Synthesis of pyrrolidine monocyclic analogues of pochonicine and its stereoisomers: Pursuit of simplified structures and potent β-N-acetylhexosaminidase inhibition

Xin Yan; Yuna Shimadate; Atsushi Kato; Yi Xian Li; Yue Mei Jia; George W.J. Fleet; Chu Yi Yu

doi:10.3390/molecules25071498

Synthesis of pyrrolidine monocyclic analogues of pochonicine and its stereoisomers: Pursuit of simplified structures and potent β-N-acetylhexosaminidase inhibition

Xin Yan, Yuna Shimadate, Atsushi Kato, Yi Xian Li, Yue Mei Jia, George W.J. Fleet, Chu Yi Yu^*

^*Corresponding author for this work

Hospital Pharmacy

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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.

Original language	English
Article number	1498
Journal	Molecules
Volume	25
Issue number	7
DOIs	https://doi.org/10.3390/molecules25071498
State	Published - 2020

Keywords

Iminosugars
Pharmacophore
Pochonicine
Structure-activity relationship
Synthesis
β-N-acetylhexosaminidase

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

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10.3390/molecules25071498

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title = "Synthesis of pyrrolidine monocyclic analogues of pochonicine and its stereoisomers: Pursuit of simplified structures and potent β-N-acetylhexosaminidase inhibition",

abstract = "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.",

keywords = "Iminosugars, Pharmacophore, Pochonicine, Structure-activity relationship, Synthesis, β-N-acetylhexosaminidase",

author = "Xin Yan and Yuna Shimadate and Atsushi Kato and Li, {Yi Xian} and Jia, {Yue Mei} and Fleet, {George W.J.} and Yu, {Chu Yi}",

note = "Publisher Copyright: {\textcopyright} 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/).",

year = "2020",

doi = "10.3390/molecules25071498",

language = "英語",

volume = "25",

journal = "Molecules",

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T1 - Synthesis of pyrrolidine monocyclic analogues of pochonicine and its stereoisomers

T2 - Pursuit of simplified structures and potent β-N-acetylhexosaminidase inhibition

AU - Yan, Xin

AU - Shimadate, Yuna

AU - Kato, Atsushi

AU - Li, Yi Xian

AU - Jia, Yue Mei

AU - Fleet, George W.J.

AU - Yu, Chu Yi

N1 - Publisher Copyright: © 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/).

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Iminosugars

KW - Pharmacophore

KW - Pochonicine

KW - Structure-activity relationship

KW - Synthesis

KW - β-N-acetylhexosaminidase

UR - http://www.scopus.com/inward/record.url?scp=85082562165&partnerID=8YFLogxK

U2 - 10.3390/molecules25071498

DO - 10.3390/molecules25071498

M3 - 学術論文

C2 - 32218360

AN - SCOPUS:85082562165

SN - 1420-3049

VL - 25

JO - Molecules

JF - Molecules

IS - 7

M1 - 1498

ER -

Synthesis of pyrrolidine monocyclic analogues of pochonicine and its stereoisomers: Pursuit of simplified structures and potent β-N-acetylhexosaminidase inhibition

Abstract

Keywords

ASJC Scopus subject areas

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