I2I Phase 1: Methods and Catalysts for Isotopic Labeling of Amino Acids

I2I 第一阶段：氨基酸同位素标记的方法和催化剂

• 批准号: 567606-2021
• 负责人: Lundgren, Rylan
• 金额: $ 9.11万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Idea to Innovation
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=728667
• 关键词: I2I; Phase; Methods; Catalysts; Isotopic

The isotopic labeling of small molecules is essential to drug development and functional imaging. Isotopic labeling groups are part of all major pharmaceutical companies and many contract research organizations are dedicated entirely to this task. Synthetic precursors for labeling with carbon-based isotopes are of limited availability, high cost, and are difficult to use in the late-stage synthesis of bioactive molecules. This makes studies that need these compounds expensive, time consuming, or in some cases completely unfeasible. We have invented a new technology for the carbon-labeling of native amino acids using *CO2 (* = 14, 13, 11). The process gives labeled products in a single step using aldehyde catalysts. As *CO2 is the most inexpensive source of labeled carbon, the technology has significant benefit compared to established protocols.The proposal aims to expand and improve this technology to meet the demands of potential end-users in the pharmaceutical, agrochemical, and medical imaging fields. We aim to create new proprietary electrophilic catalysts and reactions that can delivery C1-labeled amino acids with high efficiency and with minimal excess of *CO2. Since different classes of amino acids display differing reactivity and labeling with 14, 13, or 11-C isotopes present unique technical challenges, tailored and resin-bound catalysts and protocols will be developed. We will improve our approaches to obtaining homochiral labeled products by telescoping the carboxylate exchange reaction with enzymatic (kinetic) resolutions. Chiral aldehyde-based catalysts will be developed to provide an alternative to resolution. The new catalysts developed will be commercialized. This funding will seed long term research collaborations and agreements with both an Alberta-based business and major global pharmaceutical companies.

小分子的同位素标记对于药物开发和功能成像至关重要。同位素标记小组是所有主要制药公司的一部分，许多合同研究组织完全致力于这项任务。用于碳基同位素标记的合成前体可用性有限、成本较高，并且难以用于生物活性分子的后期合成。这使得需要这些化合物的研究变得昂贵、耗时，或者在某些情况下完全不可行。我们发明了一种使用 *CO2 (* = 14, 13, 11) 对天然氨基酸进行碳标记的新技术。该工艺使用醛催化剂一步即可生成标记产品。由于*CO2是最便宜的标记碳来源，因此与现有协议相比，该技术具有显着的优势。该提案旨在扩展和改进该技术，以满足制药、农化和医学成像领域潜在最终用户的需求。我们的目标是创造新的专有亲电子催化剂和反应，可以高效地传递 C1 标记的氨基酸，并且*CO2 过量最少。由于不同类别的氨基酸表现出不同的反应性，并且用 14、13 或 11-C 同位素进行标记会带来独特的技术挑战，因此将开发定制的树脂结合催化剂和方案。我们将通过将羧酸盐交换反应与酶促（动力学）分辨率进行伸缩来改进获得纯手性标记产品的方法。将开发手性醛基催化剂以提供拆分的替代方案。开发的新催化剂将被商业化。这笔资金将促成与阿尔伯塔省企业和全球主要制药公司的长期研究合作和协议。