Jean-Marie Coustard

Natural product hybrid and its superacid synthesized analogues: Dodoneine and its derivatives show selective inhibition of carbonic anhydrase isoforms I, III, XIII and XIV"

The natural product dodoneine (a dihydropyranone phenolic compound), extracted from African mistletoe Agelanthus dodoneifolius, has been investigated as inhibitor of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. By using superacid chemistry, analogues of the lactone phenolic hybrid lead compound have been synthesized and tested as CA inhibitors. Small chemical modifications of the basic scaffold revealed strong changes in the selectivity profile against different CA isoforms. These new compounds selectively inhibited isoforms CA I (K(I)s in the range of 0.13-0.76 μM), III (K(I)s in the range of 5.13-10.80 μM), XIII (K(I)s in the range of 0.34-0.96 μM) and XIV (K(I)s in the range of 2.44-7.24 μM), and can be considered as new leads, probably acting as non-zinc-binders, similar to other phenols/lactones investigated earlier.

Acetylation of aromatics over acid zeolites: Seeking a viable alternative to Friedel-Crafts catalysts*

Three acid zeolites (H-BEA, H-FAU, and H-MWW) were used as catalysts for acetylation in batch reactors with acetic anhydride of five aromatic compounds (benzenic and naphthalenic derivatives). The substrate reactivity is mainly governed by electronic factors (the nature of the substituents and degree of ring activation), but steric effects also play a relevant role when the reaction takes place in a narrow micropore system. In general, H-FAU was the most active catalyst, whereas with H-BEA remarkable steric constraints were observed. H-MWW showed good stability toward deactivation and an interesting activity of the sites located on the external surface.

From the vasodilator and hypotensive effects of an extract fraction from Agelanthus dodoneifolius (DC) Danser (Loranthaceae) to the active compound dodoneine.

AIM OF THE STUDY Effects of the different fractions obtained by partition of ethanolic extract (EE) of Agelanthus dodoneifolius through column chromatography were investigated on rat blood pressure and aortic relaxation and compared to those observed in the presence of crude EE. MATERIALS AND METHODS The acute hypotensive activity of EE, fractions and dodoneine, administrated intravenously, was evaluated in anaesthetized rats using the invasive method of blood pressure recording. Bioassay-guided fractionation using rat aorta pre-contracted by norepinephrine to monitor the relaxant activity led to the isolation of dodoneine. RESULTS In normotensive rats, injection of EE (0.01-10 mg/kg) produced a dose-dependent decrease in both systolic and diastolic blood pressure without any significant change in heart rate. In a similar way, the EE (0.001-3 mg/mL) caused relaxation of rat pre-contracted aorta in a concentration-dependent manner. Fractionation of the EE afforded 14 fractions, F1-F14, that were tested on rat precontracted aortic rings. At the concentration level of 1 mg/mL, a maximum relaxation effect was observed for fractions F2-F5. F4 was the most effective to elicit a concentration-dependent relaxation effect with an ED(50)=160±1.1 μg/mL (n=5) and to decreased systolic and diastolic control pressure by 56.9% and 81.6% respectively. F4 contains most of the dihydropyranone dodoneine, with 93% of the sample mass. Dodoneine separated from this fraction was also able to decrease both systolic and diastolic arterial pressure by 32.5% and 38.7% at 100 μg/kg, respectively. CONCLUSION For the first time, this study demonstrates the hypotensive property of the dodoneine present in Agelanthus dodoneifolius.

Intramolecular Cyclization of 1-(ω-Phenylalkyl)-2-(nitromethylene)pyrrolidines in Triflic Acid

Abstract 1-(ω-Phenylalkyl)-2-(nitromethylene)pyrrolidines in triflic acid undergo a C,O-diprotonation, followed by loss of water, to form conjugated iminium–hydroxynitrilium dications, which react with the tethered phenyl ring by electrophilic aromatic substitution to afford tricyclic iminium compounds as triflate salts. The scope and mechanism of this reaction are discussed. GRAPHICAL ABSTRACT