CC BY 4.0 · SynOpen 2020; 04(01): 12-16
DOI: 10.1055/s-0039-1690834
letter
(2020) The Author(s)

Synthesis of the Enantiomers of Thioridazine

a  Department of Chemistry, Norwegian University of Life Sciences, PO box 5003, 1432 Ås, Norway   Email: Simen.antonsen@nmbu.no
,
Erling B. Monsen
a  Department of Chemistry, Norwegian University of Life Sciences, PO box 5003, 1432 Ås, Norway   Email: Simen.antonsen@nmbu.no
,
Kirill Ovchinnikov
a  Department of Chemistry, Norwegian University of Life Sciences, PO box 5003, 1432 Ås, Norway   Email: Simen.antonsen@nmbu.no
,
Jens M. J. Nolsøe
a  Department of Chemistry, Norwegian University of Life Sciences, PO box 5003, 1432 Ås, Norway   Email: Simen.antonsen@nmbu.no
,
Dag Ekeberg
a  Department of Chemistry, Norwegian University of Life Sciences, PO box 5003, 1432 Ås, Norway   Email: Simen.antonsen@nmbu.no
,
Jette E. Kristiansen
b  Center for Biomembrane Physics, University of Southern Denmark, 5230, Odense, Denmark
,
Dzung B. Diep
a  Department of Chemistry, Norwegian University of Life Sciences, PO box 5003, 1432 Ås, Norway   Email: Simen.antonsen@nmbu.no
,
Yngve Stenstrøm
a  Department of Chemistry, Norwegian University of Life Sciences, PO box 5003, 1432 Ås, Norway   Email: Simen.antonsen@nmbu.no
› Author Affiliations
The authors would like to acknowledge the European Cooperation in Science and Technology (ECOST-STSM-CM1407-42899) for funding SA’s short time scientific mission (STSM).
Further Information

Publication History

Received: 22 January 2020

Accepted after revision: 03 February 2020

Publication Date:
17 February 2020 (online)


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.

Supporting Information

 
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