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

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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.