Precise Synthesis of C-Nucleosides and Relation ship between their Structures and Biological Activity

C-核苷的精确合成及其结构与生物活性的关系

• 批准号: 07554085
• 负责人: YOYOYAMA Masataka
• 金额: $ 1.66万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07554085/
• 关键词: C-Azanucleosides; C-Azadeoxynucleosides; Furanosylribose; Furanosyldeoxyribose; Anti-HIV-I; C-Azalyxonucleosides; 抗エイズ剤; β-選択的合成; C-ヌクレオシド; 抗HIV; C-ヘテロ原子-ヌクレオシド; 立体選択的合成; 生物活性評価; C-リボヌクレオシド; C-デオキシリボヌクレオシド

In the viewpoint of biological activity, especially such as antiviral drugs, the C-nucleoside like showdomycin and the azasugar like nojirimycin have been known as naturally occurring and potential compounds. As a part of our program for synthesis and evaluation of a new type of DNA subunits, we intended to synthesize the nucleosides such as C-azanucleosides and C-azadeoxy-nucleosides, which have the structual skeletons similar to two compounds mentioned above : That is, the nucleosides which have a C-C bond between sugar's anomeric position and base moiety, and further, the endocyclic ribosyl or deoxyribosyl ring oxygen is replaced with nitrogen atom. To our best knowledge, the syntheses of three known C-azanucleosides have required unavailable starting materials or contained many difficult synthetic steps. Therefore, we developed a general method for the synthesis of gram quantities of C-azanucleosides, which was C-azalyxonucleosides by X-ray analysis. As the extention of this investigation, we reported the first synthesis of both C-azadeoxylyxonucleosides and C-azalyxonucleosides bearing a natural type of base such as uracil, azapseudouridine and further, their properties and biological activities.

从生物活性的观点来看，特别是如抗病毒药物，已知C-核苷类显多霉素和氮杂糖类野尻霉素是天然存在的和潜在的化合物。作为我们合成和评价新型DNA亚基计划的一部分，我们打算合成核苷如C-氮杂核苷和C-氮脱氧核苷，它们具有与上述两种化合物相似的结构骨架：也就是说，在糖的异头位置和碱基部分之间具有C-C键的核苷，并且进一步地，内环核糖基或脱氧核糖基环上的氧被氮原子取代。据我们所知，三种已知的C-氮杂核苷的合成需要不可用的起始原料或包含许多困难的合成步骤。因此，我们开发了一种合成克量的C-氮杂核苷的通用方法，即X射线分析的C-氮杂核苷。作为本研究的延伸，我们首次合成了含天然碱基如尿嘧啶、氮杂尿嘧啶核苷的C-氮杂环己基糖苷和C-氮杂环己基糖苷，并进一步报道了它们的性质和生物活性。

项目成果

横山正孝: "Novel Water-soluble Organosilane Compounds as a Radical Reduiing Agent in Aqueous Media" Bull. Chem. Soc. Jpn.70. 2519-2523 (1997)

Masataka Yokoyama：“新型水溶性有机硅烷化合物作为水介质中的自由基还原剂”，Soc.70 (1997)。

S. Ishigami et al.: "Reaclivity of Carbocyclic Four-membered Radioals for the Preparation of Carbocyclic Analogues of Oxetanocins" J. Chem. Soc., Perkin 1. 2407-2412 (1994)

S. Ishigami 等人：“用于制备 Oxetanocins 碳环类似物的碳环四元放射性的反应性”J. Chem。

H.Togo, Y.Hoshina, M.Yokoyama: "Cyclic Amination onto Aromatic Ring via Radical Pathway with (Diacetoxyiodo) arenes" Phosphorus, Sulfur, and Silicon. 120. 449-450 (1997)

H.Togo、Y.Hoshina、M.Yokoyama：“通过自由基途径用（二乙酰氧基碘）芳烃在芳香环上进行循环胺化”磷、硫和硅。

横山 正孝: "Formation and Synthetic USE of Oxygen-centered Radioals with (Diacetoxyiodo)arenes" J.Chem.Soc.,Perkin Trains.1. 787-793 (1997)

Masataka Yokoyama：“氧中心放射性化合物与（二乙酰氧基碘）芳烃的形成和合成用途”J.Chem.Soc.，Perkin Trains.1（1997）。

横山正孝: "Stereo selective Coupling of Riboses with Metallic salts of Aromatic Heterocycles" J. Chem. Soc., Perkin Trans. 1. 29-33 (1997)

Masataka Yokoyama：“核糖与芳香杂环金属盐的立体选择性偶联”J. Chem.，Perkin Trans. 1. 29-33 (1997)