A Noven Radical Ring-Enlargement Reaction : The Reaction Mechanism and the Medicinal Chemical Application
新型自由基扩环反应:反应机理及医药化学应用
基本信息
- 批准号:11672095
- 负责人:
- 金额:$ 2.18万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We developed a regio-and stereoselective method for introducing 1-hydroxyethyl, 2-hydroxyethyl, and vinyl groups at the position β to a hydroxyl group in halohydrins or α-phenylselenoalkanols using an intramolecular radical cyclization reaction with a dimethyl-or diphenylvinylsilyl group as a temporary connecting radical-acceptor tether (Scheme 14). Thus, when a vinylsilyl ether of halohydrins or α-phenylselenoalkanols was subjected to the radical reaction with Bu_3SnH/AIBN, the selective introduction of both 1-hydroxyethyl and 2-hydroxyethyl groups can be achieved, depending on the concentration of Bu_3SnH in the reaction system, via a 5-exo-cyclization intermediate or a 6-endo-cyclization intermediate, respectively, after oxidative ring-cleavage by treating the cyclization products under Tamao oxidation conditions. A vinyl group can also be introduced by photo-irradiating the vinylsilyl ether in the presence of (Bu_3Sn)_2, and then treating the resulting atom-transfer 5-exo-cyclization product with fluoride ion. The mechanistic studies showed that the kinetically favored 5-exo-cyclized radical was trapped when the concentration of Bu_3SnH was high enough. At lower concentrations of Bu_3SnH and higher reaction temperatures, the 5-exo-cyclized radical rearranged into the more stable ring-enlarged 4-oxa-3-silacyclohexyl radical, which was then trapped with Bu_3SnH.The ring-enlarging rearrangement was experimentally proved to occur via a pentavalent-like silicon-bridging transition state. This radical reaction with a vinylsilyl tether has been successfully applied to the synthesis of 4'-branched-chain sugar nucleosides as a nucleoside unit for antisense studies and also for potent antiviral nucleosides. C-glycosides trisphosphates as potent IP_3-receptor ligands were also synthesized using the radical reaction as the key step.
我们开发了一种区域和立体选择性方法,用于在卤代醇或α-苯基硒代烷醇中的羟基的β位引入1-羟乙基、2-羟乙基和乙烯基,使用分子内自由基环化反应,用二甲基或二苯基乙烯基甲硅烷基作为临时连接自由基受体系链(方案14)。因此,卤代醇或α-苯硒代烷醇的乙烯基硅醚与Bu_3SnH/AIBN进行自由基反应时,根据Bu_3SnH在反应体系中的浓度,可以分别通过5-外环化中间体或6-内环化中间体选择性地引入1-羟乙基和2-羟乙基,在Tamao氧化条件下处理环化产物进行氧化开环后。在(Bu_3Sn)_2存在下,通过光照射乙烯基硅醚,然后用氟离子处理原子转移5-外环化产物,也可以引入乙烯基。机理研究表明,当Bu_3SnH浓度足够高时,5-外环化自由基被捕获。在较低的Bu_3SnH浓度和较高的反应温度下,5-外环化自由基重排为更稳定的4-氧杂-3-硅杂环己基,然后被Bu_3SnH捕获,实验证明扩环重排是通过类似五价硅桥过渡态发生的.这种与乙烯基甲硅烷基系链的自由基反应已成功地应用于合成4 '-支链糖核苷,作为用于反义研究的核苷单元,也用于有效的抗病毒核苷。以自由基反应为关键步骤,合成了具有IP_3受体活性的三磷酸碳苷类配体。
项目成果
期刊论文数量(37)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
S.Shuto, et al.: "Mechanistic study of the ring-enlargement reaction of (3-oxa-2-silacyclopentyl) methyl radicals into 4-oxa-3-silacyclohexyl radicals. Evidence for a pentavalent silicon-bridging radical transition state in 1,2-rearrangement reactions of
S.Shuto 等人:“(3-oxa-2-silacyclopentyl) 甲基自由基成 4-oxa-3-silacyclohexyl 自由基的扩环反应的机理研究。五价硅桥自由基过渡态的证据
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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- 通讯作者:
R.D.Marwood, et al.: "Convergent synthesis of adenophostin A analogues via a base replacement strategy."Chem.Commun.. 219-220 (2000)
R.D.Marwood 等人:“通过碱基替换策略聚合合成腺苷磷蛋白 A 类似物。”Chem.Commun. 219-220 (2000)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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- 通讯作者:
T.Kodama, et al.: "I'α-Branched-chain sugar pyrimidine ribonucleosides from uridine. The first conversion of a natural nucleoside into 1'-substituted ribonucleosides"Chem.Eur.J.. (in press).
T.Kodama 等人:“来自尿苷的 Iα-支链糖嘧啶核糖核苷。天然核苷首次转化为 1-取代核糖核苷”Chem.Eur.J.(印刷中)。
- DOI:
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- 影响因子:0
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- 通讯作者:
S.Shuto, et al.: "Stereoselective synthesis of α-and β-C-glucosides via radical cyclization with an allylsilyl tether. Control of the stereoselectivity by changing the conformation of the pyranose ring."Tetrahedron Lett.. 41. 4151-4155 (2000)
S.Shuto 等人:“通过烯丙基甲硅烷基系链的自由基环化立体选择性合成 α-和 β-C-葡萄糖苷。通过改变吡喃糖环的构象控制立体选择性。”Tetrahedron Lett.. 41. 4151- 4155 (2000)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
I.Sugimoto, et al.: "Kinetics of a novel 1,2-rearrangement reaction of β-silyl radicals"Synlett. 1766-1768 (1999)
I.Sugimoto 等人:“β-甲硅烷基自由基的新型 1,2-重排反应的动力学”Synlett,1766-1768 (1999)
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- 影响因子:0
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