Access to valuable building blocks by the regio- and enantioselective ring opening of itaconic anhydride by lipase catalysis.

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 ß-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.

Fiaud's Acid, a novel organocatalyst for diastereoselective bis α-aminophosphonates synthesis with in-vitro biological evaluation of antifungal, antioxidant and enzymes inhibition potential.

(S, S)-1-hydroxy-1-oxo-2-c,5-t-diphenylphospholane or Fiaud's acid is used as a novel and effective chiral organocatalyst for bis α-aminophosphonates synthesis with excellent diastereoselectivity and yields within short reaction time. All synthesized bis α-aminophosphonates revealed a good to excellent antifungal capacity, where the six compounds 4a, 4b, 4e, 4h, 4k and 4l are the best fungicide inhibiting the growth of Fusarium oxysporumandBotrytis cinereaby 65% to 84% with IC50 values <0.02 mg/mL. Similarly, these six products exhibited a strong antioxidant effect, whereas a low inhibition activity was obtained with both AChE and BChE. Furthermore, they displayed a very weak inhibitory activity against tyrosinase except for the compound4l.These findings suggest a possible use of these compounds as synthetic pesticides with less hazardous effects with antioxidant, and anti-tyrosinase properties.

Efficient access to both enantiomers of 3-(1-hydroxyethyl)phenol by regioselective and enantioselective CAL-B-catalyzed hydrolysis of diacetate in organic media by sodium carbonate.

In the present paper, we describe several pathways employing immobilized lipase from Candida antarctica B (CAL-B) as biocatalyst to prepare easily both enantiomers of 3-(1-hydroxyethyl)phenol. We have applied hydrolysis with Na2 CO3 in organic media under mild conditions. The reaction parameters solvent effect, amount of lipase, and Na2 CO3 were examined with 3-(1-acetoxyethyl)phenyl acetate as substrate. In alkaline hydrolysis, (R)-3-(1-hydroxyethyl)phenol was obtained with ee = 99% and (S)-(-)-3-(1-acetoxyethyl)phenol with ee = 98% at optimal conversion (c = 50%) and high selectivity (E > 200). Two other deacylation reactions were compared: alcoholysis with MeOH and with NEt3 . The acylation of 3-(1-hydroxyethyl)phenol with vinyl acetate was also examined. Alkaline hydrolysis gave the best results, while good regioselectivity and enantioselectivity were observed in alcoholysis and acylation reactions. Finally, (S)- and (R)-3-(1-hydroxyethyl)phenol (ee > 98%), key intermediates for the synthesis of important drugs, were prepared from the corresponding racemic diacetate through alkaline hydrolysis.

Asymmetric reduction of ketones by biocatalysis using clementine mandarin (Citrus reticulata) fruit grown in Annaba or by ruthenium catalysis for access to both enantiomers.

Biocatalytic reduction of prochiral ketones using freshly ripened clementine mandarin (Citrus reticulata) in aqueous medium is reported. High enantioselectivities were observed, especially for the bioreduction of indanone , tetralone , and thiochromanone with respectively 95%, 99%, and 86% enantiomeric excess (ee). Enantioselective bio- and metal-catalyzed reactions were compared. Chiral ruthenium catalysts afforded good asymmetric inductions (>75% ee) in most cases, enantiomeric excesses depending on the nature of substrate and ligand. N-aminoindanol prolinamide was revealed as the best ligand for most ketones. Interestingly, for several substrates both enantiomers could be obtained using either Citrus reticulata or ruthenium complex.

Easy preparation of enantiomerically enriched heteroaromatic alcohols through lipase-catalyzed acylation with succinic anhydride under unconventional activation.

This study reports the lipase-catalyzed resolution of heteroaromatic secondary alcohols by succinic anhydride under different activation conditions by convenient procedure with succinic anhydride. The effects of succinic anhydride and the nature of the heteroatom are discussed in standard conditions in the kinetic resolution with lipases. The results recorded under microwave activation and ultrasonication is compared. (R)-4-chromanol was obtained in optically pure form (ee > 99%) with a high selectivity E > 200 by Pseudomonas cepacia lipase (PCL) in diethyl ether, using microwave radiation and under ultrasonication. The reaction time is reduced compared to the conventional heating with a better control of the selectivity of the lipase PCL. A significant effect of the nature of the heteroatoms on the reactivity and selectivity of the lipase with succinic anhydride has been disclosed, regardless the conditions of activation. This method proved to be clean, fast, interesting alternative, and facilitates the use of a cyclic anhydride, by microwave or ultrasound especially with secondary alcohols. The process is a valuable prerequisite for the preparative scale production of enantiomerically heteroaromatic alcohols in sustainable chemistry.

Valorization of Chicken Viscera as Natural Raw Material Source: Application to Hydrolysis of Fatty Esters for Sewage Treatment.

"Chicken viscera" constitutes very abundant domestic wastes interestingly investigated in the present paper. The efficiency of this crude slaughter co-product of high protein component, as biocatalyst, for the hydrolysis of fatty acid esters was reported and that, without any pre-treatment. The crude chicken intestine powder (CIP) has shown a high reactivity for the hydrolysis of fatty esters. Two biocatalyst preparations were independently explored for the bioresolution of sec-phenyl alkyl carbinol esters: the CIP preparation and the crude chicken intestine acetone powder CIAP preparation. The last one has shown good catalytic activity during the bio-hydrolysis in biphasic medium. Furthermore, the direct hydrolysis of milk fat using CIAP (500 mg) reveals the elimination of fats present in 50 ml of treated milk. These results open up very interesting prospects for the use of this biowaste for the treatment of milk fat.

2-Hydroxymethyl-18-crown-6 as an efficient organocatalyst for α-aminophosphonates synthesized under eco-friendly conditions, DFT, molecular docking and ADME/T studies.

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.Communicated by Ramaswamy H. Sarma.

Enantioselective bio-deacylation of arylalkyl acetates using tertiary amines as additive under promiscuous conditions.

Herein, we describe the impact of the introduction of tertiary amines as additive during the enzymatic kinetic resolution via deacylation of some arylalkyl acetates 1a-8a under promiscuous conditions. Two CAL-B preparations were examined: Novozym®435 and CHIRAZYME® L-2, c.-f. C2, lyo. The influence of the introduction of seven amines is checked: Triethylamine (Et3N), Pyridine, 4-Dimethylaminopyridine (4-DMAP), 1,4-Diazabicyclo[2.2.2]octane (DABCO), Cinchonine, Cinchonidine, Quinine and Quinidine; and that in two organic solvent: diisopropylether (DIPE) and tertiobutylmethyl ether (TBME). Among the examined amines, the use of DABCO as additive recorded the best results in terms of reactivity and selectivity. It was to be highlighted that this additive was reported as an enzyme activator for the first time in the enzymatic kinetic resolution via hydrolysis of racemic acetates under non-aqueous conditions. Both CAL-B preparations showed the same behavior in the presence of the chosen additives during the biodeacylation of the resolved acetates. No direct correlation between the pKa values of several used additives and the CAL-B activation rates has been revealed. An ideal enzymatic kinetic resolution was recorded with the acetate 4a (Conv 50% and E > >200).

CAL-B-Catalyzed deacylation of benzylic acetates: Effect of amines addition. Comparison of several approaches.

Herein, we report an efficient enantioselective cleavage of the acyl-moity of some secondary benzylic acetate derivatives catalyzed by lipase B from Candida antarctica (CAL-B) in the presence of triethylamine, as additive, in non aqueous media. The influence of the hydrophobicity of two solvent, the basicity of three amines and the amount of CAL-B were studied in the presence/absence of molecular sieves 4Å. The best results in term of selectivity are achieved using the triethylamine as basic additive and in that case, the reactivity is only best at low conversion. To establish the effect of the parallel and/or competitive hydrolysis and its impact on the reactivity and selectivity of the enzymatic resolution, the kinetic profiles of three CAL-B-deacylation approaches of phenylethylacetate have been compared, using different nucleophiles in competition with the internal water mediated by: Na2CO3, EtOH and by using the Et3N as additive. Furthermore, a comparison between these deacylations with the acylation of 1-phenylethanol with isopropenylacetate, has been made. The appropriate modulation of some crucial parameters allows an optimal conversion and a high selectivity depending on the acetate structure and the introduced base. In the majority of cases, the (R)-alcohols are obtained with ee>99% and selectivities E>200 under mild conditions.