Novel 2-aryl-3,4,5-trihydroxypiperidines: Synthesis and glycosidase inhibition

Hui Zhao; Wu Bao Wang; Shinpei Nakagawa; Yue Mei Jia; Xiang Guo Hu; George W.J. Fleet; Francis X. Wilson; Robert J. Nash; Atsushi Kato; Chu Yi Yu

doi:10.1016/j.cclet.2013.06.027

Novel 2-aryl-3,4,5-trihydroxypiperidines: Synthesis and glycosidase inhibition

Hui Zhao, Wu Bao Wang, Shinpei Nakagawa, Yue Mei Jia, Xiang Guo Hu, George W.J. Fleet, Francis X. Wilson, Robert J. Nash, Atsushi Kato^*, Chu Yi Yu

^*Corresponding author for this work

Hospital Pharmacy

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

10 Scopus citations

Abstract

Three pairs of novel 2-aryl-3,4,5-trihydroxypiperidines (6-8 and their enantiomers), the piperidine analogues of the pyrrolidine alkaloids radicamine A and radicamine B, were prepared from six-membered cyclic nitrones through a concise two-step procedure, i.e., Grignard reagent addition and deprotection. These novel polyhydroxylated piperidine iminosugars were assayed against 10 types of enzymes. Only compound 8 exhibited weak inhibition (IC₅₀ 1080 μmol/L) against β-galactosidase from rat intestinal lactases.

Original language	English
Pages (from-to)	1059-1063
Number of pages	5
Journal	Chinese Chemical Letters
Volume	24
Issue number	12
DOIs	https://doi.org/10.1016/j.cclet.2013.06.027
State	Published - 2013/12

Keywords

2-Aryl polyhydroxylated piperidine
Glycosidase inhibitors
Iminosugars
Radicamine mimics

ASJC Scopus subject areas

General Chemistry

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10.1016/j.cclet.2013.06.027

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@article{082e8220b51a494ab74347a3df00ce7a,

title = "Novel 2-aryl-3,4,5-trihydroxypiperidines: Synthesis and glycosidase inhibition",

abstract = "Three pairs of novel 2-aryl-3,4,5-trihydroxypiperidines (6-8 and their enantiomers), the piperidine analogues of the pyrrolidine alkaloids radicamine A and radicamine B, were prepared from six-membered cyclic nitrones through a concise two-step procedure, i.e., Grignard reagent addition and deprotection. These novel polyhydroxylated piperidine iminosugars were assayed against 10 types of enzymes. Only compound 8 exhibited weak inhibition (IC50 1080 μmol/L) against β-galactosidase from rat intestinal lactases.",

keywords = "2-Aryl polyhydroxylated piperidine, Glycosidase inhibitors, Iminosugars, Radicamine mimics",

author = "Hui Zhao and Wang, {Wu Bao} and Shinpei Nakagawa and Jia, {Yue Mei} and Hu, {Xiang Guo} and Fleet, {George W.J.} and Wilson, {Francis X.} and Nash, {Robert J.} and Atsushi Kato and Yu, {Chu Yi}",

note = "Funding Information: Financial support from National Basic Research Program of China (Nos. 2012CB822101 and 2011CB808603 ), and the Natural Science Foundation of China (Nos. 21272240 and 21102149 ) is gratefully acknowledged. ",

year = "2013",

month = dec,

doi = "10.1016/j.cclet.2013.06.027",

language = "英語",

volume = "24",

pages = "1059--1063",

journal = "Chinese Chemical Letters",

issn = "1001-8417",

publisher = "Elsevier B.V.",

number = "12",

}

TY - JOUR

T1 - Novel 2-aryl-3,4,5-trihydroxypiperidines

T2 - Synthesis and glycosidase inhibition

AU - Zhao, Hui

AU - Wang, Wu Bao

AU - Nakagawa, Shinpei

AU - Jia, Yue Mei

AU - Hu, Xiang Guo

AU - Fleet, George W.J.

AU - Wilson, Francis X.

AU - Nash, Robert J.

AU - Kato, Atsushi

AU - Yu, Chu Yi

N1 - Funding Information: Financial support from National Basic Research Program of China (Nos. 2012CB822101 and 2011CB808603 ), and the Natural Science Foundation of China (Nos. 21272240 and 21102149 ) is gratefully acknowledged.

PY - 2013/12

Y1 - 2013/12

N2 - Three pairs of novel 2-aryl-3,4,5-trihydroxypiperidines (6-8 and their enantiomers), the piperidine analogues of the pyrrolidine alkaloids radicamine A and radicamine B, were prepared from six-membered cyclic nitrones through a concise two-step procedure, i.e., Grignard reagent addition and deprotection. These novel polyhydroxylated piperidine iminosugars were assayed against 10 types of enzymes. Only compound 8 exhibited weak inhibition (IC50 1080 μmol/L) against β-galactosidase from rat intestinal lactases.

AB - Three pairs of novel 2-aryl-3,4,5-trihydroxypiperidines (6-8 and their enantiomers), the piperidine analogues of the pyrrolidine alkaloids radicamine A and radicamine B, were prepared from six-membered cyclic nitrones through a concise two-step procedure, i.e., Grignard reagent addition and deprotection. These novel polyhydroxylated piperidine iminosugars were assayed against 10 types of enzymes. Only compound 8 exhibited weak inhibition (IC50 1080 μmol/L) against β-galactosidase from rat intestinal lactases.

KW - 2-Aryl polyhydroxylated piperidine

KW - Glycosidase inhibitors

KW - Iminosugars

KW - Radicamine mimics

UR - http://www.scopus.com/inward/record.url?scp=84888434569&partnerID=8YFLogxK

U2 - 10.1016/j.cclet.2013.06.027

DO - 10.1016/j.cclet.2013.06.027

M3 - 学術論文

AN - SCOPUS:84888434569

SN - 1001-8417

VL - 24

SP - 1059

EP - 1063

JO - Chinese Chemical Letters

JF - Chinese Chemical Letters

IS - 12

ER -

Novel 2-aryl-3,4,5-trihydroxypiperidines: Synthesis and glycosidase inhibition

Abstract

Keywords

ASJC Scopus subject areas

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