Flow reactor syntheses of the oxazole alkaloids O-methyl siphonazole and (-)-hennoxazole A

恶唑生物碱 O-甲基西吩唑和 (-)-hennoxillax A 的流动反应器合成

• 批准号: 68116605
• 负责人: Professor Dr. Malte Brasholz
• 金额: --
• 依托单位: Yusuf Hamied Department of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/68116605?language=en
• 关键词: Flow; reactor; syntheses; oxazole; alkaloids

Polymer-supported reagents have emerged as an ecologically benign alternative to homogenous reagents. Their application to organic synthesis can be regarded as green chemistry because it contributes to the preservation of natural resources and minimises the production of waste materials. Flow reactors are arrangements of linearly connected cartridges pre-packed with these immobilised reagents. An organic substrate can be eluted through such a reactor system and undergo a whole sequence of chemical transformations. The goal of this research is the production of complex target molecules using this novel technology platform. While smaller molecules have already been synthesized, the next challenge is the flow synthesis of antibiotics and antitumor agents. During recent years, the group of Professor Ley have been aiming at this vision and we consequently plan a flow synthesis of the oxazole alkaloid O-methyl siphonazole (2). We present a realistic retrosynthetic analysis of this target compound as well as a detailed plan for a flow reactor setup for its total synthesis. Following the common practice in the Ley group, we have developed a second synthesis project. We present a flexible approach to biologically active pyrrotizidine alkaloids, exemplified by hyacinthacine A5 (23). It relies on chiral butane-2,3-diacetal protected building blocks and a novel preparation of enantiopure aminoalcohols.

聚合物支持的试剂已经成为一种对生态无害的替代均相试剂的方法。它们在有机合成中的应用可以被认为是绿色化学，因为它有助于保护自然资源，并最大限度地减少废物的产生。流动反应器是由预先填充了这些固定化试剂的线性连接的药筒组成的装置。有机底物可以通过这样的反应器系统洗脱，并经历一系列的化学转化。这项研究的目标是利用这一新的技术平台生产复杂的靶分子。虽然已经合成了较小的分子，但下一个挑战是抗生素和抗肿瘤药物的流动合成。近年来，Ley教授的团队一直致力于这一愿景，因此我们计划了一种恶唑生物碱O-甲基西芬唑的流动合成(2)。我们提出了一个现实的目标化合物的反合成分析，以及为其全合成建立流动反应器的详细计划。遵循LEY小组的惯例，我们开发了第二个合成项目。我们提出了一种灵活的方法，以风信子A5(23)为例，研究具有生物活性的吡咯替丁类生物碱。它依赖于手性丁烷-2，3-二缩醛保护的构筑块和一种新的对映体氨基醇的制备。