The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• /bjoc.11.164 Abstract A simple enantioselective synthetic procedure for the preparation of mianserin and epinastine in optically pure form is described. The key step in the synthetic pathway is the asymmetric reduction of the cyclic imine using asymmetric transfer hydrogenation conditions. Keywords

• : chiral diamines; enantioselective reduction; epinastine; mianserin; ruthenium complexes; Introduction Mianserin (1) is a tetracyclic compound widely used as a drug in the treatment of depression. Despite the fact that the (S)-(+)-enantiomer of mianserin is more potent than the (R)-antipode in

• another important active substance, epinastine, in enantiomerically pure form (Figure 1). Epinastine (2) is a histamine H1 receptor antagonist and is used as racemic mixture in eye drops to relieve the symptoms of allergic conjunctivitis. Analogously as in the case of mianserin, the (S)-enantiomer is the