Novel Catalyst Systems

新型催化剂系统

• 批准号: 8196637
• 负责人: Andrew Feiring
• 金额: $ 16.7万
• 依托单位: COMPACT MEMBRANE SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196637
• 关键词: Aerobic; Alkenes; Binding; Carbon; Carbon Dioxide; Catalysis; Chemicals; Chemistry; Complex; Development; Drug Industry; Environmental Impact; Excision; Family; Hydrogenation; Industry; Ligands; Membrane; Metals; Methods; Oral; Organic Synthesis; Oxygen; Palladium; Permeability; Pharmacologic Substance; Phase; Polymers; Process; Production; Reaction; Reporting; Resistance; Safety; Solutions; Stream; Surface; System; Technology; Time; Transition Elements; Water; Work; catalyst; cost; drug candidate; economic evaluation; improved; innovation; interest; new technology; novel; oxidation; programs; pyridine; small molecule; success

DESCRIPTION (provided by applicant): Transition metal catalysts are widely used in the pharmaceutical industry for the production of active ingredients, precursors and new drug candidates. These products must be very pure, often requiring labor and energy intensive separation processes, to achieve the required purity levels. Of special concern in the present context is to avoid contaminating the product with the transition metal catalyst used during its synthesis. The above references are far from an exhaustive list but suggest the breadth and importance of the chemistry available from palladium catalysts. Palladium catalyzed reactions are ubiquitous in pharmaceutical process chemistry. Many synthetic processes rely on both heterogeneous and homogeneous catalysis. However, Pd is highly toxic, and the allowable level of palladium in an active pharmaceutical ingredient (API) is highly regulated, and must be less than 5 ppm (oral) or 0.5 ppm (parenteral). Accordingly, there is considerable interest in the development of new technologies that will ameliorate the problem of metal contamination in Pd- catalyzed processes. A variety of scavenger and filtering methods are used for removing palladium from APIs. Palladium removal essentially adds an extra step to a synthesis, and is consequently costly in terms of time and money. Although palladium catalysis is the major focus of this proposal, other metal species are also of interest. Compact Membrane Systems, Inc. (CMS) proposes a new catalyst system that provides the needed catalytic reactivity as described above but eliminates the extra steps associated with reducing/eliminating contamination. In Phase I CMS will fabricate palladium system, demonstrate its catalytic capability and determine contamination level in produce. Contingencies are included and overall economic evaluation is included. PUBLIC HEALTH RELEVANCE: It is proposed to eliminate the problem of leaching of transition metal catalysts into pharmaceutical process streams, which can contaminate the product and result in loss of costly catalyst materials. Combining fluorous technology with membranes we further enhance the ability to separate metal and other components from organic species. Successful implementation of this technology should result in higher purity, lower cost products.

描述（由申请人提供）：过渡金属催化剂广泛用于制药行业，用于生产活性成分、前体和新药候选物。这些产品必须非常纯，通常需要劳动力和能源密集型的分离过程，以达到所需的纯度水平。在本文中特别关注的是避免产物被在其合成期间使用的过渡金属催化剂污染。 上述参考文献远不是详尽的列表，但表明了可从钯催化剂获得的化学的广度和重要性。钯催化反应在制药过程化学中是普遍存在的。许多合成过程依赖于多相和均相催化。然而，Pd具有高毒性，活性药物成分（API）中钯的允许水平受到高度管制，必须低于5 ppm（口服）或0.5 ppm（胃肠外）。因此，人们对开发将改善Pd催化工艺中的金属污染问题的新技术非常感兴趣。各种清除剂和过滤方法用于从原料药中除去钯。钯的去除基本上为合成增加了额外的步骤，因此在时间和金钱方面是昂贵的。虽然钯催化是该提议的主要焦点，但其他金属物质也是令人感兴趣的。 Compact Membrane Systems，Inc. (CMS)提出了一种新的催化剂体系，其提供了如上所述的所需的催化反应性，但消除了与减少/消除污染相关的额外步骤。在第一阶段，CMS将制造钯系统，证明其催化能力，并确定生产中的污染水平。包括或有事项及整体经济评估。 公共卫生关系：提出消除过渡金属催化剂浸出到制药工艺流中的问题，该问题可能污染产物并导致昂贵的催化剂材料的损失。将氟技术与膜相结合，我们进一步提高了从有机物质中分离金属和其他组分的能力。该技术的成功实施应该会产生更高纯度、更低成本的产品。