Elodie Brun

Les motifs 1,3-polyols sont fréquemment rencontrés dans de nombreuses molécules naturelles biologiquement actives. Cependant, à ce jour, il n'existe que peu de méthodes générales et efficaces permettant d'accéder à ces motifs de manière stéréocontrôlée. Nous nous sommes particulièrement intéressés à la synthèse de 1,3,5,7-tétraols et une méthode a été mise au point pour former ces composés en utilisant deux cyclisations de Prins successives suivies d'une coupure réductrice du bis-tétrahydropyrane obtenu. Cette méthode permet d'accéder à tous les diastéréoisomères des tétraols efficacement et elle a été appliquée avec succès à la synthèse du (+)-cryptocaryol A, un composé polyhydroxylé stabilisant PdCd4, qui est une protéine inhibant le développement cellulaire. Par ailleurs, nous avons développé une approche synthétique de la filipine III, un macrolide naturel possédant des propriétés antibiotiques et antifongiques, et comportant un fragment 1,3-polyol et un fragment pentaénique. Plusieurs stratégies ont été envisagées afin d'accéder à ces deux fragments, qui ont été synthétisés de manière convergente. Leur assemblage a été réalisé grâce à une réaction d'aldolisation diastéréosélective et nous avons pu accéder au squelette carboné complet de la filipine III.

Recently, significant research activity has been devoted to thiolate-protected gold clusters due to their attractive optical and electronic properties. These properties as well as solubility and stability can be controlled by post-synthetic modification strategies. Herein, the ligand exchange reaction between Au₂₅(2-PET)₁₈ cluster (where 2-PET is 2-phenylethanethiol) and di-thiolated crown ether (t-CE) ligands bearing two chromophores was studied. The post-functionalization aimed to endow the cluster with ion binding properties. The exchange reaction was followed in situ by UV-vis, ¹H NMR and HPLC. MALDI mass analysis revealed the incorporation of up to 5 t-CE ligands into the ligand shell. Once functionalized MALDI furthermore showed complexation of sodium ions to the cluster. ATR-FTIR spectroscopic studies using aqueous solutions of K⁺, Ba²⁺, Gd³⁺ and Eu³⁺ showed noticeable spectral shifts of the C–O stretching band around 1100 cm⁻¹ upon complexation. Further spectral changes point towards a conformational change of the two chromophores that are attached to the crown ether. Density functional theory calculations indicate that the di-thiol ligand bridges two staple units on the cluster. The calculations furthermore reproduce the spectral shift of the C–O stretching vibrations upon complex formation and reveal a conformational change that involves the two chromophores attached to the crown ether. The functionalized clusters have therefore attractive ion sensing properties due to the combination of binding properties, mainly due to the crown ether, and the possibility for signal transduction via an induced conformational change involving chromophore units.

Stereoselective double hydrothiolation of bis enol ether macrocycles was achieved under photo-mediated conditions.

Varying the structure of perylene-based dimers allows tuning the excited state from an excimer to a charge-separated state.

The first observation of circular polarization of electrochemiluminescence (ECL) from a purely organic derivative is reported. A bispyrene scaffold mounted on a constrained polyether macrocycle displaying intense excimer fluorescence and highly circularly‐polarized (CP) photoluminescence has been selected for this purpose. The compound displays an ECL dissymmetry factor of about |8×10⁻³|, which is in good agreement with the corresponding photoluminescence value. This observation is the first step towards the molecular engineering of tailored dyes that can act as both ECL and CP‐ECL reporters for (bio)analysis by bringing a new level of information when dealing with chiral environments. Additionally, it provides an extra dimension to the ECL phenomenon and opens the way to chiral detection and discrimination.

The first observation of circular polarization of electrochemiluminescence (ECL) from a purely organic derivative is reported. A bispyrene scaffold mounted on a constrained polyether macrocycle displaying intense excimer fluorescence and highly circularly‐polarized (CP) photoluminescence has been selected for this purpose. The compound displays an ECL dissymmetry factor of about |8×10⁻³|, which is in good agreement with the corresponding photoluminescence value. This observation is the first step towards the molecular engineering of tailored dyes that can act as both ECL and CP‐ECL reporters for (bio)analysis by bringing a new level of information when dealing with chiral environments. Additionally, it provides an extra dimension to the ECL phenomenon and opens the way to chiral detection and discrimination.

Straightforward synthesis and resolution of a series of chiral fluorescent macrocycles are presented, together with their electronic circular dichroism (ECD), strong excimer fluorescence (EF, λ 300 to 650 nm) and allied highly circularly polarized luminescence (CPL, g_lum up to 1.7 × 10⁻²). The ECD, EF and CPL responses are strongly affected by the presence of metal ions (Na⁺, Ba²⁺) thanks to deep conformational changes. While ECD signals can be almost completely reversibly inverted upon the complexation/decomplexation of metal ions in a typical binary response, CPL signals are reversibly quenched concomitantly. The designed macrocycles display thus a remarkable combination of both +/− ECD and on/off CPL reversible switching.

A series of bis(pyreneamide) macrocycles, synthesized in two steps from THF, THP, oxepane and 1,4‐dioxane, are tested as chemosensors for a large range of mono‐, di‐ and trivalent cations. In their native states, these macrocycles exhibit a strong excimer fluorescence that is quenched upon the addition of the metal ions (alkaline, alkaline earth, p‐, d‐, and f‐block metals). UV‐Vis spectrophotometric titrations, cyclic voltammetry, excimer fluorescence quenching, and transient absorption spectroscopy experiments helped characterize the On‐Off changes occurring upon binding and demonstrate that the highest stability constants are obtained with divalent cations Ca²⁺ and Ba²⁺ specifically.

A rapid and simple method to access trifluoromethylated 1,3-dioxanes by a sequence of addition/oxa-Michael reaction has been developed; the reaction proceeds smoothly with excellent stereoselectivity.

The synthesis of the carbon skeleton of filipin III, a polyenic macrolactone possessing 11 stereogenic centers, was achieved using a convergent strategy with the longest linear sequence of 19 steps starting from hexanal. Construction of the polyene was realized using two successive Heck couplings as the key steps. Control of the stereogenic centers of the polyol fragment was performed by utilizing an Evans aldolization, a 1,3-syn aldolization, enantio- and diastereoselective allylations, a hemiacetalization/oxa-Michael sequence, and a 1,3-syn reduction. The polyol and polyenic fragments were coupled using a 1,5-anti diastereoselective aldolization followed by a 1,3-anti reduction.