Large‐Scale Synthesis of Enantiopure Molecular Cages: Chiroptical and Recognition Properties

A convenient and efficient gram‐scale synthesis for enantiopure hemicryptophane–tren (tren=tris(2‐aminoethyl)amine) derivatives has been developed. The four‐step synthesis is based on the optical resolution of a key intermediate, cyclotriveratrylene, for which the energy barrier for racemization has been measured to ensure that no racemization occurs during the two last steps of the synthetic pathway. The assignments of the absolute configurations have been performed by electronic circular dichroism and the enantiopurity was determined by NMR spectroscopy in the presence of enantiopure camphor sulfonic acid. To highlight the interest of such compounds, the recognition of norephedrine neurotransmitter was investigated and showed a remarkable enantioselectivity towards the C₃ symmetrical hosts. Finally, this highly modular synthetic pathway was used to provide eight enantiopure hemicryptophanes with different sizes, shapes, and functionalities. These results underline the high potential of this approach, which could lead to many applications in chiral recognition or asymmetric supramolecular catalysis.     

APplication of Continuous Thermodynamics to the Stability of Polymer Systems. II

A determinant criterion for the critical state in solutions and mixtures of polydisperse polymers is established within the general framework of Gibbs theory. The treatment continues an earlier paper by considering more general Gibbs free energy relations: The function replacing the x-term in the classic Flory-Huggins equation is permitted to depend on a finite number of moments of the polymer distribution(s) so as to embrace most Gibbs free energy relations of practical use. The new criterion leads to a very large reduction of computer time and of needed storage capacity compared to the traditional Gibbs determinant criterion. Some relations known from the literature are shown to be special cases of the established new criterion.     

Automated DBS Extraction Prior to Hilic/RP LC–MS/MS Target Screening of Drugs

This article describes a rapid LC–MS/MS target screening method based on an automated extraction of 5 μL dried blood spots (DBS), two 5 min chromatographic runs on orthogonal phase columns (RP and Hilic) and a data dependent acquisition (DDA) of product ions spectra for the reliable identification of the detected compounds. The extraction step was performed in 2 min by using the LC autosampler itself in 96-well plates. This procedure was evaluated using 22 model compounds frequently encountered in forensic investigations, i.e., cocaine, benzodiazepines, amphetamines, opioids, antidepressants and antipsychotics. These investigations showed that even if the extraction step was reduced to a minimum, the extraction recoveries were satisfactory (median value of 40 %) and allowed for the detection of the model compounds in their therapeutic ranges, with the exception of morphine. Moreover, the use of two different chromatographic columns broadened the number of screening targets to those that behaved poorly under RP conditions, such as amphetamines or glucuronides, while keeping chromatographic gradients very short. This procedure was applied to 34 authentic post-mortem cases. It allowed the detection of 89 % of the compounds that were quantified in the routine procedures and the formal identification of 77 % of the compounds using their product ions spectra. These results were considered more than satisfactory compared to routine screening alone (GC–MS and LC-DAD, 55 % compound identification). The method described in this article is therefore a powerful approach for a fast, reliable and efficient target screening of drugs in forensic and clinical investigations.     

A Facile Synthesis of Trifluoroacetaldehyde by Electroreduction Of Cf3Br In Dimethylformamide

Trifluoroacetaldehyde, isolated as CF₃CH(OCOCH₃)₂, is obtained in high yield by electroreduction of CF₃Br in DMF, using an undivided cell and a sacrificial aluminium anode.     

Valorization of Madagascar’s CNSL via the synthesis of one advanced intermediate (3-Pentadecylcyclohexanone)

A unique advanced intermediate: 3-Pentadecylcyclohexanone was synthetized from the crude product which contained a mixture of cardanol, cardol and 2-methylcardol, which was hydrogenated onto Pd/C at 80 °C. From this alkylated cyclohexanone: C15 alkylated adipic acid, caprolactam, caprolactone, were synthetized in high yields, such products may have many potentially applications in polymer chemistry. The condensation of the 3-pentadecyl-cyclohexanone and triethylene glycol in oxidative or reductive conditions gave aryl ether and cyclohexyl ether, this may be a way to prepare intermediate for surfactant chemistry. Therefore we show that Cashew Nut Shell Liquid (CNSL) may lead to numerous useful compounds thank to the preparation of a unique advanced intermediate.     

Straightforward preparation of polymers based on oligodimethylsiloxane and alkylamine

Novel oligodimethylsiloxane‐based polymers with alkyl side chain were synthesized in bulk by step‐growth polymerization between α,ω‐glycidyl ether oligodimethylsiloxanes and a monoalkylamine in the absence of catalyst and at temperatures ranging between 80 and 180 °C. Matrix assisted laser desorption ionization time of flight results attested for the high reactivity of the amine functions with the glycidyl groups and revealed that the main polymer structure was (A₂B₂)_n type with alkyl moieties as dangling chains. No etherification was observed during the reaction even at high temperatures and the nature of the end groups strongly depended on the molar ratio between glycidyl and amine functions. Polymerization reactions were followed by ¹H NMR and the kinetics of the glycidyl‐amine reaction pointed out the dependence of temperature, molar ratio, and the molar mass of the oligodimethylsiloxane. High conversion rates were obtained, especially with the lowest molecular weight oligodimethylsiloxane. An optimized kinetic model derived from the Horie's model was discussed and permitted to correctly fit the experimental data. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Microwave‐assisted synthesis and characterization of biodegradable block copolyesters based on poly(3‐hydroxyalkanoate)s and poly(D,L‐lactide)

Microwave (MW)‐assisted ring‐opening polymerization (ROP) provides a rapid and straightforward method for engineering a wide array of well‐defined poly(3‐hydroxyalkanoate)‐b‐poly(D,L ‐lactide) (PHA‐b‐PLA) diblock copolymers. On MW irradiation, the bulk ROP of D,L ‐lactide (LA) could be efficiently triggered by a series of monohydroxylated PHA‐based macroinitiators previously produced via acid‐catalyzed methanolysis of corresponding native PHAs, thus affording diblock copolyesters with tunable compositions. The dependence of LA polymerization on temperature, macroinitiator structure, irradiation time, and [LA]₀/[PHA]₀ molar ratio was carefully investigated. It turned out that initiator efficiency values close to 1 associated with conversions ranging from 50 to 85% were obtained only after 5 min at 115 °C. A kinetic investigation of the MW‐assisted ROP of LA gave evidence of its “living”/controlled character under the experimental conditions selected. Structural analyses and thermal properties of biodegradable diblock copolyesters were also performed. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Lipophilic phthalocyanines for their potential interest in photodynamic therapy: synthesis and photo-physical properties

Several phthalocyanines with different peripheral substituents were prepared and characterized by MALDI-TOF, ¹H NMR, UV–vis, fluorescence, and singlet oxygen quantum yields and retention time in HPLC normal phase. Zinc was used as a central metal ion to increase the photodynamic therapy efficiency. Phthalonitrile or 4-nitro phthalonitriles were used as starting materials. The influence of lipophilicity on the photophysical and photochemical properties was evaluated.