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

Daniel Best; Sarah F. Jenkinson; A. Waldo Saville; Dominic S. Alonzi; Mark R. Wormald; Terry D. Butters; Caroline Norez; Frederic Becq; Yves Blériot; Isao Adachi; Atsushi Kato; George W.J. Fleet

doi:10.1016/j.tetlet.2010.05.131

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

Daniel Best, Sarah F. Jenkinson, A. Waldo Saville, Dominic S. Alonzi, Mark R. Wormald, Terry D. Butters, Caroline Norez, Frederic Becq, Yves Blériot, Isao Adachi, Atsushi Kato, George W.J. Fleet

Hospital Pharmacy

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Abstract

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 α-glucosidase inhibitor (for rice α-glucosidase, K_i = 4 μM for isoDAB compared to K _i 14 μM 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.

Original language	English
Pages (from-to)	4170-4174
Number of pages	5
Journal	Tetrahedron Letters
Volume	51
Issue number	32
DOIs	https://doi.org/10.1016/j.tetlet.2010.05.131
State	Published - 2010/08/11

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tetlet.2010.05.131

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@article{d488d15db03541f395ffc5de52997b74,

title = "Cystic fibrosis and diabetes: IsoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars",

abstract = "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 α-glucosidase inhibitor (for rice α-glucosidase, Ki = 4 μM for isoDAB compared to K i 14 μM 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.",

author = "Daniel Best and Jenkinson, {Sarah F.} and Saville, {A. Waldo} and Alonzi, {Dominic S.} and Wormald, {Mark R.} and Butters, {Terry D.} and Caroline Norez and Frederic Becq and Yves Bl{\'e}riot and Isao Adachi and Atsushi Kato and Fleet, {George W.J.}",

note = "Funding Information: C.N. and F.B. are supported by grants from the French association {\textquoteleft}Vaincre la Mucoviscidose{\textquoteright} . Part of this work (TDB, DSA) was supported by Grant No. R01CA125642 from the National Cancer Institute.",

year = "2010",

month = aug,

day = "11",

doi = "10.1016/j.tetlet.2010.05.131",

language = "英語",

volume = "51",

pages = "4170--4174",

journal = "Tetrahedron Letters",

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publisher = "Elsevier Ltd.",

number = "32",

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TY - JOUR

T1 - Cystic fibrosis and diabetes

T2 - IsoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars

AU - Best, Daniel

AU - Jenkinson, Sarah F.

AU - Saville, A. Waldo

AU - Alonzi, Dominic S.

AU - Wormald, Mark R.

AU - Butters, Terry D.

AU - Norez, Caroline

AU - Becq, Frederic

AU - Blériot, Yves

AU - Adachi, Isao

AU - Kato, Atsushi

AU - Fleet, George W.J.

N1 - Funding Information: C.N. and F.B. are supported by grants from the French association ‘Vaincre la Mucoviscidose’ . Part of this work (TDB, DSA) was supported by Grant No. R01CA125642 from the National Cancer Institute.

PY - 2010/8/11

Y1 - 2010/8/11

N2 - 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 α-glucosidase inhibitor (for rice α-glucosidase, Ki = 4 μM for isoDAB compared to K i 14 μM 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.

AB - 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 α-glucosidase inhibitor (for rice α-glucosidase, Ki = 4 μM for isoDAB compared to K i 14 μM 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.

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U2 - 10.1016/j.tetlet.2010.05.131

DO - 10.1016/j.tetlet.2010.05.131

M3 - 学術論文

AN - SCOPUS:77955303835

SN - 0040-4039

VL - 51

SP - 4170

EP - 4174

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 32

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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