Total Synthesis of ent-Pregnanolone Sulfate and Its Biological Investigation at the NMDA Receptor

Total Synthesis of ent-Pregnanolone Sulfate and Its Biological Investigation at the NMDA Receptor

A unique asymmetric total synthesis of the unnatural enantiomer of pregnanolone, as well as a study of its biological activity at the NMDA receptor, is reported. The asymmetry is introduced by a highly atom-economic organocatalytic Robinson annulation. A new method for the construction of the cyclop...

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Veröffentlicht in:Organic letters 2018-02, Vol.20 (4), p.946-949
Hauptverfasser: Kapras, Vojtech, Vyklicky, Vojtech, Budesinsky, Milos, Cisarova, Ivana, Vyklicky, Ladislav, Chodounska, Hana, Jahn, Ullrich
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container_end_page 949
container_issue 4
container_start_page 946
container_title Organic letters
container_volume 20
creator Kapras, Vojtech
Vyklicky, Vojtech
Budesinsky, Milos
Cisarova, Ivana
Vyklicky, Ladislav
Chodounska, Hana
Jahn, Ullrich
description A unique asymmetric total synthesis of the unnatural enantiomer of pregnanolone, as well as a study of its biological activity at the NMDA receptor, is reported. The asymmetry is introduced by a highly atom-economic organocatalytic Robinson annulation. A new method for the construction of the cyclopentane D-ring consisting of CuI-catalyzed conjugate addition and oxygenation followed by thermal cyclization employing the persistent radical effect was developed. ent-Pregnanolone sulfate is surprisingly only 2.6-fold less active than the natural neurosteroid.
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title Total Synthesis of ent-Pregnanolone Sulfate and Its Biological Investigation at the NMDA Receptor
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