On the use of boronates in the Petasis reaction

Alcohols are solvents of choice to react boronates, aldehydes and either primary or secondary amines. Thus, while the reaction proceeds sluggishly, or not at all, in aprotic solvents, the desired aminoacids are in most cases obtained in high yields when conducted in methanol or hexafluoro-iso-propanol. In the case of secondary amines, microwave activation is shown to strongly accelerate the process without altering the yields.     

Study of tryptophan enantiomer binding to a teicoplanin-based stationary phase using the perturbation technique. Investigation of the role of sodium perchlorate in solute retention and enantioselectivity

The retention of D,L-tryptophan enantiomers on an immobilized teicoplanin column was investigated in relation to the mobile phase sodium perchlorate concentration using the perturbation method to determine the solute distribution isotherms. From the experimental data, it appeared that the bi-Langmuir model was able to describe D- and L-enantiomer retention on the immobilized selector over the salt concentration range. An increase in the apparent enantioselectivity with an increase in sodium perchlorate concentration was observed. The chiral recognition enhancement was governed by (i) an increase in the difference of the adsorption constants for binding to the high-affinity site (aglycone pocket) between the two enantiomers and (ii) enhancement of the number of aglycone chiral regions interacting with D-tryptophan. It is suggested that an ion-pair formation mechanism between perchlorate and solute and/or selector is responsible for this behavior. In addition, this work shows that additional secondary sites on the teicoplanin surface are involved in the apparent enantioselectivity at low sodium perchlorate concentrations.     

A case study of 2,2-dimethylthiazolidine as locked cis proline amide bond: synthesis, NMR and molecular modeling studies of a delta-conotoxin EVIA peptide analog

The delta-conotoxin EVIA from the Conus ermineus venom, a recently characterized toxin, exhibits cis-trans isomerism of the Leu12-Pro13 bond associated with the triggering of its biological activity. In this paper we use the pseudoproline concept to target the presumed bioactive cis conformation. We report the design and the synthesis of loop 2 analogs from residue 8 to 18 containing either the cis-inducing Cys(PsiMe,MePro)13 unit or the natural proline residue. NMR studies in water and molecular modeling allowed us to identify the amide bond "locked" in a cis conformation for as in the suggested bioactive form of the natural toxin.     

Effects of C-17 heterocyclic substituents on the anticancer activity of 2-ethylestra-1,3,5(10)-triene-3-O-sulfamates: synthesis, in vitro evaluation and computational modelling

The potent activity of 2-substituted estra-1,3,5(10)-triene-3-O-sulfamates against the proliferation of cancer cells in vitro and tumours in vivo highlights the therapeutic potential of such compounds. Optimal activity is derived from a combination of a 2-XMe group (where X = CH(2), O or S), a 3-O-sulfamate group in the steroidal A-ring and a H-bond acceptor around C-17 of the D-ring. Herein, we describe the synthesis and anti-proliferative activities of a series of novel 2-substituted estra-1,3,5(10)-triene-3-O-sulfamates bearing heterocyclic substituents (oxazole, tetrazole, triazole) tethered to C-17. In vitro evaluation of these molecules revealed that high anti-proliferative activity in breast and prostate cancer cells lines (GI(50) of 340-850 nM) could be retained when the heterocyclic substituent possesses H-bond acceptor properties. A good correlation between the calculated electron density of the heterocyclic ring and anti-proliferative activity was observed. Docking of the most active compounds into their putative site of action, the colchicine binding site of tubulin, suggests that they bind through a different mode to the previously described bis-sulfamate derivatives and 1 and 2, which possess similar in vitro activity.     

The effects that changes in the diaphragm aperture have on the resulting shock tube flow

In a conventional shock tube, the driver and the driven sections have similar (if not identical) cross-sectional area and the diaphragm opened area, upon rupturing, is practically equal to the tube cross-sectional area. Such geometry results in generating a well-formed shock wave in the tube’s driven section. The present experimental work checks the effects that changes in the diaphragm ruptured area have on the generated shock and rarefaction waves. Experiments were conducted in an 80?mm by 80?mm cross section shock tube generating incident shock waves having Mach numbers within the range from 1.06 to 1.25. In each run, pressure histories were recorded along the driven and the driver sections of the shock tube. The recorded pressures reveal that progressive reduction in the diaphragm open space resulted in a weaker shock and both longer time and distance until the compression waves generated close to the diaphragm coalesces into a shock wave. In addition, reducing the open space of the diaphragm resulted in a significant slow down in the high pressure reduction prevailing in the driver section.     

Design,Synthesis and SAR in 2,4,7-Trisubstituted Pyrido[3,2-d]Pyrimidine Series as Novel PI3K/mTOR Inhibitors

This work describes the synthesis, enzymatic activities on PI3K and mTOR, in silico docking and cellular activities of various uncommon 2,4,7 trisubstituted pyrido[3,2-d]pyrimidines. The series synthesized offers a chemical diversity in C-7 whereas C-2 (3-hydroxyphenyl) and C-4 groups (morpholine) remain unchanged, in order to provide a better understanding of the molecular determinants of PI3K selectivity or dual activity on PI3K and mTOR. Some C-7 substituents were shown to improve the efficiency on kinases compared to the 2,4-di-substituted pyrimidopyrimidine derivatives used as references. Six novel derivatives possess IC₅₀ values on PI3Kα between 3 and 10 nM. The compounds with the best efficiencies on PI3K and mTOR induced micromolar cytotoxicity on cancer cell lines possessing an overactivated PI3K pathway.     

Dynamic mechanical spectrometry for the study of multiphase polymer materials

The dynamic mechanical behaviour of multiphase polymer materials depends on two factors: (i) properties of each phase and (ii) geometric arrangement of these phases (so-called morphology). Analysis of experimental results has been performed in order to separate these two factors; it leads to informations about morphology, presence of interphase between main phases, chemical composition of different domains and possible changes in physical properties of one phase, induced by its neighbours. The interest in such an analysis based on mechanical spectrometry appears important because of difficulties in direct investigations (low contrast in Electron Microscopy, poor information provided by X-ray measurements on amorphous polymers … )     

A new large cross-section shock tube for studies of turbulent mixing induced by interfacial hydrodynamic instability

Abstract. A new large cross-section shock tube has been developed in order to investigate different stages of the development of the Richtmyer-Meshkov instability and the instability-induced turbulent mixing. The main benefits of such a facility are that it allows, first, to create a free turbulent mixing with the knowledge of its initial conditions and, second, to follow different transition phases from the beginning to the fully developed turbulent stage. Received 10 May 2002 / Accepted 20 July 2002 Published online 4 February 2003 Correspondence to: L. Houas (e-mail: Lazhar.Houas@polytech.univ-mrs.fr)