Design and Synthesis of New Bioactive Substances directed to Drug Discovery

面向药物发现的新生物活性物质的设计和合成

• 批准号: 09470488
• 负责人: IKEGAMI Shiro
• 金额: $ 6.02万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470488/
• 关键词: sugar ortho ester; reductive glycosylation; inositol; ring transformation; inositol phosphate; cyclophellitol; decarboxylative glycosylation; 9-cis-retinoic acid abalogue; 9-シス-レチノイン酸類縁体; 有機鉛試薬; エン-ジイン化合物

Our works directed to finding bioactive substances which have been carried out for past three years (1997-1999) are summarized as follows.1. Efficient and practical ring transformation of 6-eno-D-glycosides promoted by a catalytic amount of Palladium dichloride has been accomplished. The resulting cyclitols could be used for the synthesis of sugar-related bioactive compounds.2. Cyclophellitol and its 3-epimer which exhibit highly potent glycosidase inhibition could be synthesized efficiently.3. Novel synthesis of all diastereoisomers of Inositols and their phosphates such as IPィイD23ィエD2 and IPィイD24ィエD2 has been accomplished based on an application of the above transformation.4. Extremely efficient synthetic method for the preparation of sugar-sugar ortho esters has been found and their structures have been established by X-ray chrystallographic analysis and by MM2 computer calculation technique. Their selective reductions provided a new highly stereoselective glycosidation method.5. Application of the sugar ortho ester formation has made it possible in a short cut synthesis of voglibose, a potent glycosidase inhibitor.6. New decarboxylative glycosidation using sugar-sugar mixed carbonates has been extensively studied. Details of the reaction mochanism have also been examined7. Explitation of new synthetic technoloogy using chiral polymers has been also studies with starting design and synthesis of new type of polymers

我们在过去三年中（1997-1999）开展的寻找生物活性物质的工作总结如下：在二氯化钯的催化作用下，实现了6-烯- d -糖苷高效、实用的环转化。所制得的环醇可用于糖类生物活性化合物的合成。对糖苷酶具有较强抑制作用的环丁香醇及其3-外显体可以有效地合成。在上述转化的基础上，合成了肌醇的所有非对映异构体及其磷酸盐，如IP小伙伴D23小伙伴D2和IP小伙伴D24小伙伴D2。找到了一种制备糖-糖邻位酯的高效合成方法，并通过x射线结晶分析和MM2计算机计算技术确定了糖-糖邻位酯的结构。它们的选择性还原提供了一种新的高度立体选择性的糖苷化方法。糖邻位酯形成的应用，使其成为一种有效的糖苷酶抑制剂——伏糖糖的捷径合成成为可能。糖-糖混合碳酸盐的新型脱羧糖苷化已经得到了广泛的研究。对反应机理的细节也进行了研究。研究了利用手性聚合物开发新的合成技术，开始设计和合成新型聚合物

项目成果

H. Takahashi, H. Kittaka, and S. Ikegami: "Development of Ferrier(II) Carbocyclization Catalyzed by Pd(II) and Its Application to the Synthesia of Bioactive Substances"J.Synth.Org.Chem.Japan. 58, No.2(Japanese). 120-128 (2000)

H. Takahashi、H. Kittaka 和 S. Ikegami：“Pd(II) 催化的 Ferrier(II) 碳环化的发展及其在生物活性物质合成中的应用”J.Synth.Org.Chem.Japan。

Y. M. A. Yamada: "Efficient Baylis-Hillman Reaction Promoted by Mild Cooperative Catalysts and Their Application to Catalytic Asymmetric Synthesis"Tetrahedron Lett.. 41(in press). (2000)

Y. M. A. Yamada：“温和协同催化剂促进的高效贝利斯-希尔曼反应及其在催化不对称合成中的应用”Tetrahedron Lett.. 41（印刷中）。

H. Ohtake, T. Iimori, and S. Ikegami: "A Facile and Improved Preparation of Glycosylidene Acetals of Monosaccha-rides"Tetrahedron Lett.. 38(No.19). 3413-3414 (1997)

H. Ohtake、T. Iimori 和 S. Ikegami：“单糖化合物糖亚基缩醛的简便且改进的制备”Tetrahedron Lett.. 38（第 19 期）。

Y. M. A. Yamada and S. Ikekami: "Efficient Baylis-Hillman Reaction Promoted by Mild Cooperative Catalysts and Their Application to Catalytic Asymmetric Synthesis"Tetrahedron Lett.. 41(in press). (2000)

Y. M. A. Yamada 和 S. Ikekami：“温和协同催化剂促进的高效 Baylis-Hillman 反应及其在催化不对称合成中的应用”Tetrahedron Lett.. 41（印刷中）。

H. Takahashi, T. Iimori, and S. Ikegami: "An Efficient Synthesis of Cyclophellitol Utilizing Unusual Regioselectivity of Oxirane Ring Opening with MesィイD22ィエD2BCHィイD22ィエD2Li"Tetrahedron Lett.. 39, (No.37). 6939-6942 (1998)

H. Takahashi、T. Iimori 和 S. Ikegami：“利用 MesiD22D2BCHID22D2Li 开环的异常区域选择性环苯乙醇的高效合成”Tetrahedron Lett.. 39，（第 37 期）（1998 年）。