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Title: Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists
Author: Pereira, Nuno A. L.
Sureda, Francesc X.
Pérez Bosch, Maria
Amat Tusón, Mercedes
Santos, Maria M. M.
Keywords: Malalties neurodegeneratives
Síntesi orgànica
Neurodegenerative Diseases
Organic synthesis
Issue Date: 6-Aug-2016
Publisher: MDPI
Abstract: Enantiopure 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.
Note: Reproducció del document publicat a:
It is part of: Molecules, 2016, vol. 21, num. 8, p. 1027-1039
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ISSN: 1420-3049
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)

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