Synthesis Of Sertraline Research Articles

A method development for sertraline detection in the blood

Aim – to develop a method for isolation and determination of sertraline in biological fluids. Material and methods. For the study we used "Zoloft" drug ("Pfizer", USA). The study equipment and substances: liquid chromatograph Shimadzu LC-20 Prominence (Japan) with detector SPD-M20A, gas chromatograph Agilent Technologies (USA) 7890 A / 5977 MSD, (program MassHunter GC-MS ), waters vacuum unit and cartridges for solid-phase extraction Oasis HLB; papain enzymes (MedFloran, Russia); trypsin, chymotrypsin, hyaluronidase (Lidaza) (Samson-Med LLC, Russia); test strips from different manufacturers under trade names: "Be sure", "NarcoCHEC", "FACTOR-MED". Urine samples were obtained after administration of the drug to laboratory animals – guinea pigs. The base of sertraline from a solution of its salt was isolated by liquid-liquid extraction (LLE) with organic solvents and their mixtures at pH = 10, 11 and 12 (pKa sertraline 9.48). Obtaining data on the effectiveness of blood sample preparation methods (liquid-liquid extraction, solid-phase extraction and enzymatic hydrolysis) for sertraline was carried out on enriched model samples of donor blood according to the method proposed by Cheger. Results. Cross-positive urine test results were obtained with immunochromatographic test strips for derivatives of e 1,4-benzodiazepine and synthetic cannabimimetics ("spice"). The study with 1 mg/ml solution of sertraline gave a negative result. Desmethylsertraline, a major metabolite, was detected in the urine, a peak with a retention time of about 12.75 min, the peak of the original substance during the synthesis of sertraline – sertralinimine and the peak of the native sertraline with a retention time of about 12.65 min. A method for detecting sertraline by HPLC has been developed. Conclusion. The use of the enzymatic blood hydrolysis with trypsin allows for increasing the degree of extraction by 1.5 times when compared with liquid-liquid extraction with chloroform, and by 2 times when compared with solid-phase extraction.

Genome mining and characterisation of a novel transaminase with remote stereoselectivity

Microbial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir. Here we report a novel ω-transaminase discovered in a marine sponge Pseudovibrio sp. isolate. Remote stereoselection using a transaminase has been demonstrated for the first time using this novel protein. Application to the resolution of an intermediate in the synthesis of sertraline highlights the synthetic potential of this novel biocatalyst discovered through genomic mining. Integrated chemico-genomics revealed a unique substrate profile, while molecular modelling provided structural insights into this ‘first in class’ selectivity at a remote chiral centre.

ChemInform Abstract: Efficient Kinetic Resolution in the Asymmetric Hydrosilylation of Imines of 3-Substituted Indanones and 4-Substituted Tetralones.

Kinetic resolution of the N-methyl imines of 3-substituted indanones and 4-substituted tetralones could be accomplished by hydrosilylation with a chiral titanocene catalyst. N-Methyl imines of 4-substituted tetralones were resolved to yield, after hydrolysis of the unreacted starting materials, ketones with high ee's and the amine products with high diastereomeric and enantiomeric purity. The utility of this process was demonstrated in the synthesis of sertraline.

Synthesis of Dihydronaphthalenes via Aryne Diels−Alder Reactions: Scope and Diastereoselectivity

Novel aryne Diels-Alder reactions with functionalized acyclic dienes are reported. These give useful cis-substituted dihydronaphthalene building blocks in good yield which are not easily accessible via other means, as demonstrated in the synthesis of sertraline. The first asymmetric aryne cycloaddition with an acyclic diene is also reported, giving excellent diastereoselectivities with Oppolzer's sultam as a chiral auxiliary.

Efficient kinetic resolution in the asymmetric hydrosilylation of imines of 3-substituted indanones and 4-substituted tetralones.

Kinetic resolution of the N-methyl imines of 3-substituted indanones and 4-substituted tetralones could be accomplished by hydrosilylation with a chiral titanocene catalyst. N-Methyl imines of 4-substituted tetralones were resolved to yield, after hydrolysis of the unreacted starting materials, ketones with high ee's and the amine products with high diastereomeric and enantiomeric purity. The utility of this process was demonstrated in the synthesis of sertraline.

Chemo-enzymatic synthesis of ( R)- and ( S)-3,4-dichlorophenylbutanolide intermediate in the synthesis of sertraline

3,4-Dichlorophenacylchloride was reduced with whole cell biocatalysts to give the ( R)- or ( S)-chlorohydrine in high yields and good to high enantiomeric excess. Yields and enantiomeric purity of the ( S)-enantiomer were increased to 95 and >98%, respectively, using growing cells from Geotrichum candidum (CBS 233.76) in the presence of hydrophobic adsorbing resins at 4 g/l. The latter compound was transformed into ( R)-3,4-dichlorophenylbutanolide, intermediate in the synthesis of (+)- cis-1 S,4 S-sertraline.