Stereochemical Purification of an Anti-Inflammatory Drug in an Enzyme Membrane Reactor

酶法拆分是一种潜在的强有力的方法， 分离立体异构体。 脂肪酶和羧酸酯酶 已经为此进行了广泛的研究。 许多脂肪酶 底物，具有手性中心的复杂分子， 溶于水。 因此，生物转化必须在 具有三相的多相、乳液型酶反应器 存在--有机的、水的和固定化的酶。 多相和萃取膜反应器，基于中空- 光纤模块，提供了几个工程优势， 通过促进有效的质量传递和 简化了相和产物分离。 第二阶段提案旨在 为了优化膜生物反应器性能（生产率 和酶的稳定性），证明了酶的拆分， 大规模的模块，并进行了技术和经济 评价一种综合性的重要镇痛药，（S）-伊诺明。 开发中的新药越来越复杂， 在许多情况下需要更精细纯化 阴谋 该机构在这方面非常具体， 三维结构的识别（即， 因此，药物需要被 具有高立体化学纯度，使其具有活性。 已经对酶的使用进行了广泛的研究， 立体异构体混合物的分离。 但 这项技术的商业化必须克服某些困难。 工程路障在经济上是可行的。 基于膜的新型酶反应器的使用已被广泛应用于生物技术领域。 在第一阶段成功地解决了许多问题 问题研究 该第二阶段提案旨在优化膜 生物反应器性能，证明了在 大规模的系统，并进行技术和经济上的 评价一个综合的，酶的决议过程， （S）-吲哚的生产。

Enzymatic resolution is a potentially powerful approach for the separation of the stereoisomers. Lipases and carboxyesterases have been extensively studied for this purpose. Many lipase substrates, complex molecules with chiral centers, are poorly soluble in water. Thus bioconversions must be performed in multiphase, emulsion-type enzyme reactors with three phases present--organic, aqueous, and immobilized enzyme. Multiphase and extractive membrane reactors, based on hollow- fiber modules, offer several engineering advantages over conventional reactors by promoting efficient mass transfer and simplifying phase and product separation. This Phase II proposal seeks to optimize membrane bioreactor performance (productivity and enzyme stability), demonstrate enzymatic resolution in a large-scale module, and conduct both a technical and economic evaluation of an integrated important analgesic, (S)-Ibuprofen. New drugs under development are increasingly more complex in structure and require, in many cases, more elaborate purification schemes. The body is highly specific in regard to the recognition of the three-dimensional structure (i.e., streoisomers) of a pharmaceutical and, therefore, the drug needs to be of high stereochemical purity for it to be active. Extensive research has been conducted on the use of enzymes for the separation of mixtures of steroisomers. However, the commercialization of this technology must overcome certain engineering roadblocks to be economically feasible. The use of a novel enzyme reactor, based on membranes, has been shown to successfully address many of these problems in Phase I studies. This Phase II proposal seeks to optimize membrane bioreactor performance, demonstrate enzymatic resolution in a large-scale system, and conduct both a technical and economic evaluation of an integrated, enzymatic-resolution process for the production of (S)-Ibuprofen.