Green pharmaceutical manufacturing processes: new functional phosphorus-materials as catalyst-supports and metal-scavengers

现代药物生产方法包括至少在生产过程的一个步骤中使用过渡金属。一方面，使用金属催化一种药物前体向另一种药物的转化是有吸引力的，因为催化剂往往是高效的，对所需产品具有选择性，并且它们减少了造成废物流的副产品的产生。另一方面，催化剂通常由贵金属和磷基支持配体组成，可能很昂贵，而且出于毒性考虑，必须根据严格的规定从制药产品中移除。因此，需要有效的方法来最大限度地提高药物分子的合成效率，同时最大限度地减少金属污染物的存在。这项提案通过解决两个方面来解决这些问题，以改进现代制药生产中使用的工艺。这项工作将通过提高效率、促进贵金属的回收和再循环来实现更环保的制药过程。首先，将探索一系列新型的含磷聚合物作为潜在的金属清除剂。磷对许多药物的催化合成中使用的金属类型具有非常高的亲和力。因此，预计这些独特的磷聚合物将非常有效地将金属捕捉到支架内，并有效地将药物的金属污染降至最低。拟议研究的第二个领域涉及使用磷基聚合物作为金属催化合成药物的支撑剂。通过将金属催化剂直接结合到聚合物上，促进了金属催化剂的有效去除和回收。人们可以设想在药物发现和生产的流动过程中使用这些聚合物的固定化形式来支持催化。这些项目都承诺改善制药生产的绿色工艺。

Modern methods for the production of pharmaceuticals involve transition metals in at least one step of the production process. On one hand, the use of metals to catalyze the transformation of one drug precursor to another is attractive because catalysts tend to be highly efficient, selective towards the desired product and they reduce the generation of byproducts which contribute to the waste stream. On the other hand, the catalyst, often composed of a precious metal and a phosphorus-based supporting ligand, can be expensive and, due to toxicity concerns, must be removed from the pharmaceutical product according to strict regulations. Consequently, efficient methods are needed to maximize the efficiency of the synthesis of drug molecules while at the same time minimizing the presence of metal contaminants. This proposal addresses these problems by tackling two areas to improve processes used in modern pharmaceutical manufacture. This work will lead to greener pharmaceutical processes by improving efficiency, facilitating the recovery and recycling of precious metals. First, a set of novel phosphorus-containing polymers will be explored as potential metal scavenging agents. Phosphorus has a very high affinity for the types of metals used in the catalytic synthesis of many pharmaceuticals. Therefore, it is expected that these unique phosphorus polymers will be highly effective to "trap" metals within their scaffolds and effectively minimize metal-contamination of pharmaceuticals. The second area of proposed research involves using phosphorus-based polymers as supporting agents for the metal-catalyzed synthesis of pharmaceuticals. By binding the metal catalyst directly to the polymer, the efficient removal and recycling of the metal catalyst is facilitated. One can envision using immobilized forms of these polymers to support catalysis in a flow process for drug discovery and production. These projects each promise improved green processes to manufacture pharmaceuticals.