Sertraline antidepressant

Few methodologies have either the diversity of synthetic transformations or the high level of product selectivity as catalytic reactions with the intermediate involvement of metal carbenes [ 1-5]. They provide synthetic opportunities that are clearly demonstrated in the preparation of the antidepressant sertraline (1)... 

Deak, K., Takacs-Novak, K., Tihanyi, K., Noszal, B. Physico-chemical profiling of antidepressive sertraline solubility, ionisation, lipophilidty. Med. Chem. 2006, 2, 385-389. 

Although this type of drug has various subclasses based on physiological response, such as tranquilizers, stimulants, depressants, etc., we will subdivide and treat a few of them on the basis of their chemical classes. The leading antidepressant, sertraline (no. 10), was covered in Section 3.10. 

Attempted allylic C-H insertion by vinyldiazoacetates results in an even more complicated transformation, a combined C-H activation/Cope rearrangement [27]. These reactions tend to proceed with very high enantioselectivity as illustrated in a short enantioselective synthesis of the antidepressant (+)-sertraline (33) [27a]. Recent studies have shown that this reaction is both highly diastereose-lective and enantioselective [27b],... 

Equally successful has been the group of Quallich at Pfizer46 who reported the preparation of a substituted dihydronaphthalenone, a pivotal intermediate in the preparation of the antidepressant sertraline (Lustral ) (10) (Scheme 16.6). In this synthesis, the new chiral center created subsequently determines the absolute stereochemistry of the final product (see Chapter 31). 

An award-winning example of green chemistry being used in the redesign of a process is in the production of Pfizer s antidepressant sertraline (see Figure 3.6) (Clark, 2002 Ritter, 2002 US Environmental Protection Agency). 

Khouzam HR, Ernes R, Gill T, Raroque R. The antidepressant sertraline a review of its uses in a range of psychiatric and medical conditions. ComprTher. 2003 29 47-53. 

Draw a stepwise mechanism for the intramolecular Friedel-Crafts acylation of compound A to form B. B can be converted in one step to the antidepressant sertraline (trade name Zoloft). 

Several antidepressants seem to be able to induce a shift from a type-1 to a type-2, from a proinflammatory to an antiinflammatory immune response, since the ability of different antidepressants (sertraline, clomipramine, trazodone) to reduce the IFN-y/IL-lO ratio significantly was shown in vitro. These chugs reduced the IFN-y production significantly, while sertraline and clomipramine additionally raised the IL-10 production (Maes et al., 1999). Regarding other in-vitro studies, a significantly reduced production of IFN-y, IL-2, and sIL-2R was found after antidepressant treatment compared to pretreatment values (Seidel et al., 1995, b). A down-regulation... 

Asymmetric transfer hydrogenation with a chiral ruthenium complex is an alternative option for preparation of substituted phenethyl alcohols, which are important building blocks for the agricultural fungicide, (S)-MA20565 [47]. In the enantioselective synthesis of antidepressant sertraline (50), different chiral secondary alcohols have been proposed as pivotal intermediates (Scheme 14). Reduction of the keto ester 46 catdyzed by oxazaborolidine 45 provides chiral intermediate 47 in 90% ee [48]. Alternatively, reductive fragmentation of C2-symmetric oxa-tricyclic alkene 48 with DIBAL catalyzed by a BINAP-Ni complex generates a novel intermediate 49 in 88 % yield with 91% ee [49]. 

CYP2D6 biosensor for antidepressants (sertraline and fluxetine). Previous studies on PANI- and polythiophene-based CYP-biosensors for fluoxetine showed that the uncompetitive inhibition kinetics between the CYP enzyme and fluoxetine is based on the mono-oxygenation reaction of the enzyme [13], The response of the Au PANSA/CYP2D6... 

The pressure dependence was explained by the fact that scCHFs is a more polar solvent (has a higher dielectric constant) at higher pressures than it is at lower pressures. The enantioselectivity was better in nonpolar CHF3 than in polar CHF3, consistent with the observation that the selectivity is better in nonpolar liquid solvents than in polar liquids. The pressure independence of the enantioselectivity in SCCO2 is due to the fact that the dielectric constant of that SCF does not vary significantly with pressure. Cyclopropanations of this type can be used in the synthesis of the antidepressant sertraline (124) and of cilastatin, a stabilizer of the antibiotic imipenem (125). 

Corey EJ, Gant TG. A catalytic enantioselective synthetic route to the important antidepressant sertraline. Tetrahedron Lett 1994 35 5373-5376. 

Good ees are also obtained using cycKc and acyclic vinyl diazoacetates, such as (9.31), and the product (9.32) is converted into the cyclopropyl amino acid (9.33). The same product (9.32) has also been converted into the antidepressant Sertraline by Corey and Gant. 

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