Biaryl-basierte Naturstoffe als Strukturmotiv für pharmazeutisch relevante Verbindungen
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Notice bibliographique
Résumé
Biaryls are important structural motifs for both pharmaceutically relevant compounds as well as ligands, and catalysts in chemical transformations. With the aim of contributing to the everexpanding <br/>methodology towards biaryls, different synthesis strategies were devised and implemented to obtain synthetically relevant biaryls. Moreover, stereoselective palladium catalyzed transformations were investigated for the synthesis of bicyclic compounds. <br/>8,8′′-Biflavones, a class of biaryl-based natural products, were investigated for their bioactivity against various human pathogens. A synthesis route for the construction of highly functionalized racemic biaryl building blocks in three steps was established in a scalable fashion. Enabled by this method, the first extensive library of 8,8′′-biflavone analogues was synthesized. This dedicated library was then evaluated regarding its pharmaceutical potential in cooperation with M.Sc. Lena Berning and M.Sc. Flaminia Mazzone (Heinrich Heine University Düsseldorf). In addition to promising results for these biflavones, bichalcones obtained as key intermediates were identified as novel drug scaffolds. Based on these first hits, further amino-8,8′′-biflavones including the first non-C2-symmetrical 8,8′′-biflavone were synthesized. In cooperation with M.Sc. Céline David (Heinrich Heine University Düsseldorf) the structure activity relationship was probed, and bioactivities obtained. Next a strategy involving cyclic diaryliodonium salts towards an enantiopure building block was implemented. Extensive investigations were undertaken, and ultimately a scalable protocol successfully established. These prochiral building blocks were then applied to construct enantiopure dimeric flavonoids and thus the usefulness of the established Methodology shown. In addition to these investigations, palladium-catalyzed methods were investigated to overcome advanced synthetic challenges. For one, the Catellani reaction was used to obtain biaryls inaccessible by state-of-the-art methods. Factors critical for this transformation were identified, and a protocol for the synthesis of tri-ortho-substituted biaryls established. Moreover, first investigations into stereodynamic biaryl-based palladacycles were conducted. The proposed stereodynamics of these palladium complexes were supported by preliminary computational calculations (DFT). Finally, in collaboration with the working group of Prof. Mark Lautens (University of Toronto), the use of chiral oxabicycles as acetylene analogues was thoroughly investigated. A mechanism to explain the observed stereoselectivity of the reaction was proposed and supported by experimental findings. Finally, DFT calculations were conducted to rationalize the observed selectivities.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,004 | 0,003 |
| Méta-épidémiologie (sens large) | 0,004 | 0,002 |
| Bibliométrie | 0,002 | 0,005 |
| Études des sciences et des technologies | 0,002 | 0,001 |
| Communication savante | 0,002 | 0,002 |
| Science ouverte | 0,003 | 0,001 |
| Intégrité de la recherche | 0,005 | 0,006 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,010 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle