Synthesis and Reactivity of Aliphatic and (Hetero) Aromatic N-Alkyl-N-(Diphenyloxophosphinyl) Methyl Carboxamides and Lactams

A variety of aliphatic, aromatic and heteroaromatic N-alkyl-N-(diphenyloxophosphinyl) methyl carboxamides and lactams have been prepared by preliminar chloromethylation of the appropriate secondary amides and subsequent treatment with ethyl diphenylphosphinite.     

Synthesis and cytotoxic evaluation of cis-locked and constrained analogues of combretastatin and combretastatin A4

A series of cis-locked stilbenic compounds related to combretastatin and combretastatin A4 has been designed and synthesized. The cytotoxic effects of these rigid analogues were evaluated as well as their abilities to inhibit tubulin polymerization.     

Correlated AFM and SERS imaging of the transition from nanotriangle to nanohole arrays

Mapping the transition of Ag nanotriangle to nanohole arrays revealed that the optimal SERS response was obtained near the transition. Correlated AFM and Raman imaging provided novel experimental proof that hot spots are located on Ag islands for nanotriangle arrays and in the core area of the hole for nanohole arrays, which is in agreement with previous theoretical predictions.     

Metalation of 4-oxazolinyloxazole derivatives. A convenient route to 2,4-bifunctionalized oxazoles

The synthesis of an array of 5-phenyloxazole derivatives bearing a variety of hydroxyalkyl groups at the C-2 position of the heterocyclic nucleus and possessing a formyl or a carboxyl function at C-4 is reported. These bifunctionalized compounds have been efficiently prepared by addition of carbonylated electrophiles to the 2-lithio derivative of 5-phenyloxazole preliminarily equipped with an oxazoline unit at the 4-position of the oxazole nucleus. It is demonstrated that this protocol offers a double advantage since it suppresses the troublesome electrocyclic ring-opening reaction and allows access to the target compounds by simple chemical transformation of the oxazoline ring system.     

Neutron capture cross section measurement of 151Sm at the CERN neutron time of flight facility (n_TOF)

The151Sm(n,gamma)152Sm cross section has been measured at the spallation neutron facility n_TOF at CERN in the energy range from 1 eV to 1 MeV. The new facility combines excellent resolution in neutron time-of-flight, low repetition rates, and an unsurpassed instantaneous luminosity, resulting in rather favorable signal/background ratios. The 151Sm cross section is of importance for characterizing neutron capture nucleosynthesis in asymptotic giant branch stars. At a thermal energy of kT=30 keV the Maxwellian averaged cross section of this unstable isotope (t(1/2)=93 yr) was determined to be 3100+/-160 mb, significantly larger than theoretical predictions.     

Lattice computations for random numbers

We improve on a lattice algorithm of Tezuka for the computation of the -distribution of a class of random number generators based on finite fields. We show how this is applied to the problem of constructing, for such generators, an output mapping yielding optimal -distribution.

     

Effects of Hexane on Protein Profile,Solubility and Foaming Properties of Defatted Proteins Extracted from Tenebrio molitor Larvae

Inclusion of edible insects in human diets is increasingly promoted as a sustainable source of proteins with high nutritional value. While consumer acceptability remains the main challenge to their integration into Western food culture, the use of edible insects as meal and protein concentrate could decrease neophobia. The defatting of edible insects, mostly done with hexane, is the first step in producing protein ingredients. However, its impact on protein profiles and techno-functionality is still unclear. Consequently, this study compares the protein profiles of hexane-defatted and non-hexane-defatted yellow mealworm (Tenebrio molitor) meals and protein extracts, and evaluates the impact of hexane on protein solubility and foaming properties. Results showed that profiles for major proteins were similar between hexane-defatted and non-defatted samples, however some specific content differences (e.g., hexamerin 2) were observed and characterized using proteomic tools. Protein solubility was markedly lower for T. molitor meals compared to protein extracts. A large increase in the foaming capacity was observed for defatted fractions, whereas foam stability decreased similarly in all fractions. Consequently, although the hexane-defatting step was largely studied to produce edible insect protein ingredients, it is necessary to precisely understand its impact on their techno-functional properties for the development of food formulations.     

Asymmetric synthesis of 6-alkyl- and 6-arylpiperidin-2-ones. Enantioselective synthesis of (S)-(+)-coniine

A variety of diolefinic hydrazides (1) have been assembled in a highly diastereoselective manner by addition of allyllithium to chiral SAMP hydrazones followed by N-acylation with acryloyl chloride. Substrates 1 undergo ring-closing metathesis to give the cyclic enehydrazides (5) which can be easily converted into virtually enantiopure 6-alkyl- or 6-arylpiperidin-2-ones (7). The versatility of this hydrazone addition-RCM protocol has been further exemplified by the conversion of the unsaturated heterocycle 5b into the piperidine alkaloid (S)-(+)-coniine.     

Prediction of the disposition of a P-gp substrate in wild-type and knockout mice tissues: Development of a physiologically based pharmacokinetic (PBPK) model and its global sensitivity analysis

In order to improve understanding and prediction of drug disposition prior to in vivo experiments, we aimed to develop a PBPK model that accounts for the involvement of P-glycoprotein activity and expression in mouse brain, liver, kidney and heart tissues. Model parameters of P-gp activity and drug diffusion were mainly extrapolated from in vitro data. Model simulations, compared with tissue concentration of 3H-domperidone intravenously administered toWT and KO mice, suggest the involvement of additional membrane transporters in heart and brain tissues. The global sensitivity analysis showed that the variability of model predictions is related to the variability of the unbound fraction to plasma protein, whereas the uncertainty of the model predictions is associated with the uncertainty of the parameters related to P-gp genetic expression, and to the activity of additional transporters in heart and brain tissues. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)