New Generic Synthetic Protocols for Pharmaceutical Intermediates Based on Continuous Flow Multifunctional Platforms

药物分子的制备通常是通过一系列一个接一个的反应来完成的。当一种药物的有效成分被制备出来后，第一个中间体被制备并分离出来，然后进入第二步，在第二步中进行额外的转化。制备最终的化合物需要几个单独的步骤，在每个阶段都可能有材料的损失，而且这种方法缺乏效率。然而，大自然可以在单一物种中创造出令人难以置信的复杂分子——抗癌药物紫杉醇就是一个例子，紫杉树可以制造出一种化合物，这对实验室里的化学家来说是一个巨大的合成挑战。紫杉醇是由一系列连续发生的反应自然合成的，不需要分离中间体——这是实验室化学家通常无法获得的奢侈条件。通过设计和开发流动反应器，该项目将允许在没有常规隔离程序的情况下进行化学反应，直到所需的最终结构准备好。该项目将开发一种方法，使化学物质在流过管道时发生反应，而不是在标准的实验室设备中发生反应。当反应中的化合物流过时，它们会在合成序列中转化为下一个化合物，然后再转化为下一个化合物，直到整个合成完成。连续流动装置的一个潜在缺点是，单个反应可能需要彼此非常不同的条件——非常冷的步骤之后是非常热的步骤，可能需要改变中间体的浓度，甚至可能需要改变溶剂。这些问题将通过仔细设计反应堆模块来解决，例如可能涉及微波加热。我们将开发一系列有机反应的连续流动反应，然后开发将各个步骤耦合在一起的方法。然后将开发这些耦合步骤，以提供一些众所周知的药物的案例研究制剂。特别是，我们将准备治疗乳腺癌的主要药物他莫昔芬和治疗抑郁症的主要药物文拉法森，以及著名的抗组胺剂和镇静剂苯海拉明。

The preparation of drug molecules is usually achieved by running a series of reactions one after the other. When the active ingredient of a drug is prepared, the first intermediate is prepared and isolated, and then taken on to a second step, where an additional conversion takes place. Several separate steps are used to prepare the final compound, and at each stage there is likely to be a loss of material as well as the lack of efficiency of this approach. However, Nature can create incredibly complex molecules within a single species - the anti-cancer drug Taxol is an example where the Yew tree makes a compound which is a formidable synthetic challenge to chemists in the laboratory. The taxol is naturally synthesised by a series of reactions which take place sequentially without the isolation of intermediates - a luxury that the laboratory chemist doesn't normally have available to them.By designing and developing flow reactors, this project will allow chemical reactions to be preformed without a conventional isolation procedure until the desired final structure has been prepared. The project will develop methods for allowing chemicals to react as they flow through pipes rather than in standard laboratory apparatus. As the reacting compounds flow through they will be converted into the next compound in the synthetic sequence, and then on to the next until the entire synthesis has been completed.One of the potential drawbacks of the continuous flow apparatus is that the individual reactions may require very different conditions from each other - very cold steps followed by hot steps, changes to the concentration of intermediates may be required, or even a change in solvent. These problems will be addressed by careful design of the reactor modules, and can involve microwave heating for example. We will develop continuous flow reactions for a series of organic reactions and then develop ways to couple the individual steps together. These coupled steps will then be developed to provide case study preparations of some well know pharmaceutical drugs. In particular, we will prepare Tamoxifen, which the leading drug for the treatment of breast cancer, as well as Effexor which a leading pharmaceutical for the treatment of depression, along with Benadryl (Nytol) which is a well-known anihistamine and sedative.