Cystic fibrosis and diabetes: isoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars

被引：44

作者：

Best, Daniel ^{[1
]}

Jenkinson, Sarah F. ^{[1
]}

Saville, A. Waldo ^{[1
]}

Alonzi, Dominic S. ^{[3
]}

Wormald, Mark R. ^{[3
]}

Butters, Terry D. ^{[3
]}

Norez, Caroline ^{[4
]}

Becq, Frederic ^{[4
]}

Bleriot, Yves ^{[5
]}

Adachi, Isao ^{[2
]}

Kato, Atsushi ^{[2
]}

Fleet, George W. J. ^{[1
]}

机构：

[1] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England

[2] Toyama Univ, Dept Hosp Pharm, Toyama 9300194, Japan

[3] Univ Oxford, Oxford Glycobiol Inst, Oxford OX1 3QU, England

[4] Univ Poitiers, CNRS, Inst Physiol & Biol Cellulaires, F-86022 Poitiers, France

[5] Lab Synth & React Subst Nat, UMR 6514, F-86022 Poitiers, France

来源：

TETRAHEDRON LETTERS | 2010年 / 51卷 / 32期

关键词：

LOOKING-GLASS INHIBITORS; GLYCOSIDASE INHIBITORS; PHARMACOLOGICAL RESCUE; GLUCOSIDASE INHIBITOR; EPITHELIAL-CELLS; POTENT INHIBITOR; ANGYLOCALYX-BOUTIQUEANUS; GLYCOGEN-PHOSPHORYLASE; ARACHNIODES-STANDISHII; ALPHA-GLUCOSIDASES;

D O I：

10.1016/j.tetlet.2010.05.131

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Acetonides are the only protecting groups used in the syntheses of isoDAB from D-ribose and of isoLAB from D-tagatose. isoDAB is a potent and highly specific competitive a-glucosidase inhibitor (for rice alpha-glucosidase, K(i) = 4 mu M for isoDAB compared to K(i) 14 mu M for DAB). isoDAB is not an whereas DAB is a potent inhibitor of glycogen phosphorylase. This is the first example of any potent inhibition of glycosidases by a carbon-branched iminosugar pyrrolidine. Although isoLAB shows no inhibition of any glycosidase, preliminary experiments suggest that isoLAB partially rescues the defective F508del-CFTR function and so may have a role in the study of cystic fibrosis. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4170 / 4174

页数：5

共 1 条

[1] 4-C-Me-DAB and 4-C-Me-LAB-enantiomeric alkyl-branched pyrrolidine iminosugars-are specific and potent α-glucosidase inhibitors; acetone as the sole protecting group
da Cruz, Filipa P.
Newberry, Scott
Jenkinson, Sarah F.
Wormald, Mark R.
Butters, Terry D.
Alonzi, Dominic S.
Nakagawa, Shinpei
Becq, Frederic
Norez, Caroline
Nash, Robert J.
Kato, Atsushi
Fleet, George W. J.
TETRAHEDRON LETTERS, 2011, 52 (02) : 219 - 223

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