Studies on Design and Synthesis of Glycoconjugate Drugs with Targeting

靶向糖复合物药物的设计与合成研究

基本信息

  • 批准号:
    08557119
  • 负责人:
  • 金额:
    $ 6.14万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
  • 财政年份:
    1996
  • 资助国家:
    日本
  • 起止时间:
    1996 至 1998
  • 项目状态:
    已结题

项目摘要

Due to the rapidly recognized biological significance of saccharide residues of carbohydrate-containing biomolecules, the rational design and development of stereocontrolled glycosidation reactions are of growing importance not only in carbohydrate chemistry but also in medicinal chemistry.As part of a program to develop novel and efficient glycosidation methods capitalizing on the phosphorus-containing leaving groups, we have now found that glycosyl donors incorporating diethyl phosphite exhibit not only excellent shelf-stabilities but also the following distinct advantages in the glycosidation reactions. (1) Coupling of benzyl-protected glycopyranosyl diethyl phosphites with a variety of acceptor alcohols can be effected by the aid of BF_3-OEt_2 as a promoter even at -78゚C to exhibit the highest 1,2-trans-beta-selectivity known to date for glycosidations with a non-participating group on O-2. (2) TMSOTf-mediated glycosidation of glycosyl phosphites bearing participating groups at C-2 … More constitutes an extremely mild and general method for the stereocontrolled construction of 1,2-trans-beta-glycosidic linkages. (3) A direct method for the construction of 2-deoxy-beta-glycosidic linkages has been developed by using 2-deoxyglycopyranosyl diethyl phosphites in the presence of a catalytic amount of TMSOTf, wherein glycosidations of 2-deoxy-D-gluco- and 2-deoxy-L-rhamnopyranosyl donors with primary alcohols have been found to exhibit the highest beta-selectivity known to date. (4) A direct glycosidation for the stereocontrolled construction of 1 , 2-cis-beta-mannnosides, a long-standing and formidable problem, has been achieved by exploiting 4,6-O-benzylidene-protected mannopyranosyl diethyl phosphites in the presence ofTMSOTf, though the method is limited to primary alcohols. (5) A highly stereocontrolled 1,2-cis-alpha-glycosidation under conditions mild enough for acid-labile alcohols has been developed by using benzyl-protected glycopyranosyl diethyl phosphites as glycosyl donors in the presence of 2,6-di-tert-butylpyridinium iodide and tetrabutylammonium iodide. Less
由于含糖生物分子中糖残基的生物学意义被迅速认识,合理设计和开发立体控制的糖苷化反应不仅在碳水化合物化学中而且在药物化学中越来越重要。作为开发利用含磷离去基团的新型高效糖苷化方法计划的一部分,我们现已发现,掺入亚磷酸二乙酯的糖基供体不仅表现出优异的贮存稳定性,而且在糖苷化反应中具有以下明显的优点。(1)苄基保护的吡喃葡萄糖基亚磷酸二乙酯与各种受体醇的偶联反应可以在BF_3-OEt_2作为促进剂的帮助下进行,即使在-78 ℃下也显示出迄今为止已知的最高的1,2-反式-β-选择性,用于O-2上的非参与基团的糖苷化。(2)TMSOTf介导的在C-2处带有参与基团的糖基亚磷酸酯的糖苷化 ...更多信息 构成了用于立体控制构建1,2-反式-β-糖苷键的极其温和和通用的方法。(3)通过在催化量的TMSOTf存在下使用2-脱氧吡喃葡萄糖基亚磷酸二乙酯,已经开发了用于构建2-脱氧-β-糖苷键的直接方法,其中已经发现2-脱氧-D-葡萄糖-和2-脱氧-L-吡喃鼠李糖基供体与伯醇的糖苷化显示出迄今已知的最高β-选择性。(4)通过在TMSOTf存在下利用4,6-O-亚苄基保护的吡喃甘露糖基亚磷酸二乙酯实现了直接糖苷化立体控制构建1,2-顺式-β-甘露糖苷,这是一个长期存在的难题,尽管该方法仅限于伯醇。(5)在2,6-二叔丁基碘化吡啶鎓和四丁基碘化铵存在下,以苄基保护的吡喃葡萄糖基亚磷酸二乙酯为糖基供体,在对酸不稳定的醇足够温和的条件下进行了高度立体控制的1,2-cis-alpha-糖苷化反应。少

项目成果

期刊论文数量(25)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Shun-ichi Hashimoto: ""Armed-Disarmed" Glycosidation Strategy Based on Glycosyl Donors and Acceptors Carrying Phosphoroamidate as a Leaving Group : A Convergent Synthesis of Globotriaosylceramide" Tetrahedron Lett.38. 8969-8972 (1997)
Shun-ichi Hashimoto:“基于携带氨基磷酸酯作为离去基团的糖基供体和受体的“武装-解除武装”糖苷化策略:三酰神经酰胺的聚合合成”Tetrahedron Lett.38。
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    0
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Shun-ichi Hashimoto: "New Strategy of Oligosaccharide Chain Synthesis" Faruaw. 32. 1375-1380 (1996)
桥本俊一:“寡糖链合成新策略”Faruaw。
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    0
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橋本俊一: "″Armed-Disarmed″ Glycosidation Strategy Based on Glycosyl Donors and Acceptors Carrying Phosphoroamidate as a Leaving Group:A Convergent Synthesis of Globotriaosylceramide." Tetrahedron Letters. 38. 8969-8972 (1997)
Shunichi Hashimoto:“基于携带氨基磷酸酯作为离去基团的糖基供体和受体的“武装-解除武装”糖苷化策略:三聚神经酰胺的聚合合成。38。8969-8972(1997)。
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  • 影响因子:
    0
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橋本俊一: "An Attempt at the Direct Construction of 2-Deoxy-β-glycosidic Linkages Capitalizing on 2-Deoxyglycopyranosyl Diethyl Phospites as Glycosy Donors." Synlatt. 1271-1273 (1995)
Shunichi Hashimoto:“利用 2-脱氧吡喃二乙酯作为糖基供体直接构建 2-脱氧-β-糖苷键”1271-1273 (1995)。
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    0
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橋本俊一: "Oligosaccharide Synthesis Based on Glycosyl Donors and Acceptors Carrying Phosphorus-Containing Leaving Groups" Tetrahedron Letters. 38. 5181-5184 (1997)
Shunichi Hashimoto:“基于携带含磷离去基团的糖基供体和受体的寡糖合成”Tetrahedron Letters 38。5181-5184(1997)
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    0
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HASHIMOTO Shun-ichi其他文献

HASHIMOTO Shun-ichi的其他文献

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{{ truncateString('HASHIMOTO Shun-ichi', 18)}}的其他基金

Highly Selective Glycosylations Based on Phosphorus-containing Leaving Groups
基于含磷离去基团的高选择性糖基化
  • 批准号:
    03671013
  • 财政年份:
    1991
  • 资助金额:
    $ 6.14万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Synthetic Studies on Forskolin and Its Related Compounds
毛喉素及其相关化合物的合成研究
  • 批准号:
    01571164
  • 财政年份:
    1989
  • 资助金额:
    $ 6.14万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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    2305456
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    2024
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    Fellowship Award
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