Synthesis of Glycaro‐1,5‐lactams and Tetrahydrotetrazolopyridine‐5‐carboxylates: Inhibitors of <i>β</i>‐<scp>D</scp>‐Glucuronidase and <i>α</i>‐<scp>L</scp>‐Iduronidase
Bibliographic record
Abstract
Abstract The known glucaro‐1,5‐lactam 8, its diastereoisomers 9–11, and the tetrahydrotetrazolopyridine‐5‐carboxylates 12–14 were synthesised as potential inhibitors of β‐D‐glucuronidases and α‐L‐iduronidases. The known 2,3‐di‐O‐benzyl‐4,6‐O‐benzylidene‐D‐galactose (16) was transformed into the D‐galactaro‐ and L‐altraro‐1,5‐lactams 9 and 11 via the galactono‐1,5‐lactam 21 in twelve steps and in an overall yield of 13 and 2%, respectively. A divergent strategy, starting from the known tartaric anhydride 41, led to the D‐glucaro‐1,5‐lactam 8, D‐galactaro‐1,5‐lactam 9, L‐idaro‐1,5‐lactam 10, and L‐altraro‐1,5‐lactam 11 in ten steps and in an overall yield of 4–20%. The anhydride 41 was transformed into the L‐threuronate 46. Olefination of 46 to the (E)‐ or (Z)‐alkene 47 or 48 followed by reagent‐ or substrate‐controlled dihydroxylation, lactonisation, azidation, reduction, and deprotection led to the lactams 8–11. The tetrazoles 12–14 were prepared in an overall yield of 61–81% from the lactams 54, 28, and 67, respectively, by treatment with Tf2O and NaN3, followed by saponification, esterification, and hydrogenolysis. The lactams 8–11 and 40 and the tetrazoles 12–14 are medium‐to‐strong inhibitors of β‐D‐glucuronidase from bovine liver. Only the L‐ido‐configured lactam 10 (Ki = 94 μM) and the tetrazole 14 (Ki = 1.3 mM) inhibit human α‐L‐iduronidase.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".