Kumar Nag S, Pinto B Mario
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Carbohydr Res. 2005 Dec 12;340(17):2612-9. doi: 10.1016/j.carres.2005.09.004. Epub 2005 Sep 29.
The synthesis of analogues of the naturally occurring glycosidase inhibitor, salacinol, in which the D-arabinitol ring has been replaced by D-lyxitol or D-ribitol, is described. Salacinol is one of the active principles in the aqueous extracts of Salacia reticulata, which are traditionally used in India and Sri Lanka for the treatment of Type II diabetes. The synthetic strategy relies on the nucleophilic attack of 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio-D-lyxitol or 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio-D-ribitol at the least hindered carbon of the benzylidene-protected L-cyclic sulfate derived from L-erythritol. Screening of these compounds against recombinant human maltase glucoamylase (MGA), a critical intestinal glucosidase involved in the processing of oligosaccharides of glucose into glucose itself, shows that they are not effective inhibitors of MGA and demonstrates the importance of the d-arabinitol configuration in the heterocyclic ring for effective inhibition.
本文描述了天然存在的糖苷酶抑制剂萨拉辛醇类似物的合成，其中D-阿拉伯糖醇环已被D-来苏糖醇或D-核糖醇取代。萨拉辛醇是网状刺桐水提取物中的活性成分之一，在印度和斯里兰卡传统上用于治疗II型糖尿病。合成策略依赖于1,4-脱水-2,3,5-三-O-对甲氧基苄基-4-硫代-D-来苏糖醇或1,4-脱水-2,3,5-三-O-对甲氧基苄基-4-硫代-D-核糖醇对由L-赤藓醇衍生的亚苄基保护的L-环硫酸盐中位阻最小的碳的亲核进攻。针对重组人麦芽糖酶葡糖淀粉酶（MGA）（一种参与将葡萄糖寡糖加工成葡萄糖本身的关键肠道糖苷酶）对这些化合物进行筛选，结果表明它们不是MGA的有效抑制剂，并证明了杂环中D-阿拉伯糖醇构型对有效抑制的重要性。
