Véronique Bonnet

New Syntheses of Substituted Pyridines via Bromine–Magnesium Exchange

Abstract Bromine–magnesium exchange using i PrMgCl in THF at room temperature on 2-, 3- and 4-bromopyridines allowed the synthesis of various functionalized pyridines. The methodology was successfully used for the synthesis of 4-azaxanthone. Moreover, single exchange reactions observed on 2,6-, 3,5-, 2,3- and 2,5-dibromopyridines, with complete regioselectivity in the case of 2,3- and 2,5-dibromopyridines, afforded substituted bromopyridines, which were then involved in a second exchange step to provide difunctionalized pyridines.

Pyridylmagnesium chlorides from bromo and dibromopyridines by brominemagnesium exchange: A convenient access to functionalized pyridines

Various bromopyridines were converted to the corresponding pyridylmagnesium chlorides at room temperature by treatment with iPrMgCl. The resulting Grignard reagents were quenched by various electrophiles to afford functionalized pyridines. The brominemagnesium exchange of some dibromopyridines was also studied.

Seabirds drive plant species turnover on small Mediterranean islands at the expense of native taxa

Abstract The analysis of long-term floristic changes was conducted on nine west-Mediterranean limestone islands (size range: 2–95 ha) which have recently undergone a severe demographic explosion in their yellow-legged gull Larus cachinnans colonies. A comparison of past and present plant inventories was used to quantify extinction-colonization events, both from a classical biogeographical perspective (per island approach) and a metapopulational perspective (per species approach). In the first approach, floristic turnover intensity was negatively related to island area and positively to gull nesting density, but was independent of island isolation. In the second, species turnover rate was compared with a set of plant species life history traits (dispersal mode, Grime CSR strategy, growth form, biogeographical type). Plants which exhibited the highest turnover rate were primarily ruderal, annual, wind-dispersed species with a wide geographic range. The severe disturbance induced by seabird activities has tended to select and favour some adapted plant species groups at the expense of indigenous island taxa. The relationships between specific turnover intensity and plant life history traits justify using the metapopulation approach and point to the importance of interspecific variations in extinction-colonization patterns.

Cyclodextrin nanoassemblies: a promising tool for drug delivery.

Among the biodegradable and nontoxic compounds that can form nanoparticles for drug delivery, amphiphilic cyclodextrins are very promising. Apart from ionic cyclodextrins, which have been extensively studied and reviewed because of their application in gene delivery, our purpose is to provide a clear description of the supramolecular assemblies of nonionic amphiphilic cyclodextrins, which can form nanoassemblies for controlled drug release. Moreover, we focus on the relationship between their structure and physicochemical characteristics, which is crucial for self assembly and drug delivery. We also highlight the importance of the nanoparticle technology preparation for the stability and application of this nanodevice.

Physico-chemical investigation of asymmetrical peptidolipidyl-cyclodextrins.

A new class of amphiphilic peptidolipidyl-cyclodextrins is reported. The derivatives are chiral due to the presence of an L-leucine in the spacer arm that links a saccharide moiety and a grafted, saturated hydrocarbon chain. Self-assembly properties of the peptidolipidyl-cyclodextrins are characterized by quasi-elastic light scattering, turbidity and UV-visible absorption measurements. NMR experiments give insight into the intermolecular dipolar interactions as a function of temperature and concentration. N-dodecyl-N alpha-(6 I-amidosuccinyl-6 1-deoxy-cyclomaltoheptaose)-L-leucine (1) is poorly soluble in aqueous media. N-dodecyl-N(alpha)-(6 I-amidosuccinyl-6 I-deoxy-2 I,3 I-di-O-methyl-hexakis-(2 II-VII,3 II-VII,6 II-VII-tri-O-methyl)-cyclomaltoheptaose)-L-leucine (2) is found to be more soluble and self-assembles into stable supramolecular colloidal aggregates with nanometric dimensions above a critical aggregation concentration (CAC). It has a propensity for solubilization of hydrophobic species revealing a micellar-like behavior, which is compared to that of the non-ionic detergent octyl glucoside. On the contrary, compound 1 precipitates in a crystalline phase beyond its water solubility limit, and it does not display any solubilizing capacity. The observed behavior corroborates at the molecular level with the NMR results.

Discrimination of cyclic and linear oligosaccharides by tandem mass spectrometry using collision‐induced dissociation (CID), pulsed‐Q‐dissociation (PQD) and the higher‐energy C‐trap dissociation modes

RATIONALE Carbohydrates have essential functions in living organisms and cells, but, due to the presence of numerous linkage combinations, substituent sites and possible conformations, they are the class of biomolecules which exhibits the huge structural diversity found in nature. Thereby, due to such diversity and poor ionization, their structural deciphering by mass spectrometry is still a very challenging task. METHODS Here, we studied a series of linear and cyclic neutral oligosaccharides using electrospray with collision-induced dissociation (CID), pulsed-Q-dissociation (PQD) and the higher-energy C-trap dissociation (HCD) feature of a linear ion trap Orbitrap hybrid mass spectrometer (LTQ-Orbitrap). The collision energy necessary to obtain 50% fragmentation (CE(50) values) in CID, PQD and HCD was used to correlate both size and structures. RESULTS The default settings for activation time and/or activation Q are the most appropriate, except for HCD, where 100 ms instead of 30 ms gave more intense fragment ions. PQD exhibits a 2-8-fold lower sensitivity than CID. HCD provides signals closer or slightly superior by 1.5-fold than PQD, and offers a more balanced ion distribution through the spectrum. Furthermore, HCD offers the possibility to make fine adjustments of the energy via the eV scale to further increase the yield of low-mass fragments. CONCLUSIONS The complementarity of CID, PQD and HCD was clearly demonstrated by obtaining structural information on hexa-, hepta- and octasaccharides. Together, these results clearly indicate the usefulness of the CID/HCD pair for further structural deciphering, and analysis of more complex structures such as multi-antennary carbohydrates or glycoconjuguates alone or in mixture.

Synthesis of lipophosphoramidyl-cyclodextrins and their supramolecular properties.

The synthesis of lipophosphoramidyl-β-CD was obtained by an Atherton-Todd (AT) reaction that involved dioleylphosphite and either functionalized permethylated or native β-cyclodextrin. This AT reaction that produced dioleylphosphoramide by making use of the amino group grafted on cyclodextrin, was optimized for these cyclic oligosaccharides. These new amphiphilic compounds were fully characterized, and their self-assembling properties were investigated: the mean size diameter and polydispersity measured by Dynamic Light Scattering (DLS) were affected by the nature of the aqueous media and the temperature of storage. The encapsulation properties of these nanoparticles have been evaluated using carboxyfluorescein and scopolamine derivatives as model of guests.

Combination of 1H nuclear magnetic resonance spectroscopy and mass spectrometry as tools for investigation of the thermolytic and solvolytic effects: Case of carbamates analysis

The carbamate pesticides are a well known thermo-sensible compound class. Under unfavourable conditions, these compounds are highly prone to degradation via fragmentation and/or rearrangement mechanisms. Their transformation processes are observed in consequence of two factors: structure with fragile bonds on the one hand and a stressing environment on the other hand leading to a difficult direct gas chromatography (GC) analysis, i.e. without derivatisation. In this paper, we investigated an original methodology based on the complementarity of analysis by proton nuclear magnetic resonance spectroscopy ((1)H NMR) and those provided by GC hyphenated with ion-trap mass selective detection (GC-ITMS) to investigate combined effects of temperature and solvent nature affecting the behaviour of 16 carbamates. Among tested solvents, toluene and acetonitrile with 0.1% acetic acid were considered as the best solvents for storage and GC analysis respectively. Carbaryl, chlorpropham, carbofuran and N-sulfenylated compounds began to be thermodegraded with a loss equal to 1-5% even at 50 degrees C. An on-column injection validated as providing no degradation was used to analyse the identical solution that in (1)H NMR and it was emphasised that results of the measured degradation rates were identical at +/-2%. It was highlighted that this methodology was extensible to study mechanisms and parameters with other (bio)molecules.

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis

Summary New cyclodextrin (CD)-grafted polymers functionalized with water-soluble phosphanes were synthesized in three steps starting from polyNAS. Once characterized by NMR spectroscopy and size-exclusion chromatography, they were used as additives in Rh-catalyzed hydroformylation of 1-hexadecene. The combined supramolecular and coordinating properties of these polymers allowed increasing the catalytic activity of the reaction without affecting the selectivities.

Oxidation of galactose and derivatives catalysed by galactose oxidase: structure and complete assignments of the NMR spectra of the main product

Abstract This paper deals with the analysis of the structure of 6-oxogalactose and 6-oxogalactosides obtained from the oxidation reaction catalysed by galactose oxidase. A complete analysis of the 1 H and 13 C NMR spectra showed that 6-oxogalactose and 6-oxogalactosides were mainly present as the hydrate of the monomeric form.