Gérard Coudert

Palladium-catalyzed coupling of vinyl phosphates with aryl or heteroaryl boronic acids. Application to the synthesis of substituted nitrogen containing heterocycles

Abstract Substituted nitrogen-containing heterocycles were prepared in three steps from commercially available derivatives via an extension of the Suzuki reaction involving the palladium-catalyzed coupling of vinyl phosphates with aryl or heteroaryl boronic acids.

A mild and selective method for N-Boc deprotection

Abstract A new mild method to remove N - tert -butyloxycarbonyl groups using TBAF in refluxing THF is reported. In all cases, the corresponding N -free products are obtained in good yields. The reactions are selective for acid- and base-sensitive groups, such as tert -butyl and alkyl esters, aldehydes.

Synthesis of 3-Substituted and 2,3-Disubstituted-4H-1,4-Benzoxazines

Abstract Two new and efficient synthetic routes towards substituted 4H-1,4-benzoxazine derivatives were reported. The first one involves the synthesis in four steps of the 4-Boc-4H-1,4-benzoxazine and its regioselective substitution on C-3 following a lithiation–electrophilic substitution sequence. The second route involves palladium-catalyzed coupling reactions between organostannanes and a vinylphosphate obtained from a benzoxazin-3-one derivative.

A Novel, Unequivocal Synthesis of Polyethylene Glycols

Abstract Unequivocal synthesis of polyethyleneglycols is presented. The key step for this synthesis is the selective monobenzylation of oligoethyleneglycols by the phase transfer catalysis technique.

Palladium-catalysed coupling of vinyl phosphates with aryl or heteroaryl boronic acids. Application to the synthesis of substituted nitrogen containing heterocycles

Abstract Unusual substituted nitrogen-containing heterocycles were prepared in three steps from commercially available derivatives via an extension of the Suzuki reaction involving the palladium-catalysed coupling of vinyl phosphate with aryl or heteroarylboronic acids.

SYNTHESIS OF 3-SUBSTITUTED-4H-1,4-BENZOXAZINES VIA PALLADIUM-CATALYSED COUPLING REACTIONS

Here is described a high yield synthesis of 3-substituted 4H-1,4-benzoxazines via palladium-catalysed coupling reactions between organostannanes and a vinylphosphate obtained from a benzoxazin-3-one derivative.

Chiral separation of phospine‐containing α‐amino acid derivatives using two complementary cellulosic stationary phases in supercritical fluid chromatography

Enantiomeric separations of six amino-acid derivatives have been studied using packed-column supercritical fluid chromatography with two polysaccharide-based enantioselective stationary phases: cellulose tris(3,5-dimethylphenylcarbamate) and cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux Cellulose-1 and -2). The effect of analyte structure on retention and separation was studied. Varied mobile phase compositions were investigated: alcohol modifier percentage was increased from 3 to 40% but smaller amounts were most effective in separating these compounds. Besides, ethanol was preferred to methanol or isopropanol as it proved to be a good compromise to achieve sufficient resolution in a reasonable analysis time. Moreover, a carbon dioxide-ethanol mixture allows performing analyses in safe and green conditions. The effect of temperature at constant mobile phase composition was explored between 10 and 40 degrees C. In most cases, increasing the temperature improved the chiral separation, up to an optimum temperature. The results are discussed in line with the structure variation of the racemic derivatives analyzed and the two columns are compared. The two columns were shown to provide complementary selectivities for the investigated solutes: whereas Lux 1 provided separation for five of the six racemates, Lux 2 could resolve the last racemic mixture. Finally, optimized conditions of separation are defined.

Synthesis and biological evaluation of 7-azaindolocarbazoles

Abstract In the course of a program aimed at designing antitumor agents containing an indolocarbazole framework, an efficient synthetic scheme based on the use of 3,4-dibromo- N -methylmaleimide and 7-azaindole has been developed to elaborate a series of mono- and di-aza derivatives of arcyriaflavin. The procedure was further exploited to introduce a hydroxyl group at different positions on the indole moiety of the non-symmetrical compounds. The DNA binding capacity and cytotoxic potential of these 7-azaindolocarbazole derivatives was evaluated.

DNA interaction and cytotoxicity of a new series of indolo[2,3-b]quinoxaline and pyridopyrazino[2,3-b]indole derivatives

Absorption, melting temperature and linear dichroism measurements were performed to investigate the interaction with DNA of a series of 16 tricyclic and tetracyclic compounds related to the antiviral agent B-220. The relative DNA affinity of the test compounds containing an indolo[2,3-b]quinoxaline, pyridopyrazino[2,3-b]indoles or pyrazino[2,3-b]indole planar chromophore varies significantly depending on the nature of the side chain grafted onto the indole nitrogen. Compounds with a dimethylaminoethyl chain strongly bind to DNA and exhibit a preference for GC-rich DNA sequences, as revealed by DNase I footprinting. Weaker DNA interactions were detected with those bearing a morpholinoethyl side chain. The incorporation of a 2,3-dihydroxypropyl side chain does not reinforce the DNA interaction compared with the unsubstituted analogues. Both the DNA relaxation assay and cytotoxicity study using two human leukemia cell lines sensitive (HL-60) or resistant (HL-60/MX2) to the antitumor drug mitoxantrone, indicate that topoisomerase II is not a privileged target for the test compounds which only weakly interfere with the catalytic activity of the DNA cleaving enzyme. Cytometry studies showed that the most cytotoxic compounds induce a massive accumulation of cells in the G2/M phase of the cell cycle. Collectively, the data show a relationship between DNA binding and cytotoxicity in the indolo[2,3-b]quinoxaline series.

SYNTHESIS OF A BENZODIOXINIC ANALOG OF 8-METHOXYPSORALEN

Abstract A synthesis of a benzodioxinic analog of 8-methoxypsoralen (8-MOP), in 12 steps from the commercially available 6-acetyl-2,3-dihydro-1,4-benzodioxin, is described.