Synthesis of Physiologically Active Compounds by Using Cyclization of Carbamoylmethyl Radicals

利用氨基甲酰甲基自由基环化合成生理活性化合物

• 批准号: 03671020
• 负责人: IKEDA Masazumi
• 金额: $ 1.34万
• 依托单位: Kyoto pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03671020/
• 关键词: Carbamoylmethyl Radical; Radical cyclization; Trachelanthamidine; Mesembranol; Elwesine; Pretazettine; beta-Lactam; ALkaloid; トリブチンヒドリド; ラジカル環化; ラクタム; メセンブラノ-ル

We have found that the carbamoylmethyl radicals (=NCO-CH-) generated from alpha-cholroacetamides undergo cyclizations with intramolecular alkenes in regio- and stereo-selective manner to give a variety of lactams.1. The N-allyl-alpha-chloroacetamides, upon tratment with Bu_3SnH and azoisobutyronitrile (AIBN) in refluxing benzene, gave fie-membered lactams. This reaction was applied for the synthesis of (-)-trachelanthamidine, a kainoid analog, ((〕SY.+-.〔))-mesembranol, and ((〕SY.+-.〔))-elwesine.2. Similar treatment of omicron-alkenylphenyl-alpha, alpha-dichloroacetamides gave six- to eight-membered lactams in regioselective manner.3. The N-vinylic alpha-haloacetamides also cyclized to give either four- or five-membered lactams, depending upon the substituents which can stabilize the adical intermediates formed after cyclizations. This cyclixation was applied for the synthesis of ((〕SY.+-.〔))-cotinine, a metabolite of nicotine, and beta-lactams such as (+)-PS-5 and (+)-thienamycin.4. When N-allylic alpha-chloro-alpha-methelthioacetamides were heated with RuCl_2(PPh_3)_2 in benzene at 140ﾟC in a sealed tube, atom-transfer type cyclizations took place to give fic-membered rings. This cyclization was applied to the synthesis of (-)-trachlanthamidine and ((〕SY.+-.〔))-pretazettine.

我们发现，由α-胆红乙酰胺产生的甲酰胺甲基自由基（= NCO-CH-）在区域和立体选择方式中经历了分子内烷烃的环化，以提供各种lactams.1。在与Bu_3Snh和Azoisobutyroninitrile（AIBN）的回流中，N-酰基 - α-氯乙酰氨二酰胺在回流苯中给出了Fie成元的lactams。将该反应用于（ - ） - tracheanthamidine，Kainoid类似物的合成，（（（（> sy。+ - 。。类似的Omicron-Alkenyl-苯基 - α，α-二氯乙酰氨酰胺以调节性选择方式给出了六到八元的乳糖。3。 N- vinylicα-半乙酰氨酰胺也被环循环以产生四元或五元的lactams，具体取决于可以稳定在环化后形成的晚期中间体的子介质。该循环量用于（（>SY。+ - 。〔）） - cotinine，cotinine，一种尼古丁的代谢产物，以及β-内酰胺（例如（+） - ps-5和（+） - thienamycin.4。当N-甲基化α-氯-Alpha-甲基乙酰乙酰氨酰胺用RUCL_2（PPH_3）_2在密封管中的140°C中加热时，就会发生原子 - 转移类型的环化，以提供FIC粘合的环。这种环化应用于（ - ） - 三角兰氨基胺和（（（］ sy。+ - 。〔）） - 促狂想汀。

项目成果

石橋 弘行: "Radical Cyclizations of NーVinylic αーChloroacetamides.5ーEndoーtrig and 4ーExoーtrig Cyclizations" Terahedron Letters. 32. 1725-1728 (1991)

Hiroyuki Ishibashi：“N-乙烯基 α-氯乙酰胺的自由基环化。5-Endotrig 和 4-Exo-trig 环化”Terahedron Letters 32。1725-1728 (1991)

佐藤達典: "Regiochemistry of Radical Cyclisations(6-exo/7-endo and 7-exo/8-endo)of N-(o-Alkenylphenyl)-2,3-dichloroacetamides" J.Chem.Soc.,Perkin Trans.1. 353-359 (1991)

Tatsunori Sato：“N-(o-烯基苯基)-2,3-二氯乙酰胺的自由基环化（6-exo/7-endo 和 7-exo/8-endo）的区域化学”J.Chem.Soc.，Perkin Trans。 1. 353-359（1991）

佐藤 達典: "Regiochemistry of Radical Cyclisations (6ーexo/7ーendo and 7ーexo/8ーendo)of Nー(OーAlkenylphenyl)ー2,2ーdichloroacetーamides" J.Chem.Soc.,Perkin 1. 353-359 (1991)

Tatsunori Sato：“N-(O-烯基苯基)-2,2-二氯乙酰胺的自由基环化（6-exo/7-endo 和 7-exo/8-endo）的区域化学”J.Chem.Soc.，Perkin 1。 353-359 (1991)

佐藤 達典: "Regiochemistry of Radical Cyclisations (6-exo/7-endo and 7-exo/8-endo)of N-(o-Alkenylphenyl)-2,2-dichloro acetamides" J. Chem. Soc., Perkin Trans. 1. 353-359 (1991)

Tatsunori Sato：“N-(o-烯基苯基)-2,2-二氯乙酰胺的自由基环化（6-exo/7-endo 和 7-exo/8-endo）的区域化学”J. Chem Soc.，Perkin Trans。 1. 353-359 (1991)

Hiroyuki Ishibashi: "Synthesis of beta-Lactams by MEans of Sulfur-Controlled Regioselective Radical Cyclizations of N-Ethenyl-alpha-bromoacetamides" Synlett. 649-650 (1993)

Hiroyuki Ishibashi：“通过 N-乙烯基-α-溴乙酰胺的硫控制区域选择性自由基环化合成 β-内酰胺”Synlett。