Synthesis of the Enantiomers of Thioridazine
Abstract Thioridazine, a well-known antipsychotic drug, has shown promising effects on several bacterial strains (including Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus). Suppressive effects towards selected cancer cell-lines have also been reported. However, due to adv...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Georg Thieme Verlag KG
2020-01-01
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| Series: | SynOpen |
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| Online Access: | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1690834 |
| _version_ | 1818188816304832512 |
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| author | Simen Antonsen Erling B. Monsen Kirill Ovchinnikov Jens M. J. Nolsøe Dag Ekeberg Jette E. Kristiansen Dzung B. Diep Yngve Stenstrøm |
| author_facet | Simen Antonsen Erling B. Monsen Kirill Ovchinnikov Jens M. J. Nolsøe Dag Ekeberg Jette E. Kristiansen Dzung B. Diep Yngve Stenstrøm |
| author_sort | Simen Antonsen |
| collection | DOAJ |
| description | Abstract
Thioridazine, a well-known antipsychotic drug, has shown promising effects on several bacterial strains (including Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus). Suppressive effects towards selected cancer cell-lines have also been reported. However, due to adverse effects, the compound is no longer in use for the primary indication. More recent research has demonstrated that these side effects are limited to one of the two enantiomers, (+)-thioridazine. The question arises to whether the beneficial effects of thioridazine are limited to one enantiomer, or if (–)-thioridazine can prove itself to be useful in its pure enantiomeric state. The published procedures on the synthesis of the optically pure enantiomers of thioridazine were found to be unsatisfactory, either due to low optical purity, high cost, or problems scaling up. Herein, we have used an auxiliary-based strategy for the total synthesis of both enantiomers in high optical purity and good overall yield. The strategy can easily be scaled up. Both enantiomers were tested against several bacteria. Comparison of the racemic mixture, (–)-thioridazine and its (+)-antipode revealed that they have the same antimicrobial effects. Thus, the non-toxic enantiomer, (–)-thioridazine, can prove useful in this role and should be investigated further. |
| first_indexed | 2024-12-11T23:32:56Z |
| format | Article |
| id | doaj.art-39303286349b4555a458c1ea3e77d607 |
| institution | Directory Open Access Journal |
| issn | 2509-9396 |
| language | English |
| last_indexed | 2024-12-11T23:32:56Z |
| publishDate | 2020-01-01 |
| publisher | Georg Thieme Verlag KG |
| record_format | Article |
| series | SynOpen |
| spelling | doaj.art-39303286349b4555a458c1ea3e77d6072022-12-22T00:45:57ZengGeorg Thieme Verlag KGSynOpen2509-93962020-01-010401121610.1055/s-0039-1690834Synthesis of the Enantiomers of ThioridazineSimen Antonsen0Erling B. Monsen1Kirill Ovchinnikov2Jens M. J. Nolsøe3Dag Ekeberg4Jette E. Kristiansen5Dzung B. Diep6Yngve Stenstrøm7Department of Chemistry, Norwegian University of Life SciencesDepartment of Chemistry, Norwegian University of Life SciencesDepartment of Chemistry, Norwegian University of Life SciencesDepartment of Chemistry, Norwegian University of Life SciencesDepartment of Chemistry, Norwegian University of Life SciencesCenter for Biomembrane Physics, University of Southern DenmarkDepartment of Chemistry, Norwegian University of Life SciencesDepartment of Chemistry, Norwegian University of Life SciencesAbstract Thioridazine, a well-known antipsychotic drug, has shown promising effects on several bacterial strains (including Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus). Suppressive effects towards selected cancer cell-lines have also been reported. However, due to adverse effects, the compound is no longer in use for the primary indication. More recent research has demonstrated that these side effects are limited to one of the two enantiomers, (+)-thioridazine. The question arises to whether the beneficial effects of thioridazine are limited to one enantiomer, or if (–)-thioridazine can prove itself to be useful in its pure enantiomeric state. The published procedures on the synthesis of the optically pure enantiomers of thioridazine were found to be unsatisfactory, either due to low optical purity, high cost, or problems scaling up. Herein, we have used an auxiliary-based strategy for the total synthesis of both enantiomers in high optical purity and good overall yield. The strategy can easily be scaled up. Both enantiomers were tested against several bacteria. Comparison of the racemic mixture, (–)-thioridazine and its (+)-antipode revealed that they have the same antimicrobial effects. Thus, the non-toxic enantiomer, (–)-thioridazine, can prove useful in this role and should be investigated further.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1690834thioridazineantibacterialenantiomerstotal synthesissulfinyl aldimines |
| spellingShingle | Simen Antonsen Erling B. Monsen Kirill Ovchinnikov Jens M. J. Nolsøe Dag Ekeberg Jette E. Kristiansen Dzung B. Diep Yngve Stenstrøm Synthesis of the Enantiomers of Thioridazine SynOpen thioridazine antibacterial enantiomers total synthesis sulfinyl aldimines |
| title | Synthesis of the Enantiomers of Thioridazine |
| title_full | Synthesis of the Enantiomers of Thioridazine |
| title_fullStr | Synthesis of the Enantiomers of Thioridazine |
| title_full_unstemmed | Synthesis of the Enantiomers of Thioridazine |
| title_short | Synthesis of the Enantiomers of Thioridazine |
| title_sort | synthesis of the enantiomers of thioridazine |
| topic | thioridazine antibacterial enantiomers total synthesis sulfinyl aldimines |
| url | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1690834 |
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