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Organic Chemistry

Tutor Mgr. Eva Kudová, Ph.D.

Steroidní inhibitory / Steroidal Inhibitors

Topic Make a puzzle with steroidal skeleton: Synthesis of steroidal mimics as novel modulators of NMDA receptors

Neurosteroids are ligands for many ligand-gated ion channels. Their effect on glutamatergic ion channels – mainly NMDA receptors (NMDARs) – has been extensively described in the literature. These compounds do offer interesting potential for treatment of various CNS diseases. The structural features required for modulatory effect has been already established for classical steroidal skeleton (ABCD ring system). Besides, it has been described that perhydrophenanthrene analogues of neurosteroids - bearing only ABC ring of steroidal system - act as potent modulators of NMDARs as well. Therefore, the ABCD-system offers synthetic platform for structural puzzle. The synthesis of two possible building block for this research has been numerously described in the literature – the Wieland-Miescher ketone as the AB-ring building block and the Hajosh-Parrish ketone as the CD-ring system building block, respectively. The main aim of the Ph.D. thesis will be the synthesis of a series of compounds affording steroid-like layout and structurally mimicking steroidal ABC/ABCD-ring system using Wieland-Miescher ketone as starting material with modifications to steroidal positions C-3 and C-8 and Hajosh-Parrish ketone as starting material to steroidal positions C-3 and C-17, respectively.