Development of New Silicon Tethers and Their Application to the Synthesis of Anti-HIV Nucleosides

新型硅链的研制及其在抗HIV核苷合成中的应用

• 批准号: 13672203
• 负责人: SHUTO Satoshi
• 金额: $ 2.56万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672203/
• 关键词: Silicon tether; Ethynyl group; Radical reaction; Atom transfer; Anti-HIV agent; Nucleoside

A novel radical method for the stereoselective introduction of an ethynyl group using ethynyldimethylsilyl (EDMS) or [2-(trimethylsilyl)ethynyl]dimethylsilyl (TEDMS) as the radical acceptor tethers has been developed. When a solution of EDMS or TEDMS ethers of trans-2-iodoindanoI was treated with Et_3B followed by tetrabutylammonium fluoride in toluene, atom transfer 5-exo-cyclization and subsequent elimination occurred to give cis-2-ethynylindanol in high yield. The method was shown to be useful in the introduction of an ethynyl group in various five and six-membered ring iodohydrins. Furthermore, 2'-deoxy-2'-C-ethynyluridine and cytidine, which were designed as novel anti-HIV nucleoside analogues, were readily synthesized using this method as the key step.

发展了一种以乙炔基二甲基硅烷基（EDMS）或[2-（三甲基硅烷基）乙炔基]二甲基硅烷基（TEDMS）为自由基受体的乙炔基立体选择性引入的新方法。反式-2-碘茚满醇的EDMS或TEDMS醚与Et_3B、四丁基氟化铵在甲苯中反应，发生原子转移5-外环化和消除反应，高产率地得到顺式-2-乙炔基茚满醇。该方法被证明是有用的，在各种五元环和六元环碘代醇中引入乙炔基。此外，以该方法为关键步骤，设计合成了新型抗HIV核苷类似物2 ′-脱氧-2 ′-C-乙炔基尿苷和胞苷。

项目成果

M.Sukeda et al.: "The First Radical Method for the Introduction of an Ethynyl Group Using a Silicon Tether and its Application to the Synthesis of 2 -Deoxy-2'-C-Ethynylnucleosides"J. Org. Chem. (in press).

M.Sukeda 等人：“使用硅系链引入乙炔基的第一种激进方法及其在 2-脱氧-2-C-乙炔基核苷合成中的应用”J。

H. Abe, S. Shuto, A. Matsuda: "Highly a- and b-selective radical C-glycosylation reactions based on the conformational restriction strategy using a controlling anomeric effect. A study on the conformation-anomeric effect-stereoselectivity relationship in

H. Abe、S. Shuto、A. Matsuda：“基于使用控制异头效应的构象限制策略的高度 a-和 b-选择性自由基 C-糖基化反应。关于构象-异头效应-立体选择性关系的研究

T. Kodama, S. Shuto, S. Ichikawa, A. Matsuda: "A Highly Stereoselective Samarium Diiodide-Promoted Aldol Reaction Using 1'-Phenylseleno-2'-Keto Nucleosides. Synthesis of 1'a-Branched Uridine Derivatives"J. Org. Chem.. 67. 7706-7715 (2002)

T. Kodama、S. Shuto、S. Ichikawa、A. Matsuda：“使用 1-苯基硒代-2-酮核苷进行高度立体选择性二碘化钐促进的羟醛反应。1a-支链尿苷衍生物的合成”J。

S. Shuto, M. Kanazaki, I. Sugimoto, S. Ichikawa, Y. Nagasawa, Y. Ueno, H. Abe, N. Minakawa, M. Sukeda, T. Kodama, M. Nomura, A. Matsuda: "evelopment of new radical reactions with a vinylsilyl group and their application to the synthesis of branched-chain

S. Shuto、M. Kanazaki、I. Sugimoto、S. Ichikawa、Y. Nagasawa、Y. Ueno、H. Abe、N. Minakawa、M. Sukeda、T. Kodama、M. Nomura、A. Matsuda：“发展

M.Sukeda et al.: "A New Entry to the Stereoselective Introduction of an Ethynyl Group via Radical Reaction. Synthesis of a Potential Antimetabolite 2-Deoxy-2'-C-Ethynyluridine"Angew. Chem. Int. Ed. 41. 4748-4750 (2002)

M.Sukeda 等人：“通过自由基反应立体选择性引入乙炔基的新途径。潜在抗代谢物 2-脱氧-2-C-乙炔尿苷的合成”Angew。