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

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Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
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University of Chinese Academy of Sciences, Beijing 100049, China
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Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
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Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX13TA, UK
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National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, China
*
Authors to whom correspondence should be addressed.
Academic Editors: Ramón J. Estévez Cabanas, George Fleet, Atsushi Kato and Robert J. Nash
Molecules 2020, 25(7), 1498; https://doi.org/10.3390/molecules25071498 (registering DOI)
Received: 21 February 2020 / Revised: 18 March 2020 / Accepted: 23 March 2020 / Published: 25 March 2020
(This article belongs to the Special Issue Iminosugars: Beyond Glycosidase 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) 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. View Full-Text
Keywords: Pochonicine; pharmacophore; synthesis; β-N-acetylhexosaminidase; iminosugars; structure-activity relationship Pochonicine; pharmacophore; synthesis; β-N-acetylhexosaminidase; iminosugars; structure-activity relationship
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MDPI and ACS Style

Yan, X.; Shimadate, Y.; Kato, A.; Li, Y.-X.; Jia, Y.-M.; Fleet, G.W.J.; Yu, C.-Y. Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition. Molecules 2020, 25, 1498.

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