Résumé: An efficient preparation of (S)-N-benzyl-2-(4-isobutylphenyl)propanamide (S)-AMD via direct condensation of (S)-IBU and benzylamine catalyzed, by the immobilized Candida antarctica lipase fraction-B, is described. A mechanistic study of the enzymatic amidation is performed, aided by molecular docking. This study is coupled with the evaluation of the inhibitory potency of the prodrug amide through docking simulations into the active sites of the human hCOX-1 (6Y3C) and hCOX-2 (5KIR) enzymes. Furthermore, the potential anti-inflammatory activity of the synthesized (S)-AMD is evaluated using an albumin denaturation inhibition assay. In silico calculations of pharmacokinetic properties, toxicity and bioactivity are also reported. Based on the findings of this study, it has been shown that the prodrug presents better anti-inflammatory properties than the parent drug, (S)-Ibuprofen, and may be considered a potent selective COX-2 inhibitor.

Résumé: Eco-friendly and simple procedure has been developed for the synthesis of α-aminophosphonates that act as topoisomerase II α-inhibiting anticancer agent, using 2-hydroxymethyl-18-crown-6 as an unexpected homogeneous organocatalyst in multicomponents reaction of aromatic aldehyde, aniline and diethylphosphite in one pot via Kabachnik–Fields reaction. This efficient method proceeds with catalytic amount, transition metal-free, at room temperature within short reaction time, giving the α-aminophosphonates derivatives (4a–r) in high chemical yields (up to 80%). Theoretical DFT calculations of three compounds (4p, 4q and 4r) were carried out in a gas phase at CAM-B3LYP 6-31G (d,p) basis set to predict the molecular geometries and chemical reactivity descriptors. The frontier orbital energies (HOMO/LUMO) were described the charge transfer and used to predict structure-activity relationship study. Molecular electrostatic potential (MEP) has also been analyzed. Molecular docking studies are implemented to analyze the binding energy and compared with Adriamycin against 1ZXM receptor which to be considered as antitumor candidates. In silico pharmacological ADMET properties as Drug likeness and oral activity have been carried out based on Lipinski’s rule of five.

Résumé: The effect of four kosmotropic salts additives, namely Na2CO3, Na2SO4, Na2HPO4, and NaCl, on the reactivity and selectivity of immobilized Candida antarctica lipase B (CAL-B) and a free lipase of Pseudomonas cepacia (PCL) during the hydrolysis of rac-4-(1-methoxyphenyl) ethyl and rac − 1-phenyl ethyl acetates (1a-2a) was investigated in this study. The study was carried out in two different mediums: non-aqueous conditions and in low water content media. The impact of the anionic counter-ions was examined in four solvents: nonpolar, semipolar, protic, and aprotic, with and without the aforementioned salts. In non-aqueous media, the addition of Na2CO3 significantly enhanced CAL-B hydrolysis rates, resulting in a conversion of 50% for 1a and 44% for 2a, with high enantioselectivities (E > 200). These effects were independent of the solvent hydrophobicity. In contrast, PCL required the presence of external water for effective hydrolysis of both acetates. The addition of salt additives had an adverse impact on PCL activity during the hydrolysis of 1a in hexane, toluene, and TBME solvents. However, when 2M2B was used, the inclusion of salt additives had a notable positive effect on the conversion rates, except for NaCl, which resulted in a lower conversion rate with a value of 15.5%. The presence of Na2CO3 improved the conversion rate during the hydrolysis of 2a in both hexane and TBME. Na2HPO4 further enhanced the conversion rate, reaching 44% in TBME. However, in 2M2B solvent, the addition of Na2HPO4 significantly reduced the enantioselectivity.

Résumé: The use of fatty and aromatic acids as green acyl donors for enzymatic kinetic resolution via esterification of 1-phenylethanol and 1-phenylpropan-2-ol was described. The impact of the presence of magnesium sulfate on both reactivity and selectivity of Candida rugosa lipase (CRL) was checked. The organic solvents, the medium dilution, and the temperature revealed as determinant parameters to achieve enantioselective esterification reactions. A significant impact of the use of magnesium sulfate was revealed on the enantioselectivity of the CRL in heptane during the resolution of 1-phenylethanol, using butyric and lauric acids as acyl donors.

Résumé: Diphenylphosphinic acid was used as an efficient and simple catalyst for the synthesis of the α-aminophosphonates by multicomponent Kabachnik-Fields reaction in one pot of aromatic aldehyde, aniline and diethylphosphite. Three physicochemical factors including catalyst amount, reaction time and medium temperature were optimized using a full factorial experiment design (FFD). Additionally, a quadratic polynomial regression model was applied for the analysis of the experimental data at a confidence level of 95% with p-values < 0.05. The high signification effect of the reaction time and the medium temperature on the α-aminophosphonates synthesis were confirmed by the statistical analysis. Besides, the diphenylphosphinic acid amount showed an effect on the reaction yield. ANOVA exhibited that the coefficient determination of this model up to 99.25%. This eco-friendly procedure was extended for the preparation of series of the α-aminophosphonates in ethanol as green solvent, giving the desired products with high chemical yields up to 90%.

Résumé: The essential oils of Lavender (Lavandula angustifolia) and Tropical Basil (Ocimum basilicum) are characteristically high in both linalool and linalyl acetate esters, key constituents determining essential oil (EO) quality and activity. The enrichment of these products in linalyl acetate has a great interest in the industry. Herein, we report the production of linalyl acetate using the free lipase PPL as a catalyst in a solvent-free medium. Parametric studies referring response surface methodology (RSM) were applied to optimize the conversion. The optimal experimental condition for (R)-linalool acylation (temperature at 60°C, catalyst amount at 150 mg, volume of acetic anhydride at 1 mL, and reaction time at 5 days) was obtained from an experimental design analysis. Under these conditions, the enzymatic acylation was carried out for both pure linalool, Lavandula angustifolia and O. basilicum essential oils as substrates. 24.94% conversion of pure linalool to linalyl acetate was obtained; however, essential oils gave lower conversions (conv = 13%).

Résumé: A statistical approach was successfully applied to optimize the acylation of l-menthol 1 in the presence of natural kaolin as an eco-compatible catalyst. The influence of the main variation of the operating parameters, namely solvent volume, amount of the acyl donor, temperature and the catalytic rate of kaolin, was studied. A full factorial design (FFD) was used to search for the optimum of each parameter affecting the evolution of l-menthol 1 acylation. A quadratic polynomial regression model was applied to analyse the experimental data with a p-confidence level <.05 (95%). Statistical analysis of the data confirmed that temperature (T), acyl donor/acceptor ratio (Qa), kaolin mass (Qc) and solvent volume (V) were the significant factors affecting the l-menthol catalytic acylation process. The determination coefficient of the adopted model was in the order of 98%. A set of optimal reaction conditions was established, and experimental tests were performed to validate the optimal conditions; the threshold of 100% was reached. Monitoring the kinetic profile of the reaction by gas chromatography (GC) showed complete conversion after 30 min of reaction. An upgrade of this developed environmentally benign process was applied to some monoterpenic alcohols, and the corresponding acetates were yielding at 45%–90%.

Résumé: Currently, the use of enzymes as efficient tools for the preparation of highly valuable molecules in various industries has proven to be a tremendous development. The preparation of esters via biotechnological processes constitutes an important eco-friendly approach for several industries, especially in the field of flavour and fragrances. This is particularly due to the accrued customer’s interest in products labelled as natural ensured by using enzymes as natural catalysts. This mini-review article is dedicated to underline the recent advances (from 2010 to 2022) in the bio-acylation of achiral and chiral alcohols (esterification and transesterification). The preparation conditions, such as enzyme nature, acyl donor, solvents, etc., are highlighted.

Résumé: A novel category of phosphate-phosphonate compounds is synthesized by a sequence multicomponent reactions strategy of Kabachnik-Fields and Atherton-Todd reactions. All the designed products are obtained with good chemical yields in short reaction times, and confirmed by spectroscopy analyses. The diethyl [(4-diethylphosphate phenyl) (4-trifluoromethyl phenylamino) methyl] phosphonate 6g is characterized by single-crystal X-ray analysis. These compounds exhibited a strong antifungal effect, a low inhibition of AChE, and no inhibitory activity on BChE, with interesting antioxidant capacity. Results make them promising candidates as original organophosphorus pesticides. The DFT calculations concerning relative stability of various conformers, besides the comparison of the measured and calculated NMR spectra of selected compounds; suggest that conformational interconversion can quite easily occur in this type of molecules, so that many structures of the same compound can coexist in solution.

Résumé: Herein, we report the preparation of enantiomerically pure forms of 2,3-dihydrobenzofuran-3-ol (1), chroman-4-ol (2), thiochroman-4-ol (3), 1-(furan-2-yl) ethanol (5) and 1-(thiophen-2-yl) ethanol (6), through a kinetic resolution catalysed by Candida antarctica lipase B/Na2CO3 hydrolysis sequence in organic media. The (R)-furnished alcohols and the (S)-remained acetates are recovered enantiopures (ee >99%, E ≫ 200, Conv = 50%). Those ideal enzymatic kinetic resolution (EKRs) are well incorporated to the Mitsunobu inversion protocol in a one pot procedure to give (S)-heterocyclic acetates (1a–3a) in good to high enantiomeric excess (88%–92% ee). Whilst, the (S)-heteroaromatic acetates (5a and 6a) are given with moderate enantiomeric excess (51%–62% ee). All the (S)-acetates are given in good isolated chemical yields (>80%) allowing to overcome the maximum of 50% yield which could be usually reached in a regular kinetic resolution processes.

Résumé: Herein, we report for the first time the highly regio- and enantioselective ring opening of a biobased itaconic anhydride catalyzed by the Pseudomonas cepacia lipase (PCL) in tert-butyl methyl ether (TBME) at room temperature. This method is easy, efficient and eco-friendly and can be performed in one step with a series of highly valuable monoester itaconates (achiral or enantioenriched) using various alcohols as nucleophiles with 100% atom economy. In all cases, the β-monoester isomer was the predominant product of the reaction. Using achiral primary alcohols as substrates, a variety of novel itaconates were obtained in moderate to excellent yields (50–90%). For select examples, product characterization was carried out using X-ray diffraction, in addition to the standard techniques. The application of this approach was performed for the preparation of enantioenriched 4-monoester itaconates via enzymatic kinetic resolution.

Résumé: An efficient, easy and sustainable amidation of a set of non-activated carboxylic acids with anilines, assisted by CAL-B, as biodegradable catalyst, is reported. The enzymatic amidation reactions are performed on set of nonsteroidal anti-inflammatory drugs (NSAIDs), phenoxypropionic acid and protected-prolines by direct condensation of one equivalent of carboxylic acids and two equivalents of anilines derivatives in heptane after 72 h of reaction at 80 °C. The obtained carboxylic amides are recovered with isolated chemical yields varied between moderate and excellent. Fourteen from them are reported for the first time, and an X-ray crystal is obtained for: N-(4-iodophenyl)-2-(4-isobutylphenyl)propanamide 1d.

Résumé: An efficient enantioselective synthesis of a set of (R)-phenylalkylesters and their analogues amides via enzymatic acylation of 1-phenylethanol (rac-1) and 1-phenylethanamine (rac-2) using carboxylic acids with different chain-lengths as green acyl donor is reported. Three lipases are used: Candida antarctica B immobilized on acrylic resin (CAL-B) and two free lipases: Pseudomonas cepacia (PCL) and Candida rugosa (CRL). The CAL-B shows an excellent selectivity during the acylation of rac-1 without restriction due to the acyl carbon chain-length, the (R)- esters (1 a–1 f) were obtained enantiopures (ee up to 99 %). For the first time, the PCL catalyzed O-acylation allows smoothly to (R)-(1 d–1 f) with high selectivity (E⋙200) is described. The conversions increase with the length of the carbon-chain of the acyl donor (28.7 %≤C≤40 %). The CRL shows less selective and provided the (R) (1 b–1 e) with 77 %≤eep≤86.4 %. Due to its high thermostability, the CAL-B is used for the N-acylation of rac-2 and provides access to enantioenriched (R)-fatty amides (2 d–2 f) (60.7 %≤eep≤74.4 %) and the remained (S)-2 with ees>91 %.