{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T16:51:00Z","timestamp":1767372660825,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2016,8,6]],"date-time":"2016-08-06T00:00:00Z","timestamp":1470441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/QUI-QUI\/111664\/2009","IF\/00732\/2013"],"award-info":[{"award-number":["PTDC\/QUI-QUI\/111664\/2009","IF\/00732\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2009\/SGR00853"],"award-info":[{"award-number":["2009\/SGR00853"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u03b4-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\u2019s 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.<\/jats:p>","DOI":"10.3390\/molecules21081027","type":"journal-article","created":{"date-parts":[[2016,8,8]],"date-time":"2016-08-08T10:14:38Z","timestamp":1470651278000},"page":"1027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists"],"prefix":"10.3390","volume":"21","author":[{"given":"Nuno","family":"Pereira","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7968-3929","authenticated-orcid":false,"given":"Francesc","family":"Sureda","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, C.\/St. Lloren\u00e7 21, 43201 Reus (Tarragona), Spain"}]},{"given":"Maria","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, s\/n, 08028 Barcelona, Spain"}]},{"given":"Mercedes","family":"Amat","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, s\/n, 08028 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2239-9353","authenticated-orcid":false,"given":"Maria","family":"Santos","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2016,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/chir.22268","article-title":"Synthesis of single-enantiomer bioactive molecules: A brief overview","volume":"26","author":"Rouf","year":"2014","journal-title":"Chirality"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1021\/cr9500038","article-title":"1,2-amino alcohols and their heterocyclic derivatives as chiral auxiliaries in asymmetric synthesis","volume":"96","author":"Ager","year":"1996","journal-title":"Chem. 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