Pereira, Nuno A. L.Sureda, Francesc X.Pérez Bosch, MariaAmat Tusón, MercedesSantos, Maria M. M.2017-03-072017-03-072016-08-061420-3049https://hdl.handle.net/2445/108047Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl D-Aspartate (NMDA) receptor antagonists. The indolo[2,3-a]quinolizidine scaffold was obtained using the following key steps: (i) a stereoselective cyclocondensation of (S)- or (R)-tryptophanol with appropriate racemic -oxoesters; (ii) a stereocontrolled cyclization on the indole nucleus. The synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA receptor antagonists and one compound was identified to be 2.9-fold more potent as NMDA receptor blocker than amantadine (used in the clinic for Parkinson's disease). This compound represents a hit compound for the development of novel NMDA receptor antagonists with potential applications in neurodegenerative disorders associated with overactivation of NMDA receptors.13 p.application/pdfengcc-by (c) Pereira, Nuno A. L. et al., 2016http://creativecommons.org/licenses/by/3.0/esMalalties neurodegenerativesSíntesi orgànicaNeurodegenerative DiseasesOrganic synthesisinfo:eu-repo/semantics/article6648102017-03-07info:eu-repo/semantics/openAccess27509489