Bischoff, Matthias ; Mayer, Peter ; Meyners, Christian ; Hausch, Felix (2020)
Enantioselective synthesis of a tricyclic, sp³‐rich diazatetradecanedione: an amino acid‐based natural product‐like scaffold.
In: Chemistry – A European Journal, 26 (21)
doi: 10.1002/chem.201905144
Artikel, Bibliographie
Dies ist die neueste Version dieses Eintrags.
Kurzbeschreibung (Abstract)
6‐, 7‐, and 8‐membered rings are assembled from a linear precursor by successive cyclisation reactions to construct a tricyclic diazatricyclo[6.5.1.0⁴,⁹]‐tetradecanedione scaffold. Advanced building blocks based on d‐aspartic acid and l‐pyroglutamic acid were combined by a sp³−sp² Negishi coupling. A carbamate‐guided syn‐diastereoselective epoxidation followed by an intramolecular epoxide opening allowed the construction of the piperidine ring. An efficient one‐pot hydroxyl‐group protection twofold deprotection reaction prepared the ground for the cyclisation to the bicycle. A final deprotection of the orthogonal protecting groups and lactamisation led to the novel, sp³‐rich tricycle. The final compound is a substrate mimic of peptidyl‐prolyl cis‐trans isomerases featuring a locked trans‐amide bond. Cheminformatic analysis of 179 virtual derivatives indicates favourable physicochemical properties and drug‐like characteristics. As proof of concept we, show a low micromolar activity in a fluorescence polarisation assay towards the FK506‐binding protein 12.
| Typ des Eintrags: | Artikel | ||||
|---|---|---|---|---|---|
| Erschienen: | 2020 | ||||
| Autor(en): | Bischoff, Matthias ; Mayer, Peter ; Meyners, Christian ; Hausch, Felix | ||||
| Art des Eintrags: | Bibliographie | ||||
| Titel: | Enantioselective synthesis of a tricyclic, sp³‐rich diazatetradecanedione: an amino acid‐based natural product‐like scaffold | ||||
| Sprache: | Englisch | ||||
| Publikationsjahr: | 2020 | ||||
| Ort: | Weinheim | ||||
| Verlag: | Wiley-VCH | ||||
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Chemistry – A European Journal | ||||
| Jahrgang/Volume einer Zeitschrift: | 26 | ||||
| (Heft-)Nummer: | 21 | ||||
| DOI: | 10.1002/chem.201905144 | ||||
| Zugehörige Links: | |||||
| Kurzbeschreibung (Abstract): | 6‐, 7‐, and 8‐membered rings are assembled from a linear precursor by successive cyclisation reactions to construct a tricyclic diazatricyclo[6.5.1.0⁴,⁹]‐tetradecanedione scaffold. Advanced building blocks based on d‐aspartic acid and l‐pyroglutamic acid were combined by a sp³−sp² Negishi coupling. A carbamate‐guided syn‐diastereoselective epoxidation followed by an intramolecular epoxide opening allowed the construction of the piperidine ring. An efficient one‐pot hydroxyl‐group protection twofold deprotection reaction prepared the ground for the cyclisation to the bicycle. A final deprotection of the orthogonal protecting groups and lactamisation led to the novel, sp³‐rich tricycle. The final compound is a substrate mimic of peptidyl‐prolyl cis‐trans isomerases featuring a locked trans‐amide bond. Cheminformatic analysis of 179 virtual derivatives indicates favourable physicochemical properties and drug‐like characteristics. As proof of concept we, show a low micromolar activity in a fluorescence polarisation assay towards the FK506‐binding protein 12. |
||||
| Alternatives oder übersetztes Abstract: |
|
||||
| Freie Schlagworte: | amino acids, diastereoselective epoxidation, FK506-binding protein, natural products, sp³−sp² Negishi coupling | ||||
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie | ||||
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie |
||||
| Hinterlegungsdatum: | 24 Jan 2024 07:26 | ||||
| Letzte Änderung: | 24 Jan 2024 07:26 | ||||
| PPN: | |||||
| Zugehörige Links: | |||||
| Export: | |||||
| Suche nach Titel in: | TUfind oder in Google | ||||
Verfügbare Versionen dieses Eintrags
-
Enantioselective Synthesis of a Tricyclic, sp³‐Rich Diazatetradecanedione: an Amino Acid‐Based Natural Product‐Like Scaffold. (deposited 23 Jan 2024 13:55)
- Enantioselective synthesis of a tricyclic, sp³‐rich diazatetradecanedione: an amino acid‐based natural product‐like scaffold. (deposited 24 Jan 2024 07:26) [Gegenwärtig angezeigt]
 |
Frage zum Eintrag |
Optionen (nur für Redakteure)
 |
Redaktionelle Details anzeigen |
Drucken
Impressum