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

用于生产药物的现代方法在生产过程的至少一个步骤中涉及过渡金属。一方面，使用金属催化一种药物前体转化为另一种药物前体是有吸引力的，因为催化剂往往是高效的，对所需产物具有选择性，并且它们减少了有助于废物流的副产物的产生。另一方面，通常由贵金属和基于磷的支撑配体组成的催化剂可能是昂贵的，并且由于毒性问题，必须根据严格的规定从药物产品中除去。因此，需要有效的方法来最大化药物分子的合成效率，同时最小化金属污染物的存在。该提案通过解决两个领域来解决这些问题，以改进现代制药中使用的工艺。这项工作将通过提高效率，促进贵金属的回收和再循环，实现更绿色的制药工艺。首先，一组新的含磷聚合物将被探索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“捕获”在其支架内，并有效地最小化药物的金属污染。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持剂。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再循环。人们可以设想使用这些聚合物的固定化形式来支持药物发现和生产的流动过程中的催化。这些项目都承诺改进绿色制药工艺。

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.