Jacques Poupaert - Academia.edu (original) (raw)

Papers by Jacques Poupaert

African Journal of Pure and Applied Chemistry, Jul 31, 2011

A reaction system is described to synthesize phenytoin, a major antiepileptic drug, and structura... more A reaction system is described to synthesize phenytoin, a major antiepileptic drug, and structurally related compounds using a two-step approach. The first step involves the treatment of a benzil derivative by thiourea in dimethylsulfoxide (DMSO) in aqueous KOH under microwave activation. The resulting 2-thiohydantoin was then oxidized to the corresponding hydantoin using perhydrol in dimethylformamide (DMF) in acetic acid. Both steps proceeded in high yield. For example, with this method, phenytoin was obtained in 80% yield while by the conventional Biltz's method, the yield rarely exceeded 50%. The first step can be advantageously performed using microwave activation. Our process is based on a mechanistic approach supported by theoretical PM3 calculations.

Molecules, 2021

Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasiti... more Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was to determine triterpenic esters’ stability in different biological-like media and the main microsomal degradation products. An HPLC-PDA method was developed and validated to simultaneously analyze and quantify bioactive triterpenic esters in methanol (LOQ: 2.5 and 1.25–100 µg/mL) and plasma (LOQ: 5–125 µg/mL). Overall, both triterpenic esters showed a stable profile in aqueous and buffered solutions as well as in entire plasma, suggesting gaining access to the ester function is difficult for plasma enzymes. Conversely, after 1 h, 30% esters degradation in acidic media was observed with potential different hydrolysis mechanisms. C-3 (15 and 150 µM) and C-27 esters (150 µM) showed a relativ...

Traditional Chinese Medicine, 2015

Atchade, Bardieu ; Kpoviessi, Salomé ; Glinma, Bienvenu ; Bero, Joanne ; Gbaguidi, Fernand ; et. ... more Atchade, Bardieu ; Kpoviessi, Salomé ; Glinma, Bienvenu ; Bero, Joanne ; Gbaguidi, Fernand ; et. al. Synthèse, identification spectrométrique et activités antiparasitaires d’hydrazones substituées d’arylcetones sur Tripanosoma brucei brucei et sur Plasmodium falciparum.Colloque panafricainpaneuropéeen sur « Chimie et ressources naturelles » ((Benin) Cotonou, du 13/04/2015 au 16/04/2015). http://hdl.handle.net/2078.1/185002

A green synthesis of tetracyclone (2, 3, 4, 5-tetraphenyl-2, 4-cyclopentadien-1-one) has been con... more A green synthesis of tetracyclone (2, 3, 4, 5-tetraphenyl-2, 4-cyclopentadien-1-one) has been conceived and executed on the basis of a rationale design. Three separate, "green" processes to synthesize tetracyclone were undertaken to compare homogeneous and heterogeneous reaction conditions as well as to examine the efficacy of microwave enhancement and the utility of phase transfer catalysis. Our mechanistically-based approach involves a unique solid-liquid phase transfer catalysis, microwave activation, and nucleophilic catalysis involving anthranilic acid as a green catalyst. Use of these methods collectively resulted in a yield of 82% for the title compound with a minimal resultant waste stream.

ChemistryOpen, 2021

Research for innovative drugs is crucial to contribute to parasitic infections control and eradic... more Research for innovative drugs is crucial to contribute to parasitic infections control and eradication. Inspired by natural antiprotozoal triterpenes, a library of 12 hemisynthetic 3‐O‐arylalkyl esters was derived from ursolic and oleanolic acids through one‐step synthesis. Compounds were tested on Trypanosoma, Leishmania and the WI38 cell line alongside with a set of triterpenic acids. Results showed that the triterpenic C3 esterification keeps the antitrypanosomal activity (IC50≈1.6–5.5 μm) while reducing the cytotoxicity compared to parent acids. Unsaturation of the ester alkyl chain leads to an activity loss interestingly kept when a sterically hindered group replaces the double bond or shields the ester group. An ursane/oleanane C3 hydroxylation was the only important feature for antileishmanial activity. Two candidates, dihydrocinnamoyl and 2‐fluorophenylpropionyl ursolic acids, were tested on an acute mouse model of African trypanosomiasis with significant parasitemia reducti...

N(4)-phenyl substituted semicarbazones and thiosemicarbazones (1-4) of propiophenone and 4’- meth... more N(4)-phenyl substituted semicarbazones and thiosemicarbazones (1-4) of propiophenone and 4’- methylacetophenone have been synthesized and characterized by spectrometrical methods analyses (IR, RMN 1H &13C, SM). All compounds were evaluated for their in vitro trypanosomal activity against the bloodstream form of the strain 427 of Trypanosomabruceibrucei and have been tested on larvaeofbrine shrimp, Artemiasalina LEACH, for their toxic activity. The selectivity index (SI) of each molecule was too designed. In the group, propiophenone 4- phenyl-3-thiosemicarbazone 4 has exhibited greater trypanocidal activity with a half-inhibitory concentration (IC50) value equal to 7.63 micromolar (μM). 4’-methylacetophenone 4-phenylsemicarbazone 1 showed moderate antitrypanosomal activity (IC50 = 62.54 μM). Other, 2 and 3, presented little or no activity against the parasite (IC50> 100 μM). Except propiophenone 4-phenylsemicarbazone 2 which offered a toxic activity on larvae given the halflethal ...

African Journal of Pure and Applied Chemistry, 2013

A concise series of aldehydes and ketones were reacted in a condensation reaction with 4phenylthi... more A concise series of aldehydes and ketones were reacted in a condensation reaction with 4phenylthiosemicarbazide in order to assess the relative influence of the steric and electronic effects in the control of this reaction. While steric effects had a modest impact, electronic effects and in particular the mesomeric donating effect delivered by a phenyl ring produced a strong passivating influence on the reactivity of these aldones. Additionally, the cyclopropyl substituent totally passivated the reaction via the interfering factor of its inherent sigma-aromaticity. When reacted with cyclopropyl-phenylketone, under our standard conditions, 4-phenylthiosemicarbazide gave in 82%, an original 1, 4-dihydrotetrazine via a double consecutive self-condensation.

African Journal of Pure and Applied Chemistry, Apr 30, 2011

The thiosemicarbazones of six aromatic ketones were synthesized as well as their 1,3,4-thiadiazol... more The thiosemicarbazones of six aromatic ketones were synthesized as well as their 1,3,4-thiadiazolines derivatives obtained by cyclization under acetylating condition with yields going from 40 to 90%. The products purity was confirmed by mass spectrometry coupled with high-performance liquid chromatography (LC/MS) and there were characterized using spectrometry IR, NMR 1 H and 13 C (nuclear magnetic resonance). These compounds were then tested in vitro on Trypanosoma brucei brucei according to the "LILIT, Alamar Blue" method for a comparison of their trypanocidal activity. Thus, all thiosemicarbazones appeared much more active than their corresponding 1,3,4-thiadiazolines. Thiosemicarbazone 6a (IC 50 = 9.62 µM) was the most active of all thiosemicarbazones tested and it is the same for its thiadiazoline 6b (IC 50 = 49.03 µM) among 1,3,4-thiadiazolines.

Journal of chemical and pharmaceutical research, 2015

Relying on a straightforward « Green-Chemistry » based approach, this article reports an optimize... more Relying on a straightforward « Green-Chemistry » based approach, this article reports an optimized Diels-Alder (DA) experimental set-up allowing for this reaction to be cleanly operated in the presence of water used both as solvent and catalyst. This work was initiated to synthesize a cantharidine-derived trypanocidal pilot-molecule. Diels-Alder cyclo-addition between anthracene-9-methanol and maleimide in water was selected as benchmark reaction and demonstrated how water as a solvent can be used not only because of its more benign impact on the environment but also because it improves some key aspects (rate, yield, ease of isolation) of the reaction. Adjunction of lithium chloride into the reaction medium adds a significant incremental benefit to the overall yield due to its oxophilic character increasing electron demand at dienophile’s double bond. Our set-up illustrates a typical condition of « on-water » reaction rather then « in-water » reaction conditions. Conclusively, in th...

European Journal of Medicinal Chemistry, 2018

The bacterial cell wall and the enzymes involved in peptidoglycan synthesis are privileged target... more The bacterial cell wall and the enzymes involved in peptidoglycan synthesis are privileged targets for the development of novel antibacterial agents. In this work, a series of 1-(2-hydroxybenzoyl)-thiosemicarbazides inhibitors of D-Ala-D-Ala ligase (Ddl) were designed and synthesized in order to target resistant strains of bacteria. Among these, the 4-(3,4-dichlorophenyl)-1-(2-hydroxybenzoyl)-3thiosemicarbazide 29 was identified as a potent Ddl inhibitor with activity in the micromolar range. This compound, possessing strong antimicrobial activity including against multidrug resistant strains, was proven to act through a bactericidal mechanism and demonstrated very low cytotoxicity on THP-1 human monocytic cell line. Inhibition of Ddl activity by 29 was confirmed in bacterio using UPLC-MS/MS by demonstrating an increase in D-Ala intracellular pools accompanied by a commensurate decrease in D-Ala-D-Ala. Further structure-activity relationships (SARs) studies provided evidence that the hydroxyl substituent in the 2-position (R 1) of the benzoylthiosemicarbazide scaffold is essential for the enzymatic inhibition. This work thus highlights the 1-(2-hydroxybenzoyl)-thiosemicarbazide motif as a very promising tool for the development of novel antibacterial compounds acting through an interesting mechanism of action and low cytotoxicity.

Organic Chemistry: Current Research, 2017

The Willgerodt-Kindler (WK) reaction of is one of most synthesis methods used to access the thioa... more The Willgerodt-Kindler (WK) reaction of is one of most synthesis methods used to access the thioamides. The known to thioamides have made this reaction more attractive in catalytic synthesis methods. Heterogeneous catalysis acid with the montmorillonite K-10 applied to this reaction under activation microwave for the synthesis of phenyl (morpholino) methanethiones derivatives shows that the mixture (aldehyde, sulfur, morpholine and K-10) is not only appropriate, but optimizes the reaction. This solid catalyst was easily separated from the reaction mixture and was recycled at least twice (02) without any loss of activity. Operational simplicity, short reaction times, excellent yields and benign environmental conditions are other advantages of this protocol, thus respecting the principles of green chemistry. Among the thioamides synthesized, 4-(morpholine-4-carbonothioyl)benzoic acid (h) is a novel molecule which to our knowledge has never before been synthesized. We obtained it with a yield of 68%. In summary, we can be concluded that the heterogeneous catalysis acid conditions with the montmorillonite K-10 favourable to the Willgerodt-Kindler reaction for carbonyl compounds. The structures of thioamides synthesized were characterized and confirmed by highresolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) 1D and 2D (COSY, HSQC, HMBC).

Synthesis, characterization and trypanocidal activity of some aromatic thiosemicarbazones and the... more Synthesis, characterization and trypanocidal activity of some aromatic thiosemicarbazones and their 1,3,4-thiadiazolines derivatives

Extraction and analysis GC/FID and GC/MS showed that citral (neral + geranial) is the major compo... more Extraction and analysis GC/FID and GC/MS showed that citral (neral + geranial) is the major compound of the essential oil of Benin Cymbopogoncitratus. This aldehyde was used as target for the hemi-synthesis in situ of the semicarbazone and substituted thiosemicarbazones. Their structures were confirmed by spectrometric analysis IR, 1H and 13C NMR. Their antiparasitic activities have been evaluated on Trypanosomabruceibrucei by determining their half-inhibitory concentrations (IC50). Among them, citral 4-phenyl-3-thiosemicarbazone (IC50 = 1.96 µM) and citralthiosemicarbazone (IC50 = 7.6 µM) showed a strong trypanocidal activity. Citral 2-methyl-3- thiosemicarbazone (IC50 = 60.87 µM) showed a moderate activity. Citral 4-methyl-3-thiosemicarbazone (IC50 = 172.84 µM) and citralsemicarbazone (IC50 = 234.64 µM) were less actives. Toxicity test against Artemiasalina indicated that citral 4-phenyl-3-thiosemicarbazone is the most toxic compound (LC50 = 70.70 µM). The toxicities of other comp...

Current Green Chemistry, 2017

Background: Interest for the Diels-Alder (DA) reaction has steadily increased over the time and t... more Background: Interest for the Diels-Alder (DA) reaction has steadily increased over the time and the end of this remarkable development is not yet in sight. From its discovery on, the DA reaction has evolved through different stages of development, and since the beginning of the 21st century catalytic Diels-Alder reactions remains obviously one of the main areas of research. Methods: As there are striking similarities in the catalysis of both DA and Friedel-Crafts reaction, we therefore anticipated that DMF (a weak Lewis base) and iodine (a weak Lewis acid) could act synergistically and smoothly in the DA reaction, and we selected the cyclo-addition of maleimide to anthracene- 9-methanol as our benchmark reaction in order to be able to accurately compare our actual data with the results of our previous publications. Results: Based on Pearson's SHAB (Soft and Hard Acids and Bases) theory, we have first established that the Diels-Alder cyclo-addition of our benchmark reaction (anthracene-9-methanol and maleimide) is a process submitted to generalized acid-base catalysis and in a second step we have developed within the context of the Green Chemistry an original efficient catalyst i.e. the DMF.I2 complex where DMF acts as Lewis base and iodine as Lewis acid. In order to expand the scope of title catalyst, the cyclo-addition of tetracyclone with N-phenylmaleimide was carried out successfully using DMF.I2 in n-butanol and led to both endo and exo adducts in good yields. Conclusion: It is noteworthy that the molar ratio of diiodine vs. dienophile can be successfully scaled down to 10% without significant detrimental effect on the time of reaction and final yield (1 h, 100°C, 93%)

Data in brief, 2016

This article reports data on four carbazones of piperitone: semicarbazone 1, thiosemicarbazone 2,... more This article reports data on four carbazones of piperitone: semicarbazone 1, thiosemicarbazone 2, 4-phenyl semicarbazone 3 and 4-phenyl thiosemicarbazone 4 prepared directly in situ from essential oil of Cymbopogon schoenantus, whose GC-FID and GC-MS analysis revealed piperitone as major component (68.20%). The structures of hemi-synthesized compounds were confirmed by high throughput IR, MS, (1)H and (13)C NMR based spectrometric analysis. Their antiparasitic activities were evaluated in vitro on Trypanosoma brucei brucei (Tbb). The compound 3 (IC50=8.63±0.81 µM) and 4 (IC50=10.90±2.52 µM) exhibited antitrypanosomal activity, 2 had a moderate activity (IC50=74.58±4.44 µM) but 1 was void of significant activity (IC50=478.47 µM). The in vitro tests showed that all compounds were less cytotoxic against the human non cancer fibroblast cell line (WI38) (IC50>80 µM) while only 2 (IC50=21.16±1.37 μM) and 4 (IC50=32.22±1.66 µM) were cytotoxic against the Chinese Hamster Ovary (CHO) cell...

Journal De La Societe Ouest Africaine De Chimie, 2010

La reaction de l'acenaphtone avec la morpholine et les sulfures a ete etudiee dans le but d&#... more La reaction de l'acenaphtone avec la morpholine et les sulfures a ete etudiee dans le but d'evaluer les effets des sources d'acide ou de base additionnee dans la reaction de Willgerodt-Kindler (WK). L'ajout d'un acide fort comme la Montmorillonite K10 (particulierement benefique au cours de cette experience) a montre que ce melange est le meilleur reactif pour cette reaction. Comme les meilleures conditions impliquent l'usage d'un acide fort en presence d'un exces de morpholine (utilisee aussi comme une base), on peut deduire qu'en general les conditions de la catalyse acido-basique favorisent la reaction de W.K.

African Journal of Pure and Applied Chemistry, Mar 27, 2014

2-chloroacetophenone-thiosemicarbazone and 4-bromoacétophénone-thiosemicarbazone are compounds en... more 2-chloroacetophenone-thiosemicarbazone and 4-bromoacétophénone-thiosemicarbazone are compounds endowed with numerous pharmacological properties. In order to produce therapeutic agents using clay as excipient, this paper deals with the absorption kinetics of a clay originating from Oueme valley in Benin. A prospection in this area gave rise to the collection of 4 samples classified according to their color (yellow, white, black, and red). Toxicity studies performed on larvae gave no evidence of toxicity. These clays are highly hydrophilic and can accept a high load of organic material. The white clay, which is the least acidic, shows the best adsorption capacity. Additional experiments were carried out with this clay in ethanol. Best adsorption was obtained after 2 h. Absorption isotherms indicate low affinity between the clay and the thiosemicarbazones and can be modelized using Langmuir and Freundlich's models.