Design and Synthesis of Highly Bioactive Sugar-Related Substances

高生物活性糖相关物质的设计与合成

• 批准号: 13470472
• 负责人: IKEGAMI Shiro
• 金额: $ 8.64万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470472/
• 关键词: Coyolosa; Sugar lactone; L-Iduronic acid; 1-Methylglycoside; Selective glycosylation; Cyclitol; Antidiabetic drug; Voglibose; L-ヘキソース; L-リボース; オルトエステル; スピロ糖

The following research results have been obtained in this research project.1) Coyolosa which is a natural disaccharide having an unusual structure with a 6,6'-ether-linkage was successfully synthesized. In connection with its anti-diabetic activity, 10 kinds of analogs have been synthesized and it was concluded that the reported structure should be revised. A 6,6'-disaccharide formed from two molecules of mannose might be proposed.2) The conversion of sugar lactones to the hydroxamic acid derivatives by the ring opening operation and the recyclization under Mitsunobu conditions gives the corresponding L-sugar. By applying this conversion technique, L-ribose and L-iduronic acid were also synthesized efficiently3) Glycosylation using 1-methylenesugar afforded the corresponding α-D-glycoside stereo-selectively. This method could be applied to synthesize the various types of αglycosides such as α-oligosaccharides exhibiting a potent biological activity.

本研究项目取得了以下研究成果： 1) Coyolosa是一种具有6,6'-醚键结构的天然二糖，成功合成了10种抗糖尿病活性的化合物。类似物已经合成，并且得出的结论是应该修改所报道的结构，可能建议由两个甘露糖分子形成6,6'-二糖。2)糖内酯向糖内酯的转化。异羟肟酸衍生物通过开环操作和Mitsunobu条件下的再循环得到相应的L-糖通过应用这种转化技术，L-核糖和L-艾杜糖醛酸也被有效地合成3)使用1-亚甲基糖进行糖基化得到相应的α-。该方法可用于立体选择性合成各种类型的α糖苷，例如具有有效生物活性的α-低聚糖。

项目成果

Li, Xiaoliu: "Direct Methylation of Partially Benzyl-protected Sugar Lactones by Dimethyltitanocene"SYNLETT. No.12. 1885-1888 (2001)

李小六：“二甲基二茂钛直接甲基化部分苄基保护的糖内酯”SYNLETT。

Y.M.A.Yamada: "Assembled catalyst of palladium and non-cross-linked amphiphilic polymer ligand for the efficient heterogeneous Heck reaction"Tetrahedron. 60(in press). (2004)

Y.M.A.Yamada：“用于高效非均相 Heck 反应的钯和非交联两亲聚合物配体的组装催化剂”四面体。

X-L.Li, H.Takahashi, H.Ohtake, S.Ikegami: "Synthesis of Ketosyl Spiro-Isoxazolidine by 1,3-Dipolar Cycloaddition of 1-Methylenesugars and Nitrones -A New Access to C-Glycosyl Amino Acids"Heterocycles. 59(No.2). 547-571 (2003)

X-L.Li、H.Takahashi、H.Ohtake、S.Ikegami：“通过 1-亚甲基糖和硝酮的 1,3-偶极环加成合成酮基螺异恶唑烷 - 获得 C-糖基氨基酸的新途径”杂环。

Y.M.A. Yamada: "Development of a New Triphase Catalyst and Its Application to Epoxidation of Allylic Alcohols"Organic Letters. 3. 1837-1840 (2001)

Y.M.A.

Xiaoliu Li: "Direct Methylenation of Partially Benzyl-protected Sugar Lactones by Dimethyltitinocene"Synlett. 1885-1888 (2001)

李晓柳：“二甲基二茂钛直接甲基化部分苄基保护的糖内酯”Synlett。