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

强效α-葡萄糖苷酶抑制剂硫代糖硫酸钠内盐的合成研究

基本信息

批准号：
11672128
负责人：
MURAOKA Osamu
金额：
$ 2.05万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672128/
关键词：
salacinol Salacia reticula antidiabetic agents α-glucosidase inhibitor sulfonium sulfate inner salt azasuga cyclic sulfate coupling reaction Salacia reticulata thiosugar suldonium sulfate inner aslt sulfation

项目摘要

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

Salacinol（1）是一种潜在的α-葡萄糖苷酶抑制剂，该抑制剂是从根部的水提取物和萨拉西亚niticulata Wight的台阶中分离出来的（现在是Singhalese的Kotala himbutu），传统上是在斯里兰卡和印度使用的，用于治疗糖尿病。作者根据化学和物理证据（包括X射线晶体学分析）揭示了其内部盐的独特类型内盐结构，完成了1-脱氧-4-硫代氨基硫素阳离子和1'-脱氧硫醇3'-硫酸盐阴离子的独特结构。在这项研究中，合成了1和一些相关化合物的氮类似物2，其对α-葡萄糖苷酶的抑制活性。2，4-异丙二烯 - l-苯二醇-1，3-二晶硫酸盐前体（3），用于2，用于2的螺旋臂2，用于73％STEPS s Steps启动73％STEPS启动。 1、4-二维氧基-1、4- imino-d-drabinitol（d-4）也以良好的产量也来自D-葡萄糖。 3和D-4之间的耦合反应，然后……更多的水解给出了所需的2个。另一方面，据报道，L-4的抑制活性几乎相等的抑制活性，而L-4也以D-木糖的总收率为42％（5），并与2，4-苯甲酰乙烯-D-甲硅烷基thrito-1，3-苯甲酸酯硫酸盐（6）（6）偶联，以使eNantiomereric Ismemereric isomer 7 f s of antantiomereric isomereric isomer 7 f ins 2 in n of 2 in n of。对其的α-葡萄糖苷酶抑制活性在体外测试了肠α-葡萄糖苷酶的肠道抑制活性，并发现在用氮用1硫原子替代1的硫原子后，可以共识地降低。还原活性的起源归因于Aza-Analogues的不同立体情节，该立体是由通过3与吡咯烷的偶联反应获得的模型化合物8的单晶X射线测量所推测的。与1个离子中心的1个不同的不同，彼此相距遥远。使用相关化合物合成的α-葡萄糖苷酶抑制剂活性有关的进一步的结构活性关系已汇总。较少的