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

生产药品的现代方法至少在生产过程的一个步骤中涉及过渡金属。一方面，利用金属催化将一种药物前体转化为另一种药物前体是很有吸引力的，因为催化剂往往效率很高，对所需产物有选择性，而且它们减少了造成废物流的副产物的产生。另一方面，催化剂通常由贵金属和磷基支撑配体组成，价格昂贵，而且由于毒性问题，必须根据严格的规定从药品中去除。因此，需要有效的方法来最大限度地提高药物分子合成的效率，同时最大限度地减少金属污染物的存在。本建议通过解决两个方面的问题来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，导致更环保的制药过程。首先，将探索一组新型含磷聚合物作为潜在的金属清除剂。磷对用于许多药物催化合成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“捕获”金属在其支架内，并有效地减少药物的金属污染。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撑剂。通过将金属催化剂直接与聚合物结合，促进了金属催化剂的高效去除和回收。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流程中的催化作用。这些项目都承诺改善生产药品的绿色工艺。

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.