Novel Enzymatic Reductive Amination

新型酶还原胺化

• 批准号: 6481774
• 负责人: JAMES DAVID ROZZELL
• 金额: $ 11.46万
• 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: 2002-05-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6481774
• 关键词: amination; amine oxidoreductase; chemical synthesis; directed evolution; high throughput technology; ketones; method development; reduction; stereochemistry; stereoisomer

DESCRIPTION (provided by applicant): Chiral amines are an important class of pharmaceutical intermediates. In Phase 1 we propose to use directed evolution methods to create the first group of amine dehydrogenase enzymes evolved to catalyze the stereoselective reductive amination of ketones to the corresponding chiral amines. A patent-pending assay for use in high throughput screening has already been developed and validated for the detection of new amino acid dehydrogenase activities, and we will adapt this method to establish a high throughput screen for detecting new "amine dehydrogenases." These new enzymes will then be characterized and evaluated for the production of chiral amines by the reductive amination of ketones. In contrast to resolution methods, the reductive amination process is a chiral synthesis, and up to 100 percent of the starting material can be converted into the enantiomerically pure product in a single step using readily available, inexpensive ketone starting materials. Success in Phase 1 will lay the foundation for an expanded development of amine dehydrogenases capable of catalyzing the production of a wide range of chiral amines in Phase 2. PROPOSED COMMERCIAL APPLICATION: Chiral amines produced using the technology developed have applications as key intermediates for the synthesis of a wide range of pharmaceutically active compounds.

描述(申请人提供)：手性胺是一类重要的 医药中间体。在阶段1中，我们建议使用定向进化 方法创建第一组胺脱氢酶，进化为 催化酮的立体选择性还原胺化反应 相应的手性胺。一种用于高通量的正在申请专利的检测方法 筛查已经被开发和验证，用于检测新的 氨基酸脱氢酶活性，我们将采用这种方法来建立 用于检测新的“胺脱氢酶”的高通量筛查。这些新的 然后，将对酶进行表征，并对其进行手性生产评估。 通过酮的还原胺化反应生成的胺。与解决方案形成对比 方法，还原胺化过程为手性合成，最高可达100 起始原料的百分比可转化为对映体 使用现成、廉价的酮，一步即可生产出纯产品 起始材料。第1阶段的成功将为扩展的 催化合成α-氨基丁酸的胺脱氢酶的研究进展 第二阶段手性胺的种类繁多。 拟议的商业应用：利用所开发的技术生产的手性胺可用作合成多种药用活性化合物的关键中间体。