The Synthesis of Abiraterone O-β-D Glucuronide For Use In Clinical Trials As A Reference Standard
Bibliographic record
Abstract
INTRODUCTION Abiraterone is an active pharmaceutical ingredient (API) that is used for the treatment of hormone-resistant prostate cancers [1]. Due to the action of the human xenobiotic metabolism, Abiraterone undergoes various chemical modifications to form the phase II metabolite, Abiraterone-O- β-D- glucuronide [2]. This process occurs due to the highly soluble nature of glucuronides and their ability to act as effective agents in drug excretion. As a consequence, Abiraterone-O- β-D- glucuronide normally presents itself in urine and is thus essential for toxicological testing and an analysis of the pharmacological activity of Abiraterone [2]. However, in order to confirm the identity of Abiraterone-O- β-D- glucuronide and quantify the amount metabolised within the body via liquid chromatography-mass spectrophotometry (LC-MS) based assays and nuclear magnetic resonance (NMR) requires a reference standard that completely resembles the native form of the metabolite. METHODS The first step entails the protection of the hydroxyl moieties on a methyl glucuronate molecule via pivaloyl chloride. This is followed by the selective deprotection of the C1 hydroxyl group and the addition of an imidate moiety to form and activate a glucuronyl donor. The next stage involves the coupling of this glucuronyl donor with Abiraterone in the presence of boron trifluoride etherate to synthesize the final intermediate. Abiraterone-O- β-D- glucuronide is produced via deprotection of the remaining hydroxyl groups in tetrabutylammonium hydroxide. The final product is isolated through column chromatography. RESULTS A total of 137mg of Abiraterone-O- β-D- glucuronide was produced which corresponds to an overall yield of 26%. LC-MS analysis as shown in Figure 1 reveals a final purity of >98%. NMR results were consistent with the structure of the final compound. DISCUSSION AND CONCLUSIONS This research shows that pure synthetic Abiraterone-O- β-D- glucuronide can be successfully synthesized and used as a reference standard for clinical trials.
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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 | 0.023 | 0.031 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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; a candidate call from one teacher head, not a consensus.
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".