Total Synthesis by Alkene Metathesis: Amphidinolide X (Urpí/Vilarrasa), Dactylolide (Jennings), Cytotrienin A (Hayashi), Lepadin B (Charette), Blumiolide C (Altmann)
Bibliographic record
Abstract
To assemble the framework of the cytotoxic macrolide Amphidinolide X 3, Fèlix Urpí and Jaume Vilarrasa of the Universitat de Barcelona devised (Organic Lett. 2008, 10, 5191) the ring-closing metathesis of the alkenyl silane 1. No Ru catalyst was effective, but the Schrock Mo catalyst worked well. In the course of a synthesis of (-)-Dactylolide 6, Michael P. Jennings of the University of Alabama offered (J. Org. Chem. 2008, 73, 5965) a timely reminder of the particular reactivity of allylic alcohols in ring-closing metathesis. The cyclization of 4 to 5 proceeded smoothly, but attempted ring closing of the corresponding bis silyl ether failed. Polyenes such as ( + )-Cytotrienin A 8 are notoriously unstable. It is remarkable that Yujiro Hayashi of the Tokyo University of Science could (Angew. Chem. Int. Ed. 2008, 47, 6657) assemble the triene of 8 by the ring-closing metathesis of the highly functionalized precursor 7. Bicyclo [2.2.2] structures such as 9 are readily available by the addition of, in this case, methyl acrylate to an enantiomerically-pure 2-methylated dihydropyridine. André B. Charette of the Université de Montréal found (J. Am. Chem. Soc. 2008, 130, 13873) that 9 responded well to ring-opening/ring-closing metathesis, to give the octahydroquinoline 10. Functional group manipulation converted 10 into the Clavelina alkaloid ( + )-Lepadin B 11. The construction of trisubstituted alkenes by ring-closing metathesis can be difficult, and medium rings with their transannular strain are notoriously challenging to form. Nevertheless, Karl-Heinz Altmann of the ETH Zürich was able (Angew. Chem. Int. Ed. 2008, 47, 10081), using the H2 catalyst, to cyclize 12 to cyclononene 13, the precursor to the Xenia lactone ( + )-Blumiolide C 14. It is noteworthy that these fi ve syntheses used four different metathesis catalysts in the key alkene forming step. For the cyclization of 7, the use of the Grubbs first generation catalyst G1, that couples terminal alkenes but tends not to interact with internal alkenes, was probably critical to success.
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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 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".