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

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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.