Deracemization of Amino Acids

氨基酸的去消旋作用

• 批准号: 6439310
• 负责人: SCOTT J NOVICK
• 金额: $ 10万
• 依托单位: BIOCATALYTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6439310
• 关键词: aminoacid; aminoacid oxidase; chemical synthesis; enzyme activity; enzyme substrate; immobilized enzymes; ketoacid; method development; racemization; stereoisomer

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.

描述(申请人提供)：非天然氨基酸(UAA)正在增长 作为医药中间体的重要性，在许多领域有应用 当前和未来的药物。因为UAA通常被要求为纯 立体异构体，手性合成比拆分方法更可取 最常被雇佣的人。在这项提议中，一锅法去消解过程 将被开发来从容易制备的UAA制备纯立体异构体 可获得且价格低廉的外消旋混合物。去中心化将会实现 通过选择性地将D，L混合物中的D-氨基酸氧化到相应的 2-酮酸，使用D-氨基酸氧化酶，将2-酮酸转化为 L-氨基酸采用立体选择性的酶催化反应。收益率是 预计接近100%，提供几乎完全的转换 以外消旋为起始原料，得到光学纯的L-UAA。重要的是，这种方法 在一步反应中将外消旋氨基酸直接转化为L式 不需要保护群体或派生。此外，该方法 具有广泛的适用范围，将适用于广泛的UAA产品。二 将研究可选的偶联酶系统，并对结果进行比较 选择生物催化法。该方法将通过生产来演示 目前的四个商业目标的克数量。 建议的商业应用： 用于药物生产的中间体跨越了广泛的治疗适应症。