Biologically Active Substances by Use of Electrochemical Oxidation Associate Professor

利用电化学氧化产生生物活性物质 副教授

• 批准号: 01571133
• 负责人: MORI Miwako
• 金额: $ 1.34万
• 依托单位: Hokkaido 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: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01571133/
• 关键词: Electrochemical Reaction; Anodic Oxidation; gamma-Lactam; alpha-Acetoxy-gamma-lactam; γーラクタム; αーアセトキシーγーラクタム; γ-ラクタム; α-アセトキシ-γ-ラクタム

Anodic oxidation of lactoms was very useful for the synthetic organic chemistry. We have already reported the new synthetic method of 4-acetoxy-2-azatidinones from 4-carboxy-2-azetidinones by use of electrochemical oxidation. Namely, 4-carboxy-2-azatidinone was electrolyzed in an undivided cell using platinum plates as electrode in the presence of AcONa as electrolyte in AcOH-CH_3CN to give 4-acetoxy-2-azetidinone in high yield. Using this method, a new synthetic method of optically active 3-hydroxy-ethyl-4-acetoxy-2-azetidinone which was an intermediate for the synthesis of thienamycin and its analogues, was developed and a formal total synthesis of (+)-PS-5 was achieved. This method was applied for the synthesis of gamma-lactams. Pyroglutamic acid was electrolyzed to afford 2-acetoxy-pyrrolldone in good yield. In a similar manner, compounds2a and 2b were obtained from 1a and 1b. Subsequently, C-C bond formation at 2-position of pyrrolldone was tried. Compound 6__- which was obtained by electrolysis from compound 5__- was treated with TiCl_4 to provide indollzidine derivative in good yield. Thus, the new method for the synthesis of bicyclic lactams by electrolysis from lactams having carboxy group at alpha-position of nitrogen was developed.

乳酸的阳极氧化在有机合成中具有重要的应用价值。我们已经报道了用电化学氧化法从4-羧基-2-氮杂环丁酮合成4-乙酰氧基-2-氮杂环丁酮的新方法。即在无隔板电解槽中，以铂片为电极，AcONa为电解质，在AcOH-CH_3CN中电解4-羧基-2-氮杂环丁酮，高产率得到4-乙酰氧基-2-氮杂环丁酮。利用该方法，开发了合成硫霉素及其类似物的中间体光学活性3-羟基-乙基-4-乙酰氧基-2-氮杂环丁酮的新合成方法，并实现了（+）-PS-5的正式全合成。将该方法应用于γ-内酰胺类化合物的合成。以焦谷氨酸为原料，经电解得到2-乙酰氧基吡咯酮。以类似的方式，从1a和1b得到化合物2a和2b。随后，尝试在吡咯烷酮的2位形成C-C键。将化合物5__-电解得到的化合物6__-用TiCl_4处理，以高产率得到吲哚嗪衍生物。因此，开发了由氮的α位上具有羧基的内酰胺通过电解合成双环内酰胺的新方法。

项目成果

M. Mori: "Ring Construction of Bicyclic beta-lactams by Use of Palladium Catalyzed Carbonylation" Heterocycles. 29. 853 (1989)

M. Mori：“使用钯催化羰基化构建双环 β-内酰胺”杂环。

Miwako Mori: "Ring Construction of Bicyclic γ-Lactams by Use of Electrochemical Oxidation" Heterocycles. 29. 2089-2092 (1989)

Miwako Mori：“利用电化学氧化构建双环 γ-内酰胺”杂环。29。2089-2092 (1989)

Miwako Mori: "Ring Constrction of alphaーLactam by Use of Electrochemical Oxidation" Heterocycles. 29. 2089-2092 (1989)

Miwako Mori：“利用电化学氧化环构建 α-内酰胺”杂环。29。2089-2092 (1989)

M. Mori: "Ring Construction off Bicyclic gamma-Lactams by Use of Electrochemical Oxidation" Heterocycles. 29. 2089 (1989)

M. Mori：“通过使用电化学氧化来构建双环γ-内酰胺”杂环。

Miwako Mori: "Ring Construction of Bicyclic bataーLactam by Use of Palladium Catalyzed Carbonylation" Heterocyles. 29. 853-856 (1989)

Miwako Mori：“使用钯催化羰基化构建双环巴塔-内酰胺”杂环。 29. 853-856 (1989)