Acylation Of Methyl Research Articles

Synthesis, antimicrobial activity, molecular docking, molecular dynamics simulation, and ADMET properties of the mannopyranoside derivatives as antimicrobial agents

Multiple diseases are treated with carbohydrate-based medicinal products worldwide. Direct regioselective acylation of methyl α-D-mannopyranoside (MDMP) derivatives 2-6 afforded from the 6-O-butyryl derivative. This isolated 6-O-derivative was converted to 2,3,4-tri-O-acyl derivatives, and the resulting compounds were analyzed using FTIR, 1H-NMR, 13C-NMR, and elemental analysis. The acylated derivatives showed moderate to good antimicrobial activity. Cytotoxicity assessment indicated that compound 2 had the lowest toxicity. A SAR study demonstrated that lauroyl and myristoyl acyl chains combined with mannopyranose were particularly effective against bacteria. In this context, molecular docking analysis demonstrated crucial interactions involved in assessing the binding affinity of ligands 1-6 for the active sites of Escherichia coli (4XO8) and Aspergillus flavus (1R51). A 100-ns molecular dynamics simulation showed that all the compounds were stable at the active site of protein 1R51. In silico ADMET prediction revealed greater drug similarity for MDMP derivatives. The results of this investigation may help create MDMP derivative-based multidrug-resistant antimicrobial agents. Highlights Methyl α-D-mannopyranoside (MDMP) derivatives were designed, and synthesized, and their structures were ascertained via spectral analyses. MDMPs were assessed in vitro to identify potential antibacterial or antifungal potential antimicrobial candidate(s) against human and plant organisms. Molecular docking results revealed significant interactions between compounds 1-6 and the active sites of Escherichia coli (4XO8) and Aspergillus flavus (1R51). A 100 ns molecular dynamic simulation demonstrated that the docked ligand–receptor complex had better dynamic stability, as determined through the RMSD, RMSF, SASA, and Rg profiles. ADMET prediction revealed an improved drug-likeness profile for all MDMP derivatives.

Synthesis and some transformations of new acetophenones with carbamate function

Acylation of methyl- N -phenyl-, 2-(morpholin-4-yl)ethylphenyl-, 2-(pyridin-2-yl)ethylphenyl-carbamates with acetic anhydride in polyphosphoric acid at 50-55°C for 3 h proceeds in the para -position to the carbamate grouping to form the corresponding acetophenones. Acylation under similar conditions of methyl 2-(methoxyphenyl)carbamate occurs in the para -position to the methoxy group with the formation of methyl N -(5-acetyl-2-methoxyphenyl)carbamate. The interaction of para - and ortho -acetyl-substituted methyl- N -phenylcarbamate with N -bromosuccinimide, copper(II) acetate in the presence of dimethylformamide at 80°C and with chloro- and hydrobromic acids in the presence of DMSO in ethyl acetate at 30-33°C yielded methyl {4(2)-[(dimethylamino)(oxo)-acetyl]phenyl}- and N -[4(2)-(2-bromo-2-chloroacetyl)phenyl]-carbamates. Condensation of 2-morpholinoethyl [(pyridin-2-yl)ethyl] N -(4-acetylphenyl)carbamates with 4-methoxybenzaldehyde in the presence of a methanolic KOH solution gave the corresponding chalcones.

ChemInform Abstract: Regio‐ and Stereoselective Lipase‐Catalyzed Acylation of Methyl α‐D‐Glycopyranosides with Fluorinated β‐Lactams.

ChemInform Abstract: Regio‐ and Stereoselective Lipase‐Catalyzed Acylation of Methyl α‐D‐Glycopyranosides with Fluorinated β‐Lactams.

Regio‐ and Stereoselective Lipase‐Catalysed Acylation of Methyl α‐D‐Glycopyranosides with Fluorinated β‐Lactams

AbstractBurkholderia cepacia lipase (lipase PS‐D) catalysed acylation with 3,3‐difluoro‐4‐phenyl‐, ‐thiophen‐3‐yl‐ and ‐4‐pyridylazetidin‐2‐ones was examined for the formation of N‐Boc‐protected 6‐O‐acylated sugar–β‐amino acid conjugates from methyl α‐D‐galacto‐, ‐gluco‐ and mannopyranosides and Boc2O. The 6‐O‐acylated glycopyranoside–β‐amino acid conjugates were isolated and characterized. The low solubility of the gluco‐ and mannopyranosides and the high reactivity of the pyridylazetidinone restricted product formation. Activation of the β‐lactam ring by the presence of fluorine substituents was shown to be necessary for the enzymatic acylation reaction. The (S)‐enantiomers of the racemic β‐lactam substrates reacted with the sugars.

Synthesis of N-arylcarbamates with tetrazole fragment and some their derivatives

Reactions of methyl(ethyl) N-(2-cyanophenyl)carbamates with sodium azide in dimethylformamide at 80–90°C in the presence of anhydrous CdCl2 afforded the corresponding N-arylcarbamates with a 1,2,3,4-tetrazole fragment. The acylation of methyl N-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]carbamate with acetic anhydride followed by the condensation of the obtained N-acyl derivative with thiophene-2-carbaldehyde in the KOH methanol solution led to the formation of methyl N-(2-{1-[3-(2-thienyl)-2-propenoyl]-1H-1,2,3,4-tetrazol-5-yl}phenyl)carbamate. The reaction of cyclohexyl N-(4-aminophenyl)carbamate with a triethyl orthoformate and sodium azide in glacial AcOH yielded cyclohexyl N-[4-(1H-1,2,3,4-tetrazol-1-yl)phenyl]carbamate.

Lipases in the Regioselective Preparation of Glyceric Acid Esters of Methyl Glycosides

AbstractThe lipase‐catalyzed regioselective acylation of methyl α‐D‐galacto‐, ‐gluco‐ and ‐mannopyranosides with isopropylidene‐protected (R)‐ and (S)‐glyceric acid methyl esters in organic solvents is presented. Factors affecting the formation of the 6‐O‐mono‐ and 2,6‐O‐diacylated products are examined and preparative‐scale reactions are detailed. In addition, studies on partially protected methyl α‐D‐galactopyranosides are presented, with the 3,4‐O‐isopropylidene protected compound leading exclusively to the formation of the 6‐O‐monoacylated product even at high substrate concentrations. Application of acidic resin in methanol allows removal of the isopropylidene protection groups without disturbing the ester bond at C‐6.

Enzymatic resolution of methyl (2E, 4R*,5S*)-4-(N-benzyl-N-methyl)amino-5-hydroxyhex-2-enoate

For the purpose of preparation of optically active aminoalcohol congeners possessing both hydroxyl- and dialkylamino-substituted vicinal chiral carbons, lipase-assisted acylation of methyl (2E,4R*,5S*)-4-(N-benzyl-N-methyl)amino-5-hydroxyhex-2-enoate (4) using CAL-B with vinyl hexanoate as an acyl donor was carried out to give (4S,5R)-hexenoate (7) (44%, 99.2% ee) as the reaction product and (4R,5S)-alcohol (4) (46%, 98.2% ee) as the unreacted starting material. The E-value of the present lipase-assisted resolution was estimated to be more than 1000. Thus obtained acylated product was successfully converted into methyl β-d-vicenisaminide (12).

ChemInform Abstract: Lipase-Catalyzed Kinetic Resolution of Methyl 4-Hydroxy-5- tetradecynoate and Its Application to a Facile Synthesis of Japanese Beetle Pheromone.

Abstract A kinetic resolution of methyl 4-hydroxy-5-tetradecynoate is accomplished by a lipase-catalyzed enantioselective acylation in organic solvent. Acylation of methyl 4-hydroxy-5-tetradecynoate with succinic anhydride in an organic solvent yields methyl (R)-4-succinoyloxy-5-tetradecynoate with over 90% e.e.. Furthermore, this optically active diester was converted to (R)-5-(1-decynyl)oxacyclopentan-2-one by lipase-catalyzed enantioselective lactonization which enhanced its e.e. over 99%. The Japanese beetle pheromone (R,Z)-(-)-5-(1-decenyl)oxacyclopentan-2-one is synthesized in one step from this optically active lactone.

ChemInform Abstract: Homolytic Acylation of Methyl 3-Amino-2-pyrazinecarboxylates.

Homolytic acylation of methyl 3-amino-2-pyrazinecarboxylates 1a-c under standard Minisci conditions affords the corresponding 5- or 6-monoacylated pyrazines 3a-d or 4a,b in reasonable yields. With 1a, complete selectivity in favor of the 5-acyl products is observed

Lipase-catalyzed regioselective acylation of tritylglycosides in supercritical carbon dioxide

Candida rugosa lipase (CRL) was used to catalyze the regioselective acylation of methyl 6- O-trityl β- d-glucopyranoside in supercritical CO 2 (SCCO 2), using vinyl acetate as the acyl donor and obtained final conversion values up to 91.4%. The effect of pressure, temperature, enzyme quantity and sugar/ester molar ratio on the catalytic efficiency and regioselectivity of CRL was evaluated. The regioselectivity of the reaction was shifted towards the synthesis of 3- O-acetyl 6- O-trityl β- d-glucopyranoside and this is a function of the chemico-physical parameters of the supercritical medium employed. In fact, by varying the CO 2 pressure used in the process up to 20 MPa at constant temperature, we were able to obtain the formation of the sole 3- O-acetyl 6- O-trityl β- d-glucopyranoside regioisomer. A kinetic study was also performed and the relative kinetic parameters calculated.

An approach to address Candida rugosa lipase regioselectivity in the acylation reactions of trytilated glucosides

Candida rugosa lipase crude preparations (CRL) catalyse the regioselective acylation of methyl 6-O-trytil beta-d-glucopyranoside in organic solvents, using vinyl acetate as acyl donor. The ratio of the two products formed, namely methyl 2-O acetyl 6-O-trytil beta-d-glucopyranoside and methyl 3-O acetyl 6-O-trytil beta-d-glucopyranoside was found to be markedly affected by the nature of the reaction medium. In hydrophobic solvents values up to 80% of the monoacetylated product in position C-3 were obtained compared to less than 30% in solvents with low hydrophobicity. Computational studies were carried out to simulate the interactions between methyl 6-O-trytil beta-d-glucopyranoside and both CRL and the solvents, in order to rationalize the experimental results.

Synthesis and Structure of 4‐Indolyl‐5‐(thieno[3,2‐b]pyrrol‐6‐yl)imidazoles.

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Synthesis and Structure of 4-Indolyl-5-(thieno[3,2-b]pyrrol-6-yl)imidazoles

A procedure was proposed for regioselective acylation of methyl 2-methyl-4H-thieno[3,2-b]-pyrrole-5-carboxylate with 2-(3-indolyl)-2-oxoacetyl chloride. Reactions of the resulting methyl 6-[2-(3-indolyl)-1,2-dioxoethyl]-2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate with aromatic aldehydes and ammonium acetate in acetic acid afforded the corresponding methyl 6-[2-aryl-4-(3-indolyl)imidazol-5-yl]-2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylates. The structure of methyl 6-[2-(4-chlorophenyl)-4-(3-indolyl)imidazol-5-yl]-2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate was studied by X-ray analysis.

Selective Organocatalytic Ring-Opening Polymerization: A Versatile Route to Carbohydrate-Functionalized Poly(ε-caprolactones)

Cationic catalysis using simple carboxylic acids to combine the ring-opening polymerization of ε-caprolactone and the regioselective acylation of carbohydrates has been investigated. l-Lactic acid catalyzed the acylation of methyl β-d-glucopyranoside and sucrose with ε-caprolactone in high yield by bulk polymerization at 120 °C. The main products were regioselectively acylated on the primary hydroxyl groups of the carbohydrate end groups. The overall conversion to methyl β-d-glucopyranoside-functionalized poly(ε-caprolactone) was more than 90%, Mw 2000 and polydispersity index 1.5, with one major product methyl 6-O-poly(ε-caprolactone)-β-d-glucopyranoside, in agreement with the corresponding Candida antarctica lipase B-catalyzed acylation.

Fotochromic Dihetarylethenes: XIX. Synthesis of 1,2-Dihetarylethenes with 2,5-Dihydrothiophene Bridge from Thieno[3,2-b]pyrroles

Reductive cyclization by McMurry method was performed with diketosulfide obtained by treating with Na2S of compound prepared by regioselective acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate with chloroacetyl chloride. As a result was synthesized a photochromic 1,2-dihetarylethene where the fuzed rings are connected by a 2,5-dihydrothiophene ring. The oxidation of the latter provides 2,5-dihydrothiophene-1,1-dioxide bridge.

Regioselective Acylation of Methyl 2‐Methyl‐4H‐thieno[3,2‐b]pyrrole‐5‐carboxylate.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Addition of Organolithium Reagents to Ahc Methyl Ester. An Approach to New α‐Amino Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regioselective acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate

The influence of catalysts, acid chlorides, and solvents on the acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate was studied. The use of AlCl3 allows the regioselective introduction of the acyl group into position 3 to be performed, whereas the acyl group is regioselectively introduced into position 6 of thienopyrrole when SnCl4 is used.

Addition of organolithium reagents to Ahc methyl ester. An approach to new α-amino ketones

We have developed a versatile methodology to obtain α-amino ketones by acylation of methyl N-benzoyl-7-azabicyclo[2.2.1]heptane-1-carboxylate ( 1 ) with organolithium reagents. The reaction proceeds via a stable tetrahedral intermediate. When methyl ester 1 was treated under the same conditions but with a different work up procedure (careful addition of saturated NH 4Cl), we observed by 1H NMR spectroscopy that a new compound had appeared in the crude reaction mixture corresponding to a hemiacetal.

Synthesis of photochromic 1,2-dihetarylethene using regioselective acylation of thienopyrroles.

[formula: see text] The influence of catalysts, acid chlorides, and solvents in the acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate was studied. Conditions for the regioselective acylation processes were found. Thienopyrrole-based photochrome was synthesized for the first time.