Aldehyde-Catalyzed Carboxylate Exchange in a-Amino Acids with Isotopically Labeled CO2
Bibliographic record
Abstract
a-Amino acids are among the essential chemical building blocks of life. These structures are embedded in many small molecule pharmaceuticals and are the primary components of peptide-based therapeutics and biologics. Isotopically labeled a-amino acids and their derivatives have widespread use in structural and mechanistic biochemistry, quantitative proteomics, absorption distribution metabolism and excretion (ADME) profiling, and as imaging agents in positron emission tomography (PET) techniques. The preparation of carbon-labeled a-amino acids remains difficult and time consuming, with established methods involving label incorporation at an early stage of synthesis. This explains the high cost and scarcity of C-labeled products and presents a major challenge in 11C applications (11C t1/2 = 20 min). Here we report that simple aldehydes catalyze the isotopic carboxylate exchange of native a-amino acids with *CO2 (* = 14, 13, 11). Proteinogenic a-amino acids and many non-natural variants containing diverse functional groups undergo labeling. The reaction likely proceeds via the trapping of *CO2 by imine-carboxylate intermediates to generate aminomalonates that are prone to monodecarboxylation. Tempering catalyst electrophilicity was key to preventing irreversible aldehyde consumption. The pre-generation of the imine carboxylate intermediate allows for the rapid and late-stage 11C-radiolabeling of a-amino acids in the presence of 11CO2.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".