Chemoenzymatic Formal Total Synthesis of <i>ent</i>‐Codeine and Other Morphinans <i>via</i> Nitrone Cycloadditions and/or Radical Cyclizations. Comparison of Strategies for Control of C‐9/C‐14 Stereogenic Centers
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Formal total syntheses of ent ‐codeine and other morphinans were accomplished from 1‐phenyl‐2‐acetoxyethane, which was subjected to enzymatic dihydroxylation by toluene dioxygenase overexpressed in Eschericia coli JM109 (pDTG601A). The resulting cis ‐dihydroarenediol was coupled with a phenol derived from bromoisovanillin and a subsequent Heck reaction was used to establish the C‐13 quaternary center. Two strategies were employed to set the C‐14 center: nitrone and nitrile oxide cycloadditions to the C‐8/C‐14 olefin and a radical cyclization of an aldehyde to C‐14. Both strategies yielded tetracyclic products that were converted to known intermediates for the synthesis of ent ‐codeine, ent ‐codeinone, and ent ‐hydrocodone. Experimental and spectral data are provided for all new compounds. magnified image
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it