Olivier Duval

Synthesis, biological activity and comparative analysis of DNA binding affinities and human DNA topoisomerase I inhibitory activities of novel 12-alkoxy-benzo[c]phenanthridinium salts

New antitumor 12-alkoxy-benzo[c]phenanthridinium derivatives were obtained in high yields through multistep syntheses. Analysis of DNA binding and human DNA topoisomerase I inhibitory activities demonstrates that new compounds, combining 2, 6, and 12 substitutions, interact strongly with DNA and exhibit important topoisomerase I inhibition. The cytotoxicities against solid tumor cell lines are also determined and compared with those for fagaronine and ethoxidine.

First 2-Hydroxy-3-Methylbut-3-Enyl Substituted Xanthones Isolated From Plants: Structure Elucidation, Synthesis and Antifungal Activity

Two new 2-hydroxy-3-methylbut-3-enyl substituted xanthones, ( - )-caledol 1 and ( - )-dicaledol 2 were isolated from a dichloromethane extract of the leaves of Calophyllum caledonicum (Clusiaceae). Compounds 1 and 2 are the first 2-hydroxy-3-methylbut-3-enyl substituted xanthones isolated from natural source. Their structures were elucidated by means of combined analytical methods including HRFABMS, 1D and 2D NMR spectroscopies and also confirmed by total synthesis using biomimetic ortho -prenylphenols photooxygenation ( 1 O 2 ) as a key step. The antifungal activity against Aspergillus fumigatus is reported.

Regioselectivity in the ene reaction of singlet oxygen with ortho-prenylphenol derivatives

The ene reaction of singlet oxygen with prenylated dihydroxyacetophenones led to the 2-hydroperoxy-3-methylbut-3-enyl derivatives as the major product. This original regioselectivity outlined a new effect, in competition with the previously established large group non-bonding effect. The oxidation products distribution could be explained by a stabilising interaction between the phenolic hydrogen, ortho to the prenyl side chain, and the perepoxide intermediate.

ortho-Prenylphenol photooxygenation as a straightforward access to ortho-(2-hydroxy-3-methylbut-3-enyl)phenols

Abstract Photooxygenation (1O2) of ortho-prenylphenols followed by a reduction (PPh3) at low temperature (−30°C) yields a mixture of ortho-(2-hydroxy-3-methylbut-3-enyl)phenols and ortho-(3-hydroxy-3-methylbut-1-enyl)phenols. However, by running the two-step sequence at a higher temperature (15°C), the secondary allylic alcohol could be selectively recovered.

Nouvelle methode de synthese des (furyl-2)-2 cyclanones

Abstract A high yield new synthesis of 2-(2-furyl)-cycloalkanones is described. The first step consists in a condensation of 2,5-dimethoxy-2,5-dihydro-furan with various cyclic β-ketoesters in acidic medium. The decarboalkoxylation is then realised in the presence of lithium chloride and in a polar aprotic solvent according a modified Krapcho reaction. This synthesis is extended to cyclopentanone, cyclohexanone, tetralones-1 (simple, 6-methoxylated or 6,7-methoxylated), dimethoxy-5,6 methyl-3 indanone-1 and benzosuberone-1 β-ketoesters.

A convenient synthesis of 2-(2-furyl)-cycloalkanones : an application to benzo[c]phenanthridone ring formation

Abstract An easy, high yield synthesis of 2-(2-furyl)-cycloalkanones is described in conjunction with an integrated strategy to a useful construction of benzo[c]phenanthridone alkaloid analogs.

Synthesis and Antiviral Effect against Herpes Simplex Type 1 of 12-substituted Benzo[c]phenanthridinium Salts

The synthesis of benzo[c]phenanthridine alkaloid derivatives is described. In vitro antiviral activity against herpes simplex type 1 (HSV1) has been investigated. Contrary to the natural product fagaronine, which did not have any activity in the HSV1 antiviral tests, four 12-alkoxy derivatives showed good activity demonstrating the importance of the 12-substitution in the structure-activity relationships.

Synthèse originale des carboxy-7 benzo[c]phenanthridones

Abstract A convenient carboxy-7 benzo[c]phenanthridones synthesis is described. (Furyl-2)-2 tetralones-1 1 react with dimethylacetylenedicarboxylate to give dienic adducts 2 . Aromatisation of 2 yields phtalic derivatives 3 which are further O-methylated, hydrolysed in alcaline solution and deshydrated into anhydrides 4 . Lactamisation of 4 in the presence of ammonium acetate and in anhydrous acetic medium provides carboxy-7 benzo[c]phenanthridones 16 .

Synthesis and cytotoxic activity against a non-small-cell bronchopulmonary carcinoma line (NSCLC-N6) of benzofuran enantiomeric derivatives.

The synthesis of 2-isopropenyl-2,3-dihydrobenzofuranic enantioisomers is described. Ortho-(2-hydroxy-3-methylbut-3-enyl)phenol synthons are used as precursors to these structures. In vitro antitumor activity against a non-small-cell bronchopulmonary carcinoma line (NSCLC-N6) of these enantioisomers has been investigated.

The 24th Conference of the Groupement des Pharmacochimistes de l'Arc Atlantique (GP2A).

The GP2A European Conference is a two-day meeting focused on medicinal chemistry and the use of tools to explore all fields of drug discovery and drug design such as molecular modelling, bioorganic chemistry, MS studies, in vitro in vivo assays, and structure activity relationships. Abstracts of keynote lectures, plenary lectures, junior lectures, flash presentations, and posters presented during the meeting are collated in this report.