Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition

Ten pairs of pyrrolidine analogues of pochonicine and its stereoisomers have been synthesized from four enantiomeric pairs of polyhydroxylated cyclic nitrones. Among the ten N-acetylamino pyrrolidine analogues, only compounds with 2,5-dideoxy-2,5-imino-d-mannitol (DMDP) and pochonicine (1) configura...

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Autores principales: Yan, Xin, Shimadate, Yuna, Kato, Atsushi, Li, Yi-Xian, Jia, Yue-Mei, Fleet, George W. J., Yu, Chu-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180638/
https://www.ncbi.nlm.nih.gov/pubmed/32218360
http://dx.doi.org/10.3390/molecules25071498
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author Yan, Xin
Shimadate, Yuna
Kato, Atsushi
Li, Yi-Xian
Jia, Yue-Mei
Fleet, George W. J.
Yu, Chu-Yi
author_facet Yan, Xin
Shimadate, Yuna
Kato, Atsushi
Li, Yi-Xian
Jia, Yue-Mei
Fleet, George W. J.
Yu, Chu-Yi
author_sort Yan, Xin
collection PubMed
description Ten pairs of pyrrolidine analogues of pochonicine and its stereoisomers have been synthesized from four enantiomeric pairs of polyhydroxylated cyclic nitrones. Among the ten N-acetylamino pyrrolidine analogues, only compounds with 2,5-dideoxy-2,5-imino-d-mannitol (DMDP) and pochonicine (1) configurations showed potent inhibition of β-N-acetylhexosaminidases (β-HexNAcases); while 1-amino analogues lost almost all their inhibitions towards the tested enzymes. The assay results reveal the importance of the N-acetylamino group and the possible right configurations of pyrrolidine ring required for this type of inhibitors.
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spelling pubmed-71806382020-05-01 Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition Yan, Xin Shimadate, Yuna Kato, Atsushi Li, Yi-Xian Jia, Yue-Mei Fleet, George W. J. Yu, Chu-Yi Molecules Article Ten pairs of pyrrolidine analogues of pochonicine and its stereoisomers have been synthesized from four enantiomeric pairs of polyhydroxylated cyclic nitrones. Among the ten N-acetylamino pyrrolidine analogues, only compounds with 2,5-dideoxy-2,5-imino-d-mannitol (DMDP) and pochonicine (1) configurations showed potent inhibition of β-N-acetylhexosaminidases (β-HexNAcases); while 1-amino analogues lost almost all their inhibitions towards the tested enzymes. The assay results reveal the importance of the N-acetylamino group and the possible right configurations of pyrrolidine ring required for this type of inhibitors. MDPI 2020-03-25 /pmc/articles/PMC7180638/ /pubmed/32218360 http://dx.doi.org/10.3390/molecules25071498 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yan, Xin
Shimadate, Yuna
Kato, Atsushi
Li, Yi-Xian
Jia, Yue-Mei
Fleet, George W. J.
Yu, Chu-Yi
Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition
title Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition
title_full Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition
title_fullStr Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition
title_full_unstemmed Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition
title_short Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition
title_sort synthesis of pyrrolidine monocyclic analogues of pochonicine and its stereoisomers: pursuit of simplified structures and potent β-n-acetylhexosaminidase inhibition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180638/
https://www.ncbi.nlm.nih.gov/pubmed/32218360
http://dx.doi.org/10.3390/molecules25071498
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