Synthesis of 2-deoxy-2-fluoro and 1,2-ene derivatives of the naturally occurring glycosidase inhibitor, salacinol, and their inhibitory activities against recombinant human maltase glucoamylase

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• 作者：Niloufar Choubdar ; Lyann Sim ; David R. Rose ; B. Mario Pinto
• 关键词：Glycosidase inhibitors ; Salacinol derivatives ; 2-Deoxy-2-fluorosalacinol ; 2-Deoxy-1-ene-salacinol ; Cyclic sulfates ; Human maltase glucoamylase (MGA) inhibition
• 刊名：Carbohydrate Research
• 出版年：2008
• 期刊代码：15_00086215
• 类别：ch
• 出版时间：7 April 2008
• 卷：343
• 期：5
• 页码：951-956
• 文件大小：139 K

摘要

2-Deoxy-2-fluorosalacinol and a 1,2-ene derivative of the naturally occurring glycosidase inhibitor salacinol were synthesized for structure activity studies with human maltase glucoamylase (MGA). 2-Deoxy-2-fluorosalacinol was synthesized through the coupling reaction of 2-deoxy-2-fluoro-3,5-di-O-p-methoxybenzyl-1,4-anhydro-4-thio-d-arabinitol with 2,4-O-benzylidene-l-erythritol-1,3-cyclic sulfate in hexafluoroisopropanol (HFIP) containing 0.3 equiv of K₂CO₃. Excess of K₂CO₃ resulted in the elimination of HF from the coupled product, and the formation of an alkene derivative of salacinol. Nucleophilic attack of the 1,4-anhydro-4-thio-d-arabinitol moiety on the cyclic sulfate did not proceed in the absence of K₂CO₃. No reaction was observed in acetonitrile containing K₂CO₃. The target compounds were obtained by deprotection with TFA. The 2-deoxy-1-ene derivative of salacinol and 2-deoxy-2-fluorosalacinol inhibited recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose, with an IC₅₀ value of 150 μM and a K_i value of 6 ± 1 μM, respectively.