Combining prolinamides with 2-pyrrolidinone: Novel organocatalysts for the asymmetric aldol reaction

Peptides and especially prolinamides have been identified as excellent organocatalysts for the aldol reaction. The combination of prolinamides with derivatives bearing the 2-pyrrolidinone scaffold, deriving from pyroglutamic acid, led to the identification of novel organocatalysts for the intermolecular asymmetric aldol reaction. The new hybrids were tested both in organic and aqueous media. Among the compounds tested, 22 afforded the best results in petroleum ether, while 25 afforded the products in brine in high yields and selectivities. Then, various ketones and aldehydes were utilized and the products of the aldol reaction were obtained in high yields (up to 100%) with excellent diastereo- (up to 97:3 dr) and enantioselectivities (up to 99% ee).     

Determination of diethylhexyladipate and acetyltributylcitrate in aqueous extracts after cloud point extraction coupled with microwave assisted back extraction and gas chromatographic separation

The determination of commercial plasticizers (di-(2-ethylhexyl)adipate (DEHA) and acetyl tributyl citrate (ATBC)) in aqueous solutions is described. The newly proposed technique of applying microwaves to cloud point extracts in order to enable combination with gas chromatographic analysis has been used for this purpose. Both plasticizers were entrapped in the micelles of the non-ionic surfactant Triton X-114 and removed from the bulk phase by centrifugation. Micellization was enhanced by increasing the ionic strength of the solution with concentrated NaCl. Extraction recoveries of the proposed method were over 95% for water and 3% (w/v) aqueous acetic acid and over 85% for 10% (v/v) aqueous ethanol, respectively. The calibration curves obtained, following the proposed methodology have a linear range between 50 and 2000 microg/L for each analyte while the detection limits were as low as 15 and 19 microg/L for DEHA and ATBC, respectively, with an RSD below 5% even for low concentrations. As an analytical demonstration the proposed methodology was applied for the determination of the migration levels of the selected plasticizers from a PVC food packaging film into aqueous simulants.     

Melanotropin Receptors I. Synthesis and Biological Activity of Nα-(5-Bromovaleryl)-Nα-deacetyl-α-melanotropin

Chemical synthesis and biological activities of a new α-melanotropin derivative are described. N^α-(5-Bromovaleryl)-N^α-deacetyl-α-melanotropin contains the 5-bromopentanoyl group as a chemical ‘handle’ in place of the acetyl group of the natural hormone. The synthesis involved a new protected intermediate which allowed the selective deprotection of either the N^α or N^α amino group. The title compound reacted with sodium thiosulfate to give N^α-deacetyl-N^α-(5-(sulfothio)valeryl)-α-melanotropin, a key intermediate for the preparation of tobaccomosaic virus/α-melanotropin disulfide conjugates. As a basis for the study of the conjugates, biological activities of the title compound on Cloudman S-91 mouse melanoma cell cultures (tyrosinase stimulation, binding, and cyclic AMP accumulation) were determined. They proved to be quite similar to the corresponding α-melanotropin activities. Differences in bindings may be explained by stronger hydrophobic interaction of the new derivative with the lipid phase of the target cell membranes.     

The classification of locally conformally flat Yamabe solitons

This paper addresses the classification of locally conformally flat gradient Yamabe solitons. In the first part it is shown that locally conformally flat gradient Yamabe solitons with positive sectional curvature are rotationally symmetric. In the second part the classification of all radially symmetric gradient Yamabe solitons is given and their correspondence to smooth self-similar solutions of the fast diffusion equation on Rⁿ${\mathbb{R}}^n$ is shown. In the last section it is shown that any eternal solution to the Yamabe flow with positive Ricci curvature and with the scalar curvature attaining an interior space–time maximum must be a steady Yamabe soliton.     

An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT<Subscript>1</Subscript> Angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies

A new 1,5 disubstituted imidazole AT₁ Angiotensin II (AII) receptor antagonist related to losartan with reversion of butyl and hydroxymethyl groups at the 2-, 5-positions of the imidazole ring was synthesized and evaluated for its antagonist activity (V8). In vitro results indicated that the reorientation of butyl and hydroxymethyl groups on the imidazole template of losartan retained high binding affinity to the AT₁ receptor concluding that the spacing of the substituents at the 2,5- positions is of primary importance. The docking studies are confirmed by binding assay results which clearly show a comparable binding score of the designed compound V8 with that of the prototype losartan. An efficient, regioselective and cost effective synthesis renders the new compound as an attractive candidate for advanced toxicological evaluation and a drug against hypertension.     

Combined Effect of Temperature and Ternary Mobile Phase Composition on the Retention in Ternary Isocratic and Gradient Elution RP-LC under Isothermal Conditions. Application to the Retention Prediction of Four Macrolide Antibiotics

Retention models considering simultaneously ternary mobile phase organic contents and column temperature (T) were developed by a direct combination of equations expressing separately the dependence of the retention upon each of these factors. Thus, a combination of a linear dependence of the logarithm of the solute retention factor, ln k (T), against 1/T, i.e. ln k (T) = a + b/T, and of either a linear or a quadratic dependence of ln k upon the compositions of a binary mobile phase, gave two different expressions for the logarithm of the solute retention factor in terms of both temperature and organic contents in the ternary mobile phase. The effectiveness of the above models was tested in the prediction of isothermal retention of a mixture of four macrolide antibiotics under ternary isocratic and gradient elution conditions using mobile phases modified by methanol and acetonitrile. The limiting case of using ternary eluents with constant ratio of the concentrations of the two organic modifiers was also tested.     

Direct RP‐HPLC determination of underivatized amino acids with online dual UV absorbance,fluorescence, and multiple electrochemical detection

The combined use of a dual‐UV detector, a fluorimetric one and of a multiple electrochemical (EC) detector equipped with a dual electrode, consisting of a conventional size 3 mm diameter glassy carbon electrode (GCE) and of a pair of 30 μm thick carbon microfibers, is proposed for the determination of 15 amino acids, two dipeptides and creatinine. This online coupling of the above detection modes could partially replace amino acid analysis by derivatization methods, since it solves problems concerning the direct detection of selected underivatized amino acids. Additionally, it was proved that the use of multiple‐detection allows positive peak identification in a single chromatographic run, yields more information for free amino acids and solves in some cases the problem of chromatographic resolution. In order to optimize the detection conditions of the underivatized amino acids and related compounds by different detectors, their detection characteristics were determined by adequate preliminary experiments. The electro‐oxidation characteristics of the underivatized compounds of interest were determined by hydrodynamic voltammetry using a flow cell with a macrodisc GCE and by ex‐situ voltammetry using both a GCE of conventional size and a carbon fiber disk microelectrode. Important practical advantages of microfiber and microdisk electrodes with respect to macroelectrodes were demonstrated.     

Convexity and all‐time C∞‐regularity of the interface in flame propagation

We consider the following one‐phase free boundary problem: Find (u, Ω) such that Ω = {u > 0} and with Q_T = ?ⁿ × (0, T). Under the condition that Ω_o is convex and log u_o is concave, we show that the convexity of Ω(t) and the concavity of log u(·, t) are preserved under the flow for 0 ≤ t ≤ T as long as ?Ω(t) and u on Ω(t) are smooth. As a consequence, we show the existence of a smooth‐up‐to‐the‐interface solution, on 0 < t < T_c, with T_c denoting the extinction time of Ω(t). We also provide a new proof of a short‐time existence with C^2,α initial data on the general domain. © 2002 John Wiley & Sons, Inc.