Cystic fibrosis and diabetes: isoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars
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- 作者：Daniel Best ; Sarah F. Jenkinson ; A. Waldo Saville ; Dominic S. Alonzi ; Mark R. Wormald ; Terry D. Butters ; Caroline Norez ; Frederic Becq ; Yves Blé ; riot ; Isao Adachi ; Atsushi Kato ; George W.J. Fleet
- 刊名：Tetrahedron Letters
- 出版年：2010
- 出版时间：11 August 2010
- 年：2010
- 卷：51
- 期：32
- 页码：4170-4174
- 全文大小：451 K
文摘
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 Ki 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.