Literature DB >> 21157573

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.

Filipa P da Cruz1, Scott Newberry, Sarah F Jenkinson, Mark R Wormald, Terry D Butters, Dominic S Alonzi, Shinpei Nakagawa, Frederic Becq, Caroline Norez, Robert J Nash, Atsushi Kato, George W J Fleet.   

Abstract

The syntheses of 4-C-Me-DAB [n class="Chemical">1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pK(a) of the salt around 8.4] is discussed and illustrates the need for care in analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase K(i) 0.89 μM, IC(50) 0.41 μM) is a competitive - whereas 4-C-Me-LAB (for rat intestinal sucrase K(i) 0.95 μM, IC(50) 0.66 μM) is a non-competitive - specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB, and isoDAB - but not isoLAB - is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.

Entities:  

Year:  2011        PMID: 21157573      PMCID: PMC3000536          DOI: 10.1016/j.tetlet.2010.10.173

Source DB:  PubMed          Journal:  Tetrahedron Lett        ISSN: 0040-4039            Impact factor:   2.415


  19 in total

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