Synthesis of Pharmacologically Active Natural Products using Radical Translocation/cyclization Reactions

利用自由基易位/环化反应合成具有药理活性的天然产物

基本信息

批准号：
11672125
负责人：
IKEDA Masazumi
金额：
$ 2.24万
依托单位：
Kyoto Pharmaceutical University
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

项目摘要

The scope and limitations of tributyltin hydride (Bu_3SnH)-mediated radical translocation/cyclization reactions and an application to the synthesis of pharmacologically active natural products have been investigated. The results obtained were as follows :(1) Bu_3SnH-mediated radical translocation/cyclization reactions of methyl 1-(o-iodobenzoyl)-2-[4-(trimethylsilyl) but-3-ynyl]-piperi-dine-2-carboxylate and 1-(o-iodobenzoyl)-2-methyl-2-[4-(trimethyl-silyl)but-3-ynyl] piperidine-2-carboxylate proceeded in a regio-selective 6-exo-dig manner to give 9-azabicyclo [3.3.1] nonanes in high yield as a 1 : 1 diastereomeric mixture in both cases. 1-(o-Iodobenzoyl)-2-[4-(trimethylsilyl) but-3-ynyl] piperidine also afforded the 9-azabicyclo [3.3.1] nonane (65%), along with the hexahydropyrido [2, 1-a] isoindolone derivative (23%). Conversion of the 9-azabicyclo [3.3.1] nonane to (±)-euphococcinine was also examined.(2) The reaction of 1-(o-iodobenzoyl)-4-[3-(trimethylsilyl) prop-2-ynyl] piperidine afforded the isomeric 2-azabicyclo [3.2.1] octanes in 34 and 51% yield, along with a trace amount of the reduction product. On the other hand 1-(o-iodobenzoyl)-4-[4-(trimethyl-silyl) but-3-ynyl] piperidine proceeded more slowly to give the 2-azabicyclo [3.3.1] nonane (morphan) in 20% yield as a diastereomeric mixture. In the latter case the reduction product was obtained as a major product in 75% yield.(3) Both 1-[3-(trimethylsilyl) prop-2-ynyl]-and 1-[4-(trimethyl-silyl) but-3-ynyl]-2-(o-iodobenzoyl)-1, 2, 3, 4-tetrahydroiso-quinolines, upon treatment with Bu_3SnH, underwent smoothly either a 5-exo-dig or 6-exo-dig cyclization to give the isomeric 6, 7, 8, 9-tetrahydro-5H-benzocyclohepten-5, 8-imines (95%) and 5, 6, 7, 8, 9, 10-hexahydrobenzocycloocten-5, 9-imines (65%), respectively.

已经研究了甲基丁基二氢化酯（BU_3SNH）介导的自由基易位/环化反应的范围和局限性，并应用了对药物活性天然产物的合成的应用。获得的结果如下：（1）BU_3SNH介导的自由基易位/环化反应1-（o- iodobenzoyl）-2- [4-（trimethylsilyl）but-3-ynyl] but 1-(o-iodobenzoyl)-2-methyl-2-[4-(trimethyl-silyl)but-3-ynyl] piperiidine-2-carboxylate proceeded in a regio-selective 6-exo-dig manner to give 9-azabicyclo [3.3.1] nonanes in high yield as a 1 : 1 diastereomeric mixture in both cases. 1-（o-碘苯甲酰氮）-2- [4-（三甲基甲硅烷基）but-3-ynyl]哌啶也提供了9-扎皮克里克洛[3.3.1] nonane（65％），以及六氢吡啶[2，1-a] isoindolone衍生物（23％）。还检查了9-氮杂微粒[3.3.1]非烷至（±） - 欧普氨酸的转化。（2）（2）1-（o- iodobenzoyl）-4- [3-（trimethylsilyl）Prop-2-ynyl]的反应，以及与同体的2-齐布克里赛（3.2.1 in y 3.2.1 in actiment and Inforcement and Intress of trage）。还原产品。另一方面，1-（O-碘苯甲酰氮）-4- [4-（三甲基 - 甲硅烷基）but-3-ynyl]哌啶的piperiidine进行得更慢，以20％的产率，以20％的屈服，将2- azabicyclo [3.3.1] nonane（morphan）作为非对映体混合物。 In the later case the reduction product was obtained as a major product in 75% yield.(3) Both 1-[3-(trimethylsilyl) prop-2-ynyl]-and 1-[4-(trimethyl-silyl) but-3-ynyl]-2-(o-iodobenzoyl)-1, 2, 3, 4-tetrahydroiso-quinolines, upon treatment with Bu_3SnH, underwent顺利地，可以使异构体6、7、8、9-二氢-5H-5H-苯并杂曲菌5、8- i-Imines（95％）和5、6、6、7、7、8、9、9、9、9、9、9、9、9、9、9-二十二羟基苯二摄蛋白coclobloocolocten-5、9- 9-5％（65％）（65％）（65％）（65％）（65％）（65％）（65％）（65％）（65％）（65％）（65％）（65％）（95％）（95％）（95％）和5、6、6、7、8- imine（95％）和5、6、8- imine（95％）和65％。