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

聚合物支撑试剂已成为一种生态良性的替代均质试剂。它们在有机合成中的应用可被视为绿色化学，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。流动反应器是用这些固定试剂预先包装的线性连接的药筒的排列。有机底物可以通过这样的反应器系统洗脱，并经历整个化学转化过程。本研究的目标是利用这种新技术平台生产复杂的靶分子。虽然更小的分子已经被合成，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，因此我们计划流动合成恶唑生物碱o -甲基siphonazole(2)。我们提出了一个现实的反合成分析的目标化合物，以及一个详细的计划，为其全合成的流动反应器设置。按照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来获得具有生物活性的吡啶生物碱，例如风信子A5（23）。它依赖于手性丁烷-2,3-双缩醛保护的构建块和对映纯氨基醇的新制备。

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.