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

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• 作者：Filipa P. da Cruz ; 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.
• 刊名：Tetrahedron Letters
• 出版年：2011
• 出版时间：12 January 2011
• 年：2011
• 卷：52
• 期：2
• 页码：219-223
• 全文大小：818 K

文摘

The syntheses of 4-C-Me-DAB [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 the analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase K_i 0.89 μM, IC₅₀ 0.41 μM) is a competitive—whereas 4-C-Me-LAB (for rat intestinal sucrase K_i 0.95 μM, IC₅₀ 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.