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

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的可用性有限，成本高，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昂贵，耗时，或在某些情况下完全不可行。我们发明了一种新技术，使用 *CO2（* = 14，13，11）对天然氨基酸进行碳标记。该方法使用醛催化剂在单一步骤中得到标记的产物。由于 *CO2是最便宜的标记碳源，该技术与已建立的协议相比具有显着的优势。该提案旨在扩展和改进该技术，以满足制药，农业化学和医学成像领域潜在终端用户的需求。我们的目标是创造新的专利亲电催化剂和反应，可以提供C1标记的氨基酸，具有高效率和最小的过量 *CO2。由于不同种类的氨基酸显示出不同的反应性，并且用14、13或11-C同位素标记存在独特的技术挑战，因此将开发定制的和树脂结合的催化剂和方案。我们将改进我们的方法来获得同手性标记的产品，通过伸缩的羧酸酯交换反应与酶（动力学）决议。将开发基于手性环糊精的催化剂以提供拆分的替代方案。开发的新催化剂将商业化。这笔资金将与艾伯塔省的企业和全球主要制药公司进行长期的研究合作和协议。

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.