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:
- 金额:$ 2.05万
- 依托单位:
- 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:
- 关键词:
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) 是一种从五层龙 (Salacia reticulata WIGHT)(现为僧伽罗语中的 Kotala humbutu)的根和茎的水提取物中分离出来的有效 α-葡萄糖苷酶抑制剂,传统上在斯里兰卡和印度用于治疗糖尿病。内盐独特的螺状结构,由 1-脱氧-4-硫代阿拉伯呋喃糖基阳离子和作者根据包括X射线晶体学分析在内的化学和物理化学证据揭示了1'-脱氧赤藓糖基-3'-硫酸根阴离子。在本研究中,合成了氮类似物2 of 1和一些相关化合物。测试了对 α-葡萄糖苷酶的抑制活性。2, 4-异丙叉-L-赤藓糖醇-1, 3-环硫酸盐前体 (3),用于2 的束缚臂以 73% 的总产率从 D-葡萄糖开始合成,从 D 开始也以良好的产率合成了 1, 4-二脱氧-1, 4-亚氨基-D-阿拉伯糖醇 (D-4)。 3 和 D-4 之间发生偶联反应,然后进行水解,以良好的产率得到所需的 2。另一方面,据报道,L-4 显示出几乎相同的抑制活性。因此,L-4 也由 D-木糖 (5) 制备,总产率为 42%,并与 2, 4-亚苄基-D-赤藓糖醇-1, 3-环硫酸酯 (6) 偶联,得到以良好的产率得到对映异构体7 of 2。体外测试了它们对肠道α-葡萄糖苷酶的抑制活性,发现它们具有良好的α-葡萄糖苷酶抑制活性。 1 的硫原子被氮取代后活性降低的原因是氮杂类似物的不同立体结构,这是通过对模型化合物 8 的单晶 X 射线测量得出的。 3 与吡咯烷的偶联反应与 1 的偶联反应不同,8 中的两个离子中心彼此相距很远,使用有关 1 的 α-葡萄糖苷酶抑制剂活性的进一步结构-活性关系。已合成的相关化合物已总结较少。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
村岡 修: "Synthesis of a Nitrogen Analogue of Salacinol and its α-Glucosidase Inhibitory Activity"Chem.Pharm.Bull.. 49巻・11号. 1530-1535 (2001)
Osamu Muraoka:“Salacinol 的氮类似物的合成及其 α-葡萄糖苷酶抑制活性”Chem.Pharm.Bull.. 第 49 卷,第 11 期。1530-1535 (2001)
- DOI:
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- 影响因子:0
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Osamu Muraoka: "Synthesis of a Nitorogen Analogue of Salacinol and its α-Glucosidase Inhibitory Activity"Chem. Pharm. Bull.. 49(11). 1503-1505 (2001)
Osamu Muraoka:“Salacinol 的含氮类似物的合成及其 α-葡萄糖苷酶抑制活性”Chem. Bull. 49(11) (2001)。
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M. Yoshikawa: "Absolute Stereostructure of Potent α-Glucosidase Inhibitor, Salacinol, with Unique Thiosugar Sulfonium Sulfate Inner Salt Structure from Salacia reticulata"Bioorg. Med. Chem.. 10(5). 1547-1554 (2002)
M. Yoshikawa:“强效 α-葡萄糖苷酶抑制剂 Salacinol 的绝对立体结构,具有来自五层龙的独特硫代硫酸磺内盐结构”Bioorg Med. 10(5)。
- DOI:
- 发表时间:
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- 影响因子:0
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Osamu Muraoka: "Synthesis of a Nitorogen Analogue of Salacinol and its α-Glucosidase Inhibitory Activity"Bull. Pharm. Res. Technol. Inst.. 10. 83-89 (2001)
Osamu Muraoka:“Salacinol 的含氮类似物的合成及其 α-葡萄糖苷酶抑制活性”,药学研究所。10. 83-89 (2001)
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吉川雅之: "Absolute Stereostnicture of Potent α-Glucosidase Inhibitor, Salacinol, with Unique Thiosugar Sulfonium Sulfate Inner Salt Structure from Salacici reticulata"Bioorg.Med.Chem.. 10巻・5号. 1547-1554 (2002)
Masayuki Yoshikawa:“强效 α-葡萄糖苷酶抑制剂 Salacinol 的绝对立体结构,具有来自 Salacici reticulata 的独特硫糖硫酸磺内盐结构”Bioorg.Med.Chem.. Vol. 10,No. 5. 1547-1554 (2002)
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MURAOKA Osamu其他文献
MURAOKA Osamu的其他文献
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{{ truncateString('MURAOKA Osamu', 18)}}的其他基金
Evaluation of complementary and alternative medicinal resources and their bio-functional ingredients based on pharmaceutical food sciences
基于医药食品科学的补充替代药用资源及其生物功能成分评价
- 批准号:
16K08313 - 财政年份:2016
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The screening of the genes that involved in the determination of the neural area and the neural induction
神经区域决定及神经诱导相关基因的筛选
- 批准号:
14570034 - 财政年份:2002
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Synthesis and Biological Evaluation of New α-Glucosidase inhibitors Designated on the Basis of the Structure of Salacinol
基于Salacinol结构的新型α-葡萄糖苷酶抑制剂的合成及生物学评价
- 批准号:
14572023 - 财政年份:2002
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)