Synthesis of Selenium Analogues of the Naturally Occurring Glycosidase Inhibitor Salacinol and Their Evaluation as Glycosidase Inhibitors

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• 作者：Blair D. Johnston ; Ahmad Ghavami ; Morten T. Jensen ; Birte Svensson ; and B. Mario Pinto
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：July 17, 2002
• 年：2002
• 卷：124
• 期：28
• 页码：8245 - 8250
• 全文大小：94K
• 年卷期：v.124,no.28(July 17, 2002)
• ISSN：1520-5126

文摘

The syntheses of two selenium analogues (10 and 11) of the naturally occurring sulfonium ion,salacinol (3), are described. Salacinol is one of the active principles in the aqueous extracts of Salaciareticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The syntheticstrategy relies on the nucleophilic attack of a 2,3,5-tri-O-benzyl-1,4-anhydro-4-seleno-D-arabinitol at theleast hindered carbon of benzyl- or benzylidene-protected D- or L-erythritol-1,3-cyclic sulfate. The use of1,1,1,3,3,3-hexafluoro-2-propanol as a solvent in the coupling reaction proves to be beneficial. Enzymeinhibition assays indicate that 10 is a better inhibitor (K_i = 0.72 mM) of glucoamylase than 3, which has aK_i value of 1.7 mM. In contrast, 11 showed no significant inhibition of glucoamylase. Compounds 10 and11 showed no significant inhibition of barley-fchars/alpha.gif" BORDER=0>-amylase or porcine pancreatic-fchars/alpha.gif" BORDER=0>-amylase.