Eric Amigues

Application of NMR based metabolomics for mapping metabolite variation in European wheat

In this study, we report on the use of NMR-based metabolomics to access variation in low molecular weight polar metabolites between the European wheat cultivars Apache, Charger, Claire and Orvantis. Previous unassigned resonances in the published NMR spectra of wheat extracts were identified using 13C NMR and two dimensional proton-carbon NMR. These included a peak for trans-aconitate (δ3.43) and resonances corresponding to fructose in the crowded carbohydrate region of the spectra. Large metabolite differences were observed between two different growth stages, namely the coleoptile and two week old leaf tissue extracts which were consistent across cultivars. Two week old leaf tissue extracts had higher abundances of glutamine, glutamate, sucrose and trans-aconitate and less glucose and fructose than were observed in the coleoptile extracts. Across both growth stages the cultivars Apache and Charger showed the greatest differences in metabolite profiles. Charger had higher abundances of betaine, the single most influential metabolite in the principal component analysis, in addition to fructose and sucrose. However, Charger had lower levels of aspartate, choline and glucose than Apache. These findings demonstrate the potential for a biochemical mapping approach using NMR, across European wheat germplasm, for metabolites of known importance to functional characteristics.

Solvent-modulated reactivity of PCl3 with amines

The reactivity of phosphorus trichloride towards amines in ionic liquids has been investigated and compared with that in conventional organic solvents. In addition to easing the synthetic procedures thus far required for the preparation of aminochlorophosphines in molecular solvents, for example the ability to operate at 20 °C, under non-anhydrous and high concentration conditions with short reaction times and rapid addition of reagents, bis{(trifluoromethyl)sulfonyl}imide-based ionic liquids offer a tight control over the selectivity during the reaction and offer access to monoamination and bisamination products in high yields and chemoselectively. Furthermore, these ionic liquids offer a unique storage medium for these highly moisture sensitive aminochlorophosphines.

Selective synthesis of chlorophosphoramidites using ionic liquids

A range of chlorophosphoramidites have been prepared in ionic liquids and compared with material synthesised in molecular solvents. Through the use of ionic liquids as reaction media the moisture sensitivity and impurity issues hampering existing traditional synthetic routes have been eased. Not only can stock chemicals be used without purification, but the reactions may be conducted at room temperature and at high concentrations. Furthermore, reaction times are reduced and rapid addition of reagents is possible whilst retaining tight control over product selectivity. Beyond their role as reaction media, ionic liquids also present a unique storage medium for these highly moisture sensitive chlorophosphoramidites.

Glycosyl-Nucleolipids as New Bioinspired Amphiphiles

Four new Glycosyl-NucleoLipid (GNL) analogs featuring either a single fluorocarbon or double hydrocarbon chains were synthesized in good yields from azido thymidine as starting material. Physicochemical studies (surface tension measurements, differential scanning calorimetry) indicate that hydroxybutanamide-based GNLs feature endothermic phase transition temperatures like the previously reported double chain glycerol-based GNLs. The second generation of GNFs featuring a free nucleobase reported here presents a better surface activity (lower γlim) compared to the first generation of GNFs.

beta-1,2,3-Triazolyl-Nucleosides as Nicotinamide Riboside Mimics

The synthesis of a series of pyridine- and piperidine-substituted 1,2,3-triazolides linked to a riboside moiety is described. The presence of a triazolide substituent on the pyridine moiety permitted the facile reduction of the latter under mild hydrogenation conditions. These analogues were modelled as to define their similarity to nicotinamide riboside and quantify their ability to bind NAD-dependent protein deacetylases.

Controlled chemistry of Moisture Sensitive Reagents in Ionic Liquids

PCl3 and POCl3 are key synthetic precursors in a wide range of chemical processes, required in the synthesis of compounds ranging from bulk chemicals such as pesticides, flame retardants and plasticizers to the advanced synthetic intermediates and reagents, therapeutic precursors and metal catalysts ligands. However, whether neat or in organic solvents, these reagents and their derivatives are highly air and water sensitive and must be used under strictly anhydrous conditions, often in excess at low temperatures to allow for some level of control in order to achieve chemoselectivity and avoid side-product formation. For instance, excess of phosphitylating reagent must be used in aprotic organic solvents at low temperature under anhydrous and dissolution conditions in order to obtain mono-derivatised chlorophosphines and overcome the high chemical reactivity of the trivalent chlorophosphine’s P-Cl bonds. As such, by virtue of their chemical instability in organic media, the use of chlorophosphines in the direct phosphitylation of alcohols and amines has been limited and very difficult to control. In industry, the reagents used and available for phosphitylation reactions have been restricted to compounds such as dibenzyloxychlorophosphine, dichlorodiisopropylaminophosphite, chlorocyanoethyldiisopropyl-aminophosphite and cyanoethyl-bisdiisopropylaminophosphite. Although these reagents are commercially available and used extensively as precursors in the synthesis of many phosphoruscontaining fine chemicals, major variability can be observed in their purity and stability upon storage. As a consequence, yields of phosphitylation reactions are highly variable and thus compromise overall synthetic efficiency in particular that of automated processes such as solid phase synthesis of oligonucleotides, which require highly pure nucleoside phosphoramidites to be effective. We have established that ionic liquids can alleviate many of the issues surrounding the use and preparation of P-X containing compounds as synthetic reagents. Initially, the stability of PCl3/POCl3 in ILs and the controllable reactivity of PCl3 in this medium has been demonstrated. In addition, in the area of PCl3 manipulation, ILs was shown to permit the selective conversion of individual P-Cl bonds (Figure 1) to be performed with control not observed in molecular solvent systems. This has been particularly valuable in the formation of nucleotide phosphoramidites.