One Step Synthesis of 1,4-Benzodiazepines

1,4-苯二氮卓类化合物的一步合成

• 批准号: 60570973
• 负责人: MORI Miwako
• 金额: $ 1.09万
• 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: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570973/
• 关键词: Palladium catalyzed carbonylation; <Pd(PPh_3)_4>; carbonylation; benzodiazepine; quinazoline; antibiotics; tomaymycin; ネオスラマイシン

We have already shown the synthetic procedure of 1,4-benzodiazepines from o-halo-anilines and amino acid derivatives by use of palladium catalyzed carbonylation. Using this method, the total syntheses of pyrrolo-1,4-benzodiazepine antibiotics, namely, tomaymycin, prothracarcin, and SEN-215 were achieved from o-haloaniline derivatives and hydroxy-l-proline as the optically active forms. The structures of prothracarcin and SEN-215 were determined synthetically as E-form, respectively. Moreover, a carbon framwork of neothramycin was constructed from o-iodoaniline and l-proline by four steps including palladium catalyzed carbonylation and anodic oxidation of carbon <alpha> to nitrogen. The total synthesis of neothramycin was effected from the same intermediate for the synthesis of tomaymycin and SEN-215. During the course of this study, it was found that the quinazoline skeleton was easily formed from o-iodoaniline and five membered lactams. By the application of this method, new synthetic method of quinazoline was developed and vasicinone and rutecarpine were synthesized.

我们已经介绍了用钯催化羰基化法从邻卤苯胺和氨基酸衍生物合成1，4-苯并二氮杂卓的方法。利用该方法，以邻卤代苯胺衍生物和羟基脯氨酸为光学活性形式，实现了托马霉素、prothracarcin和SEN-215等吡咯并-1，4-苯并二氮杂类抗生素的全合成。通过合成方法确定了prothracarcin和SEN-215的结构均为E型。以邻碘苯胺和L-脯氨酸为原料，通过钯催化羰基化和碳阳极氧化为氮四步反应，构建了新红霉素的碳骨架<alpha>。新丝霉素的全合成由合成托马霉素和SEN-215的相同中间体进行。在研究过程中，发现喹唑啉骨架很容易由邻碘苯胺和五元内酰胺形成。应用该方法，开发了喹唑啉的合成新方法，并合成了长春新碱和鲁替卡品。

项目成果

M.Mori,Y.Uozumi and Y.Ban: J.C.S.Chemical Communications. 841-842 (1986)

M.Mori、Y.Uozumi 和 Y.Ban：J.C.S.Chemical Communications。

M.Mori,Y.Uozumi and Y.Ban: Heterocycles. 24. 1257-1261 (1986)

M.Mori、Y.Uozumi 和 Y.Ban：杂环。

M. Mori, H. Kobayashi, M. Kimura, and Y. Ban: "One Pot Reactions of Quinazoline Derivatives" Heterocycles. 23. 2803-2806 (1985)

M. Mori、H. Kobayashi、M. Kimura 和 Y. Ban：“喹唑啉衍生物的一锅反应”杂环。

M. Mori, Y. Uozumi, M. Kimura, and Y. Ban: "Total Syntheses of Prothracarcin and tomaymycin by Use of Palladium Catalyzed Carbonylation" Tetrahedron. 42. 3793-3806 (1986)

M. Mori、Y. Uozumi、M. Kimura 和 Y. Ban：“利用钯催化羰基化全合成 Prothracarcin 和 Tomaymycin”四面体。

M.Mori,M.Kimura Y.Uozumi,and Y.Ban: Tetrahedron Letters. 48. 5947-5950 (1985)

M.Mori、M.Kimura、Y.Uozumi 和 Y.Ban：四面体字母。