Jean-Philippe Bouillon

Incorporation of a 3‑(2,2,2-Trifluoroethyl)-γ-hydroxy-γ-lactam Motif in the Side Chain of 4‑Aminoquinolines. Syntheses and Antimalarial Activities

In this paper we report the synthesis and antimalarial properties of two series of fluoroalkylated γ-lactams derived from 4-aminoquinoline as potent chemotherapeutic agents for malaria treatment. These molecules obtained in several steps resulted in the identification of very potent structures with in vitro activity against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) in the range of 19-50 nM with resistance indices in the range of 1.0-2.5. In addition, selected molecules (50, 51, 58, 60, 63, 70, 72, 74, 78, 81, 84, and 87) that are representative of the two series of compounds did not show cytotoxicity in vitro when tested against human umbilical vein endothelial cells up to a concentration of 100 μM. The most promising compounds (82 and 84) showed significant IC₅₀ values close to 26 and 19 nM against the chloroquino-sensitive strain 3D7 and 49 and 42 nM against the multi-drug-resistant strain W2. Furthermore, two model compounds (50 and 70) were found to be quite stable over 48 h at pH 7.4 and 5.2. Overall, our preliminary data indicate that this class of structures contains promising candidates for further study.

Convex hull: a new method to determine the separation space used and to optimize operating conditions for comprehensive two-dimensional gas chromatography.

It is important to develop methods of optimizing the selection of column sets and operating conditions for comprehensive two-dimensional gas chromatography. A new method for the calculation of the percentage of separation space used was developed using Delaunays triangulation algorithms (convex hull). This approach was compared with an existing method and showed better precision and accuracy. It was successfully applied to the selection of the most convenient column set and the geometrical parameters of second column for the analysis of 49 target compounds in wastewater.

Asymmetric synthesis of (2S,3R) β-(4-F-3-NO2) phenyl serine, D-(R)-4-methoxy-3,5-bistbutyldimethylsiloxy phenylglycine and their assemblage to C-O-D ring of vancomycin

The asym. synthesis of two appropriately functionalized nonproteinogenic amino acids I (Troc = CO2CH2CCl3, TBS = SiMe2CMe3) and II (Boc = Me3CO2C) needed for the total synthesis of vancomycin is described. The assemblage of these amino acids into linear tripeptide followed by biaryl ether formation via intramol. SNAr reaction led to the fully functionalized C-O-D ring III of vancomycin. [on SciFinder (R)]

(l)- or (d)-Valine tert-butylamide grafted on permethylated β-cyclodextrin derivatives as new mixed binary chiral selectors: Versatile tools for capillary gas chromatographic enantioseparation

This work deals with the synthesis of two mixed binary chiral selectors prepared by grafting (L)- or (D)-valine tert-butylamide on permethylated cyclodextrin macrocycle. The enantioselective properties of the new chiral selectors diluted in OV11 polysiloxane (35% phenyl- and 65% methylsiloxane) were investigated by means of injections of 117 racemic mixtures. The mixed chiral selectors with (L)-valine and, to a lesser extent with (D)-valine, were found to have an improved enantioselectivity toward amino acid derivatives by comparison to permethylated cyclodextrin. The enantioseparation capability of these new chiral selectors has proven to be slightly less efficient than Chirasil-L-Val (Alltech) for amino acid derivatives, but it has been extended to include terpenes, lactones, esters, aliphatic compounds and aryl alcohols.

Synthesis of a modified carboxylate-binding pocket of vancomycin

A 16-membered tetrapeptide macrocycle I, an analog of the vancomycin binding pocket, has been designed and synthesized using the efficient macrocyclization of the corresponding linear tetrapeptide via biaryl ether formation. In acetone, I adopted a right conformation needed for binding carboxylate anion even in the absence of -Ac-D-Ala-D-Ala-OH. [on SciFinder (R)]

Fluorinated ketene dithioacetals. Part IX. Synthesis and some chemical properties of new fluorinated 3H-1,2-dithiole-3-thiones

Abstract 4-Fluoro-5-perfluoroalkyl-3 H -1,2-dithiole-3-thiones were prepared by heating the corresponding ketene dithioacetals with magnesium bromide and elemental sulfur. They reacted as dienophiles and 1,3-dipoles in cycloaddition reactions to give new fluorinated organosulfur compounds.

Use of comprehensive two-dimensional gas chromatography for the broad screening of hazardous contaminants in urban wastewaters

The list of priority chemicals included in various regulations such as the European Water Framework Directive, as well as the list of hazardous contaminants identified in the aquatic environment, are increasing at an accelerated pace. Therefore, there is a need for broad spectrum methods capable of simultaneously determining hundreds, if not thousands, of contaminants. For the analysis of non-polar or semi-polar contaminants, comprehensive two-dimensional gas chromatography (GC x GC) is more powerful than conventional gas chromatography thanks to a separation on two different stationary phases. This paper reports the use of GC x GC for a broad screening of hazardous contaminants in an urban wastewater plant. Comparison between the raw and treated wastewater has been carried out using a semi-quantitative approach. A variety of drugs, personal care products, pesticides, carcinogens and compounds toxic for reproduction, were identified. Most of these compounds were removed or decreased by this wastewater treatment plant. Preliminary results from this single plant will need to be confirmed by a more extensive study before drawing conclusions on the removal efficiency of 2D-GC amenable compounds.

First efficient synthesis of SF5-substituted pyrrolidines using 1,3-dipolar cycloaddition of azomethine ylides with pentafluorosulfanyl-substituted acrylic esters and amides

For the first time, di-, tri- and tetrasubstituted pentafluorosulfanylated pyrrolidines have been efficiently synthetized via 1,3-dipolar cycloaddition. In the case of tetra-substituted pyrrolidines, an unusual mixture of 1/1 regioisomers was obtained. Theoretical calculations have been carried out and the regioselectivity has been explained compared to the results previously obtained in the trifluoromethylated pyrrolidine series.

Fluorinated ketene dithioacetals. Part 7: New β-halo perfluorodithiocrotonic acid esters from perfluoroketene dithioacetals

Abstract Esters of β-bromo or β-chloro perfluorodithiocrotonic acid were prepared from corresponding ketenedithioacetal with anhydrous magnesium halides. These new polyfluorinated dithiocarboxylates are good dienophiles reacting selectively via the CS bond.

Synthesis and Intramolecular Aldol Reactions of 1,6- and 1,7-Bis(acylsilanes)

A series of 1,6- and 1,7-bis(acylsilanes) have been prepared using a strategy of substitution of dihalo derivatives with a synthetic equivalent of the trialkylsilylcarbonyl anion. These bis(acylsilanes) could easily be converted, under Lewis acid activation, into cis-β-hydroxyacylsilanes or the corresponding α,β-unsaturated derivatives, by means of a completely stereoselective intramolecular aldol reaction.