Synthetic Studied on Thiosugar Suronium Sulfate Inner Salt,a Potent α-Glucosidase Inhibitor

Salacinol（1）是一种有效的α-葡萄糖苷酶抑制剂，从五层龙（Salacia reticulata WIGHT，在僧伽罗语中称为Kotala himbutu）的根和茎的水提取物中分离得到，在斯里兰卡和印度传统上用于治疗糖尿病。通过X-射线晶体学分析等化学和物理化学证据，揭示了它独特的由1-脱氧-4-硫代阿拉伯呋喃糖基阳离子和1 ′-脱氧赤藓糖基-3 ′-硫酸根阴离子组成的螺状内盐结构。以D-葡萄糖为起始原料，经7步反应合成了2的含氮类似物2及相关化合物，并测定了它们对α-葡萄糖苷酶的抑制活性。以D-葡萄糖为原料，以较高的收率合成了1，4-二脱氧-1，4-亚氨基-D-阿拉伯糖醇（D-4）。3和D-4之间的偶联反应，然后 关于我们 水解以良好的产率得到所需的2。另一方面，L-4显示出与1几乎相同的抑制活性。因此，L-4也以42%的总收率从D-木糖（5）制备，并与2，4-亚苄基-D-赤藓糖醇-1，3-环硫酸酯（6）偶联，以良好的收率得到2的对映异构体7。体外测定了它们对肠道α-葡萄糖苷酶的抑制活性，发现1的硫原子被氮原子取代后，抑制活性显著降低。通过对模型化合物8的单晶X-射线衍射分析，推测氮杂环类化合物的立体结构不同是活性降低的原因。与1不同的是，8的两个离子中心相距较远。本文还对1的α-葡萄糖苷酶抑制剂活性与所合成的相关化合物的构效关系进行了综述。少

Salacinol (1) is a potent α-glucosidase inhibitor isolated from the aqueous extracts of the roots and stemps of Salacia reticulata WIGHT(nows as Kotala himbutu in Singhalese), which is traditionally used in Sri Lanka and India for the treatment of diabetes. Its unique spiro-like structure of the inner salt comprised of 1-deoxy-4-thioarabinofuranosyl cation and 1'-deoxyerythrosyl-3'-sulfate anion was revealed by the authors on the basis of chemical and physicochemical evidences including the X-ray crystallographic analysis. In this study, the nitrogen analogue 2 of 1 and some related compounds were synthesized, and their inhibitory activities against α-glucosidase tested.2, 4-Isopropylidene-L-erythritol-1, 3-cyclic sulfate precursor (3), used for the tethering arm of 2, was synthesized in 73% overall yield via seven steps starting from D-glucose. 1, 4-Dideoxy-1, 4-imino-D-arabinitol (D-4) was synthesized in good yield also from D-glucose. Coupling reaction between 3 and D-4 followed by … More hydrolysis gave the desired 2 in good yield. On the other hand, L-4 has been reported to show nearly equal inhibitory activity to that of 1.Thus, L-4 was also prepared in 42% overall yield from D-xylose (5), and was coupled with 2, 4-benzylidene-D-erythrito-1, 3-cyclic sulfate (6) to give the enantiomeric isomer 7 of 2 in good yield. The α-glucosidase inhibitory activities of them were tested for the intestinal α-glucosidase in vitro, and found to be reduced considerably upon substitution of the sulfur atom of 1 with the nitrogen. The origin of the reduced activities were attributed to the different stereosturucture of the aza-analogues, which was deduced by the single crystal X-ray measurement of the model compound 8 obtained by the coupling reaction of 3 with pyrrolidine. Different from those of 1 the two ionic centers in 8 were far apart from each other. Further structure-activity relationships concerning the α-glucosidase inhibitor activity of 1 using the related compounds synthesized have been summarized. Less