One Step Synthesis of 1,4-Benzodiazepines

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。

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.