F-60200 Compiègne, France

Silicon‐Based Chemistry: An Original and Efficient One‐Step Approach to [18F]‐Nucleosides and [18F]‐Oligonucleotides for PET Imaging

Take it eaSi! Nucleosides, dinucleotides, and one oligonucleotide, all modified by click chemistry, have for the first time been directly and very efficiently labeled with (18)F by using a silicon-based, one-step approach that opens the way for the development of a new class of positron emission tomography (PET) tracers (see graphic).

Diastereoface differentiation in addition of lithium enolates to chiral α,β-epoxyaldehydes

Abstract The aldolisation reaction of lithium ester enolates with chiral α,β-epoxyaldehydes 2a–2f has been investigated. The reaction proceeds with diastereofacial preference in favour of the anti isomer ( anti:syn ≈ 4:1) and can be greatly enhanced in the case of cis α,β-epoxy-aldehydes 2a–2c by a synergic effect of temperature and enolate excess ( anti:syn 13:1). The Felkin-Ahn model can explain the results obtained on asymmetric induction.

Stereoselective synthesis of five and/or six membered ring hydroxylactones obtained by Lewis acid mediated reaction of γ,δ-epoxy-β-hydroxyesters; access to 5-methylated 2-deoxysugars.

Abstract A stereoselective route to six and/or five membered ring lactones from optically active γ,δ-epoxy-β-hydroxyesters obtained from nerol and geraniol has been developed. The intramolecular cyclization by epoxide ring opening occurred via activation of 6-endo over the usually favoured 5-exo, and the application of this technology to the stereocontrolled synthesis of 5-methylated 2-deoxysugars was achieved.

Diastereoselection in the addition of enolates to chiral α,β-epoxyaldehydes

Abstract The stereochemistry of addition of lithium enolates to the α,β-epoxyaldehydes 1z – 3 has been investigated. Moderate to high diastereoselectivity (up to 13:1) is obtained in favour of the anti isomer, which is explained by the Felkin-Anh model for asymmetric induction.

Alpha,beta-D-CNA preorganization of unpaired loop moiety stabilizes DNA hairpin.

DNA hairpin structures can be stabilized by introduction of constraint on the sugar phosphate backbone within the unpaired loop moiety by means of dinucleotides locked with an alpha torsion angle in gauche(+) configuration.

Enhanced diastereoselectivity in the addition of ester enolate to optically active α,β-epoxyaldehydes obtained from nerol and geraniol

Abstract Optically active α,β-epoxyaldehydes obtained from nerol and geraniol were allowed to react with lithium tert-butylacetate. The diastereofacial preference of the aldolisation reaction was always anti (“Si”face attack of the carbonyl). The best diastereoselectivity ever observed in these series (>99 : anti : syn ) was obtained for the α,β-epoxyneral aldolisation.

α,β-D-CNA featuring canonical and noncanonical α/β torsional angles behaviours within oligonucleotides

α,β-D-CNA building blocks featuring either canonical gauche(−) or noncanonical gauche(+) values of the nucleic acids sugar phosphate backbone torsional angle α have been introduced into oligonucleotides, and provide new insight on conformational restriction impact on duplex formation ability by means of UV experiments and molecular dynamics simulations.

Synthèse stéréosélective de thymidine substituée en C-5′

Abstract Stereocontrolled enolate addition on thymidine C-5′ aldehydes provides functionalized nucleosides. After appropriate protections of the hydroxyl functions, and reduction of the carbonyl function these “armed” nucleosides can be tosylated to permit subsequent modification on the oligonucleotide in wich they could be incorporated.

A short synthesis of substituted β-hydroxy γ-butyrolactones and 2-deoxyhexofuranosides

Abstract The γ,δ-epoxy β-hydroxyestes obtained by diastereoselective aldolisation beetwen ester enolates and optically active α,β-epoxyaldehydes, undergo quantitative stereocontrolled lactonisation which can be followed by reduction to provide 2-deoxy hexofuranosides. The γ,δ-epoxy β-hydroxyesters 2 undergo Lewis acid promoted lactonisation. Reduction of 3 provides 2-deoxyhexofuranosides 4 .