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

沙拉辛醇(1)是一种有效的α葡萄糖苷酶抑制剂，从网状沙拉鬼魂(现在在新加坡语中称为Kotala himbuu)的根和茎的水提取物中分离出来，这是斯里兰卡和印度传统上用于治疗糖尿病的药物。根据化学和物理化学证据，包括X-射线晶体分析，揭示了其由1-脱氧-4-硫代阿拉伯糖基呋喃正离子和1‘-脱氧红酰基-3’-硫酸盐阴离子组成的独特的螺状内盐结构。本研究合成了1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-葡萄糖为起始原料，经7步反应合成了2，4-亚丙叉-L-赤藓糖醇前体(3)，总收率73%。以D-葡萄糖为原料，高产率地合成了1，4-二脱氧-1，4-亚氨基-D-阿拉伯醇(D-4)。3-D-4与…的偶联反应进一步的水解以较好的产率得到了所需的2。另一方面，据报道，L-4的抑制活性与1相当。因此，以D-木糖(5)为原料，以42%的总收率合成了L-4，并与2，4-亚甲基-D-赤红素-1，3-环硫酸酯(6)偶联，以较高的产率得到了2的对映体7。体外测定了它们对肠道α-葡萄糖苷酶的抑制活性，发现用氮取代1的硫原子后，α-葡萄糖苷酶的抑制活性显著降低。活性降低的原因是氮杂类似物的立体结构不同，这是通过对3与吡咯烷偶联反应得到的模型化合物8的单晶X射线测量得出的。与1不同的是，8的两个离子中心相距较远。利用所合成的相关化合物进一步总结了1的α-葡萄糖苷酶抑制活性的构效关系。较少

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