Bibliographic record
Abstract
Although the Na+-K+-ATPase inhibitor (+)-cassaine 4 was isolated from the bark of Erythrophleum guineense in 1935, the structure was not established until 1959. Intriguing features of 4 include the unsaturated amide and the axial secondary methyl group, both pendant to the C ring. Pierre Deslongchamps, now at Université Laval, envisioned (Org. Lett. 2013, 15, 6270) that the relative stereochemistry of the secondary methyl could be established kinetically by intramolecular Michael addition of the enolate formed by the addition of the anion of 2 to the enone 1 to give 3. The sulfoxide 2 was readily prepared by the addition (Tetrahedron Lett. 1990, 31, 3969) of the anion derived from methyl phenyl sulfoxide to methyl crotonate. The enone 1 was prepared from commercial dihydrocarvone 5. Robinson annulation with ethyl vinyl ketone 6 (Tetrahedron 2000, 56, 3409) led to 7, that was reductively methylated, reduced further, and protected to give 8. Oxidative cleavage of the pendant isopropenyl group followed by Baeyer–Villiger oxidation, hydrolysis, and further oxidation gave the ketone 9, that was methoxycarbonylated, then oxidized further to 1. The addition of the anion derived from 2 to 1 presumably gave initially the axial adduct. Subsequent intramolecular Michael addition then proceeded selectively to one face of the residual enone to give, after elimination of the sulfoxide, the enone 3. The anionic cascade annulation that formed the C ring having been accomplished, the ester of 3 was removed by exposure to ethoxide to give 10, having the alkene conjugated with the B-ring ketone. Selective reduction followed by protection gave 11. In the course of the hydrogenolytic deprotection of the A-ring alcohol, selective hydrogenation of the tetrasubstituted alkene was also observed. Increasing the H2 pressure and extending the reaction time gave complete conversion to the desired 12, the relative configuration of which was established by X-ray crystallography. A series of protection, reduction, and oxidation steps led to the C-ring ketone, that was methoxycarbonylated to give 14. Reduction followed by dehydration gave the unsaturated ester, that was reduced to the saturated ester with Mg in methanol. Reduction followed by oxidation then delivered the aldehyde 15. After some investigation, it was found that the aldehyde could be converted to the desired enol triflate by exposure to KHMDS and the Comins reagent.
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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) | 0.001 | 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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.004 |
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".