General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)

Jean Yves Goujon; David Gueyrard; Philippe Compain; Olivier R. Martin; Kyoko Ikeda; Atsushi Kato; Naoki Asano

doi:10.1016/j.bmc.2004.12.043

General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)

Jean Yves Goujon, David Gueyrard, Philippe Compain^*, Olivier R. Martin, Kyoko Ikeda, Atsushi Kato, Naoki Asano

^*Corresponding author for this work

Hospital Pharmacy

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

45 Scopus citations

Abstract

A general synthesis of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides) by ring-opening reactions of an aziridine with various heteroatomic nucleophiles, including thiol, amine, alcohol, carboxylate and phosphate, is described. The nine-step reaction sequence proceeded in an overall yield of 14-28% from tri-O-benzyl-D-glucal. Biological evaluation of α-1-C-substituted derivatives of fagomine, of the 2-deoxy analog of α-homonojirimycin 19 and its 1,N-anhydro derivative 22 as glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found to display no inhibitory activity towards glycogen phosphorylase b and phosphoglucomutase.

Original language	English
Pages (from-to)	2313-2324
Number of pages	12
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	6
DOIs	https://doi.org/10.1016/j.bmc.2004.12.043
State	Published - 2005/03/15

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmc.2004.12.043

Cite this

@article{d039f30f78174e1da4f06779011733f7,

title = "General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)",

abstract = "A general synthesis of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides) by ring-opening reactions of an aziridine with various heteroatomic nucleophiles, including thiol, amine, alcohol, carboxylate and phosphate, is described. The nine-step reaction sequence proceeded in an overall yield of 14-28% from tri-O-benzyl-D-glucal. Biological evaluation of α-1-C-substituted derivatives of fagomine, of the 2-deoxy analog of α-homonojirimycin 19 and its 1,N-anhydro derivative 22 as glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found to display no inhibitory activity towards glycogen phosphorylase b and phosphoglucomutase.",

author = "Goujon, {Jean Yves} and David Gueyrard and Philippe Compain and Martin, {Olivier R.} and Kyoko Ikeda and Atsushi Kato and Naoki Asano",

note = "Funding Information: Financial support of this study by grants from CNRS and the association {\textquoteleft}Vaincre les Maladies Lysosomales{\textquoteright} is gratefully acknowledged.",

year = "2005",

month = mar,

day = "15",

doi = "10.1016/j.bmc.2004.12.043",

language = "英語",

volume = "13",

pages = "2313--2324",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "6",

}

TY - JOUR

T1 - General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)

AU - Goujon, Jean Yves

AU - Gueyrard, David

AU - Compain, Philippe

AU - Martin, Olivier R.

AU - Ikeda, Kyoko

AU - Kato, Atsushi

AU - Asano, Naoki

N1 - Funding Information: Financial support of this study by grants from CNRS and the association ‘Vaincre les Maladies Lysosomales’ is gratefully acknowledged.

PY - 2005/3/15

Y1 - 2005/3/15

N2 - A general synthesis of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides) by ring-opening reactions of an aziridine with various heteroatomic nucleophiles, including thiol, amine, alcohol, carboxylate and phosphate, is described. The nine-step reaction sequence proceeded in an overall yield of 14-28% from tri-O-benzyl-D-glucal. Biological evaluation of α-1-C-substituted derivatives of fagomine, of the 2-deoxy analog of α-homonojirimycin 19 and its 1,N-anhydro derivative 22 as glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found to display no inhibitory activity towards glycogen phosphorylase b and phosphoglucomutase.

AB - A general synthesis of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides) by ring-opening reactions of an aziridine with various heteroatomic nucleophiles, including thiol, amine, alcohol, carboxylate and phosphate, is described. The nine-step reaction sequence proceeded in an overall yield of 14-28% from tri-O-benzyl-D-glucal. Biological evaluation of α-1-C-substituted derivatives of fagomine, of the 2-deoxy analog of α-homonojirimycin 19 and its 1,N-anhydro derivative 22 as glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found to display no inhibitory activity towards glycogen phosphorylase b and phosphoglucomutase.

UR - http://www.scopus.com/inward/record.url?scp=13844312017&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2004.12.043

DO - 10.1016/j.bmc.2004.12.043

M3 - 学術論文

C2 - 15727880

AN - SCOPUS:13844312017

SN - 0968-0896

VL - 13

SP - 2313

EP - 2324

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 6

ER -

General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)

Abstract

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this