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

绿色制药工艺：新型功能性磷材料作为催化剂载体和金属清除剂

• 批准号: 380933-2009
• 负责人: Gates, Derek
• 金额: $ 10.93万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Strategic Projects - Group
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=463250
• 关键词: Green; pharmaceutical; manufacturing; processes; new

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.

现代药物生产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很有吸引力，因为催化剂往往是高效的，对所需产物具有选择性，并且它们减少了导致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持配体组成，价格昂贵，并且由于毒性问题，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的合成效率，同时最大限度地减少金属污染物的存在。该提案通过解决两个领域来改进现代药品制造中使用的工艺来解决这些问题。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绿色的制药工艺。首先，将探索一系列新型含磷聚合物作为潜在的金属清除剂。磷对许多药物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，并有效地最大限度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药物合成的支持剂。通过将金属催化剂直接结合到聚合物上，有利于金属催化剂的有效去除和回收。人们可以设想使用这些聚合物的固定形式来支持药物发现和生产的流动过程中的催化作用。这些项目均承诺改进药品生产的绿色流程。