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α-氯乙酰胺类化合物生成的氨基甲酰甲基自由基（=NCO-CH-）与分子内烯烃发生区域和立体选择性的环化反应，生成多种内酰胺类化合物. N-烯丙基-α-氯乙酰胺在乙苯中与Bu_3SnH和偶氮异丁腈（AIBN）反应生成五元内酰胺。该反应用于合成（-）-络石脒，一种红藻氨酸类似物，（（）SY.（））-mesembranol和（）SY.（））-elwesine。2.类似的处理omicron-烯基苯基-α，α-二氯乙酰胺以区域选择性方式得到六至八元内酰胺。N-乙烯基α-卤代乙酰胺也环化得到四元或五元内酰胺，这取决于环化后形成的可稳定自由基中间体的取代基。该环化合物用于合成（（）SY.（±）-可替宁，尼古丁的代谢物，和β-内酰胺类，如（+）-PS-5和（+）-噻那霉素。N-烯丙基-α-氯代-α-甲硫基乙酰胺与RuCl_2（PPh_3）_2在苯中于140 ℃下加热，发生原子转移型环化反应，生成五元环。将此环合反应用于合成（-）-沙眼脒和（（）SY.+-。（））-普他西汀。

项目成果

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)

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)

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

Hiroyuki Ishibashi：“N-乙烯基 α-氯乙酰胺的自由基环化。5-Endo-trig 和 4-Exo-trig 环化”Tetrahedron Lett.32 (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。