Deracemization of Amino Acids

描述（由申请人提供）：非天然氨基酸（UAA）正在增长 作为药物中间体的重要性，在许多方面具有应用， 目前和未来的药物。由于UAA通常被要求为纯的， 对于立体异构体，手性合成优于拆分方法， 是最常用的。在这项提议中， 将被开发用于从容易获得的化合物中制备UAA的纯立体异构体。 可获得的和便宜的外消旋混合物。将完成去消旋化 通过将D，L-混合物中的D-氨基酸选择性氧化成相应的 2-酮酸，使用D-氨基酸氧化酶，并将2-酮酸转化为 使用立体选择性酶催化反应制备L-氨基酸。收益率 预计将接近100%，几乎完全转换的 将外消旋起始材料转化为光学纯的L-UAA。重要的是，该方法 在单一反应步骤中将外消旋氨基酸直接转化为L-型 而不需要保护基或衍生化。此外，该方法 适用范围广，适用于多种UAA产品。两 替代耦合酶系统将进行研究，并比较结果 选择生物催化方法。该方法将通过生产 四个当前商业目标的克量。 拟议的商业应用： 用于生产涵盖广泛法师治疗适应症的药物的中间体。

DESCRIPTION (provided by applicant): Unnatural amino acids (UAAs) are growing in importance as pharmaceutical intermediates, with applications in a number of current and future drugs. Since UAAs are most always required as pure stereoisomers, a chiral synthesis is preferred over the resolution methods that are most commonly employed. In this proposal a one-pot deracemization process will be developed to prepare pure stereoisomers of UAAs from the readily available and inexpensive racemic mixtures. Deracemization will be accomplished by selectively oxidizing the D-amino acid in a D,L-mixture to the corresponding 2-ketoacid, using D-amino acid oxidase, and converting the 2-ketoacid to the L-amino acid using a stereoselective enzyme-catalyzed reaction. Yields are expected to approach 100 percent, affording almost complete conversion of the racemic starting materials to the optically-pure L-UAA. Importantly, the method coverts the racemic amino acid directly to L-form in a single reaction step without the need for protecting groups or derivitization. Further, this method has broad scope, and will be applicable to a wide range of UAA products. Two alternative coupled enzymatic systems will be studied, and the results compared to select the biocatalytic method. The method will be demonstrated by producing gram quantities of four current commercial targets. PROPOSED COMMERCIAL APPLICATIONS: Intermediates for the production of pharmaceuticals spanning a wide mage of therapeutic indications.