α-1-C-butyl-1, 4-dideoxy-1, 4-imino-l-arabinitol as a second-generation iminosugar-based oral α-glucosidase inhibitor for improving postprandial hyperglycemia

…, S Miyauchi, I Adachi, T Imahori, Y Natori…

Index: Kato, Atsushi; Hayashi, Erina; Miyauchi, Saori; Adachi, Isao; Imahori, Tatsushi; Natori, Yoshihiro; Yoshimura, Yuichi; Nash, Robert J.; Shimaoka, Hideyuki; Nakagome, Izumi; Koseki, Jun; Hirono, Shuichi; Takahata, Hiroki Journal of Medicinal Chemistry, 2012 , vol. 55, # 23 p. 10347 - 10362

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Citation Number: 37

Abstract

We report on the synthesis and the biological evaluation of a series of α-1-C-alkylated 1, 4- dideoxy-1, 4-imino-l-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross- coupling as key reactions. α-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 μM, respectively. Matrix- ...